atypical presentation of heart failure

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Heart failure occurs when the heart muscle doesn't pump blood as well as it should. Blood often backs up and causes fluid to build up in the lungs and in the legs. The fluid buildup can cause shortness of breath and swelling of the legs and feet. Poor blood flow may cause the skin to appear blue or gray. Depending on your skin color, these color changes may be harder or easier to see. Some types of heart failure can lead to an enlarged heart.

If you have heart failure, your heart can't supply enough blood to meet your body's needs.

Symptoms may develop slowly. Sometimes, heart failure symptoms start suddenly. Heart failure symptoms may include:

Shortness of breath with activity or when lying down.
Fatigue and weakness.
Swelling in the legs, ankles and feet.
Rapid or irregular heartbeat.
Reduced ability to exercise.
A cough that doesn't go away or a cough that brings up white or pink mucus with spots of blood.
Swelling of the belly area.
Very rapid weight gain from fluid buildup.
Nausea and lack of appetite.
Difficulty concentrating or decreased alertness.
Chest pain if heart failure is caused by a heart attack.

When to see a doctor

See your health care provider if you think you might have symptoms of heart failure. Call 911 or emergency medical help if you have any of the following:

Chest pain.
Fainting or severe weakness.
Rapid or irregular heartbeat with shortness of breath, chest pain or fainting.
Sudden, severe shortness of breath and coughing up white or pink, foamy mucus.

These symptoms may be due to heart failure. But there are many other possible causes. Don't try to diagnose yourself.

At the emergency room, health care providers do tests to learn if your symptoms are due to heart failure or something else.

Call your health care provider right away if you have heart failure and:

Your symptoms suddenly become worse.
You develop a new symptom.
You gain 5 pounds (2.3 kilograms) or more within a few days.

Such changes could mean that existing heart failure is getting worse or that treatment isn't working.

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Chambers and valves of the heart

A typical heart has two upper and two lower chambers. The upper chambers, the right and left atria, receive incoming blood. The lower chambers, the more muscular right and left ventricles, pump blood out of the heart. The heart valves help keep blood flowing in the right direction.

Enlarged heart, in heart failure

If the heart weakens, as it can with heart failure, it begins to enlarge. This forces the heart to work harder to pump blood to the rest of the body.

Heart failure can be caused by a weakened, damaged or stiff heart.

If the heart is damaged or weakened, the heart chambers may stretch and get bigger. The heart can't pump out the needed amount of blood.
If the main pumping chambers of the heart, called the ventricles, are stiff, they can't fill with enough blood between beats.

The heart muscle can be damaged by certain infections, heavy alcohol use, illegal drug use and some chemotherapy medicines. Your genes also can play a role.

Any of the following conditions also can damage or weaken the heart and cause heart failure.

Coronary artery disease and heart attack. Coronary artery disease is the most common cause of heart failure. The disease results from the buildup of fatty deposits in the arteries. The deposits narrow the arteries. This reduces blood flow and can lead to heart attack.

A heart attack occurs suddenly when an artery feeding the heart becomes completely blocked. Damage to the heart muscle from a heart attack may mean that the heart can no longer pump as well as it should.

High blood pressure. Also called hypertension, this condition forces the heart to work harder than it should to pump blood through the body. Over time, the extra work can make the heart muscle too stiff or too weak to properly pump blood.
Heart valve disease. The valves of the heart keep blood flowing the right way. If a valve isn't working properly, the heart must work harder to pump blood. This can weaken the heart over time. Treating some types of heart valve problems may reverse heart failure.
Inflammation of the heart muscle, also called myocarditis. Myocarditis is most commonly caused by a virus, including the COVID-19 virus, and can lead to left-sided heart failure.
A heart problem that you're born with, also called a congenital heart defect. If the heart and its chambers or valves haven't formed correctly, the other parts of the heart have to work harder to pump blood. This may lead to heart failure.
Irregular heart rhythms, called arrhythmias. Irregular heart rhythms may cause the heart to beat too fast, creating extra work for the heart. A slow heartbeat also may lead to heart failure. Treating an irregular heart rhythm may reverse heart failure in some people.
Other diseases. Some long-term diseases may contribute to chronic heart failure. Examples are diabetes, HIV infection, an overactive or underactive thyroid, or a buildup of iron or protein.

Causes of sudden heart failure also include:

Allergic reactions.
Any illness that affects the whole body.
Blood clots in the lungs.
Severe infections.
Use of certain medicines.
Viruses that attack the heart muscle.

Heart failure usually begins with the lower left heart chamber, called the left ventricle. This is the heart's main pumping chamber. But heart failure also can affect the right side. The lower right heart chamber is called the right ventricle. Sometimes heart failure affects both sides of the heart.

Risk factors

Diseases and conditions that increase the risk of heart failure include:

Coronary artery disease. Narrowed arteries may limit the heart's supply of oxygen-rich blood, resulting in weakened heart muscle.
Heart attack. A heart attack is a form of coronary artery disease that occurs suddenly. Damage to the heart muscle from a heart attack may mean the heart can no longer pump as well as it should.
Heart valve disease. Having a heart valve that doesn't work properly raises the risk of heart failure.
High blood pressure. The heart works harder than it has to when blood pressure is high.
Irregular heartbeats. Irregular heartbeats, especially if they are very frequent and fast, can weaken the heart muscle and cause heart failure.
Congenital heart disease. Some people who develop heart failure were born with problems that affect the structure or function of their heart.
Diabetes. Having diabetes increases the risk of high blood pressure and coronary artery disease.
Sleep apnea. This inability to breathe properly during sleep results in low blood-oxygen levels and an increased risk of irregular heartbeats. Both of these problems can weaken the heart.
Obesity. People who have obesity have a higher risk of developing heart failure.
Viral infections. Some viral infections can damage to the heart muscle.

Medicines that may increase the risk of heart failure include:

Some diabetes medicines. The diabetes drugs rosiglitazone (Avandia) and pioglitazone (Actos) have been found to increase the risk of heart failure in some people. Don't stop taking these medicines without first talking to your health care provider.
Some other medicines. Other medicines that may lead to heart failure or heart problems include nonsteroidal anti-inflammatory drugs (NSAIDs) and some medicines used to treat high blood pressure, cancer, blood conditions, irregular heartbeats, nervous system diseases, mental health conditions, lung and urinary problems, and infections.

Other risk factors for heart failure include:

Aging. The heart's ability to work decreases with age, even in healthy people.
Alcohol use. Drinking too much alcohol may weaken the heart muscle and lead to heart failure.
Smoking or using tobacco. If you smoke, quit. Using tobacco increases the risk of heart disease and heart failure.

Complications

If you have health failure, it's important to have regular health checkups, even if symptoms improve. Your health care provider can examine you and run tests to check for complications.

Complications of heart failure depend on your age, overall health and the severity of heart disease. They may include:

Kidney damage or failure. Heart failure can reduce the blood flow to the kidneys. Untreated, this can cause kidney failure. Kidney damage from heart failure can require dialysis for treatment.
Other heart problems. Heart failure can cause changes in the heart's size and function. These changes may damage heart valves and cause irregular heartbeats.
Liver damage. Heart failure can cause fluid buildup that puts too much pressure on the liver. This fluid backup can lead to scarring, which makes it more difficult for the liver to work properly.
Sudden cardiac death. If the heart is weak, there is a risk of dying suddenly due to a dangerous irregular heart rhythm.

One way to prevent heart failure is to treat and control the conditions that can cause it. These conditions include coronary artery disease, high blood pressure, diabetes and obesity.

Some of the same lifestyle changes used to manage heart failure also may help prevent it. Try these heart-healthy tips:

Don't smoke.
Get plenty of exercise.
Eat healthy foods.
Maintain a healthy weight.
Reduce and manage stress.
Take medicines as directed.
Heart failure. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/health-topics/heart-failure. Accessed Nov. 30, 2022.
Ferri FF. Heart failure. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed Nov. 30, 2022.
Colucci WS. Determining the etiology and severity of heart failure or cardiomyopathy. https://www.uptodate.com/contents/search. Accessed Nov. 30, 2022.
Colucci WS. Evaluation of the patient with suspected heart failure. https://www.uptodate.com/contents/search. Accessed Nov. 30, 2022.
Heart failure (HF). Merck Manual Professional Version. https://www.merckmanuals.com/professional/cardiovascular-disorders/heart-failure/heart-failure-hf. Accessed Nov. 28, 2022.
Vasan RS, et al. Epidemiology and causes of heart failure. https://www.uptodate.com/contents/search. Accessed Nov. 28, 2022.
Goldman L, et al., eds. Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Nov. 28, 2022.
AskMayoExpert. Heart failure with reduced ejection fraction (HFrEF) (adult). Mayo Clinic; 2022.
Rakel D, ed. Heart failure. In: Integrative Medicine. 4th ed. Elsevier; 2018. https://www.clinicalkey.com. Accessed Nov. 28, 2022.
AskMayoExpert. Heart failure with preserved ejection fraction (HFpEF) (adult). Mayo Clinic; 2022.
Allen L. Palliative care for patients with advanced heart failure: Decision support, symptom management, and psychosocial assistance. https://www.uptodate.com/contents/search. Accessed Nov. 28, 2022.
The dying patient. Merck Manual Professional Version. http://www.merckmanuals.com/professional/special-subjects/the-dying-patient/the-dying-patient. Accessed Nov. 28, 2022.
Ami TR. Allscripts EPSi. Mayo Clinic. Oct. 4, 2022.
Mancini D. Heart transplantation in adults: Indications and contraindications. https://www.uptodate.com/contents/search. Accessed Nov. 28, 2022.
Sawalha K, et al. Systematic review of COVID-19 related myocarditis: Insights on management and outcome. Cardiovascular Revascularization Medicine. 2021; doi:10.1016/j.carrev.2020.08.028.
Armstrong PW, et al. Vericiguat in patients with heart failure and reduced ejection fraction. The New England Journal of Medicine. 2020; doi:10.1056/NEJMoa1915928.
Armstrong PW, et al. A multicenter, randomized, double-blind, placebo-controlled trial of the efficacy and safety of the oral soluble guanylate cyclase stimulator. Journal of the American College of Cardiology: Heart Failure. 2018; doi:10.1016/j.jchf.2017.08.013.
Verquvo (approval letter). New Drug Application 214377. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214377. Accessed Nov. 28, 2022.
Heidenreich PA, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: A report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022; doi:10.1161/CIR.0000000000001063.
Clarke JD, et al. Effect of inotropes on patient-reported health status in end-stage heart failure: A review of published clinical trials. Circulation: Heart Failure. 2021; doi:10.1161/CIRCHEARTFAILURE.120.007759.
Lopez-Jimenez F (expert opinion). Mayo Clinic. Dec. 2, 2021.
Types of heart failure. American Heart Association. https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Accessed Nov. 28, 2022.
Zannad F, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020; doi:10.1016/S0140-6736(20)31824-9.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors. U.S. Food and Drug Administration. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/sodium-glucose-cotransporter-2-sglt2-inhibitors. Accessed Jan. 10, 2022.
Lee MCH, et al. Clinical efficacy of SGLT2 inhibitors with different SGLT1/SGLT2 selectivity in cardiovascular outcomes among patients with and without heart failure: A systematic review and meta-analysis of randomized trials. Medicine (Baltimore). 2022; doi:10.1097/MD.0000000000032489.
Mankad R (expert opinion). Mayo Clinic. Jan. 12, 2023.
ACC, AHA, HFSA issue heart failure guideline. American Heart Association. https://newsroom.heart.org/news/acc-aha-hfsa-issue-heart-failure-guideline. Accessed Jan. 31, 2023.
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FADI SHAMSHAM, M.D., AND JUDITH MITCHELL, M.D.

Am Fam Physician. 2000;61(5):1319-1328

Although heart failure is a common clinical syndrome, especially in the elderly, its diagnosis is often missed. A detailed clinical history is crucial and should address not only current signs and symptoms of heart failure but also signs and symptoms that point to a specific cause of the syndrome, such as coronary artery disease, hypertension or valvular heart disease. It is important to determine whether the patient has had a previous cardiac event, in particular a myocardial infarction. The physical examination should include Valsalva's maneuver, a test that is highly specific and sensitive for the detection of left ventricular systolic and diastolic dysfunction in patients with heart failure. An electrocardiograph and a chest radiograph should also be obtained. Two-dimensional echocardiography of the heart helps differentiate systolic from diastolic dysfunction. Coronary angiography is indicated in patients with heart failure and anginal chest pain and should be strongly considered in patients with an electrocardiogram suggestive of ischemia or myocardial infarction.

Heart failure affects an estimated 4.9 million Americans, 1 or 1 percent of adults 50 to 60 years of age and 10 percent of adults in their 80s. 2 Each year, about 400,000 new cases of heart failure are diagnosed in the United States. 1 This clinical syndrome is the most frequent cause of hospitalizations in the elderly and is responsible for 5 to 10 percent of all hospital admissions. 1 Heart failure causes or contributes to approximately 250,000 deaths every year. 3

The clinical syndrome of heart failure manifests when cellular respiration becomes impaired because the heart cannot pump enough blood to support the metabolic demands of the body, or when normal cellular respiration can only be maintained with an elevated left ventricular filling pressure. 4

The Framingham, 5 Duke 6 and Boston 7 criteria were established before noninvasive techniques for assessing systolic and diastolic dysfunction became widely available. The three sets of criteria were designed to assist in the diagnosis of heart failure. The Boston criteria ( Table 1 ) 8 have been shown to have the highest combined sensitivity (50 percent) and specificity (78 percent ) . All of these criteria are most helpful in diagnosing advanced or severe heart failure, a condition that occurs in 20 to 40 percent of patients with a decreased ejection fraction. 9

Early diagnosis of heart failure is essential for successfully addressing underlying diseases or causes and, in some patients, preventing further myocardial dysfunction and clinical deterioration. However, initial diagnosis may be difficult because the presentations of heart failure can change from no symptoms to pulmonary edema with cardiogenic shock. It is estimated that heart failure is correctly diagnosed initially in only 50 percent of affected patients. 10 , 11 A systematic approach can improve overall accuracy in diagnosing this condition.

The first step in diagnosing heart failure is to obtain a complete clinical history. The patient should be questioned about dyspnea, cough, nocturia, generalized fatigue and other signs and symptoms of heart failure.

Dyspnea, a cardinal symptom of a failing heart, often progresses from dyspnea on exertion to orthopnea, paroxysmal nocturnal dyspnea and dyspnea on rest. Cough, usually nocturnal and nonproductive, may accompany dyspnea and often occurs in similar settings (i.e., on exertion or when the patient is supine).

Nocturia, also a frequent sign of heart failure, occurs secondary to increased renal perfusion when the patient is supine. 12 Generalized fatigue (caused by the low perfusion state) and peripheral edema with inability to wear usual footwear are frequent complaints.

As heart failure progresses, gastrointestinal symptoms (e.g., abdominal bloating, anorexia and fullness in the right upper quadrant) are occasionally seen. With severe, longstanding heart failure, cardiac cachexia (emaciation resulting from heart disease) may develop secondary to protein-losing enteropathy and increased levels of certain cytokines, such as tumor necrosis factor. Cardiac cachexia may mimic the cachexia seen in patients with disseminated malignant disease.

Confusion and altered mental status may occur because of decreased cerebral perfusion or cardiac cirrhosis. In heart failure, cirrhosis develops secondary to chronic passive congestion of the liver.

The patient should be asked about previous chest pain or myocardial infarction because coronary artery disease is responsible for up to 75 percent of cases of heart failure with decreased left ventricular function. 13 A history of myocardial infarction has a better combination of sensitivity, specificity and positive and negative predictive value for heart failure compared with other symptoms or aspects of the medical history. 14

It is important to identify a history of hypertension, in that high blood pressure is the second most frequent cause of heart failure. Information about other possible causes of heart failure should also be sought ( Table 2 ) .

Once heart failure is suspected, the functional class of the patient should be determined. The New York Heart Association (NYHA) functional classification of congestive heart failure is presented in Table 3 . 15

Physical Examination

A complete physical examination is the second component in the diagnosis of heart failure. The patient's general appearance should be assessed for evidence of resting dyspnea, cyanosis and cachexia.

BLOOD PRESSURE AND HEART RATE

The patient's blood pressure and heart rate should be recorded. High, normal or low blood pressure may be present. The prognosis is worse for patients who present with a systolic blood pressure of less than 90 to 100 mm Hg when not receiving medication (angiotensin-converting enzyme [ACE] inhibitors, beta blockers or duretics). 16 Tachycardia may be a sign of heart failure, especially in the decompensated state. The heart rate increases as one of the compensatory ways of maintaining adequate cardiac output. A decrease in the resting heart rate with medical therapy can be used as a surrogate marker for treatment efficacy. A weak, thready pulse and pulsus alternans are associated with decreased left ventricular function. The patient should also be monitored for evidence of periodic breathing (Cheyne-Stokes respiration).

JUGULAR VENOUS DISTENTION

Jugular venous distention is assessed while the patient is supine with the upper body at a 45-degree angle from the horizontal plane. The top of the waveform of the internal jugular venous pulsation determines the height of the venous distention. An imaginary horizontal line (parallel to the floor) is then drawn from this level to above the sternal angle. A height of more than 4 to 5 cm from the sternal angle to this imaginary line is consistent with elevated venous pressure ( Figure 1 ) .

Elevated jugular venous pressure is a specific (90 percent) but not sensitive (30 percent) sign of elevated left ventricular filling. The reproducibility of the jugular venous distention assessment is low. 17

POINT OF MAXIMAL IMPULSE

The point of maximal impulse of the left ventricle is usually located in the midclavicular line at the fifth intercostal space. With the patient in a sitting position, the physician uses fingertips to identify this point. Cardiomegaly usually displaces the cardiac impulse laterally and downward.

At times, the point of maximal impulse may be difficult to locate and therefore loses sensitivity (66 percent). Yet the location of this point remains a specific indicator (96 percent) for evaluating the size of the heart. 14

THIRD AND FOURTH HEART SOUNDS

A double apical impulse can represent an auscultated third heart sound (S 3 ). Just as with the displaced point of maximal impulse, a third heart sound is not sensitive (24 percent) for heart failure, but it is highly specific (99 percent). 14 Patients with heart failure and left ventricular hypertrophy can also have a fourth heart sound (S 4 ). The physician should be alert for murmurs, which can provide information about the cause of heart disease and also aid in the selection of therapy.

PULMONARY EXAMINATION

Physical examination of the lungs may reveal rales and pleural effusions. Despite the presence of pulmonary congestion, rales can be absent because of increased lymphatic drainage and compensatory changes in the perivascular structures that have occurred over time. Wheezing may be the sole manifestation of pulmonary congestion. Frequently, asthma is erroneously diagnosed in patients who actually have heart failure.

LIVER SIZE AND HEPATOJUGULAR REFLUX

The key component of the abdominal examination is the evaluation of liver size. Hepatomegaly may occur because of right-sided heart failure and venous congestion.

The hepatojugular reflux can be a useful test in patients with right-sided heart failure. This test should be performed while the patient is lying down with the upper body at a 45-degree angle from the horizontal plane. The patient keeps the mouth open and breathes normally to prevent Valsalva's maneuver, which can give a false-positive test. Moderate pressure is then applied over the middle of the abdomen for 30 to 60 seconds. Hepatojugular reflux occurs if the height of the neck veins increases by at least 3 cm and the increase is maintained throughout the compression period. 18

LOWER EXTREMITY EDEMA

Lower extremity edema, a common sign of heart failure, is usually detected when the extracellular volume exceeds 5 L. The edema may be accompanied by stasis dermatitis, an often chronic, usually eczematous condition characterized by edema, hyperpigmentation and, commonly, ulceration.

VALSALVA'S MANEUVER

Valsalva's maneuver is rarely used in the evaluation of patients with heart failure. Yet this test is simple to perform and carries one of the best combinations of specificity (91 percent) and sensitivity (69 percent) for the detection of left ventricular systolic and diastolic dysfunction in patients with heart failure. 19 , 20

Valsalva's maneuver is performed with the blood pressure cuff inflated 15 mm Hg over the systolic blood pressure. While the physician auscultates over the brachial artery, the patient is asked to perform a forced expiratory effort against a closed airway (the Valsalva's maneuver).

A normal response would be an initial rise in systolic blood pressure at the onset of straining (phase I) with Korotkoff's sounds heard ( Figure 2 ) . While the maneuver is maintained (phase II), a decrease in the blood pressure occurs with loss of Korotkoff's sounds. Release of the maneuver (phase III) is followed by an overshoot of blood pressure and the reappearance of heart sounds (phase IV). Abnormal responses occurring in patients with heart failure are maintenance of beats throughout Valsalva's maneuver (square wave) or lack of reappearance of Korotkoff's sounds after release of the maneuver (absent overshoot).

DIAGNOSTIC CHALLENGES

Diagnosing heart failure in elderly patients may be particularly challenging because of the atypical presentations in this age group. Anorexia, generalized weakness and fatigue are often the predominant symptoms of heart failure in geriatric patients. Mental disturbances and anxiety are also common.

When older persons become symptomatic on exertion, they decrease their level of activity to the point of becoming relatively asymptomatic. A cycle of symptoms on exertion and consequent decrease in activity frequently continues as the disease progresses, until the patient finally becomes symptomatic at rest (i.e., NYHA class IV).

The physical findings in older patients with heart failure may be difficult to interpret accurately. Resting tachycardia is uncommon, and pulse contour abnormalities are difficult to assess secondary to peripheral arteriosclerotic changes. At times, auscultatory findings on the lung examination are atypical because of concomitant pulmonary disease. 21

Laboratory Findings

Most patients with heart failure have normal electrolyte levels. However, extended use of kaliuretic diuretics can lead to hypokalemia, and the use of potassium-sparing diuretics and ACE inhibitors may result in hyperkalemia. Blood urea nitrogen and creatinine levels may become elevated, reflecting prerenal azotemia. Hyponatremia may be present in patients with advanced heart failure.

When the liver becomes congested, serum transaminase and bilirubin levels may become elevated, and jaundice may be present. With chronic congestive hepatomegaly, cardiac cirrhosis may occur and cause hypoalbuminemia, hypoglycemia and an increased prothrombin time.

The prognosis is worse in patients with hyponatremia or abnormalities secondary to congested hepatomegaly.

Anemia may contribute to worsening heart failure. When severe, anemia may even cause heart failure.

In all patients with newly diagnosed heart failure, thyroid function tests should be performed to rule out hypothyroidism or hyperthyroidism.

It may soon be possible to routinely obtain serum measurements of two plasma enzymes secreted by the overloaded heart. Plasma atrial natriuretic peptide is secreted in response to increased intra-atrial pressure, and brain natriuretic peptide (BNP) is secreted by the failing ventricle. Levels of these enzymes, but specifically BNP, are elevated in patients with dyspnea resulting from heart failure. In one study, elevated BNP levels had more than a 90 percent specificity and sensitivity for heart failure. 22

Diagnostic Tests

Electrocardiography.

An electrocardiogram (ECG) should be obtained in all patients who present with heart failure. No specific ECG feature is indicative of heart failure, but atrial and ventricular arrhythmias are common findings. For example, atrial fibrillation is present in 25 percent of patients with cardiomyopathy, especially elderly patients with advanced heart failure. 23 The prognosis is worse for patients with atrial fibrillation, atrial or ventricular tachycardia, or left bundle branch block. 16 , 24

Low voltage on the ECG in association with conduction disturbances may suggest the presence of amyloidosis.

CHEST RADIOGRAPHY

Chest radiographs can be helpful in the diagnosis of heart failure. Cardiomegaly is usually manifested by the presence of an increased cardiothoracic ratio (greater than 0.50) on a posteroanterior view. However, patients with predominantly diastolic dysfunction may have normal heart size, one of the distinguishing markers of diastolic versus systolic dysfunction. Right ventricular enlargement is suggested by the loss of free space between the cardiac silhouette and the sternum on a lateral view.

Signs of increased pulmonary venous pressure seen on chest radiographs may progress from redistribution of blood flow from the bases of the lungs to the apices to linear densities reflecting interstitial edema (Kerley's lines) to a hazy appearance concentrated mostly around the hila of the mediastinum and presenting a butterfly pattern.

Chest radiographs are also helpful in detecting pleural effusion secondary to heart failure.

ECHOCARDIOGRAPHY

Transthoracic two-dimensional echocardiography with Doppler flow studies is highly recommended for all patients with heart failure. 25 This test helps in the assessment of left ventricular size, mass and function.

The ejection fraction can be calculated by several methods, including visual estimation, which has good correlation with ejection fractions obtained by angiography 26 or radionuclide cineangiography. 27 Regional wall motion and valvular integrity can also be evaluated.

Transesophageal echocardiography offers higher quality images than transthoracic studies. However, this technique is invasive and is best reserved for use when the quality of the two-dimensional echocardiogram is unacceptable.

ANGIOGRAPHY

Radionuclide angiography is another non-invasive method for assessing systolic and diastolic function. This imaging technique is used when two-dimensional echocardiography is not diagnostic because adequate images could not be obtained or the findings do not agree with the clinical picture. Radionuclide angiography provides a reliable and quantitative measurement of the left ventricular ejection fraction and the regional wall motion. However, ectopic activity and atrial fibrillation adversely affect the accuracy of its measurements. 28

Left ventricular angiography can be used to assess the ejection fraction, the left ventricular volume and the severity of valvular regurgitation or stenosis. In addition, detailed measurements of ventricular filling pressures and indices of left ventricular diastolic relaxation rate can be helpful in confirming diastolic dysfunction.

OTHER TECHNIQUES

Magnetic resonance imaging (MRI) 29 and ultrafast or cine computed tomography (CT) 30 can measure the ejection fraction and assess regional wall motion. However, assessment of cardiac function using these studies is only performed in a limited number of centers, and the superiority of the studies to echocardiography and angiography has not been proved.

Sometimes coronary artery disease must be excluded as a causal factor in patients with heart failure. Cardiac catheterization and coronary angiography should be strongly considered in all patients with heart failure and angina who are candidates for interventional procedures. In patients with known coronary artery disease and heart failure but no angina, coronary arteriography or noninvasive testing (i.e., a thallium stress test or stress echocardiogram), followed by coronary arteriography in those patients with ischemia, should be considered. The intensity of the search for ischemic heart disease in patients with heart disease depends on the patient's probability of having coronary artery disease.

If imaging techniques cannot confirm the cause of cardiac dysfunction, an endomyocardial biopsy may provide important information in patients receiving cardiotoxic drugs and in patients suspected of having infectious (i.e., acute or chronic viral myocarditis), genetic or systemic diseases with possible cardiac involvement. 25 However, the diagnostic yield of this procedure is typically less than 10 percent. 31

Systolic vs. Diastolic Dysfunction

As many as 40 percent of patients with clinical heart failure have diastolic dysfunction with normal systolic function. 32 In addition, many patients with systolic dysfunction have elements of diastolic dysfunction. With systolic dysfunction, the pumping ability of the ventricle is impaired. With diastolic dysfunction, ventricular filling is defective.

Ventricular diastolic function depends on the pressure-to-volume relationship in the left ventricle. Decreased compliance of the left ventricular wall leads to a higher pressure for a given diastolic volume. The end result is impaired ventricular filling, inappropriately elevated left atrial and pulmonary venous pressure, and decreased ability to increase stoke volume. These dysfunctions lead to the clinical syndrome of heart failure.

Findings suggestive of diastolic dysfunction on the two-dimensional echocardiogram are left ventricular hypertrophy, a dilated left atrium, a normal or nearly normal ejection fraction and reversal of the normal pattern of flow velocity (measured by Doppler flow studies) across the mitral valve ( Figures 3 and 4 ) .

Differentiating between systolic and diastolic dysfunction is essential because their long-term treatments are different 33 ( Table 4 34 and Figure 5 ) . The treatments of choice in patients with systolic dysfunction are ACE inhibitors, digoxin, diuretics and beta blockers. In patients with diastolic dysfunction, the cornerstones of treatment depend on the underlying cause. Beta blockers and calcium channel blockers are frequently used when diastolic dysfunction is secondary to ischemia or hypertension.

The history, physical examination, ECG and chest radiographs provide some clues that can be helpful in differentiating systolic and diastolic dysfunction. For example, predominantly systolic dysfunction is suggested by a history of myocardial infarction and younger patient age, a displaced point of maximal impulse and an S 3 gallop on the physical examination, the presence of Q waves on the ECG and the finding of cardiomegaly on the chest radiograph. In contrast, diastolic dysfunction is suggested by a history of hypertension and older patient age, a sustained point of maximal impulse and an S 4 gallop on the physical examination, left ventricular hypertrophy on the ECG and a normal-sized heart on the chest radiograph. 36 However, the findings can overlap considerably, and echocardiography of the heart is usually necessary.

Heart and stroke statistical update. Dallas: American Heart Association, 1997.

Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J. 1991;121(3 pt 1):951-7.

Heart failure: evaluation and care of patients with left ventricular systolic dysfunction Rockville, Md: US Dept of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1994; AHCPR publication no. 94-0612.

Colucci W, Braunwald E. Pathophysiology of heart failure. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: Saunders, 1997:394–420.

McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971;285:1441-6.

Harlan WR, Oberman A, Grimm R, Rosati RA. Chronic congestive heart failure in coronary artery disease: clinical criteria. Ann Intern Med. 1977;86:133-8.

Carlson KJ, Lee DC, Goroll AH, Leahy M, Johnson RA. An analysis of physicians' reasons for prescribing long-term digitalis therapy in outpatients. J Chron Dis. 1985;38:733-9.

Marantz PR, Tobin JN, Wassertheil-Smoller S, Steingart RM, Wexler JP, Budner N, et al. The relationship between left ventricular systolic function and congestive heart failure diagnosed by clinical criteria. Circulation. 1988;77:607-12.

Redfield MM. Diagnosis and evaluation of heart failure. In: Murphy J, ed. Mayo Clinic cardiology review. Armonk, N.Y.: Futura, 1997:597–611.

Remmes J, Miettinen H, Reunanen A, Pyorala K. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J. 1991;12:315-21.

Wheeldon NM, MacDonald TM, Flucker CJ, McKendrick AD, McDevitt DG, Struthers AD. Echocardiography in chronic heart failure in the community. Q J Med. 1993;86:17-23.

Braunwald E, Grossman W. Clinical aspects of heart failure. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: Saunders, 1997:445–70.

Studies of left ventricular dysfunction (SOLVD)—rationale, design and methods: two trials that evaluate the effect of enalapril in patients with reduced ejection fraction. Am J Cardiol. 1990;66:315-22 1990;66:1026]

Davie AP, Francis CM, Caruana L, Sutherland GR, McMurray JJ. Assessing diagnosis in heart failure: which features are any use?. Q J Med. 1997;90:335-9.

Criteria Committee, New York Heart Association. Dieases of the heart and blood vessels. Nomenclature and criteria for diagnosis. 6th ed. Boston: Little, Brown, 1964:114.

Cleland JG, Dargie HJ, Ford I. Mortality in heart failure: clinical variables of prognostic value. Br Heart J. 1987;58:572-82.

Stevenson LW, Perloff JK. The limited reliability of the physical signs for estimating hemodynamics in chronic heart failure. JAMA. 1989;261:884-8.

Ducas J, Magder S, McGregor M. Validity of hepatojugular reflux as a clinical test for congestive heart failure. Am J Cardiol. 1983;52:1299-303.

Zema MJ, Masters AP, Margouleff D. Dyspnea: the heart or the lungs? Differentiation at bedside by use of the simple Valsalva maneuver. Chest. 1984;85:59-64.

Zema MJ, Restivo B, Sos T, Sniderman KW, Kline S. Left ventricular dysfunction—bedside Valsalva manoeuvre. Br Heart J. 1980;44:560-9.

Tresch DD. The clinical diagnosis of heart failure in older patients. J Am Geriatr Soc. 1997;45:1128-33.

Davis M, Espiner E, Richards G, Billings J, Town I, Neill A, et al. Plasma brain natriuretic peptide in assessment of acute dyspnoea. Lancet. 1994;343:440-4.

Wenger NK, Abelman WH, Roberts WC. Cardiomyopathy and specific heart muscle disease. In: Hurst JW, ed. The heart, arteries and veins. 7th ed. New York: McGraw-Hill, 1990:1278–1347.

Middlekauff HR, Stevenson WG, Stevenson LW. Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients. Circulation. 1991;84:40-8.

Guidelines for the evaluation and management of heart failure. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure). J Am Coll Cardiol. 1995;26:1376-98.

Mueller X, Stauffer JC, Jaussi A, Goy JJ, Kappenberger L. Subjective visual echocardiographic estimate of left ventricular ejection fractions as an alternative to conventional echocardiographic methods: comparison with contrast angiography. Clin Cardiol. 1991;14:898-902.

Amico AF, Lichtenberg GS, Reisner SA, Stone CK, Schwartz RG, Meltzer RS. Superiority of visual versus computerized echocardiographic estimation of radionuclide left ventricular ejection fraction. Am Heart J. 1989;118:1259-65.

Rumberger JA, Behrenbeck T, Bell MR, Breem JF, Johnston DL, Holmes DR, et al. Determination of ventricular ejection fraction: a comparison of available imaging methods. The Cardiovascular Imaging Working Group. Mayo Clin Proc. 1997;72:860-70.

Stratemeier EJ, Thompson R, Brady TJ, Miller SW, Saini S, Wisner GL, et al. Ejection fraction determination by MR imaging: comparison with left ventricular angiography. Radiology. 1986;158:775-7.

Rumberger JA, Sheedy PF, Breen JF. Use of ultrafast (cine) x-ray computed tomography in cardiac and cardiovascular imaging. In: Giuliani ER, Gersh BJ, McGoom MD, Hayes DL, Schaff HV, eds. Mayo Clinic practice of cardiology. 3d ed. St. Louis: Mosby, 1996:303–24.

Chow LC, Dittrich HC, Shabetai R. Endomyocardial biopsy in patients with unexplained congestive heart failure. Ann Intern Med. 1988;109:535-9.

Soufer R, Wohlgelernter D, Vita NA, Amuchestegui M, Sostman HD, Berger HJ, et al. Intact systolic left ventricular function in clinical congestive heart failure. Am J Cardiol. 1984;55:1032-6.

Coodley E. Newer drug therapy for congestive heart failure. Arch Intern Med. 1999;159:1177-83.

Young JB. Assessment of heart failure. In: Brauwnwald E. Atlas of heart disease. Vol 4. Philadelphia: Current Medicine, 1995:7.1–7.2.

Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:809-17.

Goldsmith SR, Dick C. Differentiating systolic from diastolic heart failure: pathophysiologic and therapeutic considerations. Am J Med. 1993;95:645-55.

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Treating Patients with Atypical Cardiac Presentations

This clinical review feature article is presented in conjunction with the Department of Emergency Medicine Education at the University of Texas Southwestern Medical Center, Dallas.

Glossary Terms ACE inhibitor: A medication that inhibits the angiotensin-converting enzyme. The result is the relaxation of smooth muscles, which can be found in arteries and arterioles, and lowering of blood pressure. BiPAP: Bilevel positive pressure. Comorbidities: Two or more coexisting medical conditions. Cortical failures: Failure of cortical synapses that can be associated with stroke. CPAP: Continuous positive airway pressure. Hydrostatic pressure: A capillary pressure exerted against vessel walls. This pressure is driven from cardiac contractions (or blood pressure) and forces some water out of the plasma through the capillary wall and into the interstitial space. Hypokalemia: Lower than normal potassium levels. Neuropathies: A functional disturbance and/or pathological change in the peripheral nervous system. Orthopnea: Difficulty breathing when lying in a supine position. Prodromal symptoms: A symptom indicating an onset of a disease. Learning Objectives

Discuss the contributing factors for a patient experiencing an atypical cardiac event.
Describe various atypical presentations for patients who are suffering a myocardial infarction.
Describe the currently accepted treatment for a patient suffering a myocardial infarction.
Describe the basic pathophysiology of congestive heart failure (CHF) and discuss recent changes in prehospital therapy.
Recognize the signs and symptoms of cardiogenic shock and currently

You’re called to the residence of an 85-year-old female with mild dyspnea that increases with exertion. She’s very weak and is accompanied by her daughter, who reports that she’s been taking care of her. The daughter reports changes in mentation and increasing weakness over the past three days. She reports no fever, nausea, vomiting, diarrhea, chest pain or other remarkable symptoms.

The patient has a history of congestive heart failure (CHF) and dementia. Vitals include BP of 182/98, HR 104, RR 18 and SpO2 90% on room air. Auscultation of the lungs reveals coarse and fine crackles over the perihilar regions of each lung and the bases. You also hear mild bronchial wheezing. ECG reveals sinus tachycardia with a right bundle branch block. The patient appears to be in moderate distress, and you believe she’s experiencing an acute exacerbation of her CHF. You begin to treat the patient with oxygen at 15 l/min via nonrebreather mask, sublingual nitroglycerin, morphine sulfate and furosemide. Several minutes later, the patient appears to have decreased respiratory distress, and her crackles become fainter. She is delivered to the local emergency department (ED) without additional issues. Hours later, you return to the same ED with another patient only to find that your patient didn’t have CHF and has since been intubated and admitted to the ICU. Her prognosis looks poor. You’re informed that she had severe pneumonia affecting both lungs.

Cardiac Misdiagnoses & Their Causes Between 2—27% of cardiac patients are misdiagnosed in EDs in the developed world. These misdiagnoses lead to severe complications, one in four of which are lethal.1 In fact, diagnosing a myocardial infarction (MI) in the elderly can be so difficult that in one study, only half of the elderly who had died of an MI had been correctly diagnosed before their deaths.2 The main factors behind these misdiagnoses are lack of the typical presentation of chest pain as a symptom and lack of ST elevation. The risk of death in cardiac patients who don’t experience chest pain is three times higher than in patients experiencing it. The one-year mortality of patients with a “silent MI” is double.1 Studies reveal that 43% of women, 43.7% of patients older than 65 and the majority of those older than 85 didn’t experience chest pain during an MI.2-4 Factors contributing to an atypical cardiac presentation involve advanced age, female gender, underlying disease and even the patient’s race. One study found that Asians are 64—69% more likely than Caucasians to present atypically. These patients are 70% less likely to seek emergency care in a timely manner (within three hours of onset) and are less likely to have a favorable outcome.5 Similarly, women and those older than 85 tend to delay seeking emergency care.6 Women in general, as well as our older patients, often have atypical symptoms that lead them to delay seeking care or lead health-care personnel down the wrong clinical pathway, resulting in greater delays in diagnosis and treatment. These delays in treatment are significant; the 30-day mortality of acute myocardial infarction (AMI) in patients who arrived at the hospital within one hour of onset is 5.6%, while those patients who delayed treatment for more than four hours have an 8.6% jump in mortality rate.6 Delays cost many lives and significantly contribute to poor outcomes.

AMI Acute myocardial infarction (AMI) is often overlooked or misdiagnosed. Those who present atypically often have “anginal equivalent complaints” that providers should be aware of. These include epigastric discomfort, general weakness and other nonspecific complaints. In fact, only 25% of the elderly present with the classic triad of chest pain, ECG abnormalities and serum markers corresponding to their MIs. Nondiagnostic ECG findings are present for 50—75% of elderly patients experiencing MI.2,7 Further, certain medications (like digoxin) can alter the ST segment such that a patient won’t have ST elevation.2 Patients who have an AMI often delay going to the hospital, with 40% waiting longer than six hours past symptom onset.6 This means that the patient has potentially experienced an expanded myocardial injury during this period. EMS providers must attempt to compensate for delay by quickly recognizing the AMI, treating it appropriately and transporting the patient to the appropriate facility. Neuropathies of the autonomic nervous system, cortical failure, damage to cardiac sensory nerves caused by heart disease, increased pain threshold and any comorbidities, including dementia, all contribute to atypical presentations. The most common atypical presentation of the silent AMI is dyspnea. Other likely presentations include general weakness, fatigue, cold sweats or dizziness. Providers also shouldn’t dismiss a syncopal episode as the primary symptom of an MI, as this occurs in 3% of elderly patients and is correlated with high mortality.4 A common site for the referred pain in patients with cardiac ischemia who aren’t experiencing chest pain is the craniofacial area (38—60%). For 6% of patients, this was the only complaint. The most common location is the upper throat (82%). This is followed by the mandible (45%) or the left temporomandibular joint/ear (18%). After craniofacial pain, cardiac patients tend to have referred pain in the left arm or shoulder (20%), followed by the stomach or back (12%).1 High-flow oxygen, 12-lead ECG monitoring, pulse oximetry and capnography should be promptly initiated. Aspirin, a nitrate and morphine should be given as indicated. Fentanyl or heparin are also commonly indicated. Hypotension potentially indicates worsening of the hypoperfusion of cardiac tissues, and a hypotensive MI patient should be transported immediately. Beta blockers and ACE inhibitors are important components in treating an MI and should be utilized when in the provider’s scope of practice. Fibrinolytic treatment is beneficial in the prehospital setting, and patients who are given prehospital fibrinolytics are much more likely to receive them in the two-hour period following symptom onset.8 Fibrinolytics increase the risk of hemorrhage, especially in the elderly, but are shown to be more beneficial than withholding their use in appropriate patients.2 Prehospital providers should keep in mind the goals of door-to-needle fibrinolytic therapy within 30 minutes and door-to-balloon inflation (percutaneous coronary intervention) of 90 minutes.9 In one study of women with AMI, 95% reported prodromal symptoms at least one month before their AMI. The most common symptom was unusual fatigue, which occurred in 70.7% of women. This was followed by sleep disturbances (47.8%), increased dyspnea (42.1%), the feeling of indigestion (39%), anxiety (36%), chest discomfort (30%) and increased confusion or nausea (each as the only symptom in 3% of the elderly).3 These vague symptoms are often benign taken alone but should be taken into consideration when making a field diagnosis.

Congestive Heart Failure CHF is one of the most commonly encountered cardiac emergencies in the prehospital setting. It affects 3 million people in the U.S. every year and is the most common cause of hospitalization in the elderly.10 Typically, pulmonary edema is associated with hypertension or left ventricular damage of such a nature that fluid backs up into the pulmonary system, causing an increased hydrostatic pressure that overwhelms the ability of the lymphatic system to remove the fluid. The fluid then accumulates in the alveoli, causing pulmonary edema and leading to dyspnea, orthopnea, cough, tachypnea and crackles or rales. Other symptoms associated with left-sided heart failure are diaphoresis and altered mental status as the brain becomes increasingly deprived of oxygen. Left-sided heart failure is the most common cause of right-sided (right ventricular) heart failure, which causes fluid to back up into systemic circulation. This backup leads to signs, such as peripheral edema, jugular venous distention, weight gain and tachycardia (in response to decreased cardiac output). Most CHF patients have a combination of left- and right-sided heart failure. CHF is a condition that requires careful monitoring because further deterioration of the heart’s pumping ability has the potential to lead to cardiogenic shock, a condition in which the heart can no longer meet the body’s metabolic needs. CHF is such a sensitive condition that half of all CHF patients die within five years of diagnosis.10 Prehospital treatment of CHF works toward improving oxygenation and increasing cardiac output.10 Capnography, pulse oximetry, oxygen and 12-lead ECG monitoring are indicated early on in treating these patients. However, the former gold standards of EMS treatment of CHF has changed dramatically. It had been thought that BiPAP increases the risk of AMI when used in patients with severe CHF. However, recent studies demonstrate that neither BiPAP nor CPAP contribute to a greater risk of AMI when compared to the oxygen mask.11,12 Patients with severe CHF who are placed on BiPAP and CPAP have a lower intubation rate than those on an oxygen mask. CPAP patients have greater improvement in respiratory rate, arterial pH and increased stroke volume, as well as decreased intubation rates 30 minutes into treatment. Patients who don’t require intubation have lower morbidity and shorter hospital stays than patients who require intubation.11 CPAP is becoming a standard in prehospital respiratory care and providers who have access to CPAP or BiPAP should strongly consider taking advantage of them when indicated. Another factor believed to contribute to poor outcomes in patients with CHF is morphine. CHF patients given morphine are more likely to require mechanical ventilation and have longer hospitalizations and a much greater mortality rate (13% versus 2.4% in acute decompensated heart failure).10,13 Morphine was recommended for these patients because of its effects in reducing preload and afterload as well as decreasing heart rate and anxiety.13 Many clinicians are now arguing that morphine hasn’t been proven to have a clinically beneficial effect on CHF patients, and its continued use in these situations is uncertain.13 Providers should always follow their local protocols. Diuretics, such as furosemide, are also associated with poor short-term outcomes in patients with acute CHF, which some experts believe is the result of toxicity. This leads to hypokalemia, decreased renal function and hypotension.10,12,14 Almost half of all illnesses believed to be CHF in the prehospital setting are misdiagnosed, and most are eventually discovered to be pneumonia. This creates another problem, because furosemide may be detrimental to the pneumonia patient.15 Several studies have suggested that when furosemide is given as a lower dose along with a hypertonic saline solution, the detrimental effects associated with the furosemide may be lessened.16—18 A loading dose of furosemide followed by an infusion might be less detrimental than a high-dose bolus.23 Research in this area is ongoing, and providers should follow local protocols when determining treatment. Normotensive patients without contraindications should receive 0.4 mg nitroglycerin early into treatment; hypertensive patients (systolic BP 140—180 mmHg) should receive a “stacked” dose of 0.8 mg nitroglycerin; and very hypertensive patients (systolic BP higher than 180 mmHg) should receive a stacked dose of 1.2 mg nitroglycerin.10,12 A dose of a nitrate should be repeated every three to five minutes as long as the patient is symptomatic and maintains an adequate blood pressure. Sublingual nitroglycerin is among the best options in CHF because of its speed and efficacy. However, if the patient can’t tolerate the nitrate by mouth (as in a severely dyspneic patient on CPAP) and IV is not available, topical nitrates should be considered.10 Angiotensin-converting enzyme, or ACE, inhibitors are beneficial in the treatment of CHF because they reduce afterload and cause vasodilation. Following the administration of a nitrate, an ACE inhibitor should be administered to the patient when protocols allow.9,10

Cardiogenic Shock Cardiogenic shock is a condition in which the heart is no longer able to maintain the metabolic needs of the body. It typically occurs when greater than 40% of the left ventricle is damaged, and it has a very high mortality rate even with treatment. The prehospital provider can assume that a patient is in cardiogenic shock if they have signs or symptoms of an MI along with a BP of less than 90 mmHg systolic. Altered mental status is common, as are tachydysrhythmias, especially those that are atrial in nature. A lack of peripheral pulses; cool, clammy skin; peripheral edema; and recent history of an MI are also common.9,10 Cardiogenic shock requires prompt recognition and rapid transport to a hospital with advanced cardiac capabilities in order to offer the patient the best chance of recovery. Correct any major dysrhythmias in order to eliminate the dysrhythmia as the cause of the hypotension.10 Pressor support (dopamine) should be administered, along with high-flow oxygen by mask or BVM if ventilatory support is necessary (CPAP should not be used, as it can worsen hypotension), and aspirin if indicated.10,19

Conclusion Cardiac calls are common in EMS and are often considered routine. However, the treatment of cardiac complaints is rapidly changing. As our population ages and becomes more diverse, the typical presentations are no longer typical. EMS providers should be aware of the latest trends in assessment and treatment. JEMS

Kreiner M, Okeson JP, Michelis V, et al. Craniofacial pain as the sole symptom of cardiac ischemia: A prospective multicenter study. J Am Dent Assoc. 2007;138:74—79.
Meldon SW, Ma OJ, Woolard R. Geriatric Emergency Medicine. McGraw-Hill: Upper Saddle River, N.J., 2004.
McSweeney JC, Cody M, O’Sullivan P, et al. Women’s early warning symptoms of acute myocardial infarction. Circ. 2003;108:2619—2623.
Woon VC, Lim KH. Acute Myocardial Infarction in the Elderly-the differences compared with the young. Singapore Med J. 2003;44:414—418.
King KM, Khan NA, Quan H. Ethnic variation in acute myocardial infarction presentation and access to care. Am J Cardiol. 2009;103:1368—1373.
Gurwitz JH, McLaughlin TJ, Willison DJ, et al. Delayed hospital presentation in patients who have had acute myocardial infarction. Ann Intern Med. 1997;126:652—653.
Hickey CN, Pang PS. How to evaluate the patient with syncope. Emerg Med. 2006;38:15.
Bjorklund E, Stenestrand U, Lindback J, et al. Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction. Eur Heart J. 2006;27:1146—1152.
Bledsoe BE, Porter RS, Cherry RA. Paramedic Care Principles and Practice. 3rd edition. Pearson, New York, 2009.
Bledsoe BE. Mastering CHF: Current strategies for the prehospital care of congestive heart failure. JEMS. 2003;34:60—68.
Levitt MA. A prospective, randomized trial of BiPAP in severe acute congestive heart failure. J Emerg Med. 2001;21:363—369.
Peacock WF, Fonarow GC. Society of Chest Pain Centers Recommendations for the evaluation and management of the observation stay acute heart failure patient: A report for the Society of Chest Pain Centers Acute Heart Failure Committee. Crit Pathw Cardiol. 2008;7:83—121.
Peacock WF; Hollander JE, Diercks DB; et al. Morphine and outcomes in acute decompensated heart failure: An ADHERE analysis. Emerg Med J. 2008;25:205—209.
Butler J, Forman DE, Abraham WT, et al. Relationship between heart failure treatment and development of worsening renal function among hospital patients. Am Heart J. 2004;147:193—194.
Dobson T, Jensen JL, Karim S; et al. Correlation of paramedic administration of furosemide with emergency physician diagnosis of congestive heart failure. www.jephc.com/full_article.cfm?content_id=539
Licata G, Di Pasquale P, Parrinello G, et al. Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Am Heart J. 2003;145:459—466.
Paterna S, Di Pasquale Pietro, et al. Effects of high dose furosemide and small volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Eur Journal Heart Fail. 2000;2:305—313.
Paterna S, Parrinello G, Amato P, et al. Tolerability and efficacy of high dose furosemide and small volume hypertonic saline solution in refractory congestive heart failure. Adv Ther. 1999;16:219—228.
Goss JF, Zygowiec J. Positive pressure: CPAP in the treatment of pulmonary edema. JEMS. 2006;31:48—58.

End Statement: This article originally appeared in July JEMS as “Anything but Typical.”

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Signs and symptoms of heart failure: are you asking the right questions?

Affiliation.

1 Nursing Institute at Cleveland Clinic in Cleveland, Ohio 44195, USA. [email protected]
PMID: 19940253
DOI: 10.4037/ajcc2009314

Background: Patients may not verbalize common and atypical signs and symptoms of heart failure and may not understand their association with worsening disease and treatments.

Objectives: To examine prevalence of signs and symptoms relative to demographics, care setting, and functional class.

Methods: A convenience sample of 276 patients (164 ambulatory, 112 hospitalized) with systolic heart failure completed a 1-page checklist of signs and symptoms experienced in the preceding 7 days (ambulatory) or in the 7 days before hospitalization. Demographic and medical history data were collected.

Results: Mean age was 61.6 (SD, 14.8) years, 65% were male, 58% were white, and 45% had ischemic cardiomyopathy. Hospitalized patients reported more sudden weight gain, weight loss, severe cough, low/orthostatic blood pressure, profound fatigue, decreased exercise, restlessness/confusion, irregular pulse, and palpitations (all P < .05). Patients in functional class IV reported more atypical signs and symptoms of heart failure (severe cough, nausea/vomiting, diarrhea or loss of appetite, and restlessness, confusion, or fainting, all P <or= .001). Sudden weight gain increased from 5% in functional class I to 37.5% in functional class IV (P < .001). Dyspnea occurred in all functional classes (98%-100%) and both settings (92%-100%). Profound fatigue was associated with worsening functional class (P < .001) and hospital setting (P = .001); paroxysmal nocturnal dyspnea was associated with functional class IV (P = .02) and hospital setting (P < .001).

Conclusion: Profound fatigue is more reliable than dyspnea as an indicator of functional class. Nurses must recognize atypical signs and symptoms of worsening functional class to determine clinical status and facilitate patient care decisions.

Cross-Sectional Studies
Dyspnea / diagnosis*
Dyspnea / etiology
Fatigue / diagnosis*
Fatigue / etiology
Heart Failure, Systolic / classification
Heart Failure, Systolic / diagnosis*
Heart Failure, Systolic / nursing*
Middle Aged
Outpatients
Self Report*
Severity of Illness Index*

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Current Diagnosis & Treatment Geriatrics, 3e

Chapter 16: Atypical Presentations of Illness

Michael Goldrich; Amit Shah

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General principles, defining atypical presentations.

Examples of Common Atypical Presentations
Atypical Presentations of Common Conditions
An Approach to the Older Adult with Nonspecific Symptoms
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Supplementary Content

Traditional education of clinicians hinges on typical presentations of common illnesses. The teaching of these classic presentations influences clinicians’ “illness scripts,” or preformed outlines on how a patient should present with a particular disease. Yet, what is often left out from medical training is the frequent occurrence of atypical presentations of illness in older adults. These presentations are termed atypical because they lack the usual signs and symptoms characterizing a particular condition or diagnosis. In older adults, so-called “atypical” presentations are actually quite common and can range from one-fifth to one-half of all presentations. For example, a change in behavior or functional ability is often the only sign of a new, potentially serious illness. Failure to recognize atypical presentations may lead to worse outcomes, missed diagnoses, and missed opportunities for treatment of common conditions in older patients. As in other illnesses, some of the reasons for delayed recognition may also be caused by social factors, such as lack of caregiver, lack of transportation, the fear of being hospitalized, and the risk of losing independence.

The lack of specificity of some atypical presentations, however, can also lead to unnecessary workups, treatments, and hospitalizations. For example, always treating the feared possibility of a bacterial infection in the setting of nonspecific symptoms can prompt improper use of antibiotics that can cause harm to the patient and create drug resistance in the long run. Awareness of atypical presentations of common diseases is fundamental to high-quality care of older adults and also offers a unique opportunity to introduce key geriatric principles to trainees at all levels. Furthermore, identifying atypical presentations of common diseases in the older adult is a recommended minimum geriatrics competency for medical students, internal medicine residents, family medicine residents, surgery residents, and geriatric medicine fellows.

One definition of an atypical presentation of illness in an older person is: when an older adult presents with a disease state that is missing some of the traditional core features of the illness usually seen in younger patients . Atypical presentations usually include one of three features: (1) vague presentation of illness, (2) altered presentation of illness, or (3) nonpresentation of illness (ie, underreporting).

IDENTIFYING PATIENTS AT RISK

The prevalence of atypical presentation of illness in older adults increases with age. With the aging of the world’s population, atypical presentations of illness will represent an increasingly large proportion of illness presentations. The most common risk factors include:

Increasing age (especially age 85 years or older)

Multiple medical conditions (“multimorbidity”)

Multiple medications (or “polypharmacy”)

Cognitive impairment

Residing in a care institution or functional dependence

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Heart Health Matters: A Woman’s Guide to Preventing Cardiovascular Disease

June 7, 2024

Heart health is a critical aspect of overall wellness, yet it often receives less attention than it deserves, especially among women. Cardiovascular disease remains a leading cause of mortality for women, partly due to the under-recognition of symptoms and risk factors. This blog aims to shed light on the unique aspects of women’s heart health, the importance of recognizing symptoms, and proactive steps for maintaining a healthy heart.

Recognizing Symptoms in Women’s Heart Health

Dr. Sepideh Darbandi , a popular cardiologist at the Mason City Clinic, highlights the unique presentation of heart disease in women. She explains, “Unfortunately, cardiovascular disease remains a leading cause of mortality. One of the main reasons for that, I believe, is just under-recognition of symptoms, not knowing what to watch out for, what is concerning, and when to seek care.” Women often experience atypical and uncommon symptoms, which can delay diagnosis and treatment.

While chest pain and shortness of breath are common heart attack symptoms in both men and women, women may also experience more subtle signs such as fatigue, nausea, or simple shortness of breath. These symptoms can often be mistaken for less serious conditions, which is why awareness and education are crucial.

Risk Factors for Heart Disease in Women

Understanding and managing risk factors is essential for preventing heart disease. Key risk factors include hypertension, diabetes, smoking, family history of coronary heart disease, and conditions like sleep apnea. Dr. Darbandi emphasizes the importance of regular medical care, saying, “These women certainly need to seek medical care, appointments with their primary care physicians, and seeing a cardiologist specialist to further discuss the risks of developing heart disease.”

Smoking cessation, blood pressure control, and managing conditions like diabetes and sleep apnea are vital steps in reducing the risk of heart disease. Women should actively engage with healthcare providers to monitor and manage these risk factors effectively.

Lifestyle Changes for Better Heart Health

Adopting a heart-healthy lifestyle is a proactive approach to preventing cardiovascular disease. Dr. Darbandi advises against greasy and fast foods, recommending a diet rich in seafood, lean proteins like chicken, and plenty of vegetables. She states, “Anything that you can get in the drive-through, probably not too good for you.”

Physical activity also plays a significant role in maintaining heart health. The general recommendation is at least 30 minutes of physical activity, such as walking, totaling up to 150 minutes a week. Regular exercise helps in managing weight, reducing blood pressure, and improving overall cardiovascular health.

The Role of Healthcare Providers

Healthcare providers play a crucial role in managing women’s heart health. Dr. Darbandi shares, “What I love the most about taking care of patients is being able to make that impact in someone’s life, being able to answer that question that has been bothering them and not giving them sleep at night kind of thing.” Establishing a strong patient-provider relationship ensures continuity of care and a better understanding of individual health needs.

The Emotional Impact of Heart Health

Heart disease not only affects physical health but also emotional well-being. The vulnerability associated with heart disease can be overwhelming. Dr. Darbandi finds it fulfilling to support her patients through these challenges, highlighting the importance of compassionate care in managing heart health.

Proactive Steps for Heart Health

Recognize Symptoms : Be aware of atypical symptoms like fatigue, nausea, and shortness of breath. Seek medical advice if these symptoms occur.
Manage Risk Factors : Regular check-ups, blood pressure control, smoking cessation, and managing diabetes and sleep apnea are critical.
Adopt a Heart-Healthy Diet : Avoid greasy and fast foods. Opt for seafood, lean proteins, and plenty of vegetables.
Stay Physically Active : Aim for at least 30 minutes of physical activity daily, totaling 150 minutes a week.
Build a Strong Healthcare Relationship : Regular consultations with healthcare providers ensure better management and understanding of heart health.

Women’s heart health requires attention and proactive management. By recognizing symptoms, managing risk factors, adopting a healthy lifestyle, and maintaining strong healthcare relationships, women can significantly reduce their risk of heart disease. Dr. Darbandi’s insights emphasize the importance of awareness and preventive care in ensuring a healthy heart.

For a deeper understanding of women’s heart health, watch Dr. Darbandi discuss this topic in detail in the video [ Dr. Darbandi – Meet The Doctor (Women’s Heart Heath) ].

By implementing these strategies, women can take control of their heart health and lead healthier, longer lives. Let’s prioritize heart health and make informed choices for a better future.

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Open access
Published: 01 June 2024

Blood pressure and heart failure: focused on treatment

Kyeong-Hyeon Chun 1 &
Seok-Min Kang ORCID: orcid.org/0000-0001-9856-9227 2

Clinical Hypertension volume 30 , Article number: 15 ( 2024 ) Cite this article

196 Accesses

Metrics details

Heart failure (HF) remains a significant global health burden, and hypertension is known to be the primary contributor to its development. Although aggressive hypertension treatment can prevent heart changes in at-risk patients, determining the optimal blood pressure (BP) targets in cases diagnosed with HF is challenging owing to insufficient evidence. Notably, hypertension is more strongly associated with HF with preserved ejection fraction than with HF with reduced ejection fraction. Patients with acute hypertensive HF exhibit sudden symptoms of acute HF, especially those manifested with severely high BP; however, no specific vasodilator therapy has proven beneficial for this type of acute HF. Since the majority of medications used to treat HF contribute to lowering BP, and BP remains one of the most important hemodynamic markers, targeted BP management is very concerned in treatment strategies. However, no concrete guidelines exist, prompting a trend towards optimizing therapies to within tolerable ranges, rather than setting explicit BP goals. This review discusses the connection between BP and HF, explores its pathophysiology through clinical studies, and addresses its clinical significance and treatment targets.

Heart failure (HF) remains a major public health burden, with a rapidly increasing global prevalence. In the United States, more than 5 million people aged ≥20 years are affected by HF [ 1 ], and this number is expected to increase by 46%, resulting in an estimated 8 million Americans with HF in 2030 [ 2 ]. Hypertension is one of the most frequent comorbidities [ 3 ], playing a pivotal role in the development of HF [ 4 ]. In the Framingham Heart Study, hypertension progressed to HF in 91% of patients > 20 years of age, with a doubling and tripling of the risk of HF in male and female hypertensive patients, respectively [ 5 , 6 ]. Chronic hypertension causes functional and structural changes in the heart, culminating in HF and further increasing the rate of mortality and morbidity [ 7 ]. Intensive treatment of hypertension can prevent and reverse myocardial changes in patients at risk of HF; however, defining optimal blood pressure (BP) targets for patients who have already developed HF is challenging owing to a lack of evidence.

Currently, HF is classified depending on the left ventricular ejection fraction (LVEF), with LVEF ≤40% defined as HF with reduced ejection fraction (HFrEF) and LVEF ≥50% as HF with preserved ejection fraction (HFpEF) [ 8 ]. In addition, if the LVEF is between 41 and 49%, the definition of HF with mildly reduced ejection fraction (HFmrEF) is commonly used in a dynamic trajectory to denote improvement from or deterioration to HFrEF [ 9 ]. HFmrEF occupies a spectrum between HFrEF and HFpEF, exhibiting the characteristics of both. However, this classification system is often ambiguous [ 10 ]. In the present review, rather than focusing on this detailed classification of LVEF, we focus on the classical phenotypes of HFrEF and HFpEF (implicitly including the concept of HFmrEF) and their association with BP from a more comprehensive perspective.

Development of hypertensive heart disease and HF

Traditionally, the development and progression of HF in hypertensive patients has been classified into four stages: (1) isolated left ventricular (LV) diastolic dysfunction without LV hypertrophy; (2) LV diastolic dysfunction with concentric LV hypertrophy; (3) clinical HFpEF accompanied by pulmonary edema; and (4) dilated cardiac chambers with HFrEF [ 6 ]. These stages suggest that diastolic dysfunction is an early phenomenon, and hypertension-induced LV hypertrophy leads to remodeling of the left atrium and ventricle, ultimately resulting in advanced diastolic and systolic dysfunction.

As reviewed in the article by Messerli et al. [ 6 ], hypertensive heart disease plays a pivotal role in the pathophysiology of HF through a sequential and intricate process. Initially, the LV responds to elevated BP by adapting to the hemodynamic wall stress, which results in pressure overload. This adaptation involves the thickening of the LV wall and an increase in LV mass, resulting in concentric LV hypertrophy. During this phase, the initial manifestation of cardiac dysfunction is LV diastolic dysfunction. With a persistent pressure overload, diastolic dysfunction progresses, ultimately leading to the onset of HFpEF. In the advanced stages of hypertensive heart disease, typically due to prolonged exposure to pressure overload with or without concurrent myocardial ischemia, the condition evolves into a dilated LV dimension. The final stage is characterized by reduced LVEF and development of HFrEF.

However, HFrEF and HFpEF should be considered from a slightly different perspective than that presented by Messerli et al. [ 6 ]. If HFrEF and HFpEF are considered part of a unified disease spectrum, they may be expected to respond similarly to HF treatment. However, numerous medications that have demonstrated clear improvements in HFrEF have not shown comparable beneficial effects on HFpEF [ 11 ]. Angiotensin receptor blockers (ARBs) [ 12 ], angiotensin-converting enzyme inhibitors (ACEis) [ 13 ], β-blockers [ 14 , 15 ], and mineralocorticoid receptor antagonists (MRAs) [ 16 ], all of which are also used as antihypertensive drugs, have failed to show clinically significant prognostic improvements in HFpEF, unlike in HFrEF. These differences were also evident in epidemiological studies. For example, a Japanese chronic HF registry-based study showed that most patients with HFpEF and nearly half of those with HFrEF remained in their respective categories throughout a 3-year follow-up period [ 10 ]. A study consisting of 3480 consecutive Japanese patients with HF showed that HFpEF transitioned to HFrEF in only 4% of them after 3 years, whereas HFrEF at registration transitioned to HFpEF and HFmrEF in 26 and 21% of patients, respectively, at 3 years, suggesting reverse remodeling after treatment [ 10 ]. These findings further support the idea that HFpEF and HFrEF are distinct syndromes with fundamental pathophysiological differences and etiologies. Similarly, in another long-term longitudinal study of ambulatory HFpEF patients, LVEF remained ≥50% in most patients with HFpEF for 11 years, and only 1.6% of patients evolved to LVEF < 50% [ 17 ]. Therefore, approaching HFrEF and HFpEF differently when examining their associations with hypertension is imperative.

Association between hypertension and HF

Hypertension is widely recognized as one of the most important risk factors of HFpEF [ 18 ]. Increased LV filling pressure and chronic myocardial remodeling due to hypertension are considered the primary mechanisms leading to the development of HFpEF [ 19 ]. Elevated systolic BP (SBP) is notably observed in patients with HFpEF, with a 3% rise in the likelihood of prevalent HFpEF for every 1 mmHg increase in SBP > 120 mmHg in an acute HF setting [ 20 ].

In terms of HFrEF, the association manifests distinctively. According to the European Society of Cardiology Heart Failure Long-Term Registry, the largest pan-European cohort of patients with real-world chronic HF in the full spectrum of LVEF, HFrEF accounts for approximately 60% of all patients in the registry [ 21 ]. This registry data showed that mean SBP tends to be lower in HFrEF than in other categories, with 121.6 ± 20.8 mmHg in HFrEF, 126.5 ± 21.1 mmHg in HFmrEF, and 130.9 ± 21.4 mmHg in HFpEF. The use of antihypertensive therapy differed notably between the HFrEF and HFpEF groups, with 56% for HFrEF and 67% for HFpEF. Regarding the underlying etiology of HF, nearly half of HFrEF cases (49%) occur due to ischemic heart disease, approximately one-third (35%) is caused by idiopathic dilated cardiomyopathy, and only 4.5% is due to hypertension itself. In contrast, HFpEF has a different etiology, with 18% of cases occurring due to hypertension, approximately a quarter due to ischemic heart disease, and 12% due to idiopathic dilated cardiomyopathy.

An analysis of the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry based on the United States population mirrors these distinctions [ 14 ]. The etiology of HF was ischemic in a higher percentage of patients with HFrEF than in those with HFpEF (54% vs. 38%, P < 0.0001), whereas the hypertensive etiology was more common in patients with HFpEF than in those with HFrEF (28% vs. 17%, P < 0.0001). Interestingly, when further stratified by LVEF, a hypertensive etiology was significantly predominant in HFpEF (LVEF, > 50%) than in HFmrEF (LVEF, 41–49%) at a rate of 31% versus 22% ( P < 0.0001). In the Korean Acute Heart Failure (KorAHF) registry, which is a prospective multicenter cohort registry including more than 5600 patients with acute heart failure from 10 tertiary hospitals in the Republic of Korea, the prevalence of hypertension was 62.2%; ischemic etiology accounted for 37.6%, and idiopathic dilated cardiomyopathy comprised 15.3% of the cases [ 22 ], which is in line with the European HF registry. When divided based on LVEF, the prevalence of hypertension was higher in patients with HFpEF (64%) than in those with HFrEF (56%).

These observations suggest that while some variability may be influenced by factors such as race, region, and specific registry characteristics, a stronger association exists between high BP and HFpEF than between high BP and HFrEF in the overall population with HF.

Hypertensive AHF

Acute HF (AHF) is caused by the acute or subacute deterioration of heart function, leading to pulmonary edema and subsequent symptoms such as dyspnea or edema. Given that these symptoms are primarily caused by volume overload, treatment strategies are based on this assumption [ 23 ]. However, a closer look reveals that the aggravating factors of HF are diverse, resulting in distinct phenotypes of AHF that necessitate more specialized treatments. These phenotypes can occur as acute exacerbation of preexisting chronic HF, or as a new onset (de novo) HF. Concerning the relationship between BP and AHF, lowering the ventricular filling pressure plays a crucial role in AHF management, especially when hypertension is concurrently present [ 24 ].

AHF is a complex and multifaceted condition characterized by diverse etiologies, distinct pathophysiological mechanisms, varying risk profiles, and treatment responses [ 25 , 26 ]. This heterogeneity poses significant challenges when conducting randomized controlled trials aimed at comprehensively investigating AHF. In this context, we often encounter a specific form of AHF where “high BP” is clearly the cause or is strongly suspected of contributing to the pathogenesis, which is commonly referred to as “hypertensive acute heart failure (H-AHF)”. This clinical phenomenon is characterized by a dramatic improvement in clinical signs and symptoms by BP-lowering treatment, which is also the goal of treatment. In previous studies, the H-AHF has often been defined by the following two features [ 23 , 24 , 27 , 28 ]: (1) SBP ≥ 140 mmHg and (2) acute cardiogenic pulmonary edema, often with rapid onset.

Within the spectrum of AHF, approximately half of the patients may exhibit an SBP > 140 mmHg [ 29 , 30 , 31 ], although not all cases are categorized as H-AHF. H-AHF is particularly characterized by the sudden onset of symptoms, notably pulmonary edema, which distinguishes it from other forms of AHF [ 23 , 28 ]. A more obvious characteristic of H-AHF is the presence of severely elevated BP (≥160–180 mmHg), with pulmonary edema developing in a matter of hours, and no other cause of AHF except hypertension [ 24 , 31 ]. However, because of this vague definition and characterization, there is a large variation in prevalence between the registries; this phenotype is reported as 4% in the KorAHF registry [ 22 ] and approximately 11% in the European or US HF registries [ 21 , 30 , 31 ]. In particular, for HFrEF, hypertensive etiology is reported as 4.5% in the European registry [ 21 ] and 2.9% in the KorAHF registry [ 22 ]. This difference is thought to be due to demographic variations and ambiguity in the definition of diagnosis.

Several studies have investigated the association between symptom duration and the clinical features of patients with H-AHF. One study examined whether dyspnea occurred in ≤7 or > 7 days, and found that the latter was associated with higher in-hospital worsening of HF and 1-year cardiovascular mortality and less improvement in symptoms within 48 hours [ 32 ] . In the group with onset ≤7 days, SBP was significantly higher (138 mmHg vs. 121 mmHg) and moderate-to-severe pulmonary edema was more frequent (33% vs. 8%) compared to cases with onset > 7 days. Although these findings do not precisely delineate the threshold for a “rapid” onset indicative of H-AHF pathophysiology, they do provide knowledge regarding the phenotype. In other words, H-AHF may manifest as the most severe form of AHF with high BP; however, it also exhibits a relatively favorable prognosis [ 24 , 32 , 33 , 34 , 35 , 36 ]. This is supported by studies showing that among patients with AHF presenting to the emergency department, high BP is often a predictor of low risk [ 27 , 34 , 35 , 36 ].

A recent post hoc analysis demonstrated that treatment effectiveness varied with BP [ 37 ]. It has been recommended that SBP should be lowered by ≤25% in H-AHF [ 24 , 27 , 38 ]. Patients treated with vasodilators who achieved an SBP reduction ≤25% within 6 hours of emergency room arrival had a better diuretic response and lower 1-year mortality than those with SBP reduction > 25% [ 39 ]. In this regard, vasodilators are hypothesized to improve outcomes by mitigating end-organ damage in patients with H-AHF, potentially by influencing both preload and/or afterload [ 24 ], and they can generally be used safely in H-AHF and may provide benefits when applied to appropriate patients. Unfortunately, despite numerous randomized clinical trials in this population over the past two decades, no vasodilator has shown any mortality benefit [ 40 ]. This is due to the fact that AHF is a heterogeneous condition with diverse etiologies and pathophysiology, and stratifying and enrolling specific subgroups with predictable treatment responses is challenging. Although there is a lack of evidence from randomized clinical trials, intravenous nitroglycerin, which is still the most familiar vasodilative agent among clinicians, can be administered safely and effectively to improve outcomes in patients with AHF and severely high BP [ 41 ].

Prognostic value of BP in HF

We recognize that there is no alternative to BP measurement as a source of clinical information regarding the hemodynamic status of patients with HF. Indeed, owing to its simplicity in measurement and widespread availability, BP is of paramount clinical importance in guiding the treatment of patients with HF. Furthermore, arterial hypertension is considered one of the most common comorbidities [ 3 ] and a precursor of HF [ 4 ]. Table 1 [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] shows the previous clinical trials and observational studies on the prognosis of BP in patients with and without HF.

In general, associating a higher BP with a greater incidence of HF is reasonable. In a population-based longitudinal observational study including 5888 adults aged ≥65 years, isolated systolic hypertension (SBP ≥140 mmHg) was associated with an increased risk of incident HF compared to subjects without isolated systolic hypertension during a follow-up duration of 8.7 years [ 54 ]. Regarding the clinical prognosis of low versus high BP, the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which enrolled a high-risk population of 15,244 hypertensive patients, showed no evidence for an increased risk of adverse outcome in patients with low BP [ 56 ]. This observation holds true for hypertensive patients in general and for those at high risk of cardiovascular disease without a history of HF. However, in patients who have already been diagnosed with HF, the clinical significance of BP appears to differ from that in the general population or in those with other cardiovascular diseases.

A retrospective longitudinal study showed that a low SBP (< 90 mmHg) was associated with poor survival in patients with chronic HF [ 21 ]. Notably, when the subjects were categorized based on SBP levels (< 90, 90–109, 110–129, and > 129 mmHg), as BP increased, the prognosis tended to improve in the group with SBP > 129 mmHg. Interestingly, this study also showed that pronounced long-term changes in SBP were associated with poor prognosis in this population. This result is in line with a previous study, which suggested the concept of “reverse epidemiology” that implies an improved survival rate in patients with HF with an elevated BP [ 58 ]. Several studies have reported a similar association, and this correlation is reminiscent of the “obesity paradox,” the relationship between HF and obesity. A post hoc analysis of OPTIMIZE-HF registry showed that, compared to SBP ≥ 130 mmHg at discharge, SBP < 130 mmHg was not associated with outcomes, but SBP < 120 mmHg at discharge was associated with a higher risk of death among hospitalized elderly HFpEF patients with hypertension [ 52 ]. Recent observational studies have also indicated that low SBP is associated with poor prognosis in patients with HFpEF [ 59 , 60 ].

It is not surprising that low BP might be considered harmful, as it can serve as a marker of worse health conditions. Even among patients on maximal guideline-directed medication therapy (GDMT), those with SBP < 110 mmHg have been shown to be at increased risk of readmission for HF [ 44 ], and this association remained significant despite no evidence of more severe disease or a greater burden of comorbidities in those with low BP [ 46 ].

While most of these data analyzed prognosis based on baseline BP, the analysis from the KorAHF registry focused on on-treatment BP during follow-up [ 50 ]. Among the 4487 patients hospitalized for acute HF, SBP and diastolic BP (DBP) above and below the reference BP were associated with increased mortality. A nadir of 132.4/74.2 mmHg was associated with the lowest mortality rate in this cohort, especially for those with HFpEF. However, in patients with HFrEF, the mortality risk increased significantly only in the lower BP range and not in the higher BP range. In detail, the lowest risk of mortality was observed at an SBP/DBP of 136.0/76.6 mmHg for HFrEF, and at 127.9/72.7 mmHg for HFpEF. This pattern of association with BP profile was also described in a previous study [ 61 ], although the classification of HF was comparatively different; patients with mild-to-moderate LV systolic dysfunction (LVEF, 30–50%) had a U-shaped association with mortality, but patients with severe LV systolic dysfunction (LVEF, < 30%) had a linear relationship with lower SBP, which was associated with increased mortality. Thus, it can be inferred that the association among HFrEF, HFpEF, and BP had a relatively different pattern. Taken together, these results suggest that there may be a safer BP range in HF, although it is not clear-cut; lower BP is associated with a higher risk in HFrEF and HFpEF, and while HFrEF has a wider margin of safety for higher BP, HFpEF has a narrower margin of safety because higher BP is also associated with increased risk in HFpEF compared to that in HFrEF (Fig. 1 ).

A conceptual safety margin (“green zone”) for blood pressure (BP) in each heart failure group. Heart failure with reduced ejection fraction (HFrEF) has a wide safety margin for BP, with a lower BP being at higher risk. Heart failure with preserved ejection fraction (HFpEF) has a relatively narrow safety margin for BP, with both higher and lower BP being at higher risk

Medication affecting BP in HF

Most agents proven to have a survival benefit in HF have the potential to lower BP (such as ACEis, ARBs, β-blockers, angiotensin receptor-neprilysin inhibitors [ARNIs], MRAs, and sodium glucose cotransporter 2 [SGLT2] inhibitors) to a greater or lesser extent; however, not all BP-lowering treatments have the same beneficial effects, as summarized in Table 2 [ 12 , 13 , 16 , 42 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. It is challenging to establish a direct relationship between the probability of clinical benefit and BP-lowering alone, particularly in more recent studies where the number of medications used in the study population was higher than that in previous studies. Additionally, in some cases, lowering the BP was neither beneficial nor detrimental, thereby complicating the assessment of contribution of BP to the benefits of GDMT in HF. These conflicting results have raised the question of whether reduction in BP is due to the positive effects of drugs with BP-lowering effects or, conversely, whether these drugs have deleterious effects that are offset by the benefits of neurohumoral regulation [ 79 ]. Nevertheless, the importance of treating BP in HF is consensually recognized in the HF and hypertension guidelines [ 38 , 80 , 81 ] both of which recommend drugs that have been reliably demonstrated in randomized clinical trials to improve outcomes as first-line therapy, especially for HFrEF [ 82 ].

Given that certain agents (such as metoprolol, carvedilol, and MRAs) without clear evidence of BP-lowering effect, significantly improved outcomes in HFrEF [ 70 , 83 ] and that some agents (such as calcium channel blockers [CCBs], moxonidine, and α-blockers) with significant BP-lowering effects in the general hypertensive population had no/harmful effects on HFrEF [ 84 , 85 ], it is now established that lowering BP per se is not associated with improved outcomes in HF. Instead, the focus has shifted to the class of drugs and how early they are initiated, forming the foundation of the current HF pharmacotherapy with individualized combination therapy in addition to existing agents. In this regard, patients with HF who have low BP are often undertreated, and as the Change the Management of Patients with Heart Failure (CHAMP-HF) registry data show, low BP is an independent predictor of the underuse or underdosing of neurohormonal antagonists [ 86 ]. Emphasizing that in certain cases, optimizing GDMT can be advantageous when patient tolerance permits, rather than refraining from medication solely due to BP concerns remains crucial.

Treatment for BP in patients with HF

Management of bp for incident hf.

Recognizing the explicit risk of cardiovascular disease progression in patients with uncontrolled BP, considering hypertension as a precursor to HF remains crucial. The Staging Classification of Heart Failure (A, B, C, D), introduced by the American College of Cardiology/American Heart Association in 2003, highlights the preventive aspect of HF and underscores the significance of risk factor management [ 87 , 88 ]. Accumulating evidence shows that that antihypertensive treatment is beneficial for incident HF. In a meta-analysis that demonstrated substantial reductions in cardiovascular death, stroke, and HF compared to placebo, the most significant benefit derived from antihypertensive therapy was the prevention of HF [ 89 ]. This analysis included 42 clinical trials with a total of 192,478 randomized patients and showed that low-dose diuretics significantly reduced the risk of stroke, cardiovascular mortality, and total mortality compared to placebo, with relative risks of 0.71, 0.81, and 0.90, respectively. The greatest reduction was observed in the risk of HF (relative risk, 0.51; 95% confidence interval, 0.42–0.62). More specifically, another meta-analysis by Ettehad et al. [ 90 ] showed that for each 10-mmHg reduction in SBP, the risk of HF significantly decreased by 28%.

In Hypertension in the Very Elderly Trial (HYVET) study, active antihypertensive treatment with indapamide, with or without perindopril, reduced the risk of incident HF by 64% in patients aged ≥80 years [ 91 ]. When comparing BP after 2 years of treatment, BP reduction was more modest in the perindopril group than that in the placebo group, with an additional reduction in SBP/DBP of 15.0/6.1 mmHg. In addition to placebo-controlled trials, several studies comparing active treatment with standard treatment for hypertension have reported data on the incidence of HF. The Systolic Blood Pressure Intervention Trial (SPRINT), which assessed the role of intensive antihypertensive treatment with a target SBP < 120 mmHg, showed a 38% reduction of relative risk in the development of HF in the intensive treatment group [ 57 ].

Despite increasing evidence highlighting the significant burden of HF associated with hypertensive heart disease, current hypertension treatment guidelines lack specific pharmacological strategies for managing patients beyond BP reduction [ 80 , 81 ]. However, a position paper by the Heart Failure Association, in collaboration with the European Association of Preventive Cardiology, suggests utilizing diuretics, ACEis, and ARBs to prevent HF in hypertensive patients [ 92 ]. This recommendation is based on a network meta-analysis encompassing 26 trials, which showed that these three classes of antihypertensive drugs were most effective in lowering the incidence of HF compared to placebo. Furthermore, the 2023 European Society of Hypertension guidelines recommended lowering BP with five major antihypertensive drugs including CCBs and β-blockers, in addition to the above three classes of drugs, to prevent HF development [ 93 ]. In addition, if the target blood pressure is not achieved with these medications alone, additional medications (e.g., α-blockers) are recommended as needed.

Management of BP in established HF

For patients with established HF, the prognostic meaning of BP is relatively different. Given that many HF drugs have BP-lowering effects, and that BP is one of the most important hemodynamic markers in cardiovascular disease and one of the few that can be measured directly in the clinic, BP targeting in HF is always of interest. However, there is no compelling evidence or guidelines on this aspect. Interestingly, standard HF therapy (with ACEi/ARBs, ARNIs, and β-blockers) may induce hypotension, occasionally leading to drug discontinuation. However, current HF guidelines recommend uptitrating medications to the tolerance of patients and emphasize that repeated attempts at uptitration can result in optimization, even if the initial attempts may fail [ 9 , 94 ]. This is a substantial challenge and a gap between the ideal and the reality frequently encountered in clinical practice. The following questions arise: Should we aggressively pursue different classes of HF medications, even in those who have low BP, high frailty, and especially, intolerance to BP-lowering medications? Alternatively, should we maintain a certain target BP, for example, an SBP between 110 and 130 mmHg, even if it means discontinuing certain medications? The answers to these questions can be estimated through previous literature, and we should at least attempt to learn from existing evidence.

Recommendations on BP in the treatment of HF from several guidelines for HF and hypertension are summarized in Table 3 [ 9 , 38 , 81 , 93 , 95 , 97 , 98 ]. The 2021 European Society of Cardiology HF guideline emphasizes striving to achieve target dose of each HF medication, and the 2023 European Society of Hypertension guideline recommends combining the medications (ACEis [ARBs if not tolerated], ARNIs, BBs, MRAs, and SGLT2 inhibitors) that have been shown to have outcome benefits, particularly in HFrEF. It was common across guidelines that nondihydropyridine CCB agents were not recommended in HFrEF.

Target BP in established HF

The 2017 American College of Cardiology Foundation/American Heart Association guidelines for the management of HF recommend that optimal BP in those with hypertension and an increased risk of HF (stage A) should be < 130/80 mmHg [ 81 ]. In addition, patients with HFrEF and hypertension should be treated by GDMT titration to attain a target SBP < 130 mmHg. The target BP was also updated based on several clinical trials, primarily the SPRINT trial [ 99 ]. The 2022 focused update of Korean Hypertension Society guideline for the management of hypertension also mentioned that in patients with hypertension who are at high risk for HF or with HF, it is reasonable to control BP below 130/80 mmHg [ 98 ]. However, thus far, there are no compelling data to identify a simple BP target in patients with established HF.

In 2022, the American Heart Association/American College of Cardiology/Heart Failure Society of America updated guidelines for the management of HF, which stated that the optimal BP or antihypertensive regimens are not known for HFpEF and did not mention any BP goals for HFrEF at all [ 100 ]. As more pharmacological options become available in the modern era, the recent trend is toward maximizing GDMT within a tolerable range rather than providing a target BP. Here, the tolerability of an individual to treatment is assessed using safety indicators such as hypotension or renal insufficiency. If there are no adverse events, maximizing GDMT is deemed more important, suggesting that clinicians should not passively treat by solely providing a target BP.

Differences in BP management between those with HFrEF and HFpEF

In general, guideline-recommended BP management for HFpEF was not significantly different from that for HFrEF. The difference is that hypertension is not as prevalent in HFrEF as in HFpEF, and patients with HFrEF rarely have uncontrolled BP [ 95 ]. In hypertensive patients, CCB is an option for BP control, although as mentioned above, the role of CCBs in HFrEF is limited (Table 2 ). However, the role of CCBs in HFpEF in the current era is not necessarily associated with worse HF outcomes. Although the Prospective Randomized Amlodipine Survival Evaluation-2 (PRAISE-2) study, which did not show the efficacy of amlodipine in HFrEF, had limited baseline medical treatment to ACEi (99%) and β-blocker use (19%) [ 78 ], a recent observational study on CCBs in HFpEF showed the noninferiority of CCBs, both dihydropyridines and nondihydropyridines, in addition to multiple drug usage, with β-blocker being used in more than two-thirds and MRA in one-quarter of the cases [ 101 ]. Although randomized clinical studies are required, evidence from studies on HFpEF suggests that CCB may still be effective in lowering BP and improving outcomes. In other words, it suggests that more aggressive BP management is feasible and effective by utilizing conventional antihypertensive agents to improve outcomes in patients with HFpEF compared to those with HFrEF. The 2023 European Society of Hypertension guideline also mentioned that the use of all major antihypertensive drugs including CCBs are recommended in HFpEF, and the use of ARNIs or MRAs can be considered in HFpEF with lower LVEF spectrum (Table 3 ).

Time in BP target range in HF

A practical limitation of what we learn from clinical research is that BP measurements are taken only at a certain point in time. BP is a continuous metric that changes over time, so continuous BP monitoring and “time in target range” is also important for BP management, and some recent studies reinforce this point of view. Huang et al. [ 102 ] reported a post hoc analysis of the Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist (TOPCAT) trial, which compared the efficacy of spironolactone in patients with HFpEF and showed that the duration in the target range of SBP between 110 and 130 mmHg was associated with better clinical outcomes, including mortality and hospitalizations for HF. Moreover, subgroup analyses showed that it was more significant in younger patients than in older patients.

In addition, Chen et al. [ 103 ] reported another post hoc analysis of data from the TOPCAT trial and the Beta-Blocker Evaluation of Survival Trial (BEST), which showed that a longer duration of BP in the target range of SBP between 120 and 130 mmHg was associated with a lower risk of major adverse cardiovascular events in hypertensive patients with HF. Since the BEST trial enrolled patients with HFrEF and the TOPCAT trial enrolled patients with HFpEF, this post hoc study concluded that a longer duration in the target range was highly associated with better cardiovascular outcomes regardless of LVEF. However, these studies were still limited by the fact that they did not analyze different combinations of various HF drug classes. Therefore, additional studies with similar designs are anticipated to provide additional insights into BP management in the HFrEF population.

Conclusions

Most of the HF medications have a mechanism and effect of lowering BP. Addressing patients with marginal BP poses significant therapeutic challenges, particularly considering that several other medications or clinical situations can also lower BP. Given the association of low BP with adverse prognosis, establishing a target BP and determining the ideal treatment strategy are critical, yet complex.

Many of these questions remain unanswered. How do we set a target BP? Can we unify all patients with HF using a single target BP? How do we individualize treatment and divide that subgroup? What evidence should we base our treatment on, and how do we categorize these patients for clinical research? How do we identify those who can benefit from further BP reduction and those who cannot? Which of the various HF medications should be titrated first for BP, when, and how much? Determining the optimal timing, dosage adjustments, and titration strategies for HF medication in the context of BP management requires further investigation.

Furthermore, the target BP varies depending on factors such as the patient’s condition, underlying comorbidities, etiology of HF, and the response of BP to medications. Some individuals have preserved tissue perfusion and no symptoms or signs of exercise intolerance or organ hypoperfusion even at lower BP, whereas others develop these dysfunctions even at normal or high BP. This highlights the difficulty of adopting a one-size-fits-all approach for treating HF, and it is hoped that more targeted treatments will become available depending on the underlying pathogenesis of HF.

Availability of data and materials

Not applicable.

Abbreviations

Angiotensin-converting enzyme inhibitor

American Heart Association

Acute heart failure

Angiotensin receptor blocker

Angiotensin receptor-neprilysin inhibitor

Beta-blocker Evaluation of Survival Trial

Blood pressure

Calcium channel blocker

Change the Management of Patients with Heart Failure

Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity

Confidence interval

Carvedilol Prospective Randomized Cumulative Survival

Cardiovascular

Dapagliflozin and Prevention of Adverse outcomes in Heart Failure

Diastolic blood pressure

Dapagliflozin Evaluation to Improve the Lives of patients with Preserved Ejection Fraction Feart Failure

Digitalis Investigation Group

Empagliflozin Outcome Trial in patients with Chronic Heart Failure

Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure

European Society of Cardiology

European Society of Hypertension

Guideline-Directed Medication Therapy

Hypertensive acute heart failure

Heart failure

Heart failure with mildly reduced ejection fraction

Heart failure with preserved ejection fraction

Heart failure with reduced ejection fraction

Hospitalization for heart failure

Hazard ratio

Hypertension in the Very Elderly Trial

Irbesartan in heart failure with Preserved ejection fraction

Korean Acute Heart Failure

Korean Society of Hypertension

Left ventricular

Left ventricular ejection fraction

Left ventricular hypertrophy

Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure

Myocardial infarction

Mineralocorticoid receptor antagonist

Not applicable

New York Heart Association

Organized Program to Initiate Lifesaving Treatment In Hospitalized patients with Heart Failure

Prospective Comparison of ARNI with ACEi to determine Impact on Global Mortality and Morbidity in Heart Failure

Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with preserved ejection fraction

Perindopril in Elderly People with Chronic Heart Failure

Prospective Randomized Amlodipine Survival Evaluation-2

Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization

Renin-angiotensin system

Randomized controlled trial

Systolic blood pressure

Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure

Sodium glucose cotransporter 2

Studies Of Left Ventricular Dysfunction

Systolic Blood Pressure Intervention Trial

Treating to new targets

Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist

Valsartan-Heart Failure Trial

Valsartan Antihypertensive Long-term Use Evaluation

Vericiguat Global study in subjects with Heart Failure with Reduced Ejection Fraction

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Chun, KH., Kang, SM. Blood pressure and heart failure: focused on treatment. Clin Hypertens 30 , 15 (2024). https://doi.org/10.1186/s40885-024-00271-y

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Cause of common type of heart failure may be different for women and men

by Lisa Howard, UC Davis

A new study from the UC Davis School of Medicine found striking differences at the cellular level between male and female mice with heart failure with preserved ejection fraction (HFpEF).

The findings could determine how HFpEF is treated in women compared to men.

With HFpEF, the heart muscle contracts normally but the heart is unable to fully relax and refill properly between beats. This condition is known as diastolic dysfunction. It can occur if the heart is too stiff or if the contraction process doesn't shut off quickly enough between beats.

The study showed that the diastolic dysfunction in female mice resulted from altered heart filament proteins. In male mice , it resulted from the slow removal of calcium from heart cells between heartbeats, causing a slight contraction to remain between beats.

The findings were published in Cardiovascular Research .

"This study demonstrates the importance of conducting research on both male and female populations," said Donald M. Bers, a senior author of the study. Bers is the chair of the Department of Pharmacology and the Joseph Silva Endowed Chair for Cardiovascular Research at the UC Davis School of Medicine.

"If these same molecular male-female distinctions occur in obese diabetic patients with HFpEF, it may mean that the best therapeutic strategies for HFpEF in women may differ from those for men."

Heart failure is when the heart cannot pump enough blood and oxygen to support the body. Approximately 6.2 million people in the U.S. have heart failure . The five-year mortality rate for heart failure is around 50%, although many factors can influence survival. About half of those with heart failure have HFpEF, and almost twice as many women have HFpEF compared to men. Men with heart failure may be more at risk of cardiac arrhythmias and sudden cardiac death.

'Two hit' mouse model to study HFpEF

Obesity and diabetes are common in people with HFpEF. To study the disease, the researchers created a unique "two-hit" mouse model combining two factors.

For the first factor, the researchers used mice genetically lacking a leptin receptor. Leptin is a hormone that promotes satiety. Without it, appetite remains high and the animals become obese and diabetic. For the second factor, mice were exposed to an aldosterone infusion. Aldosterone is a hormone made by the adrenal gland. High levels of aldosterone cause fluid retention.

This animal model of heart failure and diabetes develops HFpEF, allowing researchers to analyze the cellular and molecular mechanisms of muscle contraction and relaxation in male and female mice .

Dysregulation of calcium, titin

Calcium is critical in the activation of contraction and relaxation of heart muscle cells as well as the heart's electrical activity. Calcium entering the heart cell at each beat causes the muscle to contract. It also helps drive the electric signal that synchronizes the contraction of the millions of heart muscle cells required for the heart to function as an efficient pump. Calcium is removed from the cell at each beat. This allows the heart to relax between beats and fill for the next beat.

In the male mice with HFpEF, the calcium removal from the heart muscle cells was slowed, preventing complete relaxation between beats. The male HFpEF mice also exhibited more abnormal heart rhythms, known as arrhythmias.

In contrast, the females with HFpEF exhibited normal calcium movements into and out of the heart cells. Instead, the researchers observed an increase in a shorter and stiffer form of titin (N2B). Titin is a protein in the heart that acts like a supportive spring. Researchers also observed phosphorylation (a molecular reaction) of titin and another heart filament protein, troponin I. Both the titin and troponin changes made the female heart cells functionally stiffer—making the heart harder to fill—even though calcium removal was normal.

"This study reveals different drug targets in males and females and will be a stepping-stone for future trials with sex-specific targeted drugs in HFpEF," said Bence Hegyi, an associate project scientist in the Bers Lab and co-senior author of the study. "Potentially, women with this form of HFpEF could benefit from drugs that reduce cardiac stiffness. On the other hand, men with this form of HFpEF might benefit more from drugs that enhance calcium removal."

The researchers noted several limitations of the study. Although the mice in this study may be representative of the substantial number of HFpEF patients who have diabetes and are quite obese, many HFpEF patients may not be represented by this model. Multiple animal models will be needed to understand different subpopulations with HFpEF. Additional preclinical and clinical studies are needed to fully realize the potential benefits of this work.

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Watch CBS News

61% of U.S. adults will have some type of cardiovascular disease by 2050, report finds

By Sara Moniuszko

Edited By Allison Elyse Gualtieri

June 4, 2024 / 5:00 AM EDT / CBS News

Cardiovascular disease is the leading cause of death and disability in the United States — and new projections find it may become even more common in the next 30 years.

In a report released Tuesday, the American Heart Association says more than 6 in 10 U.S. adults (61%) will have some type of cardiovascular disease, or CVD, by 2050. This is particularly driven by a projected 184 million people with hypertension, or high blood pressure , which is expected to increase from 51.2% in 2020 to 61% in 2025.

"Clinically, cardiovascular disease is identified as a number of specific conditions, including coronary heart disease (including heart attack), arrhythmias (including atrial fibrillation), valvular disease, congenital heart disease, heart failure, stroke and hypertension," the association defines in its report. "However, high blood pressure is also known as a major risk factor contributing to both heart disease and stroke."

Where are other increases expected?

Total CVD diagnoses, which includes numbers for stroke but not high blood pressure, will increase from 11.3% to 15% or from 28 million to 45 million adults, during the same time.

Stroke specifically will see the largest increase, according to the report, jumping from 3.9% to 6.4%, with the "total prevalence number nearly doubling from 10 million to almost 20 million adults."

Increases were also projected for coronary heart disease (from 7.8% to 9.2%) and heart failure (from 2.7% to 3.8%).

And while there is a projected decline of high cholesterol diagnoses, other risk factors like obesity and diabetes will also increase, from 43.1% to 60.6% and 16.3% to 26.8%, respectively.

Prevalence also varies by racial and ethnic groups, the report found. For example, the increase in total projected numbers of people with CVD and poor health behaviors rose most among Hispanic adults and Asian populations, while Black adults are projected to have the highest prevalence of hypertension, diabetes and obesity.

These disparities can be attributed to "individual, structural and systemic racism, as well as socioeconomic factors and access to care," the report notes.

These 6 heart attack symptoms in women are key signs to look out for, doctor shares
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Sara Moniuszko is a health and lifestyle reporter at CBSNews.com. Previously, she wrote for USA Today, where she was selected to help launch the newspaper's wellness vertical. She now covers breaking and trending news for CBS News' HealthWatch.

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Article Contents

Introduction, case summary.

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Primary pericardial synovial sarcoma requiring emergency salvage right atrial debulking: a case report

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Ramanish Ravishankar, Rishab Makam, Mahmoud Loubani, Mubarak Chaudhry, Azar Hussain, Primary pericardial synovial sarcoma requiring emergency salvage right atrial debulking: a case report, Journal of Surgical Case Reports , Volume 2024, Issue 6, June 2024, rjae372, https://doi.org/10.1093/jscr/rjae372

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A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion between the heart and diaphragm with a right atrial (RA) filling defect, pericardial thickening and pulmonary metastasis. An RA debulking salvage operation confirmed this to be a pericardial tumour and further cytology and immunohistochemistry testing confirmed a primary synovial sarcoma. After 12 days in intensive care for ventilation, the patient was successfully discharged on warfarin and underwent oncology follow-up for chemotherapy. Following a 15-month follow-up, no mortality was observed despite the aggressive nature of the tumour.

Primary pericardial synovial sarcoma is a rare pathology with an often, uncertain prognosis. This report presents a case of a gentleman with acute respiratory failure as a result of a pericardial synovial sarcoma requiring emergency salvage debulking.

A 52-year-old gentleman was admitted to a district general hospital for shortness of breath causing type 1 respiratory failure with oxygen saturations of <90% despite high flow oxygen. His past medical history was unremarkable, and he was usually fit and well. A CT Pulmonary Angiogram (CTPA) was undertaken, which showed a heterogeneous oval-shaped lesion measuring 15 × 9 × 14 cm 3 between the heart and the diaphragm, with a median attenuation of 35 HU and no enhancement during the arterial phase. Further solid lesions of 14 mm in the right lower lobe and 5 mm in the right upper lobe raised the suspicion of a primary cardiac sarcoma with pulmonary metastasis. This is shown in Fig. 1 . Subsequent urgent CT staging ( Fig. 2 ) was undertaken, which confirmed an indeterminate space occupying the inferior pericardial space, right atrial (RA) filling defect and anterior nodular pericardial thickening. No intra-abdominal or bone lesions were identified. An echocardiogram also confirmed these finding with the addition of no flow through the tricuspid valve (TV), as shown in Fig. 3 .

CTPA showing oval-shaped heterogenous lesion as well as RA filling defect.

CT thorax-abdomen pelvis, depicting the RA filling defect as well as pericardial bulk.

Pre-operative apical four-chamber view echocardiogram showing RA bulk blocking TV flow.

Due to the critical condition of the patient, he was transferred to a tertiary centre for an emergency salvage debulking of the RA tumour via sternotomy. The goals were to improve haemodynamics, save his life and to obtain tissue histology samples.

The chest was divided with a median sternotomy and multiple pericardial adhesions were encountered on approach. Following adhesiolysis, the tumour was found to be invading the inferior surface of the diaphragm and right ventricle. This was determined to be non-resectable. Hence, the cannulation strategy was through superior vena cava, right femoral venous percutaneous cannulation and the ascending aorta. The right atrium was incised, and the tumour was debulked. Once the inferior vena cava and TV were free, the atrium was closed with 4/0 sutures. The cardiopulmonary bypass time was 43 minutes and the cross-clamp time was 15 minutes.

Tissue samples were sent for histology. Macroscopically, three pieces of grey and tan tissue measuring 100 × 80 × 15 mm 3 were found to be heterogeneous. Microscopic findings showed a malignant hypercellular neoplasm with vague fascicular to haemoangiopericytic architecture with scant intervening stroma and amphophilic cytoplasm. There was some cytoplasmic dot staining with pancytokeratin, and patchy staining with CD56 and CD99. This confirmed a synovial sarcoma that was Grade 3 (FNCLCC) with the tumour extending to the margins.

Post-operatively, the patient required stay in intensive care for 12 days for ventilatory and inotropic support. During this period, the patient required a short course of antibiotics for a hospital-acquired pneumonia. However, he was subsequently stepped down to the ward and discharged on warfarin with a target INR of 2.5. Following the diagnosis of synovial sarcoma, the patient was referred to oncology for follow-up and chemotherapy. On a 15 months’ follow-up, the patient was still alive and undergoing adjuvant therapy, although the prognosis is still uncertain.

Follow-up CT scans were undertaken during chemotherapy that showed continued reduction in the size of the RA tumour, as demonstrated in Figs 4 and 5 . The pericardial mass following chemotherapy is visualized in Fig. 6 .

Post-operative CT scan during chemotherapy showing reduction of size RA bulk.

Post-operative CT scan showing further reduction of RA bulk following chemotherapy.

Post-operative CT scan showing pericardial mass following chemotherapy.

The incidence of a pericardial synovial sarcoma is rare with only a few cases being reported in literature [ 1 , 2 ]. A series of 12 485 autopsies identified the incidence of 0.056% for primary cardiac tumours [ 3 ]. Pericardial tumours can be benign or malignant with an incidence of 80 and 20%, respectively [ 4 ]. Synovial sarcomas have been described to belong to three subtypes: biphasic, monophasic and poorly differentiated [ 2 ]. The relationship between immunohistochemistry markers and the variants of synovial sarcoma is not fully established; however, Bcl-2, CD99 and cytokeratin have been described as characteristic markers of synovial sarcomas [ 5 , 6 ].

Factors for a good prognosis and increased survival from the limited data available were noted to be location on the left side of the heart, limited necrosis, low mitotic count, no metastasis on diagnosis. Their case series had 75 patients of which the mean and median survival were 11 and 6 months, respectively [ 4 ]. However, this patient had none of these features and was undergoing chemotherapy under oncology 15 months post-operatively. Prognosis can also be directly linked to debulking, and the quantity of the tumour resected. In fact, less than a quarter of published cases have been identified to have been completely resectable due to the anatomical location and typically aggressive spread [ 2 ].

Symptoms of pericardial synovial tumours were mostly attributed to chest pain and dyspnoea, which have been noted to be attributed to an increased pericardial effusion. However, despite the large tumour, no effusion was demonstrated on echocardiogram. This case report demonstrates the patient was that of an acute scenario and an atypical presentation. Typically, careful pre-operative planning and staging is required with the use of echocardiogram, CT imaging, MRI and cytology of any pericardial effusion. However, this case has demonstrated that a successful salvage operation is feasible with adequate debulking and prompt oncology referral. A swift response is paramount to maximize prognosis.

Bezerra SG , Brandão AA , Albuquerque DC , et al. Pericardial synovial sarcoma: case report and literature review . Arq Bras Cardiol 2013 ; 101 : e103 – 6 . https://doi.org/10.5935/abc.20130235 .

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Youn HC , Lee Y , Kim SC . Pericardial synovial sarcoma presenting with large recurrent pericardial effusion . J Thorac Dis 2016 ; 8 . Available from: : E412 – 6 . https://doi.org/10.21037/jtd.2016.04.57 . https://jtd.amegroups.org/article/view/7520 .

Lam KY , Dickens P , Chan AC . Tumors of the heart. A 20-year experience with a review of 12,485 consecutive autopsies . Arch Pathol Lab Med 1993 ; 117 : 1027 – 31 .

Burke AP , Cowan D , Virmani R . Primary sarcomas of the heart . Cancer 1992 ; 69 : 387 – 95 . https://doi.org/10.1002/1097-0142(19920115)69:2<387::AID-CNCR2820690219>3.0.CO;2-N .

Cheng Y , Sheng W , Zhou X , et al. Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review . Am J Clin Pathol 2012 ; 137 : 142 – 9 . https://doi.org/10.1309/AJCP34ZVFLAUTMGL .

Kottu R , Prayaga AK . Synovial sarcoma with relevant immunocytochemistry and special emphasis on the monophasic fibrous variant . J Cytol Indian Acad Cytol 2010 ; 27 : 47 – 50 . https://doi.org/10.4103/0970-9371.70736 .

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v.15(2); 2023 Feb
PMC10048062

Atypical Presentations of Myocardial Infarction: A Systematic Review of Case Reports

Imran a khan.

1 Community and Family Medicine, Baba Raghav Das Medical College, Gorakhpur, IND

Habib Md R Karim

2 Anesthesiology, Critical Care and Pain Medicine, All India Institute of Medical Sciences, Raipur, Raipur, IND

Chinmaya K Panda

Ghazal ahmed.

3 Dermatology, Venereology and Leprosy, All India Institute of Medical Sciences, Deoghar, Deoghar, IND

Swatishree Nayak

4 Ophthalmology, Chandulal Chandrakar Memorial Government Medical College, Durg, IND

There is a rising incidence of coronary artery diseases and myocardial infarction (MI). Mortality associated with acute MI (AMI) is directly linked to the time to receive treatment and missed diagnoses. Although health professionals are aware of typical AMI presentation, atypical MI is difficult to diagnose, which on the other hand, is likely to have an impact on morbidity and mortality. Therefore, it is prudent to know such atypical presentations, especially for emergency and primary care physicians. We aimed to systematically evaluate the clinical presentations of atypical MI and analyze them to characterize the common clinical presentations of atypical MI. We researched the PubMed database, did citation tracking, and performed Google Scholar advanced search to find the cases reported on the atypical presentation of MI published from January 2000 to September 2022. Articles of all languages were included; Google Translate was used to translate articles published in languages other than English. A total of 496 (56 PubMed articles, 340 citations from included PubMed articles, and 100 articles from Google Scholar advanced search) were screened; 52 case reports were evaluated, and their data were analyzed. Atypical presentations of myocardial infarction are vast; patients may have chest pain without typical characteristics of angina pain or may not have chest pain. No typical characterization could be done. Most patients were in their fifth decade or above of their life and commonly presented with pain and discomfort in the abdomen, head, and neck regions. Prodromal symptoms were consistent findings, and many patients had two to three comorbidities out of four common comorbidities, i.e., diabetes, hypertension, dyslipidemia, and substance abuse. A patient who is 50 years old or more, having comorbidities such as diabetes, hypertension, dyslipidemia, history of tobacco or marijuana usage, presenting with prodromal symptoms like shortness of breath, dizziness, fatigue, syncope, gastrointestinal discomfort or head/neck pain should be suspected for atypical MI.

Introduction and background

Acute coronary syndrome (ACS) leading to myocardial infarction (MI) is the leading cause of mortality around the globe [ 1 ]. Acute MI (AMI) frequently leads to cardiogenic shock. Morbidity and mortality associated with MI are proportionate to the time taken to receive treatment from the onset of symptoms. Studies indicate chest pain as the most common presenting symptom (prevalence nearly 92%) in patients with suspected ACS [ 2 , 3 ]. This chest pain is often described with a few characteristics; retrosternal chest pain of squeezing/tightness/heaviness nature, which gets provoked by exertion or stress and relieved by rest or nitroglycerin. Pain may radiate to the left jaw and shoulder/arm. However, atypical clinical features, including but not limited to neck pain, pain in the back, throat pain, ear discomfort, and hiccups, are not uncommon [ 4 , 5 ]. Craniofacial pain can be the sole symptom in up to 6% of patients with AMI [ 6 ]. Women need special mention as they often present with atypical symptoms, and a high index of suspicion is required [ 7 ]. It can lead to delayed diagnosis, suboptimal treatment, and detrimental outcomes [ 8 ].

Moreover, around 5% of patients with AMI may develop cardiogenic shock with a mortality of 40-50% [ 9 ]. To avoid such mishaps, accurate and timely interpretation of atypical clinical symptomatology of AMI has a vital bearing on patient triage, treatment, and subsequent management. For example, improved survival has been demonstrated by the timely implementation of suitable reperfusion therapy [ 10 ]. With this background, we conducted a literature search and review related to atypical presentations of MI so that patients with such presentations can be suspected easily. Further, we also aimed to characterize the common atypical presentation, if possible.

Study design and selection

The present unregistered systematic review was conducted by searching the medical database in PubMed using PubMed advanced search engine and Medical Subject Heading (MeSH) index term combination of ("myocardial infarction"[Title/Abstract]) AND ("atypical presentation"[Title/Abstract]) to find the relevant articles published between 01/01/2000 and 30/09/2022. Further, we did a citation tracking of the included articles from the PubMed search process to collect and synthesize different atypical presentations of myocardial ischemia mentioned in recent literature. Furthermore, Google Scholar advanced search in the article's title with the words "myocardial infarction" (with all the words) and "atypical" (with at least one of the words) fields of the search engine was done. The period for the Google Scholar search was also limited to the same period as for PubMed. The article was searched by two researchers (Habib Md R. Karim [HK] and Ghazal Ahmed [GA]). Although our study does not require meta-analysis, the search methodology and result reporting are done as per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for the applicable segments.

Eligibility criteria

We included all case reports, letters, and commentary, with case details for atypical myocardial infarction. If case series reported individual cases, it was included, otherwise excluded. All other types of articles were excluded. If any article was available other than in the English language, we used Google Translate online to read the abstract and determine the suitability of inclusion. We did not include any grey material in the analysis. It was followed by a screening of the article by two researchers (Imran A. Khan [IK] and Chinmaya K. Panda [CP]) who were not involved in the respective database search. Tabulation of the included articles was done jointly by HK and IK, and Swatishree Nayak [SN] and CP did verification.

Statistical analysis

The characteristics (ages, gender, comorbidities, symptomatologies) of the case-based reports were further used to generate a master chart in Excell and analyzed to find the common characteristics of atypical presentation of MI. As no randomized study is feasible according to our study hypothesis and no original article has been analyzed, we have not reported any risk for bias.

Our PubMed search yielded 51 articles - 26 were related to atypical MI, and 22 were case reports. There were 430 citations in these 26 related articles that were also used for citation tracking, and ten case reports were found eligible for inclusion. Furthermore, the Google Scholar search resulted in 100 articles after filtering the citations, which were screened and analyzed, and another 20 articles were included. The flow diagram depicting the search, screening, and inclusion is presented per the PRISMA 2020 flow diagram in Figure Figure1 1 [ 11 ].

An external file that holds a picture, illustration, etc.
Object name is cureus-0015-00000035492-i01.jpg

MI - myocardial infarction; PRISMA - Preferred Reporting Items for Systematic Reviews and Meta-Analyses

The characteristics of the included case report-based articles are presented in Table Table1 1 .

AF - atrial fibrillation; CAD - coronary artery disease; CRF - chronic renal failure; CVA - cerebrovascular accidents; DM - diabetes mellitus; ESRD - end-stage renal disease; F - female; HTN - hypertension; IHD - ischemic heart disease; M - male, PCI - percutaneous coronary intervention; RBBB - right bundle branch block; TIA - transient ischemic attack; TKR - total knee replacement; TTP - thrombotic thrombocytopenic purpura

The included 52 case-based articles presented data from 56 patients; most reported cases were male, i.e., 36 (64.29%). The median, interquartile range of age of the pooled cases was 55.5 (44-65.75) years. The three most common atypical presentations were gastrointestinal discomfort, chest pain without having typical characteristics of angina pectoris, syncope, and cough and breathlessness, while the three most common comorbidities were diabetes, hypertension, and dyslipidemia (Table (Table2). 2 ). Prodromal symptoms like dizziness, weakness, and fatiguability were frequently noted in such patients despite not having typical chest pain of acute coronary syndrome (Table (Table2 2 ).

The present analysis indicates that the atypical presentation of myocardial infarction is wide. We intended to know the atypical presentation as these bear critical value for physicians and the public as patients with AMI having atypical symptoms often delay in care seeking and suspecting or diagnosing by the treating physician resulting in poor prognosis [ 61 ]. The prevalence of atypical presentations is high, epidemiological studies indicate that 26% of MI patients can present without typical chest pain [ 62 ], and the atypical presentation of MI is nearly 34% [ 63 ]. Prodromal symptoms constitute a significant portion of the atypical presentations. Khan et al. [ 64 ] analyzed the prodromal symptoms and their gender differences in 1245 patients aged less than or equal to 55 years and found that women had a higher prevalence of prodromal symptoms than men. However, the prodromal symptoms were the same among both gender, i.e., unusual fatigue, sleep disturbances, arm ache/tingling, heart racing (palpitation), frequent indigestion, increased frequency/intensity of headache, etc. Although our analysis of the pooled cases can not indicate the prevalence data, the symptoms, including the prodromal, were similar to those found in the epidemiological studies [ 62 - 64 ]. ACS is a common and potentially life-threatening condition encountered in emergency departments (ED). Clinical symptoms are usually the first step for risk stratification of ED patients presenting with suspected ACS. Despite its dreaded nature, 33% of ACS may mislead clinicians with atypical presentations [ 65 ]. The atypical symptoms tend to occur more commonly among older, female, diabetic (possibly due to autonomic neuropathy), hypertensive, and with prior heart failure. They were reported in 5.7% and 12.3% of patients with unstable angina and non-ST elevation myocardial infarction (NSTEMI), respectively [ 66 ]. A delay in the diagnosis of ACS has been associated with poor clinical outcomes and increased mortality. Moreover, women have shown increased mortality than men, and increased atypical symptom presentations associated with myocardial infarction in women are thought to contribute to delayed presentation, lower diagnosis and treatment rates might be leading to worse outcomes [ 67 ]. International guidelines reinforce the view that atypical symptoms, such as epigastric pain, dyspepsia, or breathlessness, are more likely to present in women [ 68 ]. Although our analysis of the reported cases showed a more significant number of cases in males, it cannot refute the female preponderance as it is not an epidemiological study but rather an analysis of the published atypical cases, which represents the tip of the iceberg only.

Somatic referred pain is felt at a distant site other than the noxious stimulus-affected area, often described as dull with poor localization. The pain may radiate to corresponding dermatomes such as the epigastrium, shoulders, arms, back (interscapular region), lower jaw, and neck [ 69 ]. There are usually no neurological symptoms or weakness because there is no compression or direct injury of the spinal nerves. The pathophysiology is thought to be related to the neuroanatomy of the nerves innervating the heart and dermatome. Convergence-projection theory has been postulated as a cause of this referred pain. This occurs due to the incapability of the central nervous system to differentiate between stimuli that converge on common sensory pathways [ 70 ]. Our analysis showed that myocardial infarction could present with atypical chest pain or, most of the time, without chest pain. Although the common symptoms are gastrointestinal, cough, throat pain, and otalgia were also found in nearly 10% of cases, a few patients even presented with eyeball pain, pain along the medial aspect of their left thigh, left shoulder pain, agitation, auditory hallucination, hemoptysis, severe and diffuse bone pain, leg pain, atypical hand pain, jaw pain, right sides arm, and scalp numbness. All these vast types of pain, which are not even related to the dermatomes of the heart and chest, made it difficult to find a link between them. The same was also noted for associated comorbidities. While hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and smoking have been linked in the epidemiological studies as risk factors [ 71 ], several other comorbidities were noted in our pooled cohort, i.e., recurrent reflux oesophagitis, gastric villous adenoma, thrombotic thrombocytopenic purpura, depression, post-surgery, asthma, polycystic ovarian syndrome, Reiter's syndrome, prostate cancer, myeloproliferative neoplasm, rheumatoid arthritis. However, our study can not ascertain their association with atypical presentation owing to the non-epidemiological nature of the methodology and the smaller pooled sample. Although some patients did not have proven risk factors for coronary artery disease (CAD), they had some other cardiac or vascular pathologies like pheochromocytoma with secondary cardiomyopathy, Marfan syndrome, post aortic root and arch replacement, cerebral infarction, peripheral vascular disease, papillary fibroelastoma of the aortic valve. Some patients also had a family history of HTN and ischemic heart disease (IHD) or had personal habits like tobacco chewing and marijuana addiction. Notably, 86% of the patients had comorbidities, and the majority had more than one. Interestingly two out of 57 patients also had post-COVID-19 status without any other comorbidities. While diabetes, HTN, dyslipidemia, and substance abuse are expected comorbidities, the intriguing finding was that nine (15.8%) patients had three, and another eight (14%) patients had two out of these comorbidities.

Our systematic review has only case reports, which, as such, have a low level of evidence. Although attrition, allocation, selection, blinding, and statistical analysis-related biases are unlikely in our selected articles, selective reporting of the symptoms and publication can still be possible. Further, not all cases are reported in the literature; instead, it is usually noted that unusual or unique cases are only published, so the impact of publication bias is very much feasible. The other limitation of our review is that we have not searched Embase or Web of Sciences as these were not freely accessible, which also have vast data. Although Google Scholar search and citation tracking are likely to cover up the limitation, there is still a possibility that a few cases might have been left out. We also limited our data research, including articles from the year 2000 and afterward. It was done with the intention to keep the data relevant to recent times as the definition of MI, their management, and even reporting of the cases in academic journals have undergone significant changes over the last few decades.

Conclusions

This review highlights the atypical presentations of myocardial infarctions. The analysis findings indicate that a primary care or ED physician should suspect atypical presentation of myocardial infarction even in patients who do not have chest pain or have chest pain but not having typical characteristics of angina pain. A patient is in the fifth decade of life or above, having comorbidities like DM, HTN, dyslipidemia, or having a habit of tobacco or marijuana use, significantly if associated with prodromal symptoms like feeling breathlessness, dizziness, fatiguability, or syncope, is likely to present with atypical presentation. As early diagnosis and intervention can save a life in AMI, such patients can be investigated to rule out AMI.

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Case report
Open access
Published: 04 June 2024

Sinonasal immunoglobulin G4-related disease: a case report of an atypical and rare entity

Faiq I. Gorial 1 ,
Nabaa Ihsan Awadh ORCID: orcid.org/0000-0002-7634-0146 2 ,
Shahlaa B. Ali 3 ,
Sazan Abdulwahab Mirza 4 &
Murtadha Hussein Abbas 2

Journal of Medical Case Reports volume 18 , Article number: 268 ( 2024 ) Cite this article

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Immunoglobulin G4-related disease is marked by extensive inflammation and fibrosis of an unknown autoimmune component, with an overall incidence ranging from 0.78 to 1.39 per 10 5 person-years. Sinonasal immunoglobulin G4-related disease is atypical and exceedingly uncommon in the existing literature, frequently manifesting clinically as chronic rhinosinusitis, epistaxis, and facial pain.

Case presentation

This report describes a 25-year-old Iraqi female who has been suffering from symptoms of chronic rhinosinusitis for 8 years. Despite undergoing several surgeries, there has been no improvement in her symptoms. A tissue biopsy that revealed dense lymphoplasmocytosis with noticeable plasma cell infiltration, storiform fibrosis, and obliterative angitis, along with positive immunohistochemical staining for Immunoglobulin G4 plasma cells, finally confirmed the diagnosis of sinonasal immunoglobulin G4-related disease. The patient responded well to oral prednisolone and methotrexate treatments.

Conclusions

The main objective of the current report is to raise awareness among physicians about the significance of promptly identifying and diagnosing this rarity, thus preventing the adverse consequences linked to delayed diagnosis and treatment initiation.

Peer Review reports

Immunoglobulin G4-related disease (IgG4-RD) is a condition characterized by widespread inflammation and fibrosis throughout the body with an autoimmune component of unknown cause. Estimates for the overall incidence of IgG4-RD range from 0.78 to 1.39 per 10 5 person-years [ 1 ]. It is marked by the formation of pseudotumors with storiform fibrosis, obliterative phlebitis, and infiltration of lymphoplasmacytic cells, primarily IgG4 + plasma cells. Additionally, individuals with this condition exhibit elevated levels of serum IgG4 [ 2 ]. Various organs, including the lacrimal, salivary, and thyroid glands, pancreas, biliary tract, and retroperitoneum, can be affected [ 3 ]. Conversely, the occurrence of IgG4-RD as a solitary sinonasal lesion is exceedingly uncommon in existing literature [ 4 , 5 , 6 ]. Clinical manifestations of sinonasal IgG4-RD often include facial discomfort, nosebleeds, and persistent rhinosinusitis [ 7 ].

This report highlights the first documented case from Iraq, where sinonasal symptoms were the initial sign of IgG4-RD. The purpose is to increase awareness among physicians, especially otolaryngologists, regarding the importance of early recognition and diagnosis, thereby preventing the negative outcomes associated with delayed diagnosis and treatment initiation.

Case presentation

A 25-year-old Iraqi female presented to the rheumatology consultant clinic in Baghdad Teaching Hospital after experiencing unilateral right-side painless facial swelling, specifically located below the eye on the lateral nasal side, for 1 year. However, the patient’s medical history dates back to 2015, when she started having sporadic episodes of right-side nasal epistaxis brought on by coughing, sneezing, or straining. They progressed from once a month to once a week, so she sought medical attention, and she was advised to undergo local cautery twice on separate occasions.

Regrettably, her disease advanced to impact the left nostril, resulting in the development of crustations and secretions accompanied by post-nasal drip, leading to frequent nighttime coughing. In addition, the patient experienced a symptom of nasal obstruction on the right side. Consequently, in 2017, her physician conducted a surgical procedure to address this issue. The intervention involved correcting the deviation of the nasal septum and releasing adhesions. Nevertheless, her condition progressively deteriorated, and a noticeable nose abnormality became evident, prompting her to have another surgery in 2020 for nasal bone deformity correction with pelvic grafts and adhesion release, which alleviated her complaints to some extent.

Subsequently, early in 2022, the patient experienced significant painless right-side periorbital swelling, increased tears, and no eye redness. It was diagnosed as lacrimal duct obstruction and treated surgically with a favorable outcome. Later, around the end of 2022, she experienced unilateral right-side facial swelling below the eye and lateral to the nose. It was painless and not associated with headaches or visual problems; lastly, a nasal mucosa biopsy was performed, and she was referred to our rheumatology clinic for further evaluation.

Notably, there was no fever, night sweating, loss of appetite, Raynaud’s phenomenon, photosensitivity, oral or genital ulceration, skin tightening, arthralgia, arthritis, morning stiffness, steatorrhea, diarrhea, hematamesis, malena, or abdominal pain throughout this entire period. Reviewing her medical history revealed the patient’s diagnosis of polycystic ovarian syndrome, her management with oral contraceptive pills, and her active participation in a weight loss programme that resulted in a deliberate reduction of 20 kg over an 18-month period. She also has a history of migraines, previously treated with NSAIDs, triptans, and botulinum toxin injections until their cessation in 2020. The patient received prescriptions for topical antibiotics, emollients, and oral antihistamines prior to diagnosis.

The patient’s uneventful pregnancy led to the birth of a healthy daughter with no previous miscarriages or fetal losses. Her lifestyle habits are notable for the absence of significant dental interventions, smoking, or alcohol consumption. Furthermore, there is no familial history of the patient’s condition or autoimmune diseases.

The patient, who is currently unemployed, pursues higher education and is a university candidate. She resides in an urban locale with her family, including a vaccinated indoor cat, ensuring an environment conducive to health and well-being.

The physical examination revealed normal vital signs, including a pulse rate of 90 beats per minute with good volume and regularity, a blood pressure of 110/70 mmHg, a respiratory rate of 16 breaths per minute, a temperature of 36.7 °C, and an oxygen saturation of 98% on room air. There was a mild swelling of the right side of the face below the eye lateral to the nose that was not tender without skin color change. In the submandibular region, there were palpable lymph nodes that were slightly tender, less than 1 cm mobile, and not fixed to underlying structures or skin. Organomegaly, ascites, heart abnormalities, or pulmonary abnormalities were not evident during the systemic examination. Neurological testing confirmed that all cranial nerves were intact. The patient also exhibited normal motor and sensory examinations with no evidence of arthritis.

According to the laboratory tests, the erythrocyte sedimentation rate was 34 mm/h, the hemoglobin level was 11 g/dL (11–16), and the ferritin level was 32 ng/mL (20–250). The results of the renal, liver, thyroid, virology, and urinalysis tests were within normal parameters. The results of autoimmune serology tests, including anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-Ro/SSA antibodies, anti-La/SSB antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA), including cytoplasmic-ANCA (c-ANCA) and perinuclear-ANCA (p-ANCA), were all found to be negative. The serum lgG4 level was 99 mg/dL (2.4–121 mg/dL); refer to Table 1 . Neck ultrasounds revealed normal thyroid lobes with homogeneous texture and vascularity, with mixed nodules, mostly solid isoechoic with no calcification, one in the left lobe measuring 2 × 5 mm and another in the right lobe measuring 3 × 4 mm. Bilateral cervical lymph node with intact hilum, with one lymph node in the left submadibular region lobulated in outline measuring 16 × 7 mm and another one near the left carotid vessels measuring 13 × 5.7 mm with an indistinct hilum. The chest radiograph exhibited no abnormalities. The CT scan of the paranasal sinuses (native study) reveals slight thickening of the mucosal lining in the maxillary and right frontal, right ethmoidal sinuses, as well as the nasal cavity (Fig. 1 ). A nasal mucosa biopsy revealed dense lymphoplasmocytosis with prominent plasma cell infiltration, storiform fibrosis, and obliterative angiitis (Fig. 2 ). No granuloma and no malignancy were found. An immunohistochemical stain showed increased positivity in plasma cells with IgG4-to-IgG positive plasma cells of more than 40%, as shown in Fig. 3 .

Computed tomography scan of the paranasal sinuses

A high-power Hematoxylin and Eosin (H+E) biopsy of the nasal cavity shows dense lymphoplasmocytosis with prominent plasma cell infiltration, storiform fibrosis, and inflammation around small blood vessels

Immunohistochemical stain demonstrating IgG4 positivity

The patient received a treatment regimen consisting of oral prednisolone tablets at a daily dose of 20 mg, methotrexate tablets at a weekly dose of 10 mg, and folic acid tablets at a dose of 5 mg, which resulted in a dramatic response in the form of the disappearance of facial swelling, post-nasal drip, epistaxis, and nasal discharge.

This case report delineates the journey of a 25-year-old female with chronic rhinosinusitis symptoms persisting for 8 years despite multiple surgeries. In this case, biopsy findings consistent with IgG4-related disease (IgG4-RD) in the sinonasal region were unique, as such presentations are extremely rare in the literature. The patient’s robust response to oral prednisolone and methotrexate further underscores the effectiveness of this treatment regimen for managing IgG4-RD-associated symptoms. Furthermore, this report emphasizes the importance of early recognition and diagnosis of sinonasal IgG4-RD to avoid potential adverse outcomes associated with delayed intervention. By documenting this unusual presentation, this case contributes to the growing body of literature on IgG4-RD, emphasizing the necessity for heightened awareness among healthcare providers, particularly otolaryngologists, to facilitate prompt diagnosis and appropriate management of this condition.

IgG4-related disease was described by Kamisawa in the early 2000s [ 8 ] as a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration that generally (but not always) presents as a mass-like lesion with an elevated serum IgG4 level [ 9 ]. Multiple organ systems are involved with IgG4-RD, synchronously or metachronously, and sometimes it may present with isolated organ involvement [ 10 ]. After the pancreatic and biliary systems, the head and neck are the next common sites for involvement by the disease [ 11 ]. However, sinonasal involvement is rare, with the first case not being described until 2009 by Ishida et al. [ 12 ], which is mainly because there is no definitive classification diagnostic criterion for IgG4-related rhinitis or IgG4-related rhinosinusitis established; rather, a three-tiered diagnostic algorithm in a concurrence statement was presented during the first international symposium on IgG4-RD in 2011 [ 13 ]. In spite of the fact that most of the patients outlined in literature come from the USA or Japan [ 14 ], interestingly, a recent cross-sectional study that collected cases of IgG4-RD head and neck involvement among patients from Europe, America, and Asia delineated a predilection for female patients and patients of Asian descent [ 3 ]. Our patient happens to be of Asian origin. So, it would be interesting to look for the reasons that put certain populations at risk, or whether there is a high index of clinical suspicion in certain parts of the world compared with other regions.

Presenting symptoms in cases of sinonasal involvement mimicking rhinitis or rhinosinusitis, possibly delaying or missing investigation for the disease, include chronic rhinitis, epistaxis, nasal obstruction, and facial swelling, as was noted in our case [ 10 ]. Although radiographic imaging is useful to determine the extent of disease, sinonasal involvement in IgG4-RD has nonspecific imaging manifestations [ 15 ]. The computed tomography (CT) findings of our patient were nondescriptive of the cause of the underlying disease. Impressions implied infection, malignancy, or other autoimmune processes, but no diagnosis could be made.

Many patients may also express elevated serum IgG4. This has been controversial as a diagnostic approach, in which serum levels are normal in 40% of patients with biopsy-proven disease [ 16 ]. This statement declares the importance of obtaining a biopsy specimen to confirm the diagnosis of IgG4-RD, depending on which histopathology features are met, including “dense lymphoplasmacytic infiltration with increased IgG4-positive plasmacytosis, fibrosis, often storiform in character, and obliterative phlebitis” [ 2 ], so our patient falls under the category of histologically significant [ 17 ].

Steroid monotherapy is the first-line treatment for most symptomatic IgG4-RD patients. In addition to steroid use, immunosuppressive drugs (e.g., methotrexate and azathioprine), biologic agents (e.g., rituximab), and surgery are other modalities for the treatment of IgG4-RD. It has been stated in several reports that the use of a combination of steroid and the agents mentioned above had significant responses beyond those of steroid monotherapy, as was observed in our patient [ 18 ]. Additionally, two and five cases of IgG4-RD with sinonasal involvement were reported by Keiko Ohno et al. and Masanobu Ueno et al., respectively, for which oral steroid treatment had also shown effective responses [ 19 , 20 ].

Sinonasal IgG4-RD is rare with minimal clinical recognition. The likelihood of sinonasal involvement in IgG4-RD should be considered in patients with diffuse swelling of the nasal mucosa or in some cases of refractory sinusitis. Ruling out malignancy, lymphoma, and infection is critical before considering IgG4-RD. Serological tests for IgG4 can be applied as an initial screening test, but a definitive diagnosis is based on histopathological examination. In addition, the diagnosis and treatment of this disease depend on careful analysis of clinical features and effective communication between clinicians and pathologists. Early diagnosis and successful intervention are also essential to controlling and treating the disease. Finally, we assume that this case report will contribute to better recognition of IgG4-RD among physicians and researchers and also focus attention on this rare manifestation of IgG4-RD in the sinonasal cavity.

Availability of data and materials

Not applicable.

Abbreviations

Immunoglobulin G4-related disease

Anti-neutrophil cytoplasmic antibodies

Cytoplasmic anti-neutrophil cytoplasmic antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies

Nonsteroidal antiinflammatory drugs

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Department of Internal Medicine, Rheumatology Unit, College of Medicine, University of Baghdad, Baghdad, Iraq

Faiq I. Gorial

Department of Internal Medicine, Rheumatology Unit, Baghdad Teaching Hospital, Baghdad Medical City, Baghdad, Iraq

Nabaa Ihsan Awadh & Murtadha Hussein Abbas

Department of Internal Medicine, Rheumatology Unit, Al-Imamain Al-Kadhimain Medical City, Alkarkh Health Directorate, Baghdad, Iraq

Shahlaa B. Ali

Department of Pathology and Forensic Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq

Sazan Abdulwahab Mirza

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Gorial, F.I., Awadh, N.I., Ali, S.B. et al. Sinonasal immunoglobulin G4-related disease: a case report of an atypical and rare entity. J Med Case Reports 18 , 268 (2024). https://doi.org/10.1186/s13256-024-04594-0

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College of Medicine GME research symposium continues to grow

Written by John Keenan, UNMC strategic communications
Photography by Kent Sievers
Published Jun 6, 2024

Thomas Auen, DO, left, a winner for oral presentation, reviews a poster with Subodh Lele, MD.

The 2024 Graduate Medical Education Research Symposium was held in April, drawing crowds as UNMC residents and fellows displayed their research posters and gave oral presentations.

UNMC College of Medicine Dean Bradley Britigan, MD, could be seen roaming through the event, speaking with many poster presenters.

Kristina Sevcik, MD, a poster presentation awardee, discusses her poster -- “The Optimized Parameters of Red Blood Cell Exchange by Apheresis in Transfusion-Dependent Thalassemia, A Small Case Series" -- with UNMC College of Medicine Dean Bradley Britigan.

“It is always gratifying to see the innovative and creative research produced by our house officers,” Dr. Britigan said. “I congratulate them, and our Office of Graduate Medical Education, on an impressive event.”

House officers presented their research in areas such as clinical outcomes, basic science, education, business, health policy and humanities.

There were nearly 120 research abstracts – in both oral and poster formats – presented at the event, almost 40% more than when the symposium first premiered in 2018.

Chandra Are, MBBS, associate dean for graduate medical education, said he was excited to see the research work produced by the house officers – who, he pointed out, are well-positioned to develop promising research avenues.

See a photo album from the event.

“Being in the trenches of patient care, house officers have a reliable ‘finger on the pulse’ to produce solid, clinically relevant ideas for research with near-term benefits,” Dr. Are said. “The sixth annual GME Research Symposium provided a valuable forum to highlight these projects. We could not be prouder of our residents and fellows, who went above and beyond patient care to generate such high-quality research projects.”

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Chambers and valves of the heart

Enlarged heart, in heart failure

Risk factors

Complications

Associated Procedures

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Physical Examination

BLOOD PRESSURE AND HEART RATE

JUGULAR VENOUS DISTENTION

POINT OF MAXIMAL IMPULSE

THIRD AND FOURTH HEART SOUNDS

PULMONARY EXAMINATION

LIVER SIZE AND HEPATOJUGULAR REFLUX

LOWER EXTREMITY EDEMA

VALSALVA'S MANEUVER

DIAGNOSTIC CHALLENGES

Laboratory Findings

Diagnostic Tests

CHEST RADIOGRAPHY

ECHOCARDIOGRAPHY

ANGIOGRAPHY

OTHER TECHNIQUES

Systolic vs. Diastolic Dysfunction

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Treating Patients with Atypical Cardiac Presentations

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IDENTIFYING PATIENTS AT RISK

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Heart Health Matters: A Woman’s Guide to Preventing Cardiovascular Disease

Recognizing Symptoms in Women’s Heart Health

Risk Factors for Heart Disease in Women

Lifestyle Changes for Better Heart Health

The Role of Healthcare Providers

The Emotional Impact of Heart Health

Proactive Steps for Heart Health

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Specialty care close to home

Blood pressure and heart failure: focused on treatment

Development of hypertensive heart disease and HF

Association between hypertension and HF

Hypertensive AHF

Prognostic value of BP in HF

Medication affecting BP in HF

Treatment for BP in patients with HF

Management of BP in established HF

Target BP in established HF

Differences in BP management between those with HFrEF and HFpEF

Time in BP target range in HF

Conclusions

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