I. Causes of Heart Failure: What every physician needs to know.
Heart failure (HF) is a clinical syndrome in which the heart is unable to provide sufficient blood flow to meet the metabolic needs of the body, or is only able to do so with significantly increased intracardiac filling pressure. However, this is a somewhat older definition, and many people now define heart failure as a clinical syndrome where there is structural heart disease and impaired function.
Heart failure is often referred to as congestive heart failure (CHF). Many experts believe that the term “congestion” does not uniformly apply to all patients, and the syndrome is often referred to as “heart failure” in more contemporary times.
Heart failure is most often characterized as systolic, if ejection fraction (EF) is decreased, and diastolic, if ejection fraction is preserved. “Diastolic” heart failure is also often called heart failure with preserved ejection fraction (HFPEF) or heart failure with preserved systolic function (HFPSF).
Systolic heart failure is often due to damage to the heart, such as ischemia or alcohol exposure. Diastolic heart failure is often due to longstanding hypertension or intracardiac infiltration such as with amyloid protein, which “stiffens” both ventricles. It is not usually possible to distinguish systolic from diastolic heart failure based on signs and symptoms alone, as both share substantial clinical features.
II. Diagnostic Confirmation: Are you sure your patient has Heart Failure?
Heart failure is diagnosed at the bedside using history and physical findings. There is no absolute laboratory test for the diagnosis of heart failure.
A characteristic history includes exertional dyspnea, fatigue, and edema. Physical exam would be notable for volume overload (jugular venous distention, dependent edema), S3 gallop, and often pulmonary rales.
However, it is important to note that the absence of rales does not exclude heart failure, as the lymphatic system can provide substantial compensation, particularly in patients with chronic heart failure. Pulmonary congestion is typically evident on chest radiography.
Plasma brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) levels are typically elevated, although renal failure and obesity are commonly recognized confounders. The hallmark laboratory exam of heart failure is an echocardiogram.
The presence of a decreased EF is sufficient to give a diagnosis of systolic heart failure; other modalities such as gated nuclear myocardial perfusion imaging, magnetic resonance imaging (MRI), or gated computed tomography (CT) are also able to determine EF.
Diastolic heart failure is diagnosed in the presence of the clinical syndrome of heart failure with preserved EF. Efforts should be made to determine the etiology of heart failure.
Exertional dyspnea and fatigue are virtually universal. Volume overload is usually found, but in the modern era of powerful loop diuretics, some patients do not manifest fluid overload.
Nocturnal symptoms such as orthopnea and/or paroxysmal nocturnal dyspnea (PND) are also highly suggestive of heart failure. Abdominal discomfort or fullness is also a frequently reported symptom. Patients with well-compensated heart failure may have minimal symptoms and no evidence of volume overload. Characteristics of end-stage heart failure may include cachexia and Cheyne-Stokes respirations.
Approximately half of patients with heart failure have systolic failure and the other half have diastolic heart failure. Some have features of both types. Heart failure is perhaps more common in men and in those who identify as black racially.
Risk increases with age. Regardless, the most important risk factors for developing heart failure on a population basis are hypertension, myocardial infarction, and diabetes.
The majority of diastolic heart failure is a result of longstanding hypertension, and this phenotype of heart failure is more common in women. Infiltrative diseases, such as amyloidosis and hemochromatosis, also typically lead to diastolic heart failure, often with restrictive physiology.
Prior chest radiation is another potential cause of diastolic heart failure, and the incidence may increase as prolonged cancer survivorship increases. Once patients are hospitalized with diastolic heart failure, the prognosis is approximately the same as systolic heart failure.
Hypertension and diabetes also increase the risk of systolic heart failure through the increased risk of coronary artery disease and myocardial infarctions. Thus efforts to minimize coronary artery disease would be anticipated to have substantial impact on risk of developing heart failure.
The causes of systolic heart failure are myriad, including coronary artery disease, genetic or familial, viral (including HIV), idiopathic, valvular, inflammatory (myocarditis, sarcoidosis), thyroid disease, tachycardia-mediated (often from previously unrecognized atrial fibrillation), stress-induced (also known as Takotsubo cardiomyopathy), nutritional deficiency (such as thiamine or selenium), systemic myopathies (such as muscular dystrophies), and peripartum cardiomyopathy.
Alcohol, cocaine, methamphetamines, anthracyclines, some antirheumatic medications (such as hydroxychloroquine) and tyrosine kinase inhibitors are common toxic causes of heart failure, which are typically identified through patient history.
Common alternative causes of volume overload include renal failure, liver failure, and hypoalbuminemia. Common alternative causes of exertional breathlessness are chronic obstructive pulmonary disease (COPD), pulmonary embolism (PE), and pneumonia. Coronary artery disease also may present with a dyspnea-predominant phenotype, rather than chest pain, as is classically expected.
Evaluation of the central venous pressure is of the utmost importance.
Profoundly low cardiac output states may be characterized by hypotension and/or narrow pulse pressure along with cool or mottled skin.
Sinus tachycardia is common but may be compensatory.
Chest x-ray (CXR) and EKG are essential in the evaluation of a patient with suspected heart failure. Beyond providing information supporting the diagnosis of heart failure, these diagnostic tests often provide an alternative diagnosis (atrial fibrillation, pneumonia, lung mass, etc.) that implies heart failure may not be the key diagnosis.
Echocardiogram is also essential and will provide substantial information about the size, structure, and function of the heart. MRI, which provides detailed information on the myocardium, should be considered.
MRI can provide strong, noninvasive evidence of etiology in many cases, such as prior infarction, myocarditis, hypertrophic cardiomyopathy, left ventricular noncompaction, stress or “Takotsubo” cardiomyopathy, amyloidosis, sarcoidosis, or hemochromatosis, for example. Positron emission tomography (PET) can also be used to diagnose cardiac sarcoidosis.
Endomyocardial biopsy should be considered in highly select circumstances, such as suspicion of myocarditis. Biopsy also has a role in defining the subtype of amyloid cardiomyopathy (e.g., transthyretin versus amyloid light-chain (AL)). Patients with a family history of cardiomyopathy should be offered the option of referral for genetic counseling and testing.
BNP (or NT-proBNP) should be considered, particularly if other causes of dyspnea such as COPD are being considered if there is doubt about the diagnosis. Very low levels virtually exclude heart failure, but can be confounded by obesity.
Elevated levels can be seen in renal failure without substantial heart failure, but at least suggest volume overload. Elevated BNP in the absence of renal failure is strongly suggestive of heart failure, but BNP levels are increased with age.
Basic metabolic parameters including renal and hepatic function should be measured. Renal dysfunction may be a seen as a result of low cardiac output or elevated venous filling pressure.
Hepatic parameters (ALT, AST, total bilirubin) and international normalized ratio (INR) may be elevated as a consequence of hepatic congestion. Serum albumin is helpful in excluding malnutrition as an alternative explanation for peripheral edema.
Minor elevations in troponin are characteristic of heart failure exacerbation, but typically do not rise and fall as in acute coronary syndrome; myocarditis should be considered if troponin is substantially elevated. Inflammatory markers such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) would also be typically elevated in myocarditis, but are not diagnostic if elevated. Anemia (hemoglobin or hematocrit) and gout (uric acid) and are also frequent comorbidities to consider.
Additional testing to establish the etiology of heart failure should be considered and may include: HIV, ferritin (hemochromatosis), thyroid-stimulating hormone, and serum free light chains (amyloid), for example. Testing for specific viruses other than HIV is not routinely performed, but Coxsackie, Epstein-Barr, and varicella zoster could be considered. Exclusion of connective tissue disease with antinuclear antibodies (ANA) is also often performed.
CXR film (Figure 1) may show cardiomegaly, but the absence does not exclude heart failure. Pulmonary edema is an important finding, but can be confused with pneumonitis or other causes of diffuse infiltrates. Accompanying findings such as pleural effusions may be helpful in interpretation.
Chest x-ray film demonstrating cardiomegaly and pulmonary edema.
An echocardiogram will provide size; structural detail, including evaluation of valves; and myocardial function, including EF and presence of absence of regional wall motion abnormalities. This is the most important test when considering heart failure as a diagnosis.
Abdominal ultrasound may demonstrate hepatomegaly and/or ascites, although these findings are often evident on exam and thus are not routinely indicated.
The hallmarks of treatment of diastolic heart failure are control of congestion, heart rate in the presence of atrial fibrillation to increase ventricular filling time, and control of systolic blood pressure. The majority of evidence on the treatment of heart failure has been for systolic heart failure, and is thus the focus of the remainder of this section.
There are three “to do’s” in the management of heart failure: (1) control congestion, (2) provide neurohormonal antagonists, and (3) consider sudden cardiac death prevention and cardiac resynchronization therapy (CRT). Since congestion causes most symptoms, this should be prioritized.
Congestion control is achieved with sodium and sometimes (if there is hyponatremia) moderate fluid restriction; most patients need loop diuretics. Congestion is managed the same for systolic and diastolic heart failure.
Second, neurohormonal antagonists (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), beta-blockers, aldosterone antagonists, and vasodilators in select populations) are critical for the treatment of systolic heart failure and should be initiated. Although it is critical to use the drugs and doses that were found to be effective in landmark clinical trials, very few patients will tolerate initiation of full doses of these medications, and a period of uptitration over several weeks to months should be anticipated.
There is no consensus regarding whether beta-blockers or ACEI/ARB should be initiated first, and beta-blockers should be avoided in the setting of cardiogenic shock, severe bradycardia, complete heart block, or bronchospasm. Studies of neurohormonal antagonists for diastolic heart failure have been disappointing, but neurohormonal antagonists are still often used for their antihypertensive effect, and their safety in this population is well-established.
Although there is no mortality benefit, digoxin has been noted to improve symptoms and reduce the risk of hospitalization. Finally, consideration should be given to “electrical therapy,” which consists of CRT (if QRS >130 ms) and sudden cardiac death prevention with an implantable cardioverter-defibrillator (ICD).
The risk of sudden cardiac death is much higher with an EF <35%, and in the absence of contraindications such as life expectancy less than 1 year, electrical therapy should be considered. Patients should be receiving optimal medical therapy for at least 3 months before implanting an ICD.
Wearable external defibrillators are sometimes used during the period of medical uptitration to permit reevaluation of EF; a sizable fraction of patients will improve on medical therapy to the point that an implantable ICD is not indicated.
Patients who are unable to tolerate medical therapy or experience progression despite these therapies suggest a very poor prognosis and may be considered for advanced options, such as mechanical circulatory support (MCS, also known as ventricular assist device or VAD) or heart transplant.
ACEI/ARB and beta-blockers are both initiated at minimal dose, but uptitration of ACEI/ARB is typically prioritized, as full dose can typically be achieved more quickly. Beta-blocker dose is then increased every 1 to 2 weeks to the maximally tolerated dose. Timing of the introduction of aldosterone antagonist is individualized based on need for diuretics and potassium supplementation, and often deferred to prioritize ACEI/ARB and beta-blockers.
Administration of diuretics is the hallmark of emergency treatment of heart failure and most patients respond promptly. Inadequate response should precipitate rapid escalation of a diuretic dose.
A common rule of thumb is to double an ineffective dose. Consideration should be given to vasodilators if systemic blood pressure is adequate (e.g., mean arterial pressure greater than 70 to 75 mm Hg). In the event of hypotension or cardiogenic shock, initiation of inotropes, such as dobutamine and/or dopamine, may be necessary. Noninvasive positive pressure ventilation is an option and mechanical support such as an intraaortic balloon pump may also be indicated.
In addition to evaluation of symptomatic response, physical exam findings that should be monitored while providing treatment for heart failure include frequent evaluation of jugular venous pressure and vital signs, with particular attention to blood pressure and heart rate. Sinus tachycardia is often a compensatory response and improvement is thought to represent a favorable response to treatment.
Serial examinations should also focus attention on the presence of absence of S3/S4, liver span, presence or absence of ascites, and degree and distribution of edema. Urine output should also be monitored, as this provides the most direct measure of pace of decongestion and also indicates adequate (or not) renal perfusion.
Basic metabolic panels are typically performed shortly after initiation of therapy (at least daily while hospitalized), to monitor renal function and ensure that diuretics are not causing dangerous perturbations in serum potassium levels. Following initiation of aldosterone antagonists, more frequent monitoring of potassium is indicated.
A commonly used strategy is 1 week after initiation or dose increase, and then again at 1 month. Once a stable medication regimen has been established, routine intermittent testing in heart failure patients is not typically performed. There is some data to suggest that BNP levels may be used to guide therapy.
Maintaining patients with heart failure on maximally tolerated doses of neurohormonal antagonists (ACEI/ARB, beta-blockers, aldosterone antagonists) are critical to minimizing risk of disease progression, symptomatic decompensation, hospitalization, and mortality. Application of CRT when indicated has also been shown to improve outcomes, and should be periodically reconsidered, as patient status or criteria for implant may change over time.
Education on salt avoidance, the role of fluid restriction, and self-care including daily weight monitoring are all important to reduce burden of disease and avoid hospitalization. Over time, it is not uncommon for patients with heart failure to become intolerant to maximal doses of medical therapy.
The need to decrease the doses of medications is a predictor of adverse outcome, and may be an appropriate time to consider evaluation for advanced options. For patients with end-stage disease, palliative care and/or hospice may be appropriate, and deactivation of ICD may be considered.
Digoxin is sometimes used in patients with atrial fibrillation and heart failure with insufficient rate control. Typical dose is 62.5 to 250 mcg daily.
Concurrent anemia: Treatment may improve heart failure symptoms.
Concurrent arrhythmias: Consider the role that uncontrolled arrhythmias may have on heart failure exacerbation. Improved control of atrial fibrillation or premature ventricular contractions (PVCs) may improve symptoms. Many antiarrhythmics are contraindicated in severe heart failure.
Concurrent chronic kidney disease: Continue ACEI/ARB if possible, but if necessary to discontinue, replace with isosorbide/hydralazine combination. May contribute to anemia. Aldosterone antagonists have a substantially increased risk of hyperkalemia.
Concurrent diabetes: Avoid thiazolidinediones (TZDs) in all heart failure patients and metformin if there is significant renal dysfunction.
Concurrent gout: It is likely that diuretic dosing will need to be increased if a gout flareup is treated with steroids.
Concurrent liver disease: Liver congestion is common and may result in the need to alter dose of medications metabolized by the liver.
Concurrent prostatic hypertrophy: Alpha blockers should be avoided, as they have been shown to increase mortality in heart failure patients.
Concurrent sleep apnea: Should be treated aggressively to minimize neurohormonal activation.
Aldosterone antagonists should not be used in patients with underlying chronic kidney disease.
Consider use of the Seattle Heart Failure Model or the Heart Failure Survival Score for estimating a patient’s prognosis.
Consider referral to dietitian to augment teaching on importance of low-salt diet.
Weigh yourself at the same time every day and record the result. Report increases of more than 3 lb in a day or 5 lb in a week to your doctor; however, not all decompensations are preceded by antecedent weight gain.
Avoid sodium intake and strive to keep less than 2,000 mg daily.
Take your medications as prescribed every day.
Report changes in symptoms promptly.
“2009 Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Developed in collaboration with the International Society for Heart and Lung Transplantation”.