Heart failure

The definition of congestive heart failure has evolved. In 2007, the National Library of Medicine defined heart failure as:

"defective cardiac filling and/or impaired contraction and emptying, resulting in the heart's inability to pump a sufficient amount of blood to meet the needs of the body tissues or to be able to do so only with an elevated filling pressure".

In 2009, the National Library of Medicine defined heart failure as:

"a heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity.

This, like some other terms in cardiology, can be confusing to laymen. "Heart failure" does not mean the heart has completely failed; if the heart were the fuel pump of an automobile, the diagnosis might be "pump slowdown." In like manner, "sudden cardiac death syndrome" does not mean the victim is dead; the automotive equivalent might be "running again after a jump start, but we need to know why the engine stalled."

Classification

Systolic dysfunction

Systolic heart failure is "heart failure caused by abnormal myocardial contraction during systole leading to defective cardiac emptying."

Diastolic dysfunction

Diastolic heart failure is "heart failure caused by abnormal myocardial relaxation during diastole leading to defective cardiac filling."

Etiology / cause

Heart failure may be caused by coronary heart disease, hypertension, ethanol, myocarditis, connective tissue disease and others.

• 50% are cases are idiopathic.
• 20% to 50% of idiopathic cardiomyopathy may be familial.

Diagnosis

History and physical examination

Hemodynamic Profiles

		Congestion†? (jugular venous distention and radiographic redistribution)
		No	Yes
Hypoperfusion‡? (proportional pulse pressure < 25%, cool extremities)	No	Warm and dry (33% mortality at one year)	Warm and wet
	Yes	Cold and dry	Cold and wet (46% mortality at one year)
Notes: Adapted from Figure 1 of Nohria et al. † Congestion is defined as pulmonary capillary wedge pressure of 20 mm Hg or more ‡ Hypoperfusion is defined as cardiac index of 1.8 L/min/m2. This is associated with elevate lactate. Other measures are at Critical care#Tissue_perfusion.

The best findings for detecting increased filling pressure are jugular venous distention and radiographic redistribution. The best findings for detecting systolic dysfunction are abnormal apical impulse, radiographic cardiomegaly, and q waves or left bundle branch block on an electrocardiogram.

The history and physical examination can also be used for patients with advanced heart failure to place the patient into a hemodynamic profile to guide management. Patients in the "cold and wet" category may need to "warm up in order to dry out" by stopping adrenergic beta-receptor blockaders (beta-blockers) and angiotensin-converting enzyme inhibitors (ACE inhibitors).

Brain natriuretic peptide

The role of the brain natriuretic peptide is limited when experienced physicians evaluate patients.

Clinical practice guidelines state regarding the BNP and NT-proBNP:

"Measurement of natriuretic peptides (BNP and NT-proBNP) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain. Measurement of natriuretic peptides (BNP and NT-proBNP) can be helpful in risk stratification."

Chest radiograph

The accuracy of the chest radiograph is below. For diagnosing decreased ejection fraction with: Cardiomegaly

• sensitivity = 51%
• specificity = 79%

Redistribution:

• sensitivity = 37%
• specificity = 85%

For diagnosing increased preload with: Redistribution

• sensitivity = 65%
• specificity = 67%

Various definitions have been proposed for determining redistribution; definitions with absolute measurements probably best apply to 72 inch erect, postero-anterior radiograph:

• Pulonary veins in the upper lobes are larger than the lower lobe vein. Distinguishing pulmonary veins from arteries is not important as pulmonary veins are larger than pulmonary arteries.
• Upper lobe veins 3 mm or larger in the first anterior interspace
• Upper lobe veins 7 mm or larger at the level of the pulmonary artery

Echocardiography

Echocardiography measures the fractional shortening of the ventricle which can estimate the left ventricular ejection fraction.

Various parameters on echocardiogram can estimate left ventricular end diastolic pressure.

Clinical score

Framingham score

The Framingham congestive-heart-failure score can be used (two major or one major and two minor criteria).

National Health and Nutrition Examination Survey score

The National Health and Nutrition Examination Survey (NHANES) congestive heart failure score (scores of 3 or more) can be used

Treatment

Clinical practice guidelines address management.

Treatment goals

Treating based on brain natriuretic peptide (BNP) might improve care according to a meta-analysis of randomized controlled trials conducted through 2013 and 2008. In one trial included in the meta-analysis, there was no improvement by treating for a goal of brain natriuretic peptide less than 400 pg/mL in patients younger than 75 years and less than 800 pg/mL in patients aged 75 years or older.

Subsequent randomized controlled trials report:

• Uncertain benefit from targeting NT-proBNP level < 150 pmol/l.
• An individualized goal BNP may be best. In this study of patients recently discharged after hospitalization for heart failure, the goal BNP was defined as "lowest level at discharge or 2 weeks thereafter."
• "Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment." Symptoms were measured with the New York Heart Association Functional Classification.
• Targeting a clinical score to a score of 2 or less based on the Framingham congestive-heart-failure score with the following findings may or may not be similar to targeting BNP level.

Medications

The medications for heart failure have been reviewed.

Angiotensin-converting enzyme inhibitors (ACEi)

Angiotensin-converting enzyme inhibitor can reduce morbidity from heart failure according to a systematic review of studies such as the Consensus trial.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) should not be used if:

• Baseline serum potassium is < 5.5 mmol per liter.
• No prior life-threatening adverse reactions (angioedema or anuric renal failure) during previous exposure to the drug
• They are not pregnant
• Systolic blood pressure less than 80 mm Hg
• Serum levels of creatinine greater than 3 mg per dL
• Bilateral renal artery stenosis is not present

There is conflicting evidence whether ACE inhibitors are as effective in African-American patients as in Anglo patients.

ACEi combined with angiotensin-receptor blockers

The addition of angiotensin II receptor antagonists to angiotensin-converting enzyme inhibitors is controversial. Clinical practice guidelines state:

• 2011 The National Institute for Health and Clinical Excellence
  • Consider adding an ARB, but the guideline lists the option of adding an aldosterone antagonist first
• 2008 European Society of Cardiology:
  • "Unless contraindicated or not tolerated, an ARB is recommended in patients with HF and an LVEF ≤40% who remain symptomatic despite optimal treatment with an ACEI and β-blocker, unless also taking an aldosterone antagonist."
• 2009 update of ACC/AHA guidelines:
  • "Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dL or less in men or 2.0 mg per dL or less in women and potassium should be less than 5.0 mEq per liter."
  • "potassium should be reassessed within 1 to 2 weeks after initiation and followed closely after changes in dose"

Drug toxicity includes azotemia, hyperkalemia, and symptomatic hypotension.

Beta-blockers

Two cohort studies suggest that the beta-blockers atenolol and carvedilol may be more effect than metoprolol for the treatment of heart failure.

Drugs with intrinsic sympathomimetic activity may have less benefit A systematic review of randomized controlled trials concluded "metoprolol, carvedilol, and bisoprolol all exhibited statistically significant mortality rate reductions compared with placebo, the data were inconclusive for nebivolol or atenolol" and "for every heart rate reduction of 5 beats/min with β-blocker treatment, a commensurate 18% reduction in the risk for death occurred."

There is conflicting evidence whether beta-blockers are as effective in African-American patients as in Anglo patients. This may be due to a polymorphism in African-American patients of the G protein–coupled cell surface receptor kinase (GRK5) (OMIM) that confers a natural "genetic beta-blockade".

Loop diuretics

Loop diuretics help decompensated heart failure with similar effect from low dose (a single dose equal to a patient's total daily dose) or high dose or twice a day bolus versus continuous intravenous infusion.

A meta-analysis concluded that "administering furosemide as a continuous infusion for greater diuresis and reduction in total body weight in patients hospitalized with ADHF".

Aldosterone antagonists

Aldosterone antagonists, initial dose of spironolactone 12.5 mg or eplerenone 25 mg may be used if the estimated glomerular filtration rate is >30 mL/min/1.73m2 and potassium levels are <5 mEq/dL. According to clinical practice guidelines by the American College of Cardiology, the risk of hyperkalemia is reduced by:

1. "Impaired renal function is a risk factor for hyperkalemia during treatment with aldosterone antagonists. The risk of hyperkalemia increases progressively when serum creatinine exceeds 1.6 mg/dL.* In elderly patients or others with low muscle mass in whom serum creatinine does not accurately reflect glomerular filtration rate, determination that glomerular filtration rate or creatinine clearance exceeds 30 ml per minute is recommended."
2. "Aldosterone antagonists should not be administered to patients with baseline serum potassium in excess of 5.0 mEq per liter."
3. "An initial dose of spironolactone of 12.5 mg or eplerenone 25 mg is recommended, following which the dose may be increased to spironolactone 25 mg or eplerenone 50 mg if appropriate."
4. "The risk of hyperkalemia is increased with concomitant use of higher doses of ACEIs (captopril greater than or equal to 75 mg daily; enalapril or lisinopril greater than or equal to 10 mg daily."
5. "Non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors should be avoided."
6. "Potassium supplements should be discontinued or reduced."
7. "Close monitoring of serum potassium is required; potassium levels and renal function should be checked in 3 days and at 1 week after initiating therapy and at least monthly for the first 3 months."
8. "Diarrhea or other causes of dehydration should be addressed emergently."

Spironolactone

Spironolactone can help patients who have New York Heart Association (NYHA) class IV heart failure and had a left ventricular ejection fraction of no more than 35%., although it is both used incorrectly and at the same time is underutilized. They may be used as long as:

• Serum creatinine 1.6 mg per dL or less and glomerular filtration rate or creatinine clearance exceeds 30 mL per minute.
• Baseline serum potassium is < 5.0 mEq per liter

Risk of hyperkalemia is increased if the following drugs are used:

• Higher doses of ACE inhibitors (captopril greater than or equal to 75 mg daily; enalapril or lisinopril greater than or equal to 10 mg daily).
• Nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors
• Potassium supplements

After starting aldosterone antagonists:

• Potassium levels and renal function should be checked in 3 days
• Potassium levels and renal function should be checked at 1 week
• Potassium levels and renal function should be checked monthly for the first 3 months.
• Diarrhea or other causes of dehydration should be addressed emergently

Eplerenone

Eplerenone is a selective aldosterone antagonist. In the EMPHASIS-HF randomized controlled trial, reduced death and hospitalization among patients who were "an age of at least 55 years, NYHA functional class II symptoms, an ejection fraction of no more than 30% (or, if >30 to 35%, a QRS duration of >130 msec on electrocardiography), and treatment with an angiotensin-converting–enzyme (ACE) inhibitor, an angiotensin-receptor blocker (ARB), or both and a beta-blocker (unless contraindicated) at the recommended dose or maximal tolerated dose" and without "NYHA class III or IV heart failure, a serum potassium level exceeding 5.0 mmol per liter, an estimated glomerular filtration rate (GFR) of less than 30 ml per minute per 1.73 m2 of body-surface area, a need for a potassium-sparing diuretic". However, less that 15% of the patients also received device therapy.

To avoid hyperkalemia, the following protocol was used by EPHESUS:

Starting dose of eplerenone:

• If the estimated GFR was 50 ml per minute per 1.73 m² or more: started at 25 mg once daily and was increased after 4 weeks to 50 mg once daily
• If the estimated GFR was less than 50 ml per minute per 1.73 m²: started at 25 mg on alternate days, and increased to 25 mg daily

Thereafter, investigators evaluated patients every 4 months and were instructed to decrease the dose of the study drug if the serum potassium level was 5.5 to 5.9 mmol per liter and to withhold the study drug if the serum potassium level was 6.0 mmol per liter or more. Potassium was to be remeasured within 72 hours after the dose reduction or study-drug withdrawal, and the study drug was to be restarted only if the level was below 5.0 mmol per liter.

Monitoring of serum potassium:

• At baseline, then after week 1, week 4, then every 4 months.

Isosorbide dinitrate and hydralazine combination treatment

Race-based therapeutics? The controversial approval by the U.S. Food and Drug Administration of the drug NitroMed has led to the concept of race-based therapeutics. Presumably, pharmacogenomics will lead to individualized drug treatment; until then the use of race may be a proxy of pharmacogenomic variations. Angiotensin-converting enzyme inhibitors There is conflicting evidence whether ACE inhibitors are as effective in African-American patients as in Anglo patients. Beta-blockers There is conflicting evidence whether beta-blockers are as effective in African-American patients as in Anglo patients. Isosorbide dinitrate and hydralazine combination Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with functional class III or IV heart failure. Whether this benefit is more than occurs for Anglo patients is unclear, but is suggested by two controversial post-hoc analyses of subgroups in the earlier V-HeFT-1 and V-HeFT-2 randomized controlled trials (see randomized controlled trials for details about post-hoc and subgroup analyses).

According to clinical practice guidelines:."

• "The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACEI and beta-blocker for symptomatic HF and who have persistent symptoms."
• "A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency."
• "The addition of isosorbide dinitrate and hydralazine to a standard medical regimen for HF, including ACEIs and beta-blockers, is reasonable and can be effective in blacks with NYHA functional class III or IV HF."

"Treatment with either type of drug should not be initiated in patients who have systolic blood pressures less than 80 mm Hg."

Isosorbide dinitrate and hydralazine combination treatment reduces mortality in African-American patients with functional class III or IV heart failure according to the A-HeFT randomized controlled trial. The number needed to treat is 26. The U.S. Food and Drug Administration has approved the drug BiDil for African Americans which has created controversy for reasons including the approval helped the manufacturer, NitroMed, add a second race-related patent that extended protection for BiDil for 13 years.

Whether the benefit to African-Americans is more than occurs for Anglo patients is unclear, but is suggested by two controversial post-hoc analyses of subgroups in the earlier V-HeFT-1 and V-HeFT-2

In response to the results of the A-HeFT study, the American Heart Association clinical practice guidelines state "the effect of this combination of isosorbide dinitrate and hydralazine in other patients with HF who are undergoing standard therapy is not known because the population studied was limited to blacks, but there is no reason to believe that this benefit is limited to blacks."

Digitalis glycosides

Digitalis preparations are among the oldest drugs known to medicine. Due to the variability in preparations from the foxglove plant, synthetic digoxin is most commonly used. Digoxin was the agent used in the Digitalis Investigation Group trial, the only randomized clinical trial of digitalis in chronic HF. The principal motivation for use of these drugs in HF is their positive inotropic property, increasing the contractile ability of the heart.

An additional property relevant to HF, appears to be due to neurohormonal suppressing properties. Digoxin is approved by both the U.S. Food and Drug Administration and the Canadian Cardiovascular Society for HF treatment.

Brain (B-type) natriuretic peptide

Nesiritide, a brain (B-type) natriuretic peptide, may help patients with decompensated congestive heart failure according to a randomized controlled trial. Natriuretic peptide causes diuresis, vasodilitation, and suppression of the renin-angiotensin system and sympathetic nervous system.

Vasopressin receptor inhibition

Tolvaptan, a vasopressin antagonist, may be beneficial according to a randomized controlled trial. Tolvaptan is a selective cell surface receptors V2 antagonist in the distal nephron which causes loss of free water. Other vasopressin antagonists act mainly on V1a cell surface receptors.

Statins

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) do not help according to randomized controlled trials.

Noninvasive positive pressure ventilation

Noninvasive positive pressure ventilation (NPP) can help treat acute cardiac pulmonary edema according to a meta-analyses of randomized controlled trials. Among the different modes of NPPV, CPAP may be slightly better than BiPAP. It is not clear that NPPV helps patients with normal partial pressures of carbon dioxide.

Implantable devices

Several implantable devices may help long term treatment. Both cardiac resynchronization therapy and implantable cardioverter-defibrillators should be combined in selected patients: those with New York Heart Association Functional Classification class II or III, left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec. The result of this trial contradicted an earlier meta-analysis that was based on limited studies available.

Cardiac resynchronization therapy

Clinical practice guidelines by the American Heart Association address cardiac resynchronization therapy (CRT).

According to a systematic review, cardiac resynchronization therapy (CRT), which is biventricular pacing, can reduce morbiity and mortality if the ejection fraction is less than 35%. 30 patients must be treated to avoid one death (number needed to treat is 30). Cardiac resynchronization should only be used for patients with a QRS duration of at least 120 msec.

Implantable cardioverter-defibrillator

Implantable cardioverter-defibrillators (ICD) can reduce mortality in patients who have an ejection fraction of less than 35%.

Left ventricular assist devices

Left ventricular assist devices (LVADs) may be an option for patients with end stage heart failure.

Disease management

Disease management may reduce hospitalizations. This includes contacting health care provider for weight gain of more than 2 poiunsd in one day or 4 pounds in one week.

Ultrafiltration

Ultrafiltration might help patients with cardiorenal syndrome.

Treatment of iron deficiency

Treating iron deficiency, even in the absence of iron deficiency anemia, may be beneficial according to a short randomized controlled trial.

Exercise

Exercise may improve self-reported health status and possibly combined mortality and hospitalization according to the HF-ACTION randomized controlled trial. Home based and center based cardiac rehabilitation may be equally effective.

Prognosis

Mortality can be predicted with the The Seattle Heart Failure Model, which has been independently validated. The model can show the affect of interventions on prognosis. The model is available online at http://depts.washington.edu/shfm/. Patients, especially younger patients, tend to overestimate their life expectancy.

A simpler four-item clinical prediction rule is available with similar area under the receiver operating characteristic curve:

• Risk factors for death
  • BUN > 30 mg/dl
  • SBP < 120
  • Peripheral arterial disease
  • Sodium < 135 mEq/L
• Number of risks factors and mortality at 6 months
  • 1 = 4%
  • 2 = 16%
  • 3 = 41%
  • 4 = 67%

Other risk factors

A reduced ejection fraction is independently associated with reduced survival according to an individual patient data meta-analysis.

A prolonged QRS duration of 120 ms or more is associated with reduced survival.

Blood urea nitrogen adds a small, but significant amount to the Seattle Heart Failure Model.