Heart Failure – Diagnosis and Treatment

HF is a complex clinical syndrome in which the heart is not able to provide enough blood output to meet the requirements of the tissues. It may result from any structural or functional impairment of ventricular filling (diastolic dysfunction) or ejection of blood (systolic dysfunction). Over 20 million people are affected worldwide (5 million in USA).

The clinical syndrome of HF may result from disorders of the pericardium, myocardium, endocardium, heart valves, great vessels, or from certain metabolic abnormalities, but most patients with HF have symptoms due to impaired left ventricular (LV) myocardial function. It should be emphasized that HF is not synonymous with either cardiomyopathy or LV dysfunction; these latter terms describe possible structural or functional reasons for the development of HF. It may be associated with a wide spectrum of LV functional abnormalities, which may range from patients with normal LV size and preserved EF to those with severe dilatation and/or markedly reduced EF. In most patients, abnormalities of systolic and diastolic dysfunction coexist, irrespective of EF.

ETIOLOGY:

Heart failure may be caused by many different pathological processes. Some of the causes include:

Ischemic heart disease
Hypertension
Idiopathic
Valvular disease
Myocarditis
Toxic (alcohol, cocaine)
Radiation
Peripartum
Infections
Medications (doxorubicin, trastuzumab)

CLINICAL SIGNS AND SYMPTOMS:

Patients with HF may have dyspnea on exertion or rest, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and lower extremity swelling.

Physical examination may show jugular venous distention, pulmonary rales, S3, murmurs (if valvular disease or other cardiac condition is associated), and peripheral edema. A lateral displacement of the apical impulse may be present.

During acute decompensation patients may have signs of cardiogenic pulmonary edema and respiratory failure.

USEFUL CLASSIFICATIONS AND STAGING SYSTEMS:

New York Health Association Functional HF Classification

NYHA Class	Patient Symptoms
I	No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
II	Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).
III	Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.
IV	Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.

American College of Cardiology and American Heart Association HF Staging

Stage	Description	Treatment Options
A	At risk for HF but no structural heart changes or symptoms.	- Lifestyle changes - Treatment of comorbidities - ACE inhibitors or ARBs in patients with vascular disease or DM
B	Structural heart disease but without signs or symptoms of HF.	- All of the above - ACEI or ARB as needed - Beta blockers as needed
C	Structural heart disease with signs or symptoms of HF.	- All of the above (lifestyle modifications, ACE inhibitor/ARBs, Beta blockers) - Diuretics to relieve congestion - Aldosterone antagonists - Hydralazine + Nitrates in selected patients - Digoxin for symptomatic relief if needed - ICD or CRT if appropriate
D	Refractory HF requiring advanced intervention	- All of the above - Chronic inotropes - Heart transplantation - End of life care

TYPES:

Currently, heart failure is divided in two great groups: Heart failure with preserved ejection fraction (HFpEF) and Heart failure with reduced ejection fraction (HFrEF).

Heart failure with preserved ejection fraction (HFpEF) is characterized by the presence of heart failure symptoms with normal or near normal left ventricular ejection fraction (LVEF > 50%). Previously it was believed that such condition occurred due to diastolic dysfunction so it used to be called diastolic heart failure. However the pathophysiology is more complex and changes in the systolic function and long-axis function exists despite the normal ejection fraction in the echocardiogram. HFpEF is more common among patients with hypertension, diabetes, obesity, coronary artery disease, and aging and its pathophysiology may be related to oxidative stress that starts on the endothelium (in contrast to HFrEF, in which the stress starts on the myocytes). It is also important to differentiate HFpEF from other causes of cardiomyopathy with preserved HF since the treatment of these conditions may be different. These conditions include amyloidosis, hemochromatosis, systemic sclerosis, storage diseases, hypertrophic cardiomyopathy, valvular disease, pulmonary hypertension, cardiac tamponade, among others.

Heart failure with reduced ejection fraction (HFrEF), on the other hand, is defined as heart failure symptoms with a reduced LVEF (<40%).

The LVEF range between 40-50% is considered a gray zone and there is still discussion about how to classify these patients between HFrEF and HFpEF. It is sometimes called Heart Failure with mid-range ejection fraction.

DIAGNOSIS:

History and physical examination will reveal signs and symptoms of HF.

HFrEF is diagnosed when signs and symptoms of HF are present and there is echocardiographic evidence of low LVEF (<40%).

HFpEF is diagnosed when there are signs and symptoms of HF with a normal or near normal ejection fraction (LVEF >= 50%) in the echocardiogram in absence of an alternative explanation.

Echocardiography in HFpEF may show signs of diastolic dysfunction, LV hypertrophy, concentric remodeling, left atrial enlargement and/or elevated pulmonary artery pressure. It is important to stress, however, that asymptomatic diastolic dysfunction is more common than HFpEF, and therefore patients with diastolic dysfunction without heart failure symptoms should not be considered to have HFpEF.

Echocardiography in HFrEF, on the other hand, will show systolic dysfunction, a low ejection fraction and dilated chambers.

An elevated BNP (>100 pg/mL) or NT-proBNP (>300 pg/mL) increases the probability of HF. However, in some patients the BNP may be normal (e.g. obese).

In patients in which the diagnosis of HFpEF remains uncertain but possible despite all noninvasive options, cardiac catheterization may be useful.

For both HFrEF and HFpEF chest radiography may show signs of congestion (cephalization of the pulmonary vessels, Kerley B lines) or pleural effusions. Patients with dilated cardiomyopathy may have an increase in the cardiac area.

TREATMENT:

The management of HF is different depending on the presentation. The acute management focus in hemodynamic support and symptomatic relief. The chronic management focus on quality of life improvement, symptomatic relief and reduction of the disease progression.

Acute HF decompensation management:

Precipitating factors for acute decompensation include dietary issues, nonadherence to medications, drug interactions, coronary artery disease (ACS), arrhythmias, valvular disease, drugs, anemia, pulmonary embolism, endocrine disorders, among others.

Patients presenting with acute decompensated HF should be promptly assessed and treated. Vital signs, Sat O2 and cardiac rhythm should be monitored and an IV line should be obtained. Supplemental oxygen should be provided if SpO2 < 90%.

If the patient is able to tolerate, a trial of noninvasive ventilation (NIV) may be conducted to improve the respiratory distress. If NIV is contraindicated or cannot be tolerated, intubation and mechanical ventilation may be necessary.

The hemodynamic status of the patient should be assessed. The hemodynamic status of the patient is often described according to the hemodynamic profiles below:

	Congestion Absent	Congestion Present
Adequate perfusion	Profile A (dry-warm) - PCWP normal, CI normal.	Profile B (wet-warm) - PCWP elevated, CI normal
Inadequate perfusion	Profile L (dry-cold) - PCWP low/normal, CI decreased	Profile C (wet-cold) - PCWP elevated, CI decreased.

Loop diuretics (furosemide 40mg IV or torsemide 20mg IV) should be given ASAP in congested patients. Higher doses (up to 200mg furosemide) may be necessary in patients with CKD or those that already use diuretics.

Patients with hypertension and those with acute mitral or aortic regurgitation may benefit from nitroprusside (5-10mcg/min titrated q5min) to reduce the preload.

Nitroglycerin (10 – 20mcg/min to max of 200mcg/min) may be used instead if the diuretics fail to improve the congestion .

Patients with hypotension but without congestion may receive a fluid challenge to see if the hypotension improves.

Patients with hypotension and congestion due to HFrEF should receive inotropes (dobutamine 2-20mcg/kg/min or milrinone 25-75mcg/kg bolus over 10 minutes + 0.375-0.75 mcg/kg/min) and, if hypotension remains, should be considered for an intra-aortic balloon, extracorporeal circulatory membrane oxygenation (ECMO) or ventricular assist devices. Patients with HFpEF and hypotension, on the other hand, may benefit from non-inotrope vasopressors (such as phenylephrine).

In addition to the treatment, an ECG, chest x-ray and laboratories (CBC, CMP, myocardial damage panel, ABG, BNP) should be obtained. An echocardiogram should also be performed.

Opiates should not be routinely used except if the etiology of the decompensation demands it (e.g. ACS).

If the patient remains congested despite optimum diuretic therapy, hemodialysis/ultrafiltration may be useful.

Chronic HF management:

Lifestyle modifications are useful and include cessation of smoking, restriction of alcohol consumption, cessation of drugs, salt restriction (2-3g/day), fluid retention (1.5-2L/day), weight loss in obese patients and weight monitoring (detect fluid accumulation).

Heart Failure with Reduced Ejection Fraction management:

Treatment should be started with the above mentioned lifestyle modifications and loop diuretics to control volume overload if present.

With the volume status under control, ACE inhibitors should be initiated started at low doses and titrated to goal. Enalapril (start with 2.5mg BID and slowly increase to 20mg BID), captopril (start with 6.25mg TID and end with 50mg TID), lisinopril (start with 5mg qDay and end with 40mg qDay), or others may be used. If ACE inhibitors cannot be tolerated, ARBs are an option.

Recently, the neprilysin inhibitor sacubitril is available in association with valsartan (ENTRESTO, 49/51 to 97/103 mg BID) and is indicated to reduce the risk of CV death and HF hospitalization in patients with HFrEF. It may be used instead of ACE inhibitors or ARBs alone.

Beta-blockers should also be initiated after the patient is stable with the ACE inhibitor, ARB or ARNI (started at low doses and slowly titrated to goal). Medications include carvedilol (start with 3.125mg BID and slowly increase to 25-50mg BID), metoprolol succinate (extended release, start with 12.5mg/day and increase slowly to 200mg/day) or bisoprolol (1.25mg qDay initially to a maximum of 5-10mg qDay at the end of titration). Beta-blockers may make the symptoms worse at the beginning of the treatment and the patient should be aware of that.

Patients with HF NYHA II and LVEF <30 % or NYHA III or IV and LVEF <35% should receive aldosterone antagonists (spironolactone, start with 12.5mg qDay and titrate to 50mg qDay; OR eplerenone, start with 25mg qDay and titrate to 50mg/day).

Patients with may also receive hydralazine (50-75mg TID) PLUS nitrate (isosorbide dinitrate 20-40mg TID) if they cannot tolerate ACE inhibitors or ARBs. However, hydralazine plus nitrate can also be used on patients with NYHA III – IV IN ADDITION TO all the other medications, including ACE inhibitor or ARB, if they do not respond despite optimal therapy. Black patients in particular may benefit from hydralazine plus nitrates.

Ivabradine (CORLANOR, 5 to 7.5mg BID), a If channel (funny current) inhibitor, may be used in patients to reduce the risk of hospitalization in patients with LVEF <= 35% and HR >= 70 bpm despite maximally tolerated doses of beta blockers. Target HR with ivabradine is 50-60 bpm.

Digoxin (0.125mg qDay or less, ideal serum levels 0.5-0.8ng/mL) may be useful in patients with NYHA II, III or IV that are stable but still symptomatic despite medical therapy.

Cardiac rehabilitation may be useful for patients with HFrEF NYHA class II to III if they do not have arrhythmias or limitations to exercise.

An ICD should be placed in patients with ischemic HFrEF NYHA class II or III with LVEF <=35 % for primary prevention of sudden cardiac death if they do not improve despite optimal medical therapy. Patients with HFrEF from other etiology may also benefit from the ICD. Patients with HFrEF with LVEF <=35% and NYHA class III or IV with a QRS >= 120msec may benefit from biventricular pacing plus ICD (CRT-D device).

If a patient with HF experiences an episode of sustained ventricular tachycardia or sudden cardiac arrest, he may receive an ICD for secondary prevention. Syncope is also a fair indication for ICD implantation in HF. A patient that remains with multiple arrhythmias and ICD shocks may benefit from antiarrhythmic drugs (amiodarone is the choice) or catheter ablation.

Patients with refractory HFrEF despite optimum pharmacologic and device therapy should be evaluated for candidacy for mechanical circulatory support and cardiac transplantation.

Heart Failure with Preserved Ejection Fraction management:

Unlike HFrEF, HFpEF does not have a well-established pharmacological treatment guideline. The associated conditions (hypertension, diabetes, COPD, hyperlipidemia, obesity) should be managed one by one as their improvement may also reduce the progression of HFrEF.

Lifestyle modifications, sodium restriction and moderation of alcohol consumption are useful.

Diuretics may be beneficial to reduce the volume overload and relief symptoms.

In addition to the treatment of other conditions such as hypertension (if present) and the use of diuretics in cases of congestion, the use of mineralocorticoid antagonists may improve outcomes in patients with HFpEF. If this class of drug is used, it is important to monitor the potassium and kidney function.

SOURCES & FURTHER READING: