What exactly is heart failure?
The clinical syndrome of heart failure arises when impairment of ventricular filling or ejection of blood results in the inability of the heart to provide adequate perfusion to the tissues while maintaining normal cardiac filling pressures. The ejection fraction is measured or clinical signs of a failing heart are assessed. Clinical signs which should worry the clinician are worsening dyspnoea specially the inability to perform personal functions like walking for personal tasks, changing clothes or bathing without help, loss of appetite with loss of muscle mass and cachexia, refractory fluid retention like edema, ascites, pulmonary edema. Patients with low cardiac output may have signs of poor perfusion, including narrowed pulse pressure, cool extremities, hypotension, and mental status changes.
What is the end result of heart failure?
The patient dies earlier than if they did not have heart failure, they need hospitalisation more frequently, renal dialysis may need to be initiated earlier and the general quality of life deteriorates.
How will you determine the severity and etiology of heart failure or cardiomyopathy?
There is no diagnostic test for HF, since it is largely a clinical diagnosis that is based upon a careful history and physical examination. Clinician should take note of impaired renal function tests, hypoalbuminemia, hyponatremia, a falling hemoglobin and in the case of right heart failure impaired liver function tests. Elevated serum natriuretic peptide levels are present in advanced heart failure but no specific level indicates the degree of heart failure. An ECG and an x ray chest are useful and essential tests. Patients presenting with fluid retention may complain of leg or abdominal swelling. If new episodes of ischemic heart disease are suspected check Troponin T or I.
What should you concentrate on in the history? Ask about the level of exercise that the patient can manage. Take a history according to the New York Heart Association. This is based on the ability of the patient to do physical exercise or work as given below:
- Class I – Patients with heart disease without resulting limitation of physical activity. Ordinary physical activity does not cause HF symptoms such as fatigue or dyspnea.
- Class II – Patients with heart disease resulting in slight limitation of physical activity. Symptoms of HF develop with ordinary activity but there are no symptoms at rest.
- Class III – Patients with heart disease resulting in marked limitation of physical activity. Symptoms of HF develop with less than ordinary physical activity but there are no symptoms at rest.
- Class IV – Patients with heart disease resulting in inability to carry on any physical activity without discomfort. Symptoms of HF may occur even at rest. This constitutes refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF.
To follow up your patient you must maintain accurate records.
What else will the history tell you?
- New symptoms; angina getting worse, either more frequent or prolonged or unprovoked; patient has changed his routine and is doing more exercise or carrying unaccustomed load;
- Palpitations; dizziness; syncope; disorientation.
- New medication has been prescribed like a calcium channel blocker, beta blocker or diuretic or NSAID.
- Embolic event.
- Recent infection like a cold, flue, pneumonia, UTI.
- BP has gone out of control.
- Emotional event or depression.
All these can change the stage of heart failure that the patient is in. Heart failure is classified into stages which affect the management of heart failure? Heart failure is a progressive syndrome which evolves through different stages. Staging helps to determine whether there is worsening of the failure, the need for special intervention or drugs or the need to deal with structural changes surgically. Given below are the stages.
Stages in the development of HF — There are several stages in the evolution of HF, as outlined by the American College of Cardiology Foundation/American Heart Association guidelines:
- Stage A – At high risk for HF but without structural heart disease or symptoms of HF.
- Stage B – Structural heart disease but without signs or symptoms of HF. This stage includes patients in NYHA functional class I with no prior or current symptoms or signs of HF.
- Stage C – Structural heart disease with prior or current symptoms of HF. This stage includes patients in any NYHA functional class (including class I with prior symptoms).
- Stage D – Refractory HF requiring specialized interventions. This stage includes patients in NYHA functional class IV with refractory HF.
Which diagnoses can be missed clinically? In two series, in which explanted hearts were assessed each spanning two decades, 17 and 13 percent of patients were misdiagnosed prior to transplantation, particularly patients with nonischemic cardiomyopathy (30 and 22 percent with clinical misdiagnosis).Conditions that can be missed clinically include cardiac sarcoidosis, myocarditis, arrhythmogenic right ventricular cardiomyopathy (in both series), and hypertrophic cardiomyopathy and noncompaction (in one series).
There are two basic pathophysiologic myocardial mechanisms that cause reduced cardiac output and HF: systolic and diastolic dysfunction. Systolic and diastolic dysfunction each may be due to a variety of etiologies.
What is systolic heart failure?
Heart failure with reduced ejection fraction — HF with reduced EF ([HFrEF] is also known as systolic HF or HF due to systolic dysfunction. Most randomized controlled trials for HF have enrolled patients with HFrEF, and therapy with established efficacy is available for HFrEF but not HF with preserved EF (HFpEF)
What is the etiology of heart failure with reduced ejection fraction?
Coronary artery disease accounts for 62%; hypertension was a major cause is now less frequent as the blood pressure can now be better controlled, accounts for 10%. Idiopathic dilated cardiomyopathy (DCM), and valvular disease are other likely causes.
In dilated cardiomyopathy 50% are still labelled idiopathic indicating how little we know. In diagnoses that are missed myocarditis accounts for 9% and IHD for 7%, infiltrative diseases like amyloid account for 5%, peripartum cardiomyopathy for 4% as does hypertension and HIV. Connective tissue disorders account for 3%, substance abuse also for 3%, doxorubicin and other unknown causes for 10%.
The history will help you diagnose IHD, hypertension, drug and substance abuse and, combined with a clinical examination, valvular heart disease.
Heart failure with preserved ejection fraction — HFpEF is also known as diastolic HF. This refers to HF in patients with a left ventricular EF ≥50 percent or >50 percent. Patients with left ventricular EFs between 41 and 49 may be categorized as having “HFpEF, borderline” with characteristics similar to patients with HFpEF. Previously thought to occur in the aging population is now often found in patients below the age of 60 years. The most significant symptom is chest pain with no epicardial changes in the ECG. Increasing dyspnoea and orthopnoea are other common problems as well as fatigue.
The most common stresses encountered by patients with HFpEF are exercise, AF, hypertension, intravenous fluid load, and ischemia:
When will you assess for systolic function?
- When there are signs and symptoms of heart failure or when these signs are worsening.
- Signs or symptoms suggestive of heart disease such as unexplained electrocardiographic abnormality, palpitations, stroke, or peripheral embolic event.
- When information on LV systolic function as well as diastolic function, chamber geometry, regional wall motion, and valve function is needed for diagnosis and management.
- When there are signs or symptoms of coronary artery disease assessment of regional and global LV systolic function is commonly combined with stress testing.
- The presence of ventricular arrhythmias is a common indication for evaluation of LV function and structure as part of an evaluation to determine whether there is a structural cause for the arrhythmia.
- Planned or prior exposure to potentially cardiotoxic therapy. Patients undergoing treatment with potentially cardiotoxic therapy require serial evaluation of LV systolic function for early detection of cardiotoxicity, which may affect continued treatment.
- Evaluation of cardiac risk prior to a procedure for which LV systolic dysfunction may be a risk factor or contraindication such renal transplant.
Definition — LVEF is a measure of the percentage of blood ejected during systole in relation to the total end-diastolic volume. The stroke volume (SV) is the difference between end-diastolic and end-systolic LV volumes. LVEF is calculated by dividing the SV by the end-diastolic volume as follows:
SV = (LV end-diastolic volume) – (LV end-systolic volume)
LVEF (%) = SV/ (LV end-diastolic volume) x 100
A larger ventricle requires a lower EF to achieve the same SV (as compared with a smaller ventricle).
In addition to quantitative calculation of LVEF, semi-quantitative (eg, visual estimates) and qualitative (normal, hyperdynamic, depressed) assessments of LV systolic function have also been described and used clinically
How robust or reliable is EF in clinical practice?
- LVEF does not give the cause of reduction of LV function hence is not based upon etiology or pathophysiology. It has been included in as a criterion in many clinical trials (including HF trials).
- LVEF does not indicate whether the dysfunction in the ventricle is global or regional.
- LVEF does not give the size of the ventricle.
- It commonly changes over time, may be impacted by blood pressure and valvular function, and slightly varies by the method used.
What are the methods used for measuring EF?
Echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography, and radionuclide angiography can all be used to measure EF.
When to suspect advanced heart failure.
Advanced HF should be suspected when a patient with HF experiences persistent severe symptoms despite optimal evidence-based therapy (pharmacologic therapy plus cardiac resynchronization therapy, as indicated and tolerated). The patient may already have diagnosed heart disease or may develop advanced failure at the first instant.
To evaluate advanced heart failure do an echocardiography which can be useful for assessment of biventricular function, estimating hemodynamics, and evaluation other cardiac conditions such as valve disease, congenital abnormalities, and pericardial disease.
Objective assessment of exercise capacity with a six-minute walk test and/or a cardiopulmonary exercise test can confirm the presence of severely limited exercise capacity, quantified it by measuring oxygen uptake (Vo2).
What is the refractory volume overload?
Patients with advanced HF often present with refractory volume overload despite escalating doses of diuretics.
- Volume overload: look for pulmonary congestion, peripheral edema, ascites, and elevated jugular venous pressure.
- A requirement of very high doses of loop diuretics, such as furosemide ≥160 mg/day or equivalent, or frequent use of metolazone is common in advanced HF.
- Look for worsening renal function.
- Inadequate diuresis despite escalating doses of diuretics.
What else could the symptoms be caused by?
- Differential diagnosis of fatigue include deconditioning, sleep apnea, and depression.
- Chronic obstructive pulmonary disease and HF may be difficult to distinguish.
- Patients presenting with fluid retention may complain of leg or abdominal swelling.
- HF should be distinguished from other causes of edema including venous thrombosis or insufficiency, renal sodium retention, drug side effect (eg, calcium channel blocker), and cirrhosis.
What abnormality do patients with diastolic heart failure display?
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have symptoms and signs of HF with normal or near normal left ventricular ejection fraction (LVEF ≥50 percent). Patients with HFpEF display normal LV volumes and evidence of diastolic dysfunction eg, abnormal pattern of LV filling and elevated filling pressures. HFpEF can be caused by all the conditions that cause HFrEF and specially valvular heart disease, pericardial disease, and high output HF.
How to treat HFpEF.
Pharmacological treatment of HFrEF.
The goals of pharmacologic therapy of HFrEF are to improve symptoms, reduce risk of hospitalization, slow or reverse deterioration in myocardial function, and reduce mortality.
The heart contains mineralocorticoid receptors and aldosterone is produced locally in the diseased heart in proportion to the severity of HF. The latter effect is mediated by the induction of aldosterone synthase (CYP11B2) by angiotensin II in the failing ventricle. Locally produced aldosterone may create a vicious cycle by stimulating angiotensin converting enzymes in the local renin-angiotensin system, an effect blocked by mineralocorticoid receptor antagonism. Direct effects of aldosterone on the heart may include promoting the development of cardiac hypertrophy and fibrosis, proarrhythmia, and, with chronic pressure overload, promoting the transition from hypertrophy to HF.
Activatable mineralocorticoid receptors are also present in coronary artery and aortic vascular smooth muscle cells. These receptors can be activated by aldosterone as well as by angiotensin II; thus, inhibition of this system may contribute to the beneficial effects of angiotensin inhibition in patients with HF.
Activation of these receptors may contribute to the increased incidence of stroke and coronary events in patients with primary aldosteronism compared with matched patients with primary (essential) hypertension. Ref: RALES trial.
Clinical trials in HFpEF do not show good results with treatment.
Treatment is aimed at the causative conditions.
In patients with current or recent (eg, within 60 days) elevated natriuretic peptide (either brain natriuretic peptide [BNP] ≥100 pg per mL or N-terminal pro-BNP [NT-proBNP] ≥360 pg per mL) who can be carefully monitored for changes in serum potassium and renal function, use suggest treatment with a mineralocorticoid receptor antagonist
Mineralocorticoids receptor antagonist.
- Spironolactone; the initial dose is 12.5 mg once daily, which is titrated as tolerated every four weeks to the maximum tolerated dose. The goal dose is 25 to 50 mg, provided that there is no dose-limiting hyperkalemia, worsening renal function, or hypotension.
- Eplerenone; the initial dose is 25 mg once daily, which is titrated in four weeks to 50 mg, as tolerated.
How to management hyperkalemia:
- Keep the serum potassium level >4.5; advise a low potassium diet,
- Avoid potassium containing salt substitutes,
- Avoid NSAIDs,
- Avoid ACE-I and ARBs and if it is essential to prescribe them measure potassium weekly and if it goes >5.0 mEq/L reduce MRA.
- Discontinue MRA if the serum potassium level is >5.5 mEq/L.
- If MRA usage is limited by hyperkalemia, down-titrate or discontinue ARB or ACE inhibitor to allow for treatment with MRA.
Diuretics — Diuretic therapy (loop and thiazide) are used in patients with HFpEF to treat volume overload. Use with caution to avoid excessive preload reduction and hypotension.
Calcium channel blockers — Calcium channel blockers may also be useful in the treatment of hypertension in patients with HFpEF, though the evidence is very limited
Avoid beta blockers.
Angiotensin II receptor blockers — There is no evidence from randomized clinical studies that ARB therapy directly improves overall morbidity or mortality in patients with HFpEF.
Angiotensin receptor-neprilysin inhibitor — The role of angiotensin receptor-neprilysin inhibitor in patients with HFpEF is uncertain and may evolve as further data are available.
The PARAGON-HF trial compared clinical outcomes with sacubitril-valsartan versus valsartan in 4796 patients with NYHA class II to IV HF, LVEF of ≥45 percent, and elevated natriuretic peptide levels. NYHA class improvement was slightly more frequent in the sacubitril-valsartan group.
Ineffective drugs: use of organic nitrates, phosphodiesterase-5-inhibitors or digoxin (except for ventricular rate control in atrial fibrillation) to treat patients with HFpEF does not help.
Asymptomatic diastolic dysfunction — Diastolic dysfunction with normal systolic function without HF (also known as preclinical diastolic dysfunction) is a common finding in older adults and a predictor of mortality.
Start initially with diuretic therapy (as need to treat volume overload), an renin-angiotensin system inhibitor (ARNI, ACE inhibitor, or single agent ARB), and a beta blocker.
The combination of hydralazine plus nitrate is an alternative to an angiotensin system blocker only if neither ACE inhibitor, ARNI, nor single agent ARB is tolerated.
What to do next?
Use a mineralocorticoid receptor antagonist, ivabradine, dapagliflozin, empagliflozin, hydralazine plus nitrate (in addition to initial therapy with an angiotensin system blocker or hydralazine plus nitrate), and digoxin.
Ivabradine ( a hydrochloride) is used in inappropriate sinus tachycardia, stable angina and heart failure and cardiomyopathy. It is used orally with a calibrated syringe. Begin with a dose of 2.5 mg twice a day to a maximum of 7.5 mg twice a day. Adjust to maintain a heart rate of 50-60/min.
Dapaglifozin is a antidiabetic agent, sodium-glucose cotransporter 2 (SGLT2) inhibitor used in Type 2 diabetes. Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124. opens in new tab.) In addition to diuretic and related hemodynamic actions of SGLT2 inhibitors, effects on myocardial metabolism, ion transporters, fibrosis, adipokines, and vascular function have also been proposed.
Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.)
In patients with type 2 diabetes, sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and the risk of serious adverse renal events, benefits that are not seen with other antihyperglycemic drugs. In large-scale, randomized, placebo-controlled trials, the risk of hospitalization for heart failure was 30 to 35% lower among patients who received SGLT2 inhibitors than among those who received placebo; this benefit was most striking in patients who had a left ventricular ejection fraction of 30% or less before treatment. In addition, the risk of progression of renal disease (including the occurrence of renal death or the need for dialysis or renal transplantation) was 35 to 50% lower among patients who received SGLT2 inhibitors than among those who received placebo. These cardiorenal benefits cannot be explained by an action of SGLT2 inhibitors to lower blood glucose, since similar effects have not been seen with other antidiabetic drugs that have greater antihyperglycemic actions.
A clinician should be prepared to treat HFpEF and HFrEF with different drugs. Hence it is very important to check the ejection fraction in each patient and do it repeatedly