Heart Failure in India: Need for Indian Guidelines

CHAPTER 21 Sandeep Seth

INTRODUCTIONHeart failure (HF) is a major problem in the West and is likely to become a major problem in India. As per projections there are at least 8–10 million patients with HF in India with a prevalence of about 1% adult population. A study across 6 rural villages in Haryana had shown a prevalence of 0.1% heart failure with untreated hypertension as one of the most common causes, but this could have been an underestimation picking up only the sickest patients. Studies done from Trivandrum and Hospital-based studies from All India Institute of Medical Sciences (AIIMS) suggest that rheumatic heart disease (RHD) and coronary artery disease (CAD) are both major causes of heart failure in India. India also has some unusual causes of HF like endomyocardial fibrosis and aortoarteritis.1-5

Patients with HF in India are younger, sicker and have a much higher morbidity and mortality as compared to their western counterparts. They also do not tolerate the high level of medications recommended in western guidelines. Similarly, devices and other advanced therapies are often too costly and out of reach of many of our sickest patients.

STATUS OF HEART FAILURE IN INDIA

The Trivandrum HF registry (THFR) enrolled 1205 admissions for HF (834 men, 69%). The mean age was 61.2 years. The most common etiology of HF was ischemic heart disease (72%). HF with preserved ejection fraction (HFPEF) constituted 26%.5 Patients with HF in the Trivandrum HF registry were younger, and had a higher prevalence of CAD.

In another study from AIIMS, adults of six villages in Northern India were screened, and cases of dyspnea were identified by trained health workers. Of 10,163 cases screened, chronic breathlessness was present in 128 (1.3%). Echocardiography was performed in all and HF was diagnosed in 12 of them. Thus, the prevalence of HF in this rural community was estimated to be 1.2/1000. Two-thirds of the patients had HFpEF and all of them had uncontrolled hypertension (HTN).6

The authors did a small survey of in-hospital patients (n = 500) and found that the mean age of the patients was low (39 ± 16 years). The mean age of patients from another large in-hospital data of 1985 patients was 49.2 years and the mean age in THFR was 61.2 years, meaning that this population from North India is much younger, compared to South Indian patients and still younger than Western patients. In the in-hospital group, RHD (52%) was the most common cause followed by ischemic heart disease (17%). RHD (37.1%) was the most common etiology followed by CAD (33.4%) in a tertiary hospital cohort. One reason for the higher rates of RHD could be due to the referral bias of patients from the low socioeconomic sector to public sector hospitals where the study was conducted. The authors did an estimation of the prevalence of HF in India. They estimated that prevalence of HF to be about 1% (8–10 million) individuals and the mortality attributable to HF is about 0.1–0.16 million individuals per year. Since Indian patients with HF are different and respond differently to therapy, it is necessary to create guidelines in HF therapy which are specific to Indian patients. An exercise was carried out wherein experts from AIIMS, RML, SJH, GB Pant, PGI Chandigarh and Care Hospitals got together to create a consensus statement

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on the manage ment on HF in India along with members of European Society of Cardiology (ESC).7 These were published in the Journal of Practice of Cardiovascular Sciences and are summarized further.

GUIDELINES FOR HEART FAILURE IN INDIA

Making a Diagnosis

A detailed history and examination should be done. Investi gations include echocardiogram and certain special investigations which confirm ventricular systolic and/or diastolic dysfunction.

Laboratory Investigations

Blood count, urinalysis, electrolytes (including calcium and magnesium), blood urea, serum creatinine, glucose, lipid profile, liver function tests, and thyroid-stimulating hormone. A 12-lead electrocardiogram (ECG) should be performed initially on all patients presenting with HF. Biomarkers (BNP and NT-pro BNP) are not mandatory for India and only useful if there is diagnostic doubt.

Noninvasive Cardiac Imaging

All patients should have a chest X-ray. An echocardiogram provides information on ventricular systolic and diastolic function. Radionuclide ventriculography or magnetic resonance imaging (MRI) can be done in select cases when echocardiography is not adequate. Contrast MRI is also useful in cases where infiltrative disorders or myocarditis is suspected.

Invasive Evaluation

Pulmonary artery catheterization is performed in sick patients to assess the fluid balance. Routine catheterization is not done and only when clinical assessment is not adequate is catheterization needed. Coronary angiography is done when ischemia is suspected as a cause of HF based on history or other investigations like a stress test. An endomyocardial biopsy should be done in patients with recent onset cardiomyopathy (within one month).

Management

The objective of management is to relieve symptoms and prolong life.

General MeasuresLife style changes include fluid restriction, salt restriction, alcohol restriction, weight control, a graded and supervised exercise program. Common complications like

hypertension, arrhythmias, depression and anemia must be treated. Iron deficiency even without anemia should be looked for and treated. Influenza and pneumococcal vaccinations are recommended for all HF patients.

Drug TherapyTherapy starts with symptoms relief for the patient and congested patients must be decongested with diuretics and can be given digoxin if needed. Diuretics are to relieve symptoms through achievement of euvolemia. They have not been shown to provide prognostic benefit. Digoxin is the mainstay therapy to control ventricular response in patients with HF and atrial fibrillation (AF). Its use in sinus rhythm is less, though many patients maintained on digoxin worsen on withdrawal of the drug. Therefore, it continues to play a role in symptomatic patients with repeated hospitalizations. Along with symptom relief, patients are started on vaso dilators and later beta-blockers when the patients are stable. Angiotensin-converting enzyme (ACE) inhibitors (and angiotensin receptor blockers [ARBs] in those unable to tolerate ACE inhibitors) and β-blockers are the first-line drugs for heart failure. These agents should be started at low doses and increased to the target doses. Mineralocorticoid receptor antagonists, in addition to background ACE inhibitor and β-blocker therapy, are also useful. For patients with known ischemic heart disease, aspirin, and other antiplatelet agents should be continued. Warfarin is for patients with chronic HF and AF or where there is a history of embolism.

Specific Recommendations for Drugs

The ACE inhibitor should be used in all patients as soon as possible after a myocardial infarction (MI) and be continued indefinitely if ejection fraction (EF) <40% or if HF complicates an MI and in all symptomatic or asymptomatic patients with systolic dysfunction and with an EF <40%. Angiotensin receptor blockers should be used in patients who cannot tolerate an ACE inhibitor. ARB should not be added to ACE inhibitors. Spironolactone is recommended for patients with systolic CHF with severe symptoms, despite appropriate medication. Eplerenone is recommended early post-MI in patients with left ventricular (LV) systolic dysfunction and symptoms of HF. It is also recommended in patients with systolic HF, who still have mild (NYHA Class II) symptoms. Eplerenone is costly and in this subset of patients, if patients cannot afford eplerenone they may be prescribed spironolactone though trial evidence for this is lacking. All HF patients with an EF <40% should receive a β-blocker like carvedilol, sustained release metoprolol

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or bisoprolol or nebivolol. New York Heart Association (NYHA) Class IV patients should be stabilized before initiation of a β-blocker. Studies have shown that decompensated patients can be initiated on beta-blockers before discharge, but this practice in India should be carried out very carefully. Dose titration of β-blockers should take place after the first visit after discharge. If the patient is stable and mobilized at the time of discharge, then a very low dose of β-blockers can be initiated in the hospital. Therapy is started at a low dose and titrated to the target dose used in large trials or the maximum tolerated dose if less than the target dose. β-blocker should not be given to patients with symptomatic hypotension, with symptomatic bradycardia or an atrioventricular block or severe reactive airways disease. Loop diuretics should be used for patients with HF and congestive symptoms. When acute congestion is cleared, the lowest dose should be used that is compatible with stability. In patients with persistent volume overload, a second diuretic (a thiazide or low dose metolazone) may be considered. Digoxin is recommended in patients in sinus rhythm who continue to have moderate to severe symptoms, despite optimized HF therapy to relieve symptoms and reduce hospitalizations. Digoxin is used in patients with chronic AF and poor control of ventricular rate. Isosorbide dinitrate and hydralazine is recommended in addition to standard therapy for patients unable to tolerate an ACE inhibitor or ARB because of intolerance, hyperkalemia, or renal dysfunction. Ivabradine is used in NYHA Class II to III, stable chronic HF with systolic dysfunction (EF <35%). In sinus rhythm with a heart rate of 75 beats/min bpm or more. Use ivabradine in combination with standard therapy or when beta-blocker therapy is contraindicated or not tolerated. The angiotensin receptor–neprilysin inhibitor LCZ696 with enalapril in patients who had HF with a reduced EF has recently been approved by the Food and Drug Administration (FDA). Trimetazidine is a cytoprotective drug that normalizes metabolic disturbances in ischemia. The best-known trimetazidine mechanism of action is its capacity to inhibit β-oxidation of free fatty acid and promote glucose metabolism. It has been shown to reduce HF hospitalizations. We recommend aspirin at a dose 75 mg be considered in HF patients with indications for secondary prevention of CV events. We recommend anticoagulation for patients with demonstrated intracardiac thrombus, previous systemic embolism, or after a large anterior MI or AF. In HF and AF, the ventricular rate should be controlled at rest and during exercise. Restoration and maintenance of sinus rhythm should not be performed routinely.

β-blockers are used for rate control, especially in heart failure. Digoxin can be added. If rhythm control is indicated drugs should be restricted to amiodarone. Oral anticoagulation for AF is also recommended. In established iron deficiency, oral or intravenous iron supplements should be initiated to improve functional capacity. Testing for ferritin levels and transferrin saturation will better quantify iron deficiency.

Device-based Therapies

Device-based therapies used in patients with HF are the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT). Implantation of these devices is currently recommended for patients with a low EF (i.e. 30% after MI, irrespective of the severity of symptoms, or 35% in other patients). Indian patients are different when it comes to applying these guidelines. First, we are treating a younger population that is, not represented in clinical trials. Second, devices are expensive and implementing Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II) criteria, is associated with a significant cost burden to budgets that are under pressure. Also the benefits of ICD therapy could have been overestimated in trials by the use of toxic antiarrhythmics. Proposed recommendations for treatment options with ICD or CRT for people with HF who have LV dysfunction with an LVEF of 35% or less (according to NYHA class, QRS duration, and presence of left bundle-branch block [LBBB], and on optimal medical therapy).

NYHA class

RS interval I II III IV

<130 ms ICD if there is a high risk of sudden cardiac death

ICD/CRT not clinically indicated

130–149 ms without LBBB

ICD ICD

130–149 ms with LBBB

ICD CRT-P or CRT-D

>150 ms CRT-D CRT-P or CRT-Ds

These guidelines are written after considering the economic constraints so that it is suggested that ICDs and CRT are implanted in a population likely to benefit the most from these devices. Patients in Class I and ambulatory Class IV and with QRS 120–130 also feature in other Western guidelines. Clinical benefit in this subset is likely to be less. Emphasis should be optimize medical therapy, ensure lifestyle changes and address the comorbid conditions.

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RECOMMENDATIONS FOR IMPLANTABLE CARDIOVERTER DEFIBRILLATOR

We recommend an ICD be implanted in patients with a history of hemodynamically significant sustained ventricular arrhythmia (VA) in the absence of a reversible medical cause (secondary prevention). It is important that the devices are implanted in patients who have a life expectancy of more than 2 years. Careful evaluation is necessary to exclude implants in patients with terminal CHF, and multiple comorbidities. ICD therapy is suggested for primary prevention of sudden cardiac death to reduce total mortality in selected patients with:• Nonischemic dilated cardiomyopathy or ischemic

heart disease at least 40 days post-MI.• With LVEF of 35% or less and NYHA Class II or III

symptoms, or <30% with NYHA Class I.• With one additional risk factor such as: Frequent

ventricular premature complexes or non sustained ventricular tachycardia on Holter, wide QRS on surface ECG, or history of syncope

– These are recommendations for primary prevention in Western guidelines, but for a country like India, these should be individualized and financial resources of the patient and the government also needs to be factored in, therefore, these cannot be kept as mandatory guidelines but just accepted as a subset for which there is evidence of clinical benefit. In clinical practice, not all patients in this subset are getting ICD implants

– We recommend an ICD not be implanted in NYHA Class IV HF patients who are not expected to improve with any further therapy and who are not candidates for cardiac transplant or mechanical circulatory support

– Unless there is a definite current or future need of ventricular pacing therapies, a single chamber ICD (as opposed to a dual chamber ICD) should be preferred for prevention of sudden cardiac death. This is relevant to Indian populations as the cost of dual chamber ICD is twice that of single chamber ICD.

INDICATIONS FOR CARDIAC RESYNCHRONIZATION THERAPYCardiac resynchronization therapy (CRT) is indicated for patients who have LVEF of 35% or less, sinus rhythm, LBBB with a QRS duration of 150 ms or greater, and NYHA Class III, or select ambulatory IV patients• CRT can be considered for patients who have LVEF of

35% or less, sinus rhythm, LBBB with a QRS duration of

130–149 ms, and NYHA Class II, III, or select ambulatory IV patients.

• CRT can be considered in patients with AF and LVEF of 35% or less if the patient requires ventricular pacing or otherwise meets CRT criteria and atrioventricular nodal ablation or pharmacological rate control will allow near 100% ventricular pacing with CRT.

• CRT can be considered for patients who have LVEF of 35% or less and are undergoing placement of a new or replacement device implantation with anticipated requirement for significant (>40%) ventricular pacing.

• CRT is not indicated for patients whose comorbidities limit survival to <1 year.

When CRT is implanted in younger patients, without comorbid illnesses, the risk of VAs should be carefully assessed. If patients are at high-risk of VA, CRT-D should be considered.

CARDIAC TRANSPLANTATION IndicationsCardiogenic shock requiring either continuous intravenous inotropic support or mechanical cardiac support (MCS) with an intra-aortic balloon pump counterpulsation device or MCS. Persistent NYHA Class IV CHF symptoms refractory to maximal medical therapy (LVEF <20%) and other alternative therapy including CRT. These are often patients with ischemic or dilated cardio-myopathy India. Congenital heart disease—either primary uncorrectable or failed palliated congenial. The following two indications are there in Western recommendations but not commonly followed in India, but these indications may be considered for patients with symptoms in spite of maximum medical care. Intractable or severe anginal symptoms in patients with CAD not amenable to percutaneous or surgical revascularization (this is usually not considered an indication for heart transplant in India). Intractable life-threatening arrhy-thmias unresponsive to medical therapy, catheter ablation, and/or implantation of an intracardiac defibrillator.

Ventricular Assist Device

For ventricular assist devices, the decision process is shown below: • A transplant or LV assist device (LVAD) is considered

for advanced HF. EF <20% (optimize medical treatment, CRT if QRS >120, NYHA III–IV, 6 minutes walk <300, frequent hospitalizations).

• Heart transplant or LVAD/biventricular assist device (BiVAD).

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• If not suitable for transplant (too old, high body mass index, high pulmonary vascular resistance index, recent malignancy, HIV, renal insufficiency, and liver insuffi ciency).

• Consider for LVAD/BiVAD if above contraindications for a transplant, as destination/also as an option for a bridge to transplant.

Bridge to transplantation: Patient listed for transplant with a severe hemodynamic compromise that is, unlikely to survive without mechanically-assisted circulation.

Destination therapy: Patient with HF refractory to medical management, but who is ineligible for transplant (most commonly older age, renal dysfunction, pulmonary hyper-tension, and high body mass index).

Bridge to recovery/decision: Patient with a potentially reversible cardiomyopathy requiring imminent mechanical support or candidacy for transplant cannot be determined at the time that a decision about ventricular assist device implant must be made. India is about to face a heart failure epidemic with a heart failure burden of as many as 8–10 million patients. Timely prevention by intervening at the level of risk factors of heart failure will prevent many patients from developing heart failure but when they do, guidelines and statements like these should help in improving the management of such patients.

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