Management of Heart Failure: Newer Insights (Diagnostic/Prognostic/ Therapeutic)

Introduction
Heart failure (HF) hospitalizations account for a substantial portion of the overall costs of caring for patients with HF and is associated with a staggering degree of morbidity and mortality, particularly in the elderly population. It is evident that the prognosis after an index hospitalization for HF is ominous, with a 50% rate of readmission at 6 months and a 25% to 35% incidence of death at 12 months.

Stages of Heart Failure

The current classification of heart failure (HF) lays emphasis on the development and progression of the disease. There are 4 stages in the development of the HF syndrome. The first 2 stages (A and B) are clearly not HF but are an attempt to help healthcare providers with the early identification of patients who are at risk for developing HF. Stages A and B patients are best defined as those with risk factors that clearly predispose toward the development of HF. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular (LV) function, hypertrophy, or geometric chamber distortion would be considered Stage A, whereas patients who are asymptomatic but demonstrate LV hypertrophy and/or impaired LV function would be designated as Stage B. Stage C denotes patients with current or past symptoms of HF associated with underlying structural heart disease (the bulk of patients with HF), and Stage D designates patients with truly refractory HF who might be eligible for specialized, advanced treatment strategies, such as mechanical circulatory support, procedures to facilitate fluid removal, continuous inotropic infusions, or cardiac transplantation or other innovative or experimental surgical procedures, or for end-of-life care, such as hospice.

Initial Evaluation of Patients

In general, patients with LV dysfunction or HF present in hospitals in 1 of 3 ways:

1.With a syndrome of decreased exercise tolerance. Most patients with HF seek medical attention with complaints of a reduction in their effort tolerance due to dyspnea and/or fatigue. These symptoms, which may occur at rest or during exercise, may be attributed inappropriately by the patient and/or healthcare provider to aging, other physiological abnormalities (e.g., deconditioning), or other medical disorders (e.g., pulmonary disease). Therefore, in a patient whose exercise capacity is limited by dyspnea or fatigue, the healthcare provider must determine whether the principal cause is HF or another abnormality.

2.With a syndrome of fluid retention. Patients may present with complaints of leg or abdominal swelling as their primary (or only) symptom. In these patients, the impairment of exercise tolerance may occur so gradually that it may not be noted unless the patient is questioned carefully and specifically about a change in activities of daily living.

3.With no symptoms or symptoms of another cardiac or noncardiac disorder. During their evaluation for a disorder other than HF (e.g., abnormal heart sounds or abnormal electrocardiogram or chest x-ray, hypertension or hypotension, diabetes mellitus, an acute myocardial infarction (MI), an arrhythmia, or a pulmonary or systemic thromboembolic event), patients may be found to have evidence of cardiac enlargement or dysfunction.

A variety of approaches have been used to quantify the degree of functional limitation imposed by HF. The most widely used scale is the NYHA functional classification, but this system is subject to considerable interobserver variability and is insensitive to important changes in exercise capacity. These limitations may be overcome by formal tests of exercise tolerance. Measurement of the distance that a patient can walk in 6 minutes has prognostic significance and may help to assess the level of functional impairment in sick patients, but serial changes in walking distance may not parallel changes in clinical status.

Common Factors That Precipitate Hospitalization for Heart Failure
•Noncompliance with medical regimen, sodium and/or fluid restriction
•Acute myocardial ischemia
•Uncorrected high blood pressure
•Atrial fibrillation and other arrhythmias
•Recent addition of negative inotropic drugs (e.g., verapamil, nifedipine, diltiazem, beta blockers)
•Pulmonary embolus
•Nonsteroidal anti-inflammatory drugs
•Excessive alcohol or illicit drug use
•Endocrine abnormalities (e.g., diabetes mellitus, hyperthyroidism, hypothyroidism)
•Concurrent infections (e.g., pneumonia, viral illnesses)

Clinical Work Up

A complete history and physical examination are the first steps in evaluating the structural abnormality or cause responsible for the development of HF. Direct inquiry may reveal prior or current evidence of MI, valvular disease, or congenital heart disease, whereas examination of the heart may suggest the presence of cardiac enlargement, murmurs, or a third heart sound. Although the history and physical examination may provide important clues about the nature of the underlying cardiac abnormality, identification of the structural abnormality leading to HF generally requires noninvasive or invasive imaging of the cardiac chambers or great vessels.

X-ray Chest & ECG
Chest radiography is used to estimate the degree of cardiac enlargement and pulmonary congestion or to detect the presence of pulmonary disease. A 12-lead electrocardiogram may demonstrate evidence of prior MI, LV hypertrophy, cardiac conduction abnormality (e.g., left bundle-branch block), or a cardiac arrhythmia. However, because of their low sensitivity and specificity, neither the chest x-ray nor the electrocardiogram should form the primary basis for determining the specific cardiac abnormality responsible for the development of HF.

Echocardiography

The single most useful diagnostic test in the evaluation of patients with HF is the comprehensive 2-dimensional echocardiogram coupled with Doppler flow studies to determine whether abnormalities of myocardium, heart valves, or pericardium are present and which chambers are involved. A comprehensive echocardiographic evaluation is important, because it is common for patients to have more than one cardiac abnormality that contributes to the development of HF. Furthermore, the study may serve as a baseline for comparison, because measurement of EF and the severity of structural remodeling can provide useful information in patients who have had a change in clinical status or who have experienced or recovered from a clinical event or received treatment that might have had a significant effect on cardiac function.
Three fundamental questions must be addressed: 1) Is the LV ejection fraction (EF) preserved or reduced? 2) Is the structure of the LV normal or abnormal? 3) Are there other structural abnormalities such as valvular, pericardial, or right ventricular abnormalities that could account for the clinical presentation? This information should be quantified with a numerical estimate of EF, measurement of ventricular dimensions and/or volumes, measurement of wall thickness, and evaluation of chamber geometry and regional wall motion.
Right ventricular size and systolic performance should also be assessed. Atrial size should be determined semiquantitatively and left atrial dimensions and/or volumes measured. All valves should be evaluated for anatomic and flow abnormalities to exclude the presence of primary valve disease. Secondary changes in valve function, particularly the severity of mitral and tricuspid valve insufficiency, should be determined.
Noninvasive hemodynamic data acquired at the time of echocardiography are an important additional correlate for patients with preserved or reduced EF. Combined quantification of the mitral valve inflow pattern, pulmonary venous inflow pattern, and mitral annular velocity provides data about characteristics of LV filling and left atrial pressure. Evaluation of the tricuspid valve regurgitant gradient coupled with measurement of inferior vena caval dimension and its response during respiration provides an estimate of systolic pulmonary artery pressure and central venous pressure. Stroke volume may be determined with combined dimension measurement and pulsed Doppler in the LV outflow tract. However, abnormalities can be present in any of these parameters in the absence of HF. No single parameter necessarily correlates specifically with HF; however, a totally normal filling pattern argues against clinical HF.


Coronary Angiography

An important cause of worsening HF, and for new-onset HF, is an acute MI. Because many patients admitted with acute HF have coronary artery disease, troponins are typically evaluated at admission for acute exacerbation. Actual criteria for an acute coronary event that may indicate the need for further intervention may be present in up to 20% of patients. However, many other patients may have low levels of detectable troponins not meeting criteria for an acute ischemic event but typical of chronic HF with an acute exacerbation. For the patient with newly discovered HF, clinicians should be aware of the important role of coronary artery disease in causing HF and should be certain that coronary structure and function are well delineated while simultaneously beginning treatment. Coronary visualization is an important part of the evaluation of patients hospitalized with HF.

Other Tests

These may be used to provide information regarding the nature and severity of the cardiac abnormality. Radionuclide ventriculography can provide highly accurate measurements of LV function and right ventricular EF, but it is unable to directly assess valvular abnormalities or cardiac hypertrophy. Magnetic resonance imaging or computed tomography (CT) may be useful in evaluating chamber size and ventricular mass, detecting right ventricular dysplasia, or recognizing the presence of pericardial disease, as well as in assessing cardiac function and wall motion. It may also be used to identify myocardial viability and scar tissue.

Laboratory Testing

Laboratory testing may reveal the presence of disorders or conditions that can lead to or exacerbate HF. The initial evaluation of patients with HF should include a complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), glycosylated hemoglobin, and blood lipids, as well as tests of both renal and hepatic function, a chest radiograph, and a 12-lead electrocardiogram. Thyroid function tests (especially thyroid-stimulating hormone) should be measured, because both hyperthyroidism and hypothyroidism can be a primary or contributory cause of HF. A fasting transferrin saturation in select patients is useful to screen for hemochromatosis. Magnetic resonance imaging of the heart or liver may be needed to confirm the presence of iron overload. Screening for human immunodeficiency virus (HIV) is reasonable and should be considered for all high-risk patients. However, other clinical signs of HIV infection typically precede any HF symptoms in those patients who develop HIV cardiomyopathy. Serum titers of antibodies developed in response to infectious organisms are occasionally measured in patients with a recent onset of HF, but the yield of such testing is low, and the therapeutic implications of a positive result are uncertain. Assays for connective tissue diseases and for pheochromocytoma should be performed if these diagnoses are suspected.
Several recent assays have been developed for natriuretic peptides (BNP and NT-proBNP). Several of the natriuretic peptides are synthesized by and released from the heart. Natriuretic peptides are sensitive to other biological factors, such as age, sex, weight, and renal function. Elevated levels lend support to a diagnosis of abnormal ventricular function or hemodynamics causing symptomatic HF. Elevated plasma BNP levels have been associated with reduced LVEF, LV hypertrophy, elevated LV filling pressures, and acute MI and ischemia, although they can occur in other settings, such as pulmonary embolism and chronic obstructive pulmonary disease.
BNP levels tend to be less elevated in HF with preserved EF than in HF with low EF and are lower in obese patients. Levels of natriuretic peptides may be elevated meaningfully in women and in people over 60 years of age who do not have HF, and thus these levels should be interpreted cautiously in such individuals when distinguishing between cardiac and noncardiac causes of dyspnea. Elevated natriuretic peptide levels may lend weight to a suspected diagnosis of HF or trigger consideration of HF when the diagnosis is unknown but should not be used in isolation to confirm or exclude the presence of HF.
Serum electrolytes and renal function should be monitored routinely in patients with HF. Of particular importance is the serial measurement of serum potassium concentration, because hypokalemia is a common adverse effect of treatment with diuretics and may cause fatal arrhythmias and increase the risk of digitalis toxicity, whereas hyperkalemia may complicate therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. Worsening renal function may require adjustment of the doses of diuretics, renin-angiotensin-aldosterone system antagonists, digoxin, and noncardiac medications. Development of hyponatremia or anemia may be a sign of disease progression and is associated with impaired survival.
Serial chest radiographs are not recommended in the management of chronic HF. Although the cardiothoracic ratio is commonly believed to reflect the cardiac dilatation that is characteristic of HF, enlargement of the cardiac silhouette primarily reflects changes in right ventricular volume rather than LV function, because the right ventricle forms most of the border of dilated hearts on radiographs. Similarly, changes in the radiographic assessment of pulmonary vascular congestion are too insensitive to detect any but the most extreme changes in fluid status.
Repeat assessment of EF may be most useful when the patient has demonstrated a major change in clinical status. Both improvement and deterioration may have important implications for future care, although the recommended medical regimen should be continued in most cases. Improvement may reflect recovery from a previous condition, such as viral myocarditis or hypothyroidism, or may occur after titration of recommended therapies for chronic HF. Thus, it is appropriate to obtain a repeat EF after some period of optimal medical therapy, typically 4 to 6 months, to decide about the implantation of an implantable cardioverter-defibrillator (ICD). Deterioration may reflect gradual disease progression or a new event, such as recurrent MI. Routine assessment of EF at frequent, regular, or arbitrary intervals is not recommended.

Assessment of Prognosis

Although both healthcare providers and patients may be interested in defining the prognosis of an individual patient with HF, the likelihood of survival can be determined reliably only in populations and not in individuals. However, some attempt at prognostication in HF may provide better information for patients and their families to help them appropriately plan for their futures. It also identifies patients in whom cardiac transplantation or mechanical device therapy should be considered.
Decreasing LVEF, worsening NYHA functional status, degree of hyponatremia, decreasing peak exercise oxygen uptake, decreasing hematocrit, widened QRS on 12-lead electrocardiogram, chronic hypotension, resting tachycardia, renal insufficiency, intolerance to conventional therapy, and refractory volume overload are all generally recognized key prognostic parameters. Although elevated circulating levels of neurohormonal factors have also been associated with high mortality rates, the routine assessment of neurohormones such as norepinephrine or endothelin is neither feasible nor helpful in clinical management. Likewise, elevated BNP (or NT-proBNP) levels predict higher risk of HF and other events after MI, whereas marked elevation in BNP levels during hospitalization for HF may predict rehospitalization and death. Nonetheless, the BNP measurement has not been clearly shown to supplement careful clinical assessment for management.

Therapy of Heart Failure

General Therapeutic Measures

Of the general measures that should be used in patients with HF, possibly the most effective yet least used is close observation and follow-up. Nonadherence with diet and medications can rapidly and profoundly affect the clinical status of patients, and increases in body weight and minor changes in symptoms commonly precede by several days the occurrence of major clinical episodes that require emergency care or hospitalization. Patient education and close supervision, which includes surveillance by the patient and his or her family, can reduce the likelihood of nonadherence and lead to the detection of changes in body weight or clinical status early enough to allow the patient or a healthcare provider an opportunity to institute treatments that can prevent clinical deterioration.
Moderate sodium restriction, along with daily measurement of weight, is indicated to permit effective use of lower and safer doses of diuretic drugs, even if overt sodium retention can be controlled by the use of diuretics. Immunization with influenza and pneumococcal vaccines may reduce the risk of a respiratory infection. Although most patients should not participate in heavy labor or exhaustive sports, physical activity should be encouraged (except during periods of acute exacerbation of the signs and symptoms of HF, or in patients with suspected myocarditis), because restriction of activity promotes physical deconditioning, which may adversely affect clinical status and contribute to the exercise intolerance of patients with HF.
Three classes of drugs can exacerbate the syndrome of HF and should be avoided in most patients:
1.Antiarrhythmic agents can exert important cardiodepressant and proarrhythmic effects. Of available agents, only amiodarone and dofetilide have been shown not to adversely affect survival.
2.Calcium channel blockers can lead to worsening HF and have been associated with an increased risk of cardiovascular events. Of available calcium channel blockers, only the vasoselective ones have been shown not to adversely affect survival.
3.Nonsteroidal anti-inflammatory drugs can cause sodium retention and peripheral vasoconstriction and can attenuate the efficacy and enhance the toxicity of diuretics and ACE inhibitors.

Patients with HF should be monitored carefully for changes in serum potassium, and every effort should be made to prevent the occurrence of either hypokalemia or hyperkalemia, both of which may adversely affect cardiac excitability and conduction and may lead to sudden death. Activation of both the sympathetic nervous system and renin-angiotensin system can lead to hypokalemia, and most drugs used for the treatment of HF can alter serum potassium. Even modest decreases in serum potassium can increase the risks of using digitalis and antiarrhythmic drugs, and even modest increases in serum potassium may prevent the use of treatments known to prolong life. Hence, many experts believe that serum potassium concentrations should be targeted in the 4.0 to 5.0 mmol per liter range. In some patients, correction of potassium deficits may require supplementation of magnesium and potassium. In others (particularly those taking ACE inhibitors alone or in combination with aldosterone antagonists), the routine prescription of potassium salts may be unnecessary and potentially deleterious.
Often, patients with chronic HF are admitted with acute decompensation from a number of possible precipitating causes. Clinicians should carefully review the patient’s maintenance HF medications and decide whether adjustments should be made as a result of the hospitalization. The large majority of patients with HF admitted to the hospital, especially those with concomitant hypertension, should have their oral therapy continued, or even uptitrated, during hospitalization. It is important to note that it has been shown that continuation of beta blockers for most patients is well tolerated and results in better outcomes. Withholding of or reduction in beta-blocker therapy should be considered only in patients hospitalized after recent initiation or increase in beta-blocker therapy or with marked volume overload.
Patients admitted with worsening azotemia should be considered for a reduction in or temporary discontinuation of their ACE inhibitors, ARBs, and/or aldosterone antagonists until renal function improves. Patients with marked volume overload will require intravenous diuretic therapy with uptitration of diuretic dose and/or addition of synergistic diuretic agents. It should be noted that uptitration of ACE inhibitors or beta blockers during decompensation may reduce the efficacy of the acute interventions to relieve congestion. Although it is important to ensure that evidence-based medications are instituted prior to the patient leaving the hospital, it is equally as critical to reassess medications on admission and to adjust their administration in light of the worsening HF.

Treatment of Acute Decompensation

A patient may develop acute or progressive symptoms of HF and require hospitalization. In general, there are 3 clinical profiles that describe the hospitalized patient with HF: 1) the patient with volume overload, manifested by pulmonary and/or systemic congestion, frequently precipitated by an acute increase in chronic hypertension; 2) the patient with profound depression of cardiac output manifested by hypotension, renal insufficiency, and/or a shock syndrome, and 3) the patient with signs and symptoms of both fluid overload and shock.
Irrespective of the presenting clinical picture, there have been a confusing variety of terms in the literature used to describe these patients, including acute HF syndrome, acute decompensated HF, or cardiogenic shock. However different these 3 groups of patients may be in outcome, they can all be characterized as having a change in HF signs and symptoms resulting in a need for urgent therapy. Patients with HF and preserved LVEF are just as likely to be admitted to hospital as those with HF and low LVEF. Admission with HF is often triggered by a concomitant cardiovascular event such as a symptomatic tachyarrhythmia, unstable coronary syndrome, or a cerebrovascular event; often the admission is related to medical or dietary noncompliance. The threshold for admission may also be lowered when HF exacerbation is accompanied with a noncardiac condition such as pneumonia or newly diagnosed anemia. Indeed, it is important to note that concurrent conditions and comorbidities such as coronary artery disease, hypertension, valvular heart disease, arrhythmias, renal dysfunction, diabetes, thromboembolism, and anemia are often present, more so than has usually been described in clinical trials, and may precipitate or contribute to the pathophysiology of the syndrome. Unfortunately, the precipitating event leading to hospitalization is not always readily apparent.

Diuretics
Patients admitted with evidence of significant fluid overload should initially be treated with loop diuretics, usually given intravenously. Therapy for this compelling presentation of HF should begin in the emergency department and should be initiated without delay. Early intervention has been associated with better outcomes for patients hospitalized with decompensated HF. After admission to the hospital, patients should be carefully monitored in accordance with the severity of their symptoms and the results of initial findings on the physical examination and laboratory assessment. Careful and frequent serial evaluation of the patient is important primarily to assess volume status and adequacy of circulatory support. Laboratory parameters are likewise necessary to judge efficacy of treatment. Monitoring of daily weight, supine and standing vital signs, fluid input, and output is a necessary part of daily management; assessment of daily electrolytes and renal function should be done while intravenous diuretics or active HF medication titration is being undertaken.
Intravenous loop diuretics have the potential to reduce glomerular filtration rate (GFR), further worsen neurohumoral activation, and produce electrolyte disturbances. Thus, although the use of diuretics may result in the effective relief of symptoms, their impact on mortality has not been well studied. Diuretics should be administered at doses sufficient to produce a rate of diuresis that will optimize volume status and relieve signs and symptoms of congestion without inducing an excessively rapid reduction in intravascular volume, which could result in hypotension, renal dysfunction, or both. Because loop diuretics have a relatively short half-life, sodium reabsorption in the tubules will occur once the tubular concentration of the diuretics declines. Therefore, strictly limiting sodium intake and dosing the diuretic multiple times per day will enhance effectiveness of the diuresis. Some patients may present with congestion and moderate to severe renal dysfunction. The response to diuretics may be significantly blunted, requiring higher initial doses. In many cases, reduction of fluid overload may improve not only congestion but also renal dysfunction, particularly if significant venous congestion is reduced.
When a patient with congestion fails to respond to initial doses of intravenous diuretics, several options may be considered. This is particularly important for the patient with progressive renal insufficiency. If there is substantial doubt about the fluid status of the patient, HF experts suggest that it is an appropriate time for a formal hemodynamic assessment of ventricular filling pressures and cardiac output, typically done with a right heart catheterization. If volume overload is confirmed, the dose of the loop diuretic should be initially increased to ensure that adequate drug levels reach the kidney. If this is inadequate, a second type of diuretic, typically a thiazide (metolazone or intravenous chlorothiazide) or spironolactone, can be added to improve diuretic responsiveness. As a third strategy, continuous infusion of the loop diuretic may be considered. By continuous delivery of the diuretic to the nephron, rebound resorption occurring during the time blood levels of diuretic are low is avoided and ototoxicity risk may actually be reduced. If all diuretic strategies are unsuccessful, ultrafiltration or another renal replacement strategy may be reasonable. Ultrafiltration moves water and small to medium-weight solutes across a semipermeable membrane to reduce volume overload. Because the electrolyte concentration is similar to plasma, relatively more sodium can be removed than by diuretics. Consultation with a nephrologist may be appropriate before opting for any mechanical strategy to affect diuresis.

Aldosterone Antagonists
The addition of low-dose aldosterone antagonists is recommended in carefully selected patients with moderately severe or severe HF symptoms and recent decompensation or with LV dysfunction early after MI. These recommendations are based on the strong data demonstrating reduced death and rehospitalization in 2 clinical trial populations. For both of these major trials, patients were excluded for a serum creatinine level in excess of 2.5 mg per dL. In the trial of patients after MI, there was a significant interaction between serum creatinine and benefit of eplerenone. The average serum creatinine of enrolled patients was 1.1 mg per dL, above which there was no demonstrable benefit for survival.
To minimize the risk of life-threatening hyperkalemia in patients with low LVEF and symptoms of HF, patients should have initial serum creatinine less than 2.0 to 2.5 mg per dL without recent worsening and serum potassium less than 5.0 mEq per liter without a history of severe hyperkalemia. In view of the consistency of evidence for patients with low LVEF early after MI and patients with recent decompensation and severe symptoms, it may be reasonable to consider addition of aldosterone antagonists to loop diuretics for some patients with mild to moderate symptoms of HF . The safety of the combination of ACE inhibitors, ARBs, and aldosterone antagonists has not been explored adequately, and this combination cannot be recommended.

Vasodilators
There are a number of clinical scenarios whereby the addition of vasodilators to the HF regimen of the hospitalized patient might be appropriate. For patients with adequate blood pressure and ongoing congestion not sufficiently responsive to diuretics and standard oral therapy (e.g., maintenance of prior HF medications, if applicable), intravenous vasodilators such as nitroprusside, nitroglycerin, or nesiritide may be added to the treatment regimen. Regardless of the agent used, the clinician should make certain that intravascular volume is, in fact, expanded and that the patient’s blood pressure can tolerate the addition of the vasodilating drug.
Intravenous nitroglycerin, primarily through venodilation effects, lowers preload and may help to more rapidly reduce pulmonary congestion. Patients with HF and hypertension, coronary ischemia, or significant mitral regurgitation are often cited as ideal candidates for the use of intravenous nitroglycerin. However, tachyphylaxis to nitroglycerin may develop rather quickly and up to 20% of those with HF may develop resistance to even high doses.
Sodium nitroprusside is a balanced preload-reducing venodilator and afterload-reducing arteriodilator that also dilates the pulmonary vasculature. Data demonstrating efficacy are limited, and invasive hemodynamic blood pressure monitoring is typically required. Nitroprusside has the potential for producing marked hypotension and is usually used in the intensive care setting as well; longer infusions of the drug have been associated with thiocyanate toxicity, particularly in the setting of renal insufficiency. Nitroprusside is potentially of value in severely congested patients with hypertension or severe mitral valve regurgitation complicating LV dysfunction.
Nesiritide (human BNP) reduces LV filling pressure but has variable effects on cardiac output, urinary output, and sodium excretion. The severity of dyspnea is reduced more rapidly compared to diuretics alone. Because nesiritide has a longer effective half-life than nitroglycerin or nitroprusside, side effects such as hypotension may persist longer. Conservative dosing of the drug (i.e., no bolus) and use of only the recommended doses may reduce complications. Adverse renal consequences with nesiritide have been suggested; careful monitoring of renal function is mandatory. The effects of nesiritide on mortality remain uncertain and active clinical investigation is ongoing.
The role of intravenous vasodilators for the patient hospitalized with HF cannot be generalized. The goals of HF therapy with vasodilators, in the absence of more definitive data, include a more rapid resolution of congestive symptoms; relief of anginal symptoms while awaiting coronary intervention; control of hypertension complicating HF; and, in conjunction with ongoing hemodynamic monitoring while the intravenous drug is administered, improvement of hemodynamic abnormalities prior to instituting oral HF medications.
Hydralazine and Isosorbide Dinitrate
In a large-scale trial that compared the vasodilator combination with placebo, the use of hydralazine and isosorbide dinitrate reduced mortality but not hospitalizations in patients with HF treated with digoxin and diuretics but not an ACE inhibitor or beta blocker. However, in another large-scale trial that compared the vasodilator combination with an ACE inhibitor, the ACE inhibitor produced more favorable effects on survival, a benefit not evident in the subgroup of patients with Class III to IV HF. In both trials, the use of hydralazine and isosorbide dinitrate produced frequent adverse reactions (primarily headache and gastrointestinal complaints), and many patients could not continue treatment at target doses.
The addition of hydralazine and isosorbide dinitrate to standard therapy with an ACE inhibitor and/or a beta blocker has been shown to be of significant benefit in the African American cohort. The benefit was presumed to be related to enhanced nitric oxide bioavailability. Accordingly, this combination is recommended for African Americans who remain symptomatic despite optimal medical therapy. Whether this benefit is evident in other patients with HF remains to be investigated. The combination of hydralazine and isosorbide dinitrate should not be used for the treatment of HF in patients who have no prior use of an ACE inhibitor and should not be substituted for ACE inhibitors in patients who are tolerating ACE inhibitors without difficulty.
Inotropes
Patients presenting with either predominantly low output syndrome (e.g., symptomatic hypotension) or combined congestion and low output may be considered for intravenous inotropes such as dopamine, dobutamine, and milrinone. These agents may help relieve symptoms due to poor perfusion and preserve end-organ function in patients with severe systolic dysfunction and dilated cardiomyopathy. Inotropic agents are of greatest value in patients with relative hypotension and intolerance or no response to vasodilators and diuretics. Clinicians should be cautioned again that the use of these drugs portends a very poor prognosis for their patients; a thorough hemodynamic assessment must be undertaken to ensure that the low output syndrome is responsible for the presenting clinical signs and symptoms. Likewise, clinicians should not use a specific blood pressure value that might or might not mean hypotension, to dictate the use of inotropic agents. Rather, a depressed blood pressure associated with signs of poor cardiac output or hypoperfusion (e.g., cold clammy skin, cool extremities, decreased urine output, altered mentation) should prompt a consideration for more aggressive intravenous therapy. Dobutamine requires the beta-receptor for its inotropic effects, while milrinone does not. This may be a significant consideration for patients already maintained on beta-blocking drugs. Furthermore, milrinone has vasodilating properties for both the systemic circulation and the pulmonary circulation. Despite these considerations, there is no evidence of benefit for routine use of inotropic support in patients presenting with acute HF due to congestion only. Indeed, data from several studies suggest an increase in adverse outcomes when inotropes are used. Thus, inotropes should be confined to carefully selected patients with low blood pressure and reduced cardiac output who can have blood pressure and heart rhythm monitored closely.
Routine invasive hemodynamic monitoring is not indicated for most patients hospitalized with symptoms of worsening HF. However, hemodynamic monitoring should be strongly considered in patients with 1) presumed cardiogenic shock requiring escalating pressor therapy and consideration of mechanical support, 2) severe clinical decompensation in which therapy is limited by uncertainty regarding relative contributions of elevated filling pressures, hypoperfusion, and vascular tone, 3) apparent dependence on intravenous inotropic infusions after initial clinical improvement, or 4) persistent severe symptoms despite adjustment of recommended therapies. This reinforces the concept that right heart catheterization is best reserved for those situations where a specific clinical or therapeutic question needs to be addressed.

Arrhythmias in Heart Failure

Supraventricular Arrhythmias in Heart Failure

The course of patients with HF is frequently complicated by supraventricular tachyarrhythmias, which may occur when the myocardial disease process affects the atria or when the atria are distended as a result of pressure or volume overload of the right or left ventricles. The most common treatable atrial arrhythmia is atrial fibrillation, which affects 10% to 30% of patients with chronic HF and is associated with a reduction in exercise capacity and a worse long-term prognosis.
Supraventricular tachyarrhythmias may exert adverse effects via 4 different mechanisms: 1) the loss of atrial enhancement of ventricular filling may compromise cardiac output; 2) the rapid heart rate may increase demand and decrease coronary perfusion; 3) the rapidity of ventricular response may diminish both cardiac contraction (by aggravating abnormalities of the force-frequency relation) and cardiac relaxation; and 4) the stasis of blood in the fibrillating atria may predispose patients to pulmonary or systemic emboli. In most patients with an ischemic or nonischemic dilated cardiomyopathy, the rapidity of ventricular response is more important than the loss of atrial support, because restoration of sinus rhythm does not result in predictable clinical benefits. Rapid supraventricular arrhythmias may actually cause a cardiomyopathy or may exacerbate a cardiomyopathy caused by another disorder. Hence, the control of ventricular rate and the prevention of thromboembolic events are essential elements of treatment of HF in patients with an underlying supraventricular arrhythmia.
Specific care and initially low doses should be used when beta blockers are instituted to control heart rate in patients with clinical evidence of HF decompensation. The agent previously used in clinical practice to slow the ventricular response in patients with HF and atrial fibrillation is digoxin, but the cardiac glycoside slows atrioventricular conduction more effectively at rest than during exercise. Hence, digitalis does not block the excessive exercise-induced tachycardia that may limit the functional capacity of patients with HF. Beta blockers are more effective than digoxin during exercise and are preferred because of their favorable effects on the natural history of HF. The combination of digoxin and beta blockers may be more effective than beta blockers alone for rate control. Although both verapamil and diltiazem can also suppress the ventricular response during exercise, they can depress myocardial function and increase the risk of worsening HF, especially in patients with HF and low EF, in whom these drugs should be avoided. If beta-blockers are ineffective or contraindicated in patients with atrial fibrillation and HF, amiodarone may be a useful alternative. Atrioventricular nodal ablation may be needed if tachycardia persists despite pharmacological therapy. Catheter ablation for pulmonary vein isolation has been most effective in patients without structural heart disease; the benefit for patients with established HF is not known. Regardless of the intervention used, every effort should be made to reduce the ventricular response to less than 80 to 90 bpm at rest and less than 110 to 130 bpm during moderate exercise. Anticoagulation should be maintained in all patients with HF and a history of atrial fibrillation, regardless of whether sinus rhythm is achieved, because of the high rate of silent recurrence of atrial fibrillation with its attendant embolic risk, unless a contraindication exists.
Both strategies for the management of atrial fibrillation, either to restore and maintain sinus rhythm by electrical or pharmacologic conversion, or to control ventricular rate in atrial fibrillation, have been shown to have equivalent outcomes. Most patients revert to atrial fibrillation within a short time unless they are treated with a Class I or III antiarrhythmic drug. However, patients with HF are not likely to respond favorably to Class I drugs and may be particularly predisposed to their cardiodepressant and proarrhythmic effects, which can increase the risk of death. Class III antiarrhythmic agents (e.g., sotalol, dofetilide, and amiodarone) can maintain sinus rhythm in some patients, but treatment with these drugs is associated with an increased risk of organ toxicity (amiodarone) and proarrhythmia (dofetilide). Most patients who had thromboembolic events, regardless of the strategy used, were in atrial fibrillation at the time of the event and either were not undergoing anticoagulation therapy or were undergoing therapy at subtherapeutic levels. Thus, it is reasonable to treat HF patients with atrial fibrillation with a strategy of either scrupulous rate control or an attempt at rhythm control.

Ventricular Arrhythmias in Heart failure and Prevention of Sudden Death

Patients with LV dilation and reduced LVEF frequently manifest ventricular tachyarrhythmias, both nonsustained ventricular tachycardia (VT) and sustained VT. The cardiac mortality of patients with all types of ventricular tachyarrhythmias is high. The high mortality results from progressive HF, as well as from sudden death. Sudden death is often equated with a primary arrhythmic event, but multiple causes of sudden death have been documented and include ischemic events such as acute MI, electrolyte disturbances, pulmonary or systemic emboli, or other vascular events. Although ventricular tachyarrhythmias are the most common rhythms associated with unexpected sudden death, bradycardia and other pulseless supraventricular rhythms are common in patients with advanced HF.
Sudden death can be decreased meaningfully by the therapies that decrease disease progression, as discussed elsewhere in these guidelines. For instance, clinical trials with beta blockers have shown a reduction in sudden death, as well as in all-cause mortality, in both postinfarction patients and patients with HF regardless of cause. Aldosterone antagonists decrease sudden death and overall mortality in HF early after MI and in advanced HF. Sudden unexpected death can be decreased further by the use of implanted devices that terminate sustained arrhythmias. Even when specific antiarrhythmic therapy is necessary to diminish recurrent ventricular tachyarrhythmias and device firings, the frequency and tolerance of arrhythmias may be improved with appropriate therapy for HF. In some cases, definitive therapy of myocardial ischemia or other reversible factors may prevent recurrence of tachyarrhythmia, particularly polymorphic VT, ventricular fibrillation, and nonsustained VT. Nonetheless, implantable defibrillators should be recommended in all patients who have had a life-threatening tachyarrhythmia and have an otherwise good prognosis.
The absolute frequency of sudden death is highest in patients with severe symptoms, or Stage D HF. Many patients with end-stage symptoms experience "sudden death" that is nonetheless expected. Prevention of sudden death in this population could potentially shift the mode of death from sudden to that of progressive HF without decreasing total mortality, as competing risks of death emerge. On the other hand, prevention of sudden death in mild HF may allow many years of meaningful survival. This makes it imperative for physicians to not only assess an individual patient’s risk for sudden death but also assess overall prognosis and functional capacity before consideration of device implantation.

Secondary Prevention of Sudden Death

Patients with previous cardiac arrest or documented sustained ventricular arrhythmias have a high risk of recurrent events. Implantation of an ICD has been shown to reduce mortality in cardiac arrest survivors. An ICD is indicated for secondary prevention of death from ventricular tachyarrhythmias in patients with otherwise good clinical function and prognosis, for whom prolongation of survival is a goal. Patients with chronic HF and a low EF who experience syncope of unclear origin have a high rate of subsequent sudden death and should also be considered for placement of an ICD. However, when ventricular tachyarrhythmias occur in a patient with a progressive and irreversible downward spiral of clinical HF decompensation, placement of an ICD is not indicated to prevent recurrence of sudden death, because death is likely imminent regardless of mode. An exception may exist for the small minority of patients for whom definitive therapy such as cardiac transplantation is planned.

Primary Prevention of Sudden Death

Patients with low EF without prior history of cardiac arrest, spontaneous VT, or inducible VT (positive programmed electrical stimulation study) have a risk of sudden death that is lower than for those who have experienced previous events, but it remains significant. Within this group, it has not yet been possible to identify those patients at highest risk, especially in the absence of prior MI. Approximately 50% to 70% of patients with low EF and symptomatic HF have episodes of nonsustained VT on routine ambulatory electrocardiographic monitoring; however, it is not clear whether the occurrence of complex ventricular arrhythmias in these patients with HF contributes to the high frequency of sudden death or, alternatively, simply reflects the underlying disease process.
Antiarrhythmic drugs to suppress premature ventricular depolarizations and nonsustained ventricular arrhythmias have not improved survival, although nonsustained VT may play a role in triggering ventricular tachyarrhythmias. Furthermore, most antiarrhythmic drugs have negative inotropic effects and can increase the risk of serious arrhythmia; these adverse cardiovascular effects are particularly pronounced in patients with low EF. This risk is especially high with the use of class IA agents (quinidine and procainamide), class IC agents (flecainide and propafenone), and some class III agents (D-sotalol), which have increased mortality in post-MI trials. Amiodarone is a class III antiarrhythmic agent but differs from other drugs in this class in having a sympatholytic effect on the heart. Amiodarone has been associated with overall neutral effects on survival when administered to patients with low EF and HF. Amiodarone therapy may also act through mechanisms other than antiarrhythmic effects, because amiodarone has been shown in some trials to increase LVEF and decrease the incidence of worsening HF. Side effects of amiodarone have included thyroid abnormalities, pulmonary toxicity, hepatotoxicity, neuropathy, insomnia, and numerous other reactions. Therefore, amiodarone should not be considered as part of the routine treatment of patients with HF, with or without frequent premature ventricular depolarizations or asymptomatic nonsustained VT; however, it remains the agent most likely to be safe and effective when antiarrhythmic therapy is necessary to prevent recurrent atrial fibrillation or symptomatic ventricular arrhythmias. Other pharmacological antiarrhythmic therapies, apart from beta blockers, are rarely indicated in HF but may occasionally be used to suppress recurrent ICD shocks when amiodarone has been ineffective or discontinued owing to toxicity.
The role of ICDs in the primary prevention of sudden death in patients without prior history of symptomatic arrhythmias has been explored recently in a number of trials. If sustained ventricular tachyarrhythmias can be induced in the electrophysiology laboratory in patients with previous MI or chronic ischemic heart disease, the risk of sudden death in these patients is in the range of 5% to 6% per year and can be improved by ICD implantation.
The role of ICD implantation for the primary prevention of sudden death in patients with HF and low EF and no history of spontaneous or inducible VT has been addressed by several large trials. The first of these demonstrated that ICDs, compared with standard medical therapy, decreased the occurrence of total mortality for patients with EF of 30% or less after remote MI. Absolute mortality was decreased in the ICD arm by 5.6%, a relative decrease of 31% over 20 months. In another trial examining the benefit of ICD implantation for patients with EF less than 35% and NYHA functional class II to III symptoms of HF included both ischemic and nonischemic causes of HF; absolute mortality was decreased by 7.2% over a 5-year period in the arm that received a simple "shock-box" ICD with backup pacing at a rate of 40 bpm. This represented a relative mortality decrease of 23%, which was a survival increase of 11%. There was no improvement in survival during the first year, with a 1.8% absolute survival benefit per year averaged over the next 4 years. A survival benefit has not been demonstrated with devices implanted within 6 to 40 days after an acute MI in patients who at that time had an EF less than 35% and abnormal heart rate variability. Although sudden deaths were decreased, there was an increase in other events, and ICD implantation did not confer any survival benefit in this setting.
The DEFINITE (Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation) trial compared medical therapy alone with medical therapy plus an ICD in patients with nonischemic cardiomyopathy, NYHA class I to III HF, and an LVEF less than 36%. The ICD was associated with a reduction in all-cause mortality that did not reach statistical significance but was consistent in terms of magnitude of effect (30%) with the findings of the MADIT II and the SCD-HeFT trial.
ICDs are highly effective in preventing death due to ventricular tachyarrhythmias; however, frequent shocks from an ICD can lead to a reduced quality of life, whether triggered appropriately by life-threatening rhythms or inappropriately by sinus or other supraventricular tachycardia. For symptoms from recurrent discharges triggered by ventricular arrhythmias or atrial fibrillation, antiarrhythmic therapy, most often amiodarone, may be added. For recurrent ICD discharges from VT despite antiarrhythmic therapy, catheter ablation may be effective.
It is important to recognize that ICDs have the potential to aggravate HF and have been associated with an increase in HF hospitalizations. This may result from right ventricular pacing that produces dyssynchronous cardiac contraction; however, the occurrence of excess nonsudden events with ICDs placed early after MI suggests that other factors may also limit the overall benefit from ICDs. Careful attention to the details of ICD implantation, programming, and pacing function is important for all patients with low EF who are treated with an ICD. The decision regarding the balance of potential risks and benefits of ICD implantation for an individual patient thus remains a complex one. A decrease in incidence of sudden death does not necessarily translate into decreased total mortality, and decreased total mortality does not guarantee a prolongation of survival with meaningful quality of life. This concept is particularly important in patients with limited prognosis owing to advanced HF or other serious comorbidities, because survival benefit after ICD implantation is generally evident after after the first year. Comorbidities common in the elderly population, such as prior stroke, chronic pulmonary disease, and crippling arthritic conditions, as well as nursing home residence, should be factored into discussions regarding ICD. Atrial fibrillation, a common trigger for inappropriate shocks, is more prevalent in the elderly population. The gap between community and trial populations is particularly important for a device therapy that may prolong survival but has no positive impact on function or quality of life. Some patients may suffer a diminished quality of life because of device-site complications, such as bleeding, hematoma, or infections, or after ICD discharges, particularly those that are inappropriate.
Consideration of ICD implantation is thus recommended in patients with EF less than or equal to 35% and mild to moderate symptoms of HF and in whom survival with good functional capacity is otherwise anticipated to extend beyond 1 year. Because medical therapy may substantially improve EF, consideration of ICD implants should follow documentation of sustained reduction of EF despite a course of beta blockers and ACE inhibitors or ARBs; however, ICDs are not warranted in patients with refractory symptoms of HF (Stage D) or in patients with concomitant diseases that would shorten their life expectancy independent of HF. Before implantation, patients should be fully informed of their cardiac prognosis, including the risk of both sudden and nonsudden mortality; the efficacy, safety, and risks of an ICD; and the morbidity associated with an ICD shock. Patients and families should clearly understand that the ICD does not improve clinical function or delay HF progression. Most important, the possible reasons and process for potential future deactivation of defibrillator features should be discussed long before functional capacity or outlook for survival is severely reduced.

Cardiac Resynchronization Therapy

Approximately one-third of patients with low EF and Class III to IV symptoms of HF manifest a QRS duration greater than 0.12 seconds. This electrocardiographic representation of abnormal cardiac conduction has been used to identify patients with dyssynchronous ventricular contraction. While imperfect, no other consensus definition of cardiac dyssynchrony exists as yet, although several echocardiographic measures appear promising. The mechanical consequences of dyssynchrony include suboptimal ventricular filling, a reduction in LV dP/dt (rate of rise of ventricular contractile force or pressure), prolonged duration (and therefore greater severity) of mitral regurgitation, and paradoxical septal wall motion. Ventricular dyssynchrony has also been associated with increased mortality in HF patients. Dyssynchronous contraction can be addressed by electrically activating the right and left ventricles in a synchronized manner with a biventricular pacemaker device. This approach to HF therapy, commonly called cardiac resynchronization therapy (CRT), may enhance ventricular contraction and reduce the degree of secondary mitral regurgitation. In addition, the short-term use of CRT has been associated with improvements in cardiac function and hemodynamics without an accompanying increase in oxygen use, as well as adaptive changes in the biochemistry of the failing heart.
To date, more than 4000 HF patients with ventricular dyssynchrony have been evaluated in randomized controlled trials of optimal medical therapy alone versus optimal medical therapy plus CRT with or without an ICD. CRT, when added to optimal medical therapy in persistently symptomatic patients, has resulted in significant improvements in quality of life, functional class, exercise capacity (by peak oxygen uptake) and exercise distance during a 6-minute walk test, and EF in patients randomized to CRT or to the combination of CRT and ICD. In a meta-analysis of several CRT trials, HF hospitalizations were reduced by 32% and all-cause mortality by 25%. The effect on mortality in this meta-analysis became apparent after approximately 3 months of therapy. In 1 study, subjects were randomized to optimal pharmacological therapy alone, optimal medical therapy plus CRT alone, or optimal medical therapy plus the combination of CRT and an ICD. Compared with optimal medical therapy alone, both device arms significantly decreased the combined risk of all-cause hospitalization and all-cause mortality by approximately 20%, whereas the combination of a CRT and an ICD decreased all-cause mortality significantly by 36%. More recently, in a randomized controlled trial comparing optimal medical therapy alone with optimal medical therapy plus CRT alone (without a defibrillator), CRT significantly reduced the combined risk of death of any cause or unplanned hospital admission for a major cardiovascular event (analyzed as time to first event) by 37%. In that trial, all-cause mortality was significantly reduced by 36% and HF hospitalizations by 52% with the addition of CRT.
Thus, there is strong evidence to support the use of CRT to improve symptoms, exercise capacity, quality of life, LVEF, and survival and to decrease hospitalizations in patients with persistently symptomatic HF undergoing optimal medical therapy who have cardiac dyssynchrony (as evidenced by a prolonged QRS duration). The use of an ICD in combination with CRT should be based on the indications for ICD therapy.
With few exceptions, resynchronization trials have enrolled patients in normal sinus rhythm. Although the entry criteria specified QRS duration only longer than 0.12 seconds, the average QRS duration in the large trials was longer than 0.15 seconds. Two small studies evaluated the potential benefit of CRT in HF patients with ventricular dyssynchrony and atrial fibrillation. Although both studies demonstrated the benefit of CRT in these patients, the total number of patients examined (fewer than 100) precludes a recommendation for CRT in otherwise eligible patients with atrial fibrillation. To date, only a small number of patients with "pure" right bundle-branch block have been enrolled in CRT trials.
The risks associated with CRT include peri-implant mortality of 0.4%, lead malfunction or dislodgement in 8.5%, pacemaker problems in 6.7%, and infection in 1.4% of cases. These morbidity and mortality data are derived from trials that used expert centers. Results in individual clinical centers may vary considerably and are subject to a significant learning curve for each center; however, as implantation techniques evolve and equipment improves, complication rates may also decline.

Patients With Refractory End-Stage Heart Failure (Stage D)

Most patients with HF due to reduced LVEF respond favorably to pharmacological and nonpharmacological treatments and enjoy a good quality of life and enhanced survival; however, some patients do not improve or experience rapid recurrence of symptoms despite optimal medical therapy. Such patients characteristically have symptoms at rest or on minimal exertion, including profound fatigue; cannot perform most activities of daily living; frequently have evidence of cardiac cachexia; and typically require repeated and/or prolonged hospitalizations for intensive management. These individuals represent the most advanced stage of HF and should be considered for specialized treatment strategies, such as mechanical circulatory support, continuous intravenous positive inotropic therapy, referral for cardiac transplantation, or hospice care. Before a patient is considered to have refractory HF, physicians should confirm the accuracy of the diagnosis, identify any contributing conditions, and ensure that all conventional medical strategies have been optimally employed.

Intravenous Peripheral Vasodilators and Positive Inotropic Agents

Patients with refractory HF are hospitalized frequently for clinical deterioration, and during such admissions, they commonly receive infusions of both positive inotropic agents (dobutamine, dopamine, or milrinone) and vasodilator drugs (nitroglycerin, nitroprusside, or nesiritide) in an effort to improve cardiac performance, facilitate diuresis, and promote clinical stability. Some physicians have advocated the placement of pulmonary artery catheters in patients with refractory HF, with the goal of obtaining hemodynamic measurements that might be used to guide the selection and titration of therapeutic agents. However, the logic of this approach has been questioned, because many useful drugs for HF produce benefits by mechanisms that cannot be evaluated by measuring their short-term hemodynamic effects. Regardless of whether invasive hemodynamic monitoring is used, once the clinical status of the patient has stabilized, every effort should be made to devise an oral regimen that can maintain symptomatic improvement and reduce the subsequent risk of deterioration. Assessment of the adequacy and tolerability of orally based strategies may necessitate observation in the hospital for at least 48 hours after the infusions are discontinued.
Patients who cannot be weaned from intravenous to oral therapy despite repeated attempts may require placement of an indwelling intravenous catheter to allow for the continuous infusion of dobutamine or milrinone or, as has been used more recently, nesiritide. Such a strategy is commonly used in patients who are awaiting cardiac transplantation, but it may also be used in the outpatient setting in patients who otherwise cannot be discharged from the hospital. Continuous intravenous support may provide palliation of symptoms as part of an overall plan to allow the patient to die with comfort at home. The use of continuous intravenous support to allow hospital discharge should be distinguished from the intermittent administration of infusions of such agents to patients who have been successfully weaned from inotropic support. Intermittent outpatient infusions of either vasoactive drugs such as nesiritide or positive inotropic drugs have not shown to improve symptoms or survival in patients with advanced HF.

Other Considerations
Other treatment or diagnostic strategies may be necessary for individual patients after stabilization, particularly related to the underlying cause of the acute event. The patient hospitalized with HF is at increased risk for thromboembolic complications and deep venous thrombosis and should receive prophylactic anticoagulation with either intravenous unfractionated heparin or subcutaneous preparations of unfractionated or low-molecular-weight heparin, unless contraindicated.
As the hospitalized patient becomes more clinically stable and volume status normalizes, oral HF therapy should be initiated or reintroduced. Particular caution should be used when initiating beta blockers in patients who have required inotropes during their hospital course or when initiating ACE inhibitors in those patients who have experienced marked azotemia. During additional hospital days, the patient should be fully transitioned off all intravenous therapy and oral therapy should be adjusted and maximized.

The Hospital Discharge
To ensure safe, high-quality, and efficient care for patients following hospitalization for HF, written discharge instructions or educational material should be given to patient and/or caregiver at discharge to home or during the hospital stay addressing all of the following: activity level, diet, discharge medications, follow-up appointment, weight monitoring, and what to do if symptoms worsen. Education of HF patients and their families is critical and often complex. Failure of these patients to understand how best to comply with physician’s and other healthcare providers’ instructions is often a cause of HF exacerbation leading to subsequent hospital readmission.
Large registries of hospitalized HF patients suggest that many patients are discharged before optimal volume status is achieved, or sent home without the benefit of life-saving therapies such as ACE/ARB and beta-blocker medications. Patients are discharged without adequate control of their blood pressure or the ventricular response to atrial fibrillation. Often, the treating clinician fails to appreciate the severity of the HF process or delays diagnostic testing until the patient is seen as an outpatient. These problems, and others, may account for the high rate of HF rehospitalizations. It is, therefore, incumbent on healthcare professionals to be certain that patients and their families have an understanding of the causes of HF, prognosis, therapy, dietary restrictions, activity, importance of compliance, and signs and symptoms of recurrent HF. Thorough discharge planning that includes a special emphasis on ensuring compliance with an evidence-based medication regimen is associated with improved patient outcomes.

CATARACT.

Q. What is a cataract?
A. Any opacification of the human lens of the eye is called a cataract. The human eye is like a camera – the front portion, which is clear and transparent, is called the cornea. This corresponds to the front glass of the camera. The lens is biconvex, exactly like the lens of a conventional camera and is situated behind the pupil of the eye (the jet-black window in the brown/blue/green iris of the eye). It is made up of protein and water and is normally transparent. Due to aging process, these lens proteins coagulate, losing their transparency over time. Certain drugs such as steroids as well as certain diseases such as diabetes hasten this biochemical change. Several studies blame pollution, cigarette smoking and prolonged exposure to the ultraviolet rays of the sun as some causative factors. The reason it occurs in some people at 45 while others live to be a 100 without developing any cataract is at present unclear. Whenever we doctors cannot give a logical explanation, we normally say there must be a genetic factor either causing the development of cataract or preventing it in different sets of patients.

Q. Is there a medical treatment for cataract?
A. Unfortunately,(for patients – fortunately for eye doctors!) there is no scientifically proven medical treatment for cataract. There are plenty of grandmother’s remedies touted as cures or preventive treatments, such as honey, certain vegetable extracts, cow’s urine and even auto-urine therapy. None of them work. There are also a host of eye drops made by homeopathic and ayurvedic companies which burn and sting on application (besides burning quite a hole in the pocket!), which claim to stop the progress of cataract. None of them work. The reason they become popular is many a time the cataract can stop progressing or remain stationary for years on its own, for reasons, which are unknown. If at that time the patient is using any of the above remedies, he will tell a minimum of 50 people about the miraculous drug or therapy, convinced that that is the reason for the lack of progress of the cataract. Unfortunately, patients who are on no therapy and have non-progress of their cataracts are never known to brag!

Q. Does every cataract need to undergo surgery?
A. Just as every one does not have to climb Mount Everest just because it is there, so also you do not have to undergo cataract surgery just because your doctor has diagnosed that you have a cataract. The indication for cataract surgery is when the cataract has progressed to such a stage that it hampers your day-to-day or routine activities. This varies tremendously from person to person. If you live in the US of A for example, and the cataract causes you glare and difficulty in night driving, your eye surgeon may advise surgery the next week. This is because you are probably living alone or with your spouse and if you cannot drive at night, you are considered handicapped. In case you have a medical emergency at night and have to drive to the chemist or hospital for treatment you would otherwise be in a soup! In India however, in most cities, you would be able to use a taxicab or would be able to ask your other relatives living with you or a phone call away, to take you to the hospital! A 50-year-old busy executive may feel handicapped if he finds it difficult to read the fine print in important contracts that he has to sign daily. A 75 year old housewife with a much more advanced cataract may have no complaints as she is able to see the big print of her religious books easily and is not interested in the “rubbish” they show on TV! For the executive, his early cataract may require surgery, while for the housewife, I may ask her to see me after a year for reassessment!

Q. Some people say that if I delay my cataract surgery, it may become too ‘ripe’ or may ‘burst’ and I may lose the eye permanently or it may become too ‘hard’ causing difficulty in surgery later. How true are these statements?
A. Not true. A cataract is considered ‘over-mature’ or in danger of rupture only if it is pearly white in appearance or the vision has dropped such that the patient can only see light projected into his eye but cannot recognize objects even if shown from a distance of less than one meter. As long as you are showing your eye to the ophthalmologist every 6months to a year, he will be able to guide you for surgery long before that stage is reached. As far as hardening of a cataract is considered, it is true that brown and black cataracts can harden over time, making their surgery technically a little more difficult. However, with modern day methods of cataract surgery, they no longer pose a problem to the experienced cataract surgeon.

Q. Now that I have decided to have my surgery done, what are the different options available? Which method is the “best”?
A. If you have trust in your ophthalmologist, it is wisest to allow him to decide what method of cataract extraction he should use for your eye. It depends on the type of cataract. The procedure he chooses depends on many factors, e.g. the type of cataract you have, his experience, and his familiarity with the phacoemulsification machine etc.

Q. Now that you mention it, what is ‘phacoemulsification’? How does it differ from ‘laser surgery’ for cataract, which my neighbour has undergone and paid a large sum for?
A. Phacoemulsification is the use of a machine to which is attached a probe, a pencil like instrument which vibrates at a very high frequency emitting ultrasonic energy. This breaks up or emulsifies the lens (Greek ‘phakos’=lens and ‘emulsify’ is to liquefy),
into tiny bits, which are then sucked out through tiny openings in the same probe. This is what the lay public refers to as ‘laser surgery’. In actual fact there is no use of the laser at all for cataract removal in these machines! Probably a few black sheep in the ophthalmic fraternity who do not have the time to explain Phaco-emulsification to their patients or do not feel their patient’s I.Q. level will allow them to understand such big words, combined with some inaccurate and exaggerated stories in the press have helped spread the myth of ‘laser cataract surgery’. For the record, let it be said that there are a handful of genuine laser machines, which are combined with Phacoemulsification machines for cataract surgery. However, at the current time, laser machines take more time, cannot remove hard cataracts and therefore have proved very unpopular with the vast majority of cataract surgeons.

Q. What are the other methods of cataract surgery?
A. Some surgeons are very adept at using the phaco machine and would be able to manage to remove all cataracts using this machine. Others use the Phaco machine for most cases and may use ‘a non-phaco method for certain types of cataract such as very hard cataracts or even very soft cataracts which can sometimes be a little difficult to remove safely using the phaco machine. Still others may not be conversant with the phaco machine at all and may remove the cataract by non-phaco means in all cases. In non-phaco methods, there are some, who will use a small ‘sutureless incision’ to enter the eye, while others will use a larger incision which will require to be closed with stitches.

Q. Is any method superior to the others?
A. That is a loaded question! The method using phacoemulsification and the small incision non-phaco method are both ‘sutureless’. Hence healing is rapid. Usually in about a week or so, the patient is seeing fairly well and is able to go back to a fairly normal life with no restrictions. In larger incision surgeries, where sutures are taken, the patient may have some restrictions on having a shower etc for a few weeks. It may also sometimes take a month to 6 weeks to regain good vision. In a small percentage of ‘sutured’ cases, there may be a slightly higher ‘astigmatism’ or cylinder number left over at the end of 6 weeks compared to the sutureless surgeries. However, in a majority of patients at the end of 6 weeks, there is almost no difference in the appearance of the eye or the best-corrected visual acuity irrespective of which method was used. Hence the choice of method may sometimes also depend on the lifestyle of the patient. Taking the previous example of the busy executive who needs to go back to office as soon as possible after the surgery, it may be preferable to do a phaco or a sutureless surgery on him. For the 75-year-old housewife, any of the procedures would be acceptable. Hence this decision is best taken jointly after discussing the pros and cons with your eye surgeon.

Q. What about the IOL (Intra-ocular lens) implant? How safe are they? What is the life span of the IOL? Are imported IOLs superior?
A. The IOL is a thin plastic or acrylic or silicon lens. The first ones were put shortly after the Second World War. They then became unpopular due to a high
complication rate. They were then modified and the present type has been in use since the early eighties. In the present day, almost 100% of cataract
surgeries the world over are done with the simultaneous implantation of an IOL including in most eye camps. They are extremely safe and are well tolerated
by the body. There is no rejection of the material of the lens, which is biologically inert. Judging from the complete lack of complications in the vast
majority of well-done surgeries over the past 2 decades, it is safe to extrapolate that there should be no problems due to the lens for the average life span
of the patient.
As regards the controversy of Indian versus foreign IOLs, I have no hesitation in saying with pride that Indian IOLs have come of age. They are as good as
and in some cases even superior to the imported variety and are even being exported to over 50 countries including Europe and the Americas. However, as
with most other gadgets and gizmos, there is the craze for foreign IOLs in the patient population, which we eye surgeons happily satisfy, as the patient
does not mind paying a bit more for an imported IOL!

Q. What is the difference between rigid and foldable IOLs? What are multifocal IOLs?
A. Rigid IOLs are usually made of a medical grade plastic called PMMA and have a maximum width of 5to6mm.. Hence to insert them into the eye, the incision in the eye also has to be approximately the same size. They can be inserted after any type of cataract surgery. The foldable IOLs are made of acrylic or silicon material and can be folded so as to enable them to be slipped into the eye through a smaller incision, even as small as 1mm. These can only be inserted after cataract surgery by phacoemulsification. Research is in progress to mass manufacture IOLs, which can be put in through still smaller incisions. The smaller the incision, the less chance for astigmatism or cylinder number induced by the incision. Multifocal IOLs are special IOLs, which can correct both, distance and near vision hence reducing the patient’s dependence on glasses for both distance and near. They are a little more expensive than the other IOLs. However, not all patients are suitable candidates. It is best to discuss the pros and cons of the type of lens to be inserted with your ophthalmologist before the surgery. The costliest option is not necessarily the best option for all patients.
Q. There are some latest “yellow” IOLs. What are they?
A. They are coated with a special pigment to give the patient more natural vision, especially for night driving. They are at present among the most expensive foldable IOLs available in the market.

Q. What about anaesthesia for the surgery?
A. Most surgeons would operate you under local anaesthesia. This involves giving you a tiny prick with a very fine injection needle around the eye along with some local anaesthetic eye drops. At the end of surgery, a patch is applied to keep the eye closed. This is removed a few hours later or the next day, by the surgeon. Some surgeons prefer (in very co-operative patients) to give only topical drops anaesthesia, with no injection around the eye. In such cases, there is no need to patch the eye following surgery. However, serious complications can sometimes occur if the patient inadvertently moves the eye or blinks hard during the surgery. It is best to discuss this aspect too with the surgeon before surgery, to prevent him from blaming you for any mishap later. Make sure, in case the surgeon is going to use only topical anaesthesia, that he is well experienced and is not doing this only to impress you! A tiny, tiny percentage of eye surgeons claim to operate patients with no anaesthesia at all, not even topical drop anaesthesia. Thankfully, the tribe of such surgeons is not growing.

Q. How soon will I start to see clearly after the surgery? Will I need glasses after the surgery?
A. It depends on the type of surgery. If you have had surgery with topical anaesthesia, you will see reasonably well immediately after the surgery. For those who have been patched, they will see reasonably well on removal of the patch. Some eye surgeons prefer to leave an air bubble in between the cornea and the implant after the surgery, for added safety. This air bubble can considerably blur the vision for up to a week post operatively. If your surgeon has taken sutures to close the incision, clarity may come only after a month or so. Most patients will develop a small number for distance and for near after the surgery and will need glasses to see clearly, though not of high number. It is wise to wait for a month or 6 weeks after the surgery for the number to stabilize before having glasses made, especially if stitches have been taken during surgery.

Q. What are the dos and don’ts after surgery?
A. This is very individual and varies from surgeon to surgeon. However, the number of don’ts has dropped drastically over the years, as cataract surgery got safer. Most surgeons allow you a head bath about a week after the procedure. In case stitches have been taken, you may be asked to wait a bit longer. You can read, write, watch TV, fight with your spouse and shout at your kids almost immediately after the surgery. There is usually no restriction in your diet. You do not have to stop most medication you have been taking for any other medical condition. However, if you are on aspirin, for thinning the blood, please mention it to your eye doctor. He may ask you to stop these tablets a few days before and after the cataract surgery. Your anti-diabetic pills may have to be omitted on the morning of surgery.

Q. My neighbour saw well after her surgery for 6 months. Now vision is getting blurred. Her doctor has advised her ‘YAG laser treatment’. What does this mean?
In a certain percentage of patients, the bag or capsule in which the IOL is placed can become opaque with time. This may happen as soon as one month after surgery or even many years following the surgery. In a majority of patients it does not happen at all. This can occur even after excellently done surgery. It is not considered a complication of surgery but as an unpredictable side effect, which results in haziness of vision. This is corrected by a painless 5-minute procedure called “YAG laser capsulotomy” in which an actual laser is used to burn a small hole in the centre of the capsule or bag, so as to restore vision. This is a one time procedure, which does not usually have to be repeated.

Q. Can a person operated for cataract donate his eyes after death?
A. Most certainly he can. Though the whole eyeball is removed at the time of eye donation, what is used is only the transparent layer in the front of the eye, called the cornea (this is like the transparent glass in front of a wrist watch). This is normally unaffected by successful cataract surgery, hence this cornea can restore sight to a blind person after successful cornea transplant surgery.