Patients with normal sinus rhythm and a wide QRS interval, eg, greater than 120 ms, have impaired synchronization of right and left ventricular contraction. Poor synchronization of ventricular contraction results in diminished cardiac output. Resynchronization, with left ventricular or biventricular pacing, has been shown to reduce mortality in patients with chronic heart failure who were already receiving optimal medical therapy. Because the immediate cause of death in severe heart failure is often an arrhythmia, a combined biventricular pacemaker/cardioverter-defibrillator is usually implanted.
Repeated application of a brief electric current through the myocardium during the QRS deflection of the electrocardiogram results in increased contractility, presumably by increasing Ca2+ release, in the intact heart. Preliminary clinical studies of this cardiac contractility modulation therapy are under way.
Most clinical trials have been carried out in patients with systolic dysfunction, so the evidence regarding the superiority or inferiority of drugs in HFpEF is less extensive. Most authorities support the use of the drug groups described above (Table 13–4), and the SENIORS 2009 study suggests that the β blocker nebivolol is effective in both systolic and diastolic failure. Control of hypertension is particularly important, hyperlipidemia should be treated, and revascularization should be considered if coronary artery disease is present. ACE inhibitors and ARBs are useful. Atrial fibrillation is common in HFpEF, and rhythm control is desirable. Even in sinus rhythm, tachycardia limits filling time. Therefore, bradycardic drugs, eg, ivabradine, may be particularly useful, at least in theory.
Acute heart failure occurs frequently in patients with chronic failure. Such episodes are usually associated with increased exertion, emotion, excess salt intake, nonadherence to medical therapy, or increased metabolic demand occasioned by fever, anemia, etc. A particularly common and important cause of acute failure—with or without chronic failure—is acute myocardial infarction. Measurements of arterial pressure, cardiac output, stroke work index, and pulmonary capillary wedge pressure are particularly useful in patients with acute myocardial infarction and acute heart failure. Patients with acute myocardial infarction are often treated with emergency revascularization using either coronary angioplasty and a stent, or a thrombolytic agent. Even with revascularization, acute failure may develop in such patients.
Intravenous treatment is the rule in drug therapy of acute heart failure. Among diuretics, furosemide is the most commonly used. Dopamine or dobutamine are positive inotropic drugs with prompt onset and short durations of action; they are most useful in patients with failure complicated by severe hypotension. Levosimendan has been approved for use in acute failure in Europe, and noninferiority has been demonstrated against dobutamine.
Vasodilators in use in patients with acute decompensation include nitroprusside, nitroglycerine, and nesiritide. Reduction in after-load often improves ejection fraction, but improved survival has not been documented. A small subset of patients in acute heart failure will have dilutional hyponatremia, presumably due to increased vasopressin activity. A V1a and V2 receptor antagonist, conivaptan, is approved for parenteral treatment of euvolemic hyponatremia. Some clinical trials have indicated that this drug and related V2 antagonists (tolvaptan) may have a beneficial effect in some patients with acute heart failure and hyponatremia. However, vasopressin antagonists do not seem to reduce mortality. Clinical trials are under way with the myosin activator, omecamtiv mecarbil.
Three other loop diuretics: Bumetanide and torsemide similar to furosemide; ethacrynic acid not a sulfonamide
Many other thiazides: All basically similar to hydrochlorothiazide, differing only in pharmacokinetics