Dilated Cardiomyopathy Treatment & Management

Updated: Jan 20, 2017
  • Author: Vinh Q Nguyen, MD; Chief Editor: Henry H Ooi, MD, MRCPI  more...
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Treatment

Approach Considerations

Treatment of dilated cardiomyopathy is essentially the same as treatment of chronic heart failure (CHF). CHF is a complex clinical syndrome for which many treatment modalities have emerged. Research into the biochemical alterations that occur in persons with cardiomyopathies has led to the development of many medications designed to affect these alterations. Some therapeutic interventions treat symptoms, whereas others treat factors that affect survival.

Drug classes used to manage cardiomyopathies include, but are not limited to, the following:

Based on this trial, the 2016 American College of Cardiology/American Heart Association (ACC/AHA) focused update on new pharmacologic therapy for heart failure gives sacubitril-valsartan an IB-R indication for patients with heart failure with reduced ejection fraction to reduce morbidity and mortality. [88]

  • Angiotensin-converting enzyme (ACE) inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Beta-blockers
  • Aldosterone antagonists
  • Cardiac glycosides
  • Diuretics
  • Nitrates
  • Vasodilators
  • Sacubitril-valsartan (ARNI): In patients with heart failure with reduced ejection fraction (<40%) with NYHA class II or above, sacubitril-valsartan combination was shown to be superior to enalapril in the reduction of cardiovascular mortality, hospitalization for heart failure, and improvement in symptoms based on the Kansas City Cardiomyopathy Questionaire (KCCCQ). [80]  In the PARADIGM-HF trial, primary outcome of death from cardiovascular causes or hospitalization from heart failure occurred in 21.8% of the angiotensin-neprilysin inhibition (ARNI) (sacubitril-valsartan)-treatment group versus 26.5% in the enalapril-treatment group. ARNI therapy also reduced hospitalization by 21%. Therapy with ARNI was more likely to have symptomatic hypotension but rarely required discontinuation. In contrast, enalapril was associated with high incidence of cough, as well as elevated creatinine levels above 2.5 mg/dL and serum potassium levels above 6 mmol/L. [80] ARNI therapy was not associated with increased risk of angioedema as compared to enalapril. Based on this trial, the 2016 American College of Cardiology/American Heart Association (ACC/AHA) focused update on new pharmacologic therapy for heart failure gives sacubitril-valsartan an IB-R indication for patients with heart failure with reduced ejection fraction to reduce morbidity and mortality. [88]
  • Ivabradine: In the SHIFT study (Systolic Heart failure treatment with the  I f inhibitor ivabradine Trial), patients with systolic heart failure—and left ventricular fraction (LVEF) below 35%, sinus rhythm, resting heart rate above 70 beats per minute, and who were on maximally tolerated doses of beta-blocker or who were intolerant to beta blockers—treated with ivabradine showed reduction in the primary composite endpoints of cardiovascular death or hospital admission for worsened heart failure. [89]  However, only 23% of patients took the full target beta blocker dose; 56% of patients took over 50% of the target dose. Therefore, it is not certain that ivabradine provides benefit for those on optimum doses of this beta blocker. [90]
  • Antiarrhythmics
  • Human B-type natriuretic peptide
  • Inotropic agents

Anticoagulants may be used in selected patients.

Various surgical options are available for patients with disease refractory to medical therapy. These include the following:

  • Left ventricular assist devices
  • Cardiac resynchronization therapy (biventricular pacing)
  • Automatic implantable cardioverter-defibrillators
  • Ventricular restoration surgery
  • Heart transplantation

In cases of severe acute heart failure, emergency medical services (EMS) personnel may initiate treatment with oxygen, nitrates, and furosemide en route to the hospital. Cardiac monitoring, continuous pulse oximetry, and electrocardiography (ECG) may also be performed by units with advanced life support (ALS) certification. Further ventilatory support or even intubation may be indicated if the patient is in extremis.

Treatment of dilated cardiomyopathy is essentially the same as treatment of chronic heart failure (CHF) and pulmonary edema; however, obtaining a thorough history from patients with dilated cardiomyopathy helps determine the etiology. When beginning treatment, administer oxygen, initiate continuous pulse oximetry and cardiac monitoring, and obtain intravenous access.

Mainstays of medical therapy are preload reduction, afterload reduction, diuresis, and airway support. In patients with severe refractory pulmonary edema, a trial of continuous positive airway pressure (CPAP) or bimodal positive airway pressure (BiPAP) may obviate intubation.

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Blood Pressure Control

Appropriate control of blood pressure is essential to effective therapy for persons with heart failure. The systolic blood pressure must be less than 120 mm Hg (preferably <110 mm Hg).

Patients taking medications should not be deemed hypotensive based solely on blood pressure measurements; instead, this determination should be made based primarily on symptoms and the effectiveness of organ perfusion.

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ACE Inhibitors and ARBs

Use of angiotensin-converting enzyme (ACE) inhibitors is the current criterion standard in the treatment of left ventricular dysfunction. ACE inhibitors have been shown to decrease mortality rates in both symptomatic and asymptomatic patients with left ventricular dysfunction and to reduce readmissions caused by heart failure. The absolute benefits are greater in patients with severe heart failure.

The dosage necessary for maximal benefit has been a matter of debate. One study that investigated low- and high-dose lisinopril found no significant difference in mortality rates, although it did find a difference in a combined endpoint of rehospitalization and death in favor of high-dose lisinopril.

A study by van Veldhuisen et al examined high- and low-dose ACE inhibition using imidapril and demonstrated improved exercise capacity and decreased levels of neurohormonal markers of chronic heart failure (CHF) (atrial and B-type natriuretic peptides). [91] Authorities have generally accepted that maximizing ACE inhibitor therapy is important and should be accomplished in conjunction with other necessary therapies.

The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) group in 1987 showed that the addition of enalapril to the conventional treatment of CHF yielded a 31% reduction in mortality rate at 1 year. [92] A similar study by Studies of Left Ventricular Dysfunction (SOLVD) investigators in 1991 revealed a 16% risk reduction. [93] Losartan, an angiotensin II receptor blocker (ARB), also has been effective in decreasing mortality rates.

Other ACE inhibitor trials include the following:

  • Vasodilator Heart Failure Trial II (VHeFT II) (enalapril vs hydralazine plus isosorbide dinitrate): Improved survival better than with combined treatment with hydralazine and isosorbide dinitrate
  • Assessment of Treatment with Lisinopril and Survival in Heart Failure (ATLAS; lisinopril [low and high dose]): Insignificant trend toward reduced mortality rate with high-dose lisinopril and significant reduction in hospitalization [94]
  • Survival and Ventricular Enlargement (SAVE) (captopril vs placebo): Decreased mortality rate, progression of disease, and recurrent myocardial ischemia [95]
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Beta Blockers

Previously believed to be contraindicated in patients with left ventricular dysfunction, this class of medications has moved to the forefront of heart failure treatment. Several trials have shown that beta-blockers are both safe and effective in the treatment persons with any class of heart failure and that adding beta-blockers to outpatient management of chronic heart failure (CHF) yields great reductions in mortality rates.

Carvedilol, bisoprolol, and metoprolol CR/XL are the only agents currently approved by the US Food and Drug Administration (FDA) for use in patients with heart failure. Head-to-head studies (Carvedilol or Metoprolol European Trial [COMET], carvedilol vs metoprolol) indicated that carvedilol (a beta-1, alpha, and beta-2 receptor blocker), improved survival and cardiovascular hospitalizations more than the beta-1 selective beta-blocker metoprolol tartrate. [96]

The SENIORS trial (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) showed that patients older than 70 years regardless of LVEF, nebivolol, a beta blocker with vasodilating properties, reduced the primary outcome of all-cause mortality or hospitalization for cardiovascular events. [97] However, the seconday outcome of all-cause mortality was not significant reduced.

The 1993 Metoprolol in Dilated Cardiomyopathy (MDC) study reported a 34% reduction in primary endpoints (ie, need for heart transplant, death) in heart failure patients who were treated with metoprolol in addition to conventional therapies. [98] In 1996, the US Carvedilol Study showed a 65% reduction in mortality in patients with predominantly mild symptoms of heart failure (New York Heart Association [NYHA] class II) treated with carvedilol. [99]

The international Metoprolol CR/XL Randomized Intervention Trial in CHF (MERIT-HF), the largest trial ever completed using a beta-blocker in heart failure, closed prematurely following an interim analysis that identified a highly positive effect of metoprolol-XL on all causes of mortality. [100] MERIT-HF was a randomized, double-blind trial that compared the effects of extended-release metoprolol (metoprolol-XL) with the effects of a placebo on survival and other outcome measures (eg, sudden death, hospitalization for heart failure, quality of life) in patients with mostly mild symptoms (NYHA class II).

A statistically significant 34% reduction in relative risk for total mortality at 1 year was observed; mortality rates were 7.2% in the metoprolol-XL group and 11% in the placebo group. Results at the time of study termination also revealed a 38% reduction in cardiovascular mortality, a 41% reduction in sudden death, and a 49% reduction in CHF mortality. [100, 101]

Beta-blocker trials include the following (all trials used beta-blockers in addition to standard therapy for heart failure):

  • US Carvedilol Heart Failure Study Group from 1996
  • Cardiac Insufficiency Bisoprolol Study II (CIBIS II) from 1999 (bisoprolol vs placebo), NYHA class III-IV: Showed reduced mortality and hospitalization rates [102]
  • Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) from 2000 (carvedilol vs placebo): Demonstrated reduction in mortality by 35% in a population of patients with severe symptoms of heart failure (NYHA class IV) [103]

Angiotensin receptor blockers

Data have demonstrated that angiotensin II receptor blockers (ARBs) are as effective as angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure. Their adverse-effect profile is similar to that of ACE inhibitors with regard to renal insufficiency or hyperkalemia, but they do not cause potentiation of bradykinin and therefore do not cause cough.

ARB trials include the following:

  • Evaluation of Losartan in the Elderly (ELITE) (losartan vs captopril): Losartan was associated with lower mortality and was better tolerated [104]
  • Evaluation of Losartan in the Elderly II (ELITE II): Losartan was not superior to captopril in elderly patients with left ventricular dysfunction but was better tolerated [105]
  • Valsartan Heart Failure Trial (VALHeFT; valsartan vs placebo) in addition to standard therapy: Combined mortality and morbidity rates from heart failure decreased by 13.3% in patients receiving valsartan in addition to standard therapy
  • Candesartan in Heart failure-Assessment of moRtality and Morbidity in patients treated with ACE inhibitors (CHARMED–Added): In patients with a left ventricular ejection fraction (LVEF) below 40% and NYHA class II-IV symptoms already on an ACE-inhibitor, addition of candesartan reduced cardiovascular mortality and heart failure hospitalizations. [106] There were no differences in all-cause mortality. However, addition of candesartan was associated with higher rates of hyperkalemia and serum creatinine. [106]
  • Candesartan in Heart failure-Assessment of moRtality and Morbidity in patients intolerant to ACE inhibitors (CHARMED–Alternative): In patients with an LVEF below 40% and NYHA class II-IV heart failure with intolerance to ACE inhibitors, candesartan use led to a 20% reduction in cardiovascular death and a 40% reduction in hospitalization for heart failure. [107]
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Aldosterone Antagonists

Spironolactone acts as an aldosterone receptor blocker and, with concomitant use of angiotensin-converting enzyme (ACE) inhibitors, helps break the cycle of sodium retention and fluid overload via the renin-aldosterone axis. In the Randomized Aldactone Evaluation Study (RALES) (spironolactone vs placebo), the addition of 25 mg of spironolactone daily to a standard treatment regimen for chronic heart failure (CHF) yielded a 35% reduction in hospitalization, significant improvements in New York Heart Association (NYHA) functional class, and a 30% reduction in risk of death. [108]

In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) (eplerenone vs placebo), the addition of eplerenone to standard therapy resulted in a 15% reduction in all-cause mortality and a 17% reduction in cardiovascular mortality; the combined primary endpoint of cardiovascular (CV) mortality and CV hospitalization was reduced by 13%. EPHESUS was conducted in patients with ejection fractions less than 40% post myocardial infarction and either clinical symptoms of decompensated heart failure or diabetes. [109]

The Emphasis-HF trial noted a 30% reduction in mortality and heart failure hospitalizations when eplerenone was used in addition to standard therapy in patients with class II heart failure who had a left ventricular ejection fraction (LVEF) of less than 35%. However, an increased risk of hyperkalemia was noted, similar to findings from the RALES and EPHESUS trials. [110]

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Cardiac Glycosides

Foxglove and its derivatives are the oldest treatment of heart failure, but they still have a place in medicine despite advances in other drug categories. Although little controversy exists as to the benefit of digoxin in patients with symptomatic left ventricular dysfunction and concomitant atrial fibrillation, the debate continues over its role in patients with normal sinus rhythm.

A meta-analysis of 7 double-blind, placebo-controlled trials by Jaeschke et al revealed that 1 in 9 patients with chronic heart failure showed significant clinical benefit from treatment with digoxin, but not a reduction in mortality. [111] The Digitalis Investigation Group trial demonstrated that digoxin decreases heart failure hospitalizations but has no effect on long-term survival. [112]

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Diuretics

Loop diuretics are necessary adjuncts in the medical therapy for heart failure when symptoms are due to sodium and water retention. They are the mainstay of diuretic therapy because they produce significantly more natriuresis than other diuretics, particularly in the setting of decreased glomerular rate. They provide symptomatic relief without prolonging life or altering disease course.

Loop diuretics have a tendency to cause hypokalemia and hypomagnesemia. Therefore, monitor electrolyte levels and replace as necessary.

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Antiarrhythmics

Antiarrhythmics are useful in patients with supraventricular and nonsustained ventricular tachycardias. Not all antiarrhythmics are considered safe in patients with structural heart disease. The Cardiac Arrhythmia Suppression Trial (CAST) 1 and 2 implicated class IC agents as causing increased mortality in this population.

Similarly, the Survival With Oral d-Sotalol (SWORD) trial reported increased total and cardiac mortality in patients after myocardial infarction with a reduced left ventricular ejection fraction when treated with oral d-sotalol. The class III antiarrhythmics amiodarone and dofetilide are favored in these patients for the treatment of supraventricular and ventricular dysrhythmias.

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Vasodilators

In 1986, the US Veterans Administration Cooperative study showed a 36% mortality risk reduction in patients treated with preload and afterload reducers (eg, isosorbide dinitrate, hydralazine) in addition to conventional heart failure medications. [113] Sublingual nitroglycerin spray, nitro paste, and intravenous nitroglycerin have also been advocated in the treatment of pulmonary edema secondary to chronic heart failure.

The combination of isosorbide dinitrate and hydralazine is indicated for heart failure in black patients, based in part on results of the African American Heart Failure Trial. [114] Two previous trials in patients with severe heart failure had found no benefit in the general population but suggested a benefit in black patients. Compared with placebo, black patients on standard therapy in addition to isosorbide dinitrate/hydralazine showed a 43% reduction in mortality rate, a 39% decrease in hospitalization rate, and a decrease in symptoms from heart failure in patients with NYHA class III symptoms of heart failure, when added to standard therapy.

Intravenous nitrate therapy resulted in acute improvement of dyspnea in 2 randomized trials. Similarly, morphine acts as a venodilator, and it suppresses symptoms of breathlessness; however, no rigorous studies of morphine have been performed in acute decompensated heart failure.

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Human B-Type Natriuretic Peptide

Human B-type natriuretic peptide (BNP) (nesiritide [Natrecor]) is a new class of drug in the treatment of heart failure. It is produced through recombinant DNA technology and has the same amino acid sequence as naturally occurring human BNP.

Natriuretic peptides have demonstrated effectiveness in correcting hemodynamic derangements in patients with acutely decompensated heart failure via their vasodilatory and diuretic effects. Data suggest that combined blockade of angiotensin-converting enzyme (ACE) and neutral endopeptidase also has hemodynamic and clinical benefits.

In the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial (nesiritide vs nitroglycerin vs placebo plus standard care), human BNP improved hemodynamics and symptomatology more effectively and with fewer adverse effects than intravenous nitroglycerin during 24 hours in patients with acute decompensated chronic heart failure (CHF). [115] In the Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Natrecor Therapy (PRECEDENT) trial, nesiritide was not associated with the increased heart rate or ventricular ectopy that occurred with dobutamine therapy. [116]

In the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial), in which nesiritide was compared with placebo in the treatment of acute heart failure, there was no difference in the rate of rehospitalization for heart failure or all-cause death within 30 days. [117]  Although there was no association with worsened renal function, defined as a more than 25% decrease in estimated glomerular filtration rate, increased rates of hypotension were noted. Given these findings, the investigators could not recommend nesiritide for routine use in the broad population of patients with acute heart failure. [117]

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Inotropic Agents

Long-term use of the phosphodiesterase inhibitor milrinone has deleterious effects on survival in patients with heart failure. Improvement of chronic heart failure (CHF) symptoms occurs as the trade-off for this increase in mortality. Inotropic agents are reserved for patients who need hemodynamic-directed treatment during acute decompensation, for those who are refractory to maximal standard therapy, as palliation for end-stage heart failure, or as a bridge to transplantation for appropriate candidates.

Inotrope trials include the following:

  • Prospective Randomized Milrinone Survival Evaluation (PROMISE) (milrinone vs placebo) New York Heart Association (NYHA) class III-IV: increased mortality and morbidity rates with long-term therapy [118]
  • Xamoterol in Severe Heart Failure Study (xamoterol vs placebo), NYHA class III-IV: terminated because of excess mortality in xamoterol group [119]
  • Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) (milrinone or dobutamine vs placebo): routine administration of inotrope to hospitalized patients with decompensation who normally would not require it showed no impact on length of hospitalization and increased adverse events with milrinone
  • Vesnarinone Trial (VEST) (vesnarinone vs placebo), NYHA class III-IV: increased mortality rates
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Anticoagulation

Restrict the use of anticoagulants to those patients in atrial fibrillation, with artificial valves, or with known mural thrombus.

The WATCH trial (Warfarin and Antiplatelet Therapy in Chronic Heart Failure) evaluated antithrombotics (aspirin, clopidogrel, and warfarin) in patients with a left ventricular ejection fraction (LVEF) of 35% or less in sinus rhythm and found no significant differences between the agents in the primary composite endpoints of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke. [120]  There was a 26% in reduction of heart failure hospitalization for those receiving warfarin over aspirin, but this was at the expense of greater bleeding than seen with aspirin or clopidogrel use.

Similarly, in the WARCEF trial (Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction) that involved patients with an LVEF of 35% or below who were in sinus rhythm, there was no significant difference seen in treatment with aspirin versus warfarin in the composite end point of ischemic stroke, intracranial hemorrhage, or death from any cause. [121] Warfarin was associated with a reduction in ischemic stroke but at an increased overall rate of major hemorrhage (intracerebral, intracranial, gastrointestinal, or other bleeding causing a 2-g/dL decline in hemoglobin within 48 hours). However, when further subclassified, rates of intracranial/intracerebral hemorrhage did not differ between the two groups. [121]

 

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Left Ventricular Assist Devices

Implantable left ventricular assist devices (LVADs) have been proven as a standard of care for suitable candidates with advanced heart failure when a bridge to transplantation (BTT) is needed. LVADs have also been approved for permanent implantations (ie, as destination therapy [DT]) in patients who are not candidates for heart transplantation.

The HeartMate XVE LVAD (HeartMate I) and HeartMate II LVAD were approved for destination therapy by the US Food and Drug Administration in 2004 [122] and 2010, [123] respectively. [124]

The HeartMate II BTT trial

Of 281 heart failure patients with New York Heart Association (NYHA) class IV symptoms and who were ill enough to have high priority for transplantation (United Network for Organ Sharing [UNOS] status 1A or 1B) who underwent implantation of HeartMate II LVAD for bridge to cardiac transplant, at 18-month follow-up, 79% underwent transplantation, LVAD removal for cardiac recovery, or had ongoing device support. [125] The investigators reported significant functional status improvements and 6-minute walk test evident at 6 months, and an actuarial survival of 72% at 18 months. Findings from this study demonstrated the HeartMate II provided effective hemodynamic support for at least 18 months in patients with advanced heart failure awaiting transplantation. [125]

HeartMate II DT trial

In the HeartMate II destination therapy trial, 200 patients who were ineligible for heart transplantation and also had symptoms refractory to medical management, a left ventricular ejection fraction (LVEF) below 25%, a peak oxygen consumption (VO2) below 14 mL/kg/min (or <50% of predicted value), and NYHA class IIIB or IV symptoms, or dependence on an intraaortic balloon pump were randomized to a continuous flow device (HeartMate II) versus a pulsatile device (HeartMate XVE). Patients in the continuous flow group (n = 134) had a better 2-year survival period free from the primary endpoints of disabling stroke and reoperation to repair/replace the device. [126] These patients also had superior actuarial survival rates and fewer adverse events.

ADVANCE clinical trial

The HeartWare Ventricular Assist System is a continuous-flow blood pump. In a study comprising 332 patients with NYHA class IV symptoms with UNOS class 1A or 1B listed for cardiac transplantation, survival was high 91% at 180 days and 84% at 360 days in those who received the HeartWare device. [127, 128]  There was also significant improvement in quality of life. [128]

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Cardiac Resynchronization Therapy (Biventricular Pacing)

For biventricular pacing, a pulse generator is implanted under the skin, with leads positioned in the right atrium, right ventricle, and coronary sinus to pace the left ventricle. Resynchronization pacing generators also have defibrillation capabilities. The benefits of pacing solutions for dyssynchrony were confirmed in multiple studies from the mid 1990s, which demonstrated acute and long-term functional improvements and reduced mortality and hospitalization rates compared with optimal medical therapy. [129]

A Dutch study found that heart failure patients with impaired renal function were less likely to respond to cardiac resynchronization therapy and have higher mortality rates. In patients who do respond to resynchronization, however, renal function is preserved. [130]

Current indications for class I cardiac resynchronization therapy based on the 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure guidelines are as follows [13] :

  • NYHA class I symptoms persisting longer than 40 days following myocardial infarction [MI], left ventricular ejection fraction (LVEF) at or below 30%, sinus rhythm, left ventricular bundle-branch block (LBBB) with a QRS of 150 ms or longer (Multicenter Automatic Defibrillator Implantation Trial-cardiac-resynchronization therapy [MADIT-CRT] [131] )
  • NYHA class II or greater symptoms while on guideline-directed medical therapy (GDMT), with symptoms persisting longer than 40 days post MI, LVEF of 35% or below, sinus rhythm, LBBB with QRS of 150 ms or longer
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Automatic Implantable Cardioverter-Defibrillators

Automatic implantable cardioverter-defibrillators (AICDs) are designed to detect and correct ventricular tachycardia/ventricular fibrillation. Programmable therapies include antitachycardia pacing for ventricular tachycardia and/or defibrillatory shocks when appropriate.

Indications for implantation continue to evolve, and the patient populations eligible for AICDs continue to expand. Current recommendations include patients who are clearly at high risk for ventricular arrhythmias and sudden cardiac death. Those with moderately severe left-sided ventricular dysfunction account for a significant proportion of these patients.

AICD trials (ie, the Multicenter Automatic Defibrillator Implantation Trial II [MADIT II], [132] Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT] [133] ) have defined a clear mortality benefit in patients with a history of significant left-sided ventricular dysfunction. 

Indications for ICD according to 2013 ACC/AHA include [13] :

  • Class IA: Primary prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF) 40 days post myocardial infarction (MI) with a left ventricular ejection fraction (LVEF) of 35% or below and New York Heart Association (NYHA) class II or III symptoms on guideline-directed medical therapy (GDMT) who are expected to live longer than 1 year (SCD-HeFT [133] )
  • Class IB. Primary prevention of SCD in those with HFrEF 40 days post MI and LVEF of 30% or below with NYHA class I symptoms while receiving GDMT, who are expected to live longer than 1 year (MADIT II [132] )

In the Danish ICD Study in Patients With Dilated Cardiomyopathy (DANISH), which assessed the benefit of prophylactic ICDs in patients with nonischemic cardiomyopathy and an LVEF below 35%, the primary outcome of death from any cause was not statistically different from those on standard heart failure therapy. [134] SCD occurred less often in the ICD group (4.3%) than in the control group (8.2%). When stratified by age, patients younger than 59 years old derived a mortality benefit with ICD as compared to those older than 59 years who had no difference in primary outcome. Background beta blocker therapy was administered to more than 90% of patients in both groups. [134]

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Heart Transplantation

When progressive end-stage heart failure occurs despite maximal medical therapy, when the prognosis is poor, and when there is no viable therapeutic alternative, the criterion standard for therapy has been heart transplantation. Absolute indications for heart transplantation are as follows:

  • Refractory cardiogenic shock
  • Dependence on intravenous inotropes for organ perfusion
  • Peak oxygen consumption (VO 2) less than 1 mL/kg/min with achievement of anaerobic threshold
  • Severe ischemia not amenable to any intervention
  • Symptomatic ventricular arrhythmias refractory to all therapies

Relative indications are as follows:

  • Peak VO 2 of 11-14 mL/kg/min (or <50-55% predicted for age and sex) and major limitation of daily activity
  • Recurrent instability of chronic heart failure not due to noncompliance or suboptimal medical therapy
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Diet and Activity

The importance of patient education cannot be overemphasized, especially regarding dietary restrictions. Dietary recommendations include sodium and water restrictions. An average United States diet contains 6 g of salt per day. Avoiding extra table salt decreases this intake to 3 g/day. Patients with chronic heart failure should restrict their salt intake to less than 2-4 g/day.

Fluid restriction is necessary in symptomatic stages of the disease. Patients with hyperkalemia due to angiotensin-converting enzyme (ACE) inhibitor therapy sometimes respond to a low-potassium diet.

Encourage patients to exercise moderately, because deconditioning is a very common cause of dyspnea. Cardiac rehabilitation has been shown to improve patient outcomes.

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Cardiac Rehabilitation

Benefits of cardiac rehabilitation include a 20-30% reduction in all-cause mortality rates; decreased mortality up to 5 years following rehabilitation; reduced symptoms of dyspnea, angina, and fatigue; reduction in nonfatal recurrent myocardial infarction over follow-up period of 12 months; and increased exercise performance. [135, 136, 137, 138, 139, 140]

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Investigational Therapy for Heart Failure

Gene therapies

Early animal studies using recombinant adeno-associated viral gene therapy with gene transfer of phospholamban prevented deterioration of left ventricular systolic and diastolic function in genetically predisposed animals.

The use of vascular endothelial growth factor may have beneficial effects in persons with ischemic cardiomyopathies. This form of gene therapy has demonstrated the benefits of reducing revascularization and improving angina and quality of life.

The CUPID-2 trial (calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease) assessed the effectiveness of a gene transfer vector on the basis of adeno-associated virus 1 (AAV1)'s ability to deliver SERCA2a (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase)–complementary DNA in patients with heart failure and reduced ejection fraction (LVEF <35%). [141] Compared to placebo, there were no differences in recurrent heart failure-related hospitalizations or ambulatory treatment for heart failure, as well as no difference in the rate of death, heart transplantation, or mechanical circulatory support implantation. [141]

Myoblast transplantation

Myoblast transplantation involves the injection of skeletal myoblasts as an autograft into damaged myocardium (scar).

In the Poznan (phase I) trial in Poznan, Poland, which studied 10 patients with postinfarction heart failure without viable myocardium but who had adequate coronary flow from revascularization or collateral vessels and underwent skeletal myoblast transplant injection through catheterization of cardiac veins via intravascular ultrasonographic guidance, 9 patients showed improvement in New York Heart Association (NYHA) symptoms from class II-III to class I. [142] Segmental contractility was not statistically evaluated owing to the small number of patients.

The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) trial was the first randomized placebo-controlled trial that studied myoblast transplantation in patients with left ventricular ejection fraction (LVEF) below 35% as well as with myocardial infarction and indication for coronary artery bypass graft (CABG) surgery. [143] At 6-month follow-up, autologous skeletal myoblast transplantation (low and high doses) via intraoperative injection in and around myocardial scars did not improve regional or global LV function compared to the control group, although the high-dose cell transplant group had a significant decrease in LV volumes. There was also a higher rate of postoperative arrhythmic events in myoblast-treated patients, but there were no differences in 6-month rates of major adverse cardiac events and ventricular arrhythmias. [143]

In a study evaluating autologous skeletal myoblast transplantation in patients undergoing CABG or left ventricular assist device (LVAD) implantation, follow-up positron-emission tomography (PET) scans showed glucose uptake within infarcted scars (ie, new areas of viability). [144] LVEF also increased from 28% to 36% after 2 years. Moreover, the explanted hearts showed survival of the transplanted fibroblasts. [144]

Stem cells

Human embryonic stem cells have been differentiated ex vivo to derive cardiac myocyte stem cells. When transplanted into rats that had left anterior descending coronary artery ligation, these stem cells have been shown to attenuate the adverse remodeling seen with extensive infarcts. [145]

Autologous stem cells have been given both intramyocardially and intravenously for the treatment of congestive heart failure, with varying results. Much of the early data from these trials seem to suggest that delivery mechanisms to the myocardium and the use of concomitant cytokines are equally in need of further investigation. [146]

An evaluation of the safety and efficacy of ixmyelocel-T, administered via minithoracotomy or intramyocardial catheter injections, in 2 prospective randomized phase 2A trials in patients with dilated cardiomyopathy (DCM) stratified by ischemic or nonischemic status revealed evidence that intramyocardial injection with ixmyelocel-T reduced major adverse cardiovascular events and improved symptoms in patients with ischemic DCM but not in patients with nonischemic DCM. [147] In the IMPACT-DCM trial, 39 patients were randomized to either ixmyelocel-T or standard-of-care control in a 3:1 ratio; ixmyelocel-T was administered intramyocardially via minithoracotomy. In the Catheter-DCM trial, 22 patients were randomized to either ixmyelocel-T or standard-of-care control in a 2:1 ratio; ixmyelocel-T was administered intramyocardially with the NOGA Myostar catheter.

Relative to control patients, fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up, but nonischemic patients did not have a similar benefit. [147] The most common major adverse cardiovascular event was exacerbation of heart failure. Those in the ischemic population who received ixmyelocel-T had improved NYHA class, 6-minute walk distance, and Minnesota Living with Heart Failure Questionnaire scores compared to the control group; again, the nonischemic group did now demonstrate a similar trend. [147]

In a nonrandomized prospective study involving 14 patients with end-stage ischemic heart disease who underwent transendocardial injection of autologous mononuclear bone marrow cells, Perin et al noted a significant reduction in total reversible defect, improvement in global LV function, reduction in end-systolic volume, and improvement in LVEF from 20% at baseline to 29%. [148]

CardioMEMS

CardioMEMS is a wireless implantable pulmonary artery (PA) pressure monitoring system used to guide management and reduce hospital stay. In the Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) trial, which studied patients with NYHA class III symptoms and a previous heart failure hospitalization, during the mean follow-up period of 15 months, the treatment group demonstrated a 39% reduction in heart-failure related hospitalizations relative to the control group. [149] Eligible patients included those with NYHA III symptoms for at least 3 months and a hospitalization for heart failure for the past 12 months. Ejection fraction was not an inclusion criteria.

The 2016 European Society of Cardiology (ESC) guidelines has a class IIB recommendation for CardioMEMS placement in patients with heart failure and a previous heart failure hospitalization to reduce the risk of recurrent heart failure hospitalizations. [150]

 

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Consultations

Consult an internist, an intensivist, or a cardiologist as indicated for admission when a patient has been diagnosed with dilated cardiomyopathy for the first time or for continued inpatient treatment or monitoring. Emergent consultation with a cardiologist is indicated in unstable patients for echocardiography in the emergency department.

Refer appropriate patients with New York Heart Association (NYHA) functional class III-IV dilated cardiomyopathy to cardiology services for consideration of advanced therapies, including implantation of left ventricular assist devices (LVADs) or heart transplantation.

Patients with familial dilated cardiomyopathy can register with the Dilated Cardiomyopathy Research Project (formerly Familial Dilated Cardiomyopathy [FDC] Research Group), whose contact information is as follows:

Dilated Cardiomyopathy Research Project

Telephone (toll free): (877) 800-3430

E-mail: DCM.Research@osumc.edu 

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