Restrictive Cardiomyopathy Treatment & Management

Updated: Aug 30, 2017
  • Author: Lindsay Reardon, MD; Chief Editor: Henry H Ooi, MD, MRCPI  more...
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Treatment

Approach Considerations

Restrictive cardiomyopathy (RCM) has no specific treatment. However, therapies directed at individual causes of RCM have been proven to be effective. Examples of this include corticosteroids for sarcoidosis and Loeffler endocarditis, endocardiectomy for endomyocardial fibrosis and Loeffler endocarditis, phlebotomy and chelation for hemochromatosis, and chemotherapy for amyloidosis. Familial amyloidosis has been shown to respond to novel therapies such as RNA interference or gene silencing molecules that target abnormal protein production. [29] Budesonide has been studied as a potential effective anti-inflammatory with fewer side effects than other oral corticosteroid therapy. [30]

The mainstays of medical treatment include diuretics, vasodilators, and angiotensin-converting enzyme inhibitors (ACEIs) as indicated, as well as anticoagulation (if not contraindicated). [19]

In selected patients, permanent pacing, left ventricular assist device (LVAD) therapy, and transplantation (heart or heart-liver) may be considered.

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Pharmacologic Therapy

The goal of treatment in restrictive cardiomyopathy (RCM) is to reduce symptoms by lowering elevated filling pressures without significantly reducing cardiac output. Beta blockers and cardioselective calcium channel blockers (eg, verapamil, diltiazem) may be of benefit by increasing left ventricular filling time, improving ventricular relaxation, and decreasing compensatory sympathetic stimulation. In addition, low-medium dose diuretics reduce preload and may provide symptomatic relief. Small initial doses should be administered to prevent hypotension because patients are frequently extremely sensitive to alterations in left ventricular volume. Higher doses may be needed if the serum albumin level is low secondary to concomitant nephrotic syndrome.

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II inhibitors (angiotensin II receptor blockers [ARBs]) are poorly tolerated in patients with amyloidosis. Even small doses may result in profound hypotension, which is likely secondary to an autonomic neuropathy. Beta-blockers and calcium channel blockers have not been shown to improve day-to-day symptoms or to favorably alter the natural history in patients with diastolic heart failure. No published data are available on the use of intravenous (IV) inotropic or vasodilator drugs.

Patients with a history of atrial fibrillation should be anticoagulated, and the heart rate should be adequately controlled. Atrial contraction acts to increase the efficiency of ventricular filling and ejection; thus, if removed, existing diastolic dysfunction may worsen. Likewise, rapid ventricular response may further compromise diastolic filling, creating a crisis. Therefore, maintaining sinus rhythm is important, and medications such as amiodarone and beta-blockers are often used.

Digoxin should be used with caution because it is potentially arrhythmogenic, particularly in patients with amyloidosis.

Antiplasma cell therapy with melphalan may slow the progress of systemic amyloidosis by stopping production of the paraprotein responsible for the formation of amyloid. The prognosis of patients with primary systemic amyloidosis remains poor, with a median survival of approximately 2 years despite intervention with alkylating-based chemotherapy in selected cases. In specific cases, chemotherapy has dramatic benefits, with improvement in systemic and cardiac manifestations.

The treatment of Loeffler endocarditis consists of correctly identifying the condition before the end-stage fibrosis occurs. Medical therapy with corticosteroids, cytotoxic agents (eg, hydroxyurea), and interferon to suppress the intense eosinophilic infiltration of the myocardium is appropriate during the early phase of Loeffler endocarditis and improves symptoms and survival. Conventional heart failure medication is also given.

Chelation therapy or therapeutic phlebotomy is effective in patients with hemochromatosis to decrease the iron overload.

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Pacemaker Implantation

Patients with idiopathic restrictive cardiomyopathy (RCM) may have fibrosis of the sinoatrial and atrioventricular nodes that result in complete heart block and, therefore, require permanent pacing. If cardioversion to treat atrial fibrillation is attempted, particularly in patients with amyloidosis, the abnormal sinus node may fail as an effective pacemaker. Patients with sinus node dysfunction and/or advanced conduction system disease also require treatment with implantation of a pacemaker.

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Endomyocardectomy

As noted earlier, treatment of Loeffler endocarditis depends on correctly identifying the condition before the end-stage fibrosis occurs, and it typically involves early pharmacotherapy (see Pharmacologic Therapy).

In the fibrotic stage of Loeffler endocarditis, surgical therapy, with excision of the fibrotic endocardium and replacement of the mitral and tricuspid valves, is palliative but may provide symptomatic improvement. The operative mortality is in the range of 15% to 25%.

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Cardiac Transplantation

Cardiac transplantation or ventricular mechanical support (left ventricular assist device [LVAD]) therapy can be considered in highly selected patients with refractory symptoms who have idiopathic or familial restrictive cardiomyopathy (RCM) and amyloidosis. Elevated pulmonary vascular resistance excludes patients from cardiac transplantation, and LVAD implantation may be required as a bridge to transplantation. [31] LVAD has successfully been used as a bridge to heart transplantation in infants and children. [32] When noncardiac organ involvement is absent, a few patients with amyloidosis have undergone successful cardiac transplantation in combination with postoperative high-dose chemotherapy to abolish recurrent amyloid production.

Cardiac transplantation is a widely accepted treatment to improve long-term survival in patients with advanced RCM. Unfortunately, patients face long waiting periods. Many develop irreversible pulmonary hypertension and die from heart failure complications before they can receive a donor heart. Persistent right heart failure, thickened left ventricular walls and small left ventricular chamber sizes make LVAD implantation challenging in RCM. A 2015 study by Grupper et al found that LVAD implantation is technically feasible in patients with advanced RCM, and it is associated with improved survival as compared with medical therapy, regardless of RCM etiology. [33] Left ventricular dimensions were an important predictor for outcome. The investigators showed a 1-year survival of 64% with LVAD implantation, which is higher than the reported natural history of advanced RCM. Although the cohort consisted of 28 patients, the results also showed improved long-term survival of those who underwent LVAD implantation as a bridge to transplantation. [33]

Combined heart and liver transplantation in patients with heart and liver failure due to hemochromatosis has been successful in small numbers of patients. [34] However, early morbidity and mortality are higher in dual-organ transplantation than in single-organ transplantation.

Transplantation is a treatment option for cardiac sarcoidosis, but recurrence of sarcoid granulomas can occur in the transplanted heart.

A surgical approach carries a potential for significant morbidity for RCM, but it may offer a cure for pericardial constriction. Thus, establishing a clear diagnosis is crucial, aided by the advent of sophisticated imaging technology (see Workup). Fewer patients now need exploratory open-heart surgery to establish the correct diagnosis. Finally, it is uncertain whether patients who have radiation-induced cardiac diseases are candidates for heart transplantation. This stems from data that have shown these patients have poor early and late outcomes after cardiac transplantation related to fibrosis, procedural complications, and new or recurrent malignancies. [35]

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Novel Therapies

Advancements in chemotherapy regimens and the use of autologous hematopoietic cell transplantation in some patients have been shown to improve survival for primary or amyloid light-chain (AL) amyloidosis. Mortality at 1 year, however, remains greater than 50% for those with advanced cardiac involvement. [27] Stem cell transplantation used in conjunction with high-dose chemotherapy is still considered experimental by most cardiologists. Its routine use has not yet been established.

Novel protein-specific strategies are emerging for the treatment of amyloidosis, including nonsteroidal anti-inflammatory agents (NSAIDs), novel compounds and micro-RNA inhibitors. Other treatments target the reduction of gene expression and amyloid degrading agents. [27] There are ongoing studies testing agents that block hepatocyte production of transthyretin, stabilize the tetramer in plasma, or promote clearance of already deposited fibrils. [36]  

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