Sunday, February 05, 2017

Dilated cardiomyopathy review in Circulation

The review is open access full text. I have highlighted some sections below that are of particular interest.


From the review:

The term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease.5

In clinical practice, the pathogenesis of heart failure (HF) has often been placed into 2 categories: ischemic and nonischemic cardiomyopathy. The term nonischemic cardiomyopathy has been interchangeably used with DCM. Although this approach might be practical, it fails to recognize that nonischemic cardiomyopathy can include cardiomyopathies caused by volume or pressure overload (such as hypertension or valvular heart disease) that are not conventionally accepted under the definition of DCM.1,5

The diagnostic evaluation

Figure 1 is very helpful and should be viewed in the original. A few key points from the figure follow:

Family history is an extremely important part of the initial evaluation given the frequency of familial DCM.

An ischemic work up is indicated if there are ischemic signs, symptoms or risk factors. In some patients over 35 lacking these features it still may be necessary if the etiology remains unknown after evaluation.

Myocardial biopsy for the diagnosis of giant cell/fulminant myocarditis is indicated in any of the following situations: acute decompensation requiring inotropic or mechanical support; type 2 heart block; sustained or symptomatic VT; lack of response of the heart failure syndrome to guideline based medical management within 2 weeks.

Biopsy may be indicated in occasional other situations where certain specific myocardial diseases are considered (see text).

Cardiac MRI may be indicated, particularly for infiltrative diseases.

Disease specific considerations: amyloidosis

The section on amyloidosis is long and loaded with good practical information such that I cannot do justice to it here. I will make these points:

First, I have reviewed cardiac amyloidosis extensively in prior posts. [1] [2] [3] [4] [5] [6] [7] [8]

Also there was this concerning unique aspects of pharmacologic management of heart failure due to cardiac amyloidosis:

Digoxin should be avoided in patients with amyloidosis (Level of Evidence C). Digoxin binds to amyloid fibrils and thus can predispose to toxicity even in the setting of normal serum digoxin levels.56

Calcium channel antagonists (nifedipine or verapamil) should not be administered, because they bind to amyloid fibrils and can result in exaggerated hypotensive and negative inotropic responses (Level of Evidence C).57

Alcoholic cardiomyopathy

In addition to standard guideline based treatment of heart failure there is no disease specific treatment other than alcohol cessation.

Cocaine related cardiomyopathy

Some general considerations, from the review:

Although cocaine abuse has been associated with acute coronary events and regional myocardial injury, long-term cocaine use also has been associated with global DCM without the presence of coronary artery disease (CAD) .. This has been termed cocaine-related cardiomyopathy and implies direct toxicity of cocaine on the myocardium.

Concerning treatment:

Recommendations With Moderate Level of Consensus for Cocaine-Related Cardiomyopathy

It is reasonable to treat patients with cocaine-related cardiomyopathy who have demonstrated abstinence for greater than 6 months with standard therapy for LV dysfunction, including β-blockers (Level of Evidence C).

In patients at risk for relapse for cocaine abuse, nonselective β-blocker treatment with α1-, β1-, or β2-receptor antagonism is reasonable because of potential protection against the unopposed α-agonism effects of cocaine with β1-receptor antagonist treatment alone (Level of Evidence C).

Methamphetamine and related drugs

Cessation of use is the only disease specific recommendation. I have previously reviewed this topic here.

Chemotherapeutic agents

The major culprits are anthracyclines but there are others. Cardiotoxicity may occur at lower doses than previously thought. This may be due to greater sensitivity of detection. A troponin leak acutely after first administration is predictive of clinical cardiac toxicity. Early implementation of guideline based therapies may improve function and prognosis. Much more in the full text.

Peripartum cardiomyopathy

Prognosis is variable. Up to two thirds may recover. A few progress to transplant. Treatment is according to the general heart failure guidelines with the exception of drugs contraindicated in pregnancy and during lactation. Bromocriptine as a disease specific adjunct has yet to be established.


Here are a few points from the article:

Autopsy series suggest that 20% to 50% of patients with sarcoidosis have some degree of cardiac involvement228,232,233; however, only a fraction of these patients have clinically recognized cardiac sarcoidosis…

Diagnostic criteria for cardiac sarcoidosis have been proposed that rely on pathological demonstration of cardiac granulomas or noninvasive evidence of cardiac involvement in a patient with pathologically proven extracardiac sarcoidosis…

In patients with clinically evident cardiac sarcoidosis, complete heart block is a common finding…

Because the myocardial lesions in cardiac sarcoidosis are patchy, and many involve only the LV, an RV EMB provides diagnostic evidence of cardiac sarcoidosis in only 25% to 50% of autopsy-confirmed cases.232 Cardiac MRI with late gadolinium enhancement has emerged as a valuable imaging tool for the diagnosis of cardiac involvement in sarcoidosis…

Corticosteroids are the mainstay of therapy for sarcoidosis.228,229,231 ..Although there are no randomized controlled trials that have established the efficacy of corticosteroids in cardiac sarcoidosis, retrospective studies suggest benefit .. On the basis of observational studies, steroid therapy in patients with established cardiac sarcoidosis and active inflammation should be initiated before LV systolic function declines..Corticosteroids are commonly initiated at a high dose (prednisone 40–60 mg daily) and tapered off slowly over a period of months if clinical and imaging features remain stable or improve…

Patients with cardiac sarcoidosis and reduced LVEF or symptomatic HF should also be treated with standard HF therapy.1 However, because fatal arrhythmias account for 25% to 65% of deaths caused by cardiac sarcoidosis, particular attention is needed to identify patients who would benefit from placement of a permanent pacemaker with an ICD.228,229,231 Although limited, current evidence suggests that ICDs could prevent death caused by dangerous arrhythmias or sudden cardiac death in patients with reduced LVEF, as well as those with relatively preserved LVEF.2,231 In support of this recommendation, the 2012 American College of Cardiology Foundation (ACCF)/AHA/Heart Rhythm Society guidelines for device-based therapy listed cardiac sarcoidosis as a reasonable indication for ICD implantation, with a Class IIa recommendation.240,241


This section of the paper is very dense and should be read in the original. I will list only a few points here.

The term myocarditis means inflammation of the myocardium. It does not point to a specific etiology. Some specific myocardial diseases such as sarcoidosis covered separately above may be considered forms of myocarditis.

The indications for biopsy are controversial. The paper gives a reasonable approach. There is a set of noninvasive clinical criteria that can be applied if biopsy is considered impractical. These criteria are provided in the text.

Concerning treatment, note this from the paper:

Myocarditis that presents as DCM should be treated per current guidelines for systolic HF.1,3 Individual trials and a meta-analysis suggest that immunosuppression is generally not indicated for the management of acute lymphocytic myocarditis in adults. In cases of giant cell myocarditis, cardiac sarcoidosis, or eosinophilic myocarditis, treatments directed at modifying the immune response should be considered…

Device therapy may be indicated for certain malignant ventricular arrhythmias but not solely for low EF, since ventricular function may improve as inflammation subsides.

HIV can cause DCM

In the heart failure work up, patients with DCM and risk factors for HIV should be tested for HIV as a possible etiology of DCM.

Chagas diseases

Patients who present with DCM and have epidemiologic risk factors should be screened.

Connective tissue and autoimmune diseases

From the paper:

Autoimmune diseases have long been established as rare causes of cardiomyopathy and HF. There are several proposed mechanisms, including immune-mediated myocarditis, progressive fibrosis, and apoptosis with resultant restrictive and dilated phenotypes, progressive atherosclerosis with subsequent ischemic cardiomyopathy, and HF as a result of therapies used for the primary rheumatologic disorder.289 The more well-described associations between autoimmune/rheumatologic disorders and HF include systemic lupus erythematosus (SLE), scleroderma, RA, dermatomyositis, and polyarteritis nodosa (PAN). Sporadic case reports have also associated HF with ankylosing spondylitis, psoriatic arthritis, celiac sprue, vasculitis, and inclusion body myositis through a variety of mechanisms.

Obesity cardiomyopathy

The association of obesity with heart failure is now well enough recognized to warrant this designation. However, according to the article:

Although the concept of a cardiomyopathy related to obesity has been described previously,355–357 severe LV systolic dysfunction occurs uncommonly because of obesity alone, and the presence of LV systolic dysfunction should trigger an investigation for other contributory factors before it is attributed to obesity alone.

Multiple mechanisms were discussed in the paper. Beyond those, obesity can be a cause of the syndrome of high output heart failure. In a recent series, for example, obesity was identified as the etiology of high output heart failure in 31%. Additional factors include obesity's now well known association with atrial fibrillation [9] [10] and the disturbed sodium balance inherent in obesity due to lowered levels of natriuretic peptides.

Thyroid cardiolyopathy

The pathogenesis is incompletely understood. From the article:

Triiodothyronine (T3) generally increases the force and speed of systolic contraction and the speed of diastolic relaxation, through its effects on myosin isoforms and calcium-handling proteins.368–370 In addition, T3 decreases vascular resistance, including coronary vascular tone, and increases coronary arteriolar angiogenesis. Thyroid hormones can also promote both physiological and pathological myocardial hypertrophies.371 Hypothyroidism promotes myocardial fibrosis by stimulating fibroblasts, whereas the reverse is seen in hyperthyroidism..Hyperthyroidism and hypothyroidism can both lead to cardiovascular injury, including HF. However, a DCM related only to the thyroid disorder is present only in a small proportion of these patients.

The hemodynamic effects of hyperthyroidism include decreased systemic vascular resistance, increased resting heart rate and LV contractility, and enhanced isovolumic ventricular relaxation.373 Decreased systemic vascular resistance stimulates renin release with activation of the angiotensin-aldosterone axis,…

Growth hormone disorders

Consider these if the clinical picture fits.

Stress cardiomyopathy, chronic tachycardia myopathy and PVC induced cardiomyopathy

I have discussed these entities extensively in earlier posts to numerous to link here.

LBBB induced cardiomyopathy

It is well known that myocardial diseases capable of producing DCM can cause LBBB. On the other hand, less well known is the fact that LBBB itself, even if initially an isolated finding, can lead to DCM. Device therapy (resynchronization) may be helpful.

Genetic causes

This section deals with, in addition to familial DCM and its several inheritance patterns, left ventricular non-compaction and arrhythmogenic cardiomyopathy, formerly known as arrhythmogenic right ventricular dysplasia. From the paper:

DCM was initially believed to be inherited in a small percentage of cases until Michels et al475 showed that ≈20% of patients had family members with echocardiographic evidence of DCM when family screening was performed. More recently, inherited familial DCM has been shown to occur in 30% to 50% of cases, with autosomal dominant inheritance being the predominant pattern of transmission; X-linked, autosomal recessive, and mitochondrial inheritance patterns are less common but occur.

Duchenne and Becker muscular dystrophy are genetic causes of DCM but were not mentioned.

Iron overload cardiomyopathy

This can be as a result of hereditary hemochromatosis or chronic transfusions or iron infusions. Screening for iron overload is recommended in the evaluation of new cases of DCM although by the time DCM presents due to iron overload it may be too late for disease specific treatment to be beneficial.

Eosinophilic syndromes

Although this category is included in a review of DCM, it presents initially as a restrictive CM. From the paper:

The diagnosis of hypereosinophilic syndrome is made in the presence of eosinophils greater than 1500/μL..Echocardiography and MRI can be helpful in the diagnosis of eosinophilic myocarditis; however, myocardial biopsy remains the gold standard. After diagnosis, evaluation for secondary causes is essential.. If hypereosinophilic syndrome is suspected, a hematology consultation is warranted.. Corticosteroid therapy is generally considered primary therapy for eosinophilic myocarditis, but its efficacy is not well supported.

1 comment:

james gaulte said...

Thanks for a great review of DCM and also for pointing out that LBBB is more than a interesting EKG pattern. Even a number of cardiologists I have encountered seemed unaware that LBBB can after a variable and unpredictable lag period lead to DCM.In fact, early on there is significant decrease in cardiac function, noticeable mainly on exercise while the slight decrease in resting EF is unimpressive. It is also worth mentioning that bundle of His pacing may in many cases "fix" the LBBB by pacing distal to the block which can actually occur within the His Bundle. ( it did for mealso having a exercise induced second degree A-V block.