August 14th, 2020
Symptoms of heart failure
These are encountered in 80% of patients. Heart failure is a consequence of the progressive left ventricular (LV) dilation and systolic dysfunction encountered in dilated cardiomyopathy (DCM).
This is due to supraventricular or ventricular tachyarrhythmias. DCM predisposes to arrhythmias due to the disruption of the conduction system of the heart caused by progressive dilation, and progressive interstitial fibrosis contributing to an arrhythmic substrate. In individuals with DCM caused by inflammatory or infiltrative disease, the resulting injury to the myocardium may also be a contributing factor.
These are prominent in advanced cases, and include anorexia, nausea, abdominal discomfort, and cachexia. They are a consequence of chronic heart failure.
Sudden cardiac death
Sudden cardiac death may occur following ventricular arrhythmias such as monomorphic or polymorphic ventricular tachycardia, or ventricular fibrillation. The pathophysiology underlying the occurrence of arrhythmias is discussed under "palpitations".
Positive family history
Familial transmission occurs in 20% to 35% of cases. Autosomal dominant inheritance is the most common form of transmission. However, autosomal recessive, x-linked, and mitochondrial inheritance may also occur.
Chronic alcohol abuse
Chronic alcohol abuse accounts for 21% to 36% of cases in high-income countries. In this context, the alcohol intake must have been >80-100 g/day for >10 years. Alcohol appears to exert a direct toxic effect on the myocardium, while also depressing cardiac contractility and activating the neurohormonal system. All of these factors contribute to the development of DCM.
Recreational drug use
Cocaine and methamphetamine abuse is an important cause of DCM in younger adults. These drugs are potent sympathomimetic agents. They appear to cause cardiac toxicity via myocardial ischemia due to increased oxygen consumption, prothrombotic effects, coronary vasospasm, and accelerated coronary atherosclerosis.
DCM may occur in the last month of pregnancy or within the first five (5) months of delivery, without any discernible cause. This is termed "peripartum cardiomyopathy". The underlying pathophysiology is still unclear.
DCM is an important complication of anthracycline (e.g. doxorubicin, daunorubicin, etc.) therapy. This may occur during the therapy, or any time afterwards. The causes of anthracycline-induced cardiotoxicity appear to include oxidative stress, changes in mitochondrial membrane permeability, and suppression of respiratory chain activity.
Human immunodeficiency virus (HIV) infection can also give rise to DCM, and should be considered in individuals whose DCM has no clear cause. The underlying pathogenic mechanisms include: direct myocyte toxicity, activation of indirect pathways that induce myocardial inflammation and damage, and cardiac autoimmunity.
Micronutrient deficiency is common in HIV-infected persons due to gut malabsorption, diarrhea, and wasting syndrome. The resulting free radical formation may cause further myocardial injury. Therapy with the reverse-transcriptase inhibitor zidovudine (AZT) may cause myocardial damage. AZT may potentially contribute to the above, or independently cause DCM.
Certain autoimmune conditions are known to cause DCM. These include: systemic lupus erythematosus, connective tissue diseases (such as scleroderma and dermatomyositis), and vasculitides (e.g., eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa, and Kawasaki disease). The underlying mechanisms of these conditions include immune-mediated cardiac injury and thrombotic or inflammatory microvascular coronary disease.
In endemic regions, Chagas disease (caused by infection with the protozoan parasite Trypanosoma cruzi) is an important etiology of DCM. The pathogenesis is incompletely understood but may involve several mechanisms, including: parasite-dependent myocardial damage, immune-mediated myocardial injury, and microvascular and neurogenic disturbances.