7.1: Myocardial Disease - Secondary

Myocardial disease subsequent to a known origin is termed secondary myocardial disease. Timely correction of the originating disease may result in reversal of the cardiomyopathy. Nine different etiologies can be distinguished:

• Hypertension
• Ischaemia
• Valvular disease
• Alcohol
• Metabolic cardiomyopathy
• Takotsubo cardiomyopathy
• Peripartum cardiomyopathy
• Tachycardia

Hypertension or valvular disease

Inadequately treated hypertension or aortic stenosis results in adaptation of the left ventricle by means of hypertrophy. Although primarily considered an adaptive process to systolic overload, hypertrophy of the left ventricle is associated with ventricular dysfunction, arrhythmias, and sudden cardiac death. The process of hypertrophy involves enlargement and proliferation of myocytes, and interstitial fibrosis characterized by deposition of collagen type I and III. With increasing fibrosis, the compliance of the ventricle decreases resulting in loss of diastolic function before systolic function becomes impaired. Within this process of increasing myocardial mass, the coronary vasculature fails to adapt accordingly. In an attempt to accommodate to the increase in myocardial oxygen demand, coronary autoregulatory vasodilation results in an increase in coronary flow by during resting conditions. This partial exhaustion the coronary vasodilator reserve renders the myocardium at relative high risk for ischemia, and hence, patients may suffer from anginal complaints even in the absence of significant coronary artery disease. In patients with LVH, atrial fibrillation and ventricular arrhythmias, including multifocal ventricular extrasystoles, and short runs of ventricular tachycardia, are frequently found. The combination of myocardial fybrosis, maladaptation of the vasculature causing ischemia, autonomic imbalance and a prolongation of the action potential may serve as arrhythmogenic substrate in patients with LVH, resulting in an increased risk of sudden cardiac death.

Adequate antihypertensive treatment can regress left ventricular mass. In patients with aortic stenosis, ultimate treatment is valvular replacement to relief the systolic overload of the ventricle. With regression of the ventricle, improved diastolic, and preserved systolic function result, as well as a relief of vascular maladaptation-induced ischemia; the combination of which results in a decrease in cardiovascular events.

Ischemic cardiomyopathy

Chronic myocardial ischemia due to diffuse coronary atherosclerosis can cause cardiomyopathy of the dilated type (DCM). This ischemic cardiomyopathy may occur following one or multiple (silent) myocardial infarction(s), but may also occur from chronic (silent) ischemic myocardial damage. As such, it may be a progressive course of ventricular dilatation and ventricular dysfunction, but may also be the first manifestation of ischemic heart disease.

The extent of viable, or hibernating, myocardium determines the clinical relevance of revascularization of the ischemic myocardium. In patients with viable myocardial tissue, reperfusion improves symptoms, and supposedly prognosis. Several non-invasive tests may be used for this purpose, such as nuclear techniques, dobutamine echocardiography or contrast-enhanced cardiac MRI. However, the prognosis of ischemic cardiomyopathy is worse than non-ischemic forms of DCM, mainly due to a high risk of major ventricular arrhythmias. Moreover, subsequent ischemic episodes have a high impact on ventricular function in ischemia-related DCM.

As stated previously, revascularization may improve long-term prognosis in patients with objectively viable myocardium. In the absence of viability, routine heart failure therapy is the cornerstone of treatment including beta-blockade and ACE-inhibition (or angiotensine antagonists), and ICD implantation in a selection of patients.

Alcohol

Long-term alcohol abuse, >80g of alcohol per day (equivalent to 1 liter of wine) for more than 5 years, may lead to a dilated form of cardiomyopathy. Alcohol-induced dilated cardiomyopathy is the leading cause of non-ischemic dilated cardiomyopathy, some claim that it accounts for even up to 50% of cases. Most probably a genetic predisposition for DCM also plays an important role, as excess alcohol consumption itself prevails far more often than alcoholic cardiomyopathy (ACM). Both direct toxic effects of ethanol and its metabolites, as well as frequently occurring concomitant deficiencies of vitamins, minerals or electrolytes may adversely affect myocardial function.

Two stages of ACM are recognized when the disease is left untreated. The first stage comprises asymptomatical ventricular dilatation in which diastolic dysfunction may be present, at least partly due to interstitial fibrosis of the myocardium. Fifty percent of asymptomatic patients have echocardiographic signs of LVH with preserved systolic function. The second stage is characterized by impairment of systolic function, and clinically overt heart failure. The prognosis of untreated ACM is comparable to DCM, but is far more favourable in patients that abstain from alcohol use, or dramatically reduce alcohol intake (to less than 60g of ethanol per day). Most of the improvement follows abstinence within 6 months, but ventricular function may improve for up to 2 years. Heart failure therapy may improve ventricular function, but has only been shown to benefit survival in patients that practise abstinence.

Metabolic cardiomyopathy

The group of metabolic cardiomyopathies comprises a heterogenous group of myocardial disease secondary to a disruption in metabolism. Metabolic cardiomyopathy associated with diabetes mellitus is most common. Independent of its influence on hypertension or coronary artery disease, high levels of plasma glucose are increasingly associated with a direct deteriorative effect on ventricular function. Other examples of metabolic disease able to induce cardiomyopathy are nutritional deficits such as thiamine deficiency, or storage diseases, and mutations in AMP kinase.

Tako-tsubo cardiomyopathy

The prevalence of tako-tsubo cardiomyopathy is largely unknown, but the syndrome predominantly affects women between 60 and 65 years of age. Patients with Tako-tsubo cardiomyopathy present with electrocardiographic features mimicking an acute coronary syndrome in association with elevated cardiac biomarkers, but in the absence of significant coronary artery disease. The disease has inherited its name from the distinct angiographic feature of apical ballooning, resembling an octopus-pot or "Tako-tsubo". Left ventricular function is typically impaired in the apical and mid ventricular regions, with preserved basal function, although reverse patterns may be seen. High levels of cathecholamines have been suggested to play an important role in the etiology of the syndrome, which can be associated with emotional or physical stress, or in extremes in case of subarachnoidal hemmorhage. This cathecholamine storm may induce severe peripheral coronary spasm, leading to its clinical presentation. Treatment usually consists of aspirin, ACE-inhibitors or angiotensin receptor antogonists in case of preserved blood pressure, beta-blockers to reduce heart rate, and nitrates to counteract coronary spasms. LV function may restore rapidly within a few hours or days, even when admission ejection fraction was severely impaired, and clinical outcome is good although the disease may recur in approximately 5% of patients.

Figure 7.2.1: Tako-tsubo cardiomyopathy

Peripartum cardiomyopathy

Left ventricular systolic function impairment within 1 month of delivery, or during the first 5 months post partum, in the absence of pre-existing cardiac disease, and in the absence of another recognized cause for the cardiac dysfunction is termed peripartum cardiomyopathy.

Presentation is typically with features of left ventricular failure, although many features are undistinguishable from normal changes in pregnancy, due to which mild forms may not even be recognized. An inflammatory component has been suggested, in addition to malnutrition, viral infection, an abnormal immune response, and familial predisposition. Recurrence of the disease in subsequent pregnancies is noted, and makes the previously mentioned etiologies hard to explain. Most probably, peripartum cardiomyopathy results from predisposition to DCM, triggered to uncover by the high cardiovascular burden of the pregnancy.

Standard heart failure therapy can be instituted in peripartum cardiomyopathy, but the use of ACE-inhibitors and angiotensin receptor antagonists is contraindicated during pregnancy after the first trimester due to their possible adverse effects on the fetus. In extreme cases, the potential risks for the fetus should however be balanced against the critical need for preservation of ventricular function in order to provide both the mother and the fetus the best chance for a favourable clinical outcome. Pregnancy is also associated with a high risk of thrombo-embolism, as it is a hypercoagulable state per definition, which is enhanced by the presence of an impaired ventricular function in case of peripartum cardiomyopathy, and prophylaxis is therefore recommended.

Despite optimal treatment, LV function may normalize in as less as 50% of patients, and may deteriorate to end-stage heart failure in 15%. Potential recurrence in future pregnancies requires counselling of patients to prevent subsequent episodes of symptomatic heart failure and progression of ventricular dysfunction.

Tachycardia-induced cardiomyopathy

Persistently high heart rates (above 110 beats per minute), such as in sustained ventricular tachycardia, or associated with atrial fibrillation, results in heart failure when left untreated. Normalization of the heart rate by means of beta-blockade subsequently leads to normalization of ventricular function, and is therefore the cornerstone in treatment of tachycardia-induced cardiomyopathy.