Ventricular Tachycardia in Patients With Dilated Cardiomyopathy

Definition

Dilated cardiomyopathy (DCM) is a primary disease of the heart muscle that is characterized by dilation of the heart chambers and decreased heart contractility. Two echocardiographic criteria were proposed to define DCM: left ventricular (LV) fractional shortening less than 25% or LV ejection fraction (EF) less than 45%, and LV end-diastolic diameter larger than 117% of the predicted value corrected for age and gender. The European Society of Cardiology (ESC) recognized the fact that not all patients fulfill these criteria and introduced the nondilated hypokinetic DCM as an earlier stage of DCM and part of a broader spectrum ending with the clinical picture of fully developed DCM. DCM most typically presents with symptoms of heart failure, but, rarely, it can be an incidental finding in less symptomatic or even asymptomatic patients. Palpitations or syncope stemming from ventricular and supraventricular arrhythmias can be the first manifestation of DCM as well.

Epidemiology: Prevalence and Mortality

The true prevalence of DCM is likely underreported. Older data from the Olmsted County Study estimated the DCM prevalence at 36.5 per 100,000 individuals or 1 in 2700 with a three times higher prevalence in men than in women. In a 2013 review by Hershberger et al., three approaches were used to estimate the prevalence of idiopathic DCM: (1) the known 2:1 ratio of DCM to hypertrophic cardiomyopathy (HCM); (2) the prevalence of heart failure symptoms; and (3) estimates for LV dysfunction as a surrogate for DCM. It was suggested that the prevalence of idiopathic DCM must be around 1:250. Nevertheless, there are geographic variations in the prevalence of DCM, possibly reflecting ethnic and genetic predispositions and differences in the methodology used.

Etiology

DCM is, in many cases, the common phenotypic expression of various primary and secondary myocardial diseases. Finding a specific cause for DCM is often difficult and requires elaborate diagnostic workup; however, identifying a reversible cause of DCM is important for successful treatment. The most frequent causes of secondary DCM are hypertension, valvular heart disease (mitral and aortic regurgitation); myocarditis (viral, bacterial, or protozoal including Chagas disease); systemic diseases (sarcoidosis, systemic sclerosis, lupus erythematosus, vasculitis); toxins (ethanol, heavy metals, anthracyclines, cocaine, methamphetamine); nutritional deficiencies (selenium, thiamine, carnitine, starvation); endocrine disorders (diabetes mellitus, hyperthyroidism, hypothyroidism, hyperparathyroidism, hypoparathyroidism, acromegaly); peripartum DCM; infiltrative diseases (amyloidosis, glycogen storage disease); and burned-out HCM. Moreover, multiple causes can affect one patient. Recent data suggest substantial roles of inflammation and autoimmunity in the pathophysiology of the DCM. ^, Furthermore, some genetic mutations, such as those in the TTN gene, are frequently associated with secondary forms of DCM, such as alcohol induced, anthracycline, or peripartum DCM.

In spite of an elaborate workup, a cause for DCM cannot be found in approximately 50% of patients; these patients are thus classified as primary DCM. A familial DCM is defined as the presence of two close relatives meeting the criteria for idiopathic DCM. With the introduction of next-generation sequencing, the genetic basis for many familial forms of DCM was clarified, although most of the cases seem to be sporadic. At the same time, the use of whole genome and whole exome sequencing generated a huge database of mutations with uncertain or probable pathogenic role in idiopathic DCM. Mutations of genes encoding different membrane and sarcomeric proteins are associated with most familial forms of DCM. ^, Some of them are exclusively associated with idiopathic DCM; however, there is significant genetic overlap between the main types of inherited cardiomyopathies because mutations in the same gene can cause different phenotype expressions. Currently, truncated variants of the TTN gene are the most frequently identified mutations in familial and sporadic forms of DCM. Other genes often associated with primary DCM are summarized in Table 87.1 . The autosomal-dominant inheritance is the predominant pattern of transmission in familial DCM, whereas X-linked, autosomal-recessive, and mitochondrial inheritance are less common. Two distinct forms of X-linked DCM are well described: X-linked DCM, which presents in adolescence, and Barth syndrome. The first one is caused by a mutation in the dystrophin gene and affects young males. Death usually occurs because of end-stage heart failure or ventricular arrhythmias (VAs). Mutations in the dystrophin gene are also responsible for Duchenne and Becker muscular dystrophy, in which DCM can occur along with skeletal muscular dystrophy. In Barth syndrome, mutations in the TAZ (tafazzin) gene can cause DCM, presenting with heart failure, neutropenia, and acidosis. Arrhythmias are also a frequent presentation.

Evaluation of Sudden Cardiac Death Risk in Patients With Dilated Cardiomyopathy

The prevalence of complex VA increases from 15% to 20% in New York Heart Association (NYHA) functional class I to II to 50% to 70% in NYHA IV. Although the likelihood of SCD increases with the NYHA class, VA is not the only cause of SCD in patients with DCM. In a small observational study, bradycardia or electromechanical dissociation was the most common initial presentation at SCD in patients with DCM. Several nonarrhythmic causes of sudden death are recognized. Current guidelines for ICD implantation in patients with DCM rely on two criteria: severely depressed left ventricular ejection fraction (LVEF) and high NYHA functional class that are neither specific nor sensitive enough to identify all patients at risk for SCD. Indeed, epidemiologic observations showed that many SCDs occur in patients with an LVEF greater than 35%. Moreover, long-term follow-up data of ICD recipients with DCM showed that less than one-third received an appropriate shock. These data demonstrated the poor performance of LVEF as a parameter for adequate assessment of SCD risk in DCM. New advanced imaging modalities, such as measuring the LV longitudinal strain using speckle tracking, may help improve the assessment of SCD risk in DCM. Patients with nonischemic DCM and new onset VT/VF showed significantly greater mechanical LV dispersion compared with those without arrhythmias. Mechanical LV dispersion greater than 50 ms was associated with a 12 times higher risk of VT/VF in patients with nonischemic DCM (odds ratio [OR], 12.5; 95% confidence interval [CI] ,1.1–143.4).

In a retrospective study of 137 children with nonischemic DCM, repolarization abnormalities were common. Prolongation of the JTc interval for at least 390 ms, the QTc interval for at least 510 ms, and abnormal T wave inversion were associated with an increased risk for life-threatening arrhythmia events. A recent meta-analysis of 45 studies enrolling 6088 patients with DCM evaluated the association between SCD and different predictive tests, among them baroreflex sensitivity, heart rate variability, heart rate turbulence, signal-averaged electrocardiogram, QRS duration, QRS fragmentation, LVEF, LV end-diastolic dimension, nonsustained VT, electrophysiology (EP) study, T wave alternans, and the QRS-T wave angle. Altogether, the sensitivity and specificity of these tests for prediction of SCD were modest, with T wave alternans having the highest sensitivity but low specificity for predictions of SCD (91% and 36%, respectively). On the other hand, the induction of VT/VF during an EP study had a poor sensitivity but a high specificity for arrhythmic events and SCD (29% and 87%, respectively). The odds ratio was highest for QRS fragmentation (OR, 6.73; 95% CI, 3.85–11.76) and T wave alternans (OR, 4.66; 95% CI, 2.55–8.53), and lowest for QRS duration (OR 1.51; 95% CI 1.13–2.01). None of the autonomic parameters (heart rate variability, baroreflex sensitivity, or heart rate turbulence) were predictive for SCD in DCM. New parameters can be useful to predict the probability for death in patients with DCM. In a recent study of 55 patients with nonischemic DCM who underwent catheter ablation, the size of the endocardial unipolar low voltage area (cut-off >145 cm ² ) was associated with an increased probability for cardiac death (area under the curve [AUC] 0.89, P < .0001; 83% sensitivity and 78% specificity) after adjustment for the LVEF.