Cardiac Resynchronization Therapy and Proarrhythmia: Weathering the Storm

In patients with significant left ventricular (LV) dysfunction and congestive heart failure despite optimal medical therapy, implantation of cardiac resynchronization therapy-defibrillator (CRT-D) devices has been shown to improve symptoms and diminish ventricular tachyarrhythmia susceptibility.We describe the case of a patient with dilated cardiomyopathy who developed ventricular tachycardia storm (VTS) one month after the implantation of a CRT-D device. VTS was initially controlled with pharmacotherapy, allowing the patient to continue with biventricular pacing. Two months later the patient was readmitted due to multiple episodes of polymorphic ventricular tachycardia. VTS was refractory to various intravenous antiarrhythmic drugs and it was finally controlled only when LV pacing was turned off.In patients with heart failure treated with CRT-D, VTS can occur and is best managed by turning off LV pacing. Our report raises an important and concerning issue of biventricular pacing causing ‘proarrhythmia’ in rare instances

Effect of Transient Myocardial Ischemia on QT Interval Dispersion Among Patients with Unstable Angina

Objective: Our aim was to examine the effect of transient myocardial ischemia on QT interval and QT interval dispersion in patients presenting with unstable angina.Methods: We studied 31 patients (mean age 64±10, 22 men, 16 with an old myocardial infarction, 6 with previous coronary bypass surgery) admitted with unstable angina manifestations. Patients with a history of complex ventricular ectopy, malignant ventricular arrhythmias, advanced congestive heart failure or antiarrhythmic drug therapy were excluded. The uncorrected and corrected QT interval and QT dispersion were measured during angina as well as after the relief of pain.Results: The RR intervals were not significantly changed by the ischemic event (879±121 ms at rest to 877±173 ms during angina). However, both the uncorrected and corrected QT intervals were significantly increased during angina (from 410±45 ms and 440±41 ms at rest to 425±53 ms and 460±42 ms during angina respectively, p<0.05 for both). Similarly, both the uncorrected (QTd) and the corrected (QTcd) QT dispersion values were significantly prolonged during ischemia (QTd: 58±23 ms at rest to 83±33 ms during ischemia, p<0.001, QTcd: 63±26 ms at rest to 95±36 ms during ischemia, p<0.001). The observed increment in the QTd and QTcd provoked by ischemia was not different among the unstable angina patients with and without old myocardial infarction.Conclusion: Transient myocardial ischemia besides an increase in the QT and QTc intervals provokes an increase in both the corrected and uncorrected QT interval dispersion. Under certain circumstances, this may contribute to the genesis of serious reentry ventricular arrhythmias

Specific electrocardiographic features associated with Cushing's disease.

OBJECTIVE: Hypercortisolaemia is associated with an increased risk of cardiovascular disease (CVD), either through a direct action on the myocardium or by increased traditional cardiovascular risk factors. The aim of this study was to investigate whether the alterations in the ECG in Cushing's disease (CD) are predictable from risk factor analysis alone. DESIGN: In 79 patients with a diagnosis of CD, retrospectively recruited, ECG features [corrected for heart rate QT (QTc), QTc dispersion (QTcd), left ventricular hypertrophy (ECG-LVH), right ventricular hypertrophy (ECG-RVH)], systolic (SBP) and diastolic (DBP) blood pressure were assessed. Biochemical, hormonal (cortisol at 09·00 h or cortisol day curve, CDC) and carbohydrate abnormalities (CHA), history of hypertension and cardiovascular disease were recorded. For comparison reasons, a group of 42 healthy subjects matched for gender, age and body mass index previously subjected to ECG assessment were selected. RESULTS: In patients with CD, we noted the following prevalence: metabolic syndrome 39%, hypertension 81%, CVD 21·5%, hypercholesterolaemia 37%, hypertriglyceridaemia 29%, CHA 41%, but a history of cardiac dysrhythmia was only noted in a single patient. No difference in QTc or QTcd was shown between patients with normal or low potassium levels. QTcd >50 ms was associated with both increased ECG-LVH and ECG-RVH. When compared to the control group, patients had longer QTcd (P < 0·001), more prevalent LVH (P < 0·001) and RVH (P = 0·001), and higher SBP and DBP (P < 0·001), but similar QTc. Both CD and ECG evidence of LVH predicted prolonged QTcd, but the association of CD with a prolonged QTcd was independent of other risk factors, including hypertension. CONCLUSIONS: Prolonged QTcd in association with ECG evidence of LVH appears to be the specific feature of CD. This may be relevant in the choice of medical therapy for CD and for consideration of treatment of the comorbidities that are associated with hypercortisolaemia

Implantable cardioverter defibrillator therapy activation for high risk patients with relatively well preserved left ventricular ejection fraction. Does it really work?

Background: Current guidelines for the primary prevention of sudden cardiac death have used a left ventricular ejection fraction (LVEF) <= 35% as a critical point to justify implantable cardioverter defibrillator (ICD) implantation in post myocardial infarction patients and in those with nonischemic dilated cardiomyopathy. We compared mortality and ICD activation rates among different ICD group recipients using a cut-off value for LVEF <= 35%. Methods: We followed up for a mean period of 41.1 months 495 ICD recipients (442 males, 65.6 years old, 68.9% post myocardial infarction patients, 422 with LVEF <= 35%). Prevention was considered primary in patients who fulfilled guidelines criteria or had inducible ventricular arrhythmia during programmed ventricular stimulation for patients with LVEF >35%. Results: Over the course of the trial, 84 of 495 patients died; 69 experienced cardiac death (6 sudden) and 15 non cardiac death. ICD recipients with LVEF <= 35% compared to those with preserved LVEF (mean LVEF=43%) had a greater incidence of totalmortality (18% vs. 11%, log rank p=0.028) and cardiac death (15.4% vs. 5.5%, log rank p=0.005). There was no difference in the incidence for appropriate device therapy between patients with LVEF <= 35% and those with LVEF>35% (56.9% vs. 65.8%, log rank p=0.93). In the multivariate analysis the presence of advanced New York Heart Association stage predicted both total mortality (HR=2.69, 95% CI 1.771-4.086) and cardiac death (HR=3.437, 95% CI 2.163-5.463). Conclusions: ICD therapy may protect heart failure patients at early stages from arrhythmic morbidity and mortality, based on an electrophysiology-guided risk stratification approach. (C) 2012 Elsevier Ireland Ltd. All rights reserved

Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations

Aims Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood. Methods and resultsWe have identified novel mutations in the desmosomal cadherin desmocollin 2 (DSC2 R203C, L229X, T275M, and G371fsX378). The two missense mutations (DSC2 R203C and T275M) have been functionally characterized, together with a previously reported frameshift variant (DSC2 A897fsX900), to examine their pathogenic potential towards PGs functions at the ID. The three mutant proteins were transiently expressed in various cellular systems and assayed for expression, processing, localization, and binding to other desmosomal components in comparison to wild-type DSC2a protein. The two missense mutations showed defects in proteolytic cleavage, a process which is required for the functional activation of mature cadherins. In both cases, this is thought to cause a reduction of functional DSC2 at the desmosomes in cardiac cells. In contrast, the frameshift variant was incorporated into cardiac desmosomes; however, it showed reduced binding to PG. Conclusion Despite different modes of action, for all three variants, the reduced ability to provide a ligand for PG at the desmosomes was observed. This is in agreement with the reduced intensity of PG at these structures observed in ARVC patients. © 2010 The Author

Primary prevention of sudden cardiac death in a nonischemic dilated cardiomyopathy population reappraisal of the role of programmed ventricular stimulation

Background-We considered the role of programmed ventricular stimulation in primary prevention of sudden cardiac death in an idiopathic dilated cardiomyopathy population. Methods and Results-One hundred fifty-eight patients with idiopathic dilated cardiomyopathy underwent programmed ventricular stimulation. Ventricular tachycardia/ventricular fibrillation was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II), where ventricular tachycardia/ventricular fibrillation was not induced. Sixty-nine patients with idiopathic dilated cardiomyopathy underwent implantable cardioverter- defibrillator (ICD) implantation: 41/44 in group I and 28/114 in group II. The major end points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the 2 groups. Patients with left ventricular ejection fraction ≤35% (n=119) demonstrated a higher overall mortality rate compared with the patients with left ventricular ejection fraction >35% (n=39; 16.8% versus 10.3%, log-rank P=0.025). Advanced New York Heart Association class (III and IV versus I and II) was the single independent and strongest prognostic factor of overall mortality (hazard ratio, 11.909; P<0.001; confidence interval, 3.106-45.65), as well as of cardiac mortality (hazard ratio, 14.787; P=0.001; confidence interval, 2.958-73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared with group II (30 of 41 patients-73.2% versus 5 of 28 patients-17.9%; log-rank P=0.001), either in the form of antitachycardia pacing (68.3% versus 17.9%; log-rank P=0.001) or in the shock delivery form (51.2% versus 17.9%; log-rank P=0.05). Induction of ventricular tachycardia/ventricular fibrillation during programmed ventricular stimulation in contrast to left ventricular ejection fraction was the single independent prognostic factor for future ICD activation (hazard ratio, 4.195; P=0.007; confidence interval, 1.467-11.994). Conclusions-Inducibility of ventricular tachycardia/ventricular fibrillation was associated with an increased likelihood of subsequent ICD activation and sudden cardiac death surrogate. © 2013 American Heart Association, Inc