Sudden Arrhythmic Death: Family Evaluation Identifies the Cause

A 23-year-old female professional dancer died suddenly following physical activity. Routine postmortem examination failed to establish the cause of death. No cardiac structural abnormalities were revealed. She had a history of presyncopal episodes during the last two months preceding her sudden cardiac death (SCD). Following the proband’s death, her family was referred to our department for clinical evaluation. Following informed consent, family members were evaluated with a standard protocol. All individuals underwent detailed non-invasive evaluation followed by genetic testing.The proband’s uncle was the first family member to undergo clinical investigation. He had been diagnosed with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) almost 5 years before his niece’s SCD. The proband was positive for a plakophilin-2 (PKP2) mutation and both her father and uncle had a typical form of the ARVC/D disease. To strengthen our diagnostic assessment an immunohistochemical analysis was undertaken of a myocardial sample obtained at autopsy, which pointed towards ARVC. Thus, her death was attributed to ARVC. Probably, the mutation had been inherited from her paternal grandfather. Although he had never been clinically evaluated, and no tissue was available for genetic analysis, he had a history of SCD at the age of 72, thus, raising suspicions of cardiac diseas

Continuity equation is the echocardiographic method of choice to assess degenerative mitral stenosis

We present a rare case of a patient with severe, symptomatic degenerative calcific mitral stenosis (MS). Calcification of mitral valve annulus (MVA) is a frequent finding in elderly patients. It can be isolated or associated more often with mitral valve insufficiency than MS. In rare cases, it results in severe MS. An accurate measurement of MVA in degenerative calcific MS is problematic because the limiting orifice is near the annulus and not at the leaflet tips as in rheumatic MS. Continuity equation is the best echocardiographic method to assess the MVA in degenerative MS, correlating well with invasive methods. Real-time three-dimensional echocardiography is a promising tool and provides an accurate measurement of MVA in calcific MS, with a very good correlation compared to continuity equation. On the other hand, the use of pressure half-time is often inaccurate and should be avoided, while two-dimensional planimetry is difficult and not reliable in degenerative MS. The values of mean gradient and systolic pulmonary artery pressure depend on several factors and should be only supportive signs and should not be considered as surrogate markers of the severity of MS. (Cardiol J 2011; 18, 5: 577–580

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

A Case of Asymptomatic Brugada Electrocardiographic Pattern Incidentally Unmasked During the Recovery Phase of an Exercise Stress Test

The interest about Brugada syndrome, an inherited channelopathy associated with sudden cardiac death in individuals without structural heart disease, is exponentially increasing lately. Similarly to chameleon, the electrocardiographic (ECG) signal of the disease fluctuates over time, it is often concealed, and may be unmasked under certain conditions. Recently, emergence of the characteristic ST-segment elevation during exercise stress test (EST) has been reported, probably resulting from an alteration of the autonomic tone in the different stages of exercise. We present the case of a 43-year-old, otherwise healthy male with an asymptomatic Brugada ECG pattern incidentally unmasked during the recovery phase of an EST

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 results: We 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 PG's 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

Arrhythmogenic Right Ventricular Cardiomyopathy: The Challenge of Genetic Interpretation in Clinically Suspected Cases

This is the case of a 43-year-old Caucasian man with frequent episodes of paroxysmal atrial fibrillation (AF) and normal resting electrocardiogram (ECG), who fulfilled two minor diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC): late potentials by signal-averaged ECG and regional right ventricular outflow tract (RVOT) dyskinesia with mildly dilated RVOT end-diastolic diameter. Genetic test results revealed a disease-associated missense mutation in DSC2 (p.E102K), adding a major diagnostic criterion according to recently published modified Task Force Criteria. However, 2 years after successful ablative therapy for AF, the patient remains completely asymptomatic, without any clinical signs of ARVC. Both ventricular and supraventricular arrhythmias had vanished after AF ablation. Our patient mainly suffered AF without significant ventricular arrhythmias, a very uncommon clinical presentation of ARVC. Copyright (C) 2012 S. Karger AG, Base