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The incidence of coronary artery disease (CAD) is greater in men than in women. The aim of the study was to analyze whether any gender-related differences in patients with CAD and documented spontaneous sustained ventricular tachyarrhythmias exist, and which parameters influence the induction of sustained ventricular tachyarrhythmias. The data of 250 patients [43 women (17.2%) and 207 men (82.8%)] with spontaneous sustained ventricular tachycardia [n = 190 (76%)] and fibrillation [n = 60 (24%)] who underwent coronary and left ventricular angiography, electrophysiological study, and signal-averaging electrocardiogram (ECG) form the basis of this analysis. No gender-related differences could be observed in age, number of diseased coronary arteries, history, location and number of myocardial infarctions, presence of left ventricular aneurysm, ejection fraction, type of spontaneous or induced arrhythmias, right ventricular effective refractory period, and signal-averaged ECG parameters. Age, presence of previous myocardial infarction, and ejection fraction were significant predictors (p < 0.001) of inducibility of sustained ventricular tachyarrhythmias. Once CAD has begun, female and male patients present similar clinical and electrophysiologic characteristics. Thus, both genders should benefit similarly from diagnostic and therapeutic approaches if they are referred to the hospital or to invasive interventions at similar intervals in the course of their illness.

The Brugada syndrome (BS) is a distinct form of idiopathic ventricular fibrillation and may cause sudden cardiac death in healthy young individuals. In the surface ECG, BS can be recognized by an atypical right bundle branch block and ST-segment elevation in the right precordial leads. Mutations in the cardiac sodium channel gene SCN5A are only known to cause BS. In a multi-center effort, we have collected clinical data on 44 unrelated index patients and family members and performed a complete genetic analysis of SCN5A. In 37% the disease was familial, whereas in the majority it was sporadic (63%). Five novel SCN5A mutations (2602delC, resulting in: E867X; 2581_2582del TT: F861fs951X; 2673G>A: E1225K; 4435_4437delAAG: K1479del; and 5425C>A: S1812X) were found and were randomly located in SCN5A. Mutation frequencies (SCN5A+) differed significantly between familial (38%) and sporadic disease (0%) (p=0.001). Disease penetrance was complete in the SCN5A+ adult patients, but incomplete in SCN5A+ children (17%). Genetic testing of SCN5A is especially useful in familial disease to identify individuals at cardiac risk. In sporadic cases, however, a genetic basis and the value of mutation screening has to be further determined. These results are in line with a possibly genetic and clinical heterogeneity of BS.

Recent technical developments in implantable cardioverter defibrillator (ICD) systems and reduced operative mortality and morbidity rates associated with ICD implantation have expanded the indications for ICD treatment of ventricular tachyarrhythmias. This review summarizes data regarding ICD therapy in patients with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, and idiopathic ventricular fibrillation and presents preliminary concepts for identification of patients who will benefit more from ICD therapy than from pharmacologic and other nonpharmacologic approaches. Recent studies suggest that ICD therapy may improve long-term prognosis by reliably terminating recurrences of life-threatening arrhythmias. Appropriate ICD therapies during mean follow-up periods of 12 to 36 months occurred in 30% of patients with idiopathic ventricular fibrillation to 50% of patients with arrhythmogenic right ventricular cardiomyopathy and long QT syndrome. At present no strict recommendations can be given for ICD implantation in these patients. However, at least in cardiac arrest survivors in whom the clinical arrhythmia is not reproducibly inducible during electrophysiologic study, ICD therapy appears to be superior to other treatment options with regard to long-term survival and thus should be considered as a first-line treatment. We are hopeful that continued study of long-term follow-up with and without ICD treatment and improved risk stratification will lead to better criteria for selection of treatment options.

Cine magnetic resonance imaging was used to analyze global and regional left ventricular function in seven patients with obstructive hypertrophic cardiomyopathy (HC) and 10 normal subjects. In patients with HC a 38% higher left ventricular mass index (106.4 ± 20.2 gm/m2 vs 77.0 ± 16.1 gm/m2, p < 0.005) associated with a lower end-diastolic volume index (44.9 ± 8.9 ml/m2 vs 58.3 ± 9.0 ml/m2, p < 0.005) resulted in an 85% higher mass-to-volume ratio (2.4 ± 0.52 vs 1.3 ± 0.57, p < 0.0005). Stroke volume did not differ significantly, whereas ejection fraction was higher (80.4% ± 6.5% vs 65.4% ± 7.2%, p < 0.0005) in patients with HC. Although early diastolic filiing fraction was smaller in patients with HC (61.0% ± 22.8% vs 68.4% ± 14.6%), the difference did not reach significance because of substantial variability. In patients with HC (in contrast to normal subjects) the time to maximal wall thickening was shorter (p < 0.025) in the hypertrophied basal region of the ventricle (223 ± 42 msec) than in the apical region (267 ± 35 msec), reflecting asynchrony between these regions. Additionally, in patients with HC the standard deviation of the time to maximal wall thickening in the basal region was significantly higher when compared with that of normal subjects (40.0 ± 24 msec vs 16.9 ± 17 msec, p < 0.0005), reflecting asynchrony even within one region. Thus magnetic resonance imaging can detect regional left ventricular asynchrony, an important cause of impaired diastolic function, in patients with HC and normal global systolic function. It might therefore be of value especially when analysis of left ventricular filling yields equivocal results.

It was analyzed whether the response to sotalol can predict the response to amiodarone as evaluated by programmed ventricular stimulation in 30 patients with coronary artery disease and documented recurrent sustained ventricular tachycardia (VT). Programmed ventricular stimulation was performed using 1 or 2 extrastimuli during sinus rhythm and 4 drive cycle lengths at 2 right ventricular sites. If no ventricular tachyarrhythmia was induced, a third extrastimulus was introduced during a paced cycle length of 500 ms. During the control study, VT (mean cycle length 305 +/- 63 ms) was induced in all patients, and the right ventricular effective refractory period (during S1-S1 = 500 ms) was 223 +/- 12 ms. After sotalol, sustained and nonsustained VT were inducible in 22 (73%) and 7 (23%) patients, respectively. One patient did not undergo stimulation on sotalol, because of side effects. After amiodarone, sustained and nonsustained VT were inducible in 23 (77%) and 7 (23%) patients, respectively. The mean cycle length of the induced VT was prolonged after both drugs by 17% (p0.001). The effective refractory period was prolonged by 15% (p0.001) after sotalol and by 13% (p0.001 compared with baseline study; p = NS between both drugs) after amiodarone. Thus, concordant results (effective or ineffective drug) between sotalol and amiodarone were found in 26 patients (87%).(1) The effects of sotalol and amiodarone on the cycle length of induced VT and on right ventricular effective refractory period were similar; and (2) inability to suppress VT by amiodarone can be predicted from the response to sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsed Doppler echocardiography has been repeatedly used to assess left ventricular filling in cardiac diseases associated with left ventricular hypertrophy. Abnormalities in the transmitral flow velocity curve have been found in symmetrical left ventricular hypertrophy due to pressure overload, such as arterial hypertension and aortic stenosis [1], as well as in hypertrophic cardiomyopathy [2–4], a disease characterized by an asymmetrical ventricular hypertrophy of unknown etiology. Although hypertrophic cardiomyopathy is the disease with the most severe expressions of hypertrophy in human beings, Doppler studies of transmitral flow velocity failed to consistently demonstrate the signs of impaired left ventricular filling, especially in the obstructive form of the disease [3,4]. Several possible factors have been discussed to explain that [3–5], but no attention has been paid to the influence of the position of the sample volume. Based on observations in individual patients with hypertrophic cardiomyopathy, showing impressive variations of the diastolic flow velocity curve with different positions of the sample volume along the left ventricular inflow tract, we prospectively examined, whether the specific asymmetrical left ventricular geometry in hypertrophic cardiomyopathy could have an impact on regional differences in diastolic flow velocity patterns, when compared to symmetrical forms of hypertrophy.

Brugada syndrome is an inherited arrhythmia syndrome associated with sudden cardiac death. Na+-current dysfunction is central in Brugada syndrome, but mutations in the cardiac Na+-channel gene SCN5A are present in only ∼ 20 % of probands. Since only a minority of Brugada patients has detectable mutations, we considered alternative disease mechanisms involving a consistent pattern of variations in cardiac electrogenenic processes. We specifically hypothesized that a common pattern of cardiac ion channel and transporter gene-expression might contribute to the pathophysiology of Brugada syndrome by producing a phenotypic background that facilitates expression of characteristic ECG abnormalities and arrhythmogenesis in the context of appropriate genotypic and/or environmental factors. To test this notion, we applied high-throughput real-time PCR, which permits accurate quantification of up to hundreds of transcripts in minute biological samples, to obtained full profiling of ion-channel expression in right-ventricular septal endomyocardial biopsies from 10 patients with Brugada syndrome in comparison with biopsies from 11 non-diseased organ donors, 7 heart transplant recipients, 10 patients with arrhythmogenic right-ventricular cardiomyopathy and 9 with idiopathic right-ventricular outflow-tract tachycardia. Brugada patients showed distinct and reproducible clustering differences versus the two control and two ventricular tachyarrhythmia groups, including 14 of 77 genes encoding important ion-channel/ion-transporter subunits. Nav1.5, Kv4.3 and Kir3.4 were more weakly-expressed, while Nav2.1 and TWIK1 were more strongly-expressed, in Brugada syndrome. Important differences were also seen in transcripts involved in Ca2+-homeostasis, including stronger expression of RYR2 and NCX1. The molecular profile of five Brugada patients with SCN5A mutations did not differ from Brugada patients without SCN5A mutations. Brugada patients exhibit a common ion-channel molecular expression signature, irrespective of the culprit gene. This finding has potentially important implications for our understanding of the pathophysiology of Brugada syndrome, with possible therapeutic and diagnostic implications.

Brugada Syndrome and Supraventricular Tachyarrhythmias.Introduction: The Brugada syndrome is a distinct form of idiopathic ventricular fibrillation characterized by a unique ECG pattern consisting of a right bundle branch block-like aspect and ST segment elevation in leads V1 to V3. As a high induction rate of ventricular tachyarrhythmias has been reported in Brugada syndrome, we hypothesized that this also may be true for supraventricular tachycardias in these patients. Methods and Results: Between January 1995 and December 2000, we identified 35 consecutive patients with Brugada syndrome; 26 had a history of cardiac arrest or syncope and 9 were asymptomatic. All patients underwent electrophysiologic study, including an atrial and ventricular stimulation protocol. Ten patients (29%) were found to have supraventricular tachyarrhythmias (SVT) in addition to the Brugada syndrome. These 10 patients presented with aborted sudden cardiac death (n = 3) and/or a family history of sudden cardiac death (n = 4), syncope (n = 4), or primarily with a Brugada typical ECG, a positive family history, and palpitations (n = 2). Eight of them underwent genetic testing, but only 1 had a mutation in the SCN5A gene. In 6 patients, an AV nodal reentrant tachycardia was easily and reproducibly inducible. Two patients had clinical documented and inducible episodes of an atrial tachycardia (1 in addition to an AV nodal reentrant tachycardia). One patient had paroxysmal atrial fibrillation alternating with sinus rhythm, and 2 patients with accessory pathways were identified. Conclusion: This is the first description of an association of the Brugada syndrome with SVT. Thus, the arrhythmogenic substrate in Brugada syndrome may not be restricted to the ventricular level. Palpitations in this syndrome should raise the possibility of SVT. Conversely, in patients with SVT and aborted sudden cardiac death or syncope not related to SVT, the Brugada syndrome should be considered a possible additional electrophysiologic abnormality.

BSPM and Late Potentials in Brugada Syndrome. Introduction: The value of noninvasive markers reflecting repolarization and/or conduction abnormalities in identifying patients with abnormal ECG showing a pattern of atypical right bundle branch block and ST elevation syndrome (Brugada syndrome) at risk for life-threatening arrhythmias is controversial. Because right precordial ST elevation reflects inhomogeneous repolarization, we hypothesized that a correlation between the area of ST elevation, that is, the area of inhomogeneous repolarization, and the inducibility of ventricular tachyarrhythmias (VT) exists. Therefore, the body surface area of ST elevation and the presence of late potentials were compared to the inducibility of VT in patients with the characteristic ECG of Brugada syndrome. Methods and Results: A 120-channel body surface potential map was recorded at rest and after administration of a Class I agent (ajmaline, 1 mg/kg) to measure the body surface area of ST elevation (≥0.2 mV) in 23 individuals (16 patients had been resuscitated from near sudden cardiac death or had suffered syncope) with an ECG compatible with the diagnosis of Brugada syndrome as well as in 15 healthy controls and in 15 patients with arrhythmogenic right ventricular cardiomyopathy. Late potentials were assessed in 20 of the Brugada patients using signal-averaged ECG. Programmed ventricular stimulation was performed at two ventricular sites with up to three extrastimuli. Mean body surface area of ST elevation (≥0.2 mV) of all Brugada syndrome patients was 154 ′ 139 cm 2 (control 9 ′ 9 cm 2 ; P < 0.001). In the group of patients with arrhythmogenic right ventricular cardiomyopathy, only one patient was found to have an area of ST elevation (165 cm 2 ). In the presence of ajmaline, area size increased to 330 ′ 223 cm 2 in Brugada syndrome patients (P < 0.05). In patients with inducible sustained (n = 15) and nonsustained VT (n = 3), a mean area of 183 ′ 139 cm 2 was found, whereas the area was only 52 ′ 58 cm 2 in those with no VT induction (P < 0.05). For an area ≥50 cm 2 , there were positive and negative predictive values of 92% and 60%, respectively. Positive late potentials were found in 60% of patients and correlated to the inducibility during programmed ventricular stimulation (positive predictive value 100%, negative predictive value 75%; P < 0.001). Conclusion: In patients with Brugada syndrome, the body surface area of ST elevation and the presence of late potentials correlate to the inducibility of VT during programmed ventricular stimulation and may be of value as a new noninvasive marker for risk stratification in these patients.