Decennial follow-up in patients with recurrent tachycardia originating from the right ventricular outflow tract: electrophysiologic characteristics and response to treatment.
AIMS: In the setting of right ventricular outflow tract-tachycardia (RVOT-T), data about long-term follow-up (FU) with respect to the therapeutic strategies are missing. All patients (pts) referred to our institution during the last 20 years for the treatment of RVOT-T were studied in a retrospective analysis to assess mortality and efficacy of treatment. METHODS AND RESULTS: One hundred and thirty-three patients (77 female; 39+/-13 years) with sustained RVOT-T were included in this study. At the time of first presentation, diagnosis of RVOT-T was made by complete invasive and non-invasive diagnostic assessment, including electrophysiology study and two-dimensional echocardiography. After 135+/-68 months (median 136, range 29-248), patients were invited to undergo clinical assessment. Of the 133 pts, 127 (95%) survived and six (5%) died from non-cardiac disease. Anti-arrhythmic (AA) drugs were given to 62 of the 133 pts (47%); of them 32 (52%) had recurrences during follow-up. The mean time to recurrence was 10.02 years (95% CI 7.46-12.59). The other 71 study patients (53%) underwent catheter ablation. The procedure was successful in 58 pts (82%). During follow-up, 30 (52%) of the 58 successfully treated patients had recurrences of RVOT-T. The mean time to recurrence was 6.28 years (95% CI 4.96-7.6). RVOT-T recurrences were similar in morphology to those treated previously in 33% and different in 67% of cases. CONCLUSIONS: Long-term follow-up in patients with RVOT-T is favourable. Catheter ablation is effective in this setting. However, late recurrences with similar or different morphology may arise in half of the patients after initially successful treatment. AA drug therapy is a valid initial therapeutic option, since it is effective in about half of the patients. (+info)
Association of atrial arrhythmia and sinus node dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia.
BACKGROUND: This study was performed to investigate the frequency and importance of supraventricular arrhythmia and sinus node (SN) dysfunction in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS AND RESULTS: Eight patients with CPVT (mean age: 16.8+/-8.1 years) underwent an electrophysiological study. SN recovery time (1,389+/-394 ms) was slightly prolonged, and 4 of 8 patients had abnormal values. Atrial flutter (AF) was induced by low-rate atrial pacing in 2 patients and by isoproterenol infusion in 1 patient. Atrial fibrillation (Af) was induced by isoproterenol infusion in 2 patients. One patient presented with Af during the follow-up period, and 2 of 4 patients with AF/Af presented with increased SN recovery time. CONCLUSIONS: Patients with CPVT frequently have associated with SN dysfunction, and inducible atrial tachyarrhythmias, which indicate that the pathogenesis of CPVT is limited not only to the ventricular myocardium, but also to broad regions of the heart, including the SN and atrial muscle. (+info)
Matters of the heart: the physiology of cardiac function and failure.
Heart failure as a result of a myocardial infarction (MI) is a common condition with a poor prognosis. The adaptive changes in the surviving myocardium appear to be insufficient in terms of both mechanical/contractile performance and electrical stability. The modification of the underlying myocardial physiology is complex, varying across the different layers within the wall of the ventricle and within one layer. Two therapeutic strategies are briefly discussed, as outlined here. (i) Enhancing contractility by alteration of the expression of a single protein (e.g. sarco-endoplasmic reticulum Ca(2+) ATPase, SERCA) could potentially reverse both mechanical and electrical abnormalities. However, experimental data involving the upregulation of SERCA suggest that the therapeutic range of this approach is narrow. (ii) The use of regular exercise training to improve cardiac performance in heart failure. This appears to act by normalizing a number of aspects of myocardial physiology. (+info)
Electrophysiological consequence of adipose-derived stem cell transplantation in infarcted porcine myocardium.
AIMS: Aim of this study was to investigate the effect of intracoronary administration of freshly isolated adipose-derived mononuclear cells (ADMCs) on myocardial vulnerability to arrhythmia induction after infarction. METHODS AND RESULTS: A transmural myocardial infarction in an experimental porcine model was induced by occlusion of the mid-left anterior descending artery with an angioplasty balloon for 3 h. Upon reperfusion, a cellular suspension with freshly isolated ADMCs (1.5 x 10(6) cells/kg BW) or vehicle alone was injected into the infarct artery. All animals underwent a programmed ventricular stimulation at 8 weeks follow-up for possible induction of ventricular arrhythmias using a train of 8 S1 stimuli. Cell injections did not cause acute ventricular arrhythmia, bradycardia, or conduction block. The cycle length of the ventricular arrhythmia was compared at 1 and 10 s following its induction. Despite comparable infarct size in both groups, we found that the cycle length of the induced ventricular arrhythmia in the ADMC-treated group was significantly longer compared with control animals (P < 0.05). We also found that extra-stimuli were required for arrhythmia induction in the ADMC-treated group compared with control animals. CONCLUSION: Freshly isolated autologous stem cell therapy is not proarrhythmic in pigs. (+info)
Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues.
Alternation of cardiac action potential duration (APD) from beat to beat and concurrent alternation of the amplitude of the calcium transient are regarded as important arrhythmia mechanisms. These phenomena are causally interrelated and can be reliably evoked by an increase in beat frequency or by ischemia. The first part of this historical review deals with the physiology of APD alternans. Sections recounting the evolution of knowledge about calcium-activated ion currents and calcium transient alternans are interspersed among sections describing the growth of the so-called "restitution hypothesis," which involves time-dependent recovery of potassium channels (including their passage through pre-open states) as a function of diastolic interval. Major developments are generally in chronological order, but it is necessary to move back and forth between the two theories to respect the overall time line, which runs from about l965 to the present. The concluding two sections deal with the pathophysiology of calcium transient and APD alternans during ischemia, which may be the basis for out-of-hospital cardiac arrest during the initial stages of acute myocardial infarction. (+info)
Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in DeltaKPQ Scn5a murine hearts modelling human long QT 3 syndrome.
AIM: To perform an empirical, pharmacological, separation of early afterdepolarizations (EADs) and transmural gradients of repolarization in arrhythmogenesis in a genetically modified mouse heart modelling human long QT syndrome (LQT) 3. METHODS: Left ventricular endocardial and epicardial monophasic action potentials and arrhythmogenic tendency were compared in isolated wild type (WT) and Scn5a+/Delta hearts perfused with 0.1 and 1 microm propranolol and paced from the right ventricular epicardium. RESULTS: All spontaneously beating bradycardic Scn5a+/Delta hearts displayed EADs, triggered beats and ventricular tachycardia (VT; n = 7), events never seen in WT hearts (n = 5). Perfusion with 0.1 and 1 microm propranolol suppressed all EADs, triggered beats and episodes of VT. In contrast, triggering of VT persisted following programmed electrical stimulation in 6 of 12 (50%), one of eight (12.5%), but six of eight (75%) Scn5a+/Delta hearts perfused with 0, 0.1 and 1 microm propranolol respectively in parallel with corresponding alterations in repolarization gradients, reflected in action potential duration (DeltaAPD(90)) values. Thus 0.1 microm propranolol reduced epicardial but not endocardial APD(90) from 54.7 +/- 1.6 to 44.0 +/- 2.0 ms, restoring DeltaAPD(90) from -3.8 +/- 1.6 to 3.5 +/- 2.5 ms (all n = 5), close to WT values. However, 1 microm propranolol increased epicardial APD(90) to 72.5 +/- 1.2 ms and decreased endocardial APD(90) from 50.9 +/- 1.0 to 24.5 +/- 0.3 ms, increasing DeltaAPD(90) to -48.0 +/- 1.2 ms. CONCLUSION: These findings empirically implicate EADs in potentially initiating spontaneous arrhythmogenic phenomena and transmural repolarization gradients in the re-entrant substrate that would sustain such activity when provoked by extrasystolic activity in murine hearts modelling human LQT3 syndrome. (+info)
Arrhythmogenesis research: a perspective from computational electrophysiology viewpoint.
The mechanisms by which arrhythmias are generated in the heart remains a field of intensive research. Recent advances in computational biology and electrophysiology have enabled researchers to use an alternative tool in the study of arrhythmia mechanisms, the multi-scale modeling and simulation of cardiac arrhythmogenesis at the organ level. This article reviews the recent advances and achievements using this approach. (+info)
Hyperpolarization-activated cyclic nucleotide-modulated 'HCN' channels confer regular and faster rhythmicity to beating mouse embryonic stem cells.
The hyperpolarization-activated cation current (I(f)), and the hyperpolarization-activated cyclic nucleotide-modulated 'HCN' subunits that underlie it, are important components of spontaneous activity in the embryonic mouse heart, but whether they contribute to this activity in mouse embryonic stem cell-derived cardiomyocytes has not been investigated. We address this issue in spontaneously beating cells derived from mouse embryonic stem cells (mESCs) over the course of development in culture. I(f) and action potentials were recorded from single beating cells at early, intermediate and late development stages using perforated whole-cell voltage- and current-clamp techniques. Our data show that the proportion of cells expressing I(f), and the density of I(f) in these cells, increased during development and correlated with action potential frequency and the rate of diastolic depolarization. The I(f) blocker ZD7288 (0.3 microm) reduced I(f) and the beating rate of embryoid bodies. Taken together, the activation kinetics of I(f) and results from Western blots are consistent with the presence of the HCN2 and HCN3 isoforms. At all stages of development, isoproterenol (isoprenaline) and acetylcholine shifted the voltage dependence of I(f) to more positive and negative voltages, respectively, and they also increased and decreased the beating rate of embryonic cell bodies, respectively. Together, the data suggest that current through HCN2 and HCN3 channels confers regular and faster rhythmicity to mESCs, which mirrors the developing embryonic mouse heart, and contributes to modulation of rhythmicity by autonomic stimulation. (+info)