Ventricular Ectopic Activity Research Articles

TITERS OF ANTIBODIES TO Β1-ADRENOCEPTOR AND M2 CHOLINERGIC RECEPTORS IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS WITHOUT AN ORGANIC CARDIOVASCULAR DISEASE AND THEIR POSSIBLE CLINICAL SIGNIFICANCE

Aim. To identify the most promising epitopes that simulate various sites β1-adrenergic and M2-cholinergic receptors, and to evaluate their possible contribution to the development and maintenance of cardiac arrhythmias, particularly idiopathic ventricular arrhythmia. Material and methods. Patients with ventricular arrhythmias without organic cardiovascular disease (the study group; n=70) were included in the study. The control group consisted of 20 healthy volunteers. Evaluation of levels of antibodies to antigenic determinants, modeling various sites β1-adrenergic and M2-cholinergic performed in all patients. Causal treatment with clarithromycin and valacyclovir performed in part of patients. Results. Antibodies to different peptide sequences of β1-adrenergic and M2-cholinergic receptors have been identified in 25% of main group patients. A direct correlation between the frequency of episodes of ventricular tachycardia and IgG levels to MRI-MRIV (p=0.02) revealed. Increase in titre of antibodies to β1-adrenoceptors, to a peptide sequence β8 (p=0.02), and lower titers of antibodies to the M2 acetylcholine receptor — chimera MRI-MRIV IgM (p=0.06) and ARI-MRIV IgM (p=0.07) were observed when assessing the efficacy of the therapy in the causal dynamics in the group of "untreated" patients. IgG titer reduction of ARI-MRIV (p=0.02), which is 4 times out of 10 with reduction of ventricular ectopic activity , recorded after valacyclovir therapy. Clarithromycin therapy on the level of antibodies exerted no significant effect. Conclusion. Possible involvement of antibodies to β1-adrenoceptor and M2-cholinergic receptors in the development of idiopathic ventricular arrhythmias demonstrated. The relationship between the frequency of episodes of ventricular tachycardia and levels of antibody titers to M2-cholinergic receptors found. Attempt of causal treatment, depending on the possible mechanisms of the autoimmune process is executed. Further studies to confirm or refute the results to the larger sample of patients are needed.

Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy?

To prospectively assess the safety and efficacy of ivabradine in patients with idiopathic dilated cardiomyopathy. We included 35 patients with idiopathic dilated cardiomyopathy with an ejection fraction (EF) <40% and heart rate >70 beats/min despite optimal medical therapy, according to the international guidelines in this prospective, non-randomized, single-arm, open-label safety study. Ivabradine was used as an add-on therapy to the maximally tolerated b-blocker in an increasing titrated dose till a target dose of 15 mg/day or resting heart rate of 60 beats/min for 3 months. During follow-up period the safety, patient tolerance and efficacy of this drug were assessed. All patients underwent 12-lead resting electrocardiography and Holter monitoring at inclusion and after 3 months. Statistical analysis was accomplished using paired t-test and Pearson correlation analysis. We found a significant reduction in the resting heart rate by a mean of 25.9 ± 9.4%, without a significant change of blood pressure. There was no prolongation of PR, QTc or QRS durations. Ventricular ectopic activity showed significant reduction (p<0.001). There was a significant correlation between the resting heart rate, NYHA and left ventricular ejection fraction (p<0.001 for both). One patient developed photopsia and decompensation was observed in another patient. Ivabradine is a safe and effective drug in reducing resting heart rate, improving NYHA functional class without undesirable effects on conduction parameters or ectopic activity.

Prevalence and Clinical Correlates of Ventricular Arrhythmias on 24-Hour Ambulatory Electrocardiographic Monitoring

Background Premature ventricular complexes may occur in normal individuals. Its clinical significance depends on whether it is frequent and the presence of risk factors for coronary artery disease. Studies have shown that frequent ventricular ectopic activity coupled with significant risk factors for coronary heart disease carry adverse prognostic implication in healthy individuals without obvious structural heart disease. This study examined the prevalence and clinical correlates of ventricular arrhythmias in individuals without apparent heart disease. Method 24-Hour ambulatory electrocardiogram was recorded in 60 apparently healthy subjects with normal echocardiography findings. Premature ventricular complex was analyzed and quantified in each subject. Results Premature ventricular complex was present in 27 (45%) subjects. None of the subjects had ventricular couplets or non-sustained ventricular tachycardia. The observed premature ventricular complexes were all unifocal and infrequent (< 30 PVC/hour). Conclusion This study suggests that frequent premature ventricular complexes are not uncommon in healthy individuals without clinical evidence of organic heart disease and obvious risk factors for coronary artery disease. However, further studies are needed to further confirm the implications of these findings. Keywords: premature ventricular complex, ventricular arrhythmias, Holter monitor,Electrocardiography.

Reconciling the Protean Manifestations of Arrhythmogenic Cardiomyopathy

Medical conception of a disease begins with in vivo observation and develops with recognition of cognate findings on gross anatomy, histology, and cellular pathology. It was histopathology that established myocyte disarray as the cardinal feature of hypertrophic cardiomyopathy, present even in cases where left ventricular (LV) hypertrophy is subtle or absent. To this day, clinical-pathological association retains its historical value as the primary means of gaining insight into underlying disease processes. Enhancing its appeal is its accessibility to physicians, most of whom are familiar with histopathology from medical school and attuned to visual diagnosis. Article see p 632 With the advent of molecular genetics, however, the limitations of clinical-pathological association have become apparent and nowhere more so than in the inherited arrhythmia syndromes. In the long-QT and Brugada syndromes and catecholaminergic polymorphic ventricular tachycardia, a structurally normal heart belies the propensity to ventricular arrhythmia and sudden cardiac death (SCD). How this might be possible began to unravel with the isolation of mutations in genes encoding ion channels, transporters, and binding proteins. Genetic studies also have provided fresh insights into diseases with an obvious pathological substrate, such as hypertrophic cardiomyopathy, in which sarcomeric mutations predominate. Families with a high incidence of SCD and myocyte disarray but minimal LV hypertrophy were found to have mutations in troponin T,1 lending further support to the inclusion of this phenotype within the spectrum of hypertrophic cardiomyopathy. Redefining diseases according to their genetic etiology, while attractive, is less straightforward than immediately obvious. Defects in sarcomeric components, for example, have been implicated in both hypertrophic cardiomyopathy and dilated cardiomyopathy. In some heritable disorders, such as dilated cardiomyopathy, marked locus heterogeneity precludes delineation of a single genetic determinant. The ultimate solution to disease classification involves going 1 step further and identifying a unifying molecular mechanism, which may …

Drug-Induced Arrhythmia

Prolongation of the QTc interval has been associated with proarrhythmia resulting from a potentially fatal form of polymorphic ventricular tachycardia called torsades de pointes (TdP). Genetic forms of the long-QT syndrome (LQTS) associated with high arrhythmic risk have been causally related to mutations in ion channels responsible for the cardiac action potential; genetic factors associated with milder degrees of QTc prolongation and arrhythmic risk have also been described. Acquired forms of QTc prolongation and proarrhythmia, particularly related to drug therapy, are frequently related to drug effects on the same ion channels involved in genetic forms of LQTS. As is true for genetic forms of LQTS, there is a wide spectrum of potential drug effects on the QTc interval ranging from trivial to potentially lethal. Drug-induced QTc prolongation is a complicated phenomenon related not just to the properties or dose of a particular drug but also to drug-drug interactions and a variety of patient factors, including age, gender, the presence and severity of underlying heart disease, and genetic predisposition. Additionally, drug effects on other ion channels, including blockade of sodium channels (causing prolongation of the QRS interval rather than the QTc interval), are an important cause of drug-induced proarrhythmia. The purpose of this review is to summarize the available data related to acquired forms of LQTS, with particular focus on drug-related LQTS and proarrhythmia. A brief summary is presented here of genetic LQTS because the relevant genes and proteins form the basis for an understanding of the causes of acquired LQTS, and in any given patient, the QTc is determined by genetic, substrate, and environmental factors. Emphasis is placed on practical strategies for clinicians, with the goal of minimizing the risk of dangerous proarrhythmia related to the use of both cardiac and noncardiac drugs with the potential for QTc prolongation. Genetic …

Dilated Cardiomyopathy With Conduction Disease and Arrhythmia

case presentation: A 48-year-old woman presents with exertional dyspnea and recurrent syncope. One year earlier, a permanent pacemaker was placed after she complained of fatigue and was found to have high-grade atrioventricular block. Now, she has echocardiographic evidence of moderate to severe left ventricular (LV) systolic dysfunction with regional wall-motion abnormalities. Nuclear imaging is notable for heterogeneous myocardial uptake of technetium Tc99m sestamibi, and coronary angiography reveals widely patent epicardial vessels. Multiple episodes of nonsustained ventricular tachycardia (VT) are documented on continuous ECG monitoring. What are the diagnostic considerations for this patient, and what further evaluations are indicated? This patient presents with dilated cardiomyopathy (DCM) with electric instability (DCM+E), which we define as conduction disease and arrhythmia out of proportion to the severity of LV systolic dysfunction. Diverse causes can result in DCM+E and fall into general categories of inflammatory, infectious, hereditary, and infiltrative processes. Cardiac presentation associated with these conditions is distinct from more common causes of DCM such as ischemic heart disease, viral myocarditis, valvular dysfunction, pregnancy, or substance abuse. Clinical features that are suggestive of DCM+E include supraventricular arrhythmias or conduction disease that precedes cardiomyopathy, multiple VT morphologies, and features suggestive of ischemic heart disease (Q waves, regional wall-motion abnormalities, perfusion defects, ventricular aneurysm) in the absence of epicardial stenoses. In this Clinician Update, we focus on the diagnostic approach to patients with DCM+E. Emphasis is placed on diagnoses that are relatively common or for which the clinical management would be impacted significantly by recognition of the underlying cause. Ischemic heart disease may present with conduction disease and a high burden of arrhythmia, especially in the setting of acute myocardial ischemia/infarction. The exclusion of obstructive coronary artery disease is strongly recommended in patients with DCM+E because atherosclerosis is so prevalent, evidence-based treatment is readily available, and the …

The Utility of Ambulatory Electrocardiographic Monitoring for Detecting Silent Arrhythmias and Clarifying Symptom Mechanism in an Elderly Urban Population with Heart Failure and Hypertension: Clinical Implications

Background: Atrial and ventriclar tachyarrhythmias, as well as bradyarrhythmias, in the elderly with heart failure (HF) and/or hypertension (HTN) have been well documented. However, the frequency of these arrhythmias, whether silent or symptomatic, and their association with subsequent cardiac events has not been well defi ned in patients 65 years or older with HF and other cardiovascular risk factors. Objective: To assess the value of 2 weeks of remote, transtelephonic cardiac monitoring for detecting arrhythmias in an elderly, urban population living with HF. Methods: Fi" y-four patients with a history of systolic HF and/or HTN were consented and enrolled. All wore an auto triggered cardiac loop monitor for 2 weeks that captures EKG data and both silent and symptomatic arrhythmias were recorded. Results: Mean age was 73 ± 6 years with 59% of subjects were females, 74% Hispanic, 22% black, and 4% white/other. All patients had HF and 94% had HTN. From the cardiac monitoring, 72% demonstrated ectopic atrial and ventricular activity, and 1 paroxysmal episode of atrial fi brillation was documented. In addition, 3 subjects had signifi cant non-sustained ventricular tachycardia, and 4 individuals had severe bradycardia recorded on cardiac monitoring. These 7 individuals underwent placement of an implantable cardioverter defi brillator (ICD) or pacemaker based on the documented arrhythmias which may have otherwise gone undetected. Conclusions: A substantial proportion of patients exhibited cardiac arrhythmias. Future morbidity was prevented because of the detection of arrhythmias on monitoring that led to specifi c therapies such as pacemaker or ICD implantation which otherwise may not have been implemented.

A Review of Electrocardiography in the High Altitude Environment

An ascent to altitude places considerable demands on the cardiovascular system. Changes in the rate, rhythm, and morphology of the electrocardiogram reflect the fall in the partial pressure of inspired oxygen (PiO2) and the adaptive responses that the human body makes. The effect of hypoxia on the autonomic nervous system results in changes to the heart rate during rest and exercise. Although this is raised during rest and submaximal exercise, maximal heart rate at altitude is reduced as a result of changes in parasympathetic activity. Hypoxic pulmonary vasoconstriction leads to a rise in pulmonary artery pressure and morphological changes on the electrocardiogram. Right axis deviation, right bundle branch block, and changes to P and T wave amplitudes are commonly found on ascent and resolve only after a return to low altitude. Although atrial and ventricular ectopic activity is also common, tachyarrhythmias are rare in healthy individuals. However, in those with significant cardiac disease, the hypoxic environment can be hazardous, exposing individuals to ischemia and the risk of sudden cardiac death.

Cariporide given during resuscitation promotes return of electrically stable and mechanically competent cardiac activity

Episodes of ventricular fibrillation (VF) and myocardial dysfunction commonly occur after cardiac resuscitation compromising the return of stable circulation. We investigated in a pig model of VF whether limiting Na +-induced cytosolic Ca 2+ overload using the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) inhibitor cariporide promotes resuscitation with stable circulation. Methods VF was electrically induced in 20 male pigs and left untreated for 6 min after which CPR was initiated and continued for 8 min before attempting defibrillation. Pigs were randomized to receive 3-mg/kg cariporide ( n = 10) or 0.9%-NaCl ( n = 10) before chest compression. Results Seven of 10 pigs in each group were successfully resuscitated and survived 2 h. Cariporide ameliorated post-resuscitation ventricular ectopic activity such that fewer singlets (5 ± 5 vs. 26 ± 21; p < 0.05) and fewer bigemini (1 ± 3 vs. 33 ± 25; p < 0.05) were observed during the initial 5 min post-resuscitation. Additionally, cariporide-treated pigs did not require additional post-resuscitation shocks for ventricular tachycardia or recurrent VF (0.0 ± 0.0 vs. 5.3 ± 7.8 shocks; p = 0.073). During the initial 60 min cariporide-treated pigs had higher, cardiac index (6.1 ± 0.7 vs. 4.4 ± 1.1 L/min/m 2; p < 0.01), left ventricular stroke work index (45 ± 9 vs. 36 ± 10 gm m/beat/m 2; p < 0.05), and numerically higher mean aortic pressure (104 ± 11 vs. 91 ± 12 mmHg; p = 0.054). Conclusion Cariporide administered at the start of chest compression may help restore electrically and mechanically stable circulation after resuscitation from cardiac arrest.

Arrhythmia Susceptibility in Mice after Therapy with β-Catenin-Transduced Hematopoietic Progenitor Cells after Myocardial Ischemia/Reperfusion

Background: Hematopoietic progenitor cells (HPCs) can improve cardiac function after myocardial infarction. However, occurrence of arrhythmias is a potential limitation of cell therapy. In this study, we investigated the cardiac electrophysiological properties of ex vivo expanded HPCs, generated by β-catenin gene transfer, after transcoronary delivery in a murine model of ischemia/reperfusion (I/R) injury. Methods and Results: To assess arrhythmia inducibility of ex vivo expanded HPCs, mice were subjected to I/R and assigned to sham operation (n = 8), I/R (n = 21) and HPC (n = 15) treatment. Six weeks later, mice were subjected to long-term electrocardiogram recording and in vivo transvenous electrophysiological study. After I/R, mice showed a significant prolongation of conduction and repolarization compared with sham-operated mice. There was a marked increase in ventricular ectopic activity in infarcted mice as compared with sham-operated mice. Cardiac electrophysiological parameters and ventricular ectopic activity were not altered in mice treated with HPCs in comparison with control I/R mice. Conclusion: Transcoronary delivery of genetically ex vivoexpanded HPCs did not alter the electrophysiological properties in mice after I/R. Therefore, ex vivo β-catenin-mediated HPC expansion may represent an attractive therapeutic option for cell transplantation treatment of myocardial infarction without electrophysiological side effects.

Utility of Exercise Testing in Children and Teenagers With Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is increasingly recognized as an important cause of exertional sudden death in otherwise healthy young individuals and athletes. Graded exercise testing is routinely included in the evaluation of patients with suspected ARVC, but its diagnostic utility has not been systematically assessed. Using a single-center retrospective design, the rhythm response to graded exercise testing was examined in 33 tests performed in 16 young (aged <18 years) patients with established diagnosis of ARVC. Ventricular premature complexes (VPCs) were classified as absent (graded 0), as being isolated or in couplets (graded 1), or as comprising nonsustained ventricular tachycardia (graded 2) during pretest rest, at peak exercise, and during postexercise recovery. VPCs were absent at rest in 21 of 33 studies, subsequently appearing at peak exercise in 4 studies and during recovery in 2 studies. Isolated VPCs and couplets were present at rest in 9 of 33 studies, with subsequent exercise provoking higher grade ectopic activity in 2 instances at peak exercise and in 1 case during recovery, while VPCs decreased or remained unchanged in all other cases. In all 3 instances in which ventricular tachycardia was observed during pretest rest, there was either suppression (3 at peak exercise, 2 during recovery) or no change (1 case during recovery) in VPC grade. In conclusion, the exercise response of ventricular ectopic activity is highly variable in young patients with ARVC. The diagnostic utility of graded exercise testing is thus questionable in young patients with suspected ARVC, and the absence or suppression of VPCs during exercise should not be considered reassuring in terms of its diagnostic exclusion.

Chamber‐specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea‐pig heart

Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K(+) for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV arrhythmogenicity in the guinea-pig heart.

VENTRICULAR TACHYCARDIA

Introduction: Frequent or complex patterns of ventricular ectopic activity,whether occurring during routine activity or induced by exercise, are often a marker for serious heart disease and aharbinger of sudden death. The detection of such arrhythmias is thus an important responsibility of the physician.Objective: To find the prevalence, associated characteristics and prognostic significance of exercise induced nonsustainedVT in a representative population. Material and Methods: Setting: Nishtar Hospital, Multan. Sample size:1000 patients. Duration: Two years. Study design: Descriptive, analytical study. Sampling Technique: Convenientprobability sampling done. Results: Ten subjects, 7 men and 3 women, with exercise induced VT were identified,representing 1.1% of those tested; only 1 was young than 65 years. All episodes of VT were asymptomatic and nonsustained.In 9 of 10 subjects, VT developed at or near peak exercise. The longest run of VT was 6 beats; multiple runsof VT were present in 4 subjects. Two subjects had exercise induced ST segment depression, but subsequent exercisethallium scintigraphic results were negative in each. Compared with a group of age and sex matched control subjects,those with asymptomatic, non-sustained VT displayed no difference in exercise duration, maximal heart rate, or theprevalence of coronary risk factors or exercise induced ischemia as measured by electrocardiography and thalliumscintigrahy. Over a mean follow period of 2 years, no subject has developed symptoms of heart disease or experiencedsyncope or sudden death. Thus, exercise induced VT in apparently healthy subjects occurs almost exclusively in theelderly, is limited to short, asymptomatic runs of 3 to 6 beats usually near peak exercise, and does not portendincreased cardiovascular morbidity or mortality rates over a 2 year period of observation. Conclusion: Exerciseinduced VT in apparently healthy subjects occurs almost exclusively in the elderly, is limited to short, asymptomaticruns of 3 to 6 beats usually near peak exercise, and does not show increased cardiovascular morbidity or mortalityrates over a 2 year period of observation.

Assessment, Significance and Mechanism of Ventricular Electrical Instability after Myocardial Infarction

The mechanism of reentrant tachycardia was established nearly a century ago, but the relationships between myocardial infarction and predisposition to sudden death were not unravelled until much later. In the latter half of the twentieth century many studies sought to ascertain what variables were predictive of death following myocardial infarction. Approximately one half of all deaths during the year following myocardial infarction are sudden and due to ventricular tachycardia (VT) or ventricular fibrillation (VF). We aimed to utilise non-invasive signal-averaging, along with programmed electrical stimulation of the heart, to determine whether one could predict spontaneous ventricular tachycardia and sudden death late after myocardial infarction. The sensitivity of ventricular electrical instablility (inducible ventricular tachycardia or fibrillation) as a predictor of instantaneous death or spontaneous VT was 86%, and the specificity was 83%. When other variables (delayed ventricular activation at signal-averaging, ejection fraction at gated heart pool scan, ventricular ectopic activity at ambulatory monitoring and exercise testing) were taken into account, inducible VT at electrophysiological study was the single best predictor of spontaneous VT and sudden cardiac death after myocardial infarction. The Westmead studies of Uther et al. in the decade or so from 1980 established programmed stimulation as the best predictor of sudden death after myocardial infarction. Subsequent studies by others have demonstrated a survival advantage of defibrillator implantation in patients with low ejection fraction (and inducible ventricular tachycardia) after myocardial infarction.

Creation of a Biological Pacemaker by Cell Fusion

As an alternative to electronic pacemakers, we explored the feasibility of converting ventricular myocytes into pacemakers by somatic cell fusion. The idea is to create chemically induced fusion between myocytes and syngeneic fibroblasts engineered to express HCN1 pacemaker channels (HCN1-fibroblasts). HCN1-fibroblasts were fused with freshly isolated guinea pig ventricular myocytes using polyethylene-glycol 1500. In vivo fused myocyte-HCN1-fibroblast cells exhibited spontaneously oscillating action potentials; the firing frequency increased with beta-adrenergic stimulation. The heterokaryons created ectopic ventricular pacemaker activity in vivo at the site of cell injection. Coculture of nonfused HCN1-fibroblasts and myocytes without polyethylene-glycol 1500 revealed no evidence of dye transfer, demonstrating that the I(f)-mediated pacemaker activity arises from heterokaryons rather than electrotonic coupling. This nonviral, non-stem cell approach enables autologous, adult somatic cell therapy to create biopacemakers.

Arrhythmias in Adult Patients With Congenital Heart Disease

By the time patients with congenital heart disease (CHD) reach adolescence and early adulthood, rhythm status has often become an active issue, if not the central issue, in their cardiac management. For some, arrhythmias are intrinsic to the structural malformation itself, as is the case with Wolff-Parkinson-White syndrome in the setting of Ebstein’s anomaly, or atrioventricular (AV) block in the setting of “congenitally corrected” transposition of the great arteries (L-TGA). For most other CHD patients, arrhythmias represent an acquired condition related to the unique myocardial substrate created by surgical scars in conjunction with cyanosis and abnormal pressure/volume loads of long duration. This review will attempt to address the major rhythm difficulties faced by adults with CHD, concentrating on electrophysiological features that distinguish CHD from more conventional forms of adult heart disease. A listing of specific arrhythmias and commonly associated congenital defects is provided in Table 1 to serve as an outline for the discussion. View this table: TABLE 1. Specific Arrhythmias and Associated Defects in Adults With Congenital Heart Disease As of 2001, there were estimated to be 800 000 adults with CHD living in the United States,1 a number that has grown steadily as more survivors of childhood surgery reach maturity. Of these, roughly 45% are considered to have mild forms of CHD (eg, atrial septal defect, valvar pulmonary stenosis), 40% are classified as having moderate disease (eg, tetralogy of Fallot, Ebstein’s anomaly), and 15% are considered to have complex disease (eg, single ventricle, transposition of the great arteries). Although arrhythmias can develop within any of the 3 subgroups, the incidence is highest for patients in the moderate and severe categories. Tetralogy of Fallot is an instructive example of moderate CHD with a large arrhythmia burden. As many as one third of patients with repaired tetralogy develop symptomatic atrial tachycardias by …

Increased Ventricular Ectopic Activity in Relation to C‐Reactive Protein, and NT‐Pro‐Brain Natriuretic Peptide in Subjects With No Apparent Heart Disease

Subjects with frequent ventricular premature complexes (VPC) and no apparent heart disease make a heterogenic group with regard to prognosis. Some biomarkers have recently proved useful in risk stratification in different heart diseases. We examined prognostic impact of NT-Pro-brain natriuretic peptide (NT-Pro BNP), and C-reactive protein (CRP) in relation to frequent VPC in subjects with no apparent heart disease. Six hundred seventy-eight healthy subjects between 55 and 75 years of age with no history of cardiovascular disease were included in the study. All were tested with fasting laboratory testing and 48-hour ambulatory ECG monitoring. Frequent VPC was defined as VPC > or =30/hour. In 56 subjects (8%) with frequent VPC the prognosis was much poorer compared to those without frequent VPC (Hazard ratio and 95% CI: 2.3;1.2-4.4, P = 0.01), after adjustment for conventional risk factors. In subjects with frequent VPC increased levels of CRP (above 2.5 microg/mL) was the only factor among the tested biomarkers, which was associated with a poor prognosis. Taking subjects without frequent VPC as reference, the hazard ratio and 95% CI for subjects with frequent VPC and increased CRP was 3.6;1.8-7.1, P = 0.0004, and for those with frequent VPC and normal CRP 0.8;0.2-3.5, P = 0.83, after correction for conventional risk factors. Among middle-aged and elderly subjects with no apparent heart disease and frequent VPCs, a CRP value > or =2.5 microg/mL is associated with a significantly higher risk of death and acute myocardial infarction. These subjects deserve primary prevention measures and further work up for structural heart disease.

Ventricular Arrhythmias and Risk of Death and Acute Myocardial Infarction in Apparently Healthy Subjects of Age ≥55 Years

Increased ventricular ectopic activity and even more complex arrhythmias are not uncommon in subjects without apparent heart disease. However, their prognostic significance has been controversial and not updated in recent years. The prevalence and prognostic significance of different ventricular arrhythmias were studied in a cohort of middle-aged and elderly subjects without apparent heart disease. Six hundred seventy-eight men and women aged 55 to 75 years without a history of heart disease or stroke were included. Baseline examinations included physical examinations, fasting laboratory testing, and 48-hour ambulatory electrocardiographic monitoring. All patients were followed for up to 5 years. Combined events were defined as all-cause mortality or acute myocardial infarction. A cardiovascular event was defined as cardiovascular death or acute myocardial infarction. In total, 84% had 0 to 10 ventricular premature complexes (VPCs)/hour, 8% had 11 to 30 VPCs/hour, and 8% had >30 VPCs/hour; 10.8% had >or=1 run of >or=3 VPCs. Frequent VPCs (>or=30/hour) was a significant predictor of combined (hazard ratio 2.47, 95% confidence interval 1.29 to 4.68, p = 0.006) and cardiovascular (hazard ratio 2.85, 95% confidence interval 1.16 to 7.0, p = 0.023) event rates, after adjustment for conventional risk factors. Runs of >or=4 VPCs/day or >or=2 doublets/day were also associated with a poor prognosis, but only in the presence of frequent VPCs. The detection of a single VPC on standard electrocardiography was a significant predictor of frequent VPCs and an independent predictor of events (hazard ratio 2.6, 95% confidence interval 1.02 to 6.66, p = 0.045). In conclusion, apparently healthy, middle-aged and elderly subjects with frequent VPCs (>or=30/hour) have a poor prognosis. According to current guidelines, strict risk-factor modification and primary prevention are justified in these high-risk subjects.

Relation Between Left Ventricular Geometry and Transmural Dispersion of Repolarization

Studies have shown an association between left ventricular (LV) geometry and complex ventricular ectopic activity. Increased transmural dispersion of repolarization (TDR), which correlates to the interval from the peak to the end of the T wave (Tpe) on the surface electrocardiogram, is linked to ventricular tachyarrhythmias. The relation between LV geometry and TDR is unknown. The mean Tpe interval, measured from leads V(1) to V(3) of the surface electrocardiogram, was assessed in 300 patients (50% men) who had normal LV systolic function and QRS duration and were categorized into 3 equal groups, which were matched by age and gender, according to echocardiographically determined LV geometry (normal structure, concentric remodeling, and LV hypertrophy). The Tpe interval was corrected for the QT interval using Tpe/QTc and was compared among the 3 groups. Compared with those who had normal LV structure, the Tpe interval was significantly prolonged in those who had LV hypertrophy and significantly shortened in those who had concentric remodeling (p = <0.0001 for the 2 comparisons). Correcting for the QT interval using Tpe/QTc yielded similar results. Thus, TDR was increased in patients who had LV hypertrophy but decreased in concentric remodeling compared with those who had normal cardiac structure. Although LV hypertrophy represents a maladaptive geometric process that results in an unfavorable electrical substrate, concentric remodeling may represent a structural adaptation that has a more favorable electrical milieu.

Continuous Positive Airway Pressure Treatment Improves the QT Rate Dependence Adaptation of Obstructive Sleep Apnea Patients

QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG. The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder. QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime. The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.