Search PubMed⌕ Search

Biomedical subjects

Wojciech Zareba

Publications and source records attributed to Wojciech Zareba.

At least 19 recordsLinked to original sources
PubMed2007

NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients.

We recently identified a subgroup of postinfarction patients at high-risk for recurrent coronary events defined by inflammation (high C-reactive protein) (CRP) and hypercholesterolemia. Within this subgroup, only elevated high-density lipoprotein cholesterol (HDL-C) from a set of metabolic, inflammatory and thrombogenic blood markers was associated with additional risk. To investigate the role of oxidative stress in this high-risk subgroup, we examined effects on risk of a polymorphism known to affect functional activity of NAD(P)H oxidase, an oxidative enzyme associated with generation of reactive oxygen species. The study population comprised non-diabetic patients of thrombogenic factors and recurrent coronary events (THROMBO) postinfarction study having complete blood marker and genotyping results (N=663) for C242T polymorphism of p22phox subunit (T allele associated with decreased activity). Cox multivariable regression, adjusted for significant clinical covariates, was used to assess within-subgroup risk associated with blood markers and polymorphism. In addition to elevated HDL-C (hazard ratio, 95% CI and p-value; 2.62, 1.05-6.55 and 0.039), significant independent risk was found for C242T (CC versus CT plus TT: 3.14, 1.34-7.35 and 0.0084). We conclude that oxidative stress plays a significant role in establishment of risk for recurrent coronary events in a high-risk subgroup of postinfarction patients defined by inflammation and hypercholesterolemia.

C-Reactive Protein↗
PubMed2007

Effects of on-road highway aerosol exposures on autonomic responses in aged, spontaneously hypertensive rats.

Epidemiological studies associate ambient particulate pollution with adverse health outcomes in elderly individuals with cardiopulmonary diseases. We hypothesized that freshly generated ultrafine particles (UFP) contribute to these effects, as they are present in high number concentrations on highways and vehicle passengers are exposed directly to them. Aged spontaneously hypertensive rats (9-12 mo) with implanted radiotelemetry devices were exposed to highway aerosol or filtered, gas-denuded (clean) air using an on-road exposure system to examine effects on heart rate (HR) and heart-rate variability (HRV). On the day of exposure, rats were pretreated with low-dose inhaled or injected lipopolysaccharide (LPS) to simulate respiratory tract or systemic inflammation, respectively. Exposures (6 h) in compartmentalized whole-body chambers were performed in an air conditioned compartment of a mobile laboratory on I-90 between Rochester and Buffalo, NY. HRV parameters were calculated from telemetric blood pressure signals and analyzed for the baseline period and for the first 32 h postexposure. The aerosol size (count median diameter = 15-20 nm; geometric standard deviation = 1.4-4.3) and number concentration (1.95-5.62 x 105/cm3) indicated the predominance of UFP. Intraperitoneal LPS significantly affected all of the parameters in a time-dependent manner; response patterns after inhaled or injected LPS pretreatment were similar, but more prolonged and greater in LPS-injected rats. A significant effect of highway aerosol was found, irrespective of pretreatment, which resulted in decreased HR in comparison to clean air-exposed rats. This effect was more persistent ( approximately 14 h) in those rats that received ip LPS as compared to saline. The highway aerosol also significantly affected short-term alterations in autonomic control of HR, as evidenced by elevations in normalized high frequency power and decreased vagosympathetic balance. These findings show that environmental exposure concentrations of mixed traffic-related UFP/gas-phase emissions can affect the autonomic nervous system.

Administration, Inhalation↗
PubMed2006

Relationship between electrocardiographic and biochemical variables in coronary artery disease.

BACKGROUND: ECG (electrocardiogram) markers reflecting abnormal heart rate variability and abnormal repolarization as well as several biochemical markers reflecting inflammation, endothelial dysfunction, and procoagulation states were reported to show an association with increased cardiovascular mortality. ECG and biochemical markers could operate independently or they could interrelate in pathogenetic pathways of coronary disease. In this study, we aimed to explore the relationship between ECG and biochemical markers in a longitudinal study of coronary patients. METHODS: A total of 499 observations from 52 patients with up to 12 repeated measurements were collected providing data on series of ECG (heart rate variability and repolarization) parameters and biochemical parameters. Generalized estimating equation models adjusting for repeated measurements were used for the analyses. RESULTS: There was a significant association between ECG parameters reflecting abnormal repolarization (prolonged QT interval, lower T wave amplitude) and elevated levels of C-reactive protein and fibrinogen. Abnormal heart rate variability, increased sympathetic tone (low-frequency power) was associated with increased concentrations of soluble E-selectin, a marker of endothelial cell activation. There was no association between ECG markers and parameters reflecting increased procoagulation states. CONCLUSION: These results indicate that there is an association between ECG parameters and blood markers reflecting endothelial function and inflammation in coronary artery disease patients. The pathophysiologic mechanisms of these associations remain to be elucidated.

Aged↗
PubMed2006

Repolarization duration in patients with conduction disturbances after myocardial infarction.

This study compared different measurements of repolarization duration in patients after infarction with and without conduction disturbances and evaluated the prognostic significance of repolarization parameters for predicting mortality in patients with conduction abnormalities. The study population consisted of 3,282 patients after recent myocardial infarction. Repolarization duration was measured using Bazett QTc and JTc (QTc minus QRS) and Rautaharju QT and JT(RR) formulas. All-cause mortality was the end point of the predictive models. In 259 patients with conduction disturbances, 76 (2.3%) had indeterminate ventricular conduction disturbances, 126 (3.8%) had right bundle branch block, and 47 (1.4%) had left bundle branch block. Patients with left bundle branch block demonstrated excessive prolongation of the QTc interval, which was not observed when using the JT(RR) interval. There were no significant differences in repolarization duration by gender in patients with conduction abnormalities. Repolarization parameters were uniformly dichotomized at the 75th percentile (QTc interval >490 ms, JTc interval >360 ms, QT(RR,QRS) interval >433 ms, JT(RR) interval >359 ms) to determine their prognostic significance for predicting mortality. After adjustment for significant clinical predictors of mortality, the hazard ratios were 1.65 for QTc interval (p = 0.062), 1.46 for JTc interval (p = 0.168), 1.71 for QT(RR,QRS) interval (p = 0.043), and 1.70 for JT(RR) interval (p = 0.044)(.) In conclusion, patients with left bundle branch block, right bundle branch block, or indeterminate ventricular conduction disturbances show longer repolarization duration than patients without these conduction disturbances, and QT(RR,QRS) and JT(RR) intervals reflect better than QTc repolarization duration in patients with conduction disturbances. QT(RR) and JT(RR) intervals significantly and independently predict mortality in patients after infarction with conduction disturbances.

Electrocardiography↗
PubMed2006

Relation of heart rate turbulence to severity of heart failure.

The aim of this study was to evaluate the association between heart rate turbulence (HRT) parameters and clinical, biochemical, echocardiographic, and electrocardiographic measures of heart failure (HF) in a large, prospectively enrolled population of patients with HF to determine whether HRT could be considered a marker of HF advancement and progression, giving insight into hemodynamic changes as well as changes of the autonomic nervous system. In 487 patients with HF (mean age 63 years), the following tests were performed: 12-lead surface electrocardiography, echocardiography, chest x-rays, N-terminal-pro-brain natriuretic peptide levels, and 24-hour Holter monitoring for HRT and heart rate variability analyses. Most patients were in New York Heart Association class II (82%) and had a mean left ventricular (LV) ejection fraction of 37 +/- 14%. Both HRT parameters, but especially turbulence slope, were significantly correlated with clinical indexes of HF (the third heart sound, peripheral edemas, jugular distension, and pulmonary congestion). Patients in New York Heart Association class III had significantly lower turbulence slopes and greater turbulence onset values than those in class II. Significant correlations were found between HRT parameters and the LV ejection fraction as well as with LV diameters. HRT parameters were significantly correlated with N-terminal-pro-brain natriuretic peptide levels (r = -0.47, p <0.001 for turbulence slope). Multivariate analyses showed that abnormal HRT parameters were independent predictors of HF severity measured by New York Heart Association class III and a LV ejection fraction <40%. In conclusion, the findings indicate that in patients with HF, HRT reflects well the severity of HF and associated LV dysfunction, which were verified in this study by a series of established clinical, echocardiographic, and biochemical parameters.

Adolescent↗
PubMed2006

Effectiveness of the implantable cardioverter defibrillator in blacks versus whites (from MADIT-II).

The aim of this study was to examine the effectiveness of implantable cardioverter-defibrillator (ICD) therapy in whites and blacks who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II). The study population involved 1,232 subjects, with 1,073 white patients (87%) and 102 black patients (8%). Univariate analyses revealed a significant reduction in mortality in white patients treated with ICD therapy (p <0.02), but not in black patients (p = 0.96). White patients had a significant reduction of sudden cardiac death (p <0.01), but no benefit was evident in black patients (p = 0.62). Adjusting for relevant covariates, the ICD therapy/conventional therapy hazard ratios for total mortality were favorable in whites (0.75, 95% confidence interval [CI] 0.55 to 1.02), but not in blacks (1.25, 95% CI 0.42 to 3.60); the hazard ratios for sudden cardiac death were significantly (p = 0.04) lower in whites (0.29, 95% CI 0.17 to 0.49) than in blacks (1.71, 95% CI 0.33 to 8.84). Interaction analyses revealed a pattern of progressive improvement in ICD efficacy in whites as the end point became more specific for arrhythmic death, with exactly the reverse for blacks. In conclusion, ICD therapy in MADIT-II was associated with a reduction in total mortality, cardiac death, and sudden cardiac death in whites but not in blacks.

Aged↗
PubMed2006

Heavy ion radiation up-regulates Cx43 and ameliorates arrhythmogenic substrates in hearts after myocardial infarction.

OBJECTIVE: Radiation has been shown to enhance intercellular communication in the skin and lungs through an increase of connexin43 (Cx43) expression. If analogous Cx43 up-regulation is induced in the diseased heart, it would provide a new perspective in radiation therapy for arrhythmias. The aim of the present study is to test this hypothesis. METHODS: Non-transmural myocardial infarction (MI) was created in 24 rabbits by microsphere injection into the coronary arteries. Twenty-four rabbits without MI were used as controls. Targeted external heavy ion beam irradiation (THIR; 15 Gy) was applied 2 weeks after MI with an accelerator (HIMAC, Chiba, Japan). RESULTS: The THIR was associated with an increase of Cx43 mRNA and protein levels in the left ventricle in control as well as in MI rabbits. THIR also increased lateralization of Cx43, which was no longer colocalized with cadherins. In MI hearts, immunoreactive Cx43 signals were reduced in the peri-infarct zone, and the reduction was reversed by THIR. In-vivo epicardial potential mapping on the free wall (64 unipolar electrodes to cover 7 x 7 mm) in MI hearts revealed reduced conduction velocity, whereas dispersion of the activation-recovery interval (ARI) was increased compared with controls, and these changes were reversed by THIR. The vulnerability for ventricular tachyarrhythmias (VT/VF), which was estimated by programmed stimulation, was increased in MI hearts, and this increased vulnerability to arrhythmias was reversed by THIR. CONCLUSIONS: THIR increases Cx43 expression, improves the conductivity, decreases the spatial heterogeneity of repolarization, and reduces the vulnerability of rabbit hearts to ventricular arrhythmias after MI. THIR could have an antiarrhythmic potential through an improvement of electrical coupling.

Animals↗
PubMed2006

Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome.

CONTEXT: Analysis of predictors of cardiac events in hereditary long-QT syndrome (LQTS) has primarily considered syncope as the predominant end point. Risk factors specific for aborted cardiac arrest and sudden cardiac death have not been investigated. OBJECTIVE: To identify risk factors associated with aborted cardiac arrest and sudden cardiac death during adolescence in patients with clinically suspected LQTS. DESIGN, SETTING, AND PARTICIPANTS: The study involved 2772 participants from the International Long QT Syndrome Registry who were alive at age 10 years and were followed up during adolescence until age 20 years. The registry enrollment began in 1979 at 5 cardiology centers in the United States and Europe. MAIN OUTCOME MEASURES: Aborted cardiac arrest or LQTS-related sudden cardiac death; follow-up ended on February 15, 2005. RESULTS: There were 81 patients who experienced aborted cardiac arrest and 45 who had sudden cardiac death; 9 of the 81 patients who had an aborted cardiac arrest event experienced subsequent sudden cardiac death. Significant independent predictors of aborted cardiac arrest or sudden cardiac death during adolescence included recent syncope, QTc interval, and sex. Compared with those with no syncopal events in the last 10 years, patients with 1 or 2 or more episodes of syncope 2 to 10 years ago (but none in the last 2 years) had an adjusted hazard ratio (HR) of 2.7; (95% confidence interval [CI], 1.3-5.7; P<.01) and an adjusted HR of 5.8 (95% CI, 3.6-9.4; P<.001), respectively, for life-threatening events; those with 1 syncopal episodes in the last 2 years had an adjusted HR of 11.7 (95% CI, 7.0-19.5; P<.001) and those with 2 or more syncopal episodes in the last 2 years had an adjusted HR of 18.1 (95% CI, 10.4-31.2; P<.001). Irrespective of events occurring more than 2 years ago, QTc of 530 ms or longer was associated with increased risk (adjusted HR, 2.3; 95% CI, 1.6-3.3; P<.001) compared with those having a shorter QTc. Males between the ages of 10 and 12 years had higher risk than females (HR, 4.0; 95% CI, 1.8-9.2; P = .001), but there was no significant risk difference between males and females between the ages of 13 and 20 years. Among individuals with syncope in the past 2 years, beta-blocker therapy was associated with a 64% reduced risk (HR, 0.36; 95% CI, 0.18-0.72; P<.01). CONCLUSIONS: In LQTS, the timing and frequency of syncope, QTc prolongation, and sex were predictive of risk for aborted cardiac arrest and sudden cardiac death during adolescence. Among patients with recent syncope, beta-blocker treatment was associated with reduced risk.

Adolescent↗
PubMed2006

Genotype-specific ECG patterns in long QT syndrome.

Different genetic types of the long QT syndrome (LQTS) are associated with distinct ECG manifestations, which relate to the type and magnitude of ion channel dysfunction. The QTc duration does not differentiate LQTS types, and therefore other static and dynamic ECG parameters reflecting changes in T wave morphology are used to describe phenotypic expression of different LQTS genotypes. LQT1 carriers usually have broad-based T waves, LQT2 carriers show low-amplitude T waves with high incidence of notches, and LQT3 carriers frequently have extended ST segment with relatively narrow peaked T wave. This phenotypic differentiation could be enhanced by quantifying additional ECG parameters reflecting components of repolarization morphology as well as to evaluate dynamics of repolarization parameters. Heart rate dependency and dynamic behavior of repolarization parameters differ by genotype and further show that genotype indicates ECG phenotype in patients with LQTS. However, there is a substantial variation in repolarization abnormalities observed in the same subject and in the members of the same family indicating large differences in gene penetrance. In conclusion, comprehensive analyses of static and dynamic features of repolarization provide unique opportunity to understand electrophysiology of cardiac repolarization.

Electrocardiography↗
PubMed2006

Polymorphism in the angiotensinogen gene, hypertension, and ethnic differences in the risk of recurrent coronary events.

The M235T mutation of the human angiotensinogen gene has been shown to be associated with elevated circulating angiotensinogen concentrations and essential hypertension. The frequencies of the 235T allele are significantly different in black and white subjects. We analyzed the independent contribution of the angiotensinogen M235T mutation to the development of recurrent coronary events (coronary-related death, nonfatal myocardial infarction, or unstable angina) in a cohort of 916 black (n=145) and white (n=771) postmyocardial infarction patients who were prospectively studied during an average follow-up of 28 months. The frequency of the 235T allele was significantly higher among black (82%) than among white (44%) patients (P<0.001). There was no evidence for Hardy-Weinberg disequilibrium. During follow-up, 41 cardiac events (28%) occurred in blacks and 197 (26%) in whites (P=0.49). Multivariate Cox proportional hazards regression analysis demonstrated that 235T homozygosity was independently associated with increased risk of coronary events among black (hazard ratio: 2.37; P=0.04) but not white (hazard ratio: 0.93; P=0.68) patients, with a significant ethnic-related interaction effect (P for the difference=0.04). Among hypertensive black patients, the TT genotype was associated with a 3.3-fold (P=0.02) increase in the risk of coronary events. Our findings suggest that homozygosity for the 235T mutation in the angiotensinogen gene is an independent risk factor for coronary events in black postmyocardial infarction patients. The presence of hypertension significantly augments the risk associated with this genetic mutation.

Aged↗
PubMed2006

Clinical course and risk stratification of patients affected with the Jervell and Lange-Nielsen syndrome.

INTRODUCTION: Data regarding risk factors and clinical course of patients affected with Jervell and Lange-Nielsen syndrome (JLNS), an autosomal recessive form of the congenital long-QT syndrome (LQTS), are limited to several reported cases and a retrospective analysis. METHODS AND RESULTS: We prospectively followed-up 44 JLNS patients from the U.S. portion of the International LQTS Registry and compared their clinical course with 2,174 patients with the phenotypically determined dominant form of LQTS (Romano-Ward syndrome [RWS]) and a subgroup of 285 patients with type 1 LQTS (LQT1). Mean (+/-SD) corrected QT interval (QTc) in the JLNS, RWS, and LQT1 groups were 548 +/- 73, 500 +/- 48, and 502 +/- 46 msec, respectively (P < 0.001). The cumulative rates of cardiac events from birth through age 40 among JLNS and RWS patients were 93% (mean [+/-SD] age: 5.0 +/- 7.0 years) and 54% (mean [+/-SD] age: 14.2 +/- 9.3 years), respectively (P < 0.001). The JLNS:RWS and JLNS:LQT1 adjusted hazard ratios (HR) for cardiac events were highest among patients with a baseline QTc > or = 550 msec (HR = 15.83 [P < 0.001] and 13.80 [P < 0.001], respectively). Among JLNS patients treated with beta-blockers, the cumulative probability of LQTS-related death was 35%; defibrillator therapy was associated with a 0% mortality rate during a mean (+/-SD) follow-up period of 4.9 +/- 3.4 years. CONCLUSIONS: Patients with JLNS experience a high rate of cardiac and fatal events from early childhood despite medical therapy. Defibrillator therapy appears to improve outcome in this high-risk population, although longer follow-up is needed to establish its long-term efficacy.

Adolescent↗
PubMed2006

Repolarization morphology in adult LQT2 carriers with borderline prolonged QTc interval.

BACKGROUND: At least 50% of LQT2 carriers have borderline QTc (0.42-0.47 s), and they present a diagnostic difficulty to clinicians evaluating patients suspected of having long QT syndrome (LQTS). OBJECTIVES: Because QTc in this borderline range is nondiagnostic, the purpose of this study was to investigate whether analysis of phenotypic features of T-wave morphology could help identify LQT2 carriers with normal or near-normal QTc-interval duration. METHODS: Standard 12-lead ECGs recorded without beta-blockers from LQT2 carriers (n = 90, 33 +/- 14 years, 61% female) and noncarriers (n = 69, 38 +/- 17 years, 58% female) were digitized. The following parameters were automatically measured: RR interval, QT/QTc, QT apex, T-wave amplitude, ascending (alpha(L)) and descending slopes (alpha(R)) of the T wave, and T-wave symmetry. We used a linear logistic regression model to identify the most relevant parameters for separating LQT2 carriers from noncarriers, within the overall population and among patients without overt QTc prolongation (390 </= QTc </= 470). RESULTS: Logistic regression selected three parameters: QT, RR interval, and alpha(L) in all models. In the overall population, the model provided 92.7% sensitivity and 90.0% specificity. In the group of patients without beta-blockers and near-normal QTc interval, 92.0% sensitivity (n = 46) and 81.4% specificity (n = 49) were achieved by the model including alpha(L.) CONCLUSION: Abnormal T-wave morphology is a phenotypic expression of LQT2, and its quantification could be used to identify patients with suspected LQTS who do not have overt QTc prolongation (QTc >470).

Action Potentials↗
PubMed2006

Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification.

OBJECTIVES: We evaluated the incremental prognostic information provided by multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in patients with the inherited long QT syndrome (LQTS). BACKGROUND: A baseline QTc of > or =500 ms has been shown to be associated with increased risk of cardiac events among LQTS patients. However, the value of QTc measurements on follow-up ECGs in risk assessment has not been determined. METHODS: The risk of a first LQTS-related cardiac event during adolescence was assessed in 375 patients enrolled in the International LQTS Registry for whom serial follow-up ECGs were recorded before age 10. RESULTS: The mean +/- SD difference between the minimum and maximum QTc values on serial ECGs recorded in study patients was 47 +/- 40 ms. The maximum QTc interval recorded before age 10 was the strongest predictor of cardiac events during adolescence (adjusted hazard ratio [HR] = 2.74; p < 0.001). Other follow-up QTc measures, including the baseline, the mean, and the most recent QTc interval recorded before age 10, were less significant risk factors. After adjusting for the maximum QTc value during follow-up, no significant association remained between the baseline QTc value and the risk of subsequent cardiac events (HR = 1.04; p = 0.91). CONCLUSIONS: In LQTS patients, there is a considerable variability in QTc measures in serial follow-up ECGs. The maximum QTc interval provides incremental prognostic information beyond the baseline measurement. We suggest that risk stratification in LQTS patients should include follow-up ECG data.

Adolescent↗
PubMed2006

Relations among renal function, risk of sudden cardiac death, and benefit of the implanted cardiac defibrillator in patients with ischemic left ventricular dysfunction.

Implanted cardioverter defibrillator therapy has been shown to be associated with a significant reduction in the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. However, data on the relation between renal function and SCD in this population are limited, and the effect of renal dysfunction on the implanted cardioverter defibrillator benefit has not been determined. We performed a retrospective analysis of the outcome associated with renal dysfunction, as determined by the estimated glomerular filtration rate (eGFR), in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-II. Multivariate analysis in conventionally treated patients showed that for each 10-U reduction in eGFR, the risk of all-cause mortality and SCD increased by 16% (p = 0.005) and 17% (p = 0.03), respectively. Defibrillator therapy was associated with a survival benefit in each eGFR category of > or = 35 ml/min/1.73 m2 (overall risk reduction for all-cause mortality 32%, p = 0.01 and for SCD 66%, p < 0.001). However, no implanted cardioverter defibrillator benefit was shown among patients with an eGFR < 35 ml/min/1.73 m2 (all-cause mortality hazard ratio 1.09, p = 0.84; SCD hazard ratio 0.95, p = 0.95). In conclusion, in patients with high-risk cardiac disease enrolled in the Multicenter Automatic Defibrillator Implantation Trial-II, a significant increase was found in the risk of SCD with declining renal function. Defibrillator therapy was associated with a significant survival benefit among the study patients with mild to moderate or no renal disease, but no benefit was shown among patients with more advanced renal dysfunction.

Aged↗
PubMed2006

Causes and consequences of heart failure after prophylactic implantation of a defibrillator in the multicenter automatic defibrillator implantation trial II.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy may be associated with an increased risk for heart failure (HF). The present study evaluated the frequency, causes, and consequences of HF after ICD implantation. METHODS AND RESULTS: We performed a retrospective analysis of the clinical factors and outcomes associated with postenrollment HF events in 1218 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II. The adjusted hazard ratios (HRs) of ICD:conventional therapy for first and recurrent HF events were 1.39 (P=0.02) and 1.58 (P<0.001), respectively. The risk was increased among patients who received single-chamber or dual-chamber ICDs. Development of HF was associated with an increased mortality risk (HR, 3.80; P<0.001). Among patients who received a single-chamber ICD, there was a similar survival benefit before and after the development of HF (HR, 0.59 and 0.61, respectively; P=0.92 for difference), whereas among patients with dual-chamber devices, there was a significant reduction in survival benefit after HF (HR, 0.26 and 0.83, respectively; P=0.01 for difference). Within the defibrillator arm of the trial, patients who received life-prolonging therapy from the ICD had an increased risk for first and recurrent HF events (HR, 1.90; P=0.01 and 1.74; P<0.001, respectively). CONCLUSIONS: Patients with chronic ischemic heart disease who are treated with either single-chamber or dual-chamber ICDs have improved survival but an increased risk of HF. The present data suggest that ICD therapy transforms sudden death risk to a subsequent HF risk. These findings should direct more attention to the prevention of HF in patients who receive an ICD.

Adrenergic beta-Antagonists↗
PubMed2006

Cigarette smoking and the risk of supraventricular and ventricular tachyarrhythmias in high-risk cardiac patients with implantable cardioverter defibrillators.

INTRODUCTION: Nicotine elevates serum catecholamine concentration and is therefore potentially arrhythmogenic. However, the effect of cigarette smoking on arrhythmic risk in coronary heart disease patients is not well established. METHODS AND RESULTS: The risk of appropriate and inappropriate defibrillator therapy by smoking status was analyzed in 717 patients who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II. Compared with patients who had quit smoking before study entry (past smokers) and patients who had never smoked (never smokers), patients who continued smoking (current smokers) were significantly younger and generally had more favorable baseline clinical characteristics. Despite this, the adjusted hazard ratio (HR) for appropriate ICD therapy for fast ventricular tachycardia (at heart rates >or=180 b.p.m) or ventricular fibrillation was highest among current smokers (HR = 2.11 [95% CI 1.11-3.99]) and intermediate among past smokers (HR = 1.57 [95% CI 0.95-2.58]), as compared with never smokers (P for trend = 0.02). Current smokers also exhibited a higher risk of inappropriate ICD shocks (HR = 2.93 [95% CI 1.30-6.63]) than past (HR = 1.91 [95% CI 0.97-3.77]) and never smokers (P for trend = 0.008). CONCLUSIONS: In patients with ischemic left ventricular dysfunction, continued cigarette smoking is associated with a significant increase in the risk of life-threatening ventricular tachyarrhythmias and inappropriate ICD shocks induced by rapid supraventricular arrhythmias. Our findings stress the importance of complete smoking cessation in this high-risk population.

Aged↗
PubMed2006

High lipoprotein-associated phospholipase A2 is a risk factor for recurrent coronary events in postinfarction patients.

BACKGROUND: Recent studies demonstrate that lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor for cardiovascular disease presumably deriving from generation of proinflammatory and proatherogenic species through its hydrolytic activity on lipoprotein-associated phospholipids. The goal of this study was to assess the relationship of Lp-PLA2 with a set of thrombogenic, lipid, inflammatory, and metabolic blood markers and to determine whether plasma Lp-PLA2 is a risk factor for recurrent coronary events in postinfarction patients. METHODS: Factor analysis on the set of blood markers and Lp-PLA2 was performed for 766 patients of the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction study. Recurrent coronary event risk was assessed as a function of blood marker concentrations and Lp-PLA2 by Cox proportional hazards multivariable regression adjusted for significant clinical covariates. RESULTS: Factor analysis revealed that Lp-PLA2 was associated with one factor dominated by cholesterol and apolipoprotein B and another factor dominated by HDL-cholesterol and triglycerides, with little association with an inflammatory factor dominated by C-reactive protein. Multivariable analysis demonstrated as significant and independent predictors of risk of secondary coronary events only apolipoprotein B in a model without Lp-PLA2 (hazard ratio, 1.66; 95% confidence interval, 1.14-2.40) and only Lp-PLA2 in a model with Lp-PLA2 included [1.90 (1.31-2.75)]. CONCLUSIONS: Lp-PLA2 is a significant and independent predictor of risk for recurrent coronary events in postinfarction patients, and Lp-PLA2 is related to both hypercholesterolemia and high triglyceride-low HDL dyslipidemia in this study population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗