Biomedical subjects

Sumeet S Chugh

Publications and source records attributed to Sumeet S Chugh.

14 recordsLinked to original sources

PubMed2006

Native QRS duration predicts the occurrence of arrhythmic events in ICD recipients.

AIMS: Identification of implantable cardioverter/defibrillator (ICD) recipients at higher risk of future therapies may assist in pre-empting future shocks. Native QRS duration is an established predictor of overall mortality, but the role of this parameter as a clinical predictor of arrhythmic events warrants further investigation. METHODS AND RESULTS: In an analysis of a single-centre, 13-year ICD implantation experience (1990-2002), multiple clinical parameters including QRS duration were analysed using a multiple logistic regression model. Of 562 patients followed for at least 1 year, 98 (17%) did not receive ICD therapies (event-free, group A). Comparisons were made with a randomly selected sample of 123 patients who received ICD therapies (arrhythmic events, group B). There were no significant differences in age, gender, frequency of coronary artery disease, and degree of left ventricular dysfunction. However, QRS duration was a significant determinant of arrhythmic events (> or =100 vs. <100 ms: adjusted OR 2.75, 95% CI 1.37-5.51; > or =120 vs. <120 ms: adjusted OR 1.77, 95% CI 0.97-3.23). QRS duration was also a predictor of overall mortality in the logistic regression models (> or =100 ms: adjusted OR 3.72, 95% CI 1.17-11.9; > or =120 ms: adjusted OR 3.09, 95% CI 1.39-6.85). CONCLUSION: In this ICD population, consisting largely of secondary prevention ICD recipients, longer QRS duration predicted higher likelihood of arrhythmic events. Extent of QRS prolongation could guide the decision to initiate prophylactic anti-arrhythmic therapy in ICD patients.

Arrhythmias, Cardiac↗

PubMed2006

Incidence of sudden cardiac arrest is higher in areas of low socioeconomic status: a prospective two year study in a large United States community.

BACKGROUND: A potential effect of socioeconomic status on occurrence of sudden cardiac arrest in the community is likely, but has not been evaluated fully. METHODS: All cases of sudden cardiac arrest in Multnomah County Oregon (population 660,486; February 2002-January 2004) were identified prospectively and categorized by census tract based on the address of residence and specific geographic location of occurrence of cardiac arrest. Each census tract was assigned to quartiles of median income, poverty level, median home value, and educational attainment. RESULTS: Of 714 cases (annual incidence 54 per 100,000), 697 (98%) had residential addresses that matched a county census tract successfully. For each socioeconomic status measure, the incidence of cardiac arrest was 30-80% higher in the lowest compared to the highest socioeconomic status census tracts. Annual incidence in census tracts in the lowest compared to the highest quartiles of median home value was 60.5 versus 35.1 per 100,000 (RR 1.7, 95% CI 1.4-2.2). This gradient was exaggerated significantly for age<65 years (34.5 versus 15.1 per 100,000, RR 2.3, 95% CI 1.6-3.3). Identical trends were observed for sudden cardiac arrest based on location, with 60% of all cases and 66% of cases age<65 years occurring in the two quartiles with lowest socioeconomic status. CONCLUSIONS: Low neighborhood socioeconomic status was associated with a significantly higher incidence of sudden cardiac arrest based on address of residence as well as location of cardiac arrest. For effective deployment of strategies for community-based prevention such as the automated external defibrillator, neighborhood socioeconomic status is likely to be an important consideration.

Adult↗

PubMed2006

Allelic variants of SCN5A and risk of sudden cardiac arrest in patients with coronary artery disease.

BACKGROUND: Most sudden cardiac arrests occur in patients who have associated significant coronary artery disease (CAD), but current methods of risk stratification are inadequate. OBJECTIVES: The purpose of this study was to evaluate whether allelic variation of SCN5A could determine risk of sudden cardiac arrest among patients with CAD. METHODS: This case-control study was conducted as part of the ongoing Oregon Sudden Unexpected Death Study (Ore-SUDS). Cases of sudden cardiac arrest with associated CAD were identified among residents of Multnomah County, Oregon (population 660,486). Geographically matched control subjects had significant CAD but no history of cardiac arrest, ventricular arrhythmia, or syncope. DNA was extracted from blood samples, and all 28 exons of SCN5A were screened for allelic variants using denaturing high-performance liquid chromatography. All identified variants were confirmed by direct sequencing. RESULTS: Sixty-seven cases (mean age 65 +/- 13 years, 18% female) and 91 controls (mean age 66 +/- 12 years, 30% female) were compared. Race was known in 94% of all patients; 92% of case subjects and 89% of control subjects were Caucasian. No patient had clinically manifest familial long QT syndrome. Nonsynonymous nucleotide changes were found in 4% of cases and 1% of controls (P = .31), with one novel mutation (G1291A) identified in one case subject. Synonymous nucleotide changes were found in 27% of cases and 21% of controls (P = .45). CONCLUSION: The overall prevalence of amino acid-altering polymorphisms of the SCN5A gene was relatively low in both groups. Allelic variants of SCN5A did not contribute to risk of sudden cardiac arrest in this primarily Caucasian population with significant CAD.

Aged↗

PubMed2006

Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction: two-year findings from the Oregon Sudden Unexpected Death Study.

OBJECTIVES: We sought to evaluate the contribution of left ventricular (LV) dysfunction toward occurrence of sudden cardiac death (SCD) in the general population, and to identify distinguishing characteristics of SCD in the absence of LV dysfunction. BACKGROUND: Patients who manifest warning symptoms and signs are more likely to undergo evaluation before SCD. Although prevalence of LV dysfunction in this subgroup may overestimate the prevalence in overall SCD, this is the only means of assessment in the general population. METHODS: All cases of SCD in Multnomah County, Oregon (population 660,486; 2002 to 2004) were prospectively ascertained in the ongoing Oregon Sudden Unexpected Death Study. We retrospectively assessed LV ejection fraction (LVEF) among subjects who underwent evaluation of LV function before SCD (normal: > or =55%; mildly to moderately reduced: 36% to 54%; and severely reduced: < or =35%). Of a total of 714 SCD cases (annual incidence 54 per 100,000), LV function was assessed in 121 (17%). RESULTS: The LVEF was severely reduced in 36 patients (30%), mildly to moderately reduced in 27 (22%), and normal in 58 (48%). Patients with normal LVEF were distinguishable by younger age (66 +/- 15 years vs. 74 +/- 10 years; p = 0.001), higher proportion of females (47% vs. 27%; p = 0.025), higher prevalence of seizure disorder (14% vs. 0%; p = 0.002), and lower prevalence of established coronary artery disease (50% vs. 81%; p < 0.001). CONCLUSIONS: In this community-wide study, only one-third of the evaluated SCD cases had severe LV dysfunction meeting current criteria for prophylactic cardioverter-defibrillator implantation. The SCD cases with normal LV function had several distinguishing clinical characteristics. These findings support the aggressive development of alternative screening methods to enhance identification of patients at risk.

Aged↗

PubMed2005

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.

CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.

Aged↗

PubMed2005

Arrhythmias after orthotopic heart transplantation.

BACKGROUND: Arrhythmias frequently occur after orthotopic heart transplantation (OHT). METHODS AND RESULTS: The most common are ventricular premature complexes, atrial premature complexes, sinus or junctional bradycardia, atrial fibrillation, and atrial flutter, all of which have varying clinical significance depending on associated or causative conditions. Unique etiologic factors such as allograft rejection, transplant coronary artery disease, and altered anatomy and autonomic nervous system changes require that arrhythmias be treated differently after OHT compared with the general population. CONCLUSION: The potentially severe ramifications of allograft rejection and coronary artery disease make treatment of these disorders in the setting of arrhythmias as important as treating the arrhythmias themselves. At the same time, autonomic denervation and altered anatomy after transplantation complicate drug and device therapies.

Arrhythmias, Cardiac↗

PubMed2004

Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community.

OBJECTIVES: We sought to determine the annual incidence of sudden cardiac death (SCD) in the general population using a prospective approach. To assess the validity of retrospective surveillance, a simultaneous comparison was made with a death certificate-based method of determining SCD incidence. BACKGROUND: Accurate surveillance and characterization of SCD in the general population is likely to significantly facilitate current and future community-based preventive and therapeutic interventions. METHODS: We performed a prospective evaluation of SCD among all residents of Multnomah County, Oregon (population 660,486) using multiple sources of surveillance. A comprehensive analysis of circumstances of death, medical records, and available autopsy data was performed. Comparisons were made with a retrospective, death certificate-based determination of SCD incidence using International Classification of Diseases-Version 10 codes and location of death. RESULTS: Between February 1, 2002, and January 31, 2003, 353 residents suffered SCD (incidence 53 of 100,000; median age 69 years, 57% male) accounting for 5.6% of overall mortality. Of these, 75 cases (21%) were identified using sources other than first responders. Resuscitation was attempted in 237 cases (67%) and successful (survival to hospital discharge) in 28 (8%). The retrospective death certificate-based review yielded 1,007 cases (incidence 153 of 100,000; median age 81 years, 51% male), and the positive predictive value of this methodology was 19%. CONCLUSIONS: Sudden cardiac death accounts for 5.6% of annual mortality, and prospective evaluation in the general population appears to be feasible. The use of multiple sources of ascertainment and information significantly enhances phenotyping of SCD cases. Retrospective death certificate-based surveillance results in significant overestimation of SCD incidence.

Adolescent↗

PubMed2004

Postmortem molecular screening in unexplained sudden death.

OBJECTIVES: We examined the prevalence of defects in arrhythmia-related candidate genes among patients with unexplained sudden cardiac death (SCD). BACKGROUND: Patients with unexplained sudden death may constitute up to 5% of overall SCD cases. For such patients, systematic postmortem genetic analysis of archived tissue, using a candidate gene approach, may identify etiologies of SCD. METHODS: We performed analysis of KCNQ1 (KVLQT1), KCNH2 (HERG), SCN5A, KCNE1, and KCNE2 defects in a subgroup of 12 adult subjects with unexplained sudden death, derived from a 13-year, 270-patient autopsy series of SCD. Archived, paraffin-embedded myocardial tissue blocks obtained at the original postmortem examination were the source of deoxyribonucleic acid for genetic analysis. RESULTS: Two patients were found to have the same HERG defect, a missense mutation in exon 7 (nucleotide change G1681A, coding effect A561T). The mutation was heterozygous in Patient 1, but Patient 2 appeared to be homozygous for the defect. Patch-clamp recordings showed that the A561T mutant channel expressed in human embryonic kidney cells failed to generate HERG current. Western blot analysis implicated a trafficking defect in the protein, resulting in loss of post-translational processing from the immature to the mature form of HERG. No mutations were detected among the remaining four candidate genes. CONCLUSIONS: In this autopsy series, only 2 of 12 patients with unexplained sudden death were observed to have a defect in HERG among five candidate genes tested. It is likely that elucidation of SCD mechanisms in such patients will await the discovery of multiple, novel arrhythmia-causing gene defects.

Adult↗

PubMed2004

Genomics in sudden cardiac death.

Sudden cardiac death (SCD) remains a public health problem of major magnitude. Contrary to earlier expectations, and despite decreased overall cardiac mortality, SCD rates appear to be rising in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. With the exception of the implantable defibrillator, there are few effective approaches to SCD prevention and even fewer clues concerning patient phenotypes predisposed to life-threatening arrhythmias. Clinical variables such as ejection fraction predict mortality but are not sensitive enough to identify many high SCD risk patients. The predictive power of autonomic dysregulation and markers such as lipid levels, hypertension, diabetes, and smoking is quite low in subclinical heart disease, the population in which the majority of SCDs occur. This review addresses advances in genomic science applicable to the SCD public health problem in both rare and common forms of heart disease. These include novel bioinformatic approaches to both identify candidate genes/pathways and identify previously unknown functional genetic elements, as well as methods to comprehensively screen these elements. We also discuss the possibility of applying high-density genome-wide SNP analyses to examine genetic contributions to arrhythmia susceptibility in community-based, case-control studies of common forms of SCD. The development of novel strategies to identify contributors to susceptibility in common cardiac phenotypes is most likely to lead to new and relevant therapeutic targets for SCD.

Arrhythmias, Cardiac↗

PubMed2004

Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death.

OBJECTIVE: Characterization of a distinct, and as yet unexplained phenotype of sudden cardiac death (SCD). BACKGROUND: In a subgroup of patients with SCD, postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF). The absence of confounding factors may facilitate evaluation of the relationship between myocardial fibrosis and ventricular arrhythmogenesis. METHODS: Six patients with IMF were identified from a postmortem, consecutive 13-year series of 270 subjects presenting with SCD. Ventricular interstitial remodeling was assessed quantitatively and qualitatively and comparisons made with 6 age- and sex-matched control subjects who suffered noncardiac death. Myocardial collagen volume fraction and perivascular fibrosis ratio were determined and evidence for inflammatory response and apoptotic cell death was sought. The potential role of transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was evaluated. RESULTS: Overall myocardial collagen volume fraction was 1.6-fold higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022 +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was diffuse but disproportionately so in the LV inferior wall (3.4-fold increase; .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of either myocardial inflammatory response or myocyte apoptosis in cases or controls. Expression of TGF-beta(1) was significantly increased in IMF vs controls. CONCLUSION: IMF involves diffuse and heterogeneous remodeling of the ventricular interstitium, with a predilection for the LV inferior wall. TGF-beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.

Adult↗

PubMed2003

Cardiac pathologic findings reveal a high rate of sudden cardiac death of undetermined etiology in younger women.

BACKGROUND: Between 1989 and 1998 there was a 21% increase in estimated sudden cardiac death among US women aged 35 to 44 years. In contrast, the sudden cardiac death rate in age-matched men showed a decreasing trend (-2.8%). Due to under-representation of younger adults in published autopsy series, etiologies of sudden cardiac death merit further investigation. METHODS: We reviewed autopsy and detailed cardiac pathologic findings in younger women (age 35-44 years) from a 270-patient, 13-year (1984-1996) autopsy series of sudden cardiac death, and performed comparisons with findings in age-matched men. RESULTS: Women aged 35 to 44 years constituted 32% of all women in the series compared to men, who constituted 24% of total men (P =.004 vs women). A presumptive cause of sudden cardiac death could not be determined in 13 women (50%). Among women, 6 cases (22%) had significant coronary artery disease. Findings in others included coronary artery anomalies (n = 3), myocarditis (n = 2), hypertrophic cardiomyopathy (n = 1), coronary artery dissection (n = 1) and accessory pathway (n = 1). In younger men, a presumptive cause of sudden cardiac death remained undetermined in only 24% (P =.025 vs younger women), and coronary artery disease accounted for 40% of cases. CONCLUSIONS: In younger women, despite autopsy and detailed cardiac pathologic examination, an attributable cause of sudden cardiac death was not determined in 50% of cases; a 2-fold increase compared to men of the same age. Given the dynamic and multifactorial nature of sudden cardiac death, comprehensive population-based investigations are likely to be necessary to further investigate this unexpected sex-based disparity.

Adult↗

PubMed2003

Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model.

BACKGROUND: We, and others, have previously reported a strong correlation between increased inter-ventricular dispersion of repolarization and the occurrence of fatal arrhythmia in animal models of CHF. The existence of this and other such distinct electrophysiologic phenotypes in right (RV) vs. left ventricles (LV) could be explained by chamber-specific patterns of gene expression. METHODS: We employed microarray gene profiling of 13824 sequence-verified, nonredundant rodent cDNAs to compare myocardial gene expression in RV vs. LV of rats with surgically induced myocardial infarction (MI: n=3) and in sham-operated animals (Sham: n=3). RESULTS: Significant LV infarction (32+/-4% LV) and severe CHF were observed in all MI animals at 4 weeks. In Sham animals, 937 genes exhibited significant differential expression in RV vs. LV myocardium. In MI animals, 1158 genes exhibited significant differential expression in RV vs. LV. Of those genes exhibiting significant differential expression, only 241 were common to both Sham and MI animals. Differentially expressed genes included those involved in signal transduction, cell growth and maintenance, and apoptosis. Genes with potential roles in altered dispersion of repolarization included voltage-dependent Ca(2+) channel gamma subunit (MI 8-fold increasing) and K(+) inwardly rectifying channel subfamily J, member 10 (MI 6-fold decreasing). Gap junction membrane channel protein alpha 4 (MI 6-fold decreasing) and cardiac troponin I (MI 8-fold decreasing) were also significantly differentially expressed. Inter-ventricular comparisons revealed significantly greater alterations in gene expression vs. intra-ventricular comparisons. CONCLUSIONS: Microarray gene profiling has revealed candidate genes, some of them novel, which may account for chamber-specific ventricular electrophysiologic phenotypes, both in physiologic as well as in arrhythmogenic states such as CHF.

Animals↗

PubMed2003

Nonautomatic focal atrial tachycardia: characterization and ablation of a poorly understood arrhythmia in 38 patients.

Nonautomatic focal atrial tachycardia (NAFAT) is a rare and poorly understood arrhythmia either due to microreentry or triggered mechanism. NAFAT was defined as a focal atrial tachycardia which was inducible with pacing maneuvers in the electrophysiology lab. We reviewed the charts and EP study reports of all 38 patients with NAFAT, who underwent an EP study at our center between April 1994 and September 2000. Patients' were predominantly female (n = 31, 82%), aged 11-78 years (median 46). The mean age at presentation was 31 years (range 7-71 years). None of the patients had structural heart disease or had undergone prior heart surgery. Electroanatomic mapping (EAM) was performed in 22 patients and showed no scars in the atrium. A total of 45 foci were identified (range 1-3 foci/patient). Anatomically NAFAT foci were predominantly right atrial (n = 35) rather than left (n = 10). The NAFAT cycle length ranged from 270 to 490 (mean +/- SD; 380 +/- 69 ms) and was significantly lower in patients younger than 24 years of age. Ablation, attempted for 42 foci was successful in 33 (79%). The success rate in the EAM group was 20/25 foci (80%) compared to 13/18 (72%) in the non-EAM group. In conclusion, NAFAT is a rare arrhythmia which predominantly affects women with no other associated cardiac disease. It mainly occurs in the right atrium, affects all ages and is amenable to catheter ablation.

Adult↗

PubMed2003

Apparent protective effect of increased left ventricular wall thickness in an ICD population.

BACKGROUND: Expanding indications for the implantable cardioverter defibrillator (ICD) call for further enhancement of patient selection for optimization of use. Because a subgroup of patients who receive ICDs may not receive therapies, we sought to identify clinical predictors of therapy-free survival in ICD patients. METHODS: We performed an analysis of a single-center, 13-year ICD implantation experience (1990-2002). The association between therapy-free survival and several clinical variables was evaluated. RESULTS: From a total of 562 patients included in the database, 98 patients (17%) received no shock therapies or antitachycardia pacing (group A). When compared with a randomly selected sample of 131 patients who did receive ICD therapies (group B), there were no significant differences in age, gender, frequency of coronary artery disease, or extent of left ventricular (LV) dysfunction. However, left ventricular hypertrophy (LVH; increased wall thickness by echocardiography) was significantly more common in group A versus group B (30% versus 18%; Pearson's chi-square=4.69, P=.03). The odds of patients in group A having LVH were 1.98 times higher versus group B (95% confidence interval for odds ratio: 1.06-3.71). Comparisons of calculated mean LV mass between the 2 groups were not significantly different (group A 283+/-112 gm versus group B 271+/-108, P=.58). The overall mortality rate was 17% in group A and 22% in group B (P=.29). CONCLUSIONS: Increased LV wall thickness was a significant, independent predictor of therapy-free survival in this ICD population. Because LV mass was unchanged, this finding may reflect the importance of LV dilation and wall thinning (ie, eccentric remodeling) as a risk factor for recurrent ventricular arrhythmia in ICD patients.

Aged↗