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1.  Obesity related risk of sudden cardiac death in the atherosclerosis risk in communities study 
Heart (British Cardiac Society)  2014;101(3):215-221.
To examine the association of body mass index (BMI), waist circumference (WC) and waist hip ratio (WHR) with sudden cardiac death (SCD) in community dwelling individuals.
Data from a multicentre, prospective, cohort study of 14 941 men and women (African American, and white), aged 45–64 years, participating in the Atherosclerosis Risk in Communities study was analysed. Obesity measures were assessed at baseline (1987–1989). SCD was adjudicated by a committee.
At enrolment mean±SD age of the participants was 54±6 years (55% female; 26% African American). During 12.6±2.5 years of follow-up, 253 SCD occurred (incidence rate 1.34/100 person-years). The association between obesity and SCD differed by smoking status (interaction p≤0.01). In models adjusting for age, sex, race, study centre and education level, SCD risk was positively associated (p<0.001) with BMI, WC and WHR in non-smokers, but not in smokers. WHR was more strongly associated with SCD in non-smokers than was BMI or WC (HR per SD increment (95% CI) 2.00 (1.65 to 2.42); 1.34 (1.15 to 1.56) and 1.49 (1.28 to 1.74), respectively). After adjustment for potential mediators (hypertension, diabetes, lipid profile, prevalent coronary heart disease, heart failure, and LV hypertrophy), non-smokers in the highest WHR category (>0.95 in women; >1.01 in men) had double the risk of SCD (HR 2.03, 95% CI 1.19 to 3.46; incidence rate 1.43/1000 person-years) versus those with normal WHR.
General obesity is associated with increased risk of SCD in middle-aged, non-smoking individuals, mediated by traditional cardiovascular risk factors. Central obesity, however, is independently associated with SCD by pathways that remain to be elucidated.
PMCID: PMC4791977  PMID: 25410499
2.  Atrial Flutter Ablation and Risk of Right Coronary Artery Injury 
Radiofrequency ablation (RFA) of atrial flutter (AFL) is a commonly performed procedure with low risk of complications. Several case reports and animal studies cautioned about the risk of right coronary artery (RCA) injury following AFL ablation. This risk is due to the anatomic proximity of the RCA to the cavo-tricuspid isthmus where ablation is performed. We present a case report that demonstrates postmortem evidence of RCA injury following RFA of AFL.
PMCID: PMC4330022  PMID: 25699126
Atrial flutter; Coronary artery; Cardiac arrhythmia; Myocardial infarction; Radiofrequency catheter ablation
3.  Atrial Fibrillation and the Risk of Sudden Cardiac Death: The Atherosclerosis Risk in Communities (ARIC) Study and Cardiovascular Health Study (CHS) 
JAMA internal medicine  2013;173(1):29-35.
It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.
In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15439 participants (baseline 45–64 years, 55% women, and 27% black) from baseline (1987–1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline ≥65 years, 58% women, and 15% black) from baseline (first cohort, 1989–1990; second cohort, 1992–1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD): coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.
In ARIC, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89/1000 person-years (with AF) and 1.30/1000 person-years (without AF). The multivariable hazard ratios (HRs) (95% CI) of AF for SCD and NSCD were 3.26 (2.17–4.91) and 2.43 (1.60–3.71), respectively. In CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00/1000 person-years (with AF) and 3.82/1000 person-years (without AF). The multivariable HRs (95% CI) of AF for SCD and NSCD were 2.14 (1.60–2.87) and 3.10 (2.58–3.72), respectively. The meta-analyzed HRs (95% CI) of AF for SCD and NSCD were 2.47 (1.95–3.13) and 2.98 (2.52–3.53), respectively.
Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in AF patients is warranted.
PMCID: PMC3578214  PMID: 23404043
4.  Utility of nuclear stress imaging for detecting coronary artery bypass graft disease 
The value of Single Photon Emission Computed Tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort.
Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram.
A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary significantly with ischemic territory.
Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.
PMCID: PMC3469356  PMID: 22862805
Coronary artery bypass grafts; CABG; Coronary artery imaging; Cardiac catheterization/intervention
5.  Variation of mortality after coronary artery bypass surgery in relation to hour, day and month of the procedure 
Mortality and complications after percutaneous coronary intervention is higher when performed after regular duty hours due to challenging patient characteristics, inferior processes of care and limited resources. Since these challenges are also encountered during coronary artery bypass graft (CABG) surgery that is performed after regular work hours, we assessed whether hour and day of procedure influenced mortality after CABG.
We studied 4,714 consecutive patients who underwent CABG at the Minneapolis Veterans Administration (VA) Medical Center between 1987 and 2009. We compared postoperative (30-day) mortality rates in relation to hour and day in which the operation was performed.
Operations performed on weekends and after 4 PM had higher risk patients (p < 0.0001) and were more likely to be emergent (p < 0.0001), require intra-aortic balloon pump support (p < 0.0001) and result in postoperative complications (p < 0.0001) compared to those at regular work hours. Mortality was significantly higher when CABG was performed on weekends compared to weekdays (9.4% versus 2.5%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6 to 10.4, p = 0.003), and after 4 PM compared to between 7 AM-4 PM (6.2% versus 2.2%; OR 2.9, 95% CI 1 to 8, p = 0.049). In multivariable analysis, when adjusted for the urgency of the operation and the VA estimated mortality risk score, these associations were no longer statistically significant.
Mortality after CABG is higher when surgery is performed on the weekends and after 4 PM. These variations in mortality were related to higher patient risk, and urgency of the operation rather than external factors.
PMCID: PMC3206827  PMID: 22014242
coronary artery bypass surgery; mortality
6.  Etiology of Sudden Death in the Community: Results of Anatomic, Metabolic and Genetic Evaluation 
American heart journal  2010;159(1):33-39.
Identifying persons at risk for sudden cardiac death (SCD) is challenging. A comprehensive evaluation may reveal clues about the clinical, anatomic, genetic and metabolic risk factors for SCD.
Seventy-one SCD victims (25–60 years-old) without an initially apparent cause of death were evaluated at the Hennepin County Medical Examiner’s office from August, 2001 to July, 2004. We reviewed their clinic records conducted next-of-kin interviews and performed autopsy, laboratory testing and genetic analysis for mutations in genes associated with the long-QT syndrome.
Mean age was 49.5±7 years, 86% were male and 2 subjects had history of coronary heart disease (CHD). Coronary risk factors were highly prevalent in comparison to individuals of the same age group in this community (e.g. smoking 61%; hypertension 27%; hyperlipidemia 25%) but inadequately treated. On autopsy, 80% of the subjects had high-grade coronary stenoses. Acute coronary lesions and previous silent myocardial infarction (MI) were found in 27% and 34%, respectively. Further, 32% of the subjects had recently smoked cigarettes and 50% had ingested analgesics. Possible deleterious mutations of the ion channel genes were detected in 5 (7%) subjects. Of these, 4 were in the sodium channel gene SCN5A.
Overwhelming majority of the SCD victims in the community had severe subclinical CHD, including undetected previous MI. Traditional coronary risk factors were prevalent and under-treated. Mutations in the long-QT syndrome genes were detected in a few subjects. These findings imply that improvements in the detection and treatment of subclinical CHD in the community are needed to prevent SCD.
PMCID: PMC2905235  PMID: 20102864
death; sudden; epidemiology; genetics; pathology; coronary disease
7.  Efficacy of N-acetylcysteine in preventing renal injury after heart surgery: a systematic review of randomized trials 
European Heart Journal  2009;30(15):1910-1917.
The aim of this study was to assess whether perioperative N-acetylcysteine (NAC), an antioxidant, prevents acute renal injury (ARI) after cardiac surgery.
Methods and results
We performed a systematic review of randomized controlled trials (RCTs) of NAC in adult cardiac surgery patients. The RCTs were identified by searching MEDLINE (1960–2008), website, and hand-searching references of relevant publications. Primary outcome was ARI (absolute increase >0.5 mg/dL or relative increase >25%, in serum creatinine from baseline within 5 days after surgery). Random effects model was used to perform a meta-analysis. Forest plots and I2 test were used to assess heterogeneity among studies. Ten RCTs (n = 1163 patients) were included. Mean age was 70 ± 7.4 years, 71% were male, and 66% underwent coronary artery bypass surgery. N-Acetylcysteine did not reduce ARI incidence [35% NAC vs. 37% placebo; relative risk (RR) 0.91, 95% CI 0.79–1.06, P = 0.24]. Overall, 3.3% of patients required haemodialysis (NAC vs. placebo; RR = 1.13, 95% CI 0.59–2.17) and 3% died (RR = 1.10, 95% CI 0.56–2.16). There was a trend towards reduced ARI incidence among patients with baseline chronic kidney disease assigned to intravenous NAC (RR = 0.80, 95% CI 0.64–1.01, P = 0.06).
This meta-analysis of RCTs showed that prophylactic perioperative NAC in cardiac surgery does not reduce ARI, haemodialysis, or death.
PMCID: PMC2719697  PMID: 19282300
Cardiac surgery; Kidney; Antioxidants; Meta-analysis; Mortality
8.  Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers 
Previous studies on the effects of Statins in preventing atrial fibrillation (AF) after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown.
We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG) (n = 1493) or valve surgery (n = 443) at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively).
Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30%) patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p < 0.0001). Patients with a past history of AF had a 5 times higher risk of postoperative AF (odds ratio 5.1; 95% confidence interval 3.4 to 7.7; p < 0.0001). AF occurred in 31% of patients taking statins versus 29% of the others (p = 0.49). In multivariable analysis, statins were not associated with AF (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.7 to 1.2; p = 0.59). However, in a subgroup analysis, the patients treated with Simvastatin >20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03) in comparison to those taking lower dosages.
Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages
PMCID: PMC2777853  PMID: 19889221
9.  Sudden Death after Myocardial Infarction 
Sudden cardiac death (SCD) after myocardial infarction (MI) has not recently been assessed in the community. Post-MI risk stratification for SCD commonly relies on baseline characteristics and little is known about the relationship between recurrent ischemia or heart failure (HF) and SCD.
To evaluate the risk of SCD after MI and the impact of recurrent ischemia and HF on SCD.
Design, setting, and participants
2,997 Olmsted County residents experiencing an MI between 1979 and 2005.
Main outcome measures
SCD defined as out-of-hospital death due to coronary disease. Observed survival free of SCD compared to that expected in Olmsted County.
During a median follow-up of 4.7 years (25th–75th percentile 1.6–7.1, date of last follow-up 02-29-2008), 1,160 deaths occurred, 282 (24%) SCD. The 30-day cumulative incidence of SCD was 1.2% (95% confidence interval [CI] 0.8–1.6%). Thereafter, the rate of SCD was constant at 1.2%/year yielding a 5-year cumulative incidence of 6.9% (95% CI 5.9% to 7.9%). The 30-day incidence of SCD was 4-fold higher than expected (standardized mortality ratio=4.2, 95% CI 2.9 to 5.8). In the year thereafter, the risk of SCD was lower than expected (standardized mortality ratio=0.66, 95% CI 0.50 to 0.85). The risk of SCD declined over time (hazard ratio=0.62, 95% CI 0.44 to 0.88 for MIs in 1997–2005 compared to 1979–1987; p =0.03). Recurrent events, ischemia (n=842) or HF (n=365), occurred in 2,080 patients. After adjustment for baseline characteristics, recurrent ischemia was not associated with SCD (hazard ratio=1.26, 95% CI 0.96 to 1.65; p=0.09), while HF markedly increased the risk of SCD (hazard ratio= 4.20, 95% CI 3.10 to 5.69; p<0.001)
The risk of SCD is highest during the first month after MI and declined over time. SCD is independently associated with HF but not with recurrent ischemia.
PMCID: PMC2731625  PMID: 18984889
10.  Relation of Heart Rate Parameters During Exercise Test to Sudden Death and All-cause Mortality in Asymptomatic Men 
The American journal of cardiology  2008;101(10):1437-1443.
Heart rate (HR) profile during exercise predicts all-cause mortality. However, less is known about its relation with sudden (versus non-sudden) death in asymptomatic individuals. We assessed the relation of exercise HR parameters (resting HR, target HR achievement, HR increase and HR recovery) with sudden death, coronary heart disease (CHD) death, myocardial infarction and all-cause mortality in 12,555 men who participated in the Multiple Risk Factor Intervention Trial. Participants were 35–57 years-old, without any clinical CHD but with above average Framingham risk. Trial follow-up was 7 years; post-trial extended follow-up for all-cause mortality was 25 years. After adjusting for cardiac risk factors, having to stop exercise before achieving 85% of age-specific maximal HR was associated with an increased risk of sudden death (hazard ratio 1.8, 95% CI 1.3–2.5; p=0.001), CHD death (hazard ratio 1.4, 95% CI 1.2–1.5; p<0.001) and all-cause mortality (hazard ratio 1.3, 95% CI 1.2–1.4; p<0.001). Elevated resting HR (p=0.001), attenuated HR increase (p=0.02), delayed HR recovery (p=0.04) and exercise duration (p<0.0001) were independent predictors of all-cause death in the overall study population and also among the subgroup that achieved target HR. In conclusion, middle age men without clinical CHD who stopped exercise prior to reaching 85% of maximal HR had a higher risk of sudden death. Other exercise HR parameters and exercise duration predicted all-cause mortality.
PMCID: PMC2440694  PMID: 18471455

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