Racial Disparities in Ion Channelopathies and Inherited Cardiovascular Diseases Associated With Sudden Cardiac Death.

Cardiovascular disease (CVD) continues to be the most common cause of death worldwide, and cardiac arrhythmias account for approximately one half of these deaths. The morbidity and mortality from CVD have been reduced significantly over the past few decades; however, disparities in racial or ethnic populations still exist. This review is based on available literature to date and focuses on known cardiac channelopathies and other inherited disorders associated with sudden cardiac death in African American/Black subjects and the role of epigenetics in phenotypic manifestations of CVD, and illustrates existing disparities in treatment and outcomes. The review also highlights the knowledge gaps that limit understanding of the manifestation of phenotypic abnormalities across racial or ethnic groups and discusses disparities associated with device underuse in the management of patients at risk for sudden cardiac death. We discuss factors related to reports in the United States, that the overall mortality attributed to CVD and the number of out-of-hospital cardiac arrests are higher among African American/Black subjects when compared with other racial or ethnic groups. African American/Black subjects are disproportionally affected by CVD, including cardiac arrhythmias and sudden cardiac death, thus highlighting a major concern in this population that remains underrepresented in clinical trials with limited genetic testing and device underuse. The proposed solutions include (1) early identification of genetic variants, which is crucial in tailoring a preventive management strategy; (2) inclusion of diverse racial or ethnic groups in clinical trials; (3) compliance with guideline-directed medical treatment and referral to cardiovascular subspecialists; and (4) training and mentoring of underrepresented junior faculty in cardiovascular health disparities research.

Application of Electromechanical Window Negativity as an Arrhythmia Risk Correlate in Acquired Long QT Syndrome.

Long QT syndrome is a congenital or acquired condition associated with life-threatening cardiac arrhythmias. Risk stratification measures are paramount to providing life-saving therapy. We present a case of a 30-year-old man with syncope and polymorphic ventricular tachycardia from drug-induced QTc prolongation. Electromechanical window negativity correlated with arrhythmia risk and risk predictors. (Level of Difficulty: Advanced.).

Cardiac resynchronization therapy: A comparative analysis of mortality in African Americans and Caucasians.

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients with heart failure, reduced left ventricular ejection fraction, and a prolonged QRS duration. African Americans are underrepresented in clinical trials and CRT is underutilized; consequently, the benefits and outcomes of CRT are not well-defined. METHODS: We evaluated 294 patients, determined survival using Kaplan-Meier analysis, and used Cox proportional hazards regression model to determine predictors of mortality. Propensity score-match analysis was applied to balance covariates in African Americans and Caucasians. RESULTS: The mean age for African Americans (n  =  131) and Caucasians (n  =  163) was 65 ± 12 and 70 ± 13 years (P  =  0.0003). Mortality in African Americans was 28% compared to 37% in Caucasians (P  =  0.14) over a median follow-up of 8.1 ± 0.6 years. Survival was significantly reduced in African Americans and Caucasians with a glomerular filtration rate (GFR) < 60 (6.7 ± 0.4, 95% confidence interval [CI]: 5.9-7.5 vs 8.6 ± 0.5 CI: 7.7-9.5 years, P  =  0.005), and those not treated with an aldosterone antagonist (7.1 ± 0.4, 95% CI: 6.5-7.9 vs 8.7 ± 0.6, 7.6-9.9 years, P  =  0.04), respectively. Independent predictors of mortality were a GFR <60 and low left ventricular ejection fraction. In African Americans, ischemic cardiomyopathy (ICM) and lack of therapy with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) were associated with increased mortality. CONCLUSIONS: Long-term survival benefit from CRT was similar in African Americans and Caucasians. A GFR < 60 and lack of therapy with an aldosterone antagonist were associated with decreased survival. Survival also was inversely related to the number of comorbidities. In African Americans, underutilization of an ACEI or ARB, and ICM were additional factors associated with increased mortality.

Sinus Bradycardia in Habitual Cocaine Users.

Common physiological manifestations of cocaine are related to its adrenergic effects, due to inhibition of dopamine and norepinephrine uptake at the postsynaptic terminal. Few studies have documented bradycardia secondary to cocaine use, representing the antithesis of its adrenergic effects. We assessed the prevalence of sinus bradycardia (SB) in habitual cocaine users and postulated a mechanism for this effect. One hundred sixty-two patients with a history of cocaine use were analyzed and compared with age- and gender-matched controls. SB was defined as a rate of <60 beats/min and habitual cocaine use as 2 or more documented uses >30 days apart. Propensity score-matching analysis was applied to balance covariates between cocaine users and nonusers and reduce selection bias. Patients with a history of bradycardia, hypothyroidism, or concomitant beta-blocker use were excluded. Mean age of study patients was 44 ± 8 years. SB was observed in 43 of 162 (27%) cocaine users and in 9 of 149 (6%) nonusers (p = 0.0001). Propensity score-matching analysis matched 218 patients from both groups. Among matched patients SB was observed in 25 of 109 (23%) cocaine users and in 5 of 109 (5%) nonusers (p = 0.0001). Habitual cocaine use was an independent predictor of SB and associated with a sevenfold increase in the risk of SB (95% CI 2.52 to 19.74, p = 0.0002). In conclusion, habitual cocaine use is a strong predictor of SB and was unrelated to recency of use. A potential mechanism for SB may be related to cocaine-induced desensitization of the beta-adrenergic receptor secondary to continuous exposure. Symptomatic SB was not observed; thus, pacemaker therapy was not indicated.

Mortality in African-Americans Following Cardiac Resynchronization Therapy: A Single Center Experience.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves clinical outcomes and reduces mortality in heart failure patients who remain symptomatic despite optimal medical therapy. CRT trials have reported significant hemodynamic benefits, improvement in functional status, and reduced mortality and heart failure hospitalizations. However, African-American patient representation in these studies is limited thus the results may not be applicable to them. We described baseline clinical characteristics of African-American patients undergoing CRT and determined their outcomes relative to those reported in clinical trials. METHODS: We evaluated 131 African-American patients with New York Heart Association functional class II-IV heart failure undergoing CRT and determined predictors of all-cause mortality. Kaplan-Meier survival estimates and a Cox proportional hazards model determined mortality and risk of death. RESULTS: The mean age was 65 ± 12 years. Over a 6-year period, total mortality in African-Americans was 23% as compared with 29% in the MADIT-CRT trial. Increased mortality was associated with older age (hazard rate (HR) 1.04, 95% confidence interval (CI) 1.01-1.07, P=.01), ischemic cardiomyopathy (HR 2.86, 95% CI 1.36-6.04, P=.006), and absence of treatment with either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (HR 2.75, 95% CI 1.30-5.80, P=.008), or beta-blocker (HR 2.56, 95% CI 0.98-6.69, P=.05). Hydralazine plus nitrate therapy was used in a small number of patients and did not influence mortality outcomes. CONCLUSION: African-Americans experience the same survival benefits from CRT as Caucasian patients reported in major clinical trials. Publication indices used to find publications listed in references: PubMed.

Biventricular paced QRS predictors of left ventricular lead locations in relation to mortality in cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) lead location during cardiac resynchronization therapy (CRT) has influenced mortality and heart failure events; however the biventricular paced QRS morphology has not been established as a predictor of LV lead location or mortality. METHODS: We evaluated the biventricular paced QRS morphology in 306 patients undergoing CRT in relation to specific anatomic locations. A logistic regression model and Kaplan-Meier survival estimates were used to determine predictors of LV lead location and survival. RESULTS: The mean age was 68±13years. Predictors of LV lead location from anterior, lateral, and posterior segments were: absence of R in V1, QS in aVL; and R in aVL, respectively. Absence of an R in II, III, or aVF predicted an inferior site. A QS in V4-V6 differentiated apical from basal sites (p=0.01). LV pacing from sites along the middle cardiac vein revealed a higher mortality (34%), than lateral sites (20%, p=0.02). CONCLUSIONS: Biventricular paced QRS criteria were predictive of LV lead locations. The proposed algorithm enhanced the predictive accuracy of these criteria. LV pacing sites along the middle cardiac vein were associated with increased mortality.

Asymptomatic sinus bradycardia following bariatric surgery.

Approximately 121,000 bariatric surgical procedures are performed annually, and salutary effects include a reduction in cardiovascular morbidity and mortality, risk factor modification, and improvement in sympathovagal tone. There are anecdotal accounts of unexplained sinus bradycardia (SB) after significant weight loss but no systematic studies have been conducted. The purpose of this study was to determine the frequency of incident SB, its timing, and association with weight loss, clinical characteristics, and predictors. We evaluated various clinical characteristics including resting heart rate, blood pressure, body mass index (BMI), heart rate reserve (HRR), basal metabolic rate, and exercise regimen in 151 consecutive patients who underwent bariatric surgery. Multiple logistic regression analysis was performed to determine predictors of SB. Twenty-five of 137 patients (18%) experienced postoperative SB. Patients with SB had significantly greater reduction in BMI than those without bradycardia (35 ± 9.6% and 25.7 ± 13%, respectively, p = 0.002). HRR was significantly greater in patients with SB (116 ± 14 beats/min) compared with those without bradycardia (105 ± 14 beats/min, p = 0.007). Multiple logistic regression analysis revealed that the odds of developing SB were 1.96 and 1.91 and associated with the percent decrease in BMI (95% confidence interval 1.3 to 3.0, p = 0.002) or increase in HRR (95% confidence interval 1.28 to 2.85, p = 0.002), respectively. In conclusion, SB occurred 14 ± 11 months postoperatively and its predictors were the percent reduction in BMI or increase in HRR.

Percutaneous pacemaker and implantable cardioverter-defibrillator lead extraction in 100 patients with intracardiac vegetations defined by transesophageal echocardiogram.

OBJECTIVES: We describe the feasibility, safety, and clinical outcomes of percutaneous lead extraction in patients at a tertiary care center who had intracardiac vegetations identified by transesophageal echocardiogram. BACKGROUND: Infection in the presence of intracardiac devices is a problem of considerable morbidity and mortality. Patients with intracardiac vegetations are at high risk for complications related to extraction and protracted clinical courses. Historically, lead extraction in this cohort has been managed by surgical thoracotomy. METHODS: We analyzed percutaneous lead extractions performed from January 1991 to September 2007 in infected patients with echocardiographic evidence of intracardiac vegetations, followed by a descriptive and statistical analysis. RESULTS: A total of 984 patients underwent extraction of 1,838 leads; local or systemic infection occurred in 480 patients. One hundred patients had intracardiac vegetations identified by transesophageal echocardiogram, and all underwent percutaneous lead extraction (215 leads). Mean age was 67 years. Median extraction time was 3 min per lead; median implant duration was 34 months. During the index hospitalization, a new device was implanted in 54 patients at a median of 7 days after extraction. Post-operative 30-day mortality was 10%; no deaths were related directly to the extraction procedure. CONCLUSIONS: Patients with intracardiac vegetations identified on transesophageal echocardiogram can safely undergo complete device extraction using standard percutaneous lead extraction techniques. Permanent devices can safely be reimplanted provided blood cultures remain sterile. The presence of intracardiac vegetations identifies a subset of patients at increased risk for complications and early mortality from systemic infection despite device extraction and appropriate antimicrobial therapy.

Axillary subpectoral approach for pacemaker or defibrillator implantation in patients with ipsilateral prepectoral infection and limited venous access.

PURPOSE: The prepectoral approach is the procedure of choice for pacemaker or defibrillator (device) implantation. Epicardial or transiliac approaches are reserved for patients in whom the pectoral approach is not feasible. We studied the viability of the axillary subpectoral approach for implanting devices in patients in whom the standard prepectoral approach was not feasible. METHODS: Devices and leads were extracted from 16 patients with infected devices in the prepectoral position. The contralateral site was unsuitable for reimplantation because of infection or inadequate venous access. On the side ipsilateral to that with prior prepectoral device infection, we made an incision on the anterior axillary line along the border of the pectoralis major; dissection was continued below the muscle to create a pocket for generator implantation. Axillary venous puncture was performed from the axillary incision and beneath the pectoralis major muscle using a long 14-gauge needle. Long guidewires and peel-away sheaths were used for positioning the lead. The generator was placed in the subpectoral pocket; the wound was closed with absorbable sutures. RESULTS: One patient developed a pocket hematoma; one developed a pneumothorax; no other surgical complication, lead malfunction, or recurrence of infection was observed. CONCLUSION: The axillary subpectoral approach is an acceptable, technically feasible method for reimplantation for patients with pectoral device infection and limited venous access options. It offers the advantage of a new sterile fascial plane ipsilateral to the site of prepectoral device infection.

Clinical assessment of the risk for sudden cardiac death in patients with sickle cell anemia.

BACKGROUND: Previous studies suggest that patients with sickle cell anemia (SCA) have an increased risk of sudden cardiac death; however, its etiology and mechanism are not well defined. Left ventricular hypertrophy (LVH), ventricular tachycardia (VT) and poor left ventricular systolic function are known risk factors for sudden cardiac death. An abnormal microvolt T-wave alternans (TWA) test is also a predictor of sudden cardiac death risk, but it has not been applied to this patient population. METHODS: We performed a 12-lead electrocardiogram, 24-hour Holter monitor, two-dimensional echocardiogram, nuclear stress test and microvolt TWA test to determine whether markers of sudden cardiac death could be identified. RESULTS: Twenty-six patients were evaluated with a mean age of 40 +/- 12 years. The two-dimensional echocardiogram revealed a normal ejection fraction in 23 patients and LVH in 17 (65%), whereas hypertension was noted in only five (19%). Microvolt TWA testing was abnormal in six of 22 patients (27%). Holter monitor revealed VT in two patients. Among the clinical variables tested, only LVH was predictive of an abnormal TWA test. The sensitivity, specificity, positive and negative predictive value of LVH for and abnormal TWA test was 100, 56, 46 and 100%. CONCLUSION: LVH was common in patients with SCA and disproportional to the number of patients with hypertension. Microvolt TWA tests were abnormal in 27% of patients; however, LVH was the only clinical variable that predicted an abnormal TWA test. Risk stratification of SCA patients may require echocardiographic detection of LVH and an abnormal TWA test due to the high negative predictive value. The significance of an abnormal TWA test should be further evaluated in a large study, with a longer follow-up period.

Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction.

OBJECTIVES: This study hypothesized that microvolt T-wave alternans (MTWA) improves selection of patients for implantable cardioverter-defibrillator (ICD) prophylaxis, especially by identifying patients who are not likely to benefit. BACKGROUND: Many patients with left ventricular dysfunction are now eligible for prophylactic ICDs, but most eligible patients do not benefit; MTWA testing has been proposed to improve patient selection. METHODS: Our study was conducted at 11 clinical centers in the U.S. Patients were eligible if they had a left ventricular ejection fraction (LVEF) < or =0.40 and lacked a history of sustained ventricular arrhythmias; patients were excluded for atrial fibrillation, unstable coronary artery disease, or New York Heart Association functional class IV heart failure. Participants underwent an MTWA test and then were followed for about two years. The primary outcome was all-cause mortality or non-fatal sustained ventricular arrhythmias. RESULTS: Ischemic heart disease was present in 49%, mean LVEF was 0.25, and 66% had an abnormal MTWA test. During 20 +/- 6 months of follow-up, 51 end points (40 deaths and 11 non-fatal sustained ventricular arrhythmias) occurred. Comparing patients with normal and abnormal MTWA tests, the hazard ratio for the primary end point was 6.5 at two years (95% confidence interval 2.4 to 18.1, p < 0.001). Survival of patients with normal MTWA tests was 97.5% at two years. The strong association between MTWA and the primary end point was similar in all subgroups tested. CONCLUSIONS: Among patients with heart disease and LVEF < or =0.40, MTWA can identify not only a high-risk group, but also a low-risk group unlikely to benefit from ICD prophylaxis.