A Novel Perivesical Fat Rotational Flap as an Alternative to Omental Interposition in Challenging Urological Reconstruction.

OBJECTIVE: To introduce the application of the perivesical fat rotational flap as a substitute for omental interposition during several complex urologic reconstruction. We highlight our technique using a case of salvage prostatectomy after initial high-intensity focused ultrasound for recurrent high-risk prostate cancer requiring future adjuvant radiation treatment. We have also successfully used this technique in the management of recurrent vesicovaginal, colovesical, rectourethral fistulas, and postradiation salvage prostatectomy setting. MATERIALS AND METHODS: Our first patient underwent salvage radical prostatectomy after developing high-risk localized prostate cancer after initial high-intensity focused ultrasound. The prostate was radically resected after stepwise posterior and anterior dissections. A flap of perivesical fat with a wide-based pedicle overlying the bladder dome was developed until it was rotated, positioned, and tethered overlying the anterior rectal wall in a tension-free manner. This perivesical fat interposition may have protected a radiated anterior rectal wall from future complications. In the second case, a recurrent vesicovaginal fistula that persisted for 2years postabdominal hysterectomy was repaired using the robotic approach. After fistula excision, layer closure, and perivesical flap interposition, successful repair was achieved. The third patient, who had a history of colon cancer managed with partial colectomy and radiation, developed a recurrent colovesical fistula, which was successfully repaired. Postrepair, a perivesical flap was developed and secured over the site. RESULTS: In the immediate postoperative follow-up period, there were no surgical complications. Long-term follow-up ranges from 1month to 3years without evidence of complication. CONCLUSION: In cases where omentum interposition is not feasible, our novel technique of a perivesical fat flap is a successful alternative for complex reconstruction.

Acute Cardiovascular Complications of COVID-19: A Systematic Review.

Since the pandemic in 2019, coronavirus 2019 (COVID-19) has continued to be linked with a variety of organ systems and complications. While it is generally considered a respiratory disease, its link with the heart is widely discussed in the literature. This article focuses on the acute cardiovascular complications of COVID-19 and the possible predictors of these complications. Our study included 97 articles (58 case reports, eight case series, 23 retrospective cohort studies, five prospective cohort studies, and three cross-sectional studies). Several mechanisms have been proposed to explain COVID-19-induced cardiovascular complications, with cytokine-induced inflammation and direct cardiac damage noted as the significant focus. Patients with underlying cardiovascular complications such as hypertension and diabetes were noted to be at increased risk of acute cardiovascular complications, as well as an increased risk of severe disease and death. Also, acute myocardial infarction and arrhythmias were two of the most common acute cardiovascular complications noted in our review. Other acute cardiovascular complications are myocarditis, takotsubo syndrome, acute thromboembolic events, and pericardial complications. This article provides an updated review of acute cardiovascular complications of COVID-19, its pathogenesis, and risk stratification and emphasizes the need for high suspicion in patients with underlying cardiovascular risk factors.

Tachycardia-Induced Cardiomyopathy in a Young Adult: The Significance of Early Diagnosis and Treatment.

Tachycardia-induced cardiomyopathy (TIC) is gradually gaining the attention it deserves as one of the most common causes of reversible cardiomyopathy. Although TIC appears common, there has been limited data, especially among young adults. Patients with tachycardia and left ventricular dysfunction should be suspected of having TIC, with or without established etiology of heart failure, because TIC can develop by itself or contribute to cardiac dysfunction. We present a case of a previously healthy 31-year-old woman with persistent nausea and vomiting, poor oral intake, fatigue, and persistent palpitations. Vital signs at presentation were significant for tachycardia of 124 beats per minute, which she reported was similar to her baseline heart rate of 120s per minute. There were no apparent signs of volume overload at the presentation. Labs were significant for microcytic anemia with hemoglobin/hematocrit of 10.1/34.4 g/dL, and mean corpuscular volume was low at 69.4 fL; other labs were unremarkable. Transthoracic echocardiography obtained at admission was significant for mild global left ventricular hypokinesis, systolic dysfunction with an estimated left ventricular ejection fraction of 45-50%, and mild tricuspid regurgitation. Persistent tachycardia was suggested as the primary cause of cardiac dysfunction. The patient was subsequently started on guideline-directed medical therapy, including beta blockers, angiotensin-converting enzyme inhibitors, and spironolactone, with eventual normalization of the heart rate. Anemia too was also treated. Follow-up transthoracic echocardiography done four weeks after was notable for significant interval improvement in left ventricular ejection fraction of 55-60%, with a heart rate of 82 beats per minute. The case illustrates the need for early identification of TIC regardless of the patient's age. It is essential that physicians consider it in the differential diagnosis of new-onset heart failure because prompt treatment leads to the resolution of symptoms and improvement of ventricular function.

Thyrotoxicosis-Induced Cardiogenic Shock: Acute Management Using a Multidisciplinary Approach.

The development of heart failure and cardiomyopathy has been identified as an infrequent but life-threatening complication of thyrotoxicosis or thyroid storm. Thyrotoxicosis-induced cardiomyopathy and cardiogenic shock have been shown to be one of the major causes of sudden mortality in adults. However, the treatment of thyrotoxicosis with non-cardioselective beta-blockers has been implicated in the development of severe decompensation and even cardiogenic shock if cardiac function is not known and often requires a multidisciplinary care team to address it. Here, we have reported the case of a 63-year-old male with a past medical history of hyperthyroidism who presented to the emergency room with persistent shortness of breath. Vital signs were notable for hypotension, tachycardia with an irregular heartbeat, with ECG suggestive of atrial fibrillation with a rapid ventricular rate. The thyroid function test was significant for severely suppressed TSH, and the Burch-Wartofsky Score was >45. The patient rapidly decompensated shortly after being given IV metoprolol, subsequently requiring intubation and pressor support. Two-dimensional (2D) echocardiography (or echo) done afterward was significant for four-chamber dilation with mild global hypokinesis and reduced left ventricular ejection fraction. Endocrinology, Cardiology, and Pulmonary Critical Care teams were consulted to assist in multi-modality management. The administration of a non-cardioselective beta-blocker in decompensated heart failure was suggested as the cause of the rapid deterioration. Through a multi-modality management approach, the patient subsequently improved and was eventually discharged with the resolution of thyroid storm and cardiogenic shock, and with close follow-up with the primary care provider, endocrinologist, and cardiologist. This case illustrates the significance of a multidisciplinary team approach in the acute management of thyrotoxicosis-induced cardiogenic shock, as recommendations from the team were instrumental in helping the patient recover from the acute phase of the illness. Also, this case further highlights the significance of assessing the cardiac function, preferably performing echo before starting the patient on beta-blockers.

Diversity in modern heart failure trials: Where are we, and where are we going.

Over the last three decades, increased attention has been given to the representation of historically underrepresented groups within the landscape of pivotal clinical trials. However, recent events (i.e., coronavirus pandemic) have laid bare the potential continuation of historic inequities in available clinical trials and studies aimed at the care of broad patient populations. Anecdotally, cardiovascular disease (CVD) has not been immune to these disparities. Within this review, we examine and discuss recent landmark CVD trials, with a specific focus on the representation of Blacks within several critically foundational heart failure clinical trials tied to contemporary treatment strategies and drug approvals. We also discuss solutions for inequities within the landscape of cardiovascular trials. Building a more diverse clinical trial workforce coupled with intentional efforts to increase clinical trial diversity will advance equity in cardiovascular care.

Adverse Events Following Transcatheter Edge-to-Edge Repair (TEER) Using MitraClip: Lessons Learned From the Manufacturer and User Facility Device Experience (MAUDE) Registry.

OBJECTIVE: The MitraClip from Abbott is FDA approved intracardiac implantable device for transcatheter edge-to-edge repair (TEER). Despite a few previously published studies, there is limited safety data for its use in clinical practice, hence, we designed this study using data obtained from a safety nationwide database to demonstrate the safety profile of MitraClip. METHODS: The first two of the five authors independently queried all reported adverse events from the United State Food and Drug Administration [FDA] Manufacturer and User Facility Device Experience [MAUDE] registry from January 2014 to December 2020. The primary end point was trend in reported fatal events obtained from this database. The secondary end points included the causes of reported nonfatal reports from the MAUDE registry. The trend of reported fatal events was assessed using the Cochran Armitage trend test over the period of the study. RESULTS: During the study period, subjects included 3370 patients whose MitraClip-associated adverse events were reported and captured by MAUDE registry. Of these, 211 were fatal and 3159 nonfatal events. Fatal event reports resulted deaths and reported nonfatal events were from injuries and device system malfunction. This study demonstrated an initial upward trend from 2014 to 2015 then a subsequent statistically significant downward trend in reported fatal events from 2015 to 2020 (Cochran-Armitage test P = 0.039). The peak proportion of reported fatal events occurred in 2015, (n = 44; representing 1.25% of reported adverse events) and lowest proportion of reported fatal events took place in 2020 (n = 19; representing 0.56% of reported adverse events). The most reported nonfatal events were from malfunctioning of MitraClip system (n = 1170; representing 37% of reported nonfatal events), new unremarkable repolarization abnormalities on periprocedural EKG (n = 864; representing 27% of reported nonfatal events), leaflet rupture (n = 651; representing 21% of reported nonfatal events), and cardiogenic shock (n = 170; representing 5% of reported nonfatal events). CONCLUSIONS: This analysis of the MAUDE Registry indicated, especially within the confines of this study's limitations and poor data quality of information, an apparent downward trend of reported fatal events over the study period. Even though conclusive attributions cannot be made regarding this important finding, perhaps, this points to early evidence of a potential institutional or operator learning curve with this device. However, in view of the inferior quality of the data accrued from the MAUDE Registry, more high-precision studies are needed to better understand these changes, as the utility of MitraClip, becomes more established in clinical practice.

Low Prevalence of Clinically Apparent Cardiac Amyloidosis Among Carriers of Transthyretin V122I Variant in a Large Electronic Medical Record.

BACKGROUND: Transthyretin (TTR) gene mutations are the most common cause of hereditary amyloidosis. Valine replaced by isoleucine in position 122 (V122I) variant is common, particularly in the black population. Carriers of V122I have increased risk for developing cardiac amyloidosis. Despite a relatively high prevalence, the penetrance of V122I is not firmly established. This study sought to determine the prevalence of clinically apparent cardiac amyloidosis among carriers of the TTR V122I variant. METHODS: BioVU, a Vanderbilt University resource linking DNA samples and pre-existing genetic data to de-identified electronic medical records was used to identify TTR V122I mutation carriers. Automated billing code queries (International Classification of Diseases, 9th revision codes), problem list searches, and manual chart reviews were used to identify subjects with clinically diagnosed cardiac amyloidosis. RESULTS: Among 28,429 subjects with available genotype data, 129 were V122I carriers. Carriers had a median age of 42 years (interquartile range 16-64). Noncarriers had a median age of 62 years, (interquartile range 41-77). The carrier rate was 3.7% in blacks and 0.02% in whites. Overall, the prevalence of clinically apparent cardiac amyloidosis was 0.8% in carriers and 0.04% in noncarriers (P = .05). Above age 60, the prevalence of cardiac amyloidosis was 2.6% in carriers and 0.06% in noncarriers (P = .03). CONCLUSION: Carriers of the TTR V122I variant are at a higher risk for development of cardiac amyloidosis, particularly at age>60 years. However, clinically apparent cardiac amyloidosis in this population was uncommon. These results support that the penetrance of TTR V122I is age dependent and suggest it may be significantly lower than previously reported.

The Association of Black Cardiologists (ABC) Cardiovascular Implementation Study (CVIS): A Research Registry Integrating Social Determinants to Support Care for Underserved Patients.

African Americans, other minorities and underserved populations are consistently under- represented in clinical trials. Such underrepresentation results in a gap in the evidence base, and health disparities. The ABC Cardiovascular Implementation Study (CVIS) is a comprehensive prospective cohort registry that integrates social determinants of health. ABC CVIS uses real world clinical practice data to address critical gaps in care by facilitating robust participation of African Americans and other minorities in clinical trials. ABC CVIS will include diverse patients from collaborating ABC member private practices, as well as patients from academic health centers and Federally Qualified Health Centers (FQHCs). This paper describes the rationale and design of the ABC CVIS Registry. The registry will: (1) prospectively collect socio-demographic, clinical and biospecimen data from enrolled adults, adolescents and children with prioritized cardiovascular diseases; (2) Evaluate the safety and clinical outcomes of new therapeutic agents, including post marketing surveillance and pharmacovigilance; (3) Support National Institutes of Health (NIH) and industry sponsored research; (4) Support Quality Measures standards from the Center for Medicare and Medicaid Services (CMS) and Commercial Health Plans. The registry will utilize novel data and technology tools to facilitate mobile health technology application programming interface (API) to health system or practice electronic health records (EHR). Long term, CVIS will become the most comprehensive patient registry for underserved diverse patients with cardiovascular disease (CVD) and co morbid conditions, providing real world data to address health disparities. At least 10,000 patients will be enrolled from 50 sites across the United States.

Complicated Infective Endocarditis Limited to a Chiari Network.

INTRODUCTION: The Chiari network is an uncommon vestigial structure of the heart that is often clinically insignificant. We present an unusual case of infective endocarditis affecting only the Chiari network in a patient who presented with septic emboli to the lungs and brain. CASE SUMMARY: A 61-year-old man was admitted with a 2-month history of hemoptysis, pleuritic chest pain, and right upper extremity numbness and weakness. He was found to have multifocal bilateral pulmonary opacities and an abscess collection in the brain. Blood cultures grew Streptococcus intermedius and transthoracic echocardiogram (TTE) was normal. Subsequent transesophageal echocardiogram (TEE) revealed an 8.3 × 4.6 mm vegetation arising from the Chiari network, close to the right atrial appendage, without involvement of the tricuspid valve or any of the other valves. There were no atrial or ventricular septal defects. He was treated with appropriate antibiotics with improvement of symptoms. Repeat imaging showed improvement of the lung opacities, but not the brain abscess, warranting transfer to another hospital for neurosurgical intervention. CONCLUSION: The diagnosis and management of isolated Chiari network endocarditis require a high index of clinical suspicion. A multidisciplinary approach incorporating both medical and surgical approaches where necessary is essential for optimal outcome.

Motor Response Matters: Optimizing Lead Placement Improves Sacral Neuromodulation Outcomes.

PURPOSE: We sought to determine the usefulness of motor responses during sacral neuromodulation lead placement by testing the hypothesis that a greater number of motor responses during intraoperative electrode testing would be associated with more durable therapy. MATERIALS AND METHODS: We retrospectively reviewed all sacral neuromodulation lead placements at a large academic center from 2010 to 2015. Included in study were all unilateral sacral lead placements for which the presence or absence of a motor response was documented discretely for each electrode. Motor responses were quantified into separate subscores, including bellows and toe response subscores (each range 0 to 4) for a possible maximum total score of 8 when combined. Revision surgery was the primary outcome. Univariate and multivariate analyses were performed for factors associated with lead revision. RESULTS: A total of 176 lead placements qualified for analysis. Mean ± SD cohort age was 58.4 ± 15.9 years, 86.4% of the patients were female and 93.2% had undergone implantation for overactive bladder. Median followup was 10.5 months (range 2 to 36). Overall 34 patients (19%) required lead revision. Revision was negatively associated with the total electrode response score (p = 0.027) and the toe subscore (p = 0.033) but not with the bellows subscore (p = 0.183). Predictors of revision on logistic regression included age less than 59 years at implantation (OR 5.5, 95% CI 2-14) and a total electrode response score less than 4 (OR 4.2, 95% CI 1.4-12.8). CONCLUSIONS: Fewer total electrode responses and specifically fewer toe responses were associated with sacral neuromodulation lead revision. These data suggest that placing a lead with more toe responses during testing may result in more durable sacral neuromodulation therapy.

Impact of Age and Comorbidities on Use of Sacral Neuromodulation.

PURPOSE: We investigated the influence of patient age on sacral nerve stimulation trial outcomes, device implantation and treatment durability. MATERIALS AND METHODS: We analyzed a database of all sacral nerve stimulation procedures performed between 2012 and 2014 at a high volume institution for associations of patient age with sacral nerve stimulation indication, trial stimulation success, device revision and device explantation. RESULTS: In a cohort of 356 patients those with nonobstructive urinary retention and urgency-frequency were younger than patients with urgency urinary incontinence. Trial stimulation success did not differ by age in stage 1 and percutaneous nerve evaluation trials (p = 0.51 and 0.84, respectively). Logistic regression identified greater odds of trial success in females compared to males (OR 2.97, 95% CI 1.32-6.04, p = 0.009) and for urgency urinary incontinence compared to urgency-frequency (OR 3.02, 95% CI 1.39-6.50, p = 0.006). In analyzed patients there were 119 surgical revisions, including battery replacement, and 53 explantations. Age was associated with a decreased risk of revision with 3% lower odds per each additional year of age (OR 0.97, 95% CI 0.95-0.98, p <0.0001). While age did not influence explantation, for each body mass index unit there was a 5% decrease in the odds of explantation (OR 0.95, 95% CI 0.91-0.98). CONCLUSIONS: In contrast to previous studies, older patients experienced no difference in the sacral nerve stimulation response in stimulation trials and no difference in the implantation rate. Furthermore, age was modestly protective against device revision. This suggests that age alone should not negatively predict sacral nerve stimulation responses.

Impact of Short-Stay Urethroplasty on Health-Related Quality of Life and Patient's Perception of Timing of Discharge.

Objective. To evaluate health-related quality of life in patients after a short-stay or outpatient urethroplasty. Methods. Over a 2-year period a validated health-related quality-of-life questionnaire, EuroQol (EQ-5D), was administered to all patients after urethroplasty. Postoperatively patients were offered to be sent home immediately or to stay overnight. Within 24 hours after discharge they were assessed for mobility, self-care, usual activities, pain or discomfort, and anxiety and depression. An additional question assessing timing of discharge was added to the survey. Clinical and operative characteristics were examined. Results. Forty-eight patients after anterior urethroplasty completed the survey. Mean age and mean stricture length were 51.6 years (21-78) and 60 mm (5-200 mm), respectively. Most etiologies were idiopathic (50% n = 24), trauma (19%, n = 9), and iatrogenic (19%, n = 9). Forty-one patients (85%) stayed overnight, while 7 patients (15%) chose to be discharged the same day. Overall, ninety-six percent were discharged within 23 hours of surgery. In the short-stay and the outpatient cohorts, 90% and 86%, respectively, felt they were discharged on time. No patient reported a severe problem with postoperative pain or mobility. Conclusions. The majority of patients discharged soon after their procedure felt that discharge timing was appropriate and their health-related quality of life was only minimally affected.

Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3 PUFAs and in 30 patients (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the 2 groups (hazard ratio 1.20; 95% confidence interval 0.76 to 1.90, adjusted p = 0.438). Compared with placebo, n-3 PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, N-terminal-pro-brain-type natriuretic peptide or F2-isoprostanes. In conclusion, in patients with paroxysmal or persistent AF, treatment with n-3 PUFAs 4 g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress. (Clinical trial registration number, NCT 00552084.).

Cardiovascular outcomes of a positive nuclear stress test but negative coronary angiography in a multiethnic male predominant cohort.

BACKGROUND: Patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging (MPI), but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma. They are often dismissed as having 'false-positive MPI'. Moreover, a majority of the available long-term outcome data for it has been derived from homogenous female populations. In this study, we sought to evaluate the long-term outcomes of this presentation in a multiethnic male-predominant cohort. MATERIALS AND METHODS: We retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on MPI, but with no significant angiographic disease on subsequent cardiac catheterization (cases). The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute myocardial infarction and stroke) post-index coronary angiogram was tracked. Similar data was collected for 37 patients who also presented with chest pain, but normal MPI over the same period (controls). Overall average follow-up was over 22 months. RESULTS: Fifty-three percent (26/47) of the cases had one or more of the adverse outcomes as compared with 22% (8/37) of controls (P < 0.01). Of these, 13 (50.0%) and 3 (37.5%) were males, respectively. CONCLUSIONS: Ischemia on MPI is predictive of long-term adverse cardiovascular outcomes despite normal ('false-negative') coronary angiography. This appears to be gender-neutral.

Polymorphism in the SCN9A voltage-gated sodium channel gene associated with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To determine whether an association exists between interstitial cystitis/bladder pain syndrome (IC/BPS) and a nonsynonymous single nucleotide polymorphism in the SCN9A voltage-gated sodium channel gene previously associated with other chronic pain syndromes. MATERIALS AND METHODS: Germline deoxyribonucleic acid was sampled from archived bladder biopsy specimens from patients with a documented diagnosis of IC/BPS. Deoxyribonucleic acid from hysterectomy specimens was obtained as a control population. The genotype of single nucleotide polymorphism rs6746030 was determined by deoxyribonucleic acid sequencing after polymerase chain reaction amplification. Contingency analysis of genotypes was performed using Pearson's chi-square test and Fisher's exact test. RESULTS: Polymerase chain reaction product was obtained from 26 of 31 control specimens and from 53 of 57 IC/BPS biopsy specimens. Of the 26 control subjects, 3 (11.5%) were genotype AG and 23 were GG. In contrast, AA or AG genotypes were present in 21 of 53 (39.6%) patients with IC/BPS, a statistically significant difference compared with the controls (Pearson's chi-square, P=.036). Similarly, the A allele was at a greater frequency in the IC/BPS group using Fisher's exact test (P=.009). CONCLUSION: These data strongly suggest that pain perception in at least a subset of patients with IC/BPS is influenced by this polymorphism in the SCN9A voltage-gated sodium channel.

Race-specific impact of atrial fibrillation risk factors in blacks and whites in the southern community cohort study.

Despite a greater burden of traditional risk factors, atrial fibrillation (AF) is less common among blacks than whites for reasons that are unclear. The aim of this study was to examine race- and gender-specific influences of demographic, lifestyle, anthropometric, and medical factors on AF in a large cohort of blacks and whites. Among white and black participants in the Southern Community Cohort Study (SCCS) aged ≥65 years receiving Medicare coverage from 1999 to 2008 (n = 8,836), diagnoses of AF (International Classification of Diseases, Ninth Revision, Clinical Modification code 427.3) were ascertained. Multivariate logistic regression was used to compute AF odds ratios associated with participant characteristics, including histories of hypertension, diabetes, stroke, and myocardial infarction or coronary artery bypass graft surgery, ascertained at cohort entry. Over an average of 5.7 years of Medicare coverage, AF was diagnosed in 1,062 participants. AF prevalence was significantly lower among blacks (11%) than whites (15%) (p <0.0001). Odds ratios for AF increased with age and were higher among men, the tall and obese, and patients with each of the co-morbid conditions, but the AF deficit among blacks compared to whites persisted after adjustment for these factors (odds ratio 0.64, 95% confidence interval 0.55 to 0.73). The patterns of AF risk were similar for blacks and whites, although associations with hypertension, diabetes, and stroke were somewhat stronger among blacks. In conclusion, these findings confirm the lower prevalence of AF among blacks than whites and suggest that traditional risk factors for AF apply similarly to the 2 groups and thus do not appear to explain the AF paradox in blacks.

Characterization of genome-wide association-identified variants for atrial fibrillation in African Americans.

BACKGROUND: Despite a greater burden of risk factors, atrial fibrillation (AF) is less common among African Americans than European-descent populations. Genome-wide association studies (GWAS) for AF in European-descent populations have identified three predominant genomic regions associated with increased risk (1q21, 4q25, and 16q22). The contribution of these loci to AF risk in African American is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We studied 73 African Americans with AF from the Vanderbilt-Meharry AF registry and 71 African American controls, with no history of AF including after cardiac surgery. Tests of association were performed for 148 SNPs across the three regions associated with AF, and 22 SNPs were significantly associated with AF (P<0.05). The SNPs with the strongest associations in African Americans were both different from the index SNPs identified in European-descent populations and independent from the index European-descent population SNPs (r(2)<0.40 in HapMap CEU): 1q21 rs4845396 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.13-0.67, P = 0.003), 4q25 rs4631108 (OR 3.43, 95% CI 1.59-7.42, P = 0.002), and 16q22 rs16971547 (OR 8.1, 95% CI 1.46-45.4, P = 0.016). Estimates of European ancestry were similar among cases (23.6%) and controls (23.8%). Accordingly, the probability of having two copies of the European derived chromosomes at each region did not differ between cases and controls. CONCLUSIONS/SIGNIFICANCE: Variable European admixture at known AF loci does not explain decreased AF susceptibility in African Americans. These data support the role of 1q21, 4q25, and 16q22 variants in AF risk for African Americans, although the index SNPs differ from those identified in European-descent populations.