Circulation: Arrhythmia and Electrophysiology
Epicardial fat may have paracrine effects that contribute to cardiovascular pathophysiology. This meta-analysis of 352 275 individuals demonstrates a strong association of increasing epicardial fat with atrial fibrillation, more so than for measures of abnormal or overall adiposity. Studies to assess causality, mechanisms, and the impact of therapeutic strategies are warranted.
Associations of Epicardial, Abdominal, and Overall Adiposity with Atrial Fibrillation
Christopher X. Wong, MBBS, MSc, MPH, PhD, Michelle T. Sun, MBBS, Ayodele Odutayo, MD, MSc, Connor A. Emdin, HBSc, DPhil, Rajiv Mahajan, MBBS, PhD, Dennis H. Lau, MBBS, PhD, Rajeev K. Pathak, MBBS, PhD, Dennis T. Wong, BMed, PhD, Joseph B. Selvanayagam, MBBS, DPhil, Prashanthan Sanders, MBBS, PhD, Robert Clarke, MD, FRCP
Correspondence to: Christopher X. Wong, MBBS, MSc, MPH, PhD, Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Dr, Oxford, United Kingdom. E-mail.
Background: Although adiposity is increasingly recognized as a risk factor for atrial fibrillation (AF), the importance of epicardial fat compared with other adipose tissue depots remains uncertain. We sought to characterize and compare the associations of AF with epicardial fat and measures of abdominal and overall adiposity.
Methods and Results: We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval [CI], 1.89–3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45–3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24–9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66–2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25–1.41) for waist circumference, 1.11 (95% CI, 1.08–1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17–1.27) for body mass index.
Conclusions: Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity. Further studies are needed to assess the mechanisms and clinical relevance of epicardial fat.
Circ Arrhythm Electrophysiol. 2016;9:e004378. DOI:10.1161/CIRCEP.116.004378.
Circulation: Cardiovascular Genetics
Large scale genomic research has identified many unique genetic variants associated with coronary heart disease (CHD). This study evaluated the possible improvement of the predictive capacity of genetic risk scores (GRSs) when added to traditional risk factor models with regard to CHD risk. In this large cohort of individuals of European descent, 4 genetic risk scores consisting of between 8 and 51 previously established variants were studied. The results demonstrate modest but significant improvement in discrimination and risk classification for CHD.
Clinical Utility of Multimarker Genetic Risk Scores for Prediction of Incident Coronary Heart Disease
A Cohort Study Among Over 51 Thousand Individuals of European Ancestry
Carlos Iribarren, MD, MPH, PhD, Meng Lu, MD, MS, Eric Jorgenson, PhD, Manuel Martínez, BSc, Carla Lluis-Ganella, MSc, PhD, Isaac Subirana, MSc, PhD, Eduardo Salas, MD, PhD, Roberto Elosua, MD, PhD
Correspondence to: Carlos Iribarren, MD, MPH, PhD, Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612. E-mail
Background: We evaluated whether including multilocus genetic risk scores (GRSs) into the Framingham Risk Equation improves the predictive capacity, discrimination, and reclassification of asymptomatic individuals with respect to coronary heart disease (CHD) risk.
Methods and Results: We performed a cohort study among 51 954 European-ancestry members of a Northern California integrated healthcare system (67% female; mean age 59) free of CHD at baseline (2007–2008). Four GRSs were constructed using between 8 and 51 previously identified genetic variants. After a mean (±SD) follow-up of 5.9 (±1.5) years, 1864 incident CHD events were documented. All GRSs were linearly associated with CHD in a model adjusted by individual risk factors: hazard ratio (95% confidence interval) per SD unit: 1.21 (1.15–1.26) for GRS_8, 1.20 (1.15–1.26) for GRS_12, 1.23 (1.17–1.28) for GRS_36, and 1.23 (1.17–1.28) for GRS_51. Inclusion of the GRSs improved the C statistic (ΔC statistic =0.008 for GRS_8 and GRS_36; 0.007 for GRS_12; and 0.009 for GRS_51; all P<0.001). The net reclassification improvement was 5% for GRS_8, GRS_12, and GRS_36 and 4% for GRS_51 in the entire cohort and was (after correcting for bias) 9% for GRS_8 and GRS_12 and 7% for GRS_36 and GRS_51 when analyzing those classified as intermediate Framingham risk (10% to 20%). The number required to treat to prevent 1 CHD after selectively treating with statins up-reclassified subjects on the basis of genetic information was 36 for GRS_8 and GRS_12, 41 for GRS_36, and 43 for GRS_51.
Conclusions: Our results demonstrate significant and clinically relevant incremental discriminative/predictive capability of 4 multilocus GRSs for incident CHD among subjects of European ancestry.
Circ Cardiovascular Genetics. 2016;9:531–540. DOI: 10.1161/CIRCGENETICS.116.001522.
Circulation: Cardiovascular Imaging
Although it is known that arterial dysfunction contributes to the progression of cardiovascular disease (CVD), it is not known which of the various measures of aortic stiffness and vasodilator function are most strongly associated with incident CVD. This study assessed the hazards of multiple individual measures of vascular function with incident CVD in Framingham Heart Study participants. Higher carotid pulse-wave velocity and lower hyperemic mean flow velocity were most robustly associated with events. Mediation analyses suggested that reduced flow velocity mediates a portion of the association of arterial stiffness with CVD, suggesting that microvascular damage and remodeling contribute to the association of aortic stiffness with CVD events. Further research on preventive measures focusing on aortic stiffness and microvascular remodeling is warranted.
Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events
The Framingham Heart Study
Leroy L. Cooper, PhD, Joseph N. Palmisano, MA, MPH, Emelia J. Benjamin, MD, ScM, Martin G. Larson, ScD, Ramachandran S. Vasan, MD, Gary F. Mitchell, MD, Naomi M. Hamburg, MD, MS
Correspondence to: Naomi M. Hamburg, MD, MS, Whitaker Cardiovascular Institute, Boston University School of Medicine, 88 E Newton St, Suite C-818, Boston, MA 02118. E-mail
Background: Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied.
Methods and Results: We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02–13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07–1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71–0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99–1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90–1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69–1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity.
Conclusions: Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling.
Circ Cardiovasc Imaging. 2016;9:e004979. DOI: 10.1161/CIRCIMAGING.116.004979
Circulation: Cardiovascular Interventions
Recent guidelines recommend drug-eluting stent (DES) implantation for DES restenosis; however, there are inadequate data about long-term efficacy with regard to late restenosis. This study analyzed lesions from patients with lesions treated with first-generation and second-generation DES, with scheduled angiography at 8 and 20 months after stent placement. Late restenosis (between 8 and 20 months) occurred in approximately 15% of cases and did not differ between first- and second-generation DES. This study demonstrates that late restenosis remains a problem even when second-generation DES are used to treat DES restenosis.
Late Restenosis After Both First-Generation and Second-Generation Drug-Eluting Stent Implantations Occurs in Patients with Drug-Eluting Stent Restenosis
Seiji Habara, MD, Kazushige Kadota, MD, Akimune Kuwayama, MD, Takenobu Shimada, MD, Masanobu Ohya, MD, Katsuya Miura, MD, Hidewo Amano, MD, Shunsuke Kubo, MD, Yusuke Hyodo, MD, Suguru Otsuru, MD, Takeshi Tada, MD, Hiroyuki Tanaka, MD, Yasushi Fuku, MD, Tsuyoshi Goto, MD
Correspondence to: Seiji Habara, MD, Department of Cardiology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki-shi, Okayama 710–8602, Japan. E-mail
Background: There are currently inadequate data about whether late restenosis occurs after drug-eluting stent (DES) implantation in patients with DES restenosis.
Methods and Results: We collected data for 608 patients who received revascularization for DES restenosis between 2004 and 2012 and analyzed 688 lesions: 359 lesions treated with a first-generation DES (first DES) and 329 lesions treated with a second-generation DES (second DES). Two serial angiographic follow-ups were routinely planned for the patients (at 8 and 20 months after the procedure). Early follow-up angiography was performed for 620 lesions (90.1%), and recurrent restenosis occurred in 84 lesions (25.8%) in the first DES group and in 72 lesions (24.5%) in the second DES group (P=0.78). Target lesion revascularization was performed for 69 lesions (21.2%) in the first DES group and for 48 lesions (16.3%) in the second DES group (P=0.15). Late follow-up angiography was performed for 438 (87.1%) of the remaining 503 lesions (excluding target lesion revascularization lesions), and late restenosis was found in 35 lesions (15.8%) in the first DES group and in 28 lesions (14.7%) in the second DES group (P=0.79). Nonfocal-type restenosis, percentage diameter stenosis after the procedure, previous stent size ≤2.5 mm, and right coronary artery ostial lesion were independent predictors of early restenosis. Nonfocal-type restenosis, percentage diameter stenosis at early follow-up, and stent fracture were independent predictors of late restenosis.
Conclusions: Late restenosis occurs after both first DES implantation and second DES implantation for DES restenosis.
Circ Cardiovasc Interv. 2016;9:e004449. DOI: 10.1161/CIRCINTERVENTIONS.116.004449.
Circulation: Cardiovascular Quality and Outcomes
Because of low rates of bystander delivery of cardiopulmonary resuscitation (CPR), there is a desire to simplify CPR training to allow broader dissemination. This randomized trial compared CPR quality at 6 months after training with video-only training (without a manikin) versus CPR training with a video self-instruction kit (with a manikin). The study showed noninferior results for video-only training for 1 measure of CPR quality (compression rate), but inferior results for another (compression depth). These findings suggest that while video-only training may allow for broader dissemination, there may be tradeoffs with regard to CPR quality.
Video-Only Cardiopulmonary Resuscitation Education for High-Risk Families Before Hospital Discharge
A Multicenter Pragmatic Trial
Audrey L. Blewer, MPH, Mary E. Putt, PhD, ScD, Lance B. Becker, MD, Barbara J. Riegel, PhD, RN, Jiaqi Li, PhD, Marion Leary, MPH, MSN, RN, Judy A. Shea, PhD, James N. Kirkpatrick, MD, Robert A. Berg, MD, Vinay M. Nadkarni, MD, Peter W. Groeneveld, MD, MS, Benjamin S. Abella, MD, MPhil, On behalf of the CHIP Study Group
Correspondence to: Benjamin S. Abella, MD, MPhil, Department of Emergency Medicine, Center for Resuscitation Science, University of Pennsylvania, 3400 Spruce St, Ground Ravdin, Philadelphia, PA 19104. E-mail
Background: Cardiopulmonary resuscitation (CPR) training rates in the United States are low, highlighting the need to develop CPR educational approaches that are simpler, with broader dissemination potential. The minimum training required to ensure long-term skill retention remains poorly characterized. We compared CPR skill retention among laypersons randomized to training with video-only (VO; no manikin) with those trained with a video self-instruction kit (VSI; with manikin). We hypothesized that VO training would be noninferior to the VSI approach with respect to chest compression (CC) rate.
Methods and Results: We performed a prospective, cluster randomized trial of CPR education for family members of patients with high-risk cardiac conditions on hospital cardiac units, using a multicenter pragmatic design. Eight hospitals were randomized to offer either VO or VSI training before discharge using volunteer trainers. CPR skills were assessed 6 months post training. Mean CC rate among those trained with VO compared with those trained with VSI was assessed with a noninferiority margin set at 8 CC per min; as a secondary outcome, mean differences in CC depth were assessed. From February 2012 to May 2015, 1464 subjects were enrolled and 522 subjects completed a skills assessment. The mean CC rates were 87.7 (VO) CC per min and 89.3 (VSI) CC per min; we concluded noninferiority for VO based on a mean difference of −1.6 (90% confidence interval, −5.2 to 2.1). The mean CC depth was 40.2 mm (VO) and 45.8 mm (VSI) with a mean difference of −5.6 (95% confidence interval, −7.6 to −3.7). Results were similar after multivariate regression adjustment.
Conclusions: In this large, prospective trial of CPR skill retention, VO training yielded a noninferior difference in CC rate compared with VSI training. CC depth was greater in the VSI group. These findings suggest a potential trade-off in efforts for broad dissemination of basic CPR skills; VO training might allow for greater scalability and dissemination, but with a potential reduction in CC depth.
Circ Cardiovasc Qual Outcomes. 2016;9:740–748. DOI: 10.1161/CIRCOUTCOMES.116.002493.
Circulation: Heart Failure
There are limited outcome data defining the appropriate use of extracorporeal membrane oxygenation (ECMO) despite the large increase in its utilization. This retrospective cohort analysis identified improvement in outcomes of patients receiving ECMO despite greater comorbidity, but highlighted very high mortality risk among elderly patients and those requiring CPR prior to ECMO initiation. These findings highlight a need for a selective approach when choosing to use this highly invasive procedure, particularly for elderly patients.
Extracorporeal Membrane Oxygenation in New York State
Trends, Outcomes, and Implications for Patient Selection
Jaya Batra, BA, Nana Toyoda, MD, Andrew B. Goldstone, MD, Shinobu Itagaki, MD, MS, Natalia N. Egorova, PhD, Joanna Chikwe, MD
Correspondence to: Joanna Chikwe, MD, Department of Cardiovascular Surgery, Mount Sinai Hospital, 1190 Fifth Ave, New York, NY 10029. E-mail
Background: Utilization of extracorporeal membrane oxygenation (ECMO) is expanding despite limited outcome data defining appropriate use.
Methods and Results: To quantify determinants of early and 1-year survival after ECMO in adult patients, we conducted a retrospective cohort analysis of 1286 patients aged ≥18 years who underwent ECMO in New York State from 2003 to 2014. Median follow-up time was 4.9 months (range, 0–12 months). ECMO utilization increased from 13 patients in 8 hospitals in 2003 to 330 patients in 30 hospitals in 2014. Compared with patients undergoing ECMO before 2009, later patients were older (54.4 versus 52.3 years; P=0.013) and more likely to have major comorbidity including chronic kidney disease (25.2% versus 13.2%; P=0.02) and liver disease (20.0% versus 10.7%; P=0.001). In the overall cohort, 30-day mortality was 52.2% (95% confidence interval, 49.5–54.9). Mortality at 30 days was 65.2% for patients aged ≥75 years (n=73/112) and 74.6% in patients who required cardiopulmonary resuscitation (n=91/122). Survival at 1 year was 38.4% (95% confidence interval, 35.7–41.0). The 30-day mortality and 1-year survival improved across the study period. In multivariable analysis, earlier year of ECMO, lower hospital volume, indication for ECMO after a cardiac procedure, cardiopulmonary resuscitation before ECMO placement, and age >65 years were independent predictors of worse survival.
Conclusions: Outcomes of ECMO have improved despite increasing comorbidity. Extreme mortality after ECMO in elderly patients and patients requiring cardiopulmonary resuscitation indicates that less invasive therapeutic or palliative modalities may be more appropriate in this end-of-life setting.
Circ Heart Failure. 2016;9:e003179. DOI: 10.1161/CIRCHEARTFAILURE.116.003179.
Circulation is available at http://circ.ahajournals.org.
- © 2017 American Heart Association, Inc.