Circulation: Arrhythmia and Electrophysiology
This large ECG study investigated the long-term outcomes in individuals with electrocardiographic preexcitation from a primary care population. Patients with ventricular preexcitation had higher risk of atrial fibrillation and heart failure, with the highest risk for heart failure among patients with a right anteroseptal pathway. Although the overall risk of death in those with preexcitation was not increased, a difference occurred across age groups, where patients >65 years of age and with preexcitation had a higher risk of death than the rest of the primary care population.
Electrocardiographic Preexcitation and Risk of Cardiovascular Morbidity and Mortality
Results From the Copenhagen ECG Study
Morten W. Skov, MD
Peter V. Rasmussen, MD
Jonas Ghouse, MD
Steen M. Hansen, MD
Claus Graff, MSc, PhD
Morten S. Olesen, MSc, PhD
Adrian Pietersen, MD
Christian Torp-Pedersen, MD, DMSci
Stig Haunsø, MD, DMSci
Lars Køber, MD, DMSci
Jesper H. Svendsen, MD, DMSci
Anders G. Holst, MD, PhD
Jonas B. Nielsen, MD, PhD
Correspondence to: Jonas Bille Nielsen, MD, PhD, Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, 5804 Medical Science II, 1241 E. Catherine St, Ann Arbor, MI 48109-5618. E-mail
BACKGROUND: The majority of available data on the clinical course of patients with ventricular preexcitation in the ECG originates from tertiary centers. We aimed to investigate long-term outcomes in individuals from a primary care population with electrocardiographic preexcitation.
METHODS AND RESULTS: Digital ECGs from 328 638 primary care patients were collected during 2001 to 2011. We identified 310 individuals with preexcitation (age range, 8–85 years). Data on medication, comorbidity, and outcomes were collected from Danish nationwide registries. The median follow-up time was 7.4 years (quartiles, 4.6–10.3 years). Compared with the remainder of the population, patients with preexcitation had higher adjusted hazards of atrial fibrillation (hazard ratio [HR], 3.12; 95% confidence interval [CI], 2.07–4.70) and heart failure (HR, 2.11; 95% CI, 1.27–3.50). Subgroup analysis on accessory pathway location revealed a higher adjusted hazard of heart failure for a right anteroseptal accessory pathway (HR, 5.88; 95% CI, 2.63–13.1). There was no evidence of a higher hazard of death among individuals with preexcitation when looking across all age groups (HR, 1.07; 95% CI, 0.68–1.68). However, a statistically significant (P=0.01) interaction analysis (<65 versus ≥65 years) indicated a higher hazard of death for patients with preexcitation ≥65 years (HR, 1.85; 95% CI, 1.07–3.18).
CONCLUSIONS: In this large ECG study, individuals with preexcitation had higher hazards of atrial fibrillation and heart failure. The higher hazard of heart failure seemed to be driven by a right anteroseptal accessory pathway. Among elderly people, we found a statistically significant association between preexcitation and a higher hazard of death.
Circ Arrhythm Electrophysiol. 2017;10:e004778. DOI: 10.1161/CIRCEP.116.004778.
Circulation: Cardiovascular Genetics
This study estimated the incremental value of genetic variants as lipid-specific weighted genetic risk scores to improve the prediction of adult dyslipidemia compared with clinical childhood risk factors in the Cardiovascular Risk in Young Finns Study. The results show that the weighted genetic risk scores modestly enhanced the risk prediction of adult dyslipidemia. However, the clinical use and cost effectiveness remain uncertain, and further studies are needed.
Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors
The Cardiovascular Risk in Young Finns Study
Joel Nuotio, MD
Niina Pitkänen, PhD
Costan G. Magnussen, PhD
Marie-Jeanne Buscot, MSc
Mikko S. Venäläinen, MSc
Laura L. Elo, PhD
Eero Jokinen, MD, PhD
Tomi Laitinen, MD, PhD
Leena Taittonen, MD, PhD
Nina Hutri-Kähönen, MD, PhD
Leo-Pekka Lyytikäinen, MD
Terho Lehtimäki, MD, PhD
Jorma S. Viikari, MD, PhD
Markus Juonala, MD, PhD
Olli T. Raitakari, MD, PhD
Correspondence to: Joel Nuotio, MD, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland. E-mail
BACKGROUND: Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures.
METHODS AND RESULTS: Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3–18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P=0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P<0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes.
CONCLUSIONS: The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood.
Circ Cardiovasc Genet. 2017;10:e001604. DOI: 10.1161/CIRCGENETICS.116.001604.
Circulation: Cardiovascular Imaging
This study evaluated factors associated with increased cardiovascular mortality over >10 years in 969 patients with bicuspid aortic valve and dilated proximal ascending aorta. The calculated ratio of ascending aortic area to height was independently associated with death, suggesting that the ascending aortic area/height ratio may be used to risk stratify patients with a bicuspid aortic valve and dilated aorta.
Aortic Cross-Sectional Area/Height Ratio and Outcomes in Patients With Bicuspid Aortic Valve and a Dilated Ascending Aorta
Ahmad Masri, MD
Vidyasagar Kalahasti, MD
Lars G. Svensson, MD, PhD
Alaa Alashi, MD
Paul Schoenhagen, MD
Eric E. Roselli, MD
Douglas R. Johnston, MD
L. Leonardo Rodriguez, MD
Brian P. Griffin, MD
Milind Y. Desai, MD
Correspondence to: Milind Y. Desai, MD, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Ave, Desk J1-5, Cleveland, OH 44195. E-mail
BACKGROUND: In patients with bicuspid aortic valve and dilated proximal ascending aorta, we sought to assess (1) factors associated with increased longer-term cardiovascular mortality and (2) incremental prognostic use of indexing aortic root to patient height.
METHODS AND RESULTS: We studied 969 consecutive bicuspid aortic valve patients (50±13 years; 87% men) with proximal aorta ≥4 cm, who also had a gated contrast-enhanced thoracic computed tomography or magnetic resonance angiography. A ratio of ascending aortic area/height was calculated on tomography, and ≥10 cm2/m was considered abnormal, as previously reported. Society of Thoracic Surgeons score and cardiovascular death were recorded. Greater than or equal to III+ aortic regurgitation and severe aortic stenosis were seen in 37% and 10%, respectively. Society of Thoracic Surgeons score and right ventricular systolic pressure were 2±3 and 15±16 mm Hg, respectively. Abnormal ascending aortic area/height ratio was noted in 33%; 44% underwent ascending aortic surgery at 34 days. At 10.8 years (interquartile range, 9.6–12.3), 82 (9%) died (0.4% in-hospital postoperative mortality). On multivariable Cox survival analysis, ascending aortic area/height ratio (hazard ratio, 2; 95% confidence interval, 1.20–3.35) was associated with cardiovascular death, whereas aortic surgery (hazard ratio, 0.46; confidence interval, 0.26–0.80) was associated with improved survival (both P<0.01). Of the 405 patients with ascending aortic diameter of 4.5 to 5.5 cm, 64% had an abnormal ascending aortic area/height ratio, and 70% deaths occurred in patients with an abnormal ratio.
CONCLUSIONS: In bicuspid aortic valve patients with dilated proximal ascending aorta, ascending aortic area/height ratio was independently associated with cardiovascular death.
Circ Cardiovasc Imaging. 2017;10:e006249. DOI: 10.1161/CIRCIMAGING.116.006249.
Circulation: Cardiovascular Interventions
The value of fractional flow reserve (FFR)-guided decisions in patients with acute coronary syndrome is unclear. In an analysis of 2 European FFR registries, the investigators found that the use of FFR is associated with a high rate of change of the revascularization strategy in patients with and without acute coronary syndrome. The 1-year outcomes suggest that it is safe to integrate FFR information in patients with acute coronary syndrome to reclassify patient management, including FFR-guided decisions to defer revascularization for medical management.
Impact of Routine Fractional Flow Reserve on Management Decision and 1-Year Clinical Outcome of Patients With Acute Coronary Syndromes
PRIME-FFR (Insights From the POST-IT [Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease] and R3F [French FFR Registry] Integrated Multicenter Registries-Implementation of FFR [Fractional Flow Reserve] in Routine Practice)
Eric Van Belle, MD, PhD
Sergio-Bravo Baptista, MD, PhD
Luís Raposo, MD
John Henderson, PhD
Gilles Rioufol, MD, PhD
Lino Santos, MD
Christophe Pouillot, MD
Ruben Ramos, MD
Thomas Cuisset, MD, PhD
Rita Calé, MD
Emmanuel Teiger, MD, PhD
Elisabete Jorge, MD, PhD
Loic Belle, MD
Carina Machado, MD
Didier Barreau, MD
Marco Costa, MD
Michel Hanssen, MD
Eduardo Oliveira, MD
Cyril Besnard, MD
João Costa, MD
Jean Dallongeville, MD, PhD
João Pipa, MD
Georgios Sideris, MD
Nuno Fonseca, MD
Christophe Bretelle, MD
Jorge Guardado, MD
Nicolas Lhoest, MD
Bruno Silva, MD
Pierre Barnay, MD
Maria-João Sousa, MD
Laurent Leborgne, MD, PhD
João Carlos Silva, MD
Flavien Vincent, MD
Alberto Rodrigues, MD
Luís Seca, MD
Renato Fernandes, MD
Patrick Dupouy, MD
For the PRIME-FFR Study Group
Correspondence to: Patrick Dupouy, MD, Pôle Cardio-Vasculaire Interventionnel, Hopital Privé d’Antony, Antony, France. E-mail
BACKGROUND: Fractional flow reserve (FFR) is not firmly established as a guide to treatment in patients with acute coronary syndromes (ACS). Primary goals were to evaluate the impact of integrating FFR on management decisions and on clinical outcome of patients with ACS undergoing coronary angiography, as compared with patients with stable coronary artery disease.
METHODS AND RESULTS: R3F (French FFR Registry) and POST-IT (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease), sharing a common design, were pooled as PRIME-FFR (Insights From the POST-IT and R3F Integrated Multicenter Registries - Implementation of FFR in Routine Practice). Investigators prospectively defined management strategy based on angiography before performing FFR. Final decision after FFR and 1-year clinical outcome were recorded. From 1983 patients, in whom FFR was prospectively used to guide treatment, 533 sustained ACS (excluding acute ST-segment–elevation myocardial infarction). In ACS, FFR was performed in 1.4 lesions per patient, mostly in left anterior descending (58%), with a mean percent stenosis of 58±12% and a mean FFR of 0.82±0.09. In patients with ACS, reclassification by FFR was high and similar to those with non-ACS (38% versus 39%; P=NS). The pattern of reclassification was different, however, with less patients with ACS reclassified from revascularization to medical treatment compared with those with non-ACS (P=0.01). In ACS, 1-year outcome of patients reclassified based on FFR (FFR against angiography) was as good as that of nonreclassified patients (FFR concordant with angiography), with no difference in major cardiovascular event (8.0% versus 11.6%; P=0.20) or symptoms (92.3% versus 94.8% angina free; P=0.25). Moreover, FFR-based deferral to medical treatment was as safe in patients with ACS as in patients with non-ACS (major cardiovascular event, 8.0% versus 8.5%; P=0.83; revascularization, 3.8% versus 5.9%; P=0.24; and freedom from angina, 93.6% versus 90.2%; P=0.35). These findings were confirmed in ACS explored at the culprit lesion. In patients (6%) in whom the information derived from FFR was disregarded, a dire outcome was observed.
CONCLUSIONS: Routine integration of FFR into the decision-making process of ACS patients with obstructive coronary artery disease is associated with a high reclassification rate of treatment (38%). A management strategy guided by FFR, divergent from that suggested by angiography, including revascularization deferral, is safe in ACS.
Circ Cardiovasc Interv. 2017;10:e004296. DOI: 10.1161/CIRCINTERVENTIONS.116.004296.
Circulation: Cardiovascular Quality and Outcomes
This study proposes an alternative multivariate modeling approach, categorizing hospital readmissions and emergency department visits as separate event types. The investigators used a heart failure data set to estimate a model with random effects for event types. They conclude that modeling different outcomes provides an alternative analysis with greater statistical power, insights, and efficiency.
Multitype Events and the Analysis of Heart Failure Readmissions
Illustration of a New Modeling Approach and Comparison With Familiar Composite End Points
Paul M. Brown, PhD
Justin A. Ezekowitz, MBBCh, MSc
Correspondence to: Justin A. Ezekowitz, MBBCh, MSc, 2-132 Li Ka Shing Centre for Health Research Innovation, Edmonton, AB T6G 2E1, Canada. E-mail
BACKGROUND: Heart failure–related hospital readmissions and mortality are often outcomes in clinical trials. Patients may experience multiple hospital readmissions over time with mortality acting as a dependent terminal event. Univariate composite end points are used for the analysis of readmissions. We may amend these approaches to include emergency department visits as a further outcome. An alternative multivariate modeling approach that categorizes hospital readmissions and emergency department visits as separate event types is proposed.
METHODS AND RESULTS: We seek to compare the modeling approach which handles event types as separate, correlated end points against composites that amalgamate them to create a unified end point. Using a heart failure data set for illustration, a model with random effects for event types is estimated. The time-to-first event, unmatched win-ratio, and days-alive-and-out-of-hospital composites are derived for comparison. The model provides supplementary statistics such as the correlation among event types and yields considerably more power than the competing composite end points.
CONCLUSIONS: The effect on individual outcomes is lost when they are intermingled to form a univariate composite. Simultaneously modeling different outcomes provides an alternative or supplementary analysis that may yield greater statistical power and additional insights. Improvements in software have made the multitype events model easier to implement and thus a useful, more efficient option when analyzing heart failure hospital readmissions and emergency department visits.
Circ Cardiovasc Qual Outcomes. 2017;10:e003382. DOI: 10.1161/CIRCOUTCOMES.116.003382.
Circulation: Heart Failure
For unclear reasons, women have a higher mortality rate on the national heart transplant waitlist. The investigators analyzed adults on the active heart transplant waitlist from 2004 to 2015 from the Scientific Registry of Transplant Recipients, 25% of whom were women. Stratified by sex and the initial United Network for Organ Sharing) status, women were found to have a higher mortality for United Network for Organ Sharing status 1 and lower mortality for United Network for Organ Sharing status 2. The investigators identified >20 sex interactions for mortality and transplantation, suggesting opportunities for improvement in the current allocation system.
Sex Differences in Mortality Based on United Network for Organ Sharing Status While Awaiting Heart Transplantation
Eileen M. Hsich, MD
Eugene H. Blackstone, MD
Lucy Thuita, MS
Dennis M. McNamara, MD, MS
Joseph G. Rogers, MD
Hemant Ishwaran, PhD
Jesse D. Schold, PhD
Correspondence to: Eileen Hsich, MD, Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic, J3-4, 9500 Euclid Ave, Cleveland, OH 44195. E-mail
BACKGROUND: There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear.
METHODS AND RESULTS: We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. Random survival forest was used to identify sex interactions for the competing risk of death and transplantation. There were 33 069 patients (25% women) awaiting heart transplantation. This cohort included 7681 UNOS status 1A (26% women), 13 027 UNOS status 1B (25% women), and 12 361 UNOS status 2 (26% women). During a median follow-up of 4.3 months, 1351 women and 4052 men died. After adjusting for >20 risk factors, female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01–1.29) and UNOS status 1B (adjusted hazard ratio, 1.17; 95% confidence interval, 1.05–1.30). In contrast, female sex was significantly protective for time to death among UNOS status 2 (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76–0.95). Sex differences in probability of transplantation were present for every UNOS status, and >20 sex interactions were identified for mortality and transplantation.
CONCLUSIONS: When stratified by initial UNOS status, women had a higher mortality than men as UNOS status 1 and a lower mortality as UNOS status 2. With >20 sex interactions for mortality and transplantation, further evaluation is warranted to form a more equitable allocation system.
Circ Heart Fail. 2017;10:e003635. DOI: 10.1161/CIRCHEARTFAILURE.116.003635.
- © 2017 American Heart Association, Inc.