Circulation Editors’ Picks

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HomeCirculationVol. 127, No. 23Circulation Editors’ Picks Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBCirculation Editors’ PicksMost Read Articles in Cardiovascular Quality and Outcomes The Editors The Editors Search for more papers by this author Originally published11 Jun 2013https://doi.org/10.1161/CIRCULATIONAHA.113.003639Circulation. 2013;127:e829–e836Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and Countries: An Analysis of Patients Receiving Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) TrialSummary—The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio (INR) range (TTR). Large differences in TTR have been reported between centers and countries, but the reasons are unclear. In the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, a warfarin dosing algorithm provided to participating centers recommended no change for in-range and 10% to 15% weekly dose changes for out-of-range INR values. We determined whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. Among 6022 nonvalvular atrial fibrillation patients from 44 countries, we found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R2=0.65). The degree of algorithm-consistent warfarin dosing accounted for a majority of the TTR variation between centers and countries. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65–6.59), and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85–1.00). In summary, warfarin dosing practice that does not change the dose when the INR is in range, and that makes relatively small (10% to 15%) weekly dose adjustments when the INR is out of range, is associated with improved TTR and clinical outcomes. Systems that implement algorithm-based dosing for patients with atrial fibrillation on warfarin could potentially improve outcomes on a global scale, especially in centers and countries with suboptimal INR control.Conclusions—Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale.1Outcomes of Medicare Beneficiaries Undergoing Catheter Ablation for Atrial FibrillationSummary—Catheter ablation is increasingly used in older patients with atrial fibrillation for whom medical therapy has failed. However, clinical trials of catheter ablation have enrolled relatively young patients with limited comorbidity. To describe the use of catheter ablation and associated outcomes in older persons with atrial fibrillation, we conducted a retrospective cohort study of 15 423 Medicare beneficiaries who underwent catheter ablation for atrial fibrillation between July 2007 and December 2009. For every 1000 procedures, there were 17 cases of hemopericardium requiring intervention, 8 cases of stroke, and 8 deaths within 30 days. More than 40% of patients required hospitalization within 1 year; however, atrial fibrillation or atrial flutter was the primary discharge diagnosis in only 38.4% of cases. Eleven percent of patients underwent repeat ablation within 1 year. Renal impairment, age ≥80 years, and heart failure were major risk factors for mortality within 1 year after catheter ablation. Whereas major complications after catheter ablation were associated with advanced age, they were fairly infrequent, and few patients underwent repeat ablation. Randomized trials are needed to assess the efficacy of catheter ablation in older adults and to better inform risk-benefit calculations for older patients with drug-refractory, symptomatic atrial fibrillation.Conclusions—Major complications after catheter ablation for atrial fibrillation were associated with advanced age but were fairly infrequent. Few patients underwent repeat ablation. Randomized trials are needed to inform risk-benefit calculations for older persons with drug-refractory, symptomatic atrial fibrillation.2Short- and Long-Term Outcomes of Coronary Stenting in Women Versus Men: Results From the National Cardiovascular Data Registry Centers for Medicare & Medicaid Services CohortSummary—Coronary stenting has become a standard of care for the treatment of medically refractory coronary artery disease, with approximately one third of percutaneous coronary interventions (PCIs) performed in women in the United States. Although procedural success rates are similar by sex, it remains unclear whether disparate in-hospital and long-term outcomes exist between the sexes. In addition, the long-term safety and effectiveness of drug-eluting stents relative to bare metal stents in women are poorly understood. Women have been underrepresented in prior clinical trials evaluating intracoronary stent technologies, and smaller historical observational studies have produced conflicting results. Data from >400 000 older individuals (≥65 years of age) from the National Cardiovascular Data Registry CathPCI Registry were linked to Medicare inpatient claims to study sex-specific in-hospital and long-term outcomes after an index stent procedure. Additionally, the long-term safety and effectiveness of drug-eluting stents versus bare metal stents were compared in women and men. In the contemporary PCI era, our study shows that elderly women undergoing index PCI remain at higher risk of in-hospital mortality and other complications compared with men. In contrast, long-term outcomes are similar or better in women than in men. The use of drug-eluting stents is associated with a similar benefit in both men and women. Further studies are needed to understand the causative factors for these findings.Conclusions—In contemporary coronary stenting, women have a slightly higher procedural risk than men but have better long-term survival. In both sexes, use of a drug-eluting stent is associated with lower long-term likelihood for death, myocardial infarction, and revascularization.3Impact of Sex on Cardiovascular Outcome in Patients at High Cardiovascular Risk: Analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET)Summary—Although uncontrolled epidemiological analyses suggest that sex independently contributes to cardiovascular risk, there are limited controlled large-scale clinical studies on sex-specific cardiovascular outcome. Moreover, clinical trials are often hampered by the enrollment of few female patients. In our analyses based on the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the parallel Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) with patients ≥55 years of age, we included a large proportion of female patients (29.7%). In these large interventional trials, we observed that sex greatly affects the occurrence of cardiovascular events in patients with vascular disease or high-risk diabetes mellitus. This ≈20% lower risk for combined cardiovascular events in female patients, who were under optimal, guideline-recommended pharmacological treatment, is driven mainly by a significantly lower incidence of acute myocardial infarction. However, it should be pointed out that diabetic female patients were characterized by a higher risk for acute myocardial infarction compared with diabetic male patients, whereas alcohol consumption resulted in significantly lower risk in women. Sex- and age-dependent analyses demonstrate that female patients develop cardiovascular end points ≈5 to 10 years later despite appropriately individualized cardioprotective therapy in both female and male patients. In these controlled cardiovascular end-point trials, we clearly point out significant sex-related differences, with women being at lower net cardiovascular risk than men except when diabetic. These differences should be acknowledged in daily clinical routine when female and male patients at high cardiovascular risk are treated.Conclusions—In our analysis made up of 70.3% male and 29.7% female patients, an ≈20% lower risk for the combined cardiovascular end points in female patients was observed despite treatment with cardioprotective agents. This difference was driven primarily by a significantly lower incidence of myocardial infarction. Thus, we demonstrate in a large interventional trial that sex greatly affects the occurrence of cardiovascular events in patients with vascular disease or high-risk diabetes mellitus.4Post–Cardiac Arrest Mortality Is Declining: A Study of the US National Inpatient Sample 2001 to 2009Summary—Improving the postresuscitation care of patients with cardiac arrest has received much attention over the past decade. Landmark randomized trials were published in 2001 showing a benefit in mortality and morbidity with the use of therapeutic hypothermia in selected patients. Modifications to national cardiopulmonary resuscitation guidelines emphasizing high quality chest compressions, early use of automated external defibrillators, and early coronary interventions have also been advocated. We used the National Inpatient Sample database to examine the annual population-based mortality rates of 1 190 760 patients hospitalized in the United States from 2001 to 2009. The in-hospital mortality rate decreased consistently each year from 69.6% in 2001% to 57.8% in 2009. In multivariable analysis, when controlling for age, sex, race, and comorbidities, earlier year was a strong independent predictor of in-hospital death. The odds of in-hospital mortality associated with cardiac arrest in 2001 were significantly higher than the odds of mortality in 2005 (odds ratio, 1.11; 95% confidence interval, 1.09–1.14; P<0.0001). The odds of mortality associated with cardiac arrest in 2009 were significantly lower than the odds of mortality in 2005 (odds ratio, 0.69; 95% confidence interval, 0.67–0.70; P<0.0001). This decline in mortality rate was similar across all analyzed subgroups, including sex, age, race, and stratification by comorbidity. Although we cannot definitively conclude which specific factor is responsible for the decline in mortality, our results suggest that advances in postresuscitation care have positively impacted survival rates of patients hospitalized with cardiac arrest in the United States from 2001 to 2009.Conclusions—The in-hospital mortality rate of patients hospitalized with cardiac arrest in the United States decreased by 11.8% from 2001 to 2009.5Influenza Vaccination and Major Adverse Vascular Events in High-Risk PatientsSummary—It remains uncertain whether the influenza vaccine is associated with a reduced risk of vascular events, despite at least 10 observational studies and 3 small randomized controlled trials investigating this association. The existing observational studies were limited by small size, involved only a single influenza season, and/or were at risk of significant bias resulting from study design and the presence of confounding. The 3 randomized controlled trials were small with few event rates, precluding any definitive conclusions. We therefore performed an observational study using data from a large multinational trial of patients at high risk for vascular events involving 31 546 participants from 733 centers in 40 countries. Although initial analyses suggest that influenza vaccination was associated with a reduced risk of major adverse vascular events during influenza seasons when the influenza vaccine matched the circulating virus, detailed sensitivity analyses revealed that evidence of risk of confounding bias remained. A randomized trial is needed to definitively address this question.Conclusions—Although initial analyses suggest that influenza vaccination was associated with reduced risk of major adverse vascular events during influenza seasons when the influenza vaccine matched the circulating virus, sensitivity analyses revealed that risk of bias remained. A randomized trial is needed to definitively address this question.6Expansion of a Regional ST-Segment–Elevation Myocardial Infarction System to an Entire StateSummary—Many of the decisions and processes that affect the speed of coronary artery reperfusion occur long before patients reach the cardiologist. Particularly in the case of patients who are diagnosed with ST-segment–elevation myocardial infarction (STEMI) on scene by paramedics, early catheterization laboratory activation can lead to reperfusion times <1 hour. Similarly, patients presenting to hospitals without primary percutaneous coronary intervention capability require coordinated protocols for diagnosis and transfer to be treated in <2 hours. In both scenarios, accelerated coronary reperfusion has been associated with improved survival. This article describes the largest voluntary statewide system for ST-segment–elevation myocardial infarction diagnosis and treatment. The North Carolina Regional Approach to Cardiovascular Emergencies (RACE) system included every percutaneous coronary intervention hospital (n=21), most hospitals lacking percutaneous coronary intervention capability (n=98), and >500 emergency medical service agencies in a state of 9 million people. Over a 2-year period, the implementation of common protocols resulted in significantly improved treatment times for patients presenting directly to percutaneous coronary intervention hospitals and patients requiring hospital transfer. Similar to prior work, treatment within guideline goals was associated with significantly lower mortality compared with those exceeding guideline goals (2.2% versus 5.7%; P<0.001).Conclusions—Through extension of regional coordination to an entire state, rapid diagnosis and treatment of ST-segment–elevation myocardial infarction has become an established standard of care independently of healthcare setting or geographic location.7Trends in Patients Hospitalized With Heart Failure and Preserved Left Ventricular Ejection Fraction: Prevalence, Therapies, and OutcomesSummary—Heart failure with preserved ejection fraction (HF–preserved EF) is an increasingly common syndrome, but relatively little is known about recent trends in patient characteristics and early clinical outcomes. The present study evaluated 110 621 heart failure patients from 275 hospitals participating in Get With the Guidelines–Heart Failure from January 2005 to October 2010. Patients were grouped by EF as reduced EF (EF <40% [HF–reduced EF]), borderline EF (40%≤EF<50% [HF–borderline EF]), or preserved (EF ≥50% [HF–preserved EF]). Using multivariable models, we examined trends in therapies and outcomes. There were 55% of patients with HF–reduced EF, 14% with HF–borderline EF, and 36% with HF–preserved EF. From 2005 to 2010, the proportion of hospitalizations for HF–preserved EF increased from 33% to 39% (P<0.0001). Although many heart failure quality metrics cannot be applied appropriately to the HF–preserved EF population, there are broadly applicable cardiovascular prevention goals such as blood pressure control and discharge instructions that are particularly important for patients with HF–preserved EF but less likely to be achieved. In-hospital mortality for patients with HF–preserved EF remains comparable to that for patients with HF–reduced EF. In-hospital mortality for HF–preserved EF decreased from 3.32% in 2005 to 2.35% in 2010 but was stable for patients with HF–reduced EF. Among hospitalizations for heart failure, HF–preserved EF represents a growing proportion and may overtake HF–reduced EF as the predominant form of acute heart failure. There remains an important opportunity for identification of evidence-based therapies in patients with HF–preserved EF.Conclusions—Hospitalization for HF–preserved EF is increasing relative to HF–reduced EF. Although in-hospital mortality for patients with HF–preserved EF declined over the study period, an important opportunity remains for identifying evidence-based therapies in patients with HF–preserved EF.8Application of Geographic Modeling Techniques to Quantify Spatial Access to Health Services Before and After an Acute Cardiac Event: The Cardiac Accessibility and Remoteness Index for Australia (ARIA) ProjectSummary—In an acute cardiac event, access to timely and definitive care through specialist centers is critical to survival and to improving longer-term outcomes. Similarly, for survivors, ready access to more routine health care, including specialist management (through a cardiologist and cardiac rehabilitation program) and community-based primary care, is essential in preventing potentially fatal secondary events. Although evidence-based guidelines provide advice on managing a cardiac event in ideal circumstance, in reality, their implementation is often limited by the geographic location of the initial acute event and the location and level of facilities available to manage that event in a timely manner. For example, only an estimated 20% of emergency departments in the United States are located in hospitals with a cardiac catheterization laboratory. Still fewer have the capability to perform immediate revascularization. These data reinforce the importance of ready access to more portable and potentially life-saving therapies such as defibrillators and thrombolytic therapy, as well as efficient cardiac triage and transportation. The Cardiac Accessibility and Remoteness Index of Australia (Cardiac ARIA) measured access to cardiac care through a geographic lens via an objective, comparable measure of the time and distance from any population location to evidence-based cardiac care. An index of access to health services that was independent of professional, socioeconomic, or political influences was generated. It highlighted substantial inequities in access to cardiac services in Australia. Cardiac ARIA represents a powerful and adaptable tool to optimize outcomes by informing more equitable distribution of cost-effective, life-saving health care in any given geographic location.Conclusions—The Cardiac ARIA index demonstrated substantial inequity in access to cardiac services in Australia. This methodology can be used to inform cardiology health service planning and could be applied to other common disease states within other regions of the world.9Global Variation in the Prevalence of Elevated Cholesterol in Outpatients With Established Vascular Disease or 3 Cardiovascular Risk Factors According to National Indices of Economic Development and Health System PerformanceSummary—The exponential rise in cardiovascular disease over the past decade has placed a tremendous burden on the health and economic development of countries worldwide, with unprecedented demands for an effective response from governments and other stakeholders in global health. From a large, multinational registry of outpatients with established cardiovascular disease or ≥3 risk factors, we used data from 53 570 individuals from 36 countries to examine the relationship between country-level economic and health system factors and the risk of elevated cholesterol (total cholesterol levels >200 mg/dL). The analysis was performed separately for patients with versus without previous history of hyperlipidemia; a higher proportion of the total variability in elevated cholesterol was at the country level for patients with (12.1%) versus without (7.4%) history of hyperlipidemia. Among patients with history of hyperlipidemia, after adjusting for patient-level demographic and clinical characteristics and average fat consumption at the country level, countries in the highest tertile of gross national income or World Health Organization index of health system achievement were found to have significantly lower odds of elevated cholesterol than those in each of the lower 2 tertiles, and the odds of elevated cholesterol was higher for countries in higher versus lower tertile of out-of-pocket health expenditures. No significant associations between country-level factors and elevated cholesterol were found for patients without history of hyperlipidemia. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level.Conclusions—Global variations in the prevalence of elevated cholesterol among patients with history of hyperlipidemia are associated with country-level economic development and health system indices. These results support the need for strengthening efforts toward effective cardiovascular disease prevention and control and may provide insight for health policy setting at the national level.10Prediction of Long-Term Mortality After Percutaneous Coronary Intervention in Older Adults: Results From the National Cardiovascular Data RegistrySummary—Most survival prediction models for percutaneous coronary intervention are limited to in-hospital end points. Although short-term mortality rates remain low, multiple stakeholders, including providers, patients, and payers, will be more interested in long-term survival. We linked the broadly representative, real-world clinical data from the American College of Cardiology–National Cardiovascular Data Registry CathPCI Registry with vital statistics from the Medicare 100% denominator file to construct a robust, long-term percutaneous coronary intervention survival prediction model. This study included 343 466 patients aged ≥65 years who underwent percutaneous coronary intervention either with or without ST-segment elevation myocardial infarction between 2004 and 2007. Median follow-up was 15 months, with mortality of 2.97% at 30 days, and 8.58%, 13.4%, and 18.3% at 1, 2, and 3 years, respectively. Twenty-four demographic and clinical comorbidities, prior history of disease, and indices of disease severity and acuity were identified as being associated with mortality. Discrimination, calibration, and validation of the model were all excellent. The large sample size permitted precise estimates of the influence of clinical correlates on survival. Early mortality is predicted by variables related to acuteness of presentation, whereas longer-term mortality is associated with chronic debilitating diseases such as insulin-dependent diabetes mellitus and dialysis-dependent renal failure and behaviors such as cigarette smoking. The model may be used for shared medical decision making, quality improvement, and provider benchmarking and as a basis for developing comparative effectiveness research.Conclusions—On the basis of the large and nationally representative CathPCI Registry, we have developed a model that has excellent discrimination, calibration, and validation to predict survival up to 3 years after percutaneous coronary intervention.11Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery: Results From the Society of Thoracic Surgeons Adult Cardiac Surgery Database (The ASCERT Study)Summary—Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. However, particularly as short-term mortality rates decrease, it is increasingly important for providers, patients, payers, and other stakeholders to better understand the likelihood of long-term survival. We linked broadly representative, real-world clinical data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and vital status from Medicare claims data to construct a robust, long-term coronary artery bypass grafting surgery survival prediction model. This study included 348 341 patients aged ≥65 years who underwent isolated coronary artery bypass grafting surgery between 2002 and 2007. Because of the large study cohort and clinical predictors, model performance is excellent. On the basis of the results of this study, late outcomes for patients who initially survive coronary artery bypass grafting surgery are less affected by traditional predictors of early mortality such as emergency status, shock, and reoperation. Conversely, late mortality is increasingly associated with chronic debilitating diseases such as insulin-dependent diabetes mellitus and dialysis-dependent renal failure and behaviors such as smoking. This is valuable information for shared decision making, comparative effectiveness research, quality improvement, patient counseling, and provider profiling.Conclusions—Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling.12Admission International Normalized Ratio Levels, Early Treatment Strategies, and Major Bleeding Risk Among Non–ST-Segment–Elevation Myocardial Infarction Patients on Home Warfarin Therapy: Insights From the National Cardiovascular Data RegistrySummary—Little is known about the contemporary treatment patterns and bleeding risks of non–ST-segment–elevation myocardial infarction patients on home warfarin therapy. Although expert opinion from consensus guidelines suggests withholding parenteral anticoagulant therapy in patients with admission international normalized ratio (INR) levels ≥2.0, we found that 45% of these patients were prescribed early heparin in the first 24 hours of hospitalization. Additionally, although guidelines suggest initiation of antiplatelet therapy among those with admission INR levels ≥2.0, we found that only 35% and 14% of these patients were prescribed early clopidogrel and glycoprotein IIb/IIIa inhibitor, respectively. Patients with admission INR ≥2.0 were less likely to receive an early invasive strategy despite higher ischemic risk. These findings highlight the challenge that clinicians face in balancing ischemic benefit and bleeding risk when selecting a treatment for these patients. We found that early use of antiplatelet and antithrombin therapy was associated with increased bleeding risk among non–ST-segment–elevation myocardial infarction patients on home warfarin; however, an early invasive strategy was not. After adjustment, patients with admission INR levels >3.0 were at highest risk of in-hospital major bleeding followed by those with admission INR of 2.0 to 3.0. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level. Future clinical trials are critically needed to guide treatment decisions, to determine the optimal use and timing of anticoagulant therapy, and to formulate more definitive guideline recommendations that balance the prevention of adverse ischemic events with the risk of major bleeding in this vulnerable population.Conclusions—National patterns of early antithrombotic treatment for non–ST-segment–elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.13Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Standard Care Among Inoperable Patients With Severe Aortic Stenosis: Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B)Summary—In patients deemed ineligible for cardiac surgery, the Placement of Aortic Transcatheter Valves (PARTNER) trial recently demonstrated a 20% absolute survival difference at 12 months when transcatheter aortic valve replacement (TAVR) was compared with standard nonsurgical therapy. The costs and cost effectiveness of this clinical strategy, which would typically be applied to elderly patients, have not been evaluated previously. Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the PARTNER trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs. Average costs for the initial TAVR procedure and hospital stay were $42 806 and $78 542, respectively, but follow-up costs through 12 months were approximately $24 000 lower per patient with TAVR because of higher rates of cardiovascular hospitalization with standard therapy. We projected that over a patient’s lifetime, TAVR would increase life expectancy by 1.9 years (1.6 years after application of a standard 3% discount rate to future costs and benefits) at a discounted lifetime incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained, or $61 889 per quality-adjusted life-year gained, values generally considered acceptable within the context of the US healthcare system. These estimates were only slightly altered when assumptions about future costs and survival were varied within plausible ranges.Conclusions—For patients with severe aortic stenosis who are not candidates for surgery, TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies.14Cardiac Complications in Patients With Community-