Search

The digital clinical trial is fast emerging as a pragmatic trial that can improve a trial’s design including recruitment and retention, data collection and analytics. To that end, digital platforms such as electronic health records or wearable technologies that enable passive data collection can be leveraged, alleviating burden from the participant and study coordinator. However, there are challenges. For example, many of these data sources not originally intended for research may be noisier than traditionally-obtained measures. Further, the secure flow of passively collected data and their integration for analysis is non-trivial. The Apple Heart Study was a prospective, single-arm, site-less digital trial designed to evaluate the ability of an app to detect atrial fibrillation. The study was designed with pragmatic features, such as an app for enrollment, a wearable device (the Apple Watch) for data collection, and electronic surveys for participant-reported outcomes that enabled a high volume of patient enrollment and accompanying data. These elements led to challenges including identifying the number of unique participants, maintaining participant-level linkage of multiple complex data streams, and participant adherence and engagement. Novel solutions were derived that inform future designs with an emphasis on data management. We build upon the excellent framework of the Clinical Trials Transformation Initiative to provide a comprehensive set of guidelines for data management of the digital clinical trial that include an increased role of collaborative data scientists in the design and conduct of the modern digital trial.

BackgroundCardiovascular procedural treatments were deferred at scale during the COVID-19 pandemic, with unclear impact on patients presenting with Non-ST Elevation Myocardial Infarction (NSTEMI).MethodsIn a retrospective cohort study of all patients diagnosed with NSTEMI in the U.S. Veterans Affairs Healthcare System from 1/1/19 to 10/30/22 (n=67,125), procedural treatments and outcomes were compared between the pre-pandemic period and six unique pandemic phases (1: Acute phase, 2: Community spread, 3: First Peak, 4: Post-Vaccine, 5. Second Peak, 6. Recovery). Multivariable regression analysis was performed to assess association between pandemic phases and 30-day mortality.ResultsNSTEMI volumes dropped significantly with the pandemic onset (62.7% of pre-pandemic peak) and did not revert to pre-pandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention (PCI) and/or coronary artery bypass grafting (CABG) volumes declined proportionally. Compared to the pre-pandemic period, NSTEMI patients experienced higher 30-day mortality during Phase 2 and 3, even after adjustment for COVID-19 positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted OR for Phase 2-3 combined: 1.26 [95% CI 1.13-1.43], pConclusionsHigher mortality after NSTEMI occurred during the initial spread and first peak of the pandemic, but resolved before the second, higher peak – suggesting effective adaptation of care delivery but a costly delay to implementation. Investigation into the vulnerabilities of the early pandemic spread are vital to informing future resource-constrained practices.Clinical PerspectiveWhat is New?After the initial significant decline in NSTEMI presentations during the acute phase of the pandemic, volumes of NSTEMI presentations and procedural treatment have not reverted to pre-pandemic levels despite widespread availability of vaccines in the Veterans Health Administration.Compared to the pre-pandemic period, 30-day mortality after NSTEMI increased during the initial spread and first pandemic peak (Phases 2 and 3) -- but resolved before the subsequent highest pandemic peak of Phase 5 -- suggesting a delay to implementation of adapted systems of cardiovascular care.The increased mortality was not significantly mediated by the decline in procedural volumes, suggesting appropriate triage of procedural care during the pandemic.What are the Clinical Implications?The COVID-19 pandemic appears to have had a lasting impact on health-seeking behaviors among NSTEMI patients, with unclear long-term effects of this increased threshold to obtain cardiovascular care.Investigation into the vulnerabilities that occurred during initial phases of the pandemic are urgently needed to inform ongoing and future resource-constrained practices.

Efforts to improve prescription of oral anticoagulation (OAC) drugs in patients with atrial fibrillation have had limited success in improving guideline adherence.We evaluated adherence to the American College of Cardiology/American Heart Association performance measures for OAC in eligible patients with a CHAThe median (25th, 75th percentile) age was 73 years (65, 81 years); 51% were female; and the median (25th, 75th percentile) CHAAmong hospitals participating in the GWTG-AFIB quality improvement program, OAC prescription at discharge in eligible guideline-indicated patients increased significantly and improved consistently over time. These data confirm that high-level adherence to guideline-recommended stroke prevention is achievable.

Among patients with atrial fibrillation (AF), little is known about contemporary compliance with quality measures as outlined in the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults with Atrial Fibrillation or Atrial Flutter. Measures include appropriate oral anticoagulant

Use of the CHAAmong patients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's outpatient Practice Innovation and Clinical Excellence registry (2008-2014) CHADSAdoption of the CHA

Introduction: Paroxysmal supraventricular tachycardia (PSVT) is viewed as a benign heart-rhythm disorder. However, recent studies suggest that atrial dysrhythmias other than atrial fibrillation/flutter (AF) may signify an increased stroke risk. Hypothesis: PSVT is associated with subsequent ischemic stroke in patients without documented AF. Methods: We obtained inpatient and outpatient claims data from 2010-2011 in a 5% sample of Medicare beneficiaries ≥66 years of age. We included only patients with a pacemaker or defibrillator, since such patients often undergo interrogation of heart rhythm. Patients with AF or stroke before or at the time of device implantation were excluded. Our predictor variable was PSVT. The primary outcome was ischemic stroke and the secondary outcome was embolic stroke. All diagnoses were ascertained from ICD-9-CM codes using previously validated algorithms. We used Kaplan-Meier survival analysis and the log-rank test to compare outcomes in patients with and without PSVT, which was modeled as a time-varying covariate. Patients were censored at the time of incident AF, stroke, death, or on December 31, 2011. Cox proportional hazards analysis was used to assess the relationship between PSVT and stroke while adjusting for demographic characteristics and vascular risk factors. Results: Among 42,152 eligible patients with a median 1.8 years of follow-up, 2,245 (5.3%) had PSVT and 1,007 (2.4%) developed a stroke. The incidence of stroke after a PSVT diagnosis (2.17% per year; 95% confidence interval [CI], 1.45-3.24%) was significantly higher than in patients without PSVT (0.95% per year; 95% CI, 0.87-1.03%; P < 0.001). After adjustment for demographic characteristics and vascular risk factors, PSVT was associated with a higher hazard of stroke (hazard ratio [HR], 2.0; 95% CI, 1.3-3.0). This association appeared stronger for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8). Conclusions: In Medicare beneficiaries with implantable pacemakers or defibrillators, PSVT was associated with ischemic stroke, especially embolic stroke, in the absence of documented AF. These results build on recent findings that disturbances of atrial rhythm and function other than AF may be a previously unrecognized stroke risk factor.

Background: There is increasing interest in understanding the factors that influence the use of diagnostic imaging in heart failure in US health systems. However, there is limited data examining overall use and the impact of racial disparities in the VA and Medicare. Methods: We analyzed Veterans Healthcare Administration (VA) and Medicare data from 2002 to 2009 to identify veteran patients above the age of sixty-five with a diagnosis of heart failure for at least 1 year. Patients receiving care in both systems were excluded. We examined patients undergoing echocardiography and scintigraphy each year by race and system of care. Multivariate logistic regression analyses were performed adjusting for age, gender and comorbidities. Results: A total of 2,917,307 veteran patients were included (263,778 in VA and 1,698,497 in Medicare). Overall use of echocardiography each year was 45.6% for Whites, 51.9% for Asians, 43.2% for Blacks, 39.7% for Hispanics, 42.0% for Pacific Islanders, 40.9% for Native-American and 48.1% for Other. The adjusted odds ratio of undergoing echocardiography was higher for Asians in both systems compared to Whites (Figure). In Medicare, use was lower for Native Americans, Blacks and Hispanics compared to Whites. In the VA, use among Blacks and Hispanics was higher than Whites. Conclusion: There are significant differences in echocardiography use between the VA and Medicare systems by race for veterans with heart failure. Whites were more likely to receive echocardiography compared to most races in Medicare but not in the VA.

Background: The high use of cardiac imaging in the United States is increasingly scrutinized. We sought to determine differences in cardiac imaging between the Veterans Healthcare Administration (VA) and Medicare for veterans with heart failure (HF). Methods: We analyzed VA and Medicare data from 2002 to 2009 to identify 2,536,556 unique veterans age 65 and older with a known diagnosis of HF for at least one year (those with care in both systems are excluded). The fraction of patients with an echocardiogram (ECHO) or nuclear scintigraphy (NUC) test was determined. Logistic regression was used to adjust for patient characteristics. Results: More veterans received care in Medicare (82%) than in the VA (18%) The mean age was 79 years, 93% were male and comorbidities were common: diabetes mellitus (44%), ischemic heart disease (67%), and chronic kidney disease (25%). Imaging per year was higher in Medicare compared to the VA for ECHO (51% vs. 21%) and NUC (18% vs. 8%, both p Conclusion: There is much greater use of imaging procedures among veterans in Medicare than in the VA not explained by patient characteristics and not associated with improved survival.

Background: Metabolic syndrome has been associated with increased risk of cardiovascular disease.We aimed to determine the effectiveness of a community-based screening program in identifying cardiovascular risk factors in a healthy young South Asian population. Methods: Between 2006 and 2011, 3,314 patients of all ages were recruited as a part of a prospective cohort study investigating cardiovascular risk in South Asians. We analyzed 1537 patients between the ages of 18 and 40. Demographic and baseline characteristics including baseline laboratory markers and blood pressures were obtained at initial visit. Results: The total cohort of 1537 patients was 66.5% male, and the mean age was 35±5 years. Among participants who denied a history of hypercholesterolemia, 62% had elevated LDL-C (>100 mg/dL), and 8% had markedly elevated LDL-C (>160 mg/dL). Overall, diabetes was present in 4%, hypertension was present in 12% and hyperlipidemia was present in 46%. Low HDL-C (50% of men, 52% of women) and elevated triglycerides (44% of men, 18% of women) were the most prevalent components of metabolic syndrome. Metabolic syndrome was present in 14% of men and 8% of women and one-third (30%) of men and one-fifth (19%) of women had at least two component risk factors. Discussion: This is the largest study to date assessing effectiveness of a community based screening program aiming to identify cardiovascular risk in young South Asians. We note significant modifiable risk at a young age. Such community based interventions can be effective at detecting and managing risk factors early in this vulnerable population.

Background. Warfarin anticoagulation for atrial fibrillation (AF) requires routine INR blood testing, usually performed by a single anticoagulation clinic or provider. Regular INR testing improves INR control, and monthly INR testing and adequate time in INR therapeutic range are endorsed quality and performance measures. However, many Veterans with cardiovascular disease use VA and Medicare (MC) services concurrently. We therefore evaluated the association of outpatient dual health care system use with process measures of warfarin management. Methods. Using linked VA and MC inpatient, outpatient, drug prescription, and laboratory claims, we identified MC Part A/B eligible, non-MC Advantage, Veterans age ≥ 65 with prevalent atrial fibrillation or flutter who were prescribed warfarin from the VA (index date) between 1/1/2004 and 12/31/2008. The primary predictor was the degree of dual use for INR testing, expressed as the fraction of outpatient INRs obtained in the 12 months post-index date that occurred in Medicare (MC/[VA+MC]). The outcomes were 1) the INR monitoring rate (INRMR), expressed as the proportion of calendar months±6 days in which an INR was performed (consistent with AHA/ACC performance measures) and 2) VA-based time in INR therapeutic range of 2.0-3.0 (TTR). Results. We identified 394,854 patients (age 77.2 ± 6.1 years; 1.4% female) with AF and VA-issued warfarin meeting inclusion criteria. Of these, 43.3% used VA only for INR testing, 16.6% used MC only, and 39.1% used both VA and MC. Compared to patients who used VA only, dual health care system users were older and had higher CHADS2 and comorbidity index scores. Compared to patients with VA-only care, the proportion of patients with adequate achievement of performance measures (INRMR = 1.0 or TTR ≥ 60) varied by degree of dual use (p Conclusion: More than half of Veterans age ≥ 65 with AF and VA-issued warfarin receive outpatient INR testing in MC. Dual health care system use is associated with lower achievement of process measures of quality of anticoagulation care, which could affect outcomes of stroke, hemorrhage and death.

Background South Asians have increased disk for cardiovascular disease (CVD) that is not captured by traditional risk factors, including TC and LDL-c. Low-density apolipoprotein-B (apoB) containing lipoproteins are heterogeneous in size and composition, and the particles with the greatest triglyceride content are thought to ultimately be the most atherogenic. Specific composition of low-density lipoproteins is not captured by common lipid measures (i.e. TC, LDL-c). A high proportion of triglyceride-rich low-density lipoproteins could be a mechanism for CVD risk in South Asians. Our objective was to compare mean TC, LDL-c, HDL-c, triglycerides, and apoB-triglyceride ratio (an estimate of low-density lipoprotein content) between South Asian-Americans and the US population. Methods We studied 2,876 South Asian adults living in the United States participating in a wellness program. Demographics were obtained by self-report. Lipoprotein levels were measured after 10-hour fast. US population means were calculated from NHANES (2007-2008, n = 5,113). Individuals on lipid-lowering therapy were excluded (780 (33%) South Asians, 1,194 (19%) NHANES). Results LDL-c (118mg/dL vs 116mg/dL, p Conclusions Mean TC, LDL-c, and triglycerides were normal in South Asians, however the apoB/triglyceride ratio was lower in South Asians than in the US population. This finding indicates that a higher proportion of low-density lipoproteins in South Asians are of the triglyceride-rich atherogenic type. This may portend non-HDL-c as a better indicator of CVD risk than LDL-c in South Asians. Further, low apoB/triglyceride ratio and low HDL-c occurs at a young age in South Asians, suggesting that onset of risk is early. The disappearance of these patterns after age 60 may be the result of sample bias (excluding individuals on lipid lowering therapy), and/or survival bias.

Background: Although cardiac resynchronization therapy (CRT) has been shown to slow the progression of heart failure (HF), it has not been well described whether the baseline severity of ventricular remodeling influences clinical outcomes. Methods: The COMPANION study database was analyzed retrospectively. This study randomized patients (pts) with NYHA Class III/IV HF, wide QRS, and systolic dysfunction to optimal pharmacologic therapy (OPT) alone or to OPT plus CRT either with (CRT-D) or without a defibrillator (CRT-P). For this analysis both CRT arms were combined. Ventricular remodeling was measured as left ventricular end diastolic dimension indexed by body surface area (LVEDDI). Data were stratified around the median value: LVEDDI≥ 35 mm/m 2 and < 35 mm/m 2 . CRT was compared to OPT for each cohort using functional outcomes at six months [exercise capacity, quality of life, functional status, and the Clinical Composite Endpoint] as well as event-driven outcomes [all-cause mortality alone and in combination with cause-specific hospitalization]. Results: Baseline LVEDDI data were available for 1260 pts. Pts in the larger LVEDDI cohort were characterized at baseline with wider QRS, lower EF, and a greater proportion of non-ischemic, female, and NYHA Class IV. Clinical outcomes are summarized below: Conclusion: In the COMPANION study, both cohorts demonstrated significant benefit in functional outcomes with CRT when compared to OPT. However, significant improvement in event-driven outcomes were seen only in the population with larger baseline LVEDDI. A prospective study is needed to confirm that LVEDDI can predict potential for improvement with CRT.