Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials.

BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient- and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term follow-up, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.

A systematic review of randomized trials comparing double versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: Prior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI. METHODS: Using PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed-effects and random-effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes. RESULTS: We identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial-reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94-1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02-2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53-0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p = .04; I2 = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31-0.96). CONCLUSIONS: Double therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis.

SCAI publications committee manual of standard operating procedures.

Evidence-based recommendations for clinical practice are intended to help health care providers and patients make decisions, minimize inappropriate practice variation, promote effective resource use, improve clinical outcomes, and direct future research. The Society for Cardiovascular Angiography and Interventions (SCAI) has been engaged in the creation and dissemination of clinical guidance documents since the 1990s. These documents are a cornerstone of the society's education, advocacy, and quality improvement initiatives. The publications committee is charged with oversight of SCAI's clinical documents program and has created this manual of standard operating procedures to ensure consistency, methodological rigor, and transparency in the development and endorsement of the society's documents. The manual is intended for use by the publications committee, document writing groups, external collaborators, SCAI representatives, peer reviewers, and anyone seeking information about the SCAI documents program.

A Multicenter, Prospective, Randomized, Placebo-Controlled, Double-Blind Study of a Novel Pain Management Device, AT-02, in Patients with Fibromyalgia.

OBJECTIVES: Existing treatments for fibromyalgia have limited efficacy, and only a minority of individuals clinically respond to any single intervention. This study was a prospective, multicenter, randomized, double-blind, controlled clinical trial to evaluate the feasibility of alternating magnetic field therapy in fibromyalgia patients by comparing the Angel Touch device (AT-02) with a sham control (S-01). METHODS: Two sites enrolled 44 subjects with diagnosed fibromyalgia. After informed consent, subjects taking prohibited concomitant drugs underwent a washout period of two or more weeks. All subjects then began a one-week run-in period. Numerical rating scale (NRS) pain scores were collected without device intervention for one day, followed by S-01 application to four or more painful sites for 10 minutes at each site, twice daily for six days. Subjects were then randomized to AT-02 or S-01, applied to four or more painful sites for 10 minutes at each site, twice daily for eight weeks. NRS scores were obtained twice daily during the entire treatment period. RESULTS: The primary end point (change in NRS ± SD at week 8 vs baseline) was -0.94 ± 1.33 in the AT-02 group and -0.22 ± 1.38 in the S-01 group. A trend toward a between-group difference in eight-week NRS scores favored the AT-02 group (-0.73, 95% confidence interval = -1.56 to 0.11, P = 0.086). An adjusted repeated measure analysis detected a significant difference in NRS scores (P = 0.039). CONCLUSIONS: The reduction in NRS scores for AT-02 relative to sham was comparable to reductions observed in meta-analyses of fibromyalgia drug therapy. The unadjusted results and the persistence of the pain score reductions remain encouraging.

Japan-United States of America Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (Japan-USA HARMONEE) study: primary results of the pivotal registration study of combined endothelial progenitor cell capture and drug-eluting stent in patients with ischaemic coronary disease and non-ST-elevation acute coronary syndrome.

Aims: Harmonized Assessment by Randomized Multicentre Study of OrbusNEich's Combo StEnt (HARMONEE) (NCT02073565) was a randomized pivotal registration trial of the Combo stent, which combined sirolimus and an abluminal bioabsorbable polymer with a novel endoluminal anti-CD34+ antibody coating designed to capture endothelial progenitor cells (EPC) and promote percutaneous coronary intervention (PCI) site healing. Methods and results: Clinically stabilized PCI subjects were randomized 1:1 to receive Combo or everolimus-eluting stents (EES). Between February 2014 and June 2016, 572 subjects with 675 coronary lesions underwent 1-year angiography and fractional flow reserve, with optical coherence tomography (OCT) in the first 140 patients. The primary clinical endpoint was non-inferior 1-year target vessel failure (TVF). The primary mechanistic endpoint of EPC capture activity was superior strut coverage by OCT. Target vessel failure occurred in 7.0% Combo (20/287) vs. 4.2% EES (12/285), a 2.8% [95% confidence interval (95% CI) -1.0%, 6.5%] difference, meeting the non-inferiority hypothesis (P = 0.02). There were no cardiac deaths, with one stent thrombosis observed in the EES group. Quantitative coronary angiography late loss with Combo was equivalent to EES. Optical coherence tomography strut coverage at 1 year was superior with Combo vs. EES [91.3% (95% CI 88.7%, 93.8%) vs. 74.8% (95% CI 70.0%, 79.6%), P < 0.001], with homogeneous tissue in 81.2% vs. 68.8%, respectively. Conclusion: Combo stent demonstrated non-inferior 1-year TVF and late loss in a randomized comparison to EES, with superior strut-based tissue coverage by OCT as a surrogate of EPC capture technology activity.

Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation.

BACKGROUND: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). CONCLUSIONS: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Rationale and design of the Japan-USA harmonized assessment by randomized, multicenter study of OrbusNEich's combo StEnt (Japan-USA HARMONEE): Assessment of a novel DES platform for percutaneous coronary revascularization in patients with ischemic coronary disease and non-ST-elevation acute coronary syndrome.

Tissue trauma associated with stent implantation continues to generate early thrombosis rates of 0.9% to 1.3% for both bare-metal and drug-eluting stent platforms. The Combo sirolimus-eluting stent combines an abluminal, bioabsorbable polymer with a luminal CD34+ antibody designed to capture endothelial progenitor cells. This article describes the design and methods of the HARMONEE trial (NCT02073565), which represents the first randomized controlled trial of the Combo design against a best-in-class contemporary everolimus-eluting stent. Up to 50 sites in Japan and the United States will enroll 286 subjects (271 evaluable) in each of 2 arms, for a total sample size of 572 subjects (542 evaluable). The statistical plan includes both superiority to imputed bare-metal stent control and noninferiority to everolimus-eluting stent on a primary clinical end point of target vessel failure at 1 year. In addition, fractional flow reserve assessment to evaluate the physiology of target vessels in the entire population will augment the end point definition of ischemia-driven target vessel revascularization. Finally, key safety considerations will be evaluated with a subpopulation with optical coherence tomography imaging for strut coverage, late strut malapposition, and plaque volume, as well as serial human antimurine antibody assessments. As the first international prospective randomized coronary intervention study under the "Harmonization by Doing" program, this study represents a unique collaboration between regulators and investigators in Japan and the United States.

Predictable and SuStainable Implementation of National Cardiovascular Registries (PASSION) infrastructure: A think tank report from Medical Device Epidemiological Network Initiative (MDEpiNet).

The MDEpiNet is a public-private partnership between the US Food and Drug Administration's Center for Devices and Radiological Health and participating partners. The PASSION program is an MDEpiNet-sponsored program that aims to demonstrate the goals of MDEpiNet by using cardiovascular medical device registries to bridge evidence gaps across the medical device total product life cycle. To this end, a PASSION Think Tank meeting took place in October 2014 in Silver Spring, MD, to facilitate discussion between stakeholders about the successes, challenges, and future novel applications of medical device registries, with particular emphasis on identifying pilot projects. Participants spanned a broad range of groups including patients, device manufacturers, regulators, physicians/academicians, professional societies, providers, and payers. The meeting focus included 4 areas of cardiovascular medicine intended to cultivate interest in 4 MDEpiNet disease-specific/device-specific working groups: coronary intervention, electrophysiology, valvular disease, and peripheral vascular disease. In addition, more general issues applying to registry-based infrastructure and analytical methodologies for assessing device benefit/risk were considered to provide context for the working groups as PASSION programs going forward. This article summarizes the discussions at the meeting and the future directions of the PASSION program.

Rate- and rhythm-control therapies in patients with atrial fibrillation: a systematic review.

BACKGROUND: The comparative effectiveness of treatments for atrial fibrillation (AF) is uncertain. PURPOSE: To evaluate the comparative effectiveness of rate- and rhythm-control therapies. DATA SOURCES: English-language studies in PubMed, EMBASE, and the Cochrane Database of Systematic Reviews between January 2000 and November 2013. STUDY SELECTION: Two reviewers independently screened citations to identify comparative studies that assessed rate- or rhythm-control therapies in patients with AF. DATA EXTRACTION: Reviewers extracted data on study design, participant characteristics, interventions, outcomes, applicability, and quality. DATA SYNTHESIS: 200 articles (162 studies) involving 28,836 patients were included. When pharmacologic rate- and rhythm-control strategies were compared, strength of evidence (SOE) was moderate supporting comparable efficacy with regard to all-cause mortality (odds ratio [OR], 1.34 [95% CI, 0.89 to 2.02]), cardiac mortality (OR, 0.96 [CI, 0.77 to 1.20]), and stroke (OR, 0.99 [CI, 0.76 to 1.30]) in older patients with mild AF symptoms. Few studies compared rate-control therapies and included outcomes of interest, which limited conclusions. For the effect of rhythm-control therapies in reducing AF recurrence, SOE was high favoring pulmonary vein isolation versus antiarrhythmic medications (OR, 5.87 [CI, 3.18 to 10.85]) and the surgical maze procedure (including pulmonary vein isolation) done during other cardiac surgery versus other cardiac surgery alone (OR, 7.94 [CI, 3.63 to 17.36]). LIMITATION: Studies were heterogeneous in interventions, populations, settings, and outcomes. CONCLUSION: Pharmacologic rate- and rhythm-control strategies have comparable efficacy across outcomes in primarily older patients with mild AF symptoms. Pulmonary vein isolation is better than antiarrhythmic medications at reducing recurrences of AF in younger patients with paroxysmal AF and mild structural heart disease. Future research should address uncertainties related to subgroups of interest and the effect of different therapies on long-term clinical outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Embedding a randomized clinical trial into an ongoing registry infrastructure: unique opportunities for efficiency in design of the Study of Access site For Enhancement of Percutaneous Coronary Intervention for Women (SAFE-PCI for Women).

Women are at higher risk than men for bleeding and vascular complications after percutaneous coronary intervention (PCI). Compared with femoral access, radial access reduces these complications but may be more challenging in women because of higher rates of radial artery spasm, tortuosity, and occlusion as well as lower rates of procedure success. Whether the safety advantages of radial versus femoral access in women undergoing PCI are outweighed by reduced effectiveness has not been studied. The Study of Access site For Enhancement of PCI for Women is a prospective, randomized clinical trial comparing radial with femoral arterial access in women undergoing PCI. In conjunction with the US Food and Drug Administration's Critical Path Cardiac Safety Research Consortium, this study embeds the randomized clinical trial into the existing infrastructure of the National Cardiovascular Data Registry CathPCI Registry through the National Institute of Health's National Cardiovascular Research Infrastructure. The primary efficacy end point is a composite of bleeding (Bleeding Academic Research Consortium types 2, 3, or 5) or vascular complication requiring intervention occurring at 72 hours after PCI or by hospital discharge. The primary feasibility end point is procedure success. Secondary end points include procedure duration, contrast volume, radiation dose, quality of life, and a composite of 30-day death, vascular complication, or unplanned revascularization.

TransRadial Education and Therapeutics (TREAT): shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention: a report from the Cardiac Safety Research Consortium.

Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions.

Nonfatal myocardial infarction and long-term outcomes in coronary artery disease.

BACKGROUND: Therapies may reduce short-term rates of nonfatal myocardial infarction (MI) without a detectable effect on mortality. We sought to estimate the long-term clinical implications of nonfatal MI occurring within the first 3 and 6 months after initial cardiac catheterization. METHODS: We included consecutive patients with significant coronary artery disease (≥75% stenosis in ≥1 epicardial segments) undergoing diagnostic catheterization between January 1, 1999, and September 30, 2006. Landmark analyses were performed for patients surviving at 3- and 6-month follow-up. At these times, patients were divided into groups based upon occurrence of a nonfatal MI subsequent to catheterization. RESULTS: Among 14,890 patients alive at 3 months (669 with MI and 14,221 without an MI), having an MI during the initial 3-month period was a significant predictor of reduced 4-year survival (77.1% vs 83.5%, hazard ratio 1.40, 95% CI 1.21-1.63, P < .001), survival free of MI (68.4% vs 78.5%, hazard ratio 1.50, 95% CI 1.32-1.71, P < .001), and survival free of MI or revascularization (59.7% vs 68.5%, hazard ratio 1.34, 95% CI 1.19-1.51, P < .001). Adjusted hazard ratios were similar for patients surviving to 6 months (804 with MI and 13,842 without an MI). CONCLUSIONS: Nonfatal MIs occurring within the first 3 and 6 months after diagnostic catheterization are associated with a significant increase in the risk for subsequent clinical events. Clinical studies with limited follow-up periods may underestimate the long-term value of therapies that reduce early MI rates as downstream benefits continue to accrue over time.

Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia.

The diagnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay. Addition of excess heparin to the sample decreases the optical density by 50% or more and confirms the presence of these antibodies. One hundred fifteen patients with anti-heparin/PF4 antibodies detected by enzyme-linked immunosorbent assay were classified as clinically HIT-positive or HIT-negative, followed by confirmation with excess heparin. A multivariate logistic regression model was fitted to estimate relationships between patient characteristics, laboratory findings, and clinical HIT status. This model was validated on an independent sample of 97 patients with anti-heparin/PF4 antibodies. No relationship between age, race, or sex and clinical HIT status was found. Maximal optical density and confirmatory positive status independently predicted HIT in multivariate analysis. Predictive accuracy on the training set (c-index 0.78, Brier score 0.17) was maintained when the algorithm was applied to the independent validation population (c-index 0.80, Brier score 0.20). This study quantifies the clinical utility of the confirmatory test to diagnose HIT. On the basis of data from the heparin/PF4 enzyme-linked immunosorbent assay and confirmatory assays, a predictive computer algorithm could distinguish patients likely to have HIT from those who do not.

The incremental value of angiographic features for predicting recurrent cardiovascular events: Insights from the Duke Databank for Cardiovascular Disease.

BACKGROUND AND AIMS: Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics. METHODS: We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007-12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models. RESULTS: Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03-0.08). CONCLUSIONS: The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics.

Long-term mortality of patients undergoing cardiac catheterization for ST-elevation and non-ST-elevation myocardial infarction.

BACKGROUND: There are limited contemporary data comparing long-term outcomes after cardiac catheterization for ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). METHODS AND RESULTS: We studied patients undergoing cardiac catheterization for STEMI (n=2413) and NSTEMI (n=1974) between 1999 and 2005 with at least 1 significant coronary lesion > or =75%. We compared adjusted mortality rates over restricted time intervals and the differential impact of early revascularization on mortality stratified by ST-elevation status. Between 1999 and 2007, 1274 patients died, with a median follow-up of 4 years. A piece-wise analysis showed a higher adjusted mortality risk for STEMI during the first 2 months (adjusted hazard ratio, 1.85; 95% confidence interval, 1.45 to 2.38) and a lower adjusted mortality risk for STEMI after 2 months (adjusted hazard ratio, 0.68; 95% confidence interval, 0.59 to 0.83). Compared with late or no revascularization, early revascularization was associated with a lower adjusted risk of mortality for both STEMI (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58 to 0.90) and NSTEMI (adjusted hazard ratio, 0.76; 95% confidence interval, 0.65 to 0.89) (P for interaction=0.22). CONCLUSIONS: Among a contemporary cohort of acute MI patients with significant coronary disease during cardiac catheterization, STEMI was associated with a higher risk of short-term mortality, but NSTEMI was associated with a higher risk of long-term mortality. Early revascularization was associated with a similar improvement in long-term outcomes for both STEMI and NSTEMI. These data suggest that in clinical investigations of early revascularization among patients with NSTEMI, extended follow-up may be necessary to demonstrate treatment benefit.

Splanchnic Nerve Block for Chronic Heart Failure.

OBJECTIVES: We hypothesized that splanchnic nerve blockade (SNB) would attenuate increased exercise-induced cardiac filling pressures in patients with chronic HF. BACKGROUND: Chronic heart failure (HF) is characterized by limited exercise capacity driven in part by an excessive elevation of cardiac filling pressures. METHODS: This is a prospective, open-label, single-arm interventional study in chronic HF patients. Eligible patients had a wedge pressure ≥15 mm Hg at rest or ≥25 mm Hg with exercise on baseline right heart catheterization. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment, followed by percutaneous SNB with ropivacaine. RESULTS: Nineteen patients were enrolled, 15 of whom underwent SNB. The average age was 58 ± 13 years, 7 (47%) patients were women and 6 (40%) were black. Left ventricular ejection fraction was ≤35% in 14 (93%) patients. No procedural complications were encountered. SNB reduced mean pulmonary arterial pressure at peak exercise from 54.1 ± 14.4 (pre-SNB) to 45.8 ± 17.7 mm Hg (p < 0.001) (post-SNB). Similarly, SNB reduced exercise-induced wedge pressure from 34.8 ± 10.0 (pre-SNB) to 25.1 ± 10.7 mm Hg (p < 0.001) (post-SNB). The cardiac index changed with peak exercise from 3.4 ± 1.2 (pre-SNB) to 3.8 ± 1.1 l/min/m2 (p = 0.011) (post-SNB). After SNB, patients exercised for approximately the same duration at a greater workload (33 ± 24 W vs. 50 ± 30 W; p = 0.019) and peak oxygen consumption VO2 (9.1 ± 2.5 vs. 9.8 ± 2.7 ml/kg/min; p = 0.053). CONCLUSIONS: SNB reduced resting and exercise-induced pulmonary arterial and wedge pressure with favorable effects on cardiac output and exercise capacity. Continued efforts to investigate short- and long-term effects of SNB in chronic HF are warranted. Clinical Trials Registration (Abdominal Nerve Blockade in Chronic Heart Failure; NCT03453151).

Estimating Clinical Trial Bleeding Events Using Electronic Health Record Data.

Clinical trials conducted for regulatory approval may include outcomes that are informative but not routinely collected in clinical practice. This situation can be problematic when pragmatic clinical trials (PCT) seek to use electronic health record (EHR) data to test the effectiveness of medical products and services in actual practice settings. We use TIMI bleeding events to illustrate how a complex clinical trial endpoint can be implemented using EHR data. While we were able to demonstrate that our EHR-defined bleeding events were associated with differences in patient clinical outcomes, we are not confident that these measurements could be replicated in other locations with consistent reliability and validity. We believe the development of PCT endpoint definitions is an important issue that should be addressed by medical and informatics professional societies, regulators and the medical products industry.

Late adverse events after drug-eluting stent implantation.

Stents that elute antiproliferative drugs prevent restenosis after percutaneous coronary artery revascularization, reducing the need for repeat procedures. Randomized trials in low-risk patients supported initial regulatory approval for drug-eluting stents (DES). In 2006, meta-analyses of long-term outcomes from these trials associated DES use with adverse events, believed to be attributable to late stent thrombosis, occurring more than 9 months after the initial procedure. This article appraises these late adverse effects and illustrates the power and shortcomings of large national registries, focused, well-conducted clinical trials, and meta-analyses of clinical trial data. This timely, robust evidence base reflects an alignment of academic, industry, and public health priorities.