Eric A. Secemsky

Development and Validation of a Prediction Rule for Benefit and Harm of Dual Antiplatelet Therapy Beyond 1 Year After Percutaneous Coronary Intervention

IMPORTANCE Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding. OBJECTIVE To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI. DESIGN, SETTING, AND PARTICIPANTS Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014). EXPOSURES Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin. MAIN OUTCOMES AND MEASURES Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI. RESULTS Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding. CONCLUSION AND RELEVANCE Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00977938.

Sudden cardiac death in patients with human immunodeficiency virus infection.

OBJECTIVES The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection. BACKGROUND As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described. METHODS The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria. RESULTS Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003). CONCLUSIONS SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications.

Electrocardiographic monitoring for detecting atrial fibrillation after ischemic stroke or transient ischemic attack: systematic review and meta-analysis.

Background—Atrial fibrillation (AF) is a major cause of stroke. Although standard investigations after an event include electrocardiographic monitoring, the optimal duration to detect AF is unclear. We performed a systematic review and meta-analysis to determine whether the duration of electrocardiographic monitoring after an ischemic event is related to the detection of AF. Methods and Results—Prospective studies that reported the proportion of new AF diagnosed using electrocardiographic monitoring for >12 hours in patients with recent stroke or transient ischemic attack were analyzed. Studies were excluded if the stroke was hemorrhagic or AF was previously diagnosed. A total of 31 articles met inclusion criteria. Longer duration of monitoring was associated with an increased detection of AF when examining monitoring time as a continuous variable (P<0.001 for metaregression analysis). When dichotomizing studies based on monitoring duration, studies with monitoring lasting ⩽72 hours detected AF in 5.1%, whereas monitoring lasting ≥7 days detected AF in 15%. The proportion of new diagnosis increased to 29.15% with extended monitoring for 3 months. Significant heterogeneity within studies was detected for both groups (⩽72 hours, I2=91.3%; ≥7 days, I2=75.8). When assessing the odds of AF detection in the 3 randomized controlled trial, there was a 7.26 increased odds of AF with long-term monitoring (95% confidence intervals [3.99–12.83]; P value <0.001). Conclusions—Longer duration of electrocardiographic monitoring after cryptogenic stroke is associated with a greater detection of AF. Future investigation is needed to determine the optimal duration of long-term monitoring.

Surgical Ineligibility and Mortality Among Patients With Unprotected Left Main or Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Background— Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results— All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16–18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88–4.72, P<0.001) after percutaneous coronary intervention. Conclusions— Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.

Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals

OBJECTIVES This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. BACKGROUND HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. METHODS Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. RESULTS Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. CONCLUSIONS Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.

Public reporting in cardiovascular medicine: accountability, unintended consequences, and promise for improvement.

“The Trustees of Hospitals should see to it,” wrote Dr Ernest Amory Codman in 1918, “that an effort is made to follow up each patient they treat, long enough to determine whether the treatment given has permanently relieved the condition or symptoms complained of.”1 These views did not help Dr Codman’s career. He quit his position as a staff surgeon at the Massachusetts General Hospital to protest the hospital administration’s refusal to measure and disclose outcomes and was later forced to resign as chairman of the Suffolk District Surgical Society.2 Two weeks after his death in 1940, the hospital’s trustees passed a resolution calling him a “champion of truth” who was “willing to sacrifice personal place and standing to achieve what he believed to be right.”2 In poor financial circumstances, he was buried initially without a headstone. In 2014, Dr Andrew L. Warshaw, the surgeon-in-chief emeritus and a former president of the New England Surgical Society, organized a granite and bronze memorial for Dr Codman’s gravesite in Cambridge, MA.2 More than 7 decades after Dr Codman’s death, debate persists about how to measure and report outcomes in medicine. Although the concept of measuring outcomes is now firmly embraced, risk-adjustment methods, the dissemination of outcomes data, and the incentives for healthcare providers and healthcare systems to improve outcomes remain contested. Cardiologists and cardiac surgeons have been among the first physicians to grapple with these issues, largely because cardiac disease is appealing for outcomes measurement and reporting. Not only is cardiac disease the leading cause of death in the United States, accounting for nearly one-fifth of healthcare spending,3 but the cardiovascular community has led the way in evidence-based guidelines that lend themselves to quality measurement. Globally, ischemic heart disease and stroke have become the top 2 causes …

Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.

Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population.

Effectiveness of Arterial Closure Devices for Preventing Complications With Percutaneous Coronary Intervention

Background—Bleeding is associated with poor outcomes after percutaneous coronary intervention (PCI). Although arterial closure devices (ACDs) are widely used in clinical practice, whether they are effective in reducing bleeding complications during transfemoral PCI is uncertain. The objective of this study was to evaluate the effectiveness of ACDs for the prevention of vascular access site complications in patients undergoing transfemoral PCI using an instrumental variable approach. Methods and Results—We performed a retrospective analysis of the CathPCI Registry from 2009 to 2013 at 1470 sites across the United States. Variation in the proportion of ACDs used by each individual physician operator was used as an instrumental variable to address potential confounding. A 2-stage instrumental variable analysis was used as the primary approach. The main outcome measure was vascular access site complications, and nonaccess site bleeding was used as a falsification end point (negative control) to evaluate for potential confounding. A total of 1 053 155 ACDs were used during 2 056 585 PCIs during the study period. The vascular access site complication rate was 1.5%. In the instrumental variable analysis, the use of ACDs was associated with a 0.40% absolute risk reduction in vascular access site complications (95% confidence interval, 0.31–0.42; number needed to treat=250). Absolute differences in nonaccess site bleeding were negligible (risk difference, 0.04%; 95% confidence interval, 0.01–0.07), suggesting acceptable control of confounding in the comparison. Conclusions—ACDs are associated with a modest reduction in major bleeding after PCI. The number needed to treat with ACDs to prevent 1 major bleeding event is high.

Use of Chronic Oral Anticoagulation and Associated Outcomes Among Patients Undergoing Percutaneous Coronary Intervention

Background Contemporary rates of oral anticoagulant (OAC) therapy and associated outcomes among patients undergoing percutaneous coronary intervention (PCI) have been poorly described. Methods and Results Using data from an integrated health care system from 2009 to 2014, we identified patients on OACs within 30 days of PCI. Outcomes included in‐hospital bleeding and mortality. Of 9566 PCIs, 837 patients (8.8%) were on OACs, and of these, 7.9% used non–vitamin K antagonist agents. OAC use remained stable during the study (8.1% in 2009, 9.0% in 2014; P=0.11), whereas use of non–vitamin K antagonist agents in those on OACs increased (0% in 2009, 16% in 2014; P<0.01). Following PCI, OAC‐treated patients had higher crude rates of major bleeding (11% versus 6.5%; P<0.01), access‐site bleeding (2.3% versus 1.3%; P=0.017), and non–access‐site bleeding (8.2% versus 5.2%; P<0.01) but similar crude rates of in‐hospital stent thrombosis (0.4% versus 0.3%; P=0.85), myocardial infarction (2.5% versus 3.0%; P=0.40), and stroke (0.48% versus 0.52%; P=0.88). In addition, prior to adjustment, OAC‐treated patients had longer hospitalizations (3.9±5.5 versus 2.8±4.6 days; P<0.01), more transfusions (7.2% versus 4.2%; P<0.01), and higher 90‐day readmission rates (22.1% versus 13.1%; P<0.01). In adjusted models, OAC use was associated with increased risks of in‐hospital bleeding (odds ratio 1.50; P<0.01), 90‐day readmission (odds ratio 1.40; P<0.01), and long‐term mortality (hazard ratio 1.36; P<0.01). Conclusions Chronic OAC therapy is frequent among contemporary patients undergoing PCI. After adjustment for potential confounders, OAC‐treated patients experienced greater in‐hospital bleeding, more readmissions, and decreased long‐term survival following PCI. Efforts are needed to reduce the occurrence of adverse events in this population.

Hemodynamic and Arrhythmogenic Effects of Cocaine in Hypertensive Individuals

J Clin Hypertens (Greenwich). 2011;13:744–749. ©2011 Wiley Periodicals, Inc.