Faculty Bibliography

Importance/UNASSIGNED:It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective/UNASSIGNED:To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants/UNASSIGNED:The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018. Main Outcomes and Measures/UNASSIGNED:Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported. Results/UNASSIGNED:A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging. Conclusions and Relevance/UNASSIGNED:The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01471522.

Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >25mm Hg at rest, is strongly associated with morbidity and mortality in the perioperative period. The prevalence and outcomes of PH among patients referred for major noncardiac surgery in the United States are unknown. Patients ≥18 years of age hospitalized for noncardiac surgery were identified from Healthcare Cost and Utilization Project's National Inpatient Sample data from 2004 to 2014. Pulmonary hypertension was defined by International Classification of Diseases, Ninth Revision diagnosis codes. The primary outcome was perioperative major adverse cardiovascular events (MACCE), defined as in-hospital death, myocardial infarction, or ischemic stroke. Among 17,853,194 hospitalizations for major noncardiac surgery, 143,846 (0.81%) had PH. MACCE occurred in 8.3% of hospitalizations with any diagnosis of PH in comparison to 2.0% of those without PH (p <0.001), driven by an increased frequency of death (4.4% vs 1.1%, p <0.001) and nonfatal myocardial infarction (3.2% vs 0.6%, p <0.001). After adjusting for demographics, clinical covariates, and surgery type, PH remained independently associated with MACCE (aOR 1.43, 95% CI 1.40 to 1.46). In conclusion, PH is associated with perioperative major adverse cardiovascular events. Careful patient selection, recognition of perioperative risks, and appropriate intraoperative hemodynamic monitoring may improve perioperative cardiovascular outcomes.

The association between admission blood pressure (BP) and outcomes in patients with transient ischemic attack (TIA) is not well defined. Patients in the United States national Get With The Guidelines-Stroke registry with a TIA were included. Admission systolic and diastolic BP was used to compute mean arterial pressure and pulse pressure (PP). A subset of this cohort was linked to Centers for Medicare and Medicaid claims data for postdischarge outcomes. The in-hospital outcomes of interest were: mortality, not discharged home, and inability to ambulate independently at discharge. Postdischarge, 30-day and 90-day outcomes of interest were mortality, readmission for stroke, and readmission for major cardiovascular event-composite of death, cerebrovascular, or cardiovascular readmission. Among the 218,803 patients with TIA, lower admission systolic blood pressure (SBP) was associated with worse in-hospital outcomes. Compared with patients with SBP of 150 mm Hg, a lower SBP of 120 mm Hg was associated with higher risk of in-hospital death (adjusted OR = 1.79; 95% CI = 1.50 to 2.12), not being discharged home (adjusted OR = 1.31; 95% CI = 1.27 to 1.36), or inability to ambulate independently at discharge (adjusted OR = 1.27; 95% CI = 1.23 to 1.31). Similarly, among the 64,352 patients in the Centers for Medicare and Medicaid-linked cohort, an inverse association between systolic BP and postdischarge mortality (p <0.0001), and major cardiovascular event (p = 0.0001) was observed at 30-days and at 90-days postdischarge. However, there was no relation between SBP and readmission for stroke either at 30-days (p = 0.35) or at 90-days (p = 0.11). Results were largely similar for diastolic BP, mean arterial pressure, PP, and outcomes. In conclusion, in patients with a transient ischemic attack, a BP paradox was observed, with higher admission BP associated with improved in-hospital, 30-day, and 90-day postdischarge outcomes.

: A physiologically lower heart rate, such as that seen in athletes, has been associated with better survival in epidemiological studies. In patients with coronary artery disease, heart rate is considered an independent risk factor for adverse outcomes. Higher heart rate increases cardiac work load and oxygen demand and reduces coronary perfusion by decreasing the amount of time spent in diastole, which in patients with obstructive coronary artery disease can trigger angina and myocardial infarction. Whether pharmacological reduction in heart rate by using a beta-blocker or ivabradine improves prognosis has been debated. In this review, we explore the effect of pharmacological heart rate lowering with a beta-blocker or ivabradine on cardiovascular outcomes in patients with cardiovascular disease and address the question as to whether pharmacological heart rate reduction is ready for prime time in the management of patients with coronary artery disease. Although physiologically lower heart rates are associated with improved survival, the effect of pharmacological heart rate reduction with beta-blockers (in patients without heart failure or postmyocardial infarction) or ivabradine on improvement in survival is weak at best.

BACKGROUND:Kidney transplantation (KT) is the treatment of choice for end-stage kidney disease. Cardiovascular disease is a major determinant of morbidity and mortality in patients with KT. Temporal trends in perioperative cardiovascular outcomes after KT are understudied, especially in light of an aging KT waitlist population. METHODS:We performed a retrospective observational cohort study using the National Inpatient Sample for the years 2004-2013. All adult patients undergoing KT were identified using the appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. Demographic and hospital characteristics, discharge disposition, payer status, and major adverse cardiovascular events (MACEs) were summarized using summary statistics. Multivariate logistic regression was used to identify predictors of MACEs in the perioperative period of KT. RESULTS:A total of 147,431 KTs were performed between 2004 and 2013. The mean age at KT went up from 48.1 to 51.8 years from 2004 to 2013. Medicare was the primary payer for 59.6% of the KTs. Overall average perioperative mortality was 0.5%, median length of stay was 5 days, and 6.5% of patients experienced an MACE, 78% of which were heart failures (HFs). Important predictors of perioperative MACEs were age ≥65 years (OR = 2.14), Medicare as primary payer (OR = 1.51), diabetes (OR = 1.46), recreational drug use (OR = 1.72), pulmonary circulation disorders (OR = 3.28), and malnutrition (OR = 1.91). CONCLUSION/CONCLUSIONS:Despite increases in age at the time of KT, the absolute risk of perioperative MACEs has remained stable from 2004 to 2013. HF is a major component of postoperative MACEs in KT. Malnutrition and pulmonary hypertension are major nontraditional predictors of perioperative MACE outcomes.

Background/UNASSIGNED:Perioperative cardiovascular outcomes of transplant surgery are not well defined. We evaluated the incidence of perioperative major cardiovascular and cerebrovascular events (MACCE) after non-cardiac transplant surgery from a large database of hospital admissions from the United States. Methods/UNASSIGNED:Patients ≥18 years of age undergoing non-cardiac solid organ transplant surgery from 2004 to 2014 were identified from the Healthcare Cost and Utilization Project's (HCUP) National Inpatient Sample (NIS). The primary outcome was perioperative MACCE, defined as in-hospital death, myocardial infarction (MI), or ischemic stroke. Results/UNASSIGNED:A total of 49,978 hospitalizations for transplant surgery were identified. Renal (67.3%), liver (21.6%), and lung (6.7%) transplantation were the most common surgeries. Perioperative MACCE occurred in 1,539 transplant surgeries (3.1%). Recipients of organ transplantation were more likely to have perioperative MACCE in comparison to non-transplant, non-cardiac surgery (3.1% vs. 2.0%, p < 0.001; adjusted OR [aOR] 1.29, 95% CI 1.22-1.36). MACCE after transplant surgery were driven by increased mortality (1.7% vs. 1.1%, p < 0.001; aOR 1.15, 95% CI 1.07-1.23) and MI (1.2% vs. 0.6%, p < 0.001; aOR 2.26, 95% CI 2.09-2.46) versus non-transplant surgery, with lower rates of stroke (0.3% vs. 0.5%, p < 0.001; aOR 0.56, 95% CI 0.47-0.65). Among patients hospitalized for renal, liver, and lung transplantation, MACCE occurred in 1.7%, 5.6%, and 7.5%, respectively, with no difference in the frequency of MI by surgery type. Conclusions/UNASSIGNED:Cardiovascular outcomes of transplant surgery vary by surgical subtype and are largely driven by increased perioperative death and MI. Efforts to reduce cardiovascular risks of non-cardiac organ transplant surgery are necessary.

Introduction: There are scant data on the use of P2Y12 antagonist therapy upstream of diagnostic angiography (DA), especially when administered in the ED for NSTEMI. We host a multicenter US registry to describe patterns of upstream P2Y12therapy and outcomes.
Method(s): UPSTREAM (NCT02271022) is an ongoing prospective, observational registry of consecutive NSTEMI patients, evaluated in an ED, who at the treating clinician's discretion are given a loading dose (LD) of ticagrelor, clopidogrel, or prasugrel 4 or more hrs prior to DA, which in turn is performed no more than 72 hrs after ED arrival. Data are collected on all patients through hospital discharge. Those patients receiving ticagrelor throughout the index hospitalization and at discharge are followed 30-40 days for vital status, rehospitalization, bleeding complications, and P2Y12 compliance. We report the in-hospital outcomes of the first 2512 NSTEMI patients studied at 54 hospitals.
Result(s): In this cohort over 3.5 years' enrollment, the P2Y12 upstream LD was clopidogrel in 53%, ticagrelor in 46%, and prasugrel in 1%, although agent switching during hospitalization and at discharge occurs. Overall, 1355 (54%) received at least one dose of ticagrelor? 697 (27.7%) were maintained on ticagrelor consistently and had 30-day follow-up completed. Patients had a mean age of 63 y? 19% are older than 75 y. Approximately 21% of patients had a documented prior MI, 26% had a prior stent, 15% had prior CABG, and 12% had documented CKD. The median (SD) time from ED arrival to LD was 6.4 (6.7) h, and time from LD to DA was 11.3 (9.5) h. DA was performed via femoral access in 57% of patients and radially in 43%. Post-DA management was 58% stent, 34% medical management, and 8% CABG. In-hospital CV events, including mortality, were infrequent (0.6%). Only 53 patients (31 [1.2%] CABG-related and 22 [0.9%] non-CABG) required RBC transfusion, while 23 (19 CABG-related) required a platelet transfusion. Six stent thrombosis events were recorded.
Conclusion(s): Upstream P2Y12therapy in NSTEMI patients undergoing an invasive strategy is associated with good clinical outcomes and minimal risk of bleeding. The most commonly used

Introduction: In patients presenting to non-PCI capable hospital with STEMI, the management options include transfer for primary PCI (PPCI) or administration of thrombolytics and transfer for PCI (lytics + PCI), a decision largely driven by the estimated door to device time. The 2013 AHA/ACC STEMI guidelines increased the door to device time for STEMI transfer patients from < 90 minutes to < 120 minutes. Whether this change has impacted management is not known.
Method(s): Patients in the New York (NY) State PCI Registry who underwent PCI (PPCI or lytics + PCI) for STEMI after being transferred from a non-PCI capable hospital in 2012 and 2014 were included in this study. Primary outcome was a change in the proportion of patients who underwent PPCI in relation to lytics + PCI in 2014 as compared with year 2012. Secondary outcomes were changes in transfer time (non-PCI capable transfer hospital door to PCI hospital door time), PCI hospital door to device time, transfer hospital door to device time in PPCI patients, and in-hospital mortality for all STEMI transfer patients who underwent PCI.
Result(s): There were 2019 and 1799 patients who underwent PCI (PCI or lytics +PCI) for a STEMI after presenting to a non-PCI capable hospital in NY State in 2012 and 2014 respectively. There was an increase in the proportion of patients receiving PPCI (vs lytics+ PCI) from 2012 to 2014 (74.15% to 78.32%, p = 0.0025). Moreover, in patients receiving PPCI, there was also a decrease in transfer time [median: 102 min (Q1:73, Q3162) to 97 min (Q1: 70, Q3:147),p = 0.005], PCI hospital door to device time [35 min (25,53) to 34 min (24, 51), p = 0.07), and transfer hospital door to device time [143 min (105, 220) to 134 min (102, 200), p = 0.005]. However, there was no change in mortality from 2012 to 2014 in all STEMI transfer patients who underwent PCI (2.13% vs 2.95%, p = 0.11).
Conclusion(s): Data from NY State indicates a significant increase in referral for PPCI in patients presenting with a STEMI to a non-PCI capable hospital with the change in guidelines increasing the door to device times for transfer patients. Whether such a strategy improves outcomes should be tested in further studies