Faculty Bibliography

Aortic stenosis (AS) is the most common age-related valvular condition with a prevalence of 13.1% in patients older than 75 years of age. Based on the severity of AS and symptoms, current guidelines recommend interval monitoring with transthoracic echocardiogram (TTE). However, no guidelines exist regarding screening asymptomatic persons for AS. Prevalence of AS is comparable to conditions such as colorectal cancer, lung cancer, breast cancer, and abdominal aortic aneurysm where dedicated screening programs are offered resulting in reduction of overall morbidity and mortality. We review recent advancements in treatment options, and we propose an AS screening program for high-risk individuals without known history of AS including all persons over age 75 and persons aged 70 years and older with dialysis dependent end-stage renal disease (ESRD).

BACKGROUND:Patients with acute pulmonary embolism (PE) and hypotension (high-risk PE) have high mortality. Cardiogenic shock can also occur in nonhypotensive or normotensive patients (intermediate-risk PE) but is less well characterized. OBJECTIVES/OBJECTIVE:The authors sought to evaluate the prevalence and predictors of normotensive shock in intermediate-risk PE. METHODS:) was assessed. A composite shock score consisting of markers of right ventricular function and ischemia (elevated troponin, elevated B-type natriuretic peptide, moderately/severely reduced right ventricular function), central thrombus burden (saddle PE), potential additional embolization (concomitant deep vein thrombosis), and cardiovascular compensation (tachycardia) was prespecified and assessed for its ability to identify normotensive shock patients. RESULTS:Over one-third of intermediate-risk PE patients in FLASH (131/384, 34.1%) were in normotensive shock. The normotensive shock prevalence was 0% in patients with a composite shock score of 0 and 58.3% in those with a score of 6 (highest score). A score of 6 was a significant predictor of normotensive shock (odds ratio: 5.84; 95% CI: 2.00-17.04). Patients showed significant on-table improvements in hemodynamics post-thrombectomy, including normalization of the cardiac index in 30.5% of normotensive shock patients. Right ventricular size, function, dyspnea, and quality of life significantly improved at the 30-day follow-up. CONCLUSIONS:Although hemodynamically stable, over one-third of intermediate-risk FLASH patients were in normotensive shock with a depressed cardiac index. A composite shock score effectively further risk stratified these patients. Mechanical thrombectomy improved hemodynamics and functional outcomes at the 30-day follow-up.

OBJECTIVES/OBJECTIVE:The evidence supporting the use of the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score for risk stratification is controversial. We performed a systematic review and meta-analysis of all the randomized controlled trials comparing percutaneous coronary intervention versus coronary artery bypass grafting that reported their outcomes stratified by SYNTAX score, focusing on between-strata comparisons. METHODS:A systematic review of MEDLINE, EMBASE, Cochrane Library databases was performed. Incidence rate ratios were pooled with a random effect model. Between-group statistical heterogeneity according to accepted SYNTAX score tertiles was computed in the main analysis. Ratios of incidence rate ratios were computed to appraise between-strata effect, as sensitivity analysis. Primary and secondary outcomes were major adverse cardiac and cerebrovascular events and all-cause mortality, respectively. Separate sub-analyses were performed for left main and multivessel disease. RESULTS:From 425 citations, 6 trials were eventually included (8269 patients [4134 percutaneous coronary interventions, 4135 coronary artery bypass graftings]; mean follow-up: 6.2 years [range: 3.8-10]). Overall, percutaneous coronary intervention was associated with a significant increase in major adverse cardiac and cerebrovascular events (incidence rate ratio, 1.39, 95% confidence interval, 1.27-1.51) and nonsignificant increase in all-cause mortality (incidence rate ratio, 1.17, 95% confidence interval, 0.98-1.40). There was no significant statistical heterogeneity of treatment effect by SYNTAX score for major adverse cardiac and cerebrovascular events or mortality (P = .40 and P = .34, respectively). Results were consistent also for patients with left main and multivessel disease (major adverse cardiac and cerebrovascular events: P = .85 in left main, P = .78 in multivessel disease 0.78; mortality: P = .12 in left main; P = .34 in multivessel disease). Results of analysis based on ratios of incidence rate ratios were consistent with the main analysis. CONCLUSIONS:No significant association was found between SYNTAX score and the comparative effectiveness of percutaneous coronary intervention and coronary artery bypass grafting. These findings have implications for clinical practice, future guidelines, and the design of percutaneous coronary intervention versus coronary artery bypass grafting trials.

BACKGROUND:A substantial proportion of patients with HF and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of angiotensin receptor neprilysin inhibitor (ARNI) or angiotensin-converting enzyme inhibitor (ACEI) /angiotensin receptor blocker (ARB) across the spectrum of kidney function. METHODS:Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate. To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates. RESULTS:>0.10 for both). CONCLUSION/CONCLUSIONS:The use of ARNI was associated with significant BP reduction as compared with the ACEI/ARB group overall and across the eGFR spectrum, including in advanced CKD.

BACKGROUND:The optimal duration of hemostatic compression post transradial access is controversial. Longer duration increases the risk of radial artery occlusion (RAO) while shorter duration increases the risk of access site bleeding or hematoma. As such, a target of 2 hours is typically used. Whether a shorter or longer duration is better is not known. METHODS:A PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials of different duration (<90 minutes, 90 minutes, 2 hours, and 2-4 hours) of hemostasis banding. The efficacy outcome was RAO, primary safety outcome was access site hematoma, and secondary safety outcome was access site rebleeding. Primary analysis compared the effect of various duration in reference to the 2 hours duration using a mixed treatment comparison meta-analysis. RESULTS:Of the 10 randomized clinical trials included with 4911 patients, when compared to the 2-hour reference duration, there was a significantly higher risk of access site hematoma with 90 minutes (odds ratio, 2.39 [95% CI, 1.40-4.06]) and <90 minutes (odds ratio, 3.61 [95% CI, 1.79-7.29]) but not with the 2 to 4 hours duration. When compared with the 2-hour reference, there was no significant difference in access site rebleeding or RAO with shorter or longer duration but the point estimates favored longer duration for access site rebleeding and shorter duration for RAO. Duration of <90 minutes and 90 minutes ranked 1 and duration of 2 hours ranked 2 as the most efficacious duration whereas duration of 2 hours ranked 1 and 2 to 4 hours ranked 2 as the safest duration. CONCLUSIONS:In patients undergoing transradial access for coronary angiography or intervention, a hemostasis duration of 2 hours offers the best balance for efficacy (prevention of RAO) and safety (prevention of access site hematoma/rebleeding).

BACKGROUND/UNASSIGNED:The optimal revascularization approach in patients with heart failure with reduced ejection fraction (HFrEF) and ischemic heart disease ("ischemic cardiomyopathy") is unknown. Physician preferences regarding clinical equipoise for mode of revascularization and their willingness to consider offering enrollment in a randomized trial to patients with ischemic cardiomyopathy have not been characterized. METHODS/UNASSIGNED:We conducted two anonymous online surveys: 1) a clinical case scenario-based survey to assess willingness to offer clinical trial enrollment for a patient with ischemic cardiomyopathy (overall response rate to email invitation 0.45 %), and 2) a Delphi consensus-building survey to identify specific areas of clinical equipoise (overall response rate to email invitation 37 %). RESULTS/UNASSIGNED:< 0.0001). In 17 scenarios (11.8 %), there was no difference in CABG or PCI appropriateness ratings, suggesting clinical equipoise in these settings. CONCLUSIONS/UNASSIGNED:Our findings demonstrate willingness to consider offering enrollment in a randomized clinical trial and areas of clinical equipoise, two factors that support the feasibility of a randomized trial to compare clinical outcomes after revascularization with CABG vs. PCI in selected patients with ischemic cardiomyopathy, suitable coronary anatomy and co-morbidity profile.

BACKGROUND:The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease. AIMS:The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events. METHODS:In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%. CONCLUSIONS:The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

BACKGROUND:In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). OBJECTIVES/OBJECTIVE:This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death. METHODS:Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified. RESULTS:A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy. CONCLUSIONS:In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360).