Faculty Bibliography

Background: With newer generation drug-eluting stents, the minimal duration of dual antiplatelet therapy (DAPT) recommended by guidelines has been reduced to 6 months in patients with stable coronary artery disease. Whether shorter duration of DAPT is safe in patients presenting with acute coronary syndrome (ACS) remains controversial. The aim of this study was to investigate the optimal DAPT duration (<=3 months vs. 6 months vs. 12 months vs. >12 months) among patients with ACS undergoing PCI.
Method(s): PubMed and Embase were searched through January 2020 for randomized controlled trials of DAPT duration in patients with ACS. The ischemic outcomes were all-cause death, myocardial infarction, and stent thrombosis. The safety outcome was major and/or clinically relevant bleeding.
Result(s): This search identified 14 eligible trials enrolling a total of 31,837 patients comparing different DAPT duration in patients with ACS. Short-term DAPT (<=3 months or 6 months) did not increase ischemic outcomes compared with long-term DAPT (12 months and >12 months). For bleeding outcomes, DAPT duration <=3 months was associated with significant reduction in bleeding compared with DAPT durations of 6 months, 12 months, or >12 months (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.98; HR: 0.68; 95% CI: 0.54 to 0.85; and HR: 0.43; 95% CI: 0.34 to 0.54, respectively).These findings were similar when limited to second-generation drug-eluting stents.
Conclusion(s): Data from this meta-analysis of randomized trials support short-term DAPT (<=3 months and 6 months) even in patients with ACS undergoing PCI. Guidelines should consider short-term DAPT even in patients presenting with ACS, especially in this era of newer generation drug-eluting stents. Categories: CORONARY: Acute Coronary Syndromes
Copyright

Background: The long- term clinical outcomes of percutaneous coronary intervention can be improved by replacing metallic drug-eluting stents with bioresorbable vascular scaffolds. The MeRes-1 Extend trial was designed to assess the safety and efficacy of a novel thin-strut MeRes100 bioresorbable vascular scaffold (Meril Life Sciences) in a diverse patient population.
Method(s): The MeRes-1 Extend was a prospective, multicenter, single-arm study that enrolled 64 patients in Spain, Macedonia, Brazil, South Africa, Malaysia, and Indonesia. Major adverse cardiac events, consisting of cardiac death, myocardial infarction, and ischemia-driven target lesion revascularisation, were the safety endpoint. At baseline and 6-month follow-up, quantitative coronary angiography and optical coherence tomography were performed.
Result(s): Of all patients enrolled (mean age: 58.30 +/- 9.02 years), 76.56% had hypertension, 26.56% had diabetes mellitus, 48.44% had dyslipidemia, and 28.13% had a previous myocardial infarction; 68.75% of patients presented with stable angina, 9.38% with unstable angina, and 21.88% with silent ischemia. A total of 69 target lesions (mean length: 14.37 +/- 5.89 mm) were detected of which 71.01% were type B2/C. Procedural and device success were achieved in 64 and 62 patients, respectively. Major adverse cardiac events rate was reported in 1 patient (1.61%) in the form of ischemia-driven target lesion revascularization; there were no cases of myocardial infarction, cardiac death, or scaffold thrombosis. At 6-month angiographic follow-up (n = 32), mean in-scaffold late lumen loss was 0.18 +/- 0.31 mm. Optical coherence tomography analysis (n = 21) showed 97.95 +/- 3.69% strut coverage and mean scaffold area of 7.56 +/- 1.79 mm², with no strut malapposition. Updated data will be presented during Transcatheter Cardiovascular Therapeutics 2020 annual meeting.
Conclusion(s): Two-year clinical and 6-month imaging outcomes of MeRes-1 Extend trial demonstrated favorable safety and efficacy of novel thin-strut MeRes100 sirolimus-eluting bioresorbable vascular scaffolds in patients with de novo coronary artery lesions. Categories: CORONARY: Stents: Bioresorbable Vascular Scaffolds
Copyright

Alport syndrome affects up to 60,000 people in the United States. The proposed reclassification of thin basement membrane nephropathy and some cases of focal segmental glomerulosclerosis as Alport syndrome could substantially increase the affected population. The reclassification scheme categorizes Alport syndrome as 3 distinct diseases of type IV collagen α3/4/5 based on a genetic evaluation: X-linked, autosomal, and digenic. This approach has the advantage of identifying patients at risk for progressive loss of kidney function. Furthermore, the shared molecular cause of Alport syndrome and thin basement membrane nephropathy arises from mutations in the COL4A3, COL4A4, and COL4A5 genes, which contribute to downstream pathophysiologic consequences, including chronic kidney inflammation. Recent evidence indicates that chronic inflammation and its regulation through anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2) and proinflammatory nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) transcription factors plays a central role in renal tubular and glomerular cell responses to injury. Crosstalk between the Nrf2 and NF-κB pathways is important in the regulation of inflammation in patients with chronic kidney disease; moreover, there is evidence that an insufficient Nrf2 response to inflammation contributes to disease progression. Given the association between type IV collagen abnormalities and chronic inflammation, there is renewed interest in targeted anti-inflammatory therapies in Alport syndrome and other forms of progressive chronic kidney disease.

Several machine learning (ML) algorithms have been increasingly utilized for cardiovascular disease prediction. We aim to assess and summarize the overall predictive ability of ML algorithms in cardiovascular diseases. A comprehensive search strategy was designed and executed within the MEDLINE, Embase, and Scopus databases from database inception through March 15, 2019. The primary outcome was a composite of the predictive ability of ML algorithms of coronary artery disease, heart failure, stroke, and cardiac arrhythmias. Of 344 total studies identified, 103 cohorts, with a total of 3,377,318 individuals, met our inclusion criteria. For the prediction of coronary artery disease, boosting algorithms had a pooled area under the curve (AUC) of 0.88 (95% CI 0.84-0.91), and custom-built algorithms had a pooled AUC of 0.93 (95% CI 0.85-0.97). For the prediction of stroke, support vector machine (SVM) algorithms had a pooled AUC of 0.92 (95% CI 0.81-0.97), boosting algorithms had a pooled AUC of 0.91 (95% CI 0.81-0.96), and convolutional neural network (CNN) algorithms had a pooled AUC of 0.90 (95% CI 0.83-0.95). Although inadequate studies for each algorithm for meta-analytic methodology for both heart failure and cardiac arrhythmias because the confidence intervals overlap between different methods, showing no difference, SVM may outperform other algorithms in these areas. The predictive ability of ML algorithms in cardiovascular diseases is promising, particularly SVM and boosting algorithms. However, there is heterogeneity among ML algorithms in terms of multiple parameters. This information may assist clinicians in how to interpret data and implement optimal algorithms for their dataset.

OBJECTIVE:To describe from a non-interventional registry the short-term ischemic and hemorrhagic outcomes in patients with NSTEMI managed with a loading dose of a P2Y12 inhibitor (P2Y12i) given at least four hours prior to diagnostic angiography and delineation of coronary anatomy. Prior data on the effects of such "upstream loading" have been inconsistent. METHODS:In 53 US hospitals, we evaluated the in-hospital care and outcomes of patients with confirmed NSTEMI managed with an interventional strategy and loaded upstream (at least four hours before diagnostic angiography) with P2Y12 inhibitor therapy. Patients entered into the database were grouped into one of four cohorts for analysis: (1) overall cohort, (2) thienopyridine (clopidogrel or prasugrel) load, (3) ticagrelor load, and (4) ticagrelor-consistent. The fourth cohort is a subset of cohort 3 that received ticagrelor throughout the index hospital stay and at discharge. We evaluated in-hospital clinical course and ischemic and bleeding outcomes in all patients, and also 30-d outcomes in the ticagrelor-consistent cohort. RESULTS:A total of 3,355 patients were enrolled, of whom 1,087 had 30-day follow-up. The mean (+/-SD) age was 63.3+/-12.5 y and 62.6% were male. TIMI and GRACE scores placed these patients in the intermediate risk range and CRUSADE scores were in the moderate risk range. The loading dose in UPSTREAM was clopidogrel in 45.6%, ticagrelor in 53.6%, and prasugrel in 0.8%. The median upstream interval (loading dose to angiography) was 17:27 hours and did not change appreciably over the course of the data collection period (2/15 - 10/19). Access was radial in 48.6% and femoral in 51.4%. Post-angiography management was medical only in 32.3%, PCI in 59.4%, and CABG in 8.3%. Median LOS was 2.7d, and median time from angiography to CABG was 3.6d. In-hospital mortality was 0.51% and major bleeding (TIMI) was 0.24%; the in-hospital MACE rate was 0.7% and stent thrombosis occurred in 0.18%. No significant differences were seen between the ticagrelor and clopidogrel cohorts in hospital, but 16% received more than one P2Y12i in-hospital. On follow-up (93.2% response), 86.7% of patients reported taking ticagrelor as directed. CONCLUSION/CONCLUSIONS:Upstream loading of P2Y12 inhibitors was associated with very low rates of bleeding and short LOS in a large cohort of NSTEMI patients managed invasively.

INTRODUCTION/BACKGROUND:Chronic kidney disease is an independent risk factor for cardiovascular disease. Despite careful preoperative evaluation, there is a risk of acute coronary syndromes after kidney transplant. METHODS:The National Inpatient Sample for the years 2004-2013 was used for this retrospective cohort study. All adult patients undergoing kidney transplantation were identified using the appropriate ICD-9-CM codes. Multivariate logistic regression was used to identify predictors of acute coronary syndromes in the peri-operative period after kidney transplantation. RESULTS:A total of 147,431 kidney transplants were performed from 2004 through 2013 in United States. The average peri-operative in-hospital mortality was 0.5%. Acute coronary syndrome occurred in 1.3% patients in the peri-operative period. Half of patients with acute coronary syndromes had pre-existing coronary artery disease. The strongest predictors of acute coronary syndromes included older age: 45-64 yrs. OR 3.28 95% CI (1.85-5.83), ≥65 yrs. OR 4.84 (2.59-9.05), race: African-American, OR 0.66 (0.47-0.93) and preexisting coronary artery disease OR 3.83 (2.84-5.15). The case fatality rates were 16.9% and 5.3% for STEMI and NSTEMI, respectively. The overall mortality for any ACS event was 7.1%. CONCLUSION/CONCLUSIONS:Acute coronary syndrome in the immediate peri-operative period after kidney transplantation is rare but is associated with high rates of mortality.

BACKGROUND:In the COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial, angiography-guided percutaneous coronary intervention (PCI) of nonculprit lesions with the aim of complete revascularization reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (MI) and multivessel coronary artery disease. OBJECTIVES/OBJECTIVE:The purpose of this study was to determine the effect of nonculprit-lesion stenosis severity measured by quantitative coronary angiography (QCA) on the benefit of complete revascularization. METHODS:Among 4,041 patients randomized in the COMPLETE trial, nonculprit lesion stenosis severity was measured using QCA in the angiographic core laboratory in 3,851 patients with 5,355 nonculprit lesions. In pre-specified analyses, the treatment effect in patients with QCA stenosis ≥60% versus <60% on the first coprimary outcome of CV death or new MI and the second co-primary outcome of CV death, new MI, or ischemia-driven revascularization was determined. RESULTS:The first coprimary outcome was reduced with complete revascularization in the 2,479 patients with QCA stenosis ≥60% (2.5%/year vs. 4.2%/year; hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47 to 0.79), but not in the 1,372 patients with QCA stenosis <60% (3.0%/year vs. 2.9%/year; HR: 1.04; 95% CI: 0.72 to 1.50; interaction p = 0.02). The second coprimary outcome was reduced in patients with QCA stenosis ≥60% (2.9%/year vs. 6.9%/year; HR: 0.43; 95% CI: 0.34 to 0.54) to a greater extent than patients with QCA stenosis <60% (3.3%/year vs. 5.2%/year; HR: 0.65; 95% CI: 0.47 to 0.89; interaction p = 0.04). CONCLUSIONS:Among patients with ST-segment elevation MI and multivessel coronary artery disease, complete revascularization reduced major CV outcomes to a greater extent in patients with stenosis severity of ≥60% compared with <60%, as determined by quantitative coronary angiography.