Faculty Bibliography

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.

Background: Revascularization is often performed in patients with stable ischemic heart disease (SIHD). However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. Methods: We conducted PUBMED/EMBASE/CENTRAL searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with SIHD. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. Results: Fourteen RCTs that enrolled 14,877 patients followed up for a weighted mean of 4.5 years with 64,678 patient years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function, low symptom burden and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (RR=0.99, 95% CI 0.90-1.09). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced non-procedural MI (RR=0.76, 95% CI 0.67-0.85) but also with increased procedural MI (RR=2.48, 95% CI 1.86-3.31) with no difference in overall MI (RR=0.93, 95% CI 0.83-1.03). A significant reduction in unstable angina (RR=0.64, 95% CI 0.45-0.92) and increase in freedom from angina (RR=1.10, 95% CI 1.05-1.15) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. Conclusions: In patients with SIHD, routine revascularization was not associated with improved survival, but was associated with a lower risk of non-procedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these non-fatal spontaneous events improves long-term survival.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure and mortality have been reported with the use of these drugs. It is important to have a knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.

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.

OBJECTIVES/OBJECTIVE:We aimed to investigate the efficacy and safety of different antithrombotic strategies in patients undergoing transcatheter aortic valve implantation (TAVI) using network meta-analyses. BACKGROUND:Meta-analyses comparing single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT), ± oral anticoagulant (OAC) was conducted to determine the appropriate post TAVI antithrombotic regimen. However, there was limited direct comparisons across the different therapeutic strategies. METHODS:MEDLINE and EMBASE were searched through December 2018 to investigate the efficacy and safety of different antithrombotic strategies (SAPT, DAPT, OAC, OAC + SAPT, and OAC + DAPT) in patients undergoing TAVI. The main outcome were all-cause mortality, major or life-threatening bleeding events, and stroke. RESULTS:= 0%). There was no significant difference on stroke among all antithrombotic strategies. CONCLUSION/CONCLUSIONS:Patients who underwent TAVI had similar all-cause mortality rates among different antithrombotic strategies except OAC+DAPT. Patients on SAPT had significantly lower bleeding risk than those on DAPT, OAC + SAPT, and OAC + DAPT. Our results suggest SAPT is the preferred regimen when there is no indication for DAPT or OAC. When DAPT or OAC is indicated, DAPT + OAC should be avoided.

Cardiovascular disease, and in particular coronary artery disease (CAD), remains an important contributor of morbidity and mortality among patients with chronic kidney disease (CKD). Classic symptomatology of CAD and effectiveness of established therapeutic measures is less frequent in patients with CKD. This suggests unique characteristics of CAD among patients with CKD. Two important features of CAD in CKD include increased calcific density of atherosclerotic plaques and of the vessels themselves (coronary artery calcification -- CAC), as well as a decrease in microcirculatory function -- or coronary microcirculatory dysfunction. A multitude of pathophysiologic pathways have been identified that contribute to CAC in CKD; less is known about the pathophysiology of microcirculatory dysfunction. It is not well established if these two processes are directly related to each other, but the combination results in a greater severity of effect on overall myocardial function and may in part explain the greater preponderance of silent myocardial infarction. Further investigation is needed to better understand these unique aspects of CAD in CKD as well as the role they play in overall CVD in this group, and ultimately therapeutics that may lessen the burden of disease.

BACKGROUND:There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS:We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS:Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS:We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.