Faculty Bibliography

BACKGROUND:Inflammation is associated with coronary artery disease (CAD) and myocardial infarction (MI). Patients with gout are at increased risk of MI, and colchicine is associated with a reduced risk of MI. The objective of this study was to determine whether colchicine prevents incident development of CAD in patients with gout. METHODS:This retrospective study followed a cohort of male gout patients without known CAD at the time of gout diagnosis in the VA New York Harbor Healthcare System. The association between colchicine use and development of incident CAD, defined as evidence of ischemia or obstructive CAD on stress test or angiography, was determined using an inverse probability weighted (IPW) cox proportional hazard model. RESULTS:Among 178,877 patients, 1,638 met gout criteria, of whom 722 patients without known CAD at baseline (446 colchicine users and 276 non-users) were followed for a median of 96 months [57-117]. A trend toward association between colchicine use and reduced incident CAD was observed but not statistically significant (IPW HR 0.49 [0.23-1.05]). In patients without chronic kidney disease, colchicine use was associated with a lower rate of incident CAD (interaction p=0.005, IPW HR 0.31 [0.14-0.70]). Colchicine was also associated with a lower rate of the composite of incident CAD and MI (IPW HR 0.37 [0.16-0.83]). CONCLUSIONS:In male patients with gout and no known CAD, a trend of reduced incident CAD was observed with colchicine use that was not statistically significant. Larger, prospective studies will be required to definitively assess the primary prevention benefit of colchicine.

Large registries, administrative data, and the electronic health record (EHR) offer opportunities to identify patients with heart failure, which can be used for research purposes, process improvement, and optimal care delivery. Identification of cases is challenging because of the heterogeneous nature of the disease, which encompasses various phenotypes that may respond differently to treatment. The increasing availability of both structured and unstructured data in the EHR has expanded opportunities for cohort construction. This article reviews the current literature on approaches to identification of heart failure, and looks toward the future of machine learning, big data, and phenomapping.

BACKGROUND:Myocardial infarction (MI) complicated by cardiogenic shock (CS) is associated with high mortality. Early coronary revascularization improves survival, but the optimal mode of revascularization remains uncertain. We sought to characterize practice patterns and outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with MI complicated by CS. METHODS:Patients hospitalized for MI with CS between 2002 and 2014 were identified from the United States National Inpatient Sample. Trends in management were evaluated over time. Propensity score matching was performed to identify cohorts with similar baseline characteristics and MI presentations who underwent PCI and CABG. The primary outcome was in-hospital all-cause mortality. RESULTS:A total of 386,811 hospitalizations for MI with CS were identified; 67% were STEMI. Overall, 62.4% of patients underwent revascularization, with PCI in 44.9%, CABG in 14.1%, and a hybrid approach in 3.4%. Coronary revascularization for MI and CS increased over time, from 51.5% in 2002 to 67.4% in 2014 (P for trend < .001). Patients who underwent CABG were more likely to have diabetes mellitus (35.5% vs. 29.2%, P < .001) and less likely to present with STEMI (48.7% vs. 80.9%, P < .001) than those who underwent PCI. CABG (without PCI) was associated with lower mortality than PCI (without CABG) overall (18.9% vs. 29.0%, P < .001) and in a propensity-matched subgroup of 19,882 patients (19.0% vs. 27.0%, P < .001). CONCLUSIONS:CABG was associated with lower in-hospital mortality than PCI among patients with MI complicated by CS. Due to the likelihood of residual confounding, a randomized trial of PCI versus CABG in patients with MI, CS, and multi-vessel coronary disease is warranted.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge and opportunity for translational investigators to rapidly develop safe and effective therapeutic interventions. Greater risk of severe disease in COVID-19 patients with comorbid diabetes mellitus, obesity, and heart disease may be attributable to synergistic activation of vascular inflammation pathways associated with both COVID-19 and cardiometabolic disease. This mechanistic link provides a scientific framework for translational studies of drugs developed for treatment of cardiometabolic disease as novel therapeutic interventions to mitigate inflammation and improve outcomes in patients with COVID-19.

BACKGROUND:Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation. METHODS:Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation. RESULTS:Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia. CONCLUSIONS:Initiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

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.

Cardiogenic shock (CS) complicating acute myocardial infarction (MI) is associated with high mortality. In the absence of data to support coronary revascularization beyond the infarct artery and selection of circulatory support devices or medications, clinical practice may vary substantially.

PURPOSE: Heart transplantation from Hepatitis C (HCV) viremic donors is becoming increasingly used due to advent of direct acting antiviral drugs with almost 100% cure. There are limited data about its impact on cardiac allograft vasculopathy (CAV). We report the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic amplification test positive; NAT+) compared to non-HCV infected donors (NAT-).
METHOD(S): We retrospectively reviewed coronary angiograms with intravascular ultrasound (IVUS) of heart transplant recipients at our institution from January 5, 2018 to September 17, 2019. The presence of CAV was graded according to ISHLT guidelines. IVUS was performed as per our lab protocol on the left main and left anterior descending arteries. Maximal intimal thickness (MIT) was measured with advanced quantification software as per protocol. MIT >= 5mm was considered significant for future adverse outcomes.
RESULT(S): LHC and IVUS was performed on 24 heart transplant recipients (mean age 56; 70% male) at 1- year post transplant. Eleven of these patients were transplanted from NAT+ donors. Thirteen patients received a NAT- donor heart. Two recipients (18.7%) of NAT+ donors had CAV grade >= 1 compared to 2 (16.7%) from NAT- donors (p=1). MIT >= 5mm was seen in 88.9% of NAT+ vs 50% of NAT- recipients (p=0.14) (Figure). The mean MIT was 76mm and 65mm for NAT+ and NAT- group, respectively. Both NAT+ and NAT- donor recipients exhibit mostly eccentric (84.2%) and few (15.7%) demonstrated concentric plaques. There was no heterogeneity in the data after adjusting for risk factors for CAD and donor LHC.
CONCLUSION(S): Our data show no difference in the presence of (CAV >= grade 1) or subclinical atherosclerosis at 1 year among NAT+ donor recipients. HCV viremia is a known risk factor for accelerated atherosclerosis and the consequence of prolonged donor viremia on the recipient is not known. A larger cohort and further longitudinal follow-up is needed to assess the validity of this trend and its prognostic implications.
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PURPOSE: Passive transmission of hepatitis C (HCV) viremia from actively infected donors to uninfected recipients at the time of heart transplantation may modulate response to alloantigens and risk of allograft rejection. We evaluated the one-year incidence of acute cellular rejection (ACR) in patients transplanted from nucleic amplification testing positive (NAT+) HCV donors compared to those from NAT negative (NAT-) donors.
METHOD(S): Since January 2018, 25 patients completed one-year follow-up. All recipients underwent right ventricular endomyocardial biopsy (EMB) per our institution protocol. ACR was graded according to both the 1990 and the revised 2004 International Society for Heart and Lung Transplantation (ISHLT) criteria. All NAT+ donor recipients developed viremia detected by RT-PCR. Mixed models were used to assess the association between donor HCV NAT status, recipient viremia, tacrolimus levels and ACR in the first year post-transplant.
RESULT(S): Twelve NAT+ recipients (mean age 60, 67% male) and 13 NAT- recipients (mean age 54, 77% male) completed one-year follow-up; 182 and 191 EMB were performed, respectively. NAT+ recipients were associated with higher grade rejection compared with NAT- recipients (p=0.041). At least one episode of high grade rejection (2R/3A) occurred in 4 NAT+ recipients (33%) compared with 2 NAT- recipients (15%). At least one episode of low grade rejection (1R/1B or 1R/2) occurred in 11 NAT+ recipients (92%) compared with 7 NAT- recipients (54%). These findings were independent of the presence and magnitude of viremia and tacrolimus levels. No episodes of ACR 3R or antibody mediated rejection were detected during one-year follow-up in either group. There was no allograft dysfunction or mortality related to ACR in either group.
CONCLUSION(S): One year data from our institution demonstrate increased ACR in heart transplant recipients from NAT+ donors. Most of the rejection episodes in the NAT+ group were low grade and did not translate into any adverse outcomes through one-year follow-up.
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BACKGROUND:Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. METHODS:In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. RESULTS:=0.001). CONCLUSIONS:Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT02594111, NCT01709981.