Faculty Bibliography

OBJECTIVE:To evaluate the impact of COVID-19 pandemic migitation measures on of ST-elevation myocardial infarction (STEMI) care. BACKGROUND:We previously reported a 38% decline in cardiac catheterization activations during the early phase of the COVID-19 pandemic mitigation measures. This study extends our early observations using a larger sample of STEMI programs representative of different US regions with the inclusion of more contemporary data. METHODS:Data from 18 hospitals or healthcare systems in the US from January 2019 to April 2020 were collecting including number activations for STEMI, the number of activations leading to angiography and primary percutaneous coronary intervention (PPCI), and average door to balloon (D2B) times. Two periods, January 2019-February 2020 and March-April 2020, were defined to represent periods before (BC) and after (AC) initiation of pandemic mitigation measures, respectively. A generalized estimating equations approach was used to estimate the change in response variables at AC from BC. RESULTS:Compared to BC, the AC period was characterized by a marked reduction in the number of activations for STEMI (29%, 95% CI:18-38, p < .001), number of activations leading to angiography (34%, 95% CI: 12-50, p = .005) and number of activations leading to PPCI (20%, 95% CI: 11-27, p < .001). A decline in STEMI activations drove the reductions in angiography and PPCI volumes. Relative to BC, the D2B times in the AC period increased on average by 20%, 95%CI (-0.2 to 44, p = .05). CONCLUSIONS:The COVID-19 Pandemic has adversely affected many aspects of STEMI care, including timely access to the cardiac catheterization laboratory for PPCI.

Data on ischemic and bleeding outcomes after percutaneous coronary intervention (PCI) in high bleeding risk (HBR) patients with chronic kidney disease (CKD) are scarce. We aimed to evaluate the association between CKD and ischemic and bleeding outcomes in HBR patients who underwent PCI. Among 10,502 patients in the four post-approval registries evaluating patients undergoing PCI, 2,300 patients presented with at least one major or two minor ARC-HBR criteria. CKD was defined as eGFR < 60 mL/min/1.73 m². These HBR patients were divided into 3 groups: eGFR < 30 mL/min/1.73 m² defined as severe CKD (N = 221), eGFR 30- < 60 mL/min/1.73 m² defined as moderate CKD (N = 970), eGFR ≥ 60 mL/min/1.73 m² defined as no CKD (N = 1,109). The primary endpoint was the composite of cardiac death, myocardial infarction, or stent thrombosis, and the safety endpoint was major bleeding up to 4-year follow-up. HBR patients with CKD were more often female and had higher rates of comorbidities compared to those without CKD. Reduced renal function was associated with higher rates of the primary endpoint (severe CKD vs. moderate CKD vs. no CKD: 30.2% vs. 12.5% vs. 9.1%, P < 0.01) as well as major bleeding (10.3% vs. 8.9% vs. 6.4%, P = 0.03). After adjustment, severe CKD and moderate CKD in HBR patients remained independent predictors for the primary endpoint (HR [95%CI] 2.84 [1.94-4.16], P < 0.01, 1.48 [1.10-2.00], P < 0.01) compared to those with no CKD. However, decreased renal function was no longer significantly associated with major bleeding after adjustment. In conclusions, in HBR patients undergoing PCI, CKD has an important impact on major ischemic events after PCI.

BACKGROUND:Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES/OBJECTIVE:In this post-hoc analysis from ISCHEMIA-CKD, we compared outcomes of patients not listed versus those listed according to management strategy. METHODS:In ISCHEMIA-CKD (n=777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction [MI]) and secondary (death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS:Compared with those not listed, listed patients were younger (60 versus 65 years), less likely of Asian race (15% versus 29%), more likely on dialysis (83% versus 44%), had fewer anginal symptoms, and more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for the primary outcome were 0.91 (0.54-1.54) and 1.03 (0.78-1.37) for those listed and not listed, respectively (pinteraction=0.68). Adjusted HR for secondary outcomes were 0.89 (0.55-1.46) in listed and 1.17 (0.89-1.53) in those not listed (pinteraction=0.35). CONCLUSIONS:In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant.

AIMS /UNASSIGNED:Contemporary 2nd-generation thin-strut drug-eluting stents (DES) are considered standard of care for revascularization of patients undergoing percutaneous coronary intervention. A previous meta-analysis of 10 randomized controlled trials (RCTs) with 11 658 patients demonstrated a 16% reduction in the 1-year risk of target lesion failure (TLF) with ultrathin-strut DES compared with conventional 2nd-generation thin-strut DES. Whether this benefit is sustained longer term is not known, and newer trial data may inform these relative outcomes. We therefore sought to perform an updated systematic review and meta-analysis of RCTs comparing clinical outcomes with ultrathin-strut DES (≤70 µm strut thickness) with conventional 2nd-generation thin-strut DES. METHODS AND RESULTS /UNASSIGNED:We performed a random-effects meta-analysis of all RCTs comparing ultrathin-strut DES to conventional 2nd-generation thin-strut DES. The pre-specified primary endpoint was long-term TLF, a composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included the components of TLF, stent thrombosis (ST), and all-cause death. There were 16 eligible trials in which 20 701 patients were randomized. The weighted mean follow-up duration was 2.5 years. Ultrathin-strut DES were associated with a 15% reduction in long-term TLF compared with conventional 2nd-generation thin-strut DES [relative risk (RR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.008] driven by a 25% reduction in CD-TLR (RR 0.75, 95% CI 0.62-0.92, P = 0.005). There were no significant differences between stent types in the risks of MI, ST, cardiac death, or all-cause mortality. CONCLUSIONS /UNASSIGNED:At a mean follow-up of 2.5 years, ultrathin-strut DES reduced the risk of TLF, driven by less CD-TLR compared with conventional 2nd-generation thin-strut DES, with similar risks of MI, ST, cardiac death, and all-cause mortality.

Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB- and nuclear factor, erythroid 2 like 2 (Nrf2)-mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2.

BACKGROUND:With newer generation drug eluting stents (DES), 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. Our 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 percutaneous coronary intervention (PCI). METHODS: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. RESULTS:Our 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 to long-term DAPT (12 months and >12 months). For bleeding outcomes, ≤3 months DAPT was associated with significant reduction in bleeding compared to 6 months, 12 months or >12 months DAPT (OR [95% CI]: 0.60 [0.37-0.98]; 0.68 [0.54-0.85] and 0.43 [0.34-0.54], respectively). These findings were similar when limited to 2nd generation DES. CONCLUSIONS:Data from this meta-analysis of randomized trials support short-term (≤3 months and 6 months) DAPT in patients with ACS undergoing PCI. Guidelines might need to consider short-term DAPT even in patients presenting with ACS, especially in this era of newer generation DES.

OBJECTIVES/OBJECTIVE:This study aimed to examine the concordance of coronary computed tomographic angiography (CCTA) assessment of coronary anatomy and invasive coronary angiography (ICA) as the reference standard in patients enrolled in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA). BACKGROUND:Performance of CCTA compared with ICA has not been assessed in patients with very high burdens of stress-induced ischemia and a high likelihood of anatomically significant coronary artery disease (CAD). A blinded CCTA was performed after enrollment to exclude patients with left main (LM) disease or no obstructive CAD before randomization to an initial conservative or invasive strategy, the latter guided by ICA and optimal revascularization. METHODS:Rates of concordance were calculated on a per-patient basis in patients randomized to the invasive strategy. Anatomic significance was defined as ≥50% diameter stenosis (DS) for both modalities. Sensitivity analyses using a threshold of ≥70% DS for CCTA or considering only CCTA images of good-to-excellent quality were performed. RESULTS:In 1,728 patients identified by CCTA as having no LM disease ≥50% and at least single-vessel CAD, ICA confirmed 97.1% without LM disease ≥50%, 92.2% with at least single-vessel CAD and no LM disease ≥50%, and only 4.9% without anatomically significant CAD. Results using a ≥70% DS threshold or only CCTA of good-to-excellent quality showed similar overall performance. CONCLUSIONS:CCTA before randomization in ISCHEMIA demonstrated high concordance with subsequent ICA for identification of patients with angiographically significant disease without LM disease.

Cardiac catheterization procedures have rapidly evolved and expanded in scope and techniques over the past few decades. However, although some practices have emerged based on evidence, many traditions have persisted based on beliefs and theoretical concerns. The aim of this review is to highlight common preprocedure, intraprocedure, and postprocedure catheterization laboratory practices where evidence has accumulated over the past few decades to support or discount traditionally held practices.

BACKGROUND:Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS:In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS/RESULTS:Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION/CONCLUSIONS:Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING/BACKGROUND:ReCor Medical.