Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:In patients with CKD and end-stage kidney disease (ESKD), cardiac stress testing has low sensitivity and specificity for coronary disease. Alternate markers that are derived during the stress testing may enhance the predictive characteristic of stress testing. The objective was to examine the predictive characteristic of lung-to-heart ratio (LHR) in patients with CKD and ESKD. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS/METHODS:Retrospective parallel cohort of ESKD and CKD not on dialysis (CKD-ND) who underwent stress testing with nuclear myocardial perfusion imaging utilizing sestamibi tracer and regadenoson. Stress LHR was calculated by the processing software and reported. Patients were analyzed by tertile of LHR (≤0.28, 0.29-0.32, ≥0.33). The primary outcome was a composite of all-cause mortality, hospitalization for myocardial infarction or unstable angina, or revascularization. RESULTS:There were 144 CKD-ND and 145 ESKD patients. Patients with ESKD had greater comorbidity burden than CKD-ND. Stress tests were more often performed for pre-operative risk assessment among ESKD versus CKD-ND (53.8 vs. 5.6%, p < 0.001). ESKD patients more likely had ischemia identified on stress testing (19.3 vs. 8.3%, p = 0.001). Mean LHR was 0.31 (Standard deviation - SD: 0.09) and was similar across CKD-ND stages and ESKD. Primary outcome in the lowest (23%) and highest (33.3%) LHR tertile was higher than the middle tertile (12.8%); p = 0.005. This finding was similar between CKD-ND and ESKD and persisted in multivariable analysis. CONCLUSIONS:LHR ≤0.28 and ≥0.33 are independently associated with higher risk for death in patients with CKD-ND and ESKD. Future studies are warranted to understand the association of extreme LHR values and outcomes in this high-risk population.

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.

Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.

AIMS /UNASSIGNED:Since dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, a high sodium intake can be expected to curtail life span. We tested this hypothesis by analysing the relationship between sodium intake and life expectancy as well as survival in 181 countries worldwide. METHODS AND RESULTS /UNASSIGNED:We correlated age-standardized estimates of country-specific average sodium consumption with healthy life expectancy at birth and at age of 60 years, death due to non-communicable diseases and all-cause mortality for the year of 2010, after adjusting for potential confounders such as gross domestic product per capita and body mass index. We considered global health estimates as provided by World Health Organization. Among the 181 countries included in this analysis, we found a positive correlation between sodium intake and healthy life expectancy at birth (β = 2.6 years/g of daily sodium intake, R2 = 0.66, P < 0.001), as well as healthy life expectancy at age 60 (β = 0.3 years/g of daily sodium intake, R2 = 0.60, P = 0.048) but not for death due to non-communicable diseases (β = 17 events/g of daily sodium intake, R2 = 0.43, P = 0.100). Conversely, all-cause mortality correlated inversely with sodium intake (β = -131 events/g of daily sodium intake, R2 = 0.60, P < 0.001). In a sensitivity analysis restricted to 46 countries in the highest income class, sodium intake continued to correlate positively with healthy life expectancy at birth (β = 3.4 years/g of daily sodium intake, R2 = 0.53, P < 0.001) and inversely with all-cause mortality (β = -168 events/g of daily sodium intake, R2 = 0.50, P < 0.001). CONCLUSION /UNASSIGNED:Our observation of sodium intake correlating positively with life expectancy and inversely with all-cause mortality worldwide and in high-income countries argues against dietary sodium intake being a culprit of curtailing life span or a risk factor for premature death. These data are observational and should not be used as a base for nutritional interventions.

Background: In ISCHEMIA, an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality compared with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular endpoints was myocardial infarction. Methods: ISCHEMIA prespecified that the primary and major secondary composite endpoints of the trial be analyzed using two MI definitions. For procedural MI, the primary MI definition used CK-MB as the preferred biomarker whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times URL for PCI and >10 times for CABG. Procedural MI definitions included (i) a category of elevated biomarker only events with much higher biomarker thresholds (ii) new ST segment depression of ≥ 1mm for the primary and ≥ 0.5 mm for the secondary definition and (iii) new coronary dissections ≥ NHLBI grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions. Results: Procedural MI's accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive vs conservative strategy using the primary [2.7% vs. 1.1%; adjusted HR 2.98 (95% CI 1.87, 4.73)] and secondary [8.2% vs. 2.0%; adjusted HR 5.04 (95% CI 3.64, 6.97)] MI definitions. Type 1 MI's were less frequent with the invasive vs conservative strategy using the primary [3.40% vs. 6.89%; adjusted HR 0.53 (95% CI 0.41,0.69); p<0.0001], and secondary [3.48% vs 6.89%; adjusted HR 0.53 (95% CI 0.41, 0.69); p<0.0001] definitions. The risk of subsequent cardiovascular death was higher after a type 1 MI compared to no MI using the primary [adjusted HR 3.38 (95% CI 2.03,5.61); p<0.001] or secondary MI definition [adjusted HR 3.52 (2.11, 5.88); p<0.001]. Conclusions: In ISCHEMIA, type 1 MI events using the primary and secondary definitions during 5-year follow-up were more frequent with an initial conservative strategy and associated with subsequent cardiovascular death. Procedural MI rates were greater in the invasive strategy and using the secondary MI definition. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01471522.

OBJECTIVES/OBJECTIVE:This study explores the safety and efficacy of thin strut MeRes100 sirolimus-eluting bioresorbable vascular scaffold (BRS) in patients with de novo coronary artery lesions. BACKGROUND:In interventional cardiology, the emergence of BRS technology is catalyzing the next paradigm shift. METHODS:The MeRes-1 Extend was a multicenter, prospective, single-arm, open-label study enrolling 64 patients in Spain, Macedonia, Brazil, South Africa, Malaysia, and Indonesia. The safety endpoint was major adverse cardiac events (MACE) which composed of cardiac death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (ID-TLR). The imaging efficacy endpoint was mean in-scaffold late lumen loss (LLL) evaluated by quantitative coronary angiography (QCA). Optical coherence tomography (OCT) imaging was performed at baseline and 6-month follow-up. RESULTS:and no evidence of strut malapposition. CONCLUSIONS:The clinical and imaging outcomes of MeRes-1 Extend trial demonstrated favorable safety and efficacy of MeRes100 sirolimus-eluting BRS in patients with de novo coronary artery lesions.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 6-15% of MI and disproportionately affects women. Scientific statements recommend multi-modality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) to assess mechanisms of MINOCA. Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of MI. If invasive coronary angiography revealed <50% stenosis in all major arteries, multi-vessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and non-ischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intra-plaque cavity or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% of participants undergoing CMR (62/116). A non-ischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome or non-ischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% of the women with multi-modality imaging (98/116), higher than with OCT alone (p<0.001) or CMR alone (p=0.001). An ischemic etiology was identified in 63.8% of women with MINOCA (74/116), a non-ischemic etiology was identified in 20.7% (24/116), and no mechanism was identified in 15.5% (18/116). Conclusions: Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI. Identification of the etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02905357.

OBJECTIVE:To investigate the impact of ischemic and bleeding risk factors on long-term clinical outcomes of patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents. BACKGROUND:Second-generation drug-eluting stents have substantially improved outcomes after PCI in the general population; however, DM patients continue to experience high rates of ischemic and bleeding complications. METHODS:DM patients from the pooled XIENCE V registry were divided into high or low bleeding and ischemic risk groups (HBR, LBR, HIR, and LIR) based on established bleeding (age ≥ 75 years; chronic kidney disease; anemia; prior stroke; oral anticoagulation; thrombocytopenia; prior major bleeding) and ischemic (acute coronary syndrome; prior myocardial infarction [MI]; ≥3 stents implanted; ≥3 vessels treated; ≥3 lesions treated; stent length > 60 mm; bifurcation treated with ≥2 stents; chronic total occlusion) risk factors. The primary outcomes were major adverse cardiac events (MACE; cardiac death, MI, or stent thrombosis) and major bleeding at 4-year follow-up. RESULTS:A total of 3,704 DM patients were divided into four groups (21.5% LBR/LIR; 39.0% LBR/HIR; 15.6% HBR/LIR; 23.9% HBR/HIR). Compared with LBR/LIR patients, those at HBR/HIR and HBR/LIR had a significantly higher risk of MACE (HR (95% CI) 2.7 (1.9-3.9) and 2.2 (1.5-3.2), respectively) and major bleeding (2.7 (1.6-4.8) and 2.6 (1.4-4.7), respectively), while LBR/HIR patients did not. CONCLUSIONS:Among DM patients undergoing PCI, presence of bleeding risk factors was associated with a higher risk of both ischemic and bleeding events, whereas commonly used features of ischemic risk did not impact long-term clinical outcomes.

Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI), however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL DESIGN: The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis. CONCLUSIONS: The XIENCE Short DAPT Program will provide insights into the safety and efficacy of two abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.

BACKGROUND:Mechanical circulatory support (MCS) with Impella or intra-aortic balloon pump (IABP) is used for high-risk percutaneous coronary intervention (PCI) and/or for cardiogenic shock (CS) due to acute myocardial infarction. We aimed to investigate the efficacy and safety of Impella or IABP when compared with no MCS using a network meta-analysis of randomized controlled trials (RCTs). METHODS:EMBASE and MEDLINE were searched through February 2020 for RCT evaluating efficacy of Impella vs. IABP vs. no MCS in patients undergoing high-risk PCI or CS. The primary efficacy outcome was 30 day or in-hospital all-cause mortality whereas the primary safety outcomes were major bleeding and vascular complications. RESULTS:= 1.5%). CONCLUSIONS:Neither Impella nor IABP decreased all-cause short-term mortality when compared with no MCS for high-risk PCI and/or CS. Moreover, Impella increased major bleeding compared with no MCS.