Faculty Bibliography

BACKGROUND:Potent P2Y12 inhibitors reduce cardiovascular events but increase bleeding in patients presenting with acute coronary syndrome (ACS). Elderly patients are at increased risk of bleeding and whether the benefit-risk ratio of potent P2Y12 inhibitors remains favorable is not known. OBJECTIVES/OBJECTIVE:To investigate the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS. METHODS:PUBMED and EMBASE were searched through July 2020 for randomized control trials (RCTs) or subgroup analyses of RCTs investigating potent P2Y12 inhibitors (prasugrel or ticagrelor) or clopidogrel in elderly (age ≥ 65 years) patients with ACS. The primary outcome was major adverse cardiovascular events (MACE). RESULTS:=0%). In a subgroup analysis, ticagrelor reduced all-cause mortality (HR: 0.73; 95% CI [0.55-0.98]) and cardiovascular death (HR: 0.70; 95% CI [0.54-0.90]) compared with clopidogrel. CONCLUSIONS:Among elderly patients with ACS, potent P2Y12 inhibitors reduce cardiovascular death but increase bleeding with no difference in MACE or all-cause death when compared with clopidogrel. Further RCTs are needed to refine P2Y12 inhibitor selection for elderly patients with ACS.

The concept of a direct association between coronary graft patency and clinical status is generally accepted. However, the relationship is more complex and variable than usually thought. Key issues are the lack of a common definition of graft occlusion and of a standardized imaging protocol for patients undergoing coronary bypass surgery. Factors like the type of graft, the timing of the occlusion, and the amount of myocardium at risk, as well as baseline patients' characteristics, modulate the patency-to-clinical status association. Available evidence suggests that graft occlusion is more often associated with non-fatal events rather than death. Also, graft failure due to competitive flow is generally a benign event, while graft occlusion in a graft-dependent circulation is associated with clinical symptoms. In this systematic review, we summarize the evidence on the association between graft status and clinical outcomes.

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.

Tricuspid valve endocarditis with recurrent septic pulmonary emboli is an indication for surgery. We present the case of a 36-year old man with tricuspid valve endocarditis and septic pulmonary emboli with percutaneous extraction of the vegetation. We discuss the nuances of such an approach and the need for more evidence in the management of these complex patients.

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.

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: 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.