Mahesh V. Madhavan

Coronary Artery Calcification : Pathogenesis and Prognostic Implications

Coronary artery calcification (CAC) is a risk factor for adverse outcomes in the general population and in patients with coronary artery disease. The pathogenesis of CAC and bone formation share common pathways, and risk factors have been identified that contribute to the initiation and progression of CAC. Efforts to control CAC with medical therapy have not been successful. Event-free survival is also reduced in patients with coronary calcification after both percutaneous coronary intervention (PCI) and bypass graft surgery. Although drug-eluting stents and devices for plaque modification have modestly improved outcomes in calcified vessels, adverse event rates are still high. Innovative pharmacologic and device-based approaches are needed to improve the poor prognosis of patients with CAC.

Prediction of Coronary Risk by SYNTAX and Derived Scores Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery

The introduction of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score has prompted a renewed interest for angiographic risk stratification in patients undergoing percutaneous coronary intervention. Syntax score is based on qualitative and quantitative characterization of coronary artery disease by including 11 angiographic variables that take into consideration lesion location and characteristics. Thus far, this score has been shown to be an effective tool to risk-stratify patients with complex coronary artery disease undergoing percutaneous coronary intervention in the landmark SYNTAX trial, as well as in other clinical settings. This review provides an overview of its current applications, including its integration with other nonangiographic clinical scores, and explores future applications of the SYNTAX and derived scores.

Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention on Short- and Long-Term Outcomes Pooled Analysis From the HORIZONS-AMI and ACUITY Trials

Background—Contrast-induced acute kidney injury (CI-AKI), defined as a serum creatinine increase ≥0.5 mg/dL or ≥25% within 72 hours after contrast exposure, is a common complication of procedures requiring contrast media and is associated with increased short- and long-term morbidity and mortality. Few studies describe the effects of CI-AKI in a large-scale acute coronary syndrome population, and the relationship between CI-AKI and bleeding events has not been extensively explored. We sought to evaluate the impact of CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome. Methods and Results—We pooled patient-level data for 9512 patients from the percutaneous coronary intervention cohorts of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) multicenter randomized trials. Patients were classified according to CI-AKI development, and cardiovascular outcomes at 30 days and 1 year were compared between groups. A total of 1212 patients (12.7%) developed CI-AKI. Patients with CI-AKI were older, with a more extensive comorbidity profile than without CI-AKI. Multivariable analysis confirmed several previously identified predictors of CI-AKI, including diabetes mellitus, contrast volume, age, and baseline hemoglobin. Mortality rates were significantly higher in the CI-AKI group at 30 days (4.9% versus 0.7%; P<0.0001) and 1 year (9.8% versus 2.9%; P<0.0001), as were rates of 1-year myocardial infarction, definite/probable stent thrombosis, target lesion revascularization, and major adverse cardiac events. Major bleeding (13.8% versus 5.4%; hazard ratio, 2.64; 95% confidence interval, 2.21–3.15; P<0.0001) was also higher in patients with CI-AKI. After multivariable adjustment, results were unchanged. Conclusions—CI-AKI after percutaneous coronary intervention in patients presenting with acute coronary syndrome is independently associated with increased risk of short- and long-term ischemic and hemorrhagic events. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00433966 (HORIZONS-AMI) and ACUITY (NCT00093158).

SYNTAX score and the risk of stent thrombosis after percutaneous coronary intervention in patients with non‐ST‐segment elevation acute coronary syndromes: An ACUITY trial substudy

We sought to investigate the relationship between the SYNTAX score (SS) and stent thrombosis (ST) in patients with non‐ST‐segment elevation acute coronary syndromes (NSTE‐ACS) undergoing percutaneous coronary intervention (PCI).

Effect of Baseline Thrombocytopenia on Ischemic Outcomes in Patients With Acute Coronary Syndromes Who Undergo Percutaneous Coronary Intervention.

BACKGROUND Acquired thrombocytopenia (TP) has been associated with short- and long-term adverse outcomes after percutaneous coronary intervention (PCI), but the role of baseline TP is less well defined. We sought to evaluate the effect of TP on long-term adverse outcomes in patients with acute coronary syndromes (ACS) who undergo PCI. METHODS Data from 10,603 patients who underwent PCI for non-ST-elevation ACS or ST-elevation myocardial infarction were pooled from 2 large-scale randomized trials, Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI). Patients were stratified according to baseline platelet counts. Those with platelet counts <150,000/mm(3) were considered to have normal platelet counts. Adverse event rates were compared between groups with and without multivariable adjustment. RESULTS Baseline TP was present in 607 (5.7%) patients. The unadjusted 1-year rates of death (6.7% vs 3.6%; P < 0.0001), occurrence of major adverse cardiac event (MACE) (20.8% vs 15.6%; P = 0.0002), and target lesion revascularization (TLR; 9.4% vs 7.2%; P = 0.01) were significantly higher in patients with baseline TP compared with patients with normal platelet counts. By multivariable analysis, the presence of TP at baseline was an independent predictor of 1-year death (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.12-2.69; P = 0.01), ischemic TLR (HR, 1.37; 95% CI, 1.04-1.81; P = 0.03), and MACE (HR, 1.39; 95% CI, 1.09-1.79; P = 0.009). CONCLUSIONS The presence of baseline TP in the setting of ACS patients who undergo PCI was strongly predictive of death, ischemic TLR, and MACE at 1 year. Baseline TP might be a useful baseline clinical parameter to estimate future ischemic risk after PCI.

Usefulness of the SYNTAX Score to Predict Acute Kidney Injury After Percutaneous Coronary Intervention (from the Acute Catheterization and Urgent Intervention Triage Strategy Trial)

The synergy between percutaneous coronary intervention (PCI) with Taxus and cardiac surgery (SYNTAX) score (SS) has prognostic utility for ischemic outcomes in patients undergoing PCI. Acute kidney injury (AKI) after PCI has been demonstrated to be associated with adverse outcomes. However, the relation between the SS and AKI after PCI has yet to be fully investigated. We therefore sought to study this relation in the formal angiographic substudy of the large Acute Catheterization and Urgent Intervention Triage Strategy trial. We stratified 2,268 patients who underwent PCI for non-ST-segment elevation acute coronary syndromes by postprocedural AKI status and by SS tertiles (SS<7, 7 to 12, and >12). We also assessed rates of in-hospital, 30-day, and 1-year adverse outcomes. A total of 226 patients (10%) developed AKI, and rates in the highest Acute Catheterization and Urgent Intervention Triage Strategy SS tertile (>12) were significantly greater than those in the intermediate (7 to 12) and lowest tertiles (<7; 13% vs 8.9% vs 7.7%, respectively, p=0.002). By multivariable analysis, the SS was independently associated with AKI (odds ratio per 10 SS points 1.22, 95% confidence interval 1.04 to 1.43, p=0.02. Rates of major adverse cardiovascular events and net adverse clinical events increased significantly by SS tertile and were more common in patients who developed AKI. Patients who developed AKI experienced higher in-hospital, 30-day, and 1-year rates of mortality. In this large study, the SS was independently associated with AKI after PCI for non-ST-segment elevation acute coronary syndromes, and patients who developed AKI experienced worse short-term and long-term outcomes.

Percutaneous coronary intervention of bifurcation lesions and platelet reactivity

BACKGROUND Although bifurcation percutaneous coronary intervention (PCI) is associated with lower procedural success rates and higher risk of complications, there are little data regarding outcomes after successful bifurcation PCI with contemporary stents and techniques. Whether residual platelet reactivity (PR) affects outcomes differently after bifurcation versus non-bifurcation PCI is also unknown. We studied the association between bifurcation PCI, PR, and clinical outcomes among patients undergoing successful PCI with drug-eluting stents. METHODS Patients in the prospective, multicenter ADAPT-DES study were stratified according to whether they underwent bifurcation PCI. Two-year outcomes were compared between groups using Cox proportional hazards models. Target vessel failure (TVF) was defined as the composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS Among the 8582 patients included in ADAPT-DES, 1276 (15%) had bifurcation PCI. Bifurcation PCI was independently associated with increased risk of TVF (adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08-1.46, p=0.003), driven by higher risk of myocardial infarction (5.9% vs. 4.6%, p=0.033) and ischemia-driven target vessel revascularization (13.0% vs. 9.2%, p<0.0001). There was no statistical interaction between PR and bifurcation PCI regarding TVF risk (adjusted pinteraction=0.87). Stenting of both bifurcation branches was associated with the highest risk of TVF (adjusted HR 1.91, 95% CI 1.48-2.46 versus non-bifurcation PCI; ptrend<0.001). CONCLUSIONS Bifurcation PCI is associated with a higher risk of 2-year adverse ischemic events than non-bifurcation PCI, a risk that is particularly high when both bifurcation branches are stented, and with HPR conferring similar risk for bifurcation and non-bifurcation PCI.

TCT-313 Incidence and Predictors of Very Late Major Adverse Cardiac Events After Metallic Stents: A Patient-Level Pooled Analysis from Seventeen Randomized Trials

Limited data are available regarding very late (>1 year) major adverse cardiac events (MACE) after metallic stent implantation. We therefore examined rates and predictors of very late MACE from a large pooled drug-eluting stent (DES) trial database. Patient-level data from 17 randomized DES trials

Is routine post-procedural anticoagulation warranted after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction? Insights from the HORIZONS-AMI trial.

Aim: Post-procedural anticoagulation (AC) for routine prophylaxis may be administered after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI), but the risks and benefits of this practice are uncertain. We therefore sought to assess the utility of routine post-procedural AC after primary PCI. Methods and results: Patients undergoing primary PCI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial were grouped according to whether they received post-PCI AC for routine prophylaxis. Outcomes were assessed using propensity-adjusted multivariable analysis. Among 2932 patients in whom primary PCI for STEMI was performed, 869 (29.6%) received post-PCI AC for routine prophylaxis (median duration four days) and 2063 (70.4%) received no post-PCI AC. Time from PCI to ambulation was similar in both groups (median 0.9 vs 1.0 days, p=0.40), although hospitalization was prolonged in patients receiving AC for routine prophylaxis (median 6.0 vs 4.0 days, p<0.0001). After propensity-adjustment, patients who received and did not receive AC for routine prophylaxis after PCI experienced similar rates of 30-day adverse ischemic and major bleeding events. Deep venous thrombosis or pulmonary emboli developed rarely (0.3%) within 30 days, and were not significantly reduced by use of post-PCI AC for routine prophylaxis. Conclusions: In this large-scale prospective study, use of post-procedural AC for routine prophylaxis was relatively common, and was not associated with improved clinical outcomes, although the duration of hospitalization was prolonged. These data suggest that post-PCI AC for routine prophylaxis may not provide benefit after successful primary PCI in patients in whom early ambulation is likely.

TCT-322 The Smoker’s Paradox Revisited: A 5-Year Patient-Level Pooled Analysis of 17 Randomized Controlled Trials

TCT-321 Definite and probable stent thrombosis after revascularization with drug-eluting stents with a biodegradable polymer. From the randomized SORT OUT VII Trial Lisette Okkels Jensen, Michael Maeng, Bent Raungaard, Knud Noerregaard Hansen, Johnny Kahlert, Svend Eggert Jensen, Hans Erik Bøtker, Henrik Hansen, Jens Flensted Lassen, Evald Christiansen Odense University Hospital, Odense, Denmark; Aarhus University Hospital, Aarhus N, Denmark; Aalborg University Hospital, Aalborg, Denmark; Odense Universitets Hospital, Odense, Denmark; Rutgers Robert Wood Johnson Medical School; Aalborg University Hospital, Aalborg, Denmark; Weatherhead PET Center, McGovern Medical School at UTHealth; Unknown, Odense, Denmark; The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Aarhus University Hospital, Aarhus, Denmark