David R. Holmes

2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement.

Robert A. Harrington, MD, FACC, Chair Deepak L. Bhatt, MD, MPH, FACC, Vice Chair Victor A. Ferrari, MD, FACC John D. Fisher, MD, FACC Mario J. Garcia, MD, FACC Timothy J. Gardner, MD, FACC Federico Gentile, MD, FACC Michael F. Gilson, MD, FACC Adrian F. Hernandez, MD, FACC Alice K. Jacobs

Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes

Background—Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results—A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions—Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.

Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry.

BackgroundThis study describes the impact of clinical, angiographic, and demographic characteristics on the long-term survival of Coronary Artery Surgery Study (CASS) patients while they were under medical treatment. Revascularization rates for the population are also provided. Methods and ResultsAll CASS patients who had not received heart surgery before enrollment (23467 patients) were included in this survival analysis while they were under medical treatment or surveillance. Follow-up time ranged from 0 to 17 years (median, 12 years). Long-term vital status is known for 95.8% of these patients. Log-rank tests, Kaplan-Meier survival curves, and Cox proportional- hazards regression are used to describe and assess the impact of patient characteristics on survival. Characteristics that had a significant impact on survival, in order of observed explanatory power, are age, number of diseased vessels, congestive heart failure score, smoking history, ejection fraction, sex, presence of left main coronary artery disease, presence of diabetes, left ventricular wall motion score, presence of other illnesses, history of myocardial infarction, and presence of left main equivalent disease. Overall, 12-year survival for patients with zero-, one-, two- and three-vessel disease is 88%, 74%, 59%, and 40%, respectively. Twelve-year survival for patients with at least one diseased vessel and ejection fractions in the ranges of 50% to 100%, 35% to 49%, and 0% to 34% is 73%, 54%, and 21%, respectively. High myocardial jeopardy, high anginal class, and two or three proximal diseased vessels characterize the profile of patients most likely to have received surgical treatment during follow-up. ConclusionsThese results contribute to the understanding of the natural history of coronary artery disease and are also of historical interest. The poor survival of patients with three-vessel disease and low ejection fractions continues to emphasize the importance of considering revascularization for these patients.

Three-year outcome after balloon aortic valvuloplasty: Insights into prognosis of valvular aortic stenosis

BackgroundTo identify predictors of long-term outcome after balloon aortic valvuloplasty, we analyzed data on 674 adults (mean age, 78±9 years; 56% were women) undergoing this procedure at 24 clinical centers who had a mean initial increase in aortic valve area of 0.3 cm2. Methods and ResultsBaseline data included clinical, echocardiographic, and catheterization variables. Follow-up data included mortality, cause of death, rehospitalization, 6-month echocardiography, and functional status. Kaplan-Meier curves and log-rank tests were used to evaluate survival in subgroups. Multivariate Cox regression models were used to identify independent predictors of survival. Overall survival was 55% at 1 year, 35% at 2 years, and 23% at 3 years, with the majority of deaths (70%) classified as cardiac by an independent review committee. Rehospitalization was common (64%), although 61% of survivors at 2 years reported improved symptoms. Echocardiography at 6 months (n= 115) showed restenosis from the postprocedural valve area of 0.78±0.31 cm2 to 0.65±0.25 cm2 (P < .0001). With stepwise multivariate analysis, sequentially adding clinical, echocardiographic, and catheterization variables, the overall model identified independent predictors of survival as baseline functional status, baseline cardiac output, renal function, cachexia, female gender, left ventricular systolic function, and mitral regurgitation. Baseline and postprocedural variables were examined to identify which subgroup of patients has the best outcome after aortic valvuloplasty. A “lower-risk” subgroup (28% of the study population), defined by normal left ventricular systolic function and mild clinical functional limitation, had a 3-year survival of 36% compared with 17% in the remainder of the study group. ConclusionsLong-term survival after balloon aortic valvuloplasty is poor with 1- and 3-year survival rates of 55% and 23%, respectively. Although survivors report fewer symptoms, early restenosis and recurrent hospitalization are common.

Assessment of the SYNTAX score in the Syntax study

AIMS The SYNTAX score has been designed to better anticipate the risks of percutaneous or surgical revascularisation, taking into account the functional impact of the coronary circulation with all its anatomic components including the presence of bifurcations, total occlusions, thrombus, calcification, and small vessels. The purpose of this paper is to describe the baseline assessment of the SYNTAX score in the Syntax randomised trial, the corelab reproducibility, the potential difference in score assessment between the investigator and the corelab, and to ascertain the impact on one-year outcome after either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) in patients with complex coronary artery disease. METHODS AND RESULTS To assess the reliability of Syntax scoring, 100 diagnostic angiograms from the Syntax trial were randomly selected and assessed independently by two observers. Intra-observer variability was assessed by analysing 91 sets of angiograms after an interval of at least eight weeks by one of the observers. Clinical outcomes in the randomised cohort of the Syntax trial up to one year are presented with stratification by tertile group of the SYNTAX score. The weighted kappa value for the inter-observer reproducibility on the global score was 0.45, while the intra-observer weighted kappa value was 0.59. The SYNTAX score as calculated by investigators consistently underscored the corelab score by 3.4 points. When the Syntax randomised cohort was stratified by tertiles of the SYNTAX score, there were similar or non-significantly different MACCE rates in those with low or intermediate scores; however in the top tertile the MACCE rate was greater in those receiving PCI compared to CABG. CONCLUSIONS The SYNTAX score is a visual coronary score with an acceptable corelab reproducibility that has an impact on the one-year outcome of those having PCI, whereas it has no effect on the one-year outcome following surgical revascularisation. The SYNTAX score tool is likely to be useful in a wide range of patients with complex coronary disease.

Five-Year Follow-Up After Sirolimus-Eluting Stent Implantation : Results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial

OBJECTIVES The aim of this study was to examine the 5-year clinical safety and efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial. BACKGROUND The SIRIUS trial was a double-blinded randomized study that demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS Patients (n = 1,058) with de novo native coronary artery lesions were randomized to either SES (n = 533) or control BMS (n = 525) and were followed for 5 years. RESULTS Between 1 and 5 years, additional clinical events were similarly distributed among the sirolimus and control groups. At 5 years, in sirolimus versus control patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and major adverse cardiovascular events and target vessel failure rates were 20.3% versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There were no significant differences in death, myocardial infarction, and nontarget lesion revascularization. No significant differences were observed in the cumulative incidence of stent thrombosis for sirolimus versus control patients with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium definitions (3.9% vs. 4.2%). CONCLUSIONS In patients with noncomplex coronary artery disease, clinical outcomes 5 years after implantation of SES continue to demonstrate significant reduction in the need for repeat revascularization, with similar safety (death and myocardial infarction) compared with BMS, without evidence for either disproportionate late restenosis or late stent thrombosis.

Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or bare metal stent placement for the treatment of coronary artery lesions

BACKGROUND Dual antiplatelet therapy with aspirin and thienopyridines (clopidogrel or prasugrel) is required after placement of coronary stents to prevent thrombotic complications. Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement, even longer durations may prevent thrombotic events. STUDY DESIGN The Dual Antiplatelet Therapy (DAPT) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery obstructive lesions. The DAPT Study is a multicenter, international, randomized, double-blind, placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent (DES) and 5,400 subjects treated with bare-metal stents (BMS). All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin. After 12 months, subjects who are free from death, myocardial infarction, or stroke (MACCE), repeat revascularization, and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events will be randomized to receive either 18 additional months of thienopyridine (clopidogrel or prasugrel) (30 month DAPT arm) or placebo (12 month DAPT arm) plus aspirin. Coprimary end points are MACCE and stent thrombosis. The primary safety end point is GUSTO moderate or severe bleeding. CONCLUSIONS This randomized trial is designed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents.

Differential histopathology of primary atherosclerotic and restenotic lesions in coronary arteries and saphenous vein bypass grafts: Analysis of tissue obtained from 73 patients by directional atherectomy

Vascular tissue obtained using a directional percutaneous atherectomy device was examined microscopically. Tissue was obtained from coronary arteries without prior instrumentation (primary lesions, n = 31), aortocoronary saphenous vein bypass grafts with primary lesions (n = 8), coronary arteries with lesions developing after prior balloon angioplasty or mechanical atherectomy (restenotic lesions, n = 30) and vein bypass grafts with restenotic lesions (n = 4). Primary lesions were characterized by dense intimal fibrosis with necrotic debris (83% of intimal tissue) and foam cells typical of atherosclerosis. These lesions frequently contained cholesterol crystals (45% of coronary arteries, 50% of vein grafts) and calcium deposits (65% of coronary arteries, 38% of vein grafts). Restenotic lesions were characterized by an increased proportion of loose fibroproliferative tissue (45% of coronary artery intima, 35% of vein graft intima). Immunohistochemical stains confirmed this proliferative tissue to be primarily smooth muscle cells. Thrombus was rarely observed. Comparison of resected tissues indicated that dense fibrosis and necrosis are significantly more common in primary than in restenotic lesions (83% versus 56% of intimal tissue, p = 0.0005), whereas smooth muscle cell hyperplasia is more common in restenotic than in primary lesions (44% versus 17% of intimal tissue, p less than 0.0005). Partial-thickness resection of medial tissue or full-thickness resection of media with associated adventitial tissue occurred in 27 (56%) of 39 primary atheromatous lesions and 16 (47%) of 34 restenotic lesions; subintimal tissue obtained from primary lesions appeared identical to that obtained from restenotic lesions. These data indicate that the histopathologic characteristics of the neointimal layer of restenotic lesions differ from those of the intimal layer of primary atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery bypass grafting vs. percutaneous coronary intervention for patients with three-vessel disease: final five-year follow-up of the SYNTAX trial

AIMS Coronary artery bypass grafting (CABG) has been considered the standard of care for patients with three-vessel disease (3VD), but long-term comparative results from randomized trials of CABG vs. percutaneous coronary intervention (PCI) using drug-eluting stents (DES) remain limited. METHODS AND RESULTS Patients with de novo 3VD or left main disease were randomly assigned to PCI with the paclitaxel-eluting first-generation stent or CABG in the SYNTAX trial. This pre-specified analysis presents the 5-year outcomes of patients with 3VD (n = 1095). The rate of major adverse cardiac and cerebrovascular events (MACCE) was significantly higher in patients with PCI compared with CABG (37.5 vs. 24.2%, respectively; P < 0.001). Percutaneous coronary intervention as opposed to CABG resulted in significantly higher rates of the composite of death/stroke/myocardial infarction (MI) (22.0 vs. 14.0%, respectively; P < 0.001), all-cause death (14.6 vs. 9.2%, respectively; P = 0.006), MI (9.2 vs. 4.0%, respectively; P = 0.001), and repeat revascularization (25.4 vs. 12.6%, respectively; P < 0.001); however, stroke was similar between groups at 5 years (3.0 vs. 3.5%, respectively; P = 0.66). Results were dependent on lesion complexity (P for interaction = 0.12); in patients with a low (0-22) SYNTAX score, PCI vs. CABG resulted in similar rates of MACCE (33.3% vs. 26.8%, respectively; P = 0.21) but significantly more repeat revascularization (25.4% vs. 12.6%, respectively; P = 0.038), while in intermediate (23-32) or high (≥ 33) SYNTAX score terciles, CABG demonstrated clear superiority in terms of MACCE, death, MI, and repeat revascularization. Differences in MACCE between PCI and CABG were larger in diabetics [hazard ratio (HR) = 2.30] than non-diabetics (HR = 1.51), although the P for interaction failed to reach significance for MACCE (P for interaction = 0.095) or any of the other endpoints. CONCLUSION Five-year results of patients with 3VD treated with CABG or PCI using the first-generation paclitaxel-eluting DES suggest that CABG should remain the standard of care as it resulted in significantly lower rates of death, MI, and repeat revascularization, while stroke rates were similar. For patients with low SYNTAX scores, PCI is an acceptable revascularization strategy, although at a price of significantly higher rates of repeat revascularization. CLINICAL TRIAL REGISTRATION NCT00114972.

Effect of 1.5 tesla nuclear magnetic resonance imaging scanner on implanted permanent pacemakers

Patients with a permanent pacemaker are currently restricted from diagnostic nuclear magnetic resonance (NMR) imaging because of potential adverse effects on the pacemaker by the magnet. Previous work has shown that NMR imaging will result in asynchronous pacing of the pulse generator within a given distance of the magnet. The radiofrequency signal generated by the system may also result in rapid cardiac pacing, which may have deleterious effects. This study utilized a 1.5 tesla unit in an in vivo laboratory animal to evaluate the units effects on eight different pulse generators from two manufacturers. All pacemakers functioned in an asynchronous mode when placed within a certain distance of the magnet. In addition, transient reed switch inhibition was observed. Seven of the eight pulse generators paced rapidly when exposed to the radiofrequency signal and there was a dramatic decrease in arterial blood pressure. Whether effective rapid cardiac pacing would occur could not be predicted before exposure to the magnetic resonance unit. Nuclear magnetic resonance imaging with high magnetic fields in patients with a pacemaker should continue to be avoided until the mechanism of the rapid cardiac pacing can be further delineated and either predicted or prevented.