Abstract Background Statins can regress coronary atheroma and lower clinical events. Although pre-clinical studies suggest procalcific effects of statins in vitro, it remains unclear if statins can ...modulate coronary atheroma calcification in vivo. Objectives This study compared changes in coronary atheroma volume and calcium indices (CaI) in patients receiving high-intensity statin therapy (HIST), low-intensity statin therapy (LIST), and no-statin therapy. Methods In a post-hoc patient-level analysis of 8 prospective randomized trials using serial coronary intravascular ultrasound, serial changes in coronary percent atheroma volume (PAV) and CaI were measured across matched coronary segments in patients with coronary artery disease. Results Following propensity-weighted adjustment for differences in baseline and changes in clinical, laboratory, and ultrasonic characteristics, HIST (n = 1,545) associated with PAV regression from baseline (−0.6 ± 0.1%; p < 0.001), whereas both LIST (n = 1,726) and no-statin therapy (n = 224) associated with PAV progression (+0.8 ± 0.1% and +1.0 ± 0.1%; p < 0.001, respectively; p < 0.001 for both HIST vs. LIST and HIST vs. no-statin; p = 0.35 for LIST vs. no-statin). Significant increases in CaI from baseline were noted across all groups (median interquartile range HIST, +0.044 0.0–0.12; LIST, +0.038 0.0–0.11; no-statin, +0.020 0.0–0.10; p < 0.001 for all), which could relate to statin intensity (p = 0.03 for LIST vs. no-statin; p = 0.007 for HIST vs. no-statin; p = 0.18 for HIST vs. LIST). No correlations were found between changes in CaI and on-treatment levels of atherogenic and antiatherogenic lipoproteins, and C-reactive protein, in either of the HIST groups or the no-statin group. Conclusions Independent of their plaque-regressive effects, statins promote coronary atheroma calcification. These findings provide insight as to how statins may stabilize plaque beyond their effects on plaque regression.
Background All neurologic events in the PARTNER randomized trial comparing transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (AVR) were analyzed. Methods High-risk ...patients with aortic stenosis were stratified into transfemoral (TF, n = 461) or transapical (TA, n = 196) strata based on their arterial anatomy and randomized: 657 received treatment assigned (“as treated”), 313 underwent AVR, and 344 TAVR. Neurologic events were prospectively adjudicated by an independent Clinical Events Committee. Multivariable, multiphase hazard analysis elucidated factors associated with increased likelihood of neurologic events. Results Forty-nine neurologic events (15 transient ischemic attacks, 34 strokes) occurred in 47 patients (TAVR, n = 31; AVR, n = 16). An early peaking high hazard phase occurred within the first week, which declined to a constant late hazard phase out to 2 years. The risk in the early phase was higher after TAVR than AVR, and in the TAVR arm in patients with a smaller aortic valve area index. In the late risk phase, the likelihood of neurologic event was linked to patient-related factors in both arms (“non-TF candidate,” history of recent stroke or transient ischemic attack, and advanced functional disability), but not by treatment (TAVR vs AVR) or any intraprocedural variables. The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up. Conclusions After either treatment, there were 2 distinct hazard phases for neurologic events that were driven by different risk factors. Neurologic complications occurred more frequently after TAVR than AVR early, but thereafter the risk was influenced by patient- and disease-related factors.
Abstract Background The STS/ACC Transcatheter Valve Therapy (TVT) Registry captures all procedures with Food and Drug Administration (FDA) approved transcatheter valve devices performed in the United ...States and is mandated as a condition of reimbursement by a Centers for Medicaid and Medicare Services (CMS) Objectives This annual report focuses on patient characteristics, trends, and outcomes of transcatheter aortic and mitral valve catheter-based valve procedures in the United States. Methods Data for all patients receiving commercially approved devices from 2012 through December 31, 2015 are entered in the TVT Registry. Results The 54,782 TAVR patients demonstrated decreases in expected risk of 30-day operative mortality (STS PROM) 7% to 6% and TAVR PROM (TVT PROM) 4% to 3% (both p<.0001) from 2012 to 2015. Observed in-hospital mortality decreased from 5.7% to 2.9% and one-year mortality decreased from 25.8% to 21.6. However, 30-day post procedure pacemaker insertion increased from 8.8% in 2013 to 12.0% in 2015. The 2,556 patients who underwent TMC in 2015 were similar to 2013-14 patients with hospital mortality of 2% with mitral regurgitation reduced to gradient ≤ 2 in 87% of patients (p<.0001). The 349 patients who underwent MViV and MViR procedures were high risk with, an STS PROM for MVR of 11%. The observed hospital mortality was 7.2% and 30-day post procedure was 8.5%. Summary The TVT Registry is an innovative registry that that monitors quality, patient safety and trends for these rapidly evolving new technologies. Condensed Abstract The STS/ACC TVT Registry captures all Food and Drug Administration (FDA) approved transcatheter valve devices preformed in the United States and is mandated as a condition for reimbursement by the Centers for Medicare Services. TAVR patients’ expected risks of mortality and actual in-hospital mortality decreased. Transcatheter mitral clip procedures had a low mortality with reduced in mitral regurgitation to grade ≤ 2 in 87%. Mitral valve in valve or valve in ring patients were high risk for mortality, but actual hospital mortality was lower. The TVT Registry is an innovative registry that monitors quality, safety and trends of these evolving technologies
Objectives The purpose of this study was to perform a systematic review and meta-analysis of comparative studies to compare outcomes of septal ablation (SA) with septal myectomy (SM) for treatment of ...hypertrophic obstructive cardiomyopathy (HOCM). Background SM is considered the gold standard for treatment of HOCM. However, SA has emerged as an attractive therapeutic alternative. Methods A Medline search using standard terms was conducted to determine eligible studies. Due to a lack of randomized control trials, we included observational studies for review. Results Twelve studies were found eligible for review. No significant differences between short-term (risk difference RD: 0.01; 95% confidence interval CI: −0.01 to 0.03) and long-term mortality (RD: 0.02; 95% CI: −0.05 to 0.09) were found between the SA and SM groups. In addition, no significant differences could be found in terms of post-intervention functional status as well as improvement in New York Heart Association functional class, ventricular arrhythmia occurrence, re-interventions performed, and post-procedure mitral regurgitation. However, SA was found to increase the risk of right bundle branch block (RBBB) (pooled odds ratio OR: 56.3; 95% CI: 11.6 to 273.9) along with need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9). Although the efficacy of both SA and SM in left ventricular outflow tract gradient (LVOTG) reduction seems comparable, there is a small yet significantly higher residual LVOTG amongst the SA group patients as compared with the SM group patients. Conclusion SA does seem to show promise in treatment of HOCM owing to similar mortality rates as well as functional status compared with SM; however, the caveat is increased conduction abnormalities and a higher post-intervention LVOTG. The choice of treatment strategy should be made after a thorough discussion of the procedures with the individual patient.
Although preoperative renal dysfunction (RD) is associated with increased mortality and morbidity after surgical aortic valve replacement, its impact on clinical outcomes after transcatheter aortic ...valve replacement (TAVR) is less defined.
TAVR patients in the PARTNER (Placement of Aortic Transcatheter Valves) trial with a calculable glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease equation were included. Patients were divided into three groups: GFR >60 mL/min (none/mild RD), GFR 31 to 60 mL/min (moderate RD), and GFR ≤30 mL/min (severe RD). Operative characteristics and clinical outcomes were analyzed. Cox regression models were used to determine multivariable predictors of 1-year all-cause mortality.
A total of 2,531 inoperable or high surgical risk patients from the PARTNER trial and continued access registries had a calculable GFR level: 767 (30%) had normal renal function or mild RD, 1,473 (58%) had moderate RD, and 291 (12%) presented with severe RD. The mean Society of Thoracic Surgeons Predicted Risk of Mortality for the cohort was 11.5%, and it was highest in those with severe RD (13.8%). Patients with severe RD were more often women with a higher prevalence of diabetes. Patients with severe RD had the highest incidence of 30-day and 1-year all-cause mortality and rehospitalization. The 30-day rate of death from any cause was 10.7% in the severe RD group versus 6.0% in the moderate and mild RD groups (p = 0.01). The 1-year rate of death from any cause was 34.4% in the severe RD group versus 21.5% in the moderate RD and 20.8% in the none/mild RD groups (adjusted hazard ratio HR 2.24, p < 0.0001 for severe versus none/mild; adjusted HR 1.14, p = 0.24 for severe versus moderate). Other significant predictors of 1-year all-cause mortality included lower body mass index, frailty, the transapical approach, a lower ejection fraction, oxygen-dependent chronic obstructive pulmonary disease, liver disease, and male sex.
Preoperative severe RD is a significant predictor for 1-year mortality in TAVR patients. Careful risk stratification by the heart team is required in patients with severe preprocedural RD.
Objectives The aim of this study was to investigate the relationship between intravascular ultrasound (IVUS)-derived measures of atherosclerosis and cardiovascular outcomes. Background IVUS has been ...used in clinical trials to evaluate the effect of medical therapies on coronary atheroma progression. Methods Coronary plaque progression was evaluated in 4,137 patients in 6 clinical trials that used serial IVUS. The relationship between baseline and change in percent atheroma volume (PAV) and total atheroma volume with incident major adverse cardiovascular events (MACE) was investigated. Results PAV increased by 0.3% (p < 0.001), and 19.9% of subjects experienced MACE (0.9% death, 1.8% myocardial infarction, 18.9% coronary revascularization). Greater baseline PAVs were observed in patients who experienced myocardial infarctions (42.2 ± 9.6% vs. 38.6 ± 9.1%, p = 0.001), coronary revascularization (41.2 ± 9.3% vs. 38.1 ± 9.0%, p < 0.001), or MACE (41.3 ± 9.2% vs. 38.0 ± 9.0%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.32-fold (95% confidence interval: 1.22 to 1.42; p < 0.001) greater likelihood of experiencing a MACE. During follow-up (21.1 ± 3.7 months), greater increases in PAV, but not total atheroma volume, were observed in subjects who experienced MACE compared with those who did not (0.95 ± 0.19% vs. 0.46 ± 0.16%, p < 0.001). Each standard deviation increase in PAV was associated with a 1.20-fold (95% confidence interval: 1.10 to 1.31; p < 0.001) greater risk for MACE. Multivariate analysis revealed that factors associated with MACE included baseline PAV (p < 0.0001), change in PAV (p = 0.002), smoking (p = 0.0002) and hypertension (p = 0.01). Conclusions A direct relationship was observed between the burden of coronary atherosclerosis, its progression, and adverse cardiovascular events. The relationship between disease progression and outcomes largely reflected the need for coronary revascularization. These data support the use of atherosclerosis imaging with IVUS in the evaluation of novel antiatherosclerotic therapies.
Whether the introduction of transcatheter aortic valve replacement (TAVR) has affected hospitals' surgical aortic valve replacement (SAVR) and overall aortic valve replacement (AVR) case volumes and ...outcomes in the United States is unknown.
We utilized data from The Society of Thoracic Surgeons (STS) adult cardiac surgery database and the STS/American College of Cardiology (ACC) transcatheter valve therapies registry to examine SAVR and TAVR procedures. Temporal trends in total case volume (SAVR plus TAVR), and observed and risk-adjusted in-hospital mortality rates were assessed among low-risk cases (STS predicted risk of operative mortality < 4%), intermediate-risk cases (4% to 8%), and high-risk cases (> 8%). A contemporary control was provided by non-TAVR centers.
From 2008 to 2013, the total annual volume of AVR among 246 TAVR-performing hospitals increased from 19,578 to 33,004, with a 22% growth in SAVR volumes; non-TAVR hospital (n = 555) increases were more modest (16,563 to 19,134; 16% growth). Expanded volumes at TAVR hospitals included increased SAVR use in low- and intermediate-risk cases, and TAVR use in high-risk cases. In parallel, in-hospital mortality for all AVR procedures at TAVR sites declined from 3.4% to 2.9% (observed to expected O:E ratio 0.75 to 0.58, p < 0.001); the greatest declines were among intermediate- and high-risk SAVR patients. Owing to reduced SAVR mortality, TAVR centers experienced a significantly greater decline in O:E ratio for high-risk patient in-hospital mortality than non-TAVR centers (TAVR center O:E ratio, 0.81 to 0.61; non-TAVR center O:E ratio, 0.85 to 0.76; p < 0.001). After approval of TAVR for clinical use, a trend toward higher in-hospital mortality rates and O:E ratios for TAVR procedures was observed at new (but not at established) TAVR centers (O:E ratio, 0.41 to 0.67; p = 0.08).
Since the introduction of TAVR, the total volume of AVR procedures, including higher overall use of SAVR, at TAVR sites has significantly increased in the United States. Overall, in-hospital survival of patients undergoing treatment for aortic valve stenosis continues to improve.
Objectives In this study, a meta-analysis of observational studies was performed to compare the rate of recurrent neurological events (RNE) between transcatheter closure and medical management of ...patients with cryptogenic stroke/transient ischemic attack (TIA) and concomitant patent foramen ovale (PFO). Background A significant controversy surrounds the optimal strategy for treatment of cryptogenic stroke/TIA and coexistent PFO. Methods We conducted a MEDLINE search with standard search terms to determine eligible studies. Results Adjusted incidence rates of RNE were 0.8 (95% confidence interval CI: 0.5 to 1.1) events and 5.0 (95% CI: 3.6 to 6.9) events/100 person-years (PY) in the transcatheter closure and medical management arms, respectively. Meta-analysis of the limited number of comparative studies and meta-regression analysis suggested that the transcatheter closure might be superior to the medical therapy in prevention of RNE after cryptogenic stroke. Comparison of the anticoagulation and antiplatelet therapy subgroups of the medical arm yielded a significantly lower risk of RNE within patients treated with anticoagulants. Device-related complications were encountered at the rate of 4.1 (95% CI: 3.2 to 5.0) events/100 PY, with atrial arrhythmias being the most frequent complication. After transcatheter closure, RNE did not seem to be related to the pre-treatment shunt size or the presence of residual shunting in the follow-up period. Significant benefit of transcatheter PFO closure was apparent in elderly patients, patients with concomitant atrial septal aneurysm, and patients with thrombophilia. Conclusions Rates of RNE with transcatheter closure and medical therapy in patients presenting with cryptogenic stroke or TIA were estimated at 0.8 and 5.0 events/100 PY. Further randomized controlled trials are needed to conclusively compare these 2 management strategies.
Objectives The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C). Background Despite ...achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events. Methods A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of ≤70 mg/dl (n = 951) were stratified as progressors (n = 200) and nonprogressors (n = 751) and compared. Results Despite achieving LDL-C ≤70 mg/dl, >20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 ± 42.5 mg/dl vs. 112.1 ± 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (−25.1 ± 3.4 mg/dl vs. −27.4 ± 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C ≤70 mg/dl included baseline percent atheroma volume (p = 0.001), presence of diabetes mellitus (p = 0.02), increase in systolic blood pressure (p = 0.001), less increase in high-density lipoprotein cholesterol (p = 0.01), and a smaller decrease in apolipoprotein B levels (p = 0.001), but not changes in C-reactive protein (p = 0.78) or LDL-C (p = 0.84). Conclusions Residual risk factors are associated with the likelihood of disease progression in patients who achieve very low LDL-C levels. In addition, the association between apolipoprotein B and atheroma progression highlights the potential importance of LDL particle concentration in patients with optimal LDL-C control. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease.
Abstract Objectives The purpose of this study was to determine the safety and effectiveness of the SAPIEN XT versus SAPIEN systems (Edwards Lifesciences, Irvine, California) in patients with ...symptomatic, severe aortic stenosis (AS) who were not candidates for surgery. Background Transcatheter aortic valve replacement (TAVR) has become the standard of care for inoperable patients with severe, symptomatic AS. In the PARTNER (Placement of Aortic Transcatheter Valves) IB trial, a reduction in all-cause mortality was observed in patients undergoing TAVR with the balloon-expandable SAPIEN transcatheter heart valve compared with standard therapy, but the SAPIEN valve was associated with adverse periprocedural complications, including vascular complications, major bleeding, and paravalvular regurgitation. The newer, low-profile SAPIEN XT system was developed to reduce these adverse events. Methods A total of 560 patients were enrolled at 28 sites in the United States from April 2011 to February 2012. Patients were randomized to receive the SAPIEN or SAPIEN XT systems. The primary endpoint was a nonhierarchical composite of all-cause mortality, major stroke, and rehospitalization at 1 year in the intention-to-treat population, assessed by noninferiority testing. Pre-specified secondary endpoints included cardiovascular death, New York Heart Association functional class, myocardial infarction, stroke, acute kidney injury, vascular complications, bleeding, 6-min walk distance, and valve performance (by echocardiography). Results Both overall and major vascular complications were higher at 30 days in patients undergoing TAVR with SAPIEN compared with SAPIEN XT (overall: 22.1% vs. 15.5%; p = 0.04; major: 15.2% vs. 9.5%; p = 0.04). Bleeding requiring blood transfusions was also more frequent with SAPIEN compared with SAPIEN XT (10.6% vs. 5.3%; p = 0.02). At 1-year follow-up, the nonhierarchical composite of all-cause mortality, major stroke, or rehospitalization was similar (37.7% SAPIEN vs. 37.2% SAPIEN XT; noninferiority p value <0.002); no differences in the other major pre-specified endpoints were found. Conclusions In inoperable patients with severe, symptomatic AS, the lower-profile SAPIEN XT is noninferior to SAPIEN with fewer vascular complications and a lesser need for blood transfusion. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves; NCT01314313 )
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