Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral ...embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited.
We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights.
Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 95% CI, 0.68-1.13; absolute risk difference, -0.15% 95% CI, -0.49 to 0.20). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 95% CI, 0.69-0.97; absolute risk difference, -0.28% 95% CI, -0.52 to -0.03). Results were generally consistent across the secondary end points, as well as subgroup analyses.
In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.
Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown.
We conducted a ...multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Registry data were used in the evaluation of outcomes. The infants were randomly assigned to receive prophylactic methylprednisolone (30 mg per kilogram of body weight) or placebo, which was administered into the cardiopulmonary-bypass pump-priming fluid. The primary end point was a ranked composite of death, heart transplantation, or any of 13 major complications. Patients without any of these events were assigned a ranked outcome based on postoperative length of stay. In the primary analysis, the ranked outcomes were compared between the trial groups with the use of odds ratios adjusted for prespecified risk factors. Secondary analyses included an unadjusted odds ratio, a win ratio, and safety outcomes.
A total of 1263 infants underwent randomization, of whom 1200 received either methylprednisolone (599 infants) or placebo (601 infants). The likelihood of a worse outcome did not differ significantly between the methylprednisolone group and the placebo group (adjusted odds ratio, 0.86; 95% confidence interval CI, 0.71 to 1.05; P = 0.14). Secondary analyses (unadjusted for risk factors) showed an odds ratio for a worse outcome of 0.82 (95% CI, 0.67 to 1.00) and a win ratio of 1.15 (95% CI, 1.00 to 1.32) in the methylprednisolone group as compared with the placebo group, findings suggestive of a benefit with methylprednisolone; however, patients in the methylprednisolone group were more likely than those in the placebo group to receive postoperative insulin for hyperglycemia (19.0% vs. 6.7%, P<0.001).
Among infants undergoing surgery with cardiopulmonary bypass, prophylactic use of methylprednisolone did not significantly reduce the likelihood of a worse outcome in an adjusted analysis and was associated with postoperative development of hyperglycemia warranting insulin in a higher percentage of infants than placebo. (Funded by the National Center for Advancing Translational Sciences and others; STRESS ClinicalTrials.gov number, NCT03229538.).
Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease and death, yet little data exist regarding the comparative efficacy of coronary revascularization procedures ...in CKD patients with multivessel disease. We created a cohort of 4,687 adults who underwent cardiac catheterization, had a serum creatinine value measured within 30 days, and had more than one vessel with ≥50% stenosis. We used Cox proportional hazard regression modeling weighted by the inverse probability of treatment to examine the association between 4 treatment strategies (medical management, percutaneous coronary intervention PCI with bare metal stent, PCI with drug-eluting stent, and coronary artery bypass grafting CABG) and mortality among patients across categories of estimated glomerular filtration rate; secondary outcome was a composite of mortality, myocardial infarction, or revascularization. Compared with medical management, CABG was associated with a reduced risk of death for patients of any nondialysis CKD severity (hazard ratio HR range 0.43 to 0.59). There were no significant mortality differences between CABG and PCI, except a decreased death risk in CABG-treated CKD patients (HR range 0.54 to 0.55). Compared with medical management and PCI, CABG was associated with a lower risk of death, myocardial infarction, or revascularization in nondialysis CKD patients (HR range 0.41 to 0.64). There were similar associations between decreased estimated glomerular filtration rate and increased mortality across all multivessel coronary artery disease patient treatment groups. When accounting for treatment propensity, surgical revascularization was associated with improved outcomes in patients of all CKD severities. A prospective randomized trial in CKD patients is required to confirm our findings.
Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function ...indexed to load (RV-pulmonary arterial PA coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil.
In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion TAPSE) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD.
HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
The Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial was an investigator-initiated study to evaluate if predischarge carvedilol ...initiation in stabilized patients hospitalized for heart failure (HF) increased the number of patients treated with beta-blockade at 60 days after randomization without increasing side effects or length of hospital stay.
Beta-blockers are underused in HF. Predischarge initiation may improve the use of evidence-based beta-blockade.
The IMPACT-HF was a prospective, randomized open-label trial conducted in 363 patients hospitalized for HF. Patients were randomized to carvedilol initiation pre-hospital discharge or to postdischarge initiation (>2 weeks) of beta-blockade at the physicians' discretion. The primary end point of the study was the number of patients treated with beta-blockade at 60 days after randomization. Secondary end points included the number of patients discontinuing beta-blockade, median dose achieved, and a composite of death, rehospitalization, unscheduled visit for HF, or > or =50% increase in oral diuretic, new oral diuretic, or any intravenous therapy with diuretics, inotropes, or other vasoactive agents.
At 60 days 165 patients (91.2%) randomized to predischarge carvedilol initiation were treated with a beta-blocker, compared with 130 patients (73.4%) randomized to initiation postdischarge (p < 0.0001). Predischarge initiation was not associated with an increased risk of serious adverse events. The median length of stay was five days in both groups.
Predischarge initiation of carvedilol in stabilized patients hospitalized for HF improved the use of beta-blockade at 60 days without increasing side effects or length of stay. Predischarge initiation may be one approach to improve beta-blocker use in this population.
Hospitalizations for decompensated heart failure are frequent. The Initiation Management Pre-discharge Assessment of Carvedilol Heart Failure (IMPACT-HF) registry collected observational data in ...patients hospitalized for worsening heart failure to characterize an unselected group of patients and to confirm the generalizability of the IMPACT-HF main trial population.
The IMPACT-HF registry was conducted concurrently with the IMPACT-HF study, a randomized trial of in-hospital initiation of carvedilol compared with the standard practice of postdischarge β-blocker initiation. Patients were eligible for registry enrollment if they were hospitalized for heart failure regardless of ejection fraction. There were no exclusions to participation. Patients were followed for 60 days. The IMPACT-HF Registry enrolled 567 patients. The mean age was 71 years, 52% of the patients were men and 82% were Caucasian. At discharge, 71% received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 41% received digoxin, and 62% received β-blockers. The 60-day rate of rehospitalization or death was 31%.
The IMPACT-HF registry enrolled elderly patients admitted for worsening heart failure primarily resulting from progressive volume overload. The 60-day rate of death or rehospitalization was high despite the use of evidence-based therapies. New treatments for this population are needed to decrease the morbidity and mortality associated with decompensated heart failure.
Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated ...hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function.
Abstract Differences in the clinical course of congestion by underlying ejection fraction (EF) have not been well-characterized in acute heart failure (AHF). A post-hoc analysis was performed using ...pooled data from the DOSE-AHF, CARRESS-HF, and ROSE-AHF trials. All patients were admitted for a primary diagnosis of AHF. Patients were grouped as reduced EF < 40%, borderline 40%< EF <50%, or preserved EF > 50%. Multivariable Cox regression analysis was used to assess the association between measures of congestion and the composite of unscheduled outpatient visits, rehospitalization, or death. Mean age was 68 + 13 years and 74% were male. Patients with a preserved EF were older, more likely to be female, less likely to have an ischemic etiology of HF, and had a higher prevalence of atrial fibrillation/flutter and chronic obstructive pulmonary disease. Compared to patients with a reduced EF, preserved EF patients had lower NT-proBNP levels at baseline (i.e. reduced: 5998 pg/mL 3009 pg/mL, 11414 pg/mL vs. borderline: 4420 pg/mL 1740 pg/mL, 8057 pg/mL vs. preserved: 3272 pg/mL 1687 pg/mL, 6536 pg/mL) and experienced smaller changes during hospitalization. In general, there were few differences between EF groups in the clinical course of congestion as measured by signs and symptoms of HF, body weight change, and net fluid loss. After adjusting for potential confounders, a greater improvement in global visual analogue scale was associated with lower risk of unscheduled outpatient visits, rehospitalization, or death at day 60 (Hazard Ratio 0.94 per 10 mm increase, 95% Confidence Interval 0.89-0.995). This relationship did not differ by EF (p-value = 0.54). In conclusion, among patients hospitalized for AHF there were few differences in the in-hospital trajectory or prognostic value of routine markers of congestion by EF.
Background Despite robust efficacy in the reduction of ischemic events in patients who require percutaneous coronary intervention (PCI), current P2Y12 inhibitors have limitations. In particular, they ...require hours to be effective, and they can only be administered orally. Cangrelor is an intravenous, potent, and reversible P2Y12 inhibitor with fast onset and offset of action. We designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in patients with atherosclerosis undergoing PCI. Trial Design The CHAMPION PHOENIX is a randomized, double-blind, double-dummy, superiority trial comparing cangrelor with clopidogrel standard of care in approximately 10,900 patients who have not previously received a P2Y12 inhibitor and who require PCI, including patients with stable angina and with acute coronary syndromes (with or without ST-segment elevation). The primary objective of the study is to demonstrate that cangrelor will reduce the incidence of the composite of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48 hours after randomization compared with clopidogrel without excessive periprocedural bleeding. The key secondary objective is to demonstrate that cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction will be defined according to the universal MI definition, adapting the definition of PCI-related (type 4a) MI. Bleeding will be assessed according to the thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research Consortium (BARC) scales. Conclusion The CHAMPION PHOENIX may establish the role of cangrelor in the care of patients who require PCI across the spectrum of stable and unstable coronary diseases in the setting of current treatment strategies.
Abstract Because hepatic dysfunction is common in patients with heart failure, the Model for End-Stage Liver Disease (MELD) may be attractive for risk-stratification. Although alternative scores such ...as the MELD-XI or MELD-Na may be more appropriate in heart failure populations, the short-term clinical implications of these in patients with acute heart failure (AHF) are unknown. The MELD-XI and MELD-Na were calculated at baseline in 453 patients with AHF in the DOSE-AHF and ROSE-AHF trials. The correlations and associations for each score with cardiorenal biomarkers, short-term endpoints at 72 hours including worsening renal function and clinical events to 60 days were determined. The median MELD-XI and MELD-Na was 16 and 17, respectively. Both were correlated with baseline cystatin C, NT-proBNP, and plasma renin activity (P<0.003 for all). MELD-XI≤16 and MELD-Na≤17 were associated with a slight increase in cystatin C (P<0.02 for both), higher diuretic efficiency (P<0.001 for both), but not with change in global VAS scores (P>0.05 for both) at 72 hours. Neither score was associated with CRS or worsening heart failure (P>0.05 for all). Similarly, both the MELD-XI and MELD-Na were not associated with 60-day death/any re-hospitalization and 60-day death/heart failure re-hospitalization in adjusted analyses when analyzes as a dichotomous or continuous variable (P>0.05 for all). The alternative MELD scores correlated with baseline cardiorenal biomarkers. In conclusion, lower baseline MELD scoring was associated with higher diuretic efficiency and a slight increase in cystatin C through 72 hours. However, MELD-Na and MELD-XI were not predictive of 60-day clinical events.
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