Minimal clinically important differences in patient reported outcomes after coronary artery bypass surgery in the arterial revascularization trial.

OBJECTIVES: This paper identifies minimal clinically important differences (MCIDs) in quality of life (QoL) measures among patients who had coronary artery bypass grafting (CABG) and were enrolled in the Arterial Revascularization Trial (ART). METHODS AND RESULTS: The European Quality of Life 5 Dimensions (EQ-5D) and the Short Form Health Survey 36-Item (SF-36) physical component (PC) and mental component (MC) scores were recorded at baseline, 5 and 10 years in ART. The MCIDs were calculated as changes in QoL scores anchored to 1-class improvement in the New York Heart Association Functional class (NYHA) and Canadian Cardiovascular Society scale (CCS) at 5 years. Cox proportional hazards models were used to evaluate associations between MCIDs and mortality. Patient cohorts were examined for the SF-36 PC (N = 2,671), SF-36 MC (N = 2,815) and EQ-5D (N = 2,943) measures, respectively. All QoL scores significantly improved after CABG compared to baseline. When anchored to NYHA, the MCID at 5 years was 17 (95% CI: 17-20) for SF-36 PC, 14 (14-17) for the SF-36 MC, and 0.12 (0.12-0.15) for EQ-5D. Using the CCS as anchor, the MCID at 5 years was 15 (15-17) for the SF-36 PC, 12 (13-15) for the SF-36 MC, and 0.12 (0.11-0.14) for the EQ-5D. The MCIDs for SF-36 PC and EQ-5D at 5 years were associated with lower risk of mortality at the 10-year follow-up point after surgery. CONCLUSIONS: MCIDs for CABG patients have been identified. These thresholds may have direct clinical applications in monitoring patients during follow-up and in designing new trials that include QoL as a primary study outcome.

European Association of Cardio-Thoracic Surgery (EACTS) expert consensus statement on perioperative myocardial infarction after cardiac surgery.

Cardiac surgery may lead to myocardial damage and release of cardiac biomarkers through various mechanisms such as cardiac manipulation, systemic inflammation, myocardial hypoxia, cardioplegic arrest and ischaemia caused by coronary or graft occlusion. Defining perioperative myocardial infarction (PMI) after cardiac surgery presents challenges, and the association between the current PMI definitions and postoperative outcomes remains uncertain. To address these challenges, the European Association of Cardio-Thoracic Surgery (EACTS) facilitated collaboration among a multidisciplinary group to evaluate the existing evidence on the mechanisms, diagnosis and prognostic implications of PMI after cardiac surgery. The review found that the postoperative troponin value thresholds associated with an increased risk of mortality are markedly higher than those proposed by all the current definitions of PMI. Additionally, it was found that large postoperative increases in cardiac biomarkers are prognostically relevant even in absence of additional supportive signs of ischaemia. A new algorithm for PMI detection after cardiac surgery was also proposed, and a consensus was reached within the group that establishing a prognostically relevant definition of PMI is critically needed in the cardiovascular field and that PMI should be included in the primary composite outcome of coronary intervention trials.

Very early invasive strategy in higher risk non-ST-elevation acute coronary syndrome: the RAPID NSTEMI trial.

OBJECTIVE: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months. RESULTS: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01). CONCLUSIONS: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference. TRIAL REGISTRATION NUMBER: NCT03707314.

Corrigendum: The safety and efficacy of balloon-expandable versus self-expanding trans-catheter aortic valve replacement in high-risk patients.

[This corrects the article DOI: 10.3389/fcvm.2023.1130354.].

Exaggerated elastin turnover in young individuals with Marfan syndrome: new insights from the AIMS trial.

Aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta are pathological hallmarks of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood. Methods and results: In this post hoc analysis of the AIMS randomized controlled trial, the association of plasma desmosine (pDES)-a specific biomarker of mature elastin degradation-with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls. There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults. During childhood, pDES increased and peaked during early adolescence, and thereafter decreased to lower adult levels. This trend was exaggerated in young individuals with MFS but in those above 25 years of age, pDES levels were comparable to controls despite the presence of aortic root dilation. In MFS children, increased aortic diameter relative to controls was seen at an early age and although the increase in diameter was less after adolescence, aortic root size continued to increase steadily with age. In MFS participants, there was an indication of a positive association between baseline pDES levels and aortic root dilatation during up to 5 years of follow-up. Conclusion: This study has shown that developmental age has a significant effect on levels of elastin turnover as measured by pDES in MFS individuals as well as healthy controls. This effect is exaggerated in those with MFS with increased levels seen during the period of physiologic development that plateaus towards adulthood. This suggests an early onset of pathophysiology that may present an important opportunity for disease-modifying intervention.

Influence of diabetes and obesity on ten-year outcomes after coronary artery bypass grafting in the arterial revascularisation trial.

AIMS: Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG. METHODS AND RESULTS: Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24% with diabetes, 30% with obesity). Patients in the "diabetes/no obesity" group had a higher risk of all-cause mortality following CABG (adjusted hazard ratio [aHR] 1.33, 95% confidence interval [CI] 1.08-1.64, p = 0.01) compared to the reference group of "no diabetes/no obesity". No excess risk was observed in the "no diabetes/obesity" or "diabetes/obesity" groups. Patients with insulin dependent diabetes had a significantly higher ten-year mortality risk compared to no diabetes (aHR 1.85, 95% CI 1.41-2.44, p = 0.00). Patients in the "diabetes/no obesity" and "diabetes/obesity groups" had a higher risk of sternal wound complications (HR 2.29, 95% CI 1.39-3.79, p < 0.001 and HR 3.21, 95% CI 1.89-5.45, p < 0.001 respectively). The composite outcome results were consistent with the mortality results. CONCLUSION: Diabetes, especially insulin dependent diabetes, is associated with a higher ten-year mortality risk after CABG, in contrast to obesity which does not appear to increase long term mortality compared to non-obese. The interaction between diabetes and obesity shows an apparent "protective" effect of obesity irrespective of diabetes on mortality. Both conditions are associated with a higher risk of post-operative sternal wound infections.

Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate. METHODS: Randomised clinical trials comparing early routine use of VA-ECMO versus optimal medical therapy alone in patients presenting with infarct-related cardiogenic shock were identified by searching MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and trial registries until June 12, 2023. Trials were included if at least all-cause death rate 30 days after in-hospital randomisation was reported and trial investigators agreed to collaborate (ie, providing individual patient data). Odds ratios (ORs) as primary outcome measure were pooled using logistic regression models. This study is registered with PROSPERO (CRD42023431258). FINDINGS: Four trials (n=567 patients; 284 VA-ECMO, 283 control) were identified and included. Overall, there was no significant reduction of 30-day death rate with the early use of VA-ECMO (OR 0·93; 95% CI 0·66-1·29). Complication rates were higher with VA-ECMO for major bleeding (OR 2·44; 95% CI 1·55-3·84) and peripheral ischaemic vascular complications (OR 3·53; 95% CI 1·70-7·34). Prespecified subgroup analyses were consistent and did not show any benefit for VA-ECMO (pinteraction ≥0·079). INTERPRETATION: VA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted. FUNDING: Foundation Institut für Herzinfarktforschung.

Coronary artery bypass grafting using bilateral internal thoracic arteries in patients with diabetes and obesity: A systematic review and meta-analysis.

Background: Patients with diabetes and obesity are at higher risk of adverse long-term outcomes following coronary artery bypass grafting. The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA), but BITA is not routinely used due to lack of clear evidence of efficacy and concerns over sternal wound complications. Methods: Medline, Embase and the Cochrane Library were searched for studies comparing the efficacy and safety of BITA and SITA grafting in patients with diabetes and obesity. Meta-analysis of mortality and sternal wound complications was performed. Results: We identified eight observational and ten propensity matched studies, and one RCT, comparing BITA and SITA which included patients with diabetes (n = 19,589); two propensity matched studies and one RCT which included patients with obesity (n = 6,972); mean follow up was 10.5 and 11.3 years respectively. Meta-analysis demonstrated a mortality reduction for BITA compared to SITA in patients with diabetes (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70-0.90; p = 0.0003). In patients with obesity there was a non-significant reduction in mortality in the BITA group (RR 0.73, 95% CI 0.47-1.12; p = 0.15). There was a significantly higher rate of sternal wound complications following BITA observed in patients with diabetes (RR 1.53, 95% CI 1.23-1.90; p = 0.0001) and obesity (RR 2.24, 95% CI 1.63-3.07; p < 0.00001). Conclusions: BITA is associated with better long-term survival in patients with diabetes. The effects of BITA grafting in patients with obesity are uncertain. BITA is associated with higher rates of sternal wound complications compared to SITA in both patients with diabetes and obesity.

Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.

BACKGROUND: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. AIMS: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI). METHODS: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure. RESULTS: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively). CONCLUSIONS: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

The safety and efficacy of balloon-expandable versus self-expanding trans-catheter aortic valve replacement in high-risk patients with severe symptomatic aortic stenosis.

Aim: Transfemoral Trans-catheter Aortic Valve Replacement (TF-TAVR) is a safe and effective therapy compared with surgical aortic valve replacement (SAVR) in patients across all risk profiles using balloon-expandable valves (BEV) and self-expanding valves (SEV). Our aim was to compare safety and efficacy of BEV vs. SEV in high-risk patients undergoing TF-TAVR. Methods and results: We searched PubMed, EMBASE, Clinicaltrials.gov, Scopus, and Web of sciences for studies on patients with severe aortic stenosis undergoing TAVR. Primary outcome was 30-day all-cause mortality. Secondary outcomes defined by Valve Academic Research Consortium 2 (VARC-2) criteria were also examined. Six studies with 2,935 patients (1,439 to BEV and 1,496 to SEV) were included. BEV was associated with lower risk of all-cause mortality (2.2% vs. 4.5%; RR: 0.51; 95% CI: 0.31-0.82; p < 0.006) and cardiovascular mortality [(2.5% vs. 4.3%; RR: 0.54; 95% CI: 0.32-0.90; p = 0.01) at 30 days compared with SEV. Implantation of more than one valve per procedure (0.78% vs. 5.11%; RR: 0.15; 95% CI: 0.07-0.31; p < 0.00001), and moderate/severe AR/PVL (2.5% vs. 9.01%; RR: 0.3; 95% CI: 0.17-0.48); p < 0.00001) were also lower in the BEV arm. Conclusion: BEV TAVR is associated with reduced all-cause mortality (High level of GRADE evidence), cardiovascular mortality (very low level) at 30 days compared with SEV TAVR in high surgical risk patients. Data are necessary to determine if the difference in outcomes persists in longer-term and if the same effects are seen in lower-risk patients. Systematic Review Registration: identifier, CRD42020181190.

ESC/EACTS vs. ACC/AHA guidelines for the management of severe aortic stenosis.

Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria.

Automated 4D flow cardiac MRI pipeline to derive peak mitral inflow diastolic velocities using short-axis cine stack: two centre validation study against echocardiographic pulse-wave doppler.

BACKGROUND: Measurement of peak velocities is important in the evaluation of heart failure. This study compared the performance of automated 4D flow cardiac MRI (CMR) with traditional transthoracic Doppler echocardiography (TTE) for the measurement of mitral inflow peak diastolic velocities. METHODS: Patients with Doppler echocardiography and 4D flow cardiac magnetic resonance data were included retrospectively. An established automated technique was used to segment the left ventricular transvalvular flow using short-axis cine stack of images. Peak mitral E-wave and peak mitral A-wave velocities were automatically derived using in-plane velocity maps of transvalvular flow. Additionally, we checked the agreement between peak mitral E-wave velocity derived by 4D flow CMR and Doppler echocardiography in patients with sinus rhythm and atrial fibrillation (AF) separately. RESULTS: Forty-eight patients were included (median age 69 years, IQR 63 to 76; 46% female). Data were split into three groups according to heart rhythm. The median peak E-wave mitral inflow velocity by automated 4D flow CMR was comparable with Doppler echocardiography in all patients (0.90 ± 0.43 m/s vs 0.94 ± 0.48 m/s, P = 0.132), sinus rhythm-only group (0.88 ± 0.35 m/s vs 0.86 ± 0.38 m/s, P = 0.54) and in AF-only group (1.33 ± 0.56 m/s vs 1.18 ± 0.47 m/s, P = 0.06). Peak A-wave mitral inflow velocity results had no significant difference between Doppler TTE and automated 4D flow CMR (0.81 ± 0.44 m/s vs 0.81 ± 0.53 m/s, P = 0.09) in all patients and sinus rhythm-only groups. Automated 4D flow CMR showed a significant correlation with TTE for measurement of peak E-wave in all patients group (r = 0.73, P < 0.001) and peak A-wave velocities (r = 0.88, P < 0.001). Moreover, there was a significant correlation between automated 4D flow CMR and TTE for peak-E wave velocity in sinus rhythm-only patients (r = 0.68, P < 0.001) and AF-only patients (r = 0.81, P = 0.014). Excellent intra-and inter-observer variability was demonstrated for both parameters. CONCLUSION: Automated dynamic peak mitral inflow diastolic velocity tracing using 4D flow CMR is comparable to Doppler echocardiography and has excellent repeatability for clinical use. However, 4D flow CMR can potentially underestimate peak velocity in patients with AF.

Association between sternal wound complications and 10-year mortality following coronary artery bypass grafting.

OBJECTIVE: To evaluate the association between sternal wound complications (SWC) and long-term mortality in the Arterial Revascularization Trial. METHODS: Participants in the Arterial Revascularization Trial were stratified according to the occurrence of postoperative SWC. The primary outcome was all-cause mortality at long-term follow-up. The secondary outcome was major adverse cardiovascular events. RESULTS: Three thousand one hundred two patients were included in the analysis; the median follow-up was 10 years. 115 patients (3.7%) had postoperative SWC: 85 (73.9%) deep sternal wound infections and 30 (26.1%) sterile SWC that required sternal reconstruction. Independent predictors of SWC included diabetes (odds ratio [OR], 2.77; 95% CI, 1.79-4.30; P < .001), female sex (OR, 2.73; 95% CI, 1.71-4.38; P < .001), prior stroke (OR, 2.59; 95% CI, 1.12-5.98; P = .03), chronic obstructive pulmonary disease (OR, 2.44; 95% CI, 1.60-3.71; P < .001), and use of bilateral internal thoracic artery (OR, 1.70; 95% CI, 1.12-2.59; P = .01). Postoperative SWC was significantly associated with long-term mortality. The Kaplan-Meier survival estimate was 91.3% at 5 years and 79.4% at 10 years in patients without SWC, and 86.1% and 64.3% in patients with SWC (log rank P < .001). The rate of major adverse cardiovascular events was also higher among patients who had SWC (n = 51 [44.3%] vs 758 [25.4%]; P < .001). Using multivariable analysis, the occurrence of SWC was independently associated with long-term mortality (hazard ratio, 1.81; 95% CI, 1.30-2.54; P < .001). CONCLUSIONS: In the Arterial Revascularization Trial, postoperative SWC although uncommon were significantly associated with long-term mortality.

Angiotensin receptor blockers and ß blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Angiotensin receptor blockers (ARBs) and ß blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. METHODS: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus ß blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus ß blocker; and indirectly, ß blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. FINDINGS: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with ß-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with ß blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in ß-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between ß blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042). INTERPRETATION: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a ß blocker. The effects of ß blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and ß blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. FUNDING: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.