Focus on acute myocardial infarction, sex-related differences in coronary bypass surgery, inflammation in heart failure, and infective endocarditis in prosthetic valves

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on acute cardiovascular care, cardiac and vascular surgery, heart failure and cardiomyopathies contains the Special Article ‘Ventricular septal defect complicating acute myocardial infarction: diagnosis and management. A Clinical Consensus Statement of the Association for Acute CardioVascular Care (ACVC) of the ESC, the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC, and the ESC Working Group on Cardiovascular Surgery’ by Florian Schlotter from the University of Leipzig in Germany, and colleagues.1 The authors note that ventricular septal defects (VSDs) are a rare complication after acute myocardial infarction (AMI), with a mortality close to 100% if left untreated.2,3 However, even surgical or interventional closure is associated with a very high mortality, and currently no randomized controlled trials are available addressing the optimal treatment strategy of this disease. This clinical consensus statement outlines the diagnosis, haemodynamic consequences, and treatment strategies of VSDs complicating AMI, with a focus on current available evidence and on major research questions to fill the gap in evidence. The following contribution is a Fast Track Clinical Research article entitled ‘Risk of heart failure in inflammatory bowel disease: a Swedish population-based study’ by Jiangwei Sun from the Karolinska Institutet in Stockholm, Sweden, and colleagues.4 The authors note that dysregulation of inflammatory and immune responses plays a key role in several cardiovascular diseases including heart failure (HF).5–12 However, even if inflammation is a prerequisite for inflammatory bowel disease (IBD), little is known about HF risk in IBD. In this Swedish nationwide cohort, patients with biopsy-confirmed IBD were identified between 1969 and 2017 (n = 81 749) including Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U). Each patient was matched with up to five general population reference individuals and IBD-free full siblings and followed until 31 December 2019. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) and standardized cumulative incidence for HF, with 95% confidence intervals. IBD patients had a significantly higher risk of HF than reference individuals (aHR 1.19). This increased risk remained significant ≥20 years after IBD diagnosis, leading to one extra HF case per 130 IBD patients up to then. The increased risk was also observed across IBD subtypes: CD [incident rate (IR) 47 vs. 34; aHR 1.28], UC (IR 50 vs. 39; aHR 1.14), and IBD-U (IR 61 vs. 39; aHR 1.28). Sibling-controlled analyses showed slightly attenuated association (IBD: aHR 1.10). The authors conclude that patients with IBD have a moderately higher risk than the general population of developing HF for ≥20 years after IBD diagnosis. The contribution is accompanied by an Editorial by Matthew Feinstein from the Northwestern University Feinberg School of Medicine in Chicago, IL, USA.13 Feinstein notes that ideally, the discovery and validation of viable targets in the inflammation HF axis will ultimately translate to practice. Aligning clinical and experimental model systems in a coherent, phenotype-specific way is an important step. Just as the concept of inflammatory risk for atherosclerotic cardiovascular disease has helped open the door for effective inflammation-targeted therapies, elucidating inflammatory contributors to HF may inform future inflammation-targeted approaches. Given the diversity of clinical and mechanistic contributors to similarly diverse phenotypes of HF, this will require precise, phenotypically targeted approaches. Ultimately, if these efforts yield precise, valid targets, they can inform a future of targeting immune dysregulation and inflammation in HF. Strategies to assess patients with suspected AMI using a point-of-care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay may expedite emergency care. In a Clinical Research article entitled ‘Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2 h’, Louise Cullen from the Royal Brisbane and Women’s Hospital in Australia, and colleagues report that a 2-h POC hs-cTnI strategy for emergency patients with suspected AMI was derived and validated.14 In two international, multicentre, prospective, observational studies of adult emergency patients (1486 derivation cohort and 1796 validation cohort) with suspected AMI, hs-cTnI was measured at admission and 2 h later. Adjudicated final diagnoses utilized the hs-cTn assay in clinical use. A risk stratification algorithm was derived and validated. The primary diagnostic outcome was index AMI (Types 1 and 2). The primary safety outcome was 30-day major adverse cardiac events incorporating AMI and cardiac death. Overall, 81 (5.5%) and 88 (4.9%) patients in the derivation and validation cohorts, respectively, had AMI. The 2-h algorithm defined 66% as low risk with a sensitivity of 99% and a negative predictive value of 99.9 for index AMI in the derivation cohort. In the validation cohort, 53% were low risk with a sensitivity of 99% and a negative predictive value of 99.9% for index AMI. The high-risk metrics identified 5.4% of patients with a specificity of 98% and a positive predictive value of 74% for index AMI (Figure 1). Performance of the 0-/2-h algorithm for risk assessment of myocardial infarction in the Suspected Acute Myocardial Infarction in Emergency (SAMIE) and Safe Emergency Department Discharge Rate (SEIGE) cohorts. AMI, acute myocardial infarction; CI, confidence interval; hs-cTnI, high-sensitivity cardiac troponin I; NPV, negative predictive value; POC, point of care; PPV, positive predictive value.14 The authors conclude that a 2-h algorithm a POC hs-cTnI strategy enables safe and efficient risk assessment of patients with suspected AMI. The short turnaround time of POC testing may support significant efficiencies in the management of the large proportion of emergency patients with suspected AMI. The contribution is accompanied by an Editorial by Evangelos Giannitsis, Norbert Frey, and Hugo Katus from the University Hospital Heidelberg in Germany.15 The authors conclude that the contribution is instrumental in promoting hs-cTnI POC and accelerated diagnostic classification of patients with suspected MI. While this mission is well on its way, new challenges are ahead. To capture the full potential of hs-cTn POC, prospective well-designed multicentre trials are now needed that investigate large unselected chest pain populations recruited, analysed, and treated in less sophisticated medical environments such as smaller hospitals or emergency care settings. If such a trial were to show improved patient management, better acute and long-term outcome, and cost-effectiveness of high-sensitivity POC, this would be a major breakthrough for accelerated diagnostics by high-sensitivity POC devices in the many patients with suspected MI. Infective endocarditis (IE) is a high-risk clinical condition.16–21 Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated IE. In a Clinical Research article entitled ‘Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry’, Mateo Marin-Cuartas from the Leipzig Heart Center in Germany, and colleagues assess the outcomes of patients undergoing THV explant for IE.22 All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared with those with other mechanisms of bioprosthetic valve dysfunction (BVD). A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 49% underwent THV explant due to IE and 51% due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older and had a lower Society of Thoracic Surgeons risk score compared with patients with BVD. Compared with BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality were 12.1, 16.1, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years post-surgery (30% for BVD vs. 44% for IE), Kaplan–Meier analysis showed no significant differences between groups (P = .16). The authors conclude that in the EXPLANT-TAVR registry, patients undergoing THV explant for IE have higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE have a higher 3-year mortality rate, which does not reach statistical significance given the relatively small sample size of this unique cohort and the limited number of events. This manuscript is accompanied by an Editorial by Vinod Thourani, Taylor Sirset-Becker, and Prasad Dasi from the Piedmont Heart Institute in Atlanta, GA, USA.23 The authors note that this work should stimulate the valvular heart disease community to work to improve clinical outcomes for transcatheter aortic valve replacement (TAVR) explant procedures in addition to standardizing explant methods and techniques. More broadly, their work illustrates the importance of lifetime management for patients with aortic stenosis. As we see more patients undergoing THV due to the increased number of patients receiving native TAVR procedures, we should make an effort to expand this registry and use its data to provide an empirical basis to guide treatment decision paradigms. Uncertainty exists over whether multiple arterial grafting (MAG) has a sex-related association with survival after coronary artery bypass grafting. In a Clinical Research article entitled ‘Multiple arterial vs. single arterial coronary artery bypass grafting: sex-related differences in outcomes’, Justin Ren from the University of Melbourne in Australia, and colleagues aim to compare the long-term survival of using MAG vs. single arterial grafting in women and men undergoing coronary artery bypass grafting.24 The retrospective study used the Australian and New Zealand Society of Cardiothoracic Surgical Database with linkage to the National Death Index. Patients from 2001 to 2020 were identified. A sex-stratified, inverse probability-weighted Cox proportional hazard model was used to facilitate survival comparisons. The primary outcome was all-cause mortality. A total number of ∼54 000 adult patients receiving at least two grafts in primary isolated bypass operations were analysed. In the entire study cohort, female prevalence was 20% while the prevalence of MAG procedures was 55%. At a median post-operative follow-up of 4.9 years, mortality was significantly lower in male patients undergoing multiarterial compared with single arterial procedures (aHR 0.82; P < .001). The survival benefit was also significant for females (aHR 0.83; P < .001). The interaction model from Cox regression suggested insignificant subgroup effect from sex (P = .08) on the observed survival advantage (Figure 2). The survival benefits associated with MAG were consistent across all sex-stratified subgroups, except for female patients with left main coronary disease. Comparative long-term survival outcomes in female patients following multiple and single arterial grafting. MAG, multiple arterial grafting; SAG, single arterial grafting; HR, hazard ratio; CI, confidence interval; CABG, coronary artery bypass grafting.24 The authors conclude that compared with single arterial grafting, multiple arterial revascularization is associated with improved long-term survival for women as well as for men. The contribution is accompanied by an Editorial by Torsten Doenst from the Friedrich Schiller University of Jena and Gloria Faerber from the Saarland University Medical Center in Germany.25 The authors note that MAG in >50% of patients, as achieved in the study of Ren et al., may set an example for the rest of the world. Patients need patent grafts to derive treatment effects from coronary artery bypass grafting, and properly performed arterial grafts show the best long-term patency. In the meantime, the challenge–skill balance should also be accepted by the heart team. The skill is to meet the challenge of detecting coronary disease in female patients earlier and improve decision-making to reduce peri-procedural risk. Contemporary multicentre data on the clinical and diagnostic spectrum and outcomes of myocarditis are limited. In a Clinical Research article entitled ‘Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry’, Alida Caforio from the University of Padova in Italy, and colleagues sought to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.26 Five hundred and eighty-one (68% male) patients, 493 adults, median age 38 years, and 88 children, were divided into three groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance (CMR); Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no CMR. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on CMR was found in 31% of children and in 58% of adults with biopsy-proven myocarditis. At 1-year follow-up, 2.7% of patients died, 1.7% received a heart transplant, 0.7% underwent VAD implantation, and 3.9% underwent ICD implantation. Independent predictors at diagnosis of death, heart transplantation, hospitalization, VAD implantation, or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. The authors conclude that endomyocardial biopsy is safe, and that the sensitivity of CMR using Lake Louise criteria is limited, particularly in children. Virus-negative lymphocytic myocarditis is predominant in both children and adults, and use of immunosuppressive treatments is low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis are independent predictors of unfavourable outcome events at 1 year. The manuscript is accompanied by an Editorial by Tahir Kafil from the Cleveland Clinic Foundation in the USA and Peter Liu from the University of Ottawa in Canada.27 The authors conclude that unfortunately, this registry closed enrolment before the COVID-19 outbreak. However, the ESC and the multiple myocarditis collaborators should be congratulated on successfully conducting a meaningful registry in this heterogeneous condition, with standardized inclusion criteria, and common process and outcome measures. This should engage the global community to explore follow-up registries to address new questions using state of the art technologies and expert networks involving clinical and methodological expertise. The issue is also complemented by two Discussion Forum contributions. In a commentary entitled ‘Cannabis use and cardiovascular diseases’, Viktor Čulić from the University Hospital Centre Split in Croatia and colleagues comment on the recent publication ‘Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study’ by Anders Holt from the Copenhagen University Hospital—Herlev and Gentofte in Denmark.28,29 Holt et al. respond in a separate comment.30 The editors hope that this issue of the European Heart Journal will be of interest to its readers. Dr. Crea reports speaker fees from Abbott, Amgen, Astra Zeneca, BMS, Chiesi, Daiichi Sankyo, Menarini outside the submitted work. With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.