Conflicts of interest in clinical practice: lessons learned from cardiovascular medicine.

Cardiovascular diseases represent a major burden worldwide, and clinical trials are critical to define treatment improvements. Since various conflicts of interest (COIs) may influence trials at multiple levels, cardiovascular research represents a paradigmatic example to analyze their effects and manage them effectively to re-establish the centrality of evidence-based medicine.Despite the manifest role of industry, COIs may differently affect both sponsored and non-sponsored studies in many ways. COIs influence may start from the research question, data collection and adjudication, up to result reporting, including the spin phenomenon. Outcomes and endpoints (especially composite) choice and definitions also represent potential sources for COIs interference. Since large randomized controlled trials significantly influence international guidelines, thus impacting also clinical practice, their critical assessment for COIs is mandatory. Despite specific protocols aimed to mitigate COI influence, even scientific societies and guideline panels may not be totally free from COIs, negatively affecting their accountability and trustworthiness.Shared rules, awareness of COI mechanisms and transparency with external data access may help promoting evidence-based research and mitigate COIs impact. Managing COIs effectively should preserve public trust in the cardiovascular profession without compromising the positive relationships between investigators and industry.

[Percutaneous treatment of post-acute myocardial infarction mechanical complications: state of the art]. / Trattamento percutaneo delle complicanze meccaniche dell'infarto miocardico acuto: stato dell'arte.

Left ventricular free wall rupture, ventricular pseudoaneurysm, papillary muscle rupture and ventricular septal rupture are life-threatening mechanical complications of acute myocardial infarction. Despite significant improvements over the last decades in overall mortality for patients with myocardial infarction, the outcome of subjects who develop post-infarction mechanical complications remains poor. Surgical treatment is considered the standard of care. However, percutaneous approaches (such as pericardial fibrin-glue injection for left ventricular free wall rupture, transcatheter edge-to-edge mitral repair for papillary muscle rupture and device closure for ventricular pseudoaneurysm or septal rupture) have been proposed in selected high-risk or inoperable patients, or in subjects with ideal characteristics for feasibility, as therapeutic alternatives to open surgery. The aim of the present review is to provide a comprehensive overview of the percutaneous strategies for the management of post-acute myocardial infarction mechanical complications.

Hybrid coronary revascularization: position paper of the European Society of Cardiology Working Group on Cardiovascular Surgery and European Association of Percutaneous Cardiovascular Interventions.

Myocardial revascularization in coronary artery disease via percutaneous coronary intervention or coronary artery bypass graft (CABG) surgery effectively relieves symptoms, significantly improves prognosis and quality of life when combined with guideline-directed medical therapy. Hybrid coronary revascularization is a promising alternative to percutaneous coronary intervention or CABG in selected patients and is defined as a planned and/or intended combination of consecutive CABG surgery using at least 1 internal mammary artery to the left anterior descending (LAD), and catheter-based coronary intervention to the non-LAD vessels for the treatment of multivessel disease. The main indications for hybrid coronary revascularization are (i) to achieve complete revascularization in patients who cannot undergo conventional CABG, (ii) to treat patients with acute coronary syndromes and multivessel disease with a non-LAD vessel as the culprit lesion that needs revascularization and (iii) in highly select patients with multivessel disease with complex LAD lesions and simple percutaneous coronary intervention targets for all other vessels. Hybrid coronary revascularization patients receive a left internal mammary artery graft to the LAD artery through a minimal incision along with percutaneous coronary intervention to the remaining diseased coronary vessels using latest generation drug-eluting stents. A collaborative environment with a dedicated heart team is the optimal platform to perform such interventions, which aim to improve the quality and outcome of myocardial revascularization. This position paper analyses the rationale of hybrid coronary revascularization and the currently available evidence on the various techniques and delves into the sequence of the interventions and pharmacological management during and after the procedure.

SURgical vs. PERcutaneous ACCESS in Transfemoral Transcatheter Aortic Valve Implantation (SU-PER-ACCESS Study).

Background: The transfemoral (TF) approach is the most common route in TAVI, but it is still associated with a risk of bleeding and vascular complications. The aim of this study was to compare the clinical outcomes between surgical cut-down (SC) and percutaneous (PC) approach. (2) Methods: Between January 2018 and June 2022, 774 patients underwent a transfemoral TAVI procedure. After propensity matching, 323 patients underwent TAVI in each group. (3) Results: In the matched population, 15 patients (4.6%) in the SC group vs. 34 patients in the PC group (11%) experienced minor vascular complications (p = 0.02), while no difference for major vascular complication (1.5% vs. 1.9%) were reported. The rate of minor bleeding events was higher in the percutaneous group (11% vs. 3.1%, p <.001). The SC group experienced a higher rate of non-vascular-related access complications (minor 8% vs. 1.2%; major 2.2% vs. 1.2%; p < 0.001). (4) Conclusions: SC for TF-TAVI did not alter the mortality rate at 30 days and was associated with reduced minor vascular complication and bleeding. PC showed a lower rate of non-vascular-related access complications and a lower length of stay. The specific approach should be tailored to the patient's clinical characteristics.

[Surgical treatment of isolated tricuspid valve disease: indications, new evidence, and risk stratification]. / Trattamento cardiochirurgico della patologia tricuspidale isolata: indicazioni, nuove evidenze e stratificazione del rischio.

The tricuspid valve, long neglected as a passive structure and often termed the "forgotten valve", has recently gained attention from the international medical and cardiological community due to the association of tricuspid regurgitation with an unfavorable prognosis. Isolated tricuspid regurgitation represents a relatively unknown and variable condition, closely linked to the shape and function of the right ventricle and the state of the pulmonary circulation. Currently, guidelines are not clear regarding the optimal treatment strategy, the process of patient selection, and the surgical or transcatheter procedural timing, nor for predicting patient outcomes. Surgical procedures specifically aimed at correcting isolated tricuspid regurgitation, without other concomitant indications for open-heart surgery, have been considered complex and risky, with a high rate of postoperative complications and a poorly understood impact on patient survival and life expectancy. In this review, we will attempt to examine tricuspid valve pathology by analyzing preoperative assessment, essential for risk stratification, various surgical techniques, and outcomes.

[Total artificial heart: past, present, and future]. / Cuore artificiale totale: passato, presente e futuro.

Every year, approximately 5 out of 1000 patients receive a diagnosis of advanced heart failure, with a prevalence of 1-2% in the adult population. This figure is likely underestimated, considering undiagnosed cases. Despite significant progress in medical therapy for heart failure, mortality rates persist around 20% within the first year, reaching 50-60% at 5 years from the initial diagnosis. For patients with severe end-stage heart failure, the 1-year mortality rate can reach up to 70%. Heart transplantation remains the preferred treatment for terminal stages of the disease; however, the significant challenge lies in the mismatch between available donors and recipients. Given this dilemma, both short-term solutions including extracorporeal membrane oxygenation and long-term options such as left ventricular assist devices have gained prominence. These mechanical circulatory support systems become crucial for patients in critical conditions, temporarily ineligible for heart transplantation, such as those with severe irreversible pulmonary hypertension or acute organ failure. Despite these advancements, a growing number of patients on the waiting list develops severe biventricular dysfunction, precluding the use of a left ventricular assist device as a bridge to transplant. In such cases, a total artificial heart emerges as a viable therapeutic option.

Comparison of 4 mortality scores for surgical repair of type A aortic dissection: a multicentre external validation.

OBJECTIVES: In the last decades, 4 different scores for the prediction of mortality following surgery for type A acute aortic dissection (TAAD) were proposed. We aimed to validate these scores in a large external multicentre cohort. METHODS: We retrospectively analysed patients who underwent surgery for TAAD between 2000 and 2020. Patients were enrolled from 10 centres from 2 European countries. Outcomes were the early (30-day and/or in-hospital) and 1-year mortality. Discrimination, calibration and observed/expected (O/E) ratio were evaluated. RESULTS: A total of 1895 patients (31.7% females, mean age 63.72 ± 12.8 years) were included in the study. Thirty-day mortality and in-hospital mortality were 21.7% (n = 412) and 22.5% (n = 427) respectively. The German Registry of Acute Aortic Dissection Type A (GERAADA) score shows to have the best discrimination [area under the curve (AUC) 0.671 and 0.672] in predicting as well the early and the 1-year mortality, followed by the International Registry of Acute Aortic Dissection (IRAD) model 1 (AUC 0.658 and 0.672), the Centofanti (AUC 0.645 and 0.66) and the UK aortic score (AUC 0.549 and 0.563). According to Hosmer-Lemeshow and Brier tests, the IRAD model I and GERAADA, respectively, were well calibrated for the early mortality, while the GERAADA and Centofanti for the 1-year mortality. The O/E analysis showed a marked underestimation for patients labelled as low-risk for UK aortic score and IRAD model I for both outcomes. CONCLUSIONS: The GERAADA score showed the best performance in comparison with other scores. However, none of them achieved together a fair discrimination and a good calibration for predicting either the early or the 1-year mortality.

Mechanical heart valves and oral anticoagulation: a survey of the Italian Society of Cardiac Surgery.

In the latest European guidelines for the management of valvular heart disease, mechanical valve prostheses maintain a strategic role, particularly for certain patient subsets and age groups. Despite the high number of devices implanted in clinical practice, particularly in non-European and North American regions, current scientific literature and debate seem to suggest a limited use of mechanical heart valves. The cardiac surgery community seems to be highly interested in biological and transcatheter valve prostheses but less interested in mechanical heart valves, including possible strategies for self-management of anticoagulation therapy. In this respect, the Italian Society of Cardiac Surgery (SICCH), in particular the Italian Group of Research for Outcome in Cardiac Surgery (GIROC), has promoted a survey among its members to stimulate the interest in this topic and express their opinion on this issue that, due to the prevalence of the affected population and the new treatment options for improving patients' quality of life, should be more appraised and debated in the cardiac surgery community. The recorded results, obtained on the answers to 111 questionnaires, seem to divide the specialists into 'pros' and 'contras' on a useful tool for the entire cardiac surgery community. For this reason, SICCH proposes in conclusion to declare its unified and institutional opinion on this topic.

[Choosing a tailored prosthetic valve in cardiac surgery: what is the current role of mechanical prostheses?] / Il ruolo delle protesi valvolari meccaniche oggi. Dalla letteratura alla situazione italiana.

The choice of the mechanical/biological heart valve prosthesis is a topic currently debated in the light of the transcatheter prosthetic models and the results obtained/expected with the new biological valve models. Consequently, it seems that increasingly younger patients would be indicated for an implantation of a biological prosthesis. This is also in order to improve the quality of life of patients who want to avoid oral anticoagulant therapy. On the other hand, the guidelines for the treatment of heart valve disease assign a central role to the use of mechanical valve prostheses, particularly for certain patient subsets and age groups. This means that mechanical prostheses are still widely used worldwide, especially in non-European or North American regions. The cardiac surgery community therefore seems to be very interested in biological prostheses and transcatheter implants and scarcely interested in mechanical prostheses, including possible strategies for self-management of anticoagulant therapy. Recently, the Italian Society of Cardiac Surgery promoted a survey among its members to stimulate interest in the cardiac surgery community. This review article aims to summarize the most current results recorded with the use of mechanical prostheses and possible strategies, especially for the management of oral anticoagulant therapy, which can improve the patient's quality of life.

The ISCHEMIA trial revisited: setting the record straight on the benefits of coronary bypass surgery and the misinterpretation of a landmark trial.

OBJECTIVES: The ISCHEMIA trial is a landmark study that has been the subject of heated debate within the cardiovascular community. In this analysis of the ISCHEMIA trial, we aim to set the record straight on the benefits of coronary artery bypass grafting (CABG) and the misinterpretation of this landmark trial. We sought to clarify and reorient this misinterpretation. METHODS: We herein analyse the ISCHEMIA trial in detail and describe how its misinterpretation has led to an erroneous guideline recommendation downgrading for prognosis-altering surgical therapy in these at-risk patients. RESULTS: The interim ISCHEMIA trial findings align with previous evidence where CABG reduces the long-term risks of myocardial infarction and mortality in advanced coronary artery disease. The trial outcomes of a significantly lower rate of cardiovascular mortality and a higher rate of non-cardiovascular mortality with the invasive strategy are explained according to landmark evidence. CONCLUSIONS: The ISCHEMIA trial findings are aligned with previous evidence and should not be used to downgrade recommendations in recent guidelines for the indisputable benefits of CABG.

Biology of mitral valve prolapse: from general mechanisms to advanced molecular patterns-a narrative review.

Mitral valve prolapse (MVP) represents the most frequent cause of primary mitral regurgitation. For several years, biological mechanisms underlying this condition attracted the attention of investigators, trying to identify the pathways responsible for such a peculiar condition. In the last ten years, cardiovascular research has moved from general biological mechanisms to altered molecular pathways activation. Overexpression of TGF-ß signaling, for instance, was shown to play a key role in MVP, while angiotensin-II receptor blockade was found to limit MVP progression by acting on the same signaling pathway. Concerning extracellular matrix organization, the increased valvular interstitial cells density and dysregulated production of catalytic enzymes (matrix metalloproteinases above all) altering the homeostasis between collagen, elastin and proteoglycan components, have been shown to possibly provide a mechanistic basis contributing to the myxomatous MVP phenotype. Moreover, it has been observed that high levels of osteoprotegerin may contribute to the pathogenesis of MVP by increasing collagen deposition in degenerated mitral leaflets. Although MVP is believed to represent the result of multiple genetic pathways alterations, it is important to distinguish between syndromic and non-syndromic conditions. In the first case, such as in Marfan syndrome, the role of specific genes has been clearly identified, while in the latter a progressively increasing number of genetic loci have been thoroughly investigated. Moreover, genomics is gaining more interest as potential disease-causing genes and loci possibly associated with MVP progression and severity have been identified. Animal models could be of help in better understanding the molecular basis of MVP, possibly providing sufficient information to tackle specific mechanisms aimed at slowing down MVP progression, therefore developing non-surgical therapies impacting on the natural history of this condition. Although continuous progress has been made in this field, further translational studies are advocated to improve our knowledge of biological mechanisms underlying MVP development and progression.

The importance of being the morning case in adult cardiac surgery: a propensity-matched analysis.

OBJECTIVES: The quality of the outcome after cardiac surgery with cardiopulmonary bypass depends on the patient demographics, co-morbidities, complexity of the surgical procedure and expertise of surgeons and the whole staff. The purpose of the present study is to analyse the timing of surgery (morning versus afternoon) with respect to morbidity and mortality in adult cardiac surgery. METHODS: The primary end point was the incidence of major morbidity defined according to a modified Society of Thoracic Surgeon criterion. We consecutively included all the adult (>18 years) patients receiving a cardiac surgery operation at our Institution. RESULTS: From 2017 through 2019, a total of 4003 cardiac surgery patients were operated. With a propensity-matching technique a final patient population of 1600 patients was selected, with 800 patients in the first-case surgery group and 800 in the second-case surgery group. Patients in the second-case group had a major morbidity rate of 13% vs 8.8% in the first-case group (P = 0.006), and a higher rate of 30-day mortality (4.1% vs 2.3%, P = 0.033). After correction for EuroSCORE and operating surgeon, the second-case group confirmed a higher rate of major morbidity (odds ratio 1.610, 95% confidence interval 1.16-2.23, P = 0.004). CONCLUSION: Our study suggests that patients operated as second cases are exposed to an increased morbidity and mortality probably due to fatigue, loss of attention and hurriedness in the operating room and decreased human resources in the intensive care unit.

Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions in collaboration with the ESC Working Group on Cardiovascular Surgery.

Significant coronary artery disease (CAD) is a frequent finding in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), and the management of these two conditions becomes of particular importance with the extension of the procedure to younger and lower-risk patients. Yet, the preprocedural diagnostic evaluation and the indications for treatment of significant CAD in TAVI candidates remain a matter of debate. In this clinical consensus statement, a group of experts from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery aims to review the available evidence on the topic and proposes a rationale for the diagnostic evaluation and indications for percutaneous revascularisation of CAD in patients with severe aortic stenosis undergoing transcatheter treatment. Moreover, it also focuses on commissural alignment of transcatheter heart valves and coronary re-access after TAVI and redo-TAVI.

Bilateral Internal Thoracic Arteries Improve 10-Year Outcomes of Coronary Artery Bypass Grafting.

BACKGROUND: This observational cohort study was designed by the PRIORITY (PRedictIng long-term Outcomes afteR Isolated coronary arTery bypass surgery) steering committee to evaluate the 10-year follow-up outcome of bilateral internal thoracic arteries (BITA) versus single internal thoracic artery. METHODS: The PRIORITY project was designed to evaluate long-term outcome of 2 large prospective multicenter cohort studies of coronary artery bypass grafting. Clinical data on isolated coronary artery bypass grafting were merged with administrative data to collect follow-up information. The primary endpoint was the composite outcome of major adverse cardiac and cerebrovascular events at 10-year follow-up. Secondary endpoints were individual components of major adverse cardiac and cerebrovascular events at 10 years and surgical site complications or infections. A propensity score-based inverse probability treatment weighting (IPTW) was used to overcome the selection bias related to the observational nature of the study. RESULTS: The study population consisted of 10,988 patients who underwent isolated coronary artery bypass grafting. BITA was used in 23.5%. The use of BITA is related to lower incidence of major adverse cardiac and cerebrovascular events at 10 years (adjusted hazard ratio [HR] 0.88, 95% CI 0.79-0.98, P < .001). BITA correlated with better 10-year survival (IPTW adjusted HR 0.87, 95% CI 0.78-1.00, P = .05), re-revascularization (IPTW adjusted HR 0.83, 95% CI 0.74-0.92, P < .001), and myocardial infarction (IPTW adjusted HR 0.86, 95% CI 0.77-0.95, P = .005) but to increased incidence of surgical site complications or infections (HR 2.12, 95% CI 1.39-3.24, P < .001). CONCLUSIONS: In propensity-matched patients, use of BITA was associated with improved 10-year survival, freedom from repeat revascularization, and myocardial infarction but also higher incidence of surgical site complications.

[The Gelli-Bianco Law: 5-year analysis since its emission]. / Legge Gelli-Bianco: bilancio a 5 anni dalla sua emanazione.

On April 1, 2017, the n. 24/2017 Gelli-Bianco law became effective, its aim being limiting the so-called "defensive medicine" phenomenon. The first bill was neither straightforward nor judicially flawless, thus complying evenly with the law was not obvious. As a consequence, since 2017 there were several attempts to better clarify it, yet its implementation still appears debatable. Ultimately, the Law has not been a real breakthrough in medical liability, as originally intended by the Legislator. The aim of this review is to outline "lights and shadows" of this Law 5 years after its emission.

Risk of Bias in Randomized Clinical Trials Comparing Transcatheter and Surgical Aortic Valve Replacement: A Systematic Review and Meta-analysis.

Importance: Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines highlighted some concerns about the randomized clinical trials (RCTs) comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. Quantification of these biases has not been previously performed. Objective: To assess whether randomization protects RCTs comparing TAVI and SAVR from biases other than nonrandom allocation. Data Sources: A systematic review of the literature between January 1, 2007, and June 6, 2022, on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was performed. Specialist websites were also checked for unpublished data. Study Selection: The study included RCTs with random allocation to TAVI or SAVR with a maximum 5-year follow-up. Data Extraction and Synthesis: Data extraction was performed by 2 independent investigators following the PRISMA guidelines. A random-effects meta-analysis was used for quantifying pooled rates and differential rates between treatments of deviation from random assigned treatment (DAT), loss to follow-up, and receipt of additional treatments. Main Outcomes and Measures: The primary outcomes were the proportion of DAT, loss to follow-up, and patients who were provided additional treatments and myocardial revascularization, together with their ratio between treatments. The measures were the pooled overall proportion of the primary outcomes and the risk ratio (RR) in the TAVI vs SAVR groups. Results: The search identified 8 eligible trials including 8849 participants randomly assigned to undergo TAVI (n = 4458) or SAVR (n = 4391). The pooled proportion of DAT among the sample was 4.2% (95% CI, 3.0%-5.6%), favoring TAVI (pooled RR vs SAVR, 0.16; 95% CI, 0.08-0.36; P < .001). The pooled proportion of loss to follow-up was 4.8% (95% CI, 2.7%-7.3%). Meta-regression showed a significant association between the proportion of participants lost to follow-up and follow-up time (slope, 0.042; 95% CI, 0.017-0.066; P < .001). There was an imbalance of loss to follow-up favoring TAVI (RR, 0.39; 95% CI, 0.28-0.55; P < .001). The pooled proportion of patients who had additional procedures was 10.4% (95% CI, 4.4%-18.5%): 4.6% (95% CI, 1.5%-9.3%) in the TAVI group and 16.5% (95% CI, 7.5%-28.1%) in the SAVR group (RR, 0.27; 95% CI, 0.15-0.50; P < .001). The imbalance between groups also favored TAVI for additional myocardial revascularization (RR, 0.40; 95% CI, 0.24-0.68; P < .001). Conclusions and Relevance: This study suggests that, in RCTs comparing TAVI vs SAVR, there are substantial proportions of DAT, loss to follow-up, and additional procedures together with systematic selective imbalance in the same direction characterized by significantly lower proportions of patients undergoing TAVI that might affect internal validity.

Survival and Recurrence of Endocarditis following Mechanical vs. Biological Aortic Valve Replacement for Endocarditis in Patients Aged 40 to 65 Years: Data from the INFECT-Registry.

BACKGROUND: Infective endocarditis (IE) is a serious disease, and in many cases, surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement (AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival and recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. METHODS: This was an analysis of the INFECT-REGISTRY. Trends in proportion to the use of mechanical prostheses versus biological ones over time were tested by applying the sieve bootstrapped t-test. Confounders were adjusted using the optimal full-matching propensity score. The difference in overall survival was compared using the Cox model, whereas the differences in recurrence of endocarditis were evaluated using the Gray test. RESULTS: Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549, aged between 40 and 65 years, underwent AVR. A total of 268 (48.8%) received mechanical prostheses, and 281 (51.2%) received biological ones. A significant trend in the reduction of implantation of mechanical vs. biological prostheses was observed during the study period (p < 0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546, 95% CI: 0.322-0.926, p = 0.025). Mechanical prostheses were associated with significantly less recurrent endocarditis after AVR than biological prostheses (HR 0.268, 95%CI: 0.077-0.933, p = 0.039). CONCLUSIONS: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after a mechanical aortic valve prosthesis implant for IE in middle-aged patients.