Same evidence different recommendations: a methodological assessment of transatlantic guidelines for the management of valvular heart disease.

OBJECTIVES: To identify methodological variations leading to varied recommendations between the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) valvular heart disease (VHD) Guidelines, and to suggest foundational steps towards standardizing guideline development. METHODS: An in-depth analysis was conducted to evaluate the methodologies used in developing the Transatlantic Guidelines for managing VHD. The evaluation was benchmarked against the standards proposed by the Institute of Medicine. RESULTS: Substantial discrepancies were noted in the methodologies utilized in development processes, including writing committee composition, evidence evaluation, conflict of interest management, and voting processes. Furthermore, despite their mutual differences, both methodologies also demonstrate notable deviations from the IOM standards in several essential areas, including literature review and evidence grading. These dual variances likely influenced divergent treatment recommendations. For example, the ESC/EACTS recommends transcatheter edge-to-edge repair (TEER) for patients ineligible for mitral valve surgery, while the ACC/AHA recommends TEER based on anatomy, regardless of surgical risk. ESC/EACTS guidelines recommend a mechanical aortic prosthesis for patients under 60, while ACC/AHA guidelines recommend it for patients under 50. Notably, the ACC/AHA and ESC/EACTS guidelines have differing age cut-offs for surgical over transcatheter aortic valve replacement (<65 and <75 years, respectively). CONCLUSIONS: Variations in methodologies for developing CPGs have resulted in different treatment recommendations that may significantly impact global practice patterns. Standardization of essential processes is vital to increase the uniformity and credibility of CPGs, ultimately improving healthcare quality, reducing variability and enhancing trust in modern medicine.

The Risk Of Waiting Up To One Year For Cardiac Surgery.

INTRODUCTION: Cardiac disease is associated with a risk of death, both by the cardiac condition and by comorbidities. The waiting time for surgery begins with the onset of symptoms and includes referral, completion of the diagnosis and surgical waiting list (SWL). This study was conducted during the COVID-19 pandemic, which affected surgical capacity and patients' morbidities. METHODS: The cohort includes 1914 consecutive adult patients (36.6% women, mean age 67 ±11 years), prospectively registered in the official SWL from January 2019 to December 2021. We analyzed waiting times ranging from 4 days to one year to exclude urgencies and outliers. Priority was classified by the national criteria for non-oncologic or oncology surgery. RESULTS: During the study period, 74% of patients underwent surgery, 19.2% were still waiting, and 4.3% dropped out. Most cases were valvular (41.2%) or isolated bypass procedures (34.2%). Patients were classified as non-priority in 29.7%, priority in 61.8%, and high priority in 8.6%, with significantly different SWL mean times between groups (p<0.001). The overall mean waiting time was 167 ± 135 days. Mortality on SWL was 2.5%, or 1.1 deaths per patient/weeks. There were two mortality independent predictors: age (HR 1.05) and the year 2021 versus 2019 (HR 2.07) and a trend toward higher mortality in priority patients versus non-priority (p=0.065). The overall risk increased with time with different slopes for each year. Using the time limits for SWL in oncology, there would have been a significant risk reduction (p=0.011). CONCLUSION: The increased risk observed in 2021 may be related to the pandemic, either by increasing waiting time or by direct mortality. Since risk stratification is not entirely accurate, waiting time emerges as the most crucial factor influencing mortality, and implementing stricter time limits could have led to lower mortality rates.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement.

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68-77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82-1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3-6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

2022 Joint ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease in patients at low surgical risk and anatomy suitable for PCI or CABG.

In October 2021, the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) jointly agreed to establish a Task Force (TF) to review recommendations of the 2018 ESC/EACTS Guidelines on myocardial revascularization as they apply to patients with left main (LM) disease with low-to-intermediate SYNTAX score (0-32). This followed the withdrawal of support by the EACTS in 2019 for the recommendations about the management of LM disease of the previous guideline. The TF was asked to review all new relevant data since the 2018 guidelines including updated aggregated data from the four randomized trials comparing percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary artery bypass grafting (CABG) in patients with LM disease. This document represents a summary of the work of the TF; suggested updated recommendations for the choice of revascularization modality in patients undergoing myocardial revascularization for LM disease are included. In stable patients with an indication for revascularization for LM disease, with coronary anatomy suitable for both procedures and a low predicted surgical mortality, the TF concludes that both treatment options are clinically reasonable based on patient preference, available expertise, and local operator volumes. The suggested recommendations for revascularization with CABG are Class I, Level of Evidence A. The recommendations for PCI are Class IIa, Level of Evidence A. The TF recognized several important gaps in knowledge related to revascularization in patients with LM disease and recognizes that aggregated data from the four randomized trials were still only large enough to exclude large differences in mortality.

Post-infarction ventricular septal defect surgery in Portugal.

INTRODUCTION AND OBJECTIVE: We performed a collective analysis of a dedicated national post-myocardial infarction ventricular septal defect (VSD) registry to further elucidate controversial areas of this clinical entity's surgical treatment. METHODS: A descriptive statistical analysis was carried out and cumulative survival using the Kaplan-Meier method and multivariate logistic regression of risk factors for 30-day mortality are presented. RESULTS: Median survival of the cohort (n=76) was 72 months (95% CI 4-144 months). Better cumulative survival was observed in patients who underwent VSD closure more than 10 days after myocardial infarction (log-rank p=0.036). Concomitant coronary artery bypass grafting (CABG), different closure techniques, location of the VSD, extracorporeal membrane oxygenation as bridge to closure, or intra-aortic balloon pump as bridge to closure showed no statistically significant differences at Kaplan-Meier analysis. Multivariate binary logistic regression for independent factors affecting status at 30 days showed a statistically significant effect of age (OR 1.08; 95% CI 1.01-1.15) and concomitant CABG (OR 0.23; 95% CI 0.06-0.90). CONCLUSIONS: Our results are comparable with previous reports regarding mortality, risk factors and concomitant procedures. Timing of surgery remains a controversial issue. Later closure seems to be advantageous, however, there is significant observational bias.

Pretreatment with a P2Y12 receptor inhibitor and delay to coronary artery bypass surgery in patients with non-ST segment elevation acute coronary syndrome.

BACKGROUND: 2020 ESC guidelines for non-ST elevation acute coronary syndromes (NSTE-ACS) recommend against the pretreatment with P2Y12 receptor inhibitors (P2Y12i) in patients undergoing early invasive management (<24 h). The rationale is, in part, to prevent bleeding complications and the delay of coronary artery bypass graft surgery (CABG) in patients with suitable coronary anatomy. This study aimed to analyze the theoretical impact of pretreatment with a P2Y12i on delay to CABG surgery in a real-world population with NSTE-ACS. METHODS: Single-center retrospective cohort of consecutive patients with NSTE-ACS undergoing invasive evaluation in 2019. Those with previous CABG or nonobstructive coronary disease were excluded. RESULTS: The total cohort included 262 patients (mean age 68±12 years, 69% male, 15% with unstable angina and mean GRACE score 134±35). Median time from FMC to angiography was 2 (1-4) days. Overall, 168 (64%) patients underwent percutaneous coronary intervention, 47 (18%) were proposed for CABG and the remainder received conservative management. All patients considered for CABG received pretreatment with P2Y12i (clopidogrel or ticagrelor). The median time from angiography to CABG was 12 (7-15) days. Six patients experienced recurrent angina (13%) and 2 (4%) died before surgery due to refractory ventricular fibrillation. Those who underwent CABG under P2Y12i effect were more likely to receive blood and platelets transfusions (64.7% vs. 28.6%, P=0.017 and 82.4% vs. 21.4%, P<0.001, respectively), although there were no differences regarding major bleeding. CONCLUSIONS: Pretreatment with P2Y12i was a potential but not the sole driver of CABG delay in our cohort. Adopting the new recommendations of withholding pretreatment might decrease this delay, but other factors must be considered.

Infective Endocarditis: A Prospective Registry Of Surgical Lesions.

INTRODUCTION: Infective endocarditis morbidity and mortality remains high. Surgery is performed in about half of endocarditis cases, being the ideal setting to evaluate endocarditis lesions. The aim of this study was to register and describe endocarditis lesions found during surgery; find predictors of morbidity and mortality and correlate lesions found in echocardiogram vs. surgery. MATERIALS AND METHODS: One hundred consecutive patients with endocarditis lesions seen during surgery were included between June 2014 and August 2018. Pathological lesions were coded prospectively using a coding form published by Pettersson et al. Other data were collected retrospectively. RESULTS: Prosthetic endocarditis accounted for 23% of cases. Embolic events had occurred in 41% of cases, mainly to the brain (22%). The most frequent lesions found in echocardiogram were vegetations (77%). Vegetations and valve integrity anomalies were the main lesions described during surgery (70% and 71% respectively). Invasion was present in 39% of patients. In-hospital mortality was 9%. In univariable analysis, predictors of early mortality included chronic kidney disease (P= .005), prosthetic valve endocarditis (P <.001), EuroSCORE II (P <.001) and valve integrity anomalies (P=.016). Predictors of embolic events included aortic valve vegetations seen during surgery (P= .026). Sensitivity and specificity of echocardiogram findings for identification of vegetations were 84% and 40%, for valve integrity anomalies 42% and 97% and for invasion 54% and 95%, respectively. CONCLUSIONS: Diversity of lesions found in endocarditis precludes obtaining significant predictors of morbidity or mortality with small numbers of patients. Echocardiogram lacks sensitivity for valve integrity anomalies and invasion but is highly specific.

What is the role of septal myectomy in aortic stenosis?

Asymmetric basal septal hypertrophy is present in 10% of patients with hemodynamic significant aortic valve stenosis. From the surgeon's standpoint, it represents a dilemma as it may be implicated in suboptimal short and long-term results after aortic valve replacement (AVR), but also heighten unwarranted complications at the time of surgical correction. To provide insight about the usefulness and safety of concomitant septal myectomy in this setting, we performed a literature review searching Medline from its inception to November 2020 using the Pubmed interface. Only five low evidence retrospective analyses, comprising a total of <200 patients undergoing AVR with concomitant septal myectomy, were found in the literature. In summary, routine myectomy, in the presence of suspected or directly visualized asymmetric septal hypertrophy on echocardiogram during AVR, seems to be a safe procedure, with all authors reporting a low rate or absence of complications. Overall, myectomy in this setting is associated with superior echocardiographic results concerning surrogates of LV remodelling (LVM; LVM index; LVM/height) and diastolic function (E/E'), suggesting some benefit for hemodynamic outcomes. However, to what extent hemodynamic improvement is exclusively attributable to myectomy is uncertain, as is, the clinical significance of such an improvement, with similar short and mid-term survival rates being reported.

How to deal with nonsevere stenoses in coronary artery bypass grafting - a critical perspective on competitive flow and surgical precision.

PURPOSE OF REVIEW: For invasive treatment of coronary artery disease (CAD), we assess anatomical complexity, analyse surgical risk and make heart-team decisions for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). With PCI, treating flow-relevant lesions is recommended, and reintervention easily treats disease progression. For CABG, some stenoses may only be borderline or nonsevere despite a clear surgical indication. As reoperations are not easy, the question on how to address these lesions has been around from the start, but has never satisfactorily been answered. RECENT FINDINGS: With a new mechanistic perspective, we had suggested that infarct-prevention by surgical collateralization is the main prognostic mechanism of CABG in chronic coronary syndrome. Importantly, the majority of infarctions arise from nonsevere coronary lesions. Thus, surgical collateralization may be a valid treatment option for nonsevere lesions, but graft patency moves more into focus here, because graft patency directly correlates with the severity of coronary stenoses. In addition, CABG may even accelerate native disease progression. SUMMARY: We here review the evidence for and against grafting nonsevere CAD lesions, suggesting that patency of grafts (to moderate lesions) may be improved by increasing surgical precision. In addition, we must improve our ability to predict future myocardial infarctions.

Triple valve surgery: long-term follow-up from a single centre.

AIMS: The aims of this study were to analyze early and late outcomes of TVS and identify predictors of short and long- term poor prognosis. METHODS: Single centre retrospective study with 130 patients who underwent TVS between 2007 and 2020. Most of the patients were female (72.3%), mean age of 64.4 years; 61.1% were in New York Heart Association class III/IV, with a EuroSCORE II of 7.5%. Univariable and Multivariable analyses were undertaken to identify predictors of perioperative mortality and morbidity and long-term mortality. RESULTS: In-hospital mortality was 10.8%, of which 7.6% were due to a cardiac cause. Diabetes Mellitus was an in- dependent predictor of increased perioperative mortality. This group had 27.7% rate of major perioperative complications. Elevated systolic pulmonary pressure and obesity were predictors of early morbidity. All-cause mortality was 43.1% for 14 years. The survival at 1, 5 and 10 years was 83%, 60% and 43%, respectively. Diabetes Mellitus was a risk factor for long-term mortality. CONCLUSIONS: Patients undergoing TVS have a high surgical risk making TVS an operation associated with high mor- tality and morbidity. This research suggests Diabetes Mellitus, pulmonary hypertension and obesity as risk factors for mortality in TVS.

LUNG RESECTION FOR NON-SMALL-CELL LUNG CANCER - A NEW RISK SCORE TO PREDICT MAJOR PERIOPERATIVE COMPLICATIONS.

OBJECTIVES: Identify risk factors for major perioperative complications (MPC) after anatomical lung resection for NonSmall-Cell Lung Cancer (NSCLC) and establish a scoring system. METHODS: Single center retrospective study of all consecutive patients diagnosed with NSCLC submitted to anatomical lung resection from 2015 to 2019 (N=564). EXCLUSION CRITERIA: previous lung surgery, concomitant non-lung cancer related procedures, urgency surgery. STUDY POPULATION: 520 patients. PRIMARY END-POINT: MPC defined as a composite endpoint including at least one of the in-hospital complications. Univariable and Multivariable analyses were developed to identify predictors of perioperative complications and create a risk score. Discrimination was assessed using the C-statistic. Calibration was evaluated by Hosmer and Lemeshow test and internal validation was obtained by means of bootstrap replication. RESULTS: Mean age of 65 years and 327 (62.9%) were males. Mean hospital stay of 9 days after surgery. Overall MPC rate was 23.3%. Male gender, hypertension, FEV1<75%, thoracotomy, bilobectomy/pneumectomy and additional resection were independent predictors of MPC. A risk score based on the odds ratios was developed - Major Perioperative Complications of Lung Resection (MPCLR) scoring system - and ranged between 0 and 14 points. It was divided in 5 groups: 1-2 points (positive preditive value 15%); 3-4 (PPV 25%); 5-7 (PPV 35%); 8-9 (PPV 60%); >10 points (PPV 88%). The score showed rea- sonable discrimination (C-statistic=0.70), good calibration (P=.643) and it was internally validated (C-statistic=0,70 BCa95% CI,0.65-0.79). CONCLUSIONS: This study proposes a simple and daily-life risk score system that was able to predict the incidence of perioperative complications.

Are NOACs as safe and efficient as VKA regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'Are NOACs as safe and efficient as vitamin K antagonist regarding thromboembolic prophylaxis and major bleeding in patients with surgical bioprosthesis and atrial fibrillation within 3 months of surgery?' Altogether more than 324 papers were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The RIVER and ENAVLE trials showed non-inferiority of rivaroxaban (regarding mean time free from composite of death, major cardiovascular events or major bleeding at 12 months) and edoxaban (composite of death, clinical thromboembolic events or asymptomatic intracardiac thrombosis; and major bleeding) when compared with vitamin K antagonist. These studies include a low number of patients within 3 months of index surgery and overall low statistical power regarding this particular subgroup of patients. Data derived from lower evidence studies are compatible with the aforementioned findings. The available evidence suggests that non-vitamin K antagonist anticoagulants are as safe and as efficient as vitamin K antagonist regarding thromboembolic prophylaxis and bleeding event rates in patients with surgical bioprosthesis and atrial fibrillation within 3 months of bioprosthesis implantation. However, this evidence is derived from a limited number of studies with important methodological limitations. Expanding non-vitamin K antagonist anticoagulant recommendation to the early postoperative period warrants more confirmatory research.

In low-risk patients aged >70-75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported cardiovascular composite outcomes and survival?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In low-risk patients aged >70-75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported composite outcomes and survival? More than 73 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. The only low-risk randomized control trial to date [Nordic Aortic Valve Intervention (NOTION)] regarding an elderly population did not show a statistically significant difference between the 2 approaches regarding the composite endpoint of death, stroke or myocardial infarction. A subgroup analysis of elderly patients in the 2 main low-risk randomized control trials did not yield statistically different results from those of the overall population; the results indicated the superiority of transcatheter aortic valve implantation regarding the composite of death, stroke or rehospitalization at 1 year [The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis (PARTNER 3)] and non-inferiority regarding a composite of death or stroke at 2 years [Medtronic Evolut Transcatheter Aortic Valve Replacement in Low-Risk Patients (Evolut LR)]. The results from lower evidence studies are largely consistent with these findings. Overall, there is no compelling evidence indicating that older age should be an isolated criterion for the choice between transcatheter aortic valve replacement and surgical aortic valve replacement in otherwise low-risk patients. The superiority of either technique regarding the aforementioned composite short-term outcomes in this particular subgroup of patients is unclear.

Five-year outcomes in trials comparing transcatheter aortic valve implantation versus surgical aortic valve replacement: a pooled meta-analysis of reconstructed time-to-event data.

OBJECTIVES: The incidence of outcomes in trials comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is expected to be different in the short and long term. We planned a meta-analysis of reconstructed time-to-event data from trials comparing TAVI and SAVR to evaluate their time-varying effects on outcomes. METHODS: We performed a systematic review of the literature from January 2007 through September 2021 on Medline, Embase, the Cochrane Central Register of Controlled Trials and specialistic websites, including randomized trials with allocation to TAVI or SAVR that reported at least 1-year follow-up and that graphed Kaplan-Meier curves of end points. The comparisons were done with grouped frailty Cox models in a landmark framework and fully parametric models. RESULTS: Seven trials were included (7770 participants). TAVI showed a lower incidence of the composite of death or stroke in the first 6 months [risk-stratified hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.56-0.77, P-value <0.001], with an HR reversal after 24 months favouring SAVR (risk-stratified HR 1.25; 95% CI 1.08-1.46; P-value 0.003). These outcomes were confirmed for all-cause death (risk-stratified HR after 24 months 1.18; 95% CI 1.03-1.35; P-value 0.01). TAVI was also associated with an increased incidence of rehospitalization after 6 months (risk-stratified HR 1.42; 95% CI 1.06-1.91; P-value 0.018) that got worse after 24 months (risk-stratified HR 1.67; 95% CI 1.24-2.24; P-value <0.001). CONCLUSIONS: Although it could appear that there is no difference between TAVI and SAVR in the 5-year cumulative results, TAVI shows a strong protective effect in the short term that runs out after 1 year. TAVI becomes a risk factor for all-cause mortality and the composite end point after 24 months and for rehospitalization after 6 months.

Complete surgical revascularization: Different definitions, same impact?

BACKGROUND: There are several different definitions of complete revascularization on coronary surgery across the literature. Despite the importance of this definition, there is no agreement on which one has the most impact. The aim of this study was to evaluate which definition of complete surgical revascularization correlates with early and late outcomes. METHODS: All consecutive patients submitted to isolated CABG from 2012 to 2016 with previous myocardial scintigraphy were evaluated. EXCLUSION CRITERIA: emergent procedures and previous cardiac surgery procedures. The population of 162 patients, follow-up complete in 100% patients; median 5.5; IQR: 4.4-6.9 years. Each and all of the 162 patients were classified as complying or not with the four different definitions: numerical, functional, anatomical conditional, and anatomical unconditional. Perioperative outcome: MACCE; long-term outcomes: survival and repeat revascularization. Univariable and multivariable analyses were developed to detect predictors of outcomes. RESULTS: Complete functional revascularization was a predictor of increased survival (HR: 0.47; CI 95: 0.226-0.969; p = .041). No other definitions showed effect on follow-up mortality. Age and cardiac dysfunction increased long-term mortality. The definition of complete revascularization did not have an impact on MACCE or the need for revascularization CONCLUSIONS: A uniformly accepted definition of complete coronary revascularization is lacking. This study raises awareness about the importance of viability guidance for CABG.