Effectiveness and Safety of P2Y12 Inhibitor Pretreatment for Primary PCI in STEMI: Systematic Review and Meta-analysis.

ABSTRACT: Dual antiplatelet therapy with aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We performed a systematic search of electronic databases PubMed, CENTRAL, and Scopus until April 2022. Studies were eligible if they compared P2Y12 inhibitor upstream administration with downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomes were assessed at the shortest follow-up available. Of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79,300 patients (66.1% pretreated, 66.0% treated with clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (odds ratio [OR] 0.61 [0.38-0.98]), all-cause death (OR 0.77 [0.60-0.97]), and cardiogenic shock (OR 0.60 [0.48-0.75]). It was also associated with a lower incidence of thrombolysis in myocardial infarction flow <3 pre-PCI (OR 0.78 [0.67-0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57-1.52]). Regarding safety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75-0.92]). Pretreatment with dual antiplatelet therapy, including a P2Y12 inhibitor, was associated with better pre-PCI coronary perfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.

Histopathological myocardial changes in patients with severe aortic stenosis referred for surgical valve replacement: a cardiac magnetic resonance correlation study.

AIMS: Myocardial fibrosis (MF) takes part in left ventricular (LV) remodelling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. The aim of this study was to describe histopathological changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR) and to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). METHODS AND RESULTS: One-hundred fifty-eight patients [73 (68-77) years, 50% women] were referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping, and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson's Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). Non-ischaemic LGE was present in 106 patients (67.1%) [median fraction: 5.0% (2.0-9.7)]. Native T1 was above normal [1053 ms (1024-1071)] and T2 within the normal range [39.3 ms (37.3-42.0)]. Median MF was 11.9% (6.54-19.97), with predominant type I collagen perivascular distribution (95.3%). Sub-endocardial cardiomyocyte ischaemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodelling expression. MF quantification at EMB was correlated with LGE mass (P = 0.008) but not with global ECV (P = 0.125). CONCLUSION: Patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischaemic insult. ECM remodelling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.

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.

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.

Task Force structure and summary of clinical evidence of 2022 ESC/EACTS review of the 2018 guideline recommendations on the revascularization of left main coronary artery disease. CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; LM, left main; SYNTAX, Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. a'Event' refers to the composite of death, myocardial infarction (according to Universal Definition of Myocardial Infarction if available, otherwise protocol defined) or stroke. 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.

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.

Off-pump coronary artery bypass surgery in women.

OBJECTIVE: Gender is a well-known risk factor for mortality and morbidity after coronary artery bypass grafting and various reasons have been proposed to explain the poorer results observed in women. The study objective was to determine whether female gender was still an operative risk factor with the adoption of off-pump coronary artery bypass surgery. METHODS: Of 2123 consecutive patients who underwent isolated CABG between November 2002 and December 2007, 1966 (92.6%) (481 women and 1485 men) were operated without cardiopulmonary bypass and form the study population. Women were older (69.0 vs. 64.7 years; p = 0.001) and had more severe angina (CCS class 3.1 vs. 2.7; p = 0.001), smaller body surface area (1.6 vs. 1.8 m2; p = 0.001), higher body mass index and greater incidence of diabetes (48.3% vs. 34.2%; p = 0.005) than men. There were no statistically significant differences in the incidence of three-vessel disease (69.5% vs. 71.9%) or left main disease (22.2% vs. 27.0%) but ejection fraction was higher in women (61.3% vs. 59.0%; p = 0.01). Risk factors for in-hospital mortality were identified by univariate analysis and logistic regression. RESULTS: The number of distal anastomoses was lower in women than in men (2.8 vs. 3.0; p = 0.001). In-hospital mortality was 2.0% in women and 0.8% in men (p = 0.01) and female gender was one of the eight risk factors for in-hospital mortality identified by univariate analysis. Using a logistic regression model, only age (OR: 1.7; 95% CI 1.01-1.14; p = 0.02) and logistic EuroSCORE (OR: 1.07; 95% CI 1.03-1.10; p < 0.001) were independently associated with in-hospital mortality. Logistic EuroSCORE was the only independent risk factor for major morbidity (OR: 1.07 95% CI 1.04-1.10; p < 0.001). CONCLUSION: Women who undergo coronary artery bypass grafting have an unfavorable clinical profile compared to men, resulting in higher unadjusted in-hospital mortality. However, in an unselected patient population undergoing off-pump CABG, female gender was not found to be an independent risk factor for mortality or major morbidity.

Interrupted aortic arch: an eight-year experience.

INTRODUCTION: Interrupted aortic arch (IAA) is a rare congenital heart defect with a high mortality rate in the neonatal period. Surgical correction of associated intracardiac anomalies can be performed in a one-stage (primary) or two-stage approach. OBJECTIVES: Case review of children with IAA operated in our center and to evaluate the surgical outcomes and the occurrence of complications. METHODS: A retrospective chart review of children operated from June 1998 to October 2006. RESULTS: Twelve children (nine girls and three boys) were operated. Nine patients had ventricular septal defect with septal malalignment, two had univentricular hearts and two had transposition of the great arteries. Primary correction was performed in eleven patients (aged between two and 38 days), including two Norwood procedures. There was no early mortality. The follow-up time ranged from 30 days to six years (median 2.6 years), with late mortality of 33%. Two children required reintervention for aortic arch restenosis, which was successfully treated by catheterization. DISCUSSION: Our experience is that early primary repair of IAA has low early and late mortality and is the method of choice most situations. Late mortality depends the severity of associated anomalies.

Innovation, evidence and the real world. A surgeon's perspective on the treatment of three-vessel or left main coronary artery disease with drug-eluting stents.

Percutaneous coronary intervention has been at the forefront of innovation, driven by the need to find less invasive but still safe and effective ways to treat patients with coronary artery disease. There has been real progress but high expectations at each innovative step have been repeatedly followed by a more realistic appraisal. Although the evidence-generation process for the treatment of stable angina can be debated, guidelines are the basis of clinical practice and these consider coronary artery bypass surgery the preferred treatment for left main or three-vessel coronary artery disease, particularly in diabetic patients. The current practice of multivessel drug-eluting stenting for three-vessel disease, particularly in those with diffuse disease, diabetes or unprotected left main disease, is based more on hype and hope than scientific evidence. Moreover, safety concerns regarding drug-eluting stents and the need for dual antiplatelet therapy for an unknown period to prevent late stent thrombosis make this practice questionable, particularly in the setting of untested conditions. The best treatment for the patient with stable angina and three-vessel coronary artery disease or left main disease should be discussed within multidisciplinary teams.

Less invasive coronary artery bypass surgery: early results in 1083 patients operated off-pump.

OBJECTIVE: To analyze the early results of coronary surgery without cardiopulmonary bypass using the EuroSCORE risk model. METHODS: Out of a series of 1104 consecutive patients undergoing CABG during a 20-month period and whose data were prospectively collected, 1083 patients (98.1%) were operated without cardiopulmonary bypass (CPB) and represent the patient population. Mean age was 65.6 +/- 9.9 years (31-90), 23.1% were female, 77.9% hypertensive, 38.0% diabetic, 22.8% had peripheral vascular disease, 73.0% triple-vessel disease, 54.7% previous myocardial infarction and 67.0% were in CCS class III or IV. Three hundred and forty-one patients (31.5%) were operated on urgently. Surgery was performed with the aid of cardiac stabilizers and intracoronary shunts. RESULTS: The mean number of distal anastomoses was 2.9; the left internal mammary artery was used in 99% of patients. In 10 patients (0.9%), conversion to CPB was required, without mortality or morbidity. Sixteen patients (1.5%) had myocardial infarction; mean troponin T and CK-MB at 24 h were 0.20 +/- 0.43 ng/ml and 28.2 +/- 49.9 U/l respectively. Twenty patients (1.8%) had neurologic deficit, 10 (0.9%) required hemofiltration or dialysis, 229 (21%) received blood transfusions and 135 (14.2%) had atrial fibrillation. Median intubation time was 9 h, and median ICU stay was one day. Median hospital stay was 5 days. Twelve patients died in hospital (1.1%). Thirty-day observed mortality and EuroSCORE-predicted mortality were 1.3% and 4.0% respectively (p < 0.01). CONCLUSION: Off-pump CAB surgery has become our preferred method in almost all patients undergoing coronary surgery, without compromising completeness of revascularization. Observed mortality was significantly lower than that predicted by EuroSCORE and the incidence of complications was reasonably low considering the population's risk factors.

National Adult Cardiac Surgery Registry: past, present and future.

A task force commission was created with the support of the Portuguese Society for Cardiothoracic and Vascular Surgery with the aim of organizing a National Adult Cardiac Surgery Registry, collecting clinical data and types of cardiac surgical procedure performed in Portugal. Selected variables include risk factors, cardiac status, preoperative hemodynamics, surgical procedure, hospital stay and mortality. Information is collected into a database in each institution and sent via the internet to a central database responsible for grouping and data analysis. It is hoped that this National Registry, through standardized data collection, will provide information on cardiac surgery activity in Portugal and its risk adjusted results.

Coronary surgery: which method to use?

OBJECTIVE: To compare 4 methods of myocardial protection in GABG in terms of markers of myocardial ischemia, mortality, morbidity and mid-term results. MATERIAL & METHODS: Retrospective study of 241 consecutive patients undergoing isolated > 1 CABG using one of 4 methods: off-pump (OFF, n = 108), cardiopulmonary bypass (CPB) and cardioplegia (CARD, n = 66), CPB and beating heart (BEAT, n = 47), or CPB and ventricular fibrillation (FIBR, n = 20). Mean age was 65.7 +/- 9.3 years and mean EuroSCORE was 3.2 +/- 2.3. The groups were similar in terms of age, gender distribution, body mass index, incidence of smoking, hypertension, renal insufficiency, CCS class, ventricular function and mean EuroSCORE. Serial blood samples were collected for CK-MB and troponin T, preoperatively and 1, 6, 12 and 24 hours after the procedure. RESULTS: Mean number of distal anastomoses was 3.27 BEAT, 2.98 CARD, 2.90 FIBR and 2.55 OFF (p < 0.05 OFF vs. the other 3 groups). Six patients died in hospital (2.5%), 2/47 BEAT (4.2%), 1/66 CARD (1.5%), 1/20 FIBR (5.0%), 2/108 (1.9% OFF) (p = 0.1). The incidence of atrial fibrillation, stroke/TIA and blood transfusion and length of stay were similar between groups (p = 0.1) but there was a tendency for increased incidence of Q-wave MI (p = 0.08) in OFF and combined adverse events in FIBR (p = 0.07). At 12 hours postoperatively, CK-MB and troponin T were significantly higher in FIBR than in CARD or OFF (p < 0.05) and at 24 hours, troponin T remained higher in FIBR than in all other groups (p < 0.05). After a mean follow-up of 19 months, no significant difference was observed between groups in mortality or relief of angina. CONCLUSION: We were unable to demonstrate the superiority of any one revascularization method over another in terms of mortality, morbidity or length of stay. As shown by lower levels of myocardial markers of ischemia, better myocardial protection was obtained with OFF, BEAT and CARD compared to FIBR. Mid-term survival and relief of angina were similar between groups.

Coronary surgery in patients with porcelain aorta.

Four patients with unstable angina due to left main or three-vessel disease scheduled for coronary artery bypass grafting were found intra-operatively to have porcelain ascending aorta, defined as massive calcification of the ascending aorta from the aortic valve to the transverse arch, precluding ascending aorta cannulation or clamping. A no-touch operative technique was applied using the two internal mammary arteries in three cases, with complementary Y-grafting when necessary. Three cases underwent off-pump myocardial revascularization. The fourth case was revascularized with pump-assisted beating heart and proximal saphenous graft anastomosis with an automatic connector. There was no mortality or neurologic morbidity and all patients were discharged home before post-operative day 8.

Cardiac surgery and morbid obesity.

OBJECTIVE: Obesity is considered a risk factor for the occurrence of complications after cardiac surgery. The objective of this study was to analyze mortality and morbidity in patients with morbid obesity following heart surgery. DESIGN: Retrospective study in a tertiary care setting. METHODS: Out of 1815 adult patients undergoing cardiac surgery, 50 consecutive patients (3%) with morbid obesity (defined by a body mass index (BMI) > 35 kg/m2) operated on between 7/98 and 3/01 were studied. Mean age was 61.9 +/- 10.4 years, mean BMI was 38.0 +/- 2.7 kg/m2 and mean Parsonnet score was 14.3. Thirty patients had CABG, 14 underwent valve surgery and 6 had combined valve and CABG. RESULTS: Three patients died in the first 30 days (hospital mortality = 6%). Four patients had myocardial infarction (8%), 4 patients had stroke (8%) and 13 required blood transfusion (29%). There were no deep sternal wound infections or reoperations but 9 patients (15%) presented superficial wound infections. Mean ICU and hospital stay were 2.2 +/- 2.2 and 6.8 +/- 4.1 days respectively. With a mean follow up of 13.9 +/- 8.9 months, 4 patients died; 38 (93%) out of the 41 patients reviewed are in NYHA class I or II and 27 (65%) have unrestricted physical activity. CONCLUSIONS: Cardiac surgery in patients with morbid obesity carries a higher morbidity and mortality risk. Short- and medium-term results were satisfactory with improvement in quality of life in two-thirds of the patients.