Atrial functional mitral regurgitation in cardiology and cardiac surgery.

Functional or secondary mitral regurgitation (MR) is a clear and present danger to cardiovascular health, with heightened morbidity and mortality rates. Secondary MR is caused by an imbalance between two sets of forces. There are two forces at play here. One keeps the mitral leaflets tethered, while the other closes them. The evidence clearly shows inadequate coaptation. Functional MR (FMR) is the typical form of MR. It is almost always caused by dysfunction and alterations of the left ventricle (LV) geometry. It occurs in both ischemic and non-ischemic disease states. Atrial FMR (AFMR) is a disease that has only recently come to be acknowledged. This phenomenon arises when mitral annular enlargement is caused by left atrial enlargement. This preserves the geometry and function of the LV. AFMR is most frequently encountered in individuals with chronic atrial fibrillation or heart failure, in whom a normal ejection fraction is present. Published studies and ongoing research vary in their definition of AFMR, but there is no doubt that AFMR exists. This review definitively explains the pathophysiology of AFMR and demonstrates the necessity of a common working standard for the definition of AFMR. This is essential to warrant cohesiveness in the data reported and to drive forward the much-needed research into the outcomes and treatment strategies in this critical field. A number of high-quality studies have demonstrated that restrictive mitral annuloplasty and transcatheter procedure based on edge-to-edge repair are effective in reducing MR and alleviating symptoms. The pathophysiology, echocardiographic diagnosis, and treatment of AFMR are thoroughly reviewed in this comprehensive review.

Aortic arch registry of type a aortic dissection (AoArch) - rationale, design and definition criteria.

BACKGROUND: Type A acute aortic dissection (TAAAD) is a deadly condition that demands immediate surgery, because it involves a critically. The mortality and morbidity associated with it are significant, and it is vital that the patient's conditions and treatment strategies are fully understood to ensure the appropriate management of TAAAD. This study aims to ascertain whether hemiarch repair (HAR) versus extended arch repair (EAR) with or without descending aortic intervention results in better perioperative and late outcomes for patients with TAAAD. METHODS: Four leading centers of cardiac surgery from two European countries have joined forces to create a groundbreaking multicenter observational registry (AoArch). This study was approved by the institutional review board (IRB 202201173). We conducted a retrospective review (NCT00591263) of our prospectively maintained database for patients who underwent operative repair of DeBakey type I or type II dissection from January 1, 2005 to March 2024 (NCT05927090). We will analyze how patient co-morbidities, referral conditions, and surgical strategies involving hemi-arch repair (HAR) and extended arch repair (EAR) impact early and late adverse events. We have developed a procedure urgency algorithm based on the severity of preoperative hemodynamic conditions and malperfusion due to TAAAD, and we will use it to assess the primary clinical outcomes: in-hospital mortality, late mortality, and reoperations on the aorta. We will define secondary outcomes as permanent neurologic deficit, the need for new dialysis, respiratory failure, a composite of major adverse events (myocardial infarction, cerebrovascular accidents, the need for dialysis, or the need for tracheostomy), and a composite of major adverse pulmonary events (intubation over 48 h, pneumonia, reintubation, tracheostomy), and reoperation due to bleeding. DISCUSSION: This multicenter registry will definitively determine the prognostic significance of critical preoperative conditions and the efficacy of extended arch interventions and hemiarch repair in reducing the risk of early adverse events after surgery for TAAAD. This registry will provide insights into the long-term durability of different strategies of surgical repair for TAAAD.

Sutureless Valves, a "Wireless" Option for Patients With Aortic Valve Disease: JACC State-of-the-Art Review.

Transcatheter technologies triggered the recent revision of the guidelines that progressively widened the indications for the treatment of aortic stenosis. On the surgical realm, a technology avoiding the need for sutures to anchor the prosthesis to the aortic annulus has been developed with the aim to reduce the duration of cardiopulmonary bypass and simplify the process of valve implantation. In addition to a transcatheter aortic valve replacement (TAVR)-like stent that exerts a radial force, these so-called "rapid deployment valves" or "sutureless valves" for aortic valve replacement also have cuffs to improve sealing and reduce the risk of paravalvular leak. Despite promising, the actual advantage of sutureless valves over traditional surgical procedures (surgical aortic valve replacement) or TAVR is still debated. This review summarizes the current comparative evidence reporting outcomes of "sutureless valves" for aortic valve replacement to TAVR and surgical aortic valve replacement in the treatment of aortic valve stenosis.

Native Infective Endocarditis: A State-of-the-Art-Review.

Native valve infective endocarditis (NVE) is a global phenomenon, defined by infection of a native heart valve and involving the endocardial surface. The causes and epidemiology of the disease have evolved in recent decades, with a doubling of the average patient age. A higher incidence was observed in patients with implanted cardiac devices that can result in right-sided infection of the tricuspid valve. The microbiology of the disease has also changed. Previously, staphylococci, which are most often associated with health-care contact and invasive procedures, were the most common cause of the disease. This has now been superseded by streptococci. While innovative diagnostic and therapeutic strategies have emerged, mortality rates have not improved and remain at 30%, which is higher than that for many cancer diagnoses. The lack of randomized trials and logistical constraints impede clinical management, and long-standing controversies such as the use of antibiotic prophylaxis persist. This state of the art review addresses clinical practice, controversies, and strategies to combat this potentially devastating disease. A multidisciplinary team will be established to provide care for patients with presumptive NVE. The composition of the team will include specialists in cardiology, cardiovascular surgery, and infectious disease. The prompt administration of combination antimicrobial therapy is essential for effective NVE treatment. Additionally, a meticulous evaluation of each patient is necessary in order to identify any indications for immediate valve surgery. With the intention of promoting a more comprehensive understanding of the procedural management of native infective endocarditis and to furnish clinicians with a reference, the current evidence for the utilization of distinct strategies for the diagnosis and treatment of NVE are presented.

P2Y12 Receptor Inhibitor for Antiaggregant Therapies: From Molecular Pathway to Clinical Application.

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs.

Role of gender in short- and long-term outcomes after surgery for type A aortic dissection: analysis of a multicentre European registry.

OBJECTIVES: Gender difference in the outcome after type A aortic dissection (TAAD) surgery remains an issue of ongoing debate. In this study, we aimed to evaluate the impact of gender on the short- and long-term outcome after surgery for TAAD. METHODS: A multicentre European registry retrospectively included all consecutive TAAD surgery patients between 2005 and 2021 from 18 hospitals across 8 European countries. Early and late mortality, and cumulative incidence of aortic reoperation were compared between genders. RESULTS: A total of 3902 patients underwent TAAD surgery, with 1185 (30.4%) being females. After propensity score matching, 766 pairs of males and females were compared. No statistical differences were detected in the early postoperative outcome between genders. Ten-year survival was comparable between genders (47.8% vs 47.1%; log-rank test, P = 0.679), as well as cumulative incidences of distal or proximal aortic reoperations. Ten-year relative survival compared to country-, year-, age- and sex-matched general population was higher among males (0.65) compared to females (0.58). The time-period subanalysis revealed advancements in surgical techniques in both genders over the years. However, an increase in stroke was observed over time for both populations, particularly among females. CONCLUSIONS: The past 16 years have witnessed marked advancements in surgical techniques for TAAD in both males and females, achieving comparable early and late mortality rates. Despite these findings, late relative survival was still in favour of males.

The Ross Operation Over 55 Years Later: Comparing Surgical Techniques and Outcomes.

The Ross procedure is often considered the best option for a small group of patients. Some critics argue that harvesting the pulmonary artery again can cause problems, such as exposing the native pulmonary autograft to systemic pressures and requiring further intervention. However, the pulmonary autograft is a living tissue that can adjust to growing conditions and undergo remodelling. The pathophysiology of living tissue, harvesting techniques, indications for use of pulmonary autograft in aortic valve disease, contraindications, and variations of pulmonary autograft as an aortic conduit are discussed in this seminar. Following recent updates from high-volume centres, the indications, contraindications, techniques, and variations of pulmonary autograft as an aortic conduit and, in the absence of substantial well-designed randomised controlled trials, areas where the Ross procedure needs to be reaffirmed as part of the surgical armamentarium are also discussed. Furthermore, increasing evidence suggests that the Ross procedure produces better long-term results than traditional aortic valve replacement in young and middle-aged adults. To enable cardiologists and surgeons to make appropriate decisions for their patients with aortic valve disease, the author provides a complete review of the most recent published studies on the Ross procedure.

Postoperative follow-up of 221 patients with infective endocarditis from Gaoligong mountain area of Yunnan in China: a retrospective, single-center, observational cohort study.

Background: Despite improvements in management, infective endocarditis (IE) is still associated with high mortality and morbidity. The outcome of patients with IE remains unclear in high-altitude areas of China. To characterize the epidemiological features and surgical outcomes, a retrospective analysis was conducted to 221 patients diagnosed with IE from a single center. In addition, to assess the prognosis of patients, a multivariate logistic regression model was performed to analyze the affecting risk factors. Methods: A retrospective analysis was conducted on the clinical data of 221 patients with IE who underwent surgical treatment at the Department of Cardiac Surgery of Yan'an Hospital Affiliated to Kunming Medical University from January 2013 to December 2019. The analysis evaluated patient demographics, pathogenic bacterial composition, echocardiography results, and surgical treatment outcomes. After a 1-year follow-up period, the mortality rate was statistically analyzed. The patients were divided into two groups based on their survival status: those who survived and those who did not. Relevant factors were compared between the two groups, and a multivariate logistic regression model was used to analyze the risk factors that affect the prognosis of patients with IE. Results: Out of the 221 patients diagnosed with IE, 164 were male and 57 were female, with an average age of 39.25±14.36 years. The most common underlying heart diseases were bicuspid aortic valve disease (24.9%), congenital heart disease (19.5%), rupture of aortic sinus aneurysm (5.0%) and rheumatic valvular disease (2.3%). The blood culture had a positive rate of 48.42% (107/221), with Streptococcus viridans (29.9%) and Streptococcus haematoides (13.1%) being the main specifically pathogenic bacteria identified. Transthoracic echocardiography produced positive results in 89.6% (198/221) of cases. The findings included vegetation formation (100%), valve perforation or tear (21.7%), and perivalvular abscess formation (5.6%). Out of the patients, 174 underwent elective surgery, 47 received emergency surgery, and 11 died within 1 year after surgery, resulting in a mortality rate of 5.0%. However, the death group had longer operation time, cardiopulmonary bypass (CPB) time and higher EuroSCORE II compared to the non-death group (P<0.05). Logistic regression analysis identified preoperative hematocrit decrease, prolonged operation time and CPB time, high New York Heart Association (NYHA) cardiac function grade, and liver diseases as risk factors for 1-year mortality in patients with IE (OR =1.003, 0.000, 1.006, 1.026, 1.624 and 4.746). Conclusions: IE primarily affects young and middle-aged men with rheumatic heart valvular disease as the main underlying heart disease and Streptococcus viridans as the main pathogen. Surgical intervention significantly reduces early mortality in IE patients. To improve postoperative prognosis, clinicians should remain vigilant, especially in high-risk groups with preoperative hematocrit, prolonged operation time, and CPB time, high NYHA cardiac function grade, EuroSCORE II, and vegetation formation.

Aortic arch surgery for DeBakey type 1 aortic dissection in patients aged 60 years or younger.

BACKGROUND: Extended aortic repair is considered a key issue for the long-term durability of surgery for DeBakey type 1 aortic dissection. The risk of aortic degeneration may be higher in young patients due to their long life expectancy. The early outcome and durability of aortic surgery in these patients were investigated in the present study. METHODS: The subjects of the present analysis were patients under 60 years old who underwent surgical repair for acute DeBakey type 1 aortic dissection at 18 cardiac surgery centres across Europe between 2005 and 2021. Patients underwent ascending aortic repair or total aortic arch repair using the conventional technique or the frozen elephant trunk technique. The primary outcome was 5-year cumulative incidence of reoperation on the distal aorta. RESULTS: Overall, 915 patients underwent surgical ascending aortic repair and 284 patients underwent surgical total aortic arch repair. The frozen elephant trunk procedure was performed in 128 patients. Among 245 propensity score-matched pairs, total aortic arch repair did not decrease the rate of distal aortic reoperation compared to ascending aortic repair (5-year cumulative incidence, 6.7% versus 6.7%, subdistributional hazard ratio 1.127, 95% c.i. 0.523 to 2.427). Total aortic arch repair increased the incidence of postoperative stroke/global brain ischaemia (25.7% versus 18.4%, P = 0.050) and dialysis (19.6% versus 12.7%, P = 0.003). Five-year mortality was comparable after ascending aortic repair and total aortic arch repair (22.8% versus 27.3%, P = 0.172). CONCLUSIONS: In patients under 60 years old with DeBakey type 1 aortic dissection, total aortic arch replacement compared with ascending aortic repair did not reduce the incidence of distal aortic operations at 5 years. When feasible, ascending aortic repair for DeBakey type 1 aortic dissection is associated with satisfactory early and mid-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Femoral arterial cannulation for surgical repair of stanford type A aortic dissection.

BACKGROUND: The benefits and harms associated with femoral artery cannulation over other sites of arterial cannulation for surgical repair of acute Stanford type A aortic dissection (TAAD) are not conclusively established. METHODS: We evaluated the outcomes after surgery for TAAD using femoral artery cannulation, supra-aortic arterial cannulation (i.e., innominate/subclavian/axillary artery cannulation), and direct aortic cannulation. RESULTS: 3751 (96.1%) patients were eligible for this analysis. In-hospital mortality using supra-aortic arterial cannulation was comparable to femoral artery cannulation (17.8% vs. 18.4%; adjusted OR 0.846, 95% CI 0.799-1.202). This finding was confirmed in 1028 propensity score-matched pairs of patients with supra-aortic arterial cannulation or femoral artery cannulation (17.5% vs. 17.0%, p = 0.770). In-hospital mortality after direct aortic cannulation was lower compared to femoral artery cannulation (14.0% vs. 18.4%, adjusted OR 0.703, 95% CI 0.529-0.934). Among 583 propensity score-matched pairs of patients, direct aortic cannulation was associated with lower rates of in-hospital mortality (13.4% vs. 19.6%, p = 0.004) compared to femoral artery cannulation. Switching of the primary site of arterial cannulation was associated with increased rate of in-hospital mortality (36.5% vs. 17.0%; adjusted OR 2.730, 95% CI 1.564-4.765). Ten-year mortality was similar in the study cohorts. CONCLUSIONS: In this study, the outcomes of surgery for TAAD using femoral arterial cannulation were comparable to those using supra-aortic arterial cannulation. However, femoral arterial cannulation was associated with higher in-hospital mortality than direct aortic cannulation. TRIAL REGISTRATION: ClinicalTrials.gov registration code: NCT04831073.

Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review.

The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application.

Assessing emerging causes of mitral regurgitation: atrial functional mitral regurgitation.

Functional or secondary mitral regurgitation is linked to increased cardiovascular morbidity and mortality. From a mechanical perspective, secondary mitral regurgitation occurs due to an imbalance between the forces that tether the mitral leaflets and those that close them. This results in incomplete coaptation. Most commonly, functional mitral regurgitation, which occurs in both ischaemic and non-ischaemic disease states, is usually caused by dysfunction and changes in the left ventricle. Atrial functional mitral regurgitation (AFMR) is a disease state that has been more recently recognized. It occurs when mitral annular enlargement is associated with left atrial dilatation, preserving left ventricular geometry and function. AFMR is typically seen in patients with chronic atrial fibrillation or heart failure who have a conserved ejection fraction. Published reports and ongoing investigations vary in how they define AFMR. This publication examines the pathophysiology of AFMR and highlights the importance of having a common working standard for the definition of AFMR to ensure consistency in the data reported and to drive forward the much needed research into the outcomes and treatment strategies in this area. Several studies have reported that restrictive annuloplasty and transcatheter edge-to-edge repair can reduce mitral regurgitation and improve symptoms. This narrative review will explore the pathophysiology, echocardiographic diagnosis and treatment of AFMR.

Nature of Neurological Complications and Outcome After Surgery for Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications.

Current Knowledge of Enterococcal Endocarditis: A Disease Lurking in Plain Sight of Health Providers.

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate the ability of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, such as when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis.

Interpapillary muscle distance independently predicts recurrent mitral regurgitation.

OBJECTIVE: Ischaemic secondary mitral regurgitation (ISMR) after surgery is due to the displacement of papillary muscles resulting from progressive enlargement of the left ventricle end-diastolic diameter (LVEDD). Our aim was to prove that if the interpapillary muscle distance (IPMD) is surgically stabilized, an increase in LVEDD will not lead to a recurrence of ischaemic mitral regurgitation (MR). METHODS: Ninety-six patients with ISMR, who underwent surgical revascularisation and annuloplasty, were randomly assigned in a 1:1 ratio to undergo papillary muscle approximation (PMA). At the 5-year follow-up, we assessed the correlation between PMA and echocardiographic improvements, the effect size of PMA on echocardiographic improvements, and a prediction model for recurrent MR using inferential tree analysis. RESULTS: There was a significant correlation between PMA and enhancements in both the α and ß angles (Spearman's rho > 0.7, p < 0.01). The α angle represents the angle between the annular plane and either the A2 annular-coaptation line or the P2 annular-coaptation line. The ß angle indicates the angle between the annular plane and either the A2 annular-leaflet tip line or the P2 annular-leaflet tip line. PMA led to substantial improvements in LVEDD, tenting area, α and ß angles, with a large effect size (Hedge's g ≥ 8, 95% CI ORs ≠ 1). The most reliable predictor of recurrent MR grade was the interpapillary distance, as only patients with an interpapillary distance greater than 40 mm developed ≥ 3 + grade MR. For patients with an IPMD of 40 mm or less, the best predictor of recurrent MR grade was LVEDD. Among the patients, only those with LVEDD greater than 62 mm showed moderate (2+) MR, while only those with LVEDD less than or equal to 62 mm had absent to mild (1+) MR. CONCLUSION: Prediction of recurrent ischaemic MR is not independent of progressive LVEDD increase. PMA-based surgical procedure stabilises IPMD.

Classification of the Urgency of the Procedure and Outcome of Acute Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is associated with a high risk of early mortality. The prognostic impact of a new classification of the urgency of the procedure was evaluated in this multicenter cohort study. Data on consecutive patients who underwent surgery for acute TAAD were retrospectively collected in the multicenter, retrospective European Registry of TAAD (ERTAAD). The rates of in-hospital mortality of 3,902 consecutive patients increased along with the ERTAAD procedure urgency grades: urgent procedure 10.0%, emergency procedure grade 1 13.3%, emergency procedure grade 2 22.1%, salvage procedure grade 1 45.6%, and salvage procedure grade 2 57.1% (p <0.0001). Preoperative arterial lactate correlated with the urgency grades. Inclusion of the ERTAAD procedure urgency classification significantly improved the area under the receiver operating characteristics curves of the regression model and the integrated discrimination indexes and the net reclassification indexes. The risk of postoperative stroke/global brain ischemia, mesenteric ischemia, lower limb ischemia, dialysis, and acute heart failure increased along with the urgency grades. In conclusion, the urgency of surgical repair of acute TAAD, which seems to have a significant impact on the risk of in-hospital mortality, may be useful to improve the stratification of the operative risk of these critically ill patients. This study showed that salvage surgery for TAAD is justified because half of the patients may survive to discharge.

Taking the pulse of brain death: A meta-analysis of the natural history of brain death with somatic support.

BACKGROUND AND PURPOSE: The conceptualization of brain death (BD) was pivotal in the shaping of judicial and medical practices. Nonetheless, media reports of alleged recovery from BD reinforced the criticism that this construct is a self-fulfilling prophecy (by treatment withdrawal or organ donation). We meta-analyzed the natural history of BD when somatic support (SS) is maintained. METHODS: Publications on BD were eligible if the following were reported: aggregated data on its natural history with SS; and patient-level data that allowed censoring at the time of treatment withdrawal or organ donation. Endpoints were as follows: rate of somatic expiration after BD with SS; BD misdiagnosis, including "functionally brain-dead" patients (FBD; i.e. after the pronouncement of brain-death, ≥1 findings were incongruent with guidelines for its diagnosis, albeit the lethal prognosis was not altered); and length and predictors of somatic survival. RESULTS: Forty-seven articles were selected (1610 patients, years: 1969-2021). In BD patients with SS, median age was 32.9 years (range = newborn-85 years). Somatic expiration followed BD in 99.9% (95% confidence interval = 89.8-100). Mean somatic survival was 8.0 days (range = 1.6 h-19.5 years). Only age at BD diagnosis was an independent predictor of somatic survival length (coefficient = -11.8, SE = 4, p < 0.01). Nine BD misdiagnoses were detected; eight were FBD, and one newborn fully recovered. No patient ever recovered from chronic BD (≥1 week somatic survival). CONCLUSIONS: BD diagnosis is reliable. Diagnostic criteria should be fine-tuned to avoid the small incidence of misdiagnosis, which nonetheless does not alter the prognosis of FBD patients. Age at BD diagnosis is inversely proportional to somatic survival.

Enhanced recovery protocols after surgery: A systematic review and meta-analysis of randomized trials in cardiac surgery.

BACKGROUND: Previous meta-analyses combining randomized and observational evidence in cardiac surgery have shown positive impact of enhanced recovery protocols after surgery (ERAS) on postoperative outcomes. However, definitive data based on randomized studies are missing, and the entirety of the ERAS measures and pathway, as recently systematized in guidelines and consensus statements, have not been captured in the published studies. The available literature actually focuses on "ERAS-like" protocols or only limited number of ERAS measures. This study aims at analyzing all randomized studies applying ERAS-like protocols in cardiac surgery for perioperative outcomes. METHODS: A meta-analysis of randomized controlled trials (RCTs) comparing ERAS-like with standard protocols of perioperative care was performed (PROSPERO registration CRD42021283765). PRISMA guidelines were used for abstracting and assessing data. RESULTS: Thirteen single center RCTs (N = 1704, 850 in ERAS-like protocol and 854 in the standard care group) were selected. The most common procedures were surgical revascularization (66.3%) and valvular surgery (24.9%). No difference was found in the incidence of inhospital mortality between the ERAS and standard treatment group (risk ratio [RR] 0.61 [0.31; 1.20], p = 0.15). ERAS was associated with reduced intensive care unit (standardized mean difference [SMD] -0.57, p < 0.01) and hospital stay (SMD -0.23, p < 0.01) and reduced rates of overall complications when compared to the standard protocol (RR 0.60, p < 0.01) driven by the reduction in stroke (RR 0.29 [0.13; 0.62], p < 0.01). A significant heterogeneity in terms of the elements of the ERAS protocol included in the studies was observed. CONCLUSIONS: ERAS-like protocols have no impact on short-term survival after cardiac surgery but allows for a faster hospital discharge while potentially reducing surgical complications. However, this study highlights a significant nonadherence and heterogeneity to the entirety of ERAS protocols warranting further RCTs in this field including a greater number of elements of the framework.

Transcatheter aortic valve replacement in the treatment of bicuspid aortic stenosis with "down-size" interventional valves: procedural and mid-term follow-up.

Background: Due to the influence of anatomical structure, replacing the bicuspid valve using transcatheter aortic valve replacement (TAVR) would increase the risk of perivalvular leakage and conduction block, affecting the hemodynamic effect of the interventional valve. In this study, for bicuspid and tricuspid valves, we implemented different valve selection strategies to explore the safety and effectiveness of TAVR in the treatment of bicuspid aortic stenosis with "down-size" interventional valves using the VenusA-valve system. Methods: The operation was performed with the VenusA-valve via transfemoral approach. The selected valves were appropriately sized based on the results of transthoracic echocardiography (TTE), contrast-enhanced computed tomography (CT), and the morphology of intraoperative pre-dilation balloons. For tricuspid valve cases, the VenusA valve is usually larger than the annulus diameter, whereas the "down-size" approach was adopted for bicuspid aortic valve (BAV) cases. The shape of the pre-dilation balloon allowed further sizing of the annulus diameter by the degree of lumbar constriction of the balloon, aiding in intervention valve size selection, particularly in cases of BAVs. Results: A total of 65 patients underwent TAVR for aortic stenosis with VenusA-valve systems. Of these, 29 cases had a BAV and 36 cases had a tricuspid aortic valve (TAV). The distribution of VenusA-valve sizes differed between TAV and BAV cases (P=0.007). Furthermore, there was a significant decrease in the average mean gradient in TAV patients from 54.7 to 12.2 mmHg (P<0.001), and in BAV patients from 61.6 to 14.3 mmHg (P<0.001). The percentage of paravalvular leakage greater than mild was 6.90% in the BAVs and 5.56% in the TAVs at procedural outcomes (P=0.955). The mean follow-up period was 22.23 months (range, 12 to 39 months). The proportion of New York Heart Association (NYHA) class III/IV decreased from 78.5% preoperatively to 11.3% at the last follow-up (P<0.001). A total of 27 patients with TAV and 19 patients with BAV underwent TTE at 1-year follow-up after operation. There was no significant contrast in the average pressure difference between TAVs and BAVs at 1-year follow-up (11.9 vs. 14.3 mmHg, P=0.18). Conclusions: The VenusA-valve for TAVR produced positive clinical outcomes and valve functionality in both BAVs and TAVs. In the case of BAVs, selecting a smaller interventional valve size was deemed viable.

In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.

The use of next-generation sequencing has provided new insights into the causes and mechanisms of congenital heart disease (CHD). Examinations of the whole exome sequence have detected detrimental gene variations modifying single or contiguous nucleotides, which are characterised as pathogenic based on statistical assessments of families and correlations with congenital heart disease, elevated expression during heart development, and reductions in harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities are enriched for gene classes meeting these criteria, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data have revealed the expression of genes associated with CHD in specific cell types, and emerging evidence suggests that genetic mutations disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole-genome sequencing studies.