Science of left ventricular unloading.

The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.

Evolution of distal limb perfusion management in adult peripheral venoarterial extracorporeal membrane oxygenation with femoral artery cannulation.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

Defining and understanding the "extra-corporeal membrane oxygenation gap" in the veno-venous configuration: Timing and causes of death.

In-hospital mortality of adult veno-venous extracorporeal membrane oxygenation (V-V ECMO) patients remains invariably high. However, little is known regarding timing and causes of in-hospital death, either on-ECMO or after weaning. The current review aims to investigate the timing and causes of death of adult patients during hospital admittance for V-V ECMO, and to define the V-V ECMO gap, which is represented by the patients that are successfully weaned of ECMO but still die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-V ECMO patients from January 2006 to December 2020 were screened. Studies that did not report on at least on-ECMO mortality and discharge rate were excluded from analysis as they could not provide the required information regarding the proposed V-V ECMO-gap. Mortality rates on-ECMO and after weaning, as well as weaning and discharge rates, were analyzed as primary outcomes. Secondary outcomes were the causes of death and complications. Initially, 35 studies were finally included in this review. Merely 24 of these studies (comprising 975 patients) reported on prespecified V-V ECMO outcomes (on-ECMO mortality and discharge rate). Mortality on V-V ECMO support was 27.8% (95% confidence interval (CI) 22.5%-33.2%), whereas mortality after successful weaning was 12.7% (95% CI 8.8%-16.6%, defining the V-V ECMO gap). 72.2% of patients (95% CI 66.8%-77.5%) were weaned successfully from support and 56.8% (95% CI 49.9%-63.8%) of patients were discharged from hospital. The most common causes of death on ECMO were multiple organ failure, bleeding, and sepsis. Most common causes of death after weaning were multiorgan failure and sepsis. Although the majority of patients are weaned successfully from V-V ECMO support, a significant proportion of subjects still die during hospital stay, defining the V-V ECMO gap. Overall, timing and causes of death are poorly reported in current literature. Future studies on V-V ECMO should describe morbidity and mortality outcomes in more detail in relation to the timing of the events, to improve patient management, due to enhanced understanding of the clinical course.

Mortality Predictors in Elderly Patients With Cardiogenic Shock on Venoarterial Extracorporeal Life Support. Analysis From the Extracorporeal Life Support Organization Registry.

OBJECTIVES: Because significantly higher mortality is observed in elderly patients undergoing venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock, decision-making in this setting is challenging. We aimed to elucidate predictors of unfavorable outcomes in these elderly (≥ 70 yr) patients. DESIGN: Analysis of international worldwide extracorporeal life support organization registry. SETTING: Refractory cardiogenic shock due to various etiologies (cardiac arrest excluded). PATIENTS: Elderly patients (≥ 70 yr). INTERVENTIONS: Venoarterial extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Three age groups (70-74, 75-79, ≥80 yr) were in-depth analyzed. Uni- and multivariable analysis were performed. From January 1997 to December 2018, 2,644 patients greater than or equal to 70 years (1,395 [52.8%] 70-74 yr old, 858 [32.5%] 75-79 yr, and 391 [14.8%] ≥ 80 yr old) were submitted to venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock with marked increase in the most recent years. Peripheral access was applied in majority of patients. Median extracorporeal membrane oxygenation support duration was 3.5 days (interquartile range: 1.6-6.1 d), (3.9 d [3.7-4.6 d] in patients ≥ 80 yr) (p < 0.001). Weaning from extracorporeal membrane oxygenation was possible in 1,236 patients (46.7%). Overall in-hospital mortality was estimated at 68.3% with highest crude mortality rates observed in 75-79 years old subgroup (70.1%). Complications were mostly cardiovascular and bleeding, without apparent differences between subgroups. Airway pressures, 24-hour pH after extracorporeal membrane oxygenation start, extracorporeal membrane oxygenation duration, and renal replacement therapy were predictive of higher mortality. In-hospital mortality was lower in heart transplantation recipients, posttranscatheter aortic valve replacement, and pulmonary embolism; conversely, higher mortality followed extracorporeal membrane oxygenation institution after coronary artery bypass + valve and in decompensated chronic heart failure, and nearly 100% mortality followed in extracorporeal membrane oxygenation for sepsis. CONCLUSIONS: This study confirmed the remarkable increase of venoarterial extracorporeal membrane oxygenation use in elderly affected by refractory cardiogenic shock. Despite in-hospital mortality remains high, venoarterial extracorporeal membrane oxygenation should still be considered in such setting even in elderly patients, since increasing age itself was not linked to increased mortality, whereas several predictors may guide indication and management.

Understanding the "extracorporeal membrane oxygenation gap" in veno-arterial configuration for adult patients: Timing and causes of death.

Timing and causes of hospital mortality in adult patients undergoing veno-arterial extracorporeal membrane oxygenation (V-A ECMO) have been poorly described. Aim of the current review was to investigate the timing and causes of death of adult patients supported with V-A ECMO and subsequently define the "V-A ECMO gap," which represents the patients who are successfully weaned of ECMO but eventually die during hospital stay. A systematic search was performed using electronic MEDLINE and EMBASE databases through PubMed. Studies reporting on adult V-A ECMO patients from January 1993 to December 2020 were screened. The studies included in this review were studies that reported more than 10 adult, human patients, and no mechanical circulatory support other than V-A ECMO. Information extracted from each study included mainly mortality and causes of death on ECMO and after weaning. Complications and discharge rates were also extracted. Sixty studies with 9181 patients were included for analysis in this systematic review. Overall mortality was 38.0% (95% confidence intervals [CIs] 34.2%-41.9%) during V-A ECMO support (reported by 60 studies) and 15.3% (95% CI 11.1%-19.5%, reported by 57 studies) after weaning. Finally, 44.0% of patients (95% CI 39.8-52.2) were discharged from hospital (reported by 60 studies). Most common causes of death on ECMO were multiple organ failure, followed by cardiac failure and neurological causes. More than one-third of V-A ECMO patients die during ECMO support. Additionally, many of successfully weaned patients still decease during hospital stay, defining the "V-A ECMO gap." Underreporting and lack of uniformity in reporting of important parameters remains problematic in ECMO research. Future studies should uniformly define timing and causes of death in V-A ECMO patients to better understand the effectiveness and complications of this support.

The impact of Centre's heart transplant status and volume on in-hospital outcomes following extracorporeal membrane oxygenation for refractory post-cardiotomy cardiogenic shock: a meta-analysis.

BACKGROUND: Postcardiotomy cardiogenic shock (PCS) that is refractory to inotropic support remains a major concern in cardiac surgery and is almost universally fatal unless treated with mechanical support. While reported mortality rates on ECMO vary from center to center, aim of the current report is assess if the outcomes differ between centres according to volume and heart transplantation status. METHODS: A systematic search was performed according to PRISMA statement using PubMed/Medline databases between 2010 and 2018. Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and heart transplantation status of the centre. Paediatric and congenital heart surgery-related studies along with those conducted in the setting of veno-venous ECMO for respiratory distress syndrome were excluded. Differences were assessed by means of subgroup meta-analysis and meta-regression. RESULTS: Fifty-four studies enrolling N = 4421 ECMO patients were included. Of those, 6 series were performed in non-HTx centres (204 pts.;4.6%). Overall 30-day survival (95% Confidence Intervals) was 35.3% (32.5-38.2%) and did not statistically differ between non-HTx: 33.3% (26.8-40.4%) and HTx centres: 35.7% (32.7-38.8%); Pinteraction = 0.531. There was no impact of centre volume on survival as well: ßcoef = 0.0006; P = 0.833. No statistical differences were seen between HTx and non-HTx with respect to ECMO duration, limb complications, reoperations for bleeding, kidney injury and sepsis. There were however significantly less neurological complications in the HTx as compared to non-HTx centres: 11.9% vs 19.5% respectively; P = 0.009; an inverse relationship was seen for neurologic complications in centres performing more ECMOs annually ßcoef = - 0.0066; P = 0.031. Weaning rates and bridging to HTx and/or VADs were higher in HTx facilities. CONCLUSIONS: There was no apparent difference in survival after ECMO implantation for refractory PCS according to centre's ECMO volume and transplantation status. Potentially different risk profiles of patients in these centres must be taken account for before definite conclusions are drawn.

Acute myocardial infarction complicating ischemic stroke: is there room for cangrelor?

Acute myocardial infarction (AMI) complicating ischemic stroke is a well known and undertreated event. A conservative management is not infrequent in these settings, due to the fear of hemorrhagic complications related to antithrombotic therapy. Notably, an invasive approach with a primary percutaneous coronary intervention (PCI) has been shown to be associated with a lower in-hospital mortality in patients with concomitant ischemic stroke and AMI. The optimal antiplatelet regimen in these cases has been not clearly defined, yet. We report two cases of patients with AMI complicating ischemic stroke, successfully treated with cangrelor infusion, which was started during PCI and maintained up to 48 h at bridge therapy dosage (0.75 mcg/kg/min). Both patients underwent successful PCI in the acute phase, and neither ischemic nor hemorrhagic complications occurred during in-hospital stay.

Extracorporeal life support for phaeochromocytoma-induced cardiogenic shock: a systematic review.

INTRODUCTION: Phaeochromocytoma is a catecholamine-secreting tumour associated with clinical presentation ranging from paroxysmal hypertension to intractable cardiogenic shock. Extracorporeal life support, in veno-arterial mode, application in refractory acute heart dysfunction is sharply increasing worldwide. However, its clinical utility in phaeochromocytoma-induced cardiogenic shock remains still unclear. METHODS: A systematic review of published reports was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement. Searches were accomplished on PubMed, Embase and Google Scholar to identify articles describing the use of extracorporeal life support in the setting of phaeochromocytoma-induced cardiogenic shock (PROSPERO: CRD42019125225). RESULTS: Thirty-five reports, including 62 patients supported with extracorporeal life support because of intractable phaeochromocytoma crisis, were included for the analysis. Almost all the subjects underwent peripheral cannulation for extracorporeal life support. The median duration of the mechanical circulatory support was 5 days, and most of the patients recovered normal myocardial function (left ventricular ejection fraction ⩾50%). In-hospital survival was 87%. Phaeochromocytoma was removed surgically during extracorporeal life support in 10 patients (16%), while in the remaining after haemodynamic stabilization and weaning from the mechanical support. CONCLUSION: Successful management of phaeochromocytoma-induced cardiogenic shock depends on prompt recognition and immediate treatment of shock. In this scenario, extracorporeal life support may play a significant role allowing cardiac and end-organ recovery and giving time for accurate diagnosis and specific treatment.

Baseline surgical status and short-term mortality after extracorporeal membrane oxygenation for post-cardiotomy shock: a meta-analysis.

OBJECTIVE: While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown. METHODS: A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords "postcardiotomy," "cardiogenic shock," "extracorporeal membrane oxygenation," and "extracorporeal life support." Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well. RESULTS: Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling <50 versus ⩾50% of emergency/salvage cases was found: respective event rates were 66.9% (63.1-70.4%) versus 64.4% (57.3-70.8%); p = 0.525. Yet, there was a significant positive association between increasing percentage of emergency/salvage cases and rates of neurological complications (p < 0.001), limb complications (p < 0.001), and bleeding (p = 0.051). Incidence of brain death (p = 0.099) and sepsis (p = 0.134) was increased as well. CONCLUSION: Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

In-hospital outcomes after emergency or prophylactic veno-arterial extracorporeal membrane oxygenation during transcatheter aortic valve implantation: a comprehensive review of the literature.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has been used to deal with life-threatening complications as well as back-up or active cardiovascular support during high-risk procedures in patients undergoing transcatheter aortic valve implantation (TAVI). PubMed and MEDLINE electronic databases were searched in order to identify studies with emergency or prophylactic V-A ECMO application in association with TAVI procedures. From November 2012 to November 2017, 14 relevant studies were identified that included 5,115 TAVI patients of whom 102 (2%) required V-A ECMO (22 prophylactically, 66 as an emergency and 14 without a reported indication). The reason for emergency V-A ECMO institution was detailed in 64 patients: left ventricle free wall rupture (n = 14), haemodynamic instability (n = 12), ventricular arrhythmias (n = 7), aortic annulus rupture (n = 6), coronary obstruction (n = 6), low left ventricular output (ejection fraction <35%) (n = 5), uncontrollable bleeding (n = 5), severe aortic regurgitation (n = 4), prosthesis embolisation (n = 3), aortic dissection (n = 1) and respiratory failure (n = 1). Femoral arterial and vein cannulation was the most common access technique for V-A ECMO institution. Major bleeding (n = 7) and vascular access complications (n = 7) were reported after ECMO institution. The overall in-hospital survival was 73% (61% in the emergency vs. 100% in the prophylactic group). V-A ECMO support should be available at any centre performing TAVI and provides effective mechanical circulatory support in an emergency setting. We present an algorithm to aid decisions about prophylactic circulatory assistance with V-A ECMO and it should form part of the heart team discussion before a TAVI procedure is undertaken.

Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?

BACKGROUND: Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO. METHODS: Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed. RESULTS: During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge. CONCLUSION: IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.

Determinants of carotid-femoral pulse wave velocity progression in hypertensive patients over a 3.7 years follow-up.

OBJECTIVE: The role of risk factors on the progression of arterial stiffness has not yet been extensively evaluated. The aim of the current longitudinal study was to evaluate the determinants of the PWV progression over a 4 years follow-up period in hypertensive subjects. MATERIALS AND METHODS: We enrolled 333 consecutive hypertensive outpatients 18-80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). At baseline anamnestic, clinical, BP, laboratory data and cfPWV were assessed. We performed a PWV follow-up examination with a median time amounting to 3.75 ± 0.53 years. RESULTS: At baseline the mean age was 54.5 ± 12.6 years, SBP and DBP were 141.3 ± 18.6 and 86.4 ± 10.4 mmHg and PWV was 8.56 ± 1.92 m/s. Despite an improvement in BP control (from 37 to 60%), at follow-up the population showed a PWV increase (ΔPWV 0.87 ± 3.05 m/s). PWV and ΔPWV gradually increased in age decades. In patients with uncontrolled BP values at follow-up ΔPWV showed a greater increase as compared to patients with controlled BP (1.46 ± 3.67 vs 0.62 ± 2.61 m/s, p < .05). The independent predictors of ΔPWV were age, baseline PWV, baseline SBP/MBP and ΔSBP/MBP. CONCLUSIONS: the accelerated arterial aging in treated hypertensive subjects is in large measure explained by age and BP values. PWV changes over time would probably give important information that need further future research studies.

Long-Term Outcomes of Bioprosthetic Valves in the Mitral Position: A Pooled Meta-Analysis of Reconstructed Time-to-Event Individual Patient Data.

Bioprosthetic mitral valve replacement (bMVR) use is increasing; however, data regarding long-term durability are lacking. We sought to perform a reconstructed individual patient data meta-analysis from published Kaplan-Meier curves to ascertain survival, freedom from valve degeneration, and reoperation in studies published since 2010. We explored the effects of age and valve type (bovine pericardial or porcine valve) on outcomes. We searched MEDLINE, OVID, Embase, and Cochrane CENTRAL for studies reporting at least 3 years of follow-up after bMVR and published since 2010. The Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool was used to assess methodologic quality. Kaplan-Meier curves were digitized to extract individual patient data and reconstructed estimates for overall survival, freedom from structural valve deterioration (SVD), and freedom from reoperation. A total of 20 studies (16,465 patients) were included. A total of 9 studies reported on porcine valves, 6 reported on bovine, and 7 did not specify the valve type. The overall survival after bMVR at 15 years was 40% (confidence interval 38% to 42%), freedom from reoperation at 15 years was 79% (confidence interval 76% to 82%), and freedom from SVD at 15 years was 64% (58% to 70%). Freedom from SVD was improved in the 70+ years age group (93% up to 25 years, hazard ratio 6.6 [2.5 to 17] for 18 to 59 vs >70 years, p <0.0001). There was no difference in valve durability or survival between bovine pericardial or porcine valves. In this meta-analysis of patients who underwent bMVR using newer generation valves, the inverse relation between age and SVD was reiterated in the 70+ years age group. The prosthesis type made no difference in the outcomes.

Looking Back, Going Forward: Understanding Cardiac Pathophysiology from Pressure-Volume Loops.

Knowing cardiac physiology is essential for health care professionals working in the cardiovascular field. Pressure-volume loops (PVLs) offer a unique understanding of the myocardial working and have become pivotal in complex pathophysiological scenarios, such as profound cardiogenic shock or when mechanical circulatory supports are implemented. This review provides a comprehensive summary of the left and right ventricle physiology, based on the PVL interpretation.

Tailoring the Best Positive End-Expiratory Pressure Through Invasive Right Ventricular Pressure-Volume Loops in a Patient Supported by Veno-Arterial Extracorporeal Membrane Oxygenation.

Patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) typically suffer from cardiogenic pulmonary edema and lung atelectasis, which can exacerbate right ventricular (RV) dysfunction through an increase in lung elastance and RV afterload. Invasive mechanical ventilation settings, and positive end-expiratory pressure (PEEP) in particular, can help to improve RV performance by optimizing lung recruitment and minimizing alveolar overdistention. In this report, we present a VA-ECMO supported patient in whom in vivo RV pressure-volume (PV) loops were measured during a decremental PEEP trial, leading to the identification of an optimum PEEP level from a cardio-respiratory viewpoint. This innovative approach of tailoring mechanical ventilation settings according to cardio-respiratory physiology through in vivo RV PV loops may provide a novel way to optimize hemodynamics and patient outcomes.

Surgical Coronary Revascularization in Patients With Underlying Atrial Fibrillation: State-of-the-Art Review.

The number of individuals referred for coronary artery bypass grafting (CABG) with preoperative atrial fibrillation (AF) is reported to be 8% to 20%. Atrial fibrillation is a known marker of high-risk patients as it was repeatedly found to negatively influence survival. Therefore, when performing surgical revascularization, consideration should be given to the concomitant treatment of the arrhythmia, the clinical consequences of the arrhythmia itself, and the selection of adequate surgical techniques. This state-of-the-art review aimed to provide a comprehensive analysis of the current understanding of, advancements in, and optimal strategies for CABG in patients with underlying AF. The following topics are considered: stroke prevention, prophylaxis and occurrence of postoperative AF, the role of surgical ablation and left atrial appendage occlusion, and an on-pump vs off-pump strategy. Multiple acute complications can occur in patients with preexisting AF undergoing CABG, each of which can have a significant effect on patient outcomes. Long-term results in these patients and the future perspectives of this scientific area were also addressed. Preoperative arrhythmia should always be considered for surgical ablation because such an approach improves prognosis without increasing perioperative risk. While planning a revascularization strategy, it should be noted that although off-pump coronary artery bypass provides better short-term outcomes, conventional on-pump approach may be beneficial at long-term follow-up. By collecting the current evidence, addressing knowledge gaps, and offering practical recommendations, this state-of-the-art review serves as a valuable resource for clinicians involved in the management of patients with AF undergoing CABG, ultimately contributing to improved outcomes and enhanced patient care.

Systematic review and meta-analysis of left atrial appendage closure's influence on early and long-term mortality and stroke.

Objective: Left atrial appendage closure (LAAC) concomitant to heart surgery in patients with underlying atrial fibrillation (AF) has gained attention because of long-term reduction of thromboembolic complications. As of mortality benefits in the setting of non-AF, data from both observational studies and randomized controlled trials are conflicting. Methods: On-line databases were screened for studies comparing LAAC versus no LAAC concomitant to other heart surgery. End points assessed were all-cause mortality and stroke at early and longest-available follow-up. Subgroup analyses stratified on preoperative AF were performed. Risk ratios (RR) with 95% CIs served as primary statistics. Results: Electronic search yielded 25 studies (N = 660 [158 patients]). There was no difference between LAAC and no LAAC in terms of early mortality. In the overall population analysis, LAAC reduced long-term mortality (RR, 0.86; 95% CI, 0.74-1.00; P = .05; I 2 = 88%), reduced early stroke risk by 19% (RR, 0.81; 95% CI, 0.72-0.93; P = .002; I 2 = 57%), and reduced late stroke risk by 13% (RR, 0.87; 95% CI, 0.84-0.90; P < .001; I 2 = 58%). Subgroup analysis showed lower mortality (RR, 0.85; 95% CI, 0.72-1.01; P = .06; I 2 = 91%), short-, and long-term stroke risk reduction only in patients with preoperative AF (RR, 0.81; 95% CI, 0.71-0.93; P = .003; I 2 = 71% and RR, 0.87; 95% CI, 0.84-0.91; P < .001; I 2 = 70%, respectively). No benefit of LAAC in patients without AF was found. Conclusions: Concomitant LAAC was associated with reduced stroke rates at early and long-term and possibly reduced all-cause mortality at the long-term follow-up but the benefits were limited to patients with preoperative AF. There is not enough evidence to support routine concomitant LAAC in non-AF settings.

Regional antibiotic delivery for sternal wound infection prophylaxis a systematic review and meta-analysis of randomized controlled trials.

Despite evidence suggesting the benefit of prophylactic regional antibiotic delivery (RAD) to sternal edges during cardiac surgery, it is seldom performed in clinical practice. The value of topical vancomycin and gentamicin for sternal wound infections (SWI) prophylaxis was further questioned by recent studies including randomized controlled trials (RCTs). The aim of this systematic review and meta-analysis was to comprehensively assess the safety and effectiveness of RAD to reduce the risk of SWI.We screened multiple databases for RCTs assessing the effectiveness of RAD (vancomycin, gentamicin) in SWI prophylaxis. Random effects meta-analysis was performed. The primary endpoint was any SWI; other wound complications were also analysed. Odds Ratios served as the primary statistical analyses. Trial sequential analysis (TSA) was performed.Thirteen RCTs (N = 7,719 patients) were included. The odds of any SWI were significantly reduced by over 50% with any RAD: OR (95%CIs): 0.49 (0.35-0.68); p < 0.001 and consistently reduced in vancomycin (0.34 [0.18-0.64]; p < 0.001) and gentamicin (0.58 [0.39-0.86]; p = 0.007) groups (psubgroup = 0.15). Similarly, RAD reduced the odds of SWI in diabetic and non-diabetic patients (0.46 [0.32-0.65]; p < 0.001 and 0.60 [0.44-0.83]; p = 0.002 respectively). Cumulative Z-curve passed the TSA-adjusted boundary for SWIs suggesting adequate power has been met and no further trials are needed. RAD significantly reduced deep (0.60 [0.43-0.83]; p = 0.003) and superficial SWIs (0.54 [0.32-0.91]; p = 0.02). No differences were seen in mediastinitis and mortality, however, limited number of studies assessed these endpoints. There was no evidence of systemic toxicity, sternal dehiscence and resistant strains emergence. Both vancomycin and gentamicin reduced the odds of cultures outside their respective serum concentrations' activity: vancomycin against gram-negative strains: 0.20 (0.01-4.18) and gentamicin against gram-positive strains: 0.42 (0.28-0.62); P < 0.001. Regional antibiotic delivery is safe and effectively reduces the risk of SWI in cardiac surgery patients.

Additional bypass graft or concomitant surgical ablation? Insights from the HEIST registry.

BACKGROUND: Surgical ablation for atrial fibrillation at the time of isolated coronary artery bypass grafting is reluctantly attempted. Meanwhile, complete revascularization is not always possible in these patients. We attempted to counterbalance the long-term benefits of surgical ablation against the risks of incomplete revascularization. METHODS: Atrial fibrillation patients undergoing isolated coronary artery bypass grafting for multivessel disease between 2012 to 2022 and included in the HEart surgery In atrial fibrillation and Supraventricular Tachycardia registry were divided into complete revascularization, complete revascularization with additional grafts, and incomplete revascularization cohorts; these were further split into surgical ablation and non-surgical ablation subgroups. RESULTS: A total of 8,405 patients (78% men; age 69.3 ± 7.9) were included; of those, 5,918 (70.4%) had complete revascularization, and 556 (6.6%) had surgical ablation performed. Number of anastomoses was 2.7 ± 1.2. The median follow-up was 5.1 [interquartile range 2.1-8.8] years. In patients in whom complete revascularization was achieved, surgical ablation was associated with long-term survival benefit: hazard ratio 0.69; 95% confidence intervals (0.50-0.94); P = .020 compared with grafting additional lesions. Similarly, in patients in whom complete revascularization was not achieved, surgical ablation was associated with a long-term survival benefit of 0.68 (0.49-0.94); P = .019. When comparing surgical ablation on top of incomplete revascularization against complete revascularization without additional grafts or surgical ablation, there was no difference between the 2: 0.84 (0.61-1.17); P = .307, which was also consistent in the propensity score-matched analysis: 0.75 (0.39-1.43); P = .379. CONCLUSION: To achieve complete revascularization is of utmost importance. However, when facing incomplete revascularization at the time of coronary artery bypass grafting in a patient with underlying atrial fibrillation, concomitant surgical ablation on top of incomplete revascularization is associated with similar long-term survival as complete revascularization without surgical ablation.

Does the 9p region affect arterial stiffness? Results from a cohort of hypertensive individuals.

OBJECTIVE: Evidence exists that arterial stiffness, i.e. an independent predictor of cardiovascular and all-causes mortality, has a genetic component. The 9p21 region is associated with a greater susceptibility to coronary disease. Whether this can be ascribed to the fact that genes located on chromosome 9p may also regulate arterial stiffness is largely unknown, however. We evaluate the influence of single nucleotide polymorphisms (SNPs) from 9p on carotid-femoral pulse wave velocity (C-F PWV), measured via the Complior method, in a cohort of 821 hypertensive subjects. DESIGN: The selected tagSNPs were screened with a custom-designed 384-plex VeraCode GoldenGate Genotyping assay on Illumina BeadXpress Reader platform. Association analysis was done using PLINK considering C-F PWV as a quantitative trait (linear regression assuming an additive model) adjusting for sex, age, systolic blood pressure and body mass index (BMI). We used false discovery rate (FDR) to account for multiple testing. RESULTS: Although none of the 384 SNPs was significant after adjusting for multiple testing, probably due to the small sample size of the study population, a trend of association with C-F PWV was observed for rs300622 and rs2381640. CONCLUSIONS: These data suggest that SNPs located on chromosome 9p may affect arterial stiffness. Further studies are needed to confirm our finding on a larger sample and define the physiopathological link of the present results.