Surgical Ablation for Atrial Fibrillation: Risk Factors for Recurrence and Long-Term Outcome.

OBJECTIVES: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Due to the insufficient efficacy of antiarrhythmic drugs and their adverse side effects, there has been considerable interest in the interventional treatment of AF, including both catheter ablation and surgical ablation. Surgical ablation or the maze procedure is a treatment option for patients with AF undergoing concomitant or isolated cardiac surgery. DESIGN: We performed a retrospective study of prospectively collected data to investigate short- and long-term outcomes of patients who underwent the surgical ablation of AF. Outcome variables included freedom from recurrent atrial arrhythmias and mortality at 1-, 3-, 5-, and 7-year follow-ups. We also identified risk factors for arrhythmia recurrence and mortality. SETTING: Israel's largest university tertiary care center. PARTICIPANTS: The study population comprised 668 patients operated on between January 1, 2006, and June 30, 2022. All patient data were extracted from our departmental database. INTERVENTIONS: Concomitant or stand-alone surgical AF ablation. MEASUREMENTS AND MAIN RESULTS: The mean duration of follow-up was 106 ± 66.7 months. Freedom from AF was 97.6% (n = 615) and mortality was 3% (n = 20) at the 1-year follow-up, 95.3% (n = 574) and 6.1% (n = 45) at 3 years, 90.1% (n = 396) and 9.1% (n = 61) at 5 years, and 77.5% (n = 308) and 10.8% (n = 72) at 7 years. According to logistic regression analysis, age and female sex determined the 7-year freedom from AF, and risk factors for 7-year mortality included diabetes mellitus, age, and valve surgery. CONCLUSIONS: Surgical ablation had a high success rate, with freedom from recurrent atrial arrhythmia at 1-, 3-, 5-, and 7-year follow-ups. Age and female sex were factors determining the 5- and 7-year recurrence of AF.

Surgical ablation for atrial fibrillation: impact of Diabetes Mellitus type 2.

BACKGROUND: Diabetes mellitus (DM) type 2 is an independent risk factor for atrial fibrillation (AF). Surgical ablation or "maze procedure" is an option for patients with AF undergoing concomitant or isolated cardiac surgery. The aim of this study was to evaluate the impact of DM type 2 on early and long-term outcomes of patients following surgical AF ablation. METHODS: We performed an observational cohort study in Israel's largest tertiary care center. All data of patients who underwent surgical AF ablation, between 2006 and 2021 were extracted from our departmental database. Patients were divided into Group I (non-diabetic patients) and Group II (DM type 2 patients). We compared the two groups with respect to freedom from recurrent atrial arrhythmia, and mortality rate. RESULTS: The study population included 606 patients. Group I (non-DM patients), consisting of 484 patients, and Group II (DM type 2 patients), comprised 122 patients. Patients with DM were older, had more hypertension and incidence of cerebrovascular accident (CVA)/transient ischemic attack (TIA), higher EuroSCORE (p < .05 for all), and a longer bypass time-130 ± 40 vs. 122 ± 36 min (p = 0.028). The mean follow-up duration was 39.0 ± 22.7 months. Freedom from atrial fibrillation was similar between the non-DM and DM type 2 groups after a 1-year follow-up, 414 (88.2%) vs. 101 (87.1%) (p = 0.511), after a 3-year follow-up, 360 (86.3%) vs. 84 (79.9%) (p = 0.290) and after a 5-year follow-up, 226 (74.1%) vs. 55 (71.5%) (p = 0.622) respectively. Furthermore, 1- and 3-year mortality was similar between non-DM and DM type 2 groups, 2.5% vs. 4.9%, (p = 0.226) and 5.6% vs. 10.5% (p = 0.076) respectively. 5-year mortality was higher in Group II (DM type 2 patients) compared with Group I (non-DM patients), 11.1% vs. 23.4% (p = 0.009). CONCLUSION: Surgical ablation had a high success rate, with freedom from recurrent atrial arrhythmia at 1- 3- and 5- years follow-up in both the DM type 2 and non-DM groups. Furthermore,1- and 3-year mortality after surgical ablation was also similar in both groups. However, 5-year mortality was higher in the DM type 2 group.

BNT162b2-vaccine-induced neutralization responses are immune correlates of clinical protection against SARS-CoV-2 in heart transplant recipients.

BACKGROUND: Defining immune correlates of protection against COVID-19 is pivotal for optimizing the use of COVID-19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next-generation vaccines. We aimed to identify vaccine-induced immune correlates of protection against COVID-19-related hospitalizations in a highly vaccinated heart transplant (HT) cohort. METHODS: In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine-induced neutralization of the wild-type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID-19 hospitalization. ROC analyses were performed. Primary outcomes were COVID-19 hospitalizations and severity of SARS-CoV-2 breakthrough infection. RESULTS: The study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty-six (61%) patients with COVID-19 were hospitalized; most cases were non-severe (58, 98%). For hospitalized (vs. non-hospitalized) COVID-19 patients, vaccine-induced neutralization titers were significantly lower against all SARS-CoV-2 variants (p < .005). Vaccine-induced neutralization of the wild-type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID-19-related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID-19 hospitalizations were 96 (wild-type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5). CONCLUSIONS: BNT162b2-vaccine-induced neutralization responses are immune correlates of protection and confer clinical protection against COVID-19 hospitalizations.

Extracellular Vesicles From Epicardial Fat Facilitate Atrial Fibrillation.

BACKGROUND: The role of epicardial fat (eFat)-derived extracellular vesicles (EVs) in the pathogenesis of atrial fibrillation (AF) has never been studied. We tested the hypothesis that eFat-EVs transmit proinflammatory, profibrotic, and proarrhythmic molecules that induce atrial myopathy and fibrillation. METHODS: We collected eFat specimens from patients with (n=32) and without AF (n=30) during elective heart surgery. eFat samples were grown as organ cultures, and the culture medium was collected every 2 days. We then isolated and purified eFat-EVs from the culture medium, and analyzed the EV number, size, morphology, specific markers, encapsulated cytokines, proteome, and microRNAs. Next, we evaluated the biological effects of unpurified and purified EVs on atrial mesenchymal stromal cells and endothelial cells in vitro. To establish a causal association between eFat-EVs and vulnerability to AF, we modeled AF in vitro using induced pluripotent stem cell-derived cardiomyocytes. RESULTS: Microscopic examination revealed excessive inflammation, fibrosis, and apoptosis in fresh and cultured eFat tissues. Cultured explants from patients with AF secreted more EVs and harbored greater amounts of proinflammatory and profibrotic cytokines, and profibrotic microRNA, as well, than those without AF. The proteomic analysis confirmed the distinctive profile of purified eFat-EVs from patients with AF. In vitro, purified and unpurified eFat-EVs from patients with AF had a greater effect on proliferation and migration of human mesenchymal stromal cells and endothelial cells, compared with eFat-EVs from patients without AF. Last, whereas eFat-EVs from patients with and without AF shortened the action potential duration of induced pluripotent stem cell-derived cardiomyocytes, only eFat-EVs from patients with AF induced sustained reentry (rotor) in induced pluripotent stem cell-derived cardiomyocytes. CONCLUSIONS: We show, for the first time, a distinctive proinflammatory, profibrotic, and proarrhythmic signature of eFat-EVs from patients with AF. Our findings uncover another pathway by which eFat promotes the development of atrial myopathy and fibrillation.

Surgical treatment on infective endocarditis: impact of diabetes on mortality.

BACKGROUND: Type 2 diabetes mellitus (DM) is a frequent co-morbidity among patients suffering from infective endocarditis (IE). The aim of the study was to evaluate the impact of type 2 DM on the early-, intermediate- and long-term mortality of patients who underwent surgical treatment of endocarditis. METHODS: We performed an observational cohort study in the large tertiary center in Israel during 14 years. All data of patients who underwent surgical treatment of endocarditis, performed between 2006 and 2020 were extracted from the departmental database. Patients were divided into two groups: Group I (non-diabetic patients), and Group II (diabetic patients). RESULTS: The study population includes 420 patients. Group I (non-diabetic patients), comprise 326 patients, and Group II (diabetic patients), comprise 94 patients. Mean follow-up duration was 39.3 ± 28.1 months. Short-term, 30-day and in-hospital mortality, also intermediate-term mortality (1- and 3-year) was higher in the DM group compared with the non-DM group, but did not reach statistical significance: 11.7% vs. 7.7%. (p = 0.215); 12.8% vs. 8.3% (p = 0.285); 20.2% vs. 13.2% (p = 0.1) and 23.4% vs. 15.6% (p = 0.09) respectively. Long-term, 5-year mortality was significantly higher in the DM group, compared to the non-DM group: 30.9% vs. 16.6% (p = 0.003). Furthermore, predictors for long-term mortality included diabetes (CI 1.056-2.785, p = 0.029), as demonstrated by regression analysis. CONCLUSIONS: Diabetic patients have trend to increasing mortality at the short- and intermediate period post-surgery for IE, but this is not statistically significant. Survival of diabetic patients deteriorates after more than three years follow surgery. Diabetes is an independent predictor for long-term, 5-year mortality after surgical treatment of endocarditis, regardless of the patients age and comorbidities. Trial registration Ethical Committee of Sheba Medical Centre, Israel on 02.12. 2014, Protocol 4257.

Revascularization outcomes in diabetic patients presenting with acute coronary syndrome with non-ST elevation.

BACKGROUND: To compare the outcomes of diabetic patients hospitalized with non-ST elevation myocardial infarction (NSTEMI) or unstable angina (UA) referred for revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in a real-life setting. METHODS: The study included 1987 patients with diabetes mellitus enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for NSTEMI or UA, and underwent either PCI (N = 1652, 83%) or CABG (N = 335, 17%). Propensity score-matching analysis compared all-cause mortality in 200 pairs (1:1) who underwent revascularization by either PCI or CABG. RESULTS: Independent predictors for CABG referral included 3-vessel coronary artery disease (OR 4.9, 95% CI 3.6-6.8, p < 0.001), absence of on-site cardiac surgery (OR 1.4, 95% CI 1.1-1.9, p = 0.013), no previous PCI (OR 1.5, 95% CI 1.1-2.2, p = 0.024) or MI (OR 1.7, 95% CI 1.2-2.6, p = 0.002). While at 2 years of follow-up, survival analysis revealed no differences in mortality risk between the surgical and percutaneous revascularization groups (log-rank p = 0.996), after 2 years CABG was associated with a significant survival benefit (HR 1.53, 95% CI 1.07-2.21; p = 0.021). Comparison of the propensity score matching pairs also revealed a consistent long-term advantage toward CABG (log-rank p = 0.031). CONCLUSIONS: In a real-life setting, revascularization by CABG of diabetic patients hospitalized with NSTEMI/UA is associated with better long-term outcomes. Prospective randomized studies are warranted in order to provide more effective recommendations in future guidelines.

Frailty and clinical outcomes following aortic valve replacement.

BACKGROUND AND AIMS: The Norton score is a well-known scale to assess frailty. Frailty and a low Norton score are associated with complications and mortality in hospitalized patients. We aimed to evaluate whether a low Norton score is associated with surgical complications and death after aortic valve replacement (AVR). METHODS: From 2004 through 2020, we performed an observational study in a large tertiary medical center, which included all patients who had undergone isolated AVR surgery. Of the 1469 study patients, 618 patients (42%) had a low (<18) and 851 patients (58%) a high Norton score (≥18). RESULTS: Frailer patients with a low Norton score had higher in-hospital mortality compared to those with a high Norton score (5.5% vs. 0.8%, p < .001). The Norton score was significantly higher among patients who survived compared to those who died (17.5 ± 2.4 vs. 11.5 ± 5.2, p < .001). A low Norton score was associated with a threefold increased risk of in-hospital mortality (odds ratio 3.03; 95% confidence interval [CI] 1.14-0.09, p = .034). Ten-year mortality rate was higher among frailer patients with a low compared with a high Norton score (25.9%, 13.3%; hazard ratio 0.69, CI 0.48-0.82, p < .001). By adding a Norton score to standard prognostic factors (age, gender, comorbidities, left ventricular ejection fraction, functional class) we showed a significant improvement of 59.4% (p < .001) for predicting 1-year mortality, and 40.6% (p < .001) for predicting 10-year mortality. CONCLUSIONS: Our findings show that the admission Norton score is a powerful marker of short- and long-term mortality, and, therefore, should be considered as a risk stratification tool in patients who are candidates for AVR.

The predictive value of five glomerular filtration rate formulas for long-term mortality in patients undergoing coronary artery bypass grafting.

BACKGROUND AND AIMS: Renal function plays an important role in the management of patients referred for coronary artery bypass grafting (CABG). Current data is insufficient for precise risk stratification using the estimated glomerular filtration rate (eGFR). METHODS: This retrospective study includes 3744 consecutive patients who underwent CABG between 2004 and 2020. We assessed five different eGFR formulas: Cockcroft-Gault (CG), modification of diet in renal disease (MDRD), chronic kidney disease Epidemiology Collaboration (CKD-EPI), Mayo, and inulin clearance-based (IB). RESULTS: The Mayo formula yielded the highest mean eGFR (90 ± 24 ml/min per 1.73 m2 ) and CKD-EPI the lowest (74 ± 21 ml/min per 1.73 m2 ). As a result, more patients were classified as having a normal renal function (57%) with the Mayo formula as compared with the others. Using MDRD as the reference formula, there was a significant and stronger correlation between the values obtained from the CKD-EPI (r = .95, p < .001) and Mayo (Mayo: r = .87, p < .001) compared to the IB (r = .8, p < .001) and CG (r = .79, p < .001) formulas. Multivariable analysis demonstrated that decreased renal function is an independent predictor of 10-year mortality in all five formulas, with risk increasing by 13-17% for each 10-unit decrease in eGFR. Despite the similarities between the formulas, the ability to predict mortality was highest in the Mayo formula and lowest in the CG and IB. CONCLUSIONS: Our data suggest that the Mayo formula may be superior to the other formulas in prognosticating mortality after CABG. We have shown that the Mayo equation classified fewer individuals as having renal dysfunction and more accurately categorized the risk for mortality than did all other formulas.

The Impact of Initiation of an Intensivist-Led Patient Management Protocol on Outcomes After Cardiac Surgery.

OBJECTIVES: Prolonged intensive care unit stay after cardiac surgery is associated with high mortality. The aim of this study was to evaluate the impact of the introduction of a quality improvement program under the supervision of an intensivist on the long-term mortality of high-risk patients with prolonged intensive care unit (ICU) stay after cardiac surgery. DESIGN: Retrospective study of prospectively collected data. SETTING: Cardiac surgery ICU. PARTICIPANTS: A total of 7,549 patients after cardiac surgery. INTERVENTIONS: Patients were divided into two periods: 2004 to 2007, before introducing the quality improvement program (3,315 patients), and 2009 to 2014, after introduction of the program (4,234 patients). In the period from 2004 to 2007, patients were divided into group I (ICU stay ≥ seven days), which included 242 patients, and group III (ICU stay < seven days), which included 3,073 patients. Also, in the period from 2009 to 2014 patients, were divided into group II (ICU stay ≥seven days), which included 326 patients, and group IV (ICU stay < seven days), which included 3,908 patients. Patient outcomes were compared. Follow-up was five years for each group. MEASUREMENTS AND MAIN RESULTS: The European System for Cardiac Operative Risk Evaluation did not differ significantly among the groups. When comparing between group I and group II, 30-day mortality decreased significantly from 24.8% to 16.6%, six-month mortality from 27.3% to 19.3%, one-year mortality from 42.1% to 32.2%, 3-year mortality from 54.5% to 43.3%, and 5-year mortality from 61.2% to 51.8%. In comparing between group III and group IV, the authors did not observe a statistically significant decrease of mortality. CONCLUSIONS: Intensivist-led patient management protocol is associated with decreased long-term mortality in high-risk patients with a prolonged ICU stay.

Acute pulmonary embolism following acute type A aortic dissection in a patient with COVID-19.

Acute aortic dissection and acute pulmonary embolism (PE) are life-threatening emergencies that can mimic each other at presentation. Immediate and accurate diagnosis of these scenarios is crucial to initiate the appropriate interventions. In this case report we present a 73-year-old patient, who was admitted to our Medical Center with acute type A aortic dissection. She was tested for coronavirus disease 2019 (COVID-19) infection and was found to be positive. During her admission in the COVID-19 designated intensive care unit, she diagnosed with acute PE in the main right and left pulmonary arteries. She underwent surgery that included bilateral pulmonary embolectomy and aortic dissection repair. The patient was discharged from our hospital on the ninth postoperative day without any complications. Frequency of simultaneous presentation of acute aortic dissection and acute PE is increased with a history of coagulation abnormalities as seen in patients with COVID-19.

Type 2 diabetes mellitus increases the mortality risk after acute coronary syndrome treated with coronary artery bypass surgery.

BACKGROUND: Type 2 diabetes mellitus (DM) is a risk factor for cardiovascular diseases and is common among patients undergoing coronary artery bypass grafting (CABG) surgery. The main objective of our study was to investigate the impact of DM type 2, and its treatment subgroups, on short- and long-term mortality in patients with acute coronary syndrome (ACS) who undergo CABG. METHODS: The study included 1307 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 527 (40%) patients were with and 780 (60%) were without DM. RESULTS: Compared with the non-diabetic group, the diabetic group of patients comprised more women and had more comorbidities such as hypertension, dyslipidemia, renal impairment, peripheral vascular disease and prior ischemic heart disease. Overall 30-day mortality rate was similar between DM and non-DM patients (4.2% vs. 4%, p = 0.976). Ten-year mortality rate was higher in DM compared with non-diabetic patients (26.6% vs. 17.7%, log-rank p < 0.001), and higher in the subgroup of insulin-treated patients compared to non-insulin treated patients (31.5% vs. 25.6%, log-rank p = 0.019). Multivariable analysis showed that DM increased the mortality hazard by 1.61-fold, and insulin treatment among the diabetic patients increased the mortality hazard by 1.57-fold. CONCLUSIONS: While type 2 DM did not influence the in-hospital mortality hazard, we showed that the presence of DM among patients with ACS referred to CABG, is a powerful risk factor for long-term mortality, especially when insulin was included in the diabetic treatment strategy.

Surgical Pericardiectomy for Constrictive Pericarditis: A Single Tertiary Center Experience.

BACKGROUND: Although surgery is the sole therapeutic option for patients with constrictive pericarditis (CP), reports on high postoperative mortality rates have led to hesitant surgery referral. The aim of this study was to report the short- and long-term outcomes of surgical pericardiectomy (SP) from a large tertiary center. METHODS: Between January 2005 and January 2017, 55 consecutive patients underwent SP after comprehensive echocardiography, computed tomography, and hemodynamic studies. Detailed clinical, imaging, surgical techniques and follow-up outcomes were recorded. RESULTS: The most common etiology was idiopathic (n = 27, 49%) and 33 patients (60%) were in functional class 3/4. Sixteen patients (29%) underwent concomitant interventions during SP, and cardiopulmonary bypass (CPB) was used in these, as well as in four additional cases. Complete resection, independent of CPB, was achieved in 96%. One patient died during the index hospitalization, and four (7%) needed re-explorations due to bleeding. While 12 patients (22%) died during a mean follow-up of 52 ± 39 months, only 1 death was due to right heart failure. Functional class significantly improved (with a p-value < 0.001), diuretics were discontinued in all, and significant reductions of right atrial pressures were recorded. None of these outcomes differed as a result of concomitant interventions at the time of SP. CONCLUSION: Short- and long-term outcomes of SP, performed either alone or concomitantly with other procedures, indicate high safety and favorable clinical and hemodynamic efficacy for the treatment of CP.

Bicuspid aortic valve area in normal heart.

INTRODUCTION: Bicuspid aortic valve (BAV) is a common congenital valve abnormality. There are no data in the literature regarding the range of aortic valve area (AVA) in normal functioning BAV. We aimed to evaluate the normal range of BAV area and to compare it to subjects with tricuspid aortic valve (TAV). METHODS: Bicuspid aortic valve subjects were identified from Sheba medical center echocardiographic database and were compared with TAV subjects. Inclusion criteria were normal tissue leaflets appearance and normal functioning valve in the presence of normal echocardiogram. Echocardiographic data, patients hemodynamics, and size were collected. AVA was measured with both planimetry and the continuity equation. RESULTS: Fifty BAV and 50 control subjects were studied (37 men, age 40 ± 13 years). All studies were performed with normal hemodynamics. Fusion between the coronary leaflets was the most common morphology (82%), followed by fusion between the right coronary leaflet with the noncoronary leaflet (18%). The left ventricular outflow tract (LVOT) diameter in BAV group was significantly larger (2.3 ± 0.3 cm vs 2.1 ± 0.2; P < .001). The BAV group presented with a larger AVA planimetry (3.8 ± 0.9 vs 3.3 ± 0.6; P < .001). However, measuring AVA using continuity equation has shown no differences between groups. If using the principles of coefficient of contraction, it seems that measuring AVA by planimetry overestimates the real anatomic AVA. CONCLUSION: This data provide normal values for echocardiographically determined AVA in BAV subjects. This population was characterized by large LVOT diameter and large AVA. The larger AVA measured with the planimetry emphasizes the limitation of this method in BAV population.

Outcomes of isolated surgical aortic valve replacement in the era of transcatheter aortic valve implantation.

BACKGROUND AND AIMS: Until early into the 21st century, the only therapeutic option for aortic valve (AV) stenosis was surgical aortic valve replacement (AVR), but this changed with the introduction of transcatheter aortic valve implantation (TAVI). Our objective was to present the results of surgical AVR performed in low-risk patients in the era of TAVI, in a large tertiary medical center. METHODS: Data from low surgical risk patients (defined as Euroscore < 5) greater than 60 years of age, who underwent isolated AVR surgery between 2004 and 2018, were obtained from our departmental database. Of the 313 study patients, 110 (35%) underwent isolated AVR before 2010 (early period) and 203 patients (65%) underwent the same procedure from 2010 onward (late period). RESULTS: Mean age was 67 ± 5 years and 182 (58%) were male. Fifty-six patients (18%) had a unicuspid or bicuspid AV. Patient characteristics were similar between the early and late periods. There was no in-hospital or 30-day mortality throughout the entire cohort, with one case (0.3%) of postoperative stroke. Permanent pacemaker implantation was required in 2.2% (N = 7). Patients in the early period required significantly more re-exploration due to bleeding/tamponade (8.2% vs 1.5%; P = .008). Long-term mortality (1, 3, and 5 years) was higher in the early compared with the late period (2.7% vs 1%, 7.3% vs 3%, and 15.5% vs 3.4%, respectively; log-rank P = .005). CONCLUSIONS: Surgical AVR provides excellent short- and long-term results with low morbidity and mortality in low surgical risk patients. While patient characteristics did not change dramatically over the years, the long-term results were encouraging.

Differential microRNAs expression in calcified versus rheumatic aortic valve disease.

BACKGROUND: The aortic valve (AV) is the most commonly affected valve in valvular heart diseases (VHDs). The objective of the study is to identify microRNA (miRNA) molecules expressed in VHDs and the differential expression patterns of miRNA in AVs with either calcification or rheumatism etiologies. METHODS: Human AVs were collected during valve replacement surgery. RNA was extracted and miRNA containing libraries were prepared and sequenced using the next generation sequencing (NGS) approach. miRNAs identified as differentially expressed between the two etiologies were validated by quantitative real-time polymerase chain reaction (qPCR). The receiver operating characteristic (ROC) curve analysis was performed to examine the ability of relevant miRNA to differentiate between calcification and rheumatism etiologies. RESULTS: Rheumatic and calcified AV samples were prepared for the NGS and were successfully sequenced. The expression was validated by the qPCR approach in 46 AVs, 13 rheumatic, and 33 calcified AVs, confirming that miR-145-5p, miR-199a-5p, and miR-5701 were significantly higher in rheumatic AVs as compared with calcified AVs. ROC curve analysis revealed that miR-145-5p had a sensitivity of 76.92% and a specificity of 94.12%, area under the curve (AUC) = 0.88 (P = .0001), and miR-5701 had a sensitivity of 84.62% and a specificity of 76.47%, AUC = 0.78 (P = .0001), whereas miR-199a-5p had a sensitivity of 84.62%, and a specificity of 57.58%, AUC = 0.73 (P = .0083). CONCLUSION: We documented differential miRNA expression between AV disease etiologies. The miRNAs identified in this study advance our understanding of the mechanisms underlining AV disease.

Type 2 diabetes mellitus increases long-term mortality risk after isolated surgical aortic valve replacement.

BACKGROUND: Diabetes mellitus (DM) adversely affects morbidity and mortality for major atherosclerosis-related cardiovascular diseases and is associated with increased risk for the development of aortic stenosis. Clinical data regarding the impact of DM on outcomes of patients undergoing aortic valve replacement (AVR) have revealed inconsistent results. The aim of the current study was to investigate and compare the impact of type 2 DM on short-, intermediate- and long-term mortality between DM and non-DM patients who undergo isolated AVR. METHODS: We performed an observational study in a large tertiary medical center over a 14-year period (2004-2018), which included all patients who had undergone isolated AVR surgery for the first time. Of the 1053 study patients, 346 patients (33%) had type 2 DM (DM group) and were compared with non-DM (non-DM group) patients (67%). Short-term (in-hospital), intermediate (1- and 3-years), and late (5- and 10-years) mortality were evaluated. Mean follow-up of was 69 ± 43 months. RESULTS: Short-term (in-hospital) mortality was similar between the DM compared with the non-DM group: 3.5% and 2.5% (p = 0.517). Intermediate-term mortality (1- and 3-year) was higher in the DM group compared with the non-DM group, but did not reach statistical significance: 8.1% vs. 5.7% (p = 0.169) and 12.1% vs. 8.3% (p = 0.064) respectively. Long-term (5- and 10-year) mortality was significantly higher in the DM group, compared to the non-DM group: 19.4% vs. 12.9% (p = 0.007) and 30.3% vs. 23.5% (p = 0.020) respectively. Among the 346 DM patients, 55 (16%) were treated with insulin and 291 (84%) with oral antiglycemic medication only. Overall in-hospital mortality among insulin-treated DM patients was 7.3% compared with 2.7% among non insulin-treated DM patients (p = 0.201). Long-term mortality was higher in the subgroup of insulin-treated DM patients compared with the subgroup of non-insulin treated DM patients with an overall mortality rate of 36.4% vs. 29.2% (p = 0.039). Furthermore, predictors for late mortality included DM (HR 1.39 CI 1.03-1.86, p = 0.031) and insulin treatment (HR 1.76 CI 1.05-2.94, p = 0.033), as demonstrated after adjustment for confounders by multivariable analysis. CONCLUSIONS: Type 2 DM is an independent predictor for long-term mortality after isolated AVR surgery.

Acute Respiratory Distress Syndrome following Cardiac Surgery: Comparison of the American-European Consensus Conference Definition versus the Berlin Definition.

BACKGROUND: Lung injury with development of the acute respiratory distress syndrome (ARDS) is a serious complication which can occur after major surgery, including cardiac surgery. OBJECTIVE: The aim of our study was to compare the prevalence, risk factors, and mortality of ARDS following cardiac surgery according to the American-European Consensus Conference (AECC) definition and the new Berlin definition of ARDS. METHODS: We performed a retrospective, observational study that included prospectively collected data from consecutive adult patients, aged from 18 to 92 years, who had undergone cardiac surgery (both on and off pump) at a large tertiary university hospital over 5 years (from September 2012 to September 2017). RESULTS: During the study period, 3,972 patients underwent cardiac surgery, and 3,946 patients were included in the study. Fifty-five patients developed ARDS (1.14%) according to the AECC definition and 59 patients (1.15%) according to the Berlin definition, with a mortality of 32.7 and 30.5%, respectively (18 patients). Multivariate regression analysis identified prior cardiac surgery, complex cardiac surgery, emergency procedures, and transfusion of > 3 packed red blood cell units as predictors for ARDS. CONCLUSION: The development of ARDS in patients after cardiac surgery is a rare but serious complication associated with significant mortality. Moreover, our findings showed that prevalence, mortality, and risk factors for developing ARDS were similar according to both the AECC and the new Berlin definition.

Sildenafil for Pulmonary Hypertension in the Early Postoperative Period After Mitral Valve Surgery.

OBJECTIVES: The phosphodiesterase-5 inhibitor sildenafil was developed for the treatment of pulmonary hypertension. The authors investigated the efficacy and safety of sildenafil in the early postoperative period after mitral valve surgery in patients with pulmonary hypertension. DESIGN: A double-blind, placebo-controlled randomized trial was performed. SETTING: The trial was performed in a single tertiary referral center. PARTICIPANTS: Fifty consecutive patients who experienced pulmonary hypertension and underwent mitral valve surgery. INTERVENTIONS: Patients were randomly assigned to the following 2 groups: 25 patients received 20 mg sildenafil every 8 hours, and the remaining 25 patients received placebo during the same period. Hemodynamic parameters were studied by using a pulmonary artery catheter at baseline and every 6 hours up to 36 hours. RESULTS: Patients who received sildenafil showed a decrease in mean pulmonary pressure, from 32 ± 7 mmHg at baseline to 26 ± 3 mmHg after 36 hours, whereas no change was seen in patients who received placebo (mean pulmonary pressure 34 ± 6 mmHg at baseline and 35 ± 5 mmHg after 36 h) (p < 0.001). No significant changes in systemic hemodynamic and oxygenation were observed. Patients who received sildenafil compared with those who received placebo had a median mechanical lung ventilation time of 16 (10-31) hours versus 19 (13-41) hours (p = 0.431), intensive care unit stay of 74 (44-106) hours versus 91 (66-141) hours (p = 0.410), and a total hospitalization stay of 7 (5-10) days versus 11 (7-15) days (p = 0.009). CONCLUSIONS: The immediate postoperative administration of sildenafil after mitral valve surgery is safe. Sildenafil demonstrates a favorable decreasing effect on pulmonary vascular pressure without systemic hypotension and ventilation-perfusion mismatch.

Pulmonary Endarterectomy Surgery for Chronic Thromboembolic Pulmonary Hypertension: A Small-Volume National Referral Center Experience.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience. OBJECTIVES: To describe the establishment of a national CTEPH-PEA center in Israel and present results of surgery. METHODS: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH-PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center. RESULTS: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity. CONCLUSIONS: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.

Impact of type 2 diabetes mellitus on short- and long-term mortality after coronary artery bypass surgery.

BACKGROUND: Type 2 diabetes mellitus (DM) is a frequent co-morbidity among patients undergoing coronary artery bypass grafting (CABG) surgery. The aim of this study was to evaluate the impact of DM on the early- and long-term outcomes of patients who underwent isolated CABG. METHODS: We performed an observational cohort study in a large tertiary medical center over a period of 11 years. All data from patients who had undergone isolated CABG surgery between 2004 and 2014 were obtained from our departmental database. The study population included 2766 patients who were divided into two groups: Group I (1553 non-diabetic patients), and Group II (1213 patients suffering from type 2 DM). Group II patients were then divided into two subgroups: subgroup IIA (981 patients treated with oral antihyperglycemic medications) and subgroup IIB (232 insulin-treated patients with or without additional oral antihyperglycemic drugs). In-hospital, 1-, 3-, 5- and 10-year mortality outcome variables were evaluated. Mean follow-up was 97 ± 41 months. RESULTS: In-hospital mortality was similar between Group I and Group II patients (1.87% vs. 2.31%, p = 0.422) and between the subgroups IIA and IIB (2.14% vs. 3.02%, p = 0.464). Long-term mortality (1, 3, 5 and 10 years) was higher in Group II (DM type 2) compared with Group I (non-diabetic patients) (5.3% vs. 3.6%, p = 0.038; 9.3% vs. 5.6%, p < 0.001; 15.3% vs. 9.3%, p < 0.001 and 47.3% vs. 29.6% p < 0.001). Kaplan-Meier analysis demonstrated that all-cause mortality was higher in Group II compared with Group I (p < 0.001) and in subgroup IIB compared with subgroup IIA (p = 0.001). Multivariable analysis showed that DM increased the mortality hazard by twofold, and among diabetic patients, insulin treatment increased the mortality hazard by twofold. CONCLUSIONS: Diabetic and non-diabetic patients have similar in-hospital mortality rates. Survival rates of diabetic patients start to deteriorate 3 year after surgery. Type 2 DM is an independent predictor for long-term mortality after isolated CABG surgery. Mortality is even higher when the diabetes treatment strategy included insulin.