Interaction of heparin with human cardiac troponin complex and its influence on the immunodetection of troponins in human blood samples.

OBJECTIVES: Heparin is a highly charged polysaccharide used as an anticoagulant to prevent blood coagulation in patients with presumed myocardial infarction and to prepare heparin plasma samples for laboratory tests. There are conflicting data regarding the effects of heparin on the measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT), which are used for the immunodiagnosis of acute myocardial infarction. In this study, we investigated the influence of heparin on the immunodetection of human cardiac troponins. METHODS: Gel filtration (GF) techniques and sandwich fluoroimmunoassay were performed. The regions of сTnI and cTnT that are affected by heparin were investigated with a panel of anti-cTnI and anti-cTnT monoclonal antibodies, specific to different epitopes. RESULTS: Heparin was shown to bind to the human cardiac full-size ternary troponin complex (ITC-complex) and free cTnT, which increased their apparent molecular weights in GF studies. Heparin did not bind to the low molecular weight ITC-complex and to binary cTnI-troponin С complex. We did not detect any sites on cTnI in the ITC-complex that were specifically affected by heparin. In contrast, cTnT regions limited to approximately 69-99, 119-138 and 145-164 amino acid residues (aar) in the ITC-complex and a region that lies approximately between 236 and 255 aar of free cTnT were prone to heparin influence. CONCLUSIONS: Heparin binds to the ITC-complex via cTnT, interacting with several sites on the N-terminal and/or central parts of the cTnT molecule, which might influence the immunodetection of analytes in human blood.

Extracorporeal membrane oxygenation in obstetric patients: An Israeli nationwide study.

BACKGROUND: The leading causes of maternal mortality include respiratory failure, cardiovascular events, infections, and hemorrhages. The use of extracorporeal membrane oxygenation (ECMO) as rescue therapy in the peripartum period for cardiopulmonary failure is expanding in critical care medicine. METHODS: This retrospective observational study was conducted on a nationwide cohort in Israel. During the 3-year period, between September 1, 2019, and August 31, 2022, all women in the peripartum period who had been supported by ECMO for respiratory or circulatory failure at 10 large Israeli hospitals were identified. Indications for ECMO, maternal and neonatal outcomes, details of ECMO support, and complications were collected. RESULTS: During the 3-year study period, in Israel, there were 540 234 live births, and 28 obstetric patients were supported by ECMO, with an incidence of 5.2 cases per 100 000 or 1 case per 19 000 births (when excluding patients with COVID-19, the incidence will be 2.5 cases per 100 000 births). Of these, 25 were during the postpartum period, of which 16 (64%) were connected in the PPD1, and 3 were during pregnancy. Eighteen patients (64.3%) were supported by V-V ECMO, 9 (32.1%) by V-A ECMO, and one (3.6%) by a VV-A configuration. Hypoxic respiratory failure (ARDS) was the most common indication for ECMO, observed in 21 patients (75%). COVID-19 was the cause of ARDS in 15 (53.7%) patients. The indications for the V-A configuration were cardiomyopathy (3 patients), amniotic fluid embolism (2 patients), sepsis, and pulmonary hypertension. The maternal and fetal survival rates were 89.3% (n = 25) and 100% (n = 28). The average ECMO duration was 17.6 ± 18.6 days and the ICU stay was 29.8 ± 23.8 days. Major bleeding complications requiring surgical intervention were observed in one patient. CONCLUSIONS: The incidence of using ECMO in the peripartum period is low. The maternal and neonatal survival rates in patients treated with ECMO are high. These results show that ECMO remains an important treatment option for obstetric patients with respiratory and/or cardiopulmonary failure.

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.

Perfusion-Dependent Focal Neurologic Deficits in a Critically Ill Heart Transplant Recipient: A Case of Tacrolimus-Associated Reversible Cerebral Vasospasm Syndrome?

TACROLIMUS, a mainstay of immunosuppression after orthotopic heart transplantation (OHT), is associated with a broad range of side effects. Vasoconstriction caused by tacrolimus has been proposed as a mechanism underlying common side effects such as hypertension and renal injury. Neurologic side effects attributed to tacrolimus include headaches, posterior reversible encephalopathy syndrome (PRES), or reversible cerebral vasospasm syndrome (RCVS). Six case reports have been published describing RCVS in the setting of tacrolimus administration after OHT. The authors report a case of perfusion-dependent focal neurologic deficits attributed to tacrolimus-induced RCVS in an OHT recipient.

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.

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.

[ETHICAL CHALLENGES IN TREATING CRITICAL CORONAVIRUS PATIENTS: EXPERIENCE FROM THE SHEBA MEDICAL CENTER ON THE FIRST COVID-19 PANDEMIC OUTBREAK].

INTRODUCTION: As the coronavirus pandemic emerged in late 2019, a task force was founded in the Sheba Medical Center and began preparing for the arrival of the pandemic to Israel. Several wards were put in charge of isolated COVID-19 patients. A new intensive care unit was formed for the most critical COVID-19 patients, requiring mechanical ventilation and multi-organ treatment. The Corona ICU began operating in March 2020, with a multi-disciplinary team, gathered from ICU units, an internal medicine ward, an anesthesiology department, social workers and psychologists. Simultaneously, the routine medical center functions in non-corona sections were maintained, as much as possible. The coronavirus pandemic entails challenges of many aspects: an unfamiliar pathogen causing an unknown illness, a necessity for social distancing, ambiguity regarding the risk factors for contamination and illness severity, and medical crews put at risk. Consequently, the pandemic involves ethical, social, economic and moral aspects, affecting the medical crew members and system, the patients and their families, and our society as a whole. In this article we review our joint experience in the Sheba Medical Center Corona ICU, of the medical, ethical and moral dilemmas that emerged from the first COVID-19 wave.

Donor thyroid hormone therapy is associated with an increased risk of graft dysfunction after heart transplantation.

OBJECTIVE: Heart transplantation (HT) is uniquely associated with the potential impact of thyroid hormone therapy at three intersecting levels-donor, operation, and recipient. We aimed to study the effect of thyroid hormone therapy of the donor on primary graft dysfunction (PGD). METHODS: A retrospective cohort study was conducted on 209 HT recipients assessed from 1997 to 2018; for 33 of the recipients, the donors had received T4 (DT4 group), and for 176, the donors had not (NoDT4 group). The primary endpoint was PGD defined according to the International Society for Heart and Lung consensus statement. RESULTS: Both the incidence (58% vs 35%, P = .022) and the severity of PGD (42% vs 25% moderate/severe, P = .007) were significantly higher in the DT4 recipients. Multivariable analysis showed donor T4 therapy to be independently associated with a ~3.5-fold increased risk for PGD (OR = 3.44, 95% CI 1.26-9.86). These results remained consistent after propensity score analysis. CONCLUSIONS: Donor thyroid hormone therapy is independently associated with an increased risk of PGD. Hypothesizing a "withdrawal effect" as the cause, we suggest that administration of thyroid hormone to the recipient at time of reperfusion could counter this negative effect. Prospective studies are needed to validate this hypothesis-generating study.

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.

Full-Size and Partially Truncated Cardiac Troponin Complexes in the Blood of Patients with Acute Myocardial Infarction.

BACKGROUND: The measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) is widely used for the diagnosis of acute myocardial infarction (AMI). However, there are conflicting data regarding what forms of cTnI and cTnT are present in the blood of AMI patients. We investigated cTnI and cTnT as components of troponin complexes in the blood of AMI patients. METHODS: Gel filtration techniques, sandwich fluoroimmunoassays, and Western blotting were used. RESULTS: Plasma samples from patients with AMI contained the following troponin complexes: (a) a cTnI-cTnT-TnC complex (ITC) composed of full-size cTnT of 37 kDa or its 29-kDa fragment and full-size cTnI of 29 kDa or its 27-kDa fragments; (b) ITC with lower molecular weight (LMW-ITC) in which cTnT was truncated to the 14-kDa C-terminal fragments; and (c) a binary cTnI-cTnC complex composed of truncated cTnI of approximately 14 kDa. During the progression of the disease, the amount of ITC in AMI samples decreased, whereas the amounts of LMW-ITC and short 16- to 20-kDa cTnT central fragments increased. Almost all full-size cTnT and a 29-kDa cTnT fragment in AMI plasma samples were the components of ITC. No free full-size cTnT was found in AMI plasma samples. Only 16- to 27-kDa central fragments of cTnT were present in a free form in patient blood. CONCLUSIONS: A ternary troponin complex exists in 2 forms in the blood of patients with AMI: full-size ITC and LMW-ITC. The binary cTnI-cTnC complex and free cTnT fragments are also present in patient blood.

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.

Does duration of donor brain injury impact heart transplantation outcomes?

AIM: We aimed to study the implications of pre-transplantation time intervals on HT outcomes. METHODS: Brain injury time (BIT) was defined as the period from the donor brain injury to brain death declaration. Brain death interval (BDI) was defined as the period from brain death to application of an aortic cross-clamp during donor heart procurement. Allograft ischemia was defined as the time from donor aortic cross-clamp to aortic unclamping. End points included mortality and rejections. RESULTS: Between 1997 and 2017, we assessed 173 patients. Kaplan-Meier analyses showed that prolonged donor BIT, BDI, allograft ischemia, and total injury time had no significant effect on mortality and rejections. Patients were subdivided into short BIT (<97 hours, n = 87) and long BIT (≥97 hours, n = 86) groups. No differences in rejection scores nor in time to first rejection were noted. Kaplan-Meier analysis showed a similar long-term survival in the two groups. Sub-analysis of both groups according to their median BDI (12 hours) revealed no differences in mortality or time to rejection. CONCLUSIONS: Pre-transplantation time intervals do not affect mortality or rejection. Our findings have important clinical implications regarding HT allocation and organ availability.

Does donor-recipient age difference matter in outcome of heart transplantation?

OBJECTIVE: Potential interactions between donor-recipient age difference and outcomes after heart transplantation are not well known. We thus aimed to study the impact of donor-recipient age difference on heart transplantation outcomes. METHODS: Between 1995 and 2017, we assessed 234 heart transplantation patients. Based on donor-recipient age difference histogram, we stratified these patients into three groups: older donors (donor-recipient difference > 0; n = 48), younger donors (donor-recipient difference 0 to -20 years; n = 82), and much younger donors (donor-recipient difference <-20 years; n = 104). RESULTS: The baseline metabolic risk profile of the recipients was significantly higher for the much younger donor group compared with the younger and older groups, including hypertension (52% vs 33% vs 25%, P = 0.002), dyslipidemia (51% vs 51% vs 29%, P = 0.027), diabetes (30% vs 16% vs 17%, P = 0.044), and smoking history (53% vs 46% vs 29%, P = 0.024), respectively. There were no significant differences between the groups in long-term survival, cardiac allograft vasculopathy, or rejection-free survival in unadjusted and adjusted analyses. In the much younger donor group, gender matching was associated with a lower incidence of primary graft dysfunction (37% vs 58% P = 0.05). CONCLUSIONS: Donor-recipient age difference does not significantly impact long-term heart transplantation outcomes.

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.

Full-Size Cardiac Troponin I and Its Proteolytic Fragments in Blood of Patients with Acute Myocardial Infarction: Antibody Selection for Assay Development.

BACKGROUND: In the blood of patients with acute myocardial infarction (AMI), cardiac troponin I (cTnI) presents as an intact molecule with a repertoire of proteolytic fragments. The degradation of cTnI might negatively influence its precise immunodetection. In this study we identified cTnI fragments and calculated their ratio in the blood of patients at different times after AMI to discriminate the most stable part(s) of cTnI. METHODS: Serial serum samples were collected from AMI patients within 1 to 36 h after the onset of chest pain both before and after stenting. cTnI and its fragments were immunoextracted from serum samples and analyzed by Western blotting with monoclonal antibodies (mAbs) specific to the different epitopes of cTnI and by 2 in-house immunoassays specific to the central and terminal portions of cTnI. RESULTS: Intact cTnI and its 11 major fragments were detected in blood of AMI patients. The ratio of the fragments in serial samples did not show large changes in the period 1-36 h after AMI. mAbs specific to the epitopes located approximately between amino acid residues (aar) 34 and 126 stained all extracted cTnI. mAbs specific to aar 23-36 and 126-196 recognized approximately 80% to 90% (by abundance) of cTnI. CONCLUSIONS: In addition to mAbs specific to the central part of cTnI (approximately aar 34-126), antibodies specific to the adjacent epitopes (approximately aar 23-36 and 126-196) could be used in assays because they recognize ≥80% of cTnI in patients' blood samples within the first 36 h after AMI.