Long-term predictors of morbidity and mortality in patients following LVAD replacement.

BACKGROUND: As heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first-time LVAD replacements. METHODS: The study cohort consisted of all consecutive patients between 2006 and 2020 that received a first-time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan-Meier, univariate, and multivariate Cox hazard ratio analyses. RESULTS: In total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065-0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87-14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87-14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01-3.86, and p = 0.045). CONCLUSIONS: Replacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.

Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial.

BACKGROUND: Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. OBJECTIVE: To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. DESIGN: A prospective, single-centre, double-blinded, randomised controlled trial. SETTING: Rabin Medical Centre, Beilinson Hospital, Israel. PATIENTS: Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. INTERVENTIONS: For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. OUTCOME MEASURES: The primary outcome was the incidence of hypoxaemia, defined as a paO2/FiO2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. RESULTS: Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P = 0.042, and higher paO2/FiO2 ratios at all time points, F (1,30) = 6.08, P = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. CONCLUSIONS: Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher paO2/FiO2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04807413).

A single center Israeli experience in pregnancy post lung transplantation: Feasibility of successful two or more full-term pregnancies in individual lung transplant recipients.

INTRODUCTION: Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post-transplant management and improved survival. We report our experience with pregnancy in LTRs, with an emphasis on two or more successful full-term pregnancies in individual transplant recipients. METHODS: We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes. RESULTS: In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full-term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre-pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post-transplantation and a mean of 4.5 years after childbirth. CONCLUSION: Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full-term pregnancies.

Lung Transplantation for Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-center Experience.

BACKGROUND: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients. OBJECTIVES: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications. METHODS: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel. RESULTS: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15-53, range 3-60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12-80). The median time from HSCT to LTx was 96 months (IQR 63-120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications. CONCLUSIONS: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Ubiquitin Proteasome System Role in Diabetes-Induced Cardiomyopathy.

This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. The mRNA levels of USP18 (deubiquitinating enzyme), PSMB8, and PSMB9 (proteasome ß-subunits) were down-regulated in db/db mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system.

BACKGROUND: Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice. METHODS: Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested. RESULTS: ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment. CONCLUSION: Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.

Robotic versus port-access mitral repair: A propensity score analysis.

BACKGROUND: Port-access (PORT) and robotic (ROBO) mitral repair are well established, but differences in patient selection and outcomes are not well documented. METHODS: A retrospective analysis was performed on 129 ROBO and 628 PORT mitral repairs at one institution. ROBO patients had 4 cm nonrib spreading incisions with robotic assistance, while PORT patients had 6-8 cm rib spreading incisions with thoracoscopic assistance. Propensity score analysis matched patients for differences in baseline characteristics. RESULTS: Unmatched ROBO patients were younger (58 ± 11 vs. 61 ± 13, p = .05), had a higher percentage of males (77% vs. 63%, p = .003) and had less NYHA Class 3-4 symptoms (11% vs. 21%, p < .01), less atrial fibrillation (19% vs. 29%, p = .02) and less tricuspid regurgitation (14% vs. 24%, p = .01). Propensity score analysis of matched patients showed that pump time (275 ± 57 vs. 207 ± 55, p < .0001) and clamp time (152 ± 38 vs. 130 ± 34, p < .0001) were longer for ROBO patients. However, length of stay, postoperative morbidity, and 5-year survival (97 ± 1% vs. 96 ± 3%, p = .7) were not different. For matched patients with degenerative valve disease, 5-year incidence of mitral reoperation (3 ± 2% vs. 1 ± 1%), severe mitral regurgitation (MR) (6 ± 4% vs. 1 ± 1%), or ≥2 + MR (12 ± 5% vs. 12 ± 4%), were not significantly different between ROBO versus PORT approaches. Predictors of recurrent moderate MR were connective tissue disease, functional etiology, and non-White race, but not surgical approach. CONCLUSIONS: In this first comparison out to 5 years, robotic versus port-access approach to mitral repair had longer pump and clamp times. Perioperative morbidity, 5-year survival, and 5-year repair durability were otherwise similar.

Long-term outcomes of aortic root replacement for endocarditis.

BACKGROUND: Infective endocarditis (IE) involving the aortic valve and root is associated with high risk requiring thoughtful surgical decision-making. The impact of valve and conduit choices and patient factors on long-term outcomes in this patient population is poorly documented. METHODS: From January 1976 to December 2013, 485 patients underwent aortic root and valve replacement at a single institution. Cox's proportional hazard model identified predictors of long-term survival and cumulative incidence functions were compared to assess need for reoperation with death as a competing risk. RESULTS: Median age at time of operation was 56.6 years (interquartile range: 23.1) with the indication for operation being endocarditis in 14.6% (n = 71). Stentless root replacement was used in 70% IE versus 34% non-IE (p < .001). Endocarditis at time of root replacement did not have a significant impact on survival through 15 years (IE: 37.3% vs. non-IE: 42.5%; log-rank; p = .13). After multivariable adjustment, survival was similar between patients with and without endocarditis (hazard ratio: 1.1; 95% confidence interval: [0.77, 1.62]; p = .57). Freedom from reoperation at 15 years did not vary significantly by endocarditis status (IE: 95.9% vs. non-IE: 73.6%; p = .07). Among endocarditis patients, freedom from reoperation at 10 years was similar between homograft and stentless bioprosthetic conduits (95.3% vs. 88.5%; log-rank; K-sample; p = .46). CONCLUSIONS: In a sample with frequent use of stentless prostheses, aortic root replacement for infective endocarditis had acceptable risk and long-term survival similar to root replacement for other indications. In the setting of endocarditis, root replacement with homograft or stentless bioprosthetic root has excellent durability through 15 years.

Cardiac Fibroblast-Induced Pluripotent Stem Cell-Derived Exosomes as a Potential Therapeutic Mean for Heart Failure.

The limited regenerative capacity of the injured myocardium leads to remodeling and often heart failure. Novel therapeutic approaches are essential. Induced pluripotent stem cells (iPSC) differentiated into cardiomyocytes are a potential future therapeutics. We hypothesized that organ-specific reprogramed fibroblasts may serve an advantageous source for future cardiomyocytes. Moreover, exosomes secreted from those cells may have a beneficial effect on cardiac differentiation and/or function. We compared RNA from different sources of human iPSC using chip gene expression. Protein expression was evaluated as well as exosome micro-RNA levels and their impact on embryoid bodies (EBs) differentiation. Statistical analysis identified 51 genes that were altered (p ≤ 0.05), and confirmed in the protein level, cardiac fibroblasts-iPSCs (CF-iPSCs) vs. dermal fibroblasts-iPSCs (DF-iPSCs). Several miRs were altered especially miR22, a key regulator of cardiac hypertrophy and remodeling. Lower expression of miR22 in CF-iPSCs vs. DF-iPSCs was observed. EBs treated with these exosomes exhibited more beating EBs p = 0.05. vs. control. We identify CF-iPSC and its exosomes as a potential source for cardiac recovery induction. The decrease in miR22 level points out that our CF-iPSC-exosomes are naïve of congestive heart cell memory, making them a potential biological source for future therapy for the injured heart.

Percutaneous Intervention for Left Ventricular Assist Device Outflow Obstruction.

Left ventricular assist devices (LVADs) are used to support patients with advanced systolic heart failure (HF). These patients might develop LVAD dysfunction and consequent HF symptoms. Occasionally, outflow graft obstruction is responsible for LVAD dysfunction. Here, we describe percutaneous techniques to repair the outflow graft and avoid re-sternotomy.

Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.

BACKGROUND/OBJECTIVES: Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications. MATERIALS/METHODS: After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing. RESULTS: Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%. CONCLUSIONS: 3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications.

Controlling axillary intra-aortic balloon pump inflation is a viable option for turning an acute heart failure patient into a chronic one.

Intra-aortic balloon pump (IABP) is often used to support patients in decompensated heart failure. Placement of the IABP via the axillary artery facilitates long-term support with the device and may allow for the conversion of an acute heart failure (HF) patient into a chronic HF patient using a modified weaning protocol; allowing for medical symptom management and removal of mechanical support. We will discuss strategies for supporting these complicated patients.

The Ubiquitin Proteasome System in Ischemic and Dilated Cardiomyopathy.

Dilated (DCM) and ischemic cardiomyopathies (ICM) are associated with cardiac remodeling, where the ubiquitin-proteasome system (UPS) holds a central role. Little is known about the UPS and its alterations in patients suffering from DCM or ICM. The aim of this study is to characterize the UPS activity in human heart tissue from cardiomyopathy patients. Myocardial tissue from ICM (n = 23), DCM (n = 28), and control (n = 14) patients were used to quantify ubiquitinylated proteins, E3-ubiquitin-ligases muscle-atrophy-F-box (MAFbx)/atrogin-1, muscle-RING-finger-1 (MuRF1), and eukaryotic-translation-initiation-factor-4E (eIF4E), by Western blot. Furthermore, the proteasomal chymotrypsin-like and trypsin-like peptidase activities were determined fluorometrically. Enzyme activity of NAD(P)H oxidase was assessed as an index of reactive oxygen species production. The chymotrypsin- (p = 0.71) and caspase-like proteasomal activity (p = 0.93) was similar between the groups. Trypsin-like proteasomal activity was lower in ICM (0.78 ± 0.11 µU/mg) compared to DCM (1.06 ± 0.08 µU/mg) and control (1.00 ± 0.06 µU/mg; p = 0.06) samples. Decreased ubiquitin expression in both cardiomyopathy groups (ICM vs. control: p < 0.001; DCM vs. control: p < 0.001), as well as less ubiquitin-positive deposits in ICM-damaged tissue (ICM: 4.19% ± 0.60%, control: 6.28% ± 0.40%, p = 0.022), were detected. E3-ligase MuRF1 protein expression (p = 0.62), NADPH-oxidase activity (p = 0.63), and AIF-positive cells (p = 0.50). Statistical trends were detected for reduced MAFbx protein expression in the DCM-group (p = 0.07). Different levels of UPS components, E3 ligases, and UPS activation markers were observed in myocardial tissue from patients affected by DCM and ICM, suggesting differential involvement of the UPS in the underlying pathologies.

Early Referral to Coronary Artery Bypass Grafting Following Acute Coronary Syndrome, Trends and Outcomes from the Acute Coronary Syndrome Israeli Survey (ACSIS) 2000-2010.

BACKGROUND: Limited information exists on whether changes in medical practices over the study decades have affected the outcomes of acute coronary syndrome (ACS) patients who undergo early coronary artery bypass surgery (CABG) during index hospitalisation. METHODS: Data on trends for early CABG referral and associated outcomes were obtained among 11,485 ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) 2000-2010. RESULTS: Among 11,485 patients, 566 (5%) were referred to early CABG. These patients displayed higher risk characteristics, including Killip class >II, anterior myocardial infarction, greater left ventricular dysfunction, and more frequent use of mechanical ventilation and intra-aortic balloon pump (all p<0.01). Nevertheless, mortality rates of patients referred to early CABG vs. treated with percutaneous coronary intervention (PCI) or medically, was similar (11.4% vs. 10.2%; log-rank p-value=0.40). There was a significant decline in the referral trend over the study decade (6.7% - 1.7%; p<0.001). One year survival was similar between patients referred to early CABG during the late (years: 2006-2010) vs. early (years: 2000-2005) period (85.7% vs. 90%; log-rank p-value=0.15), whereas, among patients who didn't undergo early CABG, and underwent percutaneous coronary intervention (PCI) or medical management only, enrolment during the late periods was associated with a significant survival benefit (91.5% vs. 88.1%; log-rank p-value<0.001). CONCLUSIONS: Over the study decade there was a significant decline in referral for early CABG, without a difference in the one-year mortality between the early and non-early CABG group.

Strain Analysis in the Detection of Myocardial Infarction at the Acute and Chronic Stages.

BACKGROUND: Myocardial ischemia causes contractile dysfunction in ischemic, stunned, and tethered regions with larger infarcted zones having a negative prognostic impact on patients' outcomes. To distinguish the infarcted myocardium from the other regions, we investigated the diagnostic potential of circumferential strain (CS) and radial strain (RS) during the acute and chronic stages of myocardial infarction. METHODS: Ten pigs underwent 90-minute occlusion of the left anterior descending artery, followed by reperfusion. Echocardiography was performed at baseline, after 90-minute occlusion, and at 2 hours, 30, and 60 days postreperfusion. CS and RS were measured using speckle tracking echocardiography. Subsequently, the pigs were sacrificed, and histological analysis for infarct size was performed. RESULTS: After 90-minute occlusion, reduced strains were detected for all segments (infarcted anterior wall - baseline: CS: -17.6 ± 5.7%, RS: 54.4 ± 16.9%; 90 min: CS: -10.3 ± 3.0%, RS: 23.3 ± 7.0%; tethered posterior wall - baseline: CS: -18.4 ± 3.5%, RS: 68.7 ± 21.1%; 90 min: CS: -10.7 ± 6.4%, RS: 34.5 ± 14.7%, P < 0.001). However, postsystolic shortening was detected only in the infarcted segments, and the time-to-peak CS was 25% longer (P < 0.05). At 30 and 60 days postreperfusion, time-to-peak CS could only detect large scars in the anterior and anterior-septum walls (P < 0.05), while peak CS also detected smaller scars in the lateral wall (P < 0.05). RS failed to distinguish between normal, stunned/tethered, and infarcted myocardium. CONCLUSIONS: During occlusion and 2 hours postreperfusion, time-to-peak CS could distinguish between infarcted and stunned/tethered myocardial segments, while at 30 and 60 days postreperfusion, peak CS was the best detector of infarction.

TVP1022: A Novel Cardioprotective Drug Attenuates Left Ventricular Remodeling After Ischemia/Reperfusion in Pigs.

BACKGROUND: The current cornerstone treatment of myocardial infarction (MI) is restoration of coronary blood flow by means of thrombolytic therapy or primary percutaneous coronary intervention. However, reperfusion of ischemic myocardium can actually provoke tissue damage, defined as "ischemia-reperfusion (I/R) injury." TVP1022 [the S-isomer of rasagiline (Azilect), FDA-approved anti-Parkinson's drug] was found to exert cardioprotective activities against various cardiac insults, such as chronic heart failure and I/R, in rat models. Therefore, we tested the hypothesis that TVP1022 will provide cardioprotection against I/R injury and post-MI remodeling in a pig model. METHODS: For inducing MI, we used an I/R model of midleft anterior descending artery occlusion for 90 minutes followed by follow-up for 8 weeks in 18 farm pigs (9 pigs in each group, MI + TVP1022 or MI + Vehicle). Echocardiographic measurements were performed and cardiac scar size was calculated using histopathological methods. For fibrosis evaluation, we measured the interstitial collagen volume fraction in the remote noninfarcted tissue. RESULTS: TVP1022 administration significantly decreased cardiac scar size, attenuated left ventricular dilation, and improved cardiac function assessed by segmental circumferential strain analysis. Furthermore, TVP1022 significantly reduced myocardial fibrosis 8 weeks post-MI. CONCLUSIONS: Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R pig model.

The Clinical SYNTAX score predicts survival better than the SYNTAX score in coronary revascularization.

BACKGROUND: The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) trial showed that the SYNTAX score (SS) is a useful tool for customizing revascularization treatment for patients with multivessel coronary disease. In the past decade, the Clinical SS (CSS) has emerged as a comprehensive tool. This novel tool considers the SS as well as patient clinical parameters such as age, creatinine clearance, and ejection fraction, which were shown to be relevant for patient prognosis. Thus, in the current work we set out to compare the survival predictive values of the SS versus the CSS and their future application in real-world implementation of the revascularization guidelines. METHODS: This study was a subanalysis of data collected in a prospective national registry in Israel that enrolled consecutive patients with left main and/or 2- to 3-vessel coronary artery disease involving the proximal or mid-left anterior descending artery; the MULTI-vessel Coronary Artery Disease (MULTICAD). The revascularization method was chosen by the physicians taking care of the patients at each hospital and the patients were followed for 5 years. Patients were categorized according to their SS, the CSS, and their revascularization method (primary coronary intervention [PCI] vs coronary artery bypass grafting [CABG]) and patient survival were compared. RESULTS: A total of 585 patients were enrolled in the study and were followed for 5 years. The median CSS was 27, with 288 patients showing a CSS ≥27, with a mean CSS of 47.85 and a mean SS of 29.05. At 3 and 5 years post-treatment, the CSS ≥27 group had a lower survival probability, CSS ≥27 was associated with a lower survival probability among patients who underwent PCI compared with those who underwent CABG. More specifically, the high-CSS CABG group had a 5-year mortality rate of 16.8%, whereas the high-CSS PCI group had a 5-year mortality rate of 32.2%. In a comparison of SS with CSS for the 5-year mortality outcome prediction, CSS was superior to SS with a higher area under the curve. CONCLUSIONS: This prospective registry of real-world revascularization strategies in patients with multivessel disease showed that CSS is a better predictive tool of postrevascularization survival than SS. Moreover, it showed that surgical revascularization in patients with CSS ≥27 is associated with better all-cause mortality outcome after CABG as compared with after PCI. This attests to the need for a score that considers clinical parameters in a real-world scenario.