Human immunodeficiency virus infection is associated with greater risk of pneumonia and readmission after cardiac surgery.

Objective: Human immunodeficiency virus infection (HIV+) is associated with a 2-fold increased risk of cardiovascular disease. Increasingly, patients who are HIV + are being evaluated to undergo cardiac surgery. Current risk-adjusted scoring systems, including the Society of Thoracic Surgeons Predicted Risk of Mortality score, fail to stratify HIV + risk. Unfortunately, there exists a paucity of cardiac surgery outcomes data in modern patients who are HIV+. Methods: We conducted a retrospective review of PearlDiver, an all-payer claims administrative database. In total, 14,714,743 patients were captured between 2010 and 2020. Of these, 59,695 (0.4%) of patients had a history of HIV+, and 1759 (2.95%) of these patients underwent cardiac surgery. Patients who were HIV+ were younger, more often male, and had greater comorbidity, history of hypertension, chronic obstructive pulmonary disease, chronic liver disease, chronic kidney disease, chronic lung disease, and heart failure. Results: Postoperatively, patients who were HIV + had significantly greater rates of pneumonia (relative risk, 1.70; P = .0003) and 30-day all-cause readmission (relative risk, 1.28, P < .0001). After linear regression analysis, these results remained significant. Data also show that a lesser proportion of patients with HIV + underwent coronary artery bypass grafting, aortic valve replacement, and any cardiac surgery compared with controls. Conclusions: Patients who are HIV + undergoing cardiac surgery are at greater risk of pneumonia and readmission. Moreover, we discovered lower rates of cardiac surgery in patients who are HIV+, which may reflect limited access to surgery when indicated. Today's risk-adjusted scoring systems in cardiac surgery need to better account for the modern patient who is HIV+.

Features and Outcomes of Females and Males Requiring Postcardiotomy Extracorporeal Life Support.

BACKGROUND: Although cardiogenic shock requiring extracorporeal life support (ECLS) after cardiac surgery is associated with high mortality, the impact of sex on outcomes of post-cardiotomy ECLS remains unclear with conflicting results in literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring post-cardiotomy ECLS. METHODS: This retrospective, multicentre (34 centres), observational study included adults requiring post-cardiotomy ECLS between 2000 and 2020. Pre-operative, procedural, and ECLS characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed-Cox proportional hazards models. RESULTS: This analysis included 1823 patients [females:40.8%; median age:66.0 (interquartile range:56.2-73.0 years)]. Females underwent more mitral (females:38.4%, males:33.1%, p=0.019) and tricuspid (females:18%, males:12.4%, p<0.001) valve surgery, while males had more coronary artery surgery (females:45.9%, males:52.4%, p=0.007). ECLS implantation was more common intra-operatively in females (females:64.1%, males:59.1%) and post-operatively in males (females:35.9%, males:40.9%, p=0.036). Ventricular unloading (females:25.1%, males:36.2%, p<0.001) and intra-aortic balloon pump (females: 25.8%, males:36.8%, p<0.001) were most frequently used in males. Females suffered more post-operative right ventricular failure (females:24.1%, males:19.1%, p=0.016) and limb ischemia (females:12.3%, males:8.8%, p=0.23). In-hospital mortality was 64.9% in females and 61.9% in males (p=0.199) with no differences in 5-year survival (females:20%, 95%CI:17-23; males:24%, 95%CI:21-28;p=0.069). Crude hazard ratio for in-hospital mortality in females was 1.12 (95%CI: 0.99-1.27,p=0.069) and did not change after adjustments. CONCLUSIONS: This study demonstrates that females and males requiring post-cardiotomy ECLS have different pre-operative and ECLS characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survival.

On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.

BACKGROUND: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year. RESULTS: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality. CONCLUSIONS: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.

Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study.

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.

Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.

OBJECTIVES: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes. RESULTS: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86). CONCLUSIONS: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.

The Relation Between Obesity and Mortality in Postcardiotomy Venoarterial Membrane Oxygenation.

BACKGROUND: Obesity is an important health problem in cardiac surgery and among patients requiring postcardiotomy venoarterial extracorporeal membrane oxygenation (V-A ECMO). Still, whether these patients are at risk for unfavorable outcomes after postcardiotomy V-A ECMO remains unclear. The current study evaluated the association between body mass index (BMI) and in-hospital outcomes in this setting. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS-1) study is an international, multicenter study. Patients requiring postcardiotomy V-A ECMO in 36 centers from 16 countries between 2000 and 2020 were included. Patients were divided in 6 BMI categories (underweight, normal weight, overweight, class I, class II, and class III obesity) according to international recommendations. Primary outcome was in-hospital mortality, and secondary outcomes included major adverse events. Mixed logistic regression models were applied to evaluate associations between BMI and mortality. RESULTS: The study cohort included 2046 patients (median age, 65 years; 838 women [41.0%]). In-hospital mortality was 60.3%, without statistically significant differences among BMI classes for in-hospital mortality (P = .225) or major adverse events (P = .126). The crude association between BMI and in-hospital mortality was not statistically significant after adjustment for comorbidities and intraoperative variables (class I: odds ratio [OR], 1.21; 95% CI, 0.88-1.65; class II: OR, 1.45; 95% CI, 0.86-2.45; class III: OR, 1.43; 95% CI, 0.62-3.33), which was confirmed in multiple sensitivity analyses. CONCLUSIONS: BMI is not associated to in-hospital outcomes after adjustment for confounders in patients undergoing postcardiotomy V-A ECMO. Therefore, BMI itself should not be incorporated in the risk stratification for postcardiotomy V-A ECMO.

Mesenchymal stem cell secretions improve donor heart function following ex vivo cold storage.

OBJECTIVES: Heart transplantation is the gold standard of treatments for end-stage heart failure, but its use is limited by extreme shortage of donor organs. The time "window" between procurement and transplantation sets the stage for myocardial ischemia/reperfusion injury, which constrains the maximal storage time and lowers use of donor organs. Given mesenchymal stem cell (MSC)-derived paracrine protection, we aimed to evaluate the efficacy of MSC-conditioned medium (CM) and extracellular vesicles (EVs) when added to ex vivo preservation solution on ameliorating ischemia/reperfusion-induced myocardial damage in donor hearts. METHODS: Mouse donor hearts were stored at 0°C-4°C of <1-hour cold ischemia (<1hr-I), 6hr-I + vehicle, 6hr-I + MSC-CM, 6hr-I + MSC-EVs, and 6hr-I + MSC-CM from MSCs treated with exosome release inhibitor. The hearts were then heterotopically implanted into recipient mice. At 24 hours postsurgery, myocardial function was evaluated. Heart tissue was collected for analysis of histology, apoptotic cell death, microRNA (miR)-199a-3p expression, and myocardial cytokine production. RESULTS: Six-hour cold ischemia significantly impaired myocardial function, increased cell death, and reduced miR-199a-3p in implanted hearts versus <1hr-I. MSC-CM or MSC-EVs in preservation solution reversed the detrimental effects of prolong cold ischemia on donor hearts. Exosome-depleted MSC-CM partially abolished MSC secretome-mediated cardioprotection in implanted hearts. MiR-199a-3p was highly enriched in MSC-EVs. MSC-CM and MSC-EVs increased cold ischemia-downregulated miR-199a-3p in donor hearts, whereas exosome-depletion neutralized this effect. CONCLUSIONS: MSC-CM and MSC-EVs confer improved myocardial preservation in donor hearts during prolonged cold static storage and MSC-EVs can be used for intercellular transport of miRNAs in heart transplantation.

Bone marrow- or adipose-mesenchymal stromal cell secretome preserves myocardial transcriptome profile and ameliorates cardiac damage following ex vivo cold storage.

BACKGROUND: Heart transplantation, a life-saving approach for patients with end-stage heart disease, is limited by shortage of donor organs. While prolonged storage provides more organs, it increases the extent of ischemia. Therefore, we seek to understand molecular mechanisms underlying pathophysiological changes of donor hearts during prolonged storage. Additionally, considering mesenchymal stromal cell (MSC)-derived paracrine protection, we aim to test if MSC secretome preserves myocardial transcriptome profile and whether MSC secretome from a certain source provides the optimal protection in donor hearts during cold storage. METHODS AND RESULTS: Isolated mouse hearts were divided into: no cold storage (control), 6 h cold storage (6 h-I), 6 h-I + conditioned media from bone marrow MSCs (BM-MSC CM), and 6 h-I + adipose-MSC CM (Ad-MSC CM). Deep RNA sequencing analysis revealed that compared to control, 6 h-I led to 266 differentially expressed genes, many of which were implicated in modulating mitochondrial performance, oxidative stress response, myocardial function, and apoptosis. BM-MSC CM and Ad-MSC CM restored these gene expression towards control. They also improved 6 h-I-induced myocardial functional depression, reduced inflammatory cytokine production, decreased apoptosis, and reduced myocardial H2O2. However, neither MSC-exosomes nor exosome-depleted CM recapitulated MSC CM-ameliorated apoptosis and CM-improved mitochondrial preservation during cold ischemia. Knockdown of Per2 by specific siRNA abolished MSC CM-mediated these protective effects in cardiomyocytes following 6 h cold storage. CONCLUSIONS: Our results demonstrated that using MSC secretome (BM-MSCs and Ad-MSCs) during prolonged cold storage confers preservation of the normal transcriptional "fingerprint", and reduces donor heart damage. MSC-released soluble factors and exosomes may synergistically act for donor heart protection.

Long term survival after lung transplantation: A single center experience.

BACKGROUND: There are approximately 2000 lung transplants performed across the United States annually. There is limited data to identify factors predictive of long-term survival. OBJECTIVE: We evaluated 10-year survivors after lung transplant to determine predictors of long-term survival. METHODS: Data were collected from the United Network for Organ Sharing registry database from a single institution. Inclusion criteria were: patients who received a lung transplant between 1989 and 2005. Descriptive statistics were calculated, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: Three hundred sixty-one patients received a lung transplant between 1989 and 2005, and 77 patients survived at least 10 years (21%). Diagnoses at the time of transplant included: chronic obstructive pulmonary disease/emphysema 45 (58.4%), idiopathic pulmonary fibrosis 12 (15.6%), alpha 1 anti-trypsin deficiency 6 (7.8%), cystic fibrosis 4 (5.2%), primary pulmonary hypertension 2 (2.6%), and Eisenmenger's syndrome 1 (1.3%). Seventy-four recipients (96.10%) were Caucasian; 46 (59.74%) were female. Age at the time of transplant ranged from 19 to 67 years (mean 50.8; median 52). Forty-two patients (54.5%) were double lung recipients. Survival ranged from 10.0 to 21.9 years (mean 15.5y; median 15.48y). Forty-two (54.5%) subjects are currently alive; the most common causes of death included: chronic rejection (20%), and infection (17.14%). CONCLUSIONS: Ten-year survivors were significantly younger, weighed less, and had significantly shorter lengths of hospitalization after transplantation. Bilateral lung transplantation was a significant factor in prolonged survival. Survival also improved with institutional experience.

Structured review of post-cardiotomy extracorporeal membrane oxygenation: part 1-Adult patients.

Cardiogenic shock, cardiac arrest, acute respiratory failure, or a combination of such events, are all potential complications after cardiac surgery which lead to high mortality. Use of extracorporeal temporary cardio-circulatory and respiratory support for progressive clinical deterioration can facilitate bridging the patient to recovery or to more durable support. Over the last decade, extracorporeal membrane oxygenation (ECMO) has emerged as the preferred temporary artificial support system in such circumstances. Many factors have contributed to widespread ECMO use, including the relative ease of implantation, effectiveness, versatility, low cost relative to alternative devices, and potential for full, not just partial circulatory support. While there have been numerous publications detailing the short and midterm outcomes of ECMO support, specific reports about post-cardiotomy ECMO (PC-ECMO), are limited, single-center experiences. Etiology of cardiorespiratory failure leading to ECMO implantation, associated ECMO complications, and overall patient outcomes may be unique to the PC-ECMO population. Despite the rise in PC-ECMO use over the past decade, short-term survival has not improved. This report, therefore, aims to present a comprehensive overview of the literature with respect to the prevalence of ECMO use, patient characteristics, ECMO management, and in-hospital and early post-discharge patient outcomes for those treated for post-cardiotomy heart, lung, or heart-lung failure.

Postischemic application of estrogen ameliorates myocardial damage in an in vivo mouse model.

BACKGROUND: Cardioprotection provided by estrogen has been recognized for many years. It is noteworthy that most of these studies employ a means of preinjury application in experimental research and the preventive usage in clinical studies. Compared to pretreatment, postischemic administration of estrogen will be more practical in treating myocardial ischemia. On the other hand, defect in circadian clock gene period2 (Per2) has been shown to aggravate ischemia-induced heart damage. Given that Per2 expression decreases as a consequence of menopause, in this study, we aim to determine (1) potential improvement of myocardial function by postischemic administration of 17ß-estradiol (E2) using an in vivo mouse myocardial ischemia/reperfusion (I/R) model and (2) the role of E2 in regulating myocardial Per2 expression following I/R. METHODS: Thirty-minute occlusion of left anterior descending artery followed by 24-h reperfusion was performed on adult C57BL ovariectomized female mice. Groups (n = 3-6/group) were as follows: (1) Sham, (2) I/R + vehicle, and (3) I/R + E2. Vehicle or 0.5 mg/kg of E2 was subcutaneously injected right after 30-min ischemia. Following 24-h reperfusion, myocardial function was determined. Heart tissue was collected for analysis of cleaved caspase-3 and Per2 expression by Western blotting, as well as proinflammatory cytokine production (IL-1ß, IL-6, and TNF-α) by enzyme-linked immunosorbent assay. RESULTS: I/R significantly impaired left ventricular function and increased myocardial levels of active caspase-3, IL-1ß, and IL-6. Importantly, postischemic treatment of E2 markedly restored I/R-depressed myocardial function, reduced caspase-3 activation, and decreased proinflammatory cytokine production (IL-1ß, IL-6, and TNF-α). Intriguingly, a trend of the decreased Per2 level was observed in ovariectomized female hearts subjected to I/R, whereas E2 treatment upregulated myocardial Per2 expression. CONCLUSIONS: Our study represents the initial evidence that postischemic administration of E2 effectively preserves the myocardium against I/R injury and this protective effect of E2 may involve upregulation of Per2 in ischemic heart.

Surgical Thoracic Transplant Training: Super Fellowship-Is It Super?

OBJECTIVE: The quality of training provided to thoracic transplant fellows is a critical step in the care of complex patients undergoing transplant. The training varies since it is not an accreditation council for graduate medical education accredited fellowship. METHOD: A total of 104 heart or lung transplant program directors throughout the United States were sent a survey of 24 questions focusing on key aspects of training, fellowship training content and thoracic transplant job satisfaction. Out of the 104 programs surveyed 45 surveys (43%) were returned. RESULTS: In total, 26 programs offering a transplant fellowship were included in the survey. Among these programs 69% currently have fellows of which 56% are American Board of Thoracic Surgery board eligible. According to the United Network for Organ Sharing (UNOS) requirements, 46% of the programs do not meet the requirements to be qualified as a primary heart transplant surgeon. A total of 23% of lung transplant programs also perform less than the UNOS minimum requirements. Only 24% have extra-surgical curriculum. Out of the participating programs, only 38% of fellows secured a job in a hospital setting for performing transplants. An astounding 77% of replies site an unpredictable work schedule as the main reason that makes thoracic transplant a less than favorable profession among new graduates. Long hours were also a complaint of 69% of graduates who agreed that their personal life is affected by excessive work hours. CONCLUSION: Annually, almost half of all thoracic transplant programs perform fewer than the UNOS requirements to be a primary thoracic surgeon. This results in a majority of transplant fellows not finding a suitable transplant career. The current and future needs for highly qualified thoracic transplant surgeons will not be met through our existing training mechanisms.

Successful Delivery in a Patient With Left Ventricular Assist Device and Unplanned Pregnancy.

We report the case of a woman supported by a left ventricular assist device (LVAD) who presented at 20 weeks of gestation and decided against recommendations to continue with her pregnancy. This was managed with well-developed plan for a multidisciplinary team approach. With close and regular follow-up and regular adjustment of the patient's medications and LVAD parameters, successful delivery and outcome for both the mother and the newborn were achieved.

Regulation of myocardial stromal cell-derived factor 1α/CXCL12 by tumor necrosis factor signaling.

BACKGROUND: Global myocardial ischemia-reperfusion (I/R) occurs during cardiac operations. This I/R injury leads to increased production of tumor necrosis factor α (TNF) instantly and upregulated expression of stromal cell-derived factor 1 α (SDF-1). On the basis of the published data from our laboratory and other groups, locally produced TNF contributes to cardiac dysfunction mainly via binding to its receptor (tumor necrosis factor receptor 1 [TNFR1]), whereas ischemia-induced myocardial SDF-1 mediates cardioprotection. Although TNF has been shown to work as an upstream initiator for induction of other cytokines and chemokines, there is no information regarding the interaction among TNF, TNFRs, and myocardial SDF-1 expression. In this study, given that TNF downregulated SDF-1 in vascular endothelial cells, we therefore hypothesized that TNF would have a negative effect on myocardial SDF-1 production, which is attributable to TNFR-initiated actions. METHODS: Using a Langendorff model, isolated male mouse hearts were infused with TNF for 45 min. Male adult mouse hearts from wild type, TNFR1 knockout (TNFR1KO), TNFR2KO, and TNFR1/2KO were subjected to global I/R. H9c2 cells with small interfering RNA transfection were used as an in vitro model. The levels of SDF-1 (protein and messenger RNA) were detected by enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction . Protein kinases of IκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α) and c-jun N-terminal kinase were also determined using Western blot assay. RESULTS: TNF infusion downregulated myocardial SDF-1 production in a dose-dependent manner in the hearts. In addition, using TNF significantly decreased SDF-1 expression in cardiomyoblasts (H9c2 cells), which was associated with reduced IκB level. Knockdown of TNFR1 or TNFR2 by small interfering RNAs neutralized TNF-suppressed SDF-1 in H9c2 cells. Furthermore, deletion of TNFR1/2 or TNFR2 increased SDF-1 production in the hearts after I/R. CONCLUSIONS: Our study represents the initial evidence showing that TNF plays an inhibitory role in modulating myocardial SDF-1 production and blockade of TNF signaling by ablation of TNFR1 and TNFR2 genes increased SDF-1 expression in the heart. These data expand on TNF signaling-initiated mechanisms in myocardium, which may lend a more complete understanding of SDF-1 and TNFR-derived actions in hopes of advancing ischemic heart injury treatments.

Use of extracorporeal membranous oxygenator in transcatheter aortic valve replacement.

The superiority of transcatheter aortic valve replacement (TAVR) compared with medical therapy for patients with aortic stenosis (AS) who are not suitable candidates for surgery had been proven. Cardiopulmonary bypass (CPB) is rarely used in TAVR. Reports of early use of extracorporeal membranous oxygenator (ECMO) have promising outcomes. ECMO offers the option of cardiac support rescue in case of intraoperative hemodynamic instability and can be instituted in advance when hemodynamic instability is expected. Here we review the English literature about the use of ECMO in TAVR procedures, and discuss the indications and rationale for its use as well as its advantages.

Evaluation of Alemtuzumab Versus Basiliximab Induction: A Retrospective Cohort Study in Lung Transplant Recipients.

BACKGROUND: Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation. METHODS: A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012. RESULTS: The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P < 0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P < 0.0001). CONCLUSIONS: Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.

Impact of donor age on survival after heart transplantation: an analysis of the United Network for Organ Sharing (UNOS) registry.

BACKGROUND: Data are limited regarding the influence of donor age on outcomes after heart transplantation. We sought to determine if advanced donor age is associated with differences in survival after heart transplantation and how this compares to waitlist survival. METHODS: All adult heart transplants from 2000 to 2012 were identified using the United Network for Organ Sharing database. Donors were stratified into four age groups: 18-39 (reference group), 40-49, 50-54, and 55 and above. Propensity scoring was used to compare status IA waitlist patients who did not undergo transplantation with IA recipients who received hearts from advanced age donors. The primary outcome of interest was recipient survival and this was analyzed with multivariate Cox regression analysis and the Kaplan-Meier method. RESULTS: A total of 22,960 adult heart transplant recipients were identified. Recipients of hearts from all three older donor groups had significantly increased risk of mortality (HR, 1.187-1.426, all p < 0.001) compared to recipients from donors age 18 to 39. Additionally, propensity-matched status IA patients managed medically without transplantation had significantly worse adjusted survival than status IA recipients who received hearts from older donors age ≥55 (HR, 1.362, p < 0.001). CONCLUSIONS: Compared to donors aged 18-39, age 40 and above is associated with worse adjusted recipient survival in heart transplantation. This survival difference becomes more pronounced as age increases to above 55. However, the survival rate among status IA patients who receive hearts from advanced age donors (≥55) is significantly better compared to similar status IA patients who are managed without transplantation.

Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling.

Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm(2) field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF.

Evaluation of GI bleeding after implantation of left ventricular assist device.

BACKGROUND: Left ventricular assist devices (LVADs) have revolutionized the management of end-stage heart failure (ESHF). However, unexpectedly high rates of GI bleeding (GIB) have been described, and etiology and outcome remain unclear. OBJECTIVE: To determine the prevalence, etiology, and outcome of GIB in LVAD recipients. DESIGN: Retrospective case series. SETTING: Tertiary care academic university hospital. PATIENTS: 154 ESHF patients (55.4 years, 122 men/32 women) with LVADs implanted over a 10-year period. MAIN OUTCOME MEASUREMENTS: Overt or occult GIB prompting endoscopic evaluation ≥ 7 days after LVAD implantation. RESULTS: Over a mean of 0.9 ± 0.1 years of follow-up, 29 patients (19%) experienced 44 GIB episodes. Patients with GIB were older and received anticoagulation therapy before devices were implanted (P ≤ .02 for each). GIB was overt (n = 31) rather than occult (n = 13), and most patients presented with melena (n = 22, 50%); hemodynamic instability was observed in 13.6%. Each bleeding episode required 2.1 ± 0.1 diagnostic or therapeutic procedures, and a source was localized in 71%. Upper endoscopy provided the highest diagnostic yield; peptic bleeding (n = 14) and vascular malformations (n = 8) dominated the findings. Endoscopy was safe and well tolerated. Overall mortality was 35%, none directly from GIB. LIMITATION: Retrospective design. CONCLUSIONS: Rates of GIB with LVADs are higher than that seen in other patient populations, including those receiving anticoagulation and antiplatelet therapy. GIB episodes are mostly overt and predominantly from the upper GI tract. Endoscopy is safe in the LVAD population.