Myocardial hypothermia increases autophagic flux, mitochondrial mass and myocardial function after ischemia-reperfusion injury.

Animal studies have demonstrated beneficial effects of therapeutic hypothermia on myocardial function, yet exact mechanisms remain unclear. Impaired autophagy leads to heart failure and mitophagy is important for mitigating ischemia/reperfusion injury. This study aims to investigate whether the beneficial effects of therapeutic hypothermia are due to preserved autophagy and mitophagy. Under general anesthesia, the left anterior descending coronary artery of 19 female farm pigs was occluded for 90 minutes with consecutive reperfusion. 30 minutes after reperfusion, we performed pericardial irrigation with warm or cold saline for 60 minutes. Myocardial tissue analysis was performed one and four weeks after infarction. Therapeutic hypothermia induced a significant increase in autophagic flux, mitophagy, mitochondrial mass and function in the myocardium after infarction. Cell stress, apoptosis, inflammation as well as fibrosis were reduced, with significant preservation of systolic and diastolic function four weeks post infarction. We found similar biochemical changes in human samples undergoing open chest surgery under hypothermic conditions when compared to the warm. These results suggest that autophagic flux and mitophagy are important mechanisms implicated in cardiomyocyte recovery after myocardial infarction under hypothermic conditions. New therapeutic strategies targeting these pathways directly could lead to improvements in prevention of heart failure

\u3ci\u3eRising in the Night\u3c/i\u3e

When Gina sprang out of bed that night she did it joyfully. Her eyes swept open at once, her legs from the thighs to the toes felt life in them

A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients

Background. Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. Methods. The mean recipient age was 50.7±13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5±21.7 years. The mean cold ischemia time was 30.5±9.2 hr. The mean follow-up is 15±7 months. Results. The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double-therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6±0.8 mg/dL A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. Conclusions. This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids

Platelet Mapping by Thromboelastography and Whole Blood Aggregometry in Adult Patients Supported by Mechanical Circulatory Support Device on Aspirin Therapy.

Patients on mechanical circulatory support (MCS) devices are placed on aspirin and may require platelet function testing (PFT) to monitor the adequacy of therapy. Routine laboratory PFT is performed using whole blood aggregation (WBA) which typically has a long turnaround time (4-5 hours) and may not be readily available. By contrast, platelet mapping by thromboelastography (TPM) can provide results within 45 minutes. The objective of this study was to compare the results of TPM with WBA. We compared platelet mapping maximal amplitude (MA) by TPM with that of arachidonic acid (AA) to WBA with AA by impedance. We analyzed paired samples where both TPM and WBA were available. Of 45 paired samples, 34 were from 29 MCS patients and 11 were from non-MCS patients. When applying institutional interpretation guidelines with an MAActivator cutoff of ≤40 mm, WBAAA vs TPM MAAA in non-MCS and MCS patients correlated well with an accuracy of 100 and 94.4%, respectively. MAActivator >40 had poor correlation with an accuracy of 37.5%. Irrespective of MAActivator value, TPM AA inhibition expressed in percent of inhibition had poor accuracy. When used with proper guidelines for interpretation, specifically when MAActivator ≤ 40 mm, TPM is a suitable and reliable test to use for MCS patients on aspirin

High Molecular Weight von Willebrand Factor Multimer Loss and Bleeding in Patients with Short-Term Mechanical Circulatory Support Devices: A Case Series.

Acquired von Willebrand syndrome (VWS) due to loss of high-molecular-weight multimers (HMWMs) has been reported with longer term mechanical devices and is associated with mucosal bleeding, a primary hemostasis type of bleeding. However, little is known whether a similar defect occurs in patients with short-term mechanical circulatory support (STMCS) devices. We reviewed von Willebrand factor (VWF) profiles in patients with STMCS devices who underwent VWS workup from December 2015 to March 2017 at an academic quaternary care hospital. There were a total of 18 patients (57.0 ± 12.7 years old; 83.3% male) including nine with mucosal bleeding and nine with decreasing hemoglobin. The STMCS devices included Impella (n = 11), Impella and right ventricular assist device (n = 2), and an extracorporeal membrane oxygenator (n = 5). The mean HMWM by quantitative VWF multimer analysis was 3.6% ± 1.3% (normal cutoff: 18-34%). In all 10 cases in which VWF activity, fibrinogen, factor VIII, or VWF antigen level were obtained, they were either normal or elevated. All cases demonstrated high normal or elevated levels of low molecular weight multimers (LMWMs). These findings are consistent with type 2 VWS (qualitative defect). This is the first study that quantitatively describes STMCS device-associated HMWM loss, which may contribute to mucosal bleeding. This finding may have implications for intraoperative management during implantation of longer term devices or heart transplantation or other surgery while on STMCS

Left Ventricular Reconstruction for Postinfarction Left Ventricular Aneurysm: Review of Surgical Techniques.

Different surgical techniques, each with its own advantages and disadvantages, have been used to reverse adverse left ventricular remodeling due to postinfarction left ventricular aneurysm. The most appropriate surgical technique depends on the location and size of the aneurysm and the scarred tissue, the patients preoperative characteristics, and surgeon preference. This review covers the reconstructive surgical techniques for postinfarction left ventricular aneurysm

Heart transplantation in patients from socioeconomically distressed communities.

BACKGROUND: Studies examining heart transplantation disparities have focused on individual factors such as race or insurance status. We characterized the impact of a composite community socioeconomic disadvantage index on heart transplantation outcomes. METHODS: From the Scientific Registry of Transplant Recipients (SRTR), we identified 49,340 primary, isolated adult heart transplant candidates and 32,494 recipients (2005-2020). Zip code-level socioeconomic disadvantage was characterized using the Distressed Community Index (DCI: 0-most prosperous, 100-most distressed) based on education, poverty, unemployment, housing vacancies, median income, and business growth. Patients from distressed communities (DCI ≥ 80) were compared to all others. RESULTS: Patients from distressed communities were more often non-white, less educated, and had public insurance (all p < 0.01). Distressed patients were more likely to require ventricular assist devices at listing (29.4 vs 27.1%) and before transplant (44.8 vs 42.0%, both p < 0.001), and they underwent transplants at lower-volume centers (23 vs 26 cases/year, p < 0.01). Distressed patients had higher 1-year waitlist mortality or deterioration (12.3% [95% confidence interval (CI) 11.6-13.0] vs 10.9% [95% CI 10.5-11.3]) and inferior 5-year survival (75.3% [95% CI 74.0-76.5] vs 79.5% [95% CI 79.0-80.0]) (both p < 0.001). After adjustment, living in a distressed community was independently associated with an increased risk of waitlist mortality or deterioration hazard ratio (HR 1.10, 95% CI 1.02-1.18) and post-transplant mortality (HR 1.13, 95% CI 1.06-1.20). CONCLUSIONS: Patients from socioeconomically distressed communities have worse waitlist and post-transplant mortality. These findings should not be used to limit access to heart transplantation, but rather highlight the need for further studies to elucidate mechanisms underlying the impact of community-level socioeconomic disparity

Heart transplantation in the era of the SARS-CoV-2 pandemic: Is it safe and feasible?

As the SARS-CoV-2-pandemic continues to unfold, the number of heart transplants completed in the United States has been declining steadily. The current case series examines the immediate short-term outcomes of seven heart transplant recipients transplanted during the SARS-CoV-2 pandemic. We hope to illustrate that with proper preparation, planning, and testing, heart transplantation can be continued during a pandemic. We assessed 7 patients transplanted from March 4, 2020, to April 15, 2020. The following endpoints were noted: in-hospital survival, in-hospital freedom from rejection, in-hospital nonfatal major cardiac adverse events (NF-MACE), severe primary graft dysfunction, hospital length of stay, and ICU length of stay. There were no expirations throughout the hospital admission. In addition, there were no patients with NF-MACE or treated rejection, and 1 patient developed severe primary graft dysfunction. Average length of stay was 17.2 days with a standard deviation of 5.9 days. ICU length of stay was 7.7 days with a standard deviation of 2.3 days. Despite the decreasing trend in completed heart transplants due to SARS-CoV-2, heart transplantation appears to be feasible in the immediate short term. Further follow-up is needed, however, to assess the impact of SARS-CoV-2 on post-heart transplant outcomes months after transplantation

Heart retransplant recipients with renal dysfunction benefit from simultaneous heart-kidney transplantation.

BACKGROUND: Given ongoing donor shortages, appropriate patient selection for dual-organ transplantation is critical. We evaluated outcomes of heart retransplant with simultaneous kidney transplant (HRT-KT) vs isolated heart retransplant (HRT) across varying levels of renal dysfunction. METHODS: The United Network for Organ Sharing database identified 1189 adult patients undergoing heart retransplantation between 2005 and 2020. Recipients undergoing HRT-KT (n = 251) were compared to those undergoing HRT (n = 938). The primary outcome was 5-year survival; subgroup analyses and multivariable adjustment were performed utilizing the following 3 estimated glomerular filtration (eGFR) groups: <30 ml/min/1.73m2, 30-45 ml/min/1.73m2, and >45 ml/min/1.73m2. RESULTS: HRT-KT recipients were older and had longer waitlist times, longer inter-transplant periods, and lower eGFR levels. HRT-KT recipients were less likely to require pretransplant ventilator (1.2% vs 9.0%, p < 0.001) or ECMO (2.0% vs 8.3%, p < 0.001) support but were more likely to have severe functional limitation (63.4% vs 52.6%, p = 0.001). After retransplantation, HRT-KT recipients had less treated acute rejection (5.2% vs 9.3%, p = 0.02) and more dialysis requirement (29.1% vs 20.2%, p < 0.001) before discharge. Survival at 5-years was 69.1% after HRT and 80.5% after HRT-KT (p < 0.001). After adjustment, HRT-KT was associated with improved 5-year survival among recipients with eGFR <30 ml/min/1.73m2 (HR:0.42, 95% CI: 0.26-0.67) and 30 to 45 ml/min/1.73m2 (HR:0.29, 95% CI 0.13-0.65), but not among those with eGFR>45 ml/min/1.73sm2 (HR 0.68, 95% CI 0.30-1.54). CONCLUSION: Simultaneous kidney transplantation is associated with improved survival following heart retransplantation in patients with eGFR <45 ml/min/1.73m2 and should be strongly considered to optimize organ allocation stewardship

Simultaneous heart-kidney transplant in patients with borderline estimated glomerular filtration rate without dialysis dependency.

BACKGROUND: Appropriate patient selection for simultaneous heart-kidney transplantation (sHK) in patients with moderate renal dysfunction remains challenging. METHODS: From the United Network for Organ Sharing database (2003-2020), we identified 5678 adults with an estimated pre-transplant glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 and no pre-transplant dialysis. Patients undergoing sHK (n = 293) were compared with those undergoing heart transplantation alone (n = 5385) using 1:3 propensity score matching. RESULTS: The sHK utilization rate increased from 1.8% in 2003 to 12.2% in 2020 (p < .001). After matching, 1 and 5-year survival was 87.7% (95% confidence interval [CI] 83.3-91.0) and 80.0% (95% CI 74.2-84.6) after sHK, and 87.3% (95% CI 85.2-89.1) and 71.8% (95% CI 68.4-74.9) after heart transplant alone (p = .04). In the subgroup analysis, sHK was associated with a 5-year survival benefit only in patients with 30 < eGFR ≤ 35 mL/min/1.73 m2 (p = .05) but not in those with 35 < eGFR < 45 mL/min/1.73 m2 (p = .45). Patients who underwent heart transplants alone also had a higher incidence of becoming chronic dialysis-dependent after transplant within 5-year follow-up (10.2%, 95% CI 8.0-12.6 vs. 3.8%, 95% CI 1.7-7.1, p = .004). The 5-year incidence of subsequent kidney waitlisting and transplants after heart transplants alone was 5.6% and 1.9%, respectively. CONCLUSION: Among propensity-matched patients without pre-transplant dialysis, compared to heart transplants alone, sHK had improved 5-year survival in those with 30 < eGFR ≤ 35 but not in those with 35 < eGFR < 45 mL/min/1.73 m2 . One-year survival was similar irrespective of eGFR. Receiving a kidney after a heart transplant alone is rare under the current allocation system