Relationship between donor ejection fraction, left ventricular wall thickness and mortality in heart transplants recipients.

This study explored the impact of donor left ventricular ejection fraction (EF) and left ventricular wall thickness (LVWT) on mortality among heart transplant (HTx) recipients. Utilizing data from the United Network for Organ Sharing (UNOS) registry, adult HTx recipients between 2006-2022 were analyzed. Patients were categorized into four groups based on donor EF(>50 % or ≤50 %) and LVWT(<1.4 cm or ≥1.4 cm). 21,012 patients were included. There were significant differences in baseline characteristics among the groups. Unadjusted mortality was 6.3 %, 6.0 %, 6.0 %, and 2.4 %(p=0.86) at 30-days; 16.2 %, 13.5 %, 16.8 %, and 7.3 %(p=0.08) at 1-year; and 32.2 %, 29.2 %, 35.4 %, and 29.0 %(p=0.18) at 5-years, respectively. In addition, adjusted mortality did not differ across the groups. There were no significant differences in recipient mortality in groups based on donor EF and LVWT. Expanding the donor selection criteria would allow for increase in the donor pool and assist in decreasing the mortality, while on the waitlist for HTx.

Incidental detection of pheochromocytoma during workup for symptomatic aortic stenosis: A case report and management discussion.

Pheochromocytoma patients with high levels of circulating catecholamines are at risk of cardiovascular complications related to hypertensive emergencies and subsequent organ damage. A patient with concomitant aortic stenosis and pheochromocytoma has compounded risk of cardiovascular complications, especially during surgery, which complicates medical decision-making. We report a patient with Turner syndrome and congenital heart defects (CHDs) who was incidentally discovered to have a pheochromocytoma during workup of symptomatic severe bioprosthetic aortic stenosis. Management included laparoscopic adrenalectomy followed by Transcatheter Aortic Valve Replacement (TAVR). We describe considerations for multidisciplinary management in this complex clinical case.

Cardiopulmonary Injury in the Syrian Hamster Model of COVID-19.

The Syrian hamster has proved useful in the evaluation of therapeutics and vaccines for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). To advance the model for preclinical studies, we conducted serial sacrifice of lungs, large pulmonary vessels, and hearts from male and female Syrian hamsters for days 1-4, and 8 post-infection (dpi) following infection with a high dose of SARS-CoV-2. Evaluation of microscopic lung histopathology scores suggests 4 and 8 dpi as prime indicators in the evaluation of moderate pathology with bronchial hyperplasia, alveolar involvement and bronchiolization being key assessments of lung disease and recovery, respectively. In addition, neutrophil levels, red blood cell count and hematocrit showed significant increases during early infection. We present histological evidence of severe damage to the pulmonary vasculature with extensive leukocyte transmigration and the loss of endothelial cells and tunica media. Our evidence of endothelial and inflammatory cell death in the pulmonary vessels suggests endothelialitis secondary to SARS-CoV-2 epithelial cell infection as a possible determinant of the pathological findings along with the host inflammatory response. Lastly, pathological examination of the heart revealed evidence for intracardiac platelet/fibrin aggregates in male and female hamsters on 8 dpi, which might be indicative of a hypercoagulative state in these animals.

PTEN as a Therapeutic Target in Pulmonary Hypertension Secondary to Left-heart Failure: Effect of HO-3867 and Supplemental Oxygenation.

Pulmonary hypertension (PH) is a condition when the pressure in the lung blood vessels is elevated. This leads to increase in thickness of the blood vessels and increases the workload of the heart and lungs. The incidence and prevalence of PH has been on the increase in the last decade. It is estimated that PH affects about 1% of the global population and about 10% of individuals >65 years of age. Of the various types, Group 2 PH is the most common type seen in the elderly population. Fixed PH or PH refractive to therapies is considered a contraindication for heart transplantation; the 30-day mortality in heart transplant recipients is significantly increased in the subset of this population. In general, the pathobiology of PH involves multiple factors including hypoxia, oxidative stress, growth factor receptors, vascular stress, etc. Hence, it is challenging and important to identify specific mechanisms, diagnosis and develop effective therapeutic strategies. The focus of this manuscript is to review some of the important pathobiological processes and mechanisms in the development of PH. Results from our previously reported studies, including targeted treatments along with some new data on PH secondary to left-heart failure, are presented.

Targeting ticagrelor: a novel therapy for emergency reversal.

Newer P2Y12 inhibitors are prescribed in place of clopidogrel for patients with acute coronary syndrome (ACS) and are associated with significant bleeding risks. Currently, limited options exist for the management of life-threatening bleeding or acute reversal for patients on P2Y12 inhibitor therapy, specifically ticagrelor. Various interventions, including platelet transfusion and desmopressin, have been studied for ticagrelor reversal demonstrating limited success. PB2452 is a novel monoclonal antibody which binds to both ticagrelor and its active metabolite resulting in a rapid return of platelet aggregation. PB2452 has been studied in animal models and, most recently, in a Phase I trial in healthy volunteers. In animal models, PB2452 displayed rapid reversal of ticagrelor and its metabolites and return to near normal levels of platelet aggregation within 60 min. In healthy human volunteers, cohorts that received higher dose bolus and infusions of PB2452 over 12-16 h resulted in maximal and sustained reversal of ticagrelor inhibition of platelet aggregation. While it is currently not US Food and Drug Administration approved, future Phase 2 and 3 studies are currently underway that may lead to new directions for patients on ticagrelor therapy who require urgent reversal.

Does recipient work status pre-transplant affect post-heart transplant survival? A United Network for Organ Sharing database review.

BACKGROUND: Recipient-related factors, such as education level and type of health insurance, are known to affect heart transplantation outcomes. Pre-operative employment status has shown an association with survival in abdominal organ transplant patients. We sought to evaluate the effect of work status of heart transplant (HTx) recipients at the time of listing and at the time of transplantation on short- and long-term survival. METHODS: We evaluated the United Network for Organ Sharing (UNOS) registry for all adult HTx recipients from 2001 to 2014. Recipients were grouped based on their work status at listing and at heart transplantation. Kaplan-Meier estimates illustrated 30-day, 1-year, 5-year, and 10-year survival comparing working with non-working groups. The Cox proportional hazards regression model was applied to adjust for covariates that could potentially confound the post-transplantation survival analysis. RESULTS: Working at listing for HTx was not significantly associated with 30-day and 1-year survival. However, 5- and 10-year mortality were 14.5% working vs 19.8% not working (p < 0.0001) and 16% working vs 26% not working (p < 0.0001), respectively. Working at HTx appeared to be associated with a survival benefit at every time interval, with a trend toward improved survival at 30 days and 1 year and a significant association at 5 and 10 years. Kaplan-Meier analysis demonstrated a 5% and 10% decrease in 5- and 10-year mortality, respectively, for the working group compared with the group not working at transplantation. The Cox proportional hazards regression model showed that working at listing and working at transplantation were each associated with decreased mortality (hazard ratio [HR] = 0.8, 95% confidence interval [CI] 0.71 to 0.91; and HR = 0.76, 95% CI 0.65 to 0.89, respectively). CONCLUSIONS: This study is the first analysis of UNOS STAR data on recipient work status pre-HTx demonstrating: (1) an improvement in post-transplant survival for working HTx candidates; and (2) an association between working pre-HTx and longer post-HTx survival. Given that work status before HTx may be a modifiable risk factor for better outcomes after HTx, we strongly recommend that UNOS consider these important findings for moving forward this patient-centered research on work status. Working at listing and working at HTx are associated with long-term survival benefits. The association may be reciprocal, where working identifies less ill patients and also improves well-being. Consideration should be given to giving additional weight to work status during organ allocation. Work status may also be a modifiable factor associated with better post-HTx outcomes.

Circulating platelet aggregates damage endothelial cells in culture.

BACKGROUND: Presence of circulating endothelial cells (CECs) in systemic circulation may be an indicator of endothelial damage and/or denudation, and the body's response to repair and revascularization. Thus, we hypothesized that aggregated platelets (AgPlts) can disrupt/denude the endothelium and contribute to the presence of CEC and EC-derived particles (ECDP). METHODS: Endothelial cells were grown in glass tubes and tagged with/without 0.5 µm fluorescent beads. These glass tubes were connected to a mini-pump variable-flow system to study the effect of circulating AgPlts on the endothelium. ECs in glass tube were exposed to medium alone, nonaggregated platelets (NAgPlts), AgPlts, and 90 micron polystyrene beads at a flow rate of 20 mL/min for various intervals. Collected effluents were cultured for 72 h to analyze the growth potential of dislodged but intact ECs. Endothelial damage was assessed by real time polymerase chain reaction (RT-PCR) for inflammatory genes and Western blot analysis for von Willebrand factor. RESULTS AND CONCLUSION: No ECs and ECDP were observed in effluents collected after injecting medium alone and NAgPlts, whereas AgPlts and Polybeads drastically dislodged ECs, releasing ECs and ECDP in effluents as the time increased. Effluents collected when endothelial cell damage was seen showed increased presence of von Willebrand factor as compared to control effluents. Furthermore, we analyzed the presence of ECs and ECDPs in heart failure subjects, as well as animal plasma samples. Our study demonstrates that circulating AgPlts denude the endothelium and release ECs and ECDP. Direct mechanical disruption and shear stress caused by circulating AgPlts could be the underlying mechanism of the observed endothelium damage.

Lung transplantation with lungs from older donors: an analysis of survival in elderly recipients.

BACKGROUND: The average ages of lung transplant (LTx) recipients and donors are increasing. With older recipients considered to be especially at high risk of posttransplant mortality, we sought to determine whether the use of allografts from older donors affects survival among older patients undergoing LTx. METHODS: The United Network for Organ Sharing registry was used to identify patients aged 65-80 y receiving a first-time LTx between 1987 and 2013. Survival analysis examined implications of a donor-recipient age difference >10 y using Cox proportional hazards regression. RESULTS: The cohort selected for analysis included 3227 elderly LTx recipients, of whom 263 (8.15%) had donors within 10 y of their age at transplantation. Univariate Cox models found no differences with LTx involving donors at least 10 y younger than the recipient with respect to overall survival (hazard ratio = 0.979; 95% confidence interval [CI] = 0.807-1.188; P = 0.831) or conditional survival past 1 y (hazard ratio = 1.067; 95% CI = 0.819-1.391; P = 0.629) relative to LTx involving donors within 10 y of an elderly recipient's age. These findings were substantiated in multivariate analysis adjusting for potential confounders. CONCLUSIONS: In elderly LTx recipients aged 65-80 y at transplantation, intermediate-term survival was not influenced by donor age. For the viable elderly LTx candidate, a carefully selected older donor should be considered to increase donor availability.

Surgical considerations for the explantation of the Parachute left ventricular partitioning device and the implantation of the HeartMate II left ventricular assist device.

Chronic heart failure is the leading cause of death in the world. With newer therapies, the burden of this disease has decreased; however, a significant number of patients remain refractive to existing therapies. Myocardial infarction often leads to ventricular remodeling and eventually contributes to heart failure. The Parachute™ (Cardiokinetix, Menlo Park, CA) is the first device designed for percutaneous ventricular restoration therapy, which reduces left ventricular volume and minimizes the risk of open surgical procedures. For the first time, we report a case of explantation of the Parachute ventricular partitioning device and transition to a HeartMate II™ left ventricular assist device and the surgical considerations for a successful outcome.

Successful heart transplantation using a donor heart afflicted by takotsubo cardiomyopathy.

Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.

The aortic stenosis complex: aortic valve, atherosclerosis, aortopathy.

BACKGROUND: Aortic stenosis may be related to coronary atherosclerosis in patients with tricuspid aortic valve, while aortic dilatation often is present in patients with bicuspid aortic valve. We sought to define associations among aortic stenosis, coronary atherosclerosis, and thoracic aortic aneurysm in patients with tricuspid or bicuspid aortic valve undergoing surgery for aortic stenosis in a large referral medical center. METHODS: Two hundred seventy patients with severe aortic stenosis (tricuspid 175, bicuspid 95) undergoing surgical aortic valve replacement (AVR) were studied. RESULTS: Coronary artery bypass grafting (CABG) surgery plus AVR was required more often in tricuspid compared to bicuspid aortic valve [62.2% versus 26.3%; p<0.0001; odds ratio 4.5, confidence interval (CI) 2.5-8.3]. The incidence of coronary atherosclerosis requiring CABG in bicuspid aortic valve (26.3%) was greater than that expected in the general population for similar age. Thoracic aorta surgery due to aortic aneurysm plus AVR was performed more often in bicuspid compared to tricuspid aortic valve (27.3% versus 3.4%; p<0.0001; odds ratio 7.7, CI 3.0-22.1). The incidence of ascending aorta aneurysm requiring surgery, however, was not more common in tricuspid aortic valve (3.4%) to that expected in the general population for similar age. CONCLUSION: Incidence of coronary atherosclerosis is high in patients with aortic stenosis, both in those with tricuspid and bicuspid aortic valve. Incidence of ascending aortic aneurysm is high in patients with bicuspid, but not those with tricuspid aortic valve. These findings should be taken into consideration in the evaluation and management of patients with the aortic stenosis complex.

Elevated transaortic valvular gradients after combined aortic valve and mitral valve replacement: an intraoperative dilemma.

High transaortic valvular gradients, after combined aortic valve and mitral valve replacement, require prompt intraoperative diagnosis and appropriate management. The presence of high transaortic valvular gradients after cardiopulmonary bypass, in this setting, can be secondary to the following conditions: prosthesis dysfunction, left ventricular outflow tract obstruction, supravalvular obstruction, prosthesis-patient mismatch, hyperkinetic left ventricle from administration of inotropes, left ventricular intracavitary gradients, pressure recovery phenomenon, and increased transvalvular blood flow resulting from hyperdynamic circulation or anemia. Transesophageal echocardiography is an extremely useful tool for timely diagnosis and treatment of this complication. We describe a case of a critically ill patient with endocarditis and acute lung injury, who presented for combined aortic valve and mitral valve replacement. Transesophageal echocardiographic assessment, post-cardiopulmonary bypass, revealed high transaortic valvular gradients due to encroachment of the mitral prosthesis strut on the left ventricular outflow tract, which was compounded by a small, hypertrophied, and hyperkinetic left ventricle. Discontinuation of inotropic support, administration of fluids, phenylephrine, and esmolol led to resolution of the high gradients and prevented further surgery.

Impact of induction immunosuppression on survival in heart transplant recipients: a contemporary analysis of agents.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing (UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction (NONE) or the contemporary agents (INDUCED) of either: basiliximab/daclizumab (IL-2Rab), alemtuzumab, or ATG/ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized. RESULTS: Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant (HR = 0.948; 95% CI: 0.850-1.058; p = 0.341). CONCLUSION: In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates.

Laparoscopic sleeve gastrectomy in morbidly obese patients with end-stage heart failure and left ventricular assist device: medium-term results.

BACKGROUND: Morbid obesity precludes patients with end-stage heart failure from becoming cardiac transplant candidates. This study evaluates the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) as a means to transplant candidacy in such patients. METHODS: Morbidly obese patients with end-stage heart failure, who were ineligible for cardiac transplantation and underwent LSG between 2008 and 2013, were reviewed retrospectively. Demographic characteristics, perioperative details, percentage of excess weight loss (%EWL), and status of transplant candidacy were analyzed. RESULTS: Six patients (3 men) with end-stage heart failure and morbid obesity underwent LSG. Three patients (50%) had a left ventricular assist device (LVAD) in place at the time of surgery. Median age was 34 (31-66) years and mean preoperative body mass index (BMI) was 47.6±3.0 kg/m2. Median operative time was 90 (66-141) minutes, with a median length of stay of 7 (4-16) days. There were no perioperative deaths. One patient suffered a spontaneous flank hematoma. The same patient also had thrombosis of the LVAD pump at 3 weeks postoperatively, requiring an uneventful device exchange. At median follow-up of 22 (12-70) months, the mean %EWL was 51.4±10.3% with a decrease in BMI to 34.3±2.4 kg/m2 (P<.05). All patients had lost sufficient weight to become transplant eligible within 12 months of surgery. Two patients had undergone successful transplantation and another 2 were on the transplant list. CONCLUSION: LSG appears to be a safe, technically feasible, and effective method for obtaining adequate weight loss in morbidly obese patients with end-stage heart failure and mechanical circulatory support, subsequently improving their access to cardiac transplantation. This is the largest case series to date of this high-risk group of patients undergoing LSG.

Donor selection in heart transplantation.

There is increased scrutiny on the quality in health care with particular emphasis on institutional heart transplant survival outcomes. An important aspect of successful transplantation is appropriate donor selection. We review the current guidelines as well as areas of controversy in the selection of appropriate hearts as donor organs to ensure optimal outcomes. This decision is paramount to the success of a transplant program as well as recipient survival and graft function post-transplant.

Endovascular abdominal aortic aneurysm repair in patients with ventricular assist devices.

Long-term mechanical circulatory support devices are currently an established therapy for the management of end-stage heart failure, and current evidence supports their superiority in comparison to maximal medical therapy in these patients. Screening for peripheral arterial disease and abdominal aortic aneurysm (AAA) before left ventricular assist device (LVAD) implantation is recommended. Although repair of AAA before or during LVAD placement has been reported, management of patients with AAA after LVAD implantation needs to be further investigated. We describe our management and operative strategies in 2 patients on destination LVAD therapy who underwent successful endovascular AAA repair.

Type of Valvular Heart Disease Requiring Surgery in the 21st Century: Mortality and Length-of-Stay Related to Surgery.

AIM: While the incidence of rheumatic heart disease has declined dramatically over the last half-century, the number of valve surgeries has not changed. This study was undertaken to define the most common type of valvular heart disease requiring surgery today, and determine in-hospital surgical mortality and length-of-stay (LOS) for isolated aortic or mitral valve surgery in a United States tertiary-care hospital. METHODS: Patients with valve surgery between January 2002 to June 2008 at The Ohio State University Medical Center were studied. Patients only with isolated aortic or mitral valve surgery were analyzed. RESULTS: From 915 patients undergoing at least aortic or mitral valve surgery, the majority had concomitant cardiac proce-dures mostly coronary artery bypass grafting (CABG); only 340 patients had isolated aortic (n=204) or mitral (n=136) valve surgery. In-hospital surgical mortality for mitral regurgitation (n=119), aortic stenosis (n=151), aortic insufficiency (n=53) and mitral stenosis (n=17) was 2.5% (replacement 3.4%; repair 1.6%), 3.9%, 5.6% and 5.8%, respectively (p=NS). Median LOS for aortic insufficiency, aortic stenosis, mitral regurgitation, and mitral stenosis was 7, 8, 9 (replacement 11.5; repair 7) and 11 days, respectively (p<0.05 for group). In-hospital surgical mortality for single valve surgery plus CABG was 10.2% (p<0.005 compared to single valve surgery). CONCLUSIONS: Aortic stenosis and mitral regurgitation are the most common valvular lesions requiring surgery today. Surgery for isolated aortic or mitral valve disease has low in-hospital mortality with modest LOS. Concomitant CABG with valve surgery increases mortality substantially. Hospital analysis is needed to monitor quality and stimulate improvement among Institutions.

First evidence of sternal wound biofilm following cardiac surgery.

Management of deep sternal wound infection (SWI), a serious complication after cardiac surgery with high morbidity and mortality incidence, requires invasive procedures such as, debridement with primary closure or myocutaneous flap reconstruction along with use of broad spectrum antibiotics. The purpose of this clinical series is to investigate the presence of biofilm in patients with deep SWI. A biofilm is a complex microbial community in which bacteria attach to a biological or non-biological surface and are embedded in a self-produced extracellular polymeric substance. Biofilm related infections represent a major clinical challenge due to their resistance to both host immune defenses and standard antimicrobial therapies. Candidates for this clinical series were patients scheduled for a debridement procedure of an infected sternal wound after a cardiac surgery. Six patients with SWI were recruited in the study. All cases had marked dehiscence of all layers of the wound down to the sternum with no signs of healing after receiving broad spectrum antibiotics post-surgery. After consenting patients, tissue and/or extracted stainless steel wires were collected during the debridement procedure. Debrided tissues examined by Gram stain showed large aggregations of Gram positive cocci. Immuno-fluorescent staining of the debrided tissues using a specific antibody against staphylococci demonstrated the presence of thick clumps of staphylococci colonizing the wound bed. Evaluation of tissue samples with scanning electron microscope (SEM) imaging showed three-dimensional aggregates of these cocci attached to the wound surface. More interestingly, SEM imaging of the extracted wires showed attachment of cocci aggregations to the wire metal surface. These observations along with the clinical presentation of the patients provide the first evidence that supports the presence of biofilm in such cases. Clinical introduction of the biofilm infection concept in deep SWI may advance the current management strategies from standard antimicrobial therapy to anti-biofilm strategy.