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.

Heart Failure at Admission Complicating ST-Elevation Myocardial Infarction in a Middle-Income Country. Experience of the ARGEN-IAM-ST Registry.

Despite advances in the management of ST-elevation myocardial infarction (STEMI), when associated with heart failure (HF) its prognosis remains ominous. This study assessed the differences in admission and mortality of HF complicating STEMI at admission (HFad) in a middle-income country. Data from the National Registry of STEMI of Argentina (ARGEN-IAM-ST) from January 1, 2016, to September 30, 2020, were analyzed. HFad was defined by the identification of Killip/Kimball ≥2 at admission. About 3174 patients were analyzed (22.3% had HFad). Patients with HFad were older, more often women, hypertensive, and diabetic. Received less reperfusion (87.6% vs 92.6%, P < 0.001) and had increased in-hospital mortality (28.4% vs 3.0%, P < 0.001). In multivariate analysis HFad was an independent predictor of death (OR: 4.88 [95%CI: 3.33-7.18], P < 0.001) and reperfusion adjusted to HFad was associated with lower mortality (OR: 0.57 [95%CI: 0.34-0.95], P = 0.03). HFad in STEMI is associated with a worse clinical profile, receives fewer reperfusion strategies, and carries a higher risk of in-hospital mortality while reperfusion reduces mortality.

Retrospective analysis of the impact of pre-transplant implantable cardioverter-defibrillator status on long-term prognosis in heart transplant patients.

BACKGROUND: Sudden cardiac death (SCD) post-heart transplantation affects 8%-35% of patients; however, the risk profile remains to be completely elucidated. While pre-transplant ICDs are typically removed during transplantation, no information exists to suggest if this pre-transplant risk stratification is also associated with post-transplant outcomes. The objective of this study was to assess the impact of pre-transplant ICD status on long-term prognosis post-heart transplant. METHODS: The United Network for Organ Sharing registry was queried for all adult heart transplant recipients from 2010 to 2018. Patients were categorized as with versus without ICD prior to heart transplantation. Survival was compared using Kaplan-Meier analysis. Proportional hazards regression analysis assessed the impact of ICDs adjusting for clinical and demographic covariates. RESULTS: Of 19 026 patients included, 78.6% (n = 14 960) had received an ICD at time of registration. Patients with an ICD were older [54.9 (±11.6) years vs. 48.6 (±15.3) years, p < .001], less likely to be female [25.7% (n = 3842) vs. 31.2% (n = 1269), p < .001], and more commonly diabetic [29.3% (n = 4376) vs 23.5% (n = 954), p < .001]. Kaplan-Meier analysis showed no difference in unadjusted survival trajectory by ICD status (chi-square = .48, p = .49). Survival was unrelated to ICD status in the multivariable model (HR = .98; 95% CI .90-1.07). CONCLUSIONS: Patients receiving an ICD pre-transplant had a higher prevalence of risk factors for SCD than non-ICD patients, yet ICD status prior to heart transplantation was not associated with a change in long-term prognosis post-heart transplantation.

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.

Detection of cytomegalovirus disease by real-time quantitative PCR targeting immediate early gene (ppUL83) in different samples among post-renal-transplant recipients.

Renal transplantation is a treatment option for end-stage renal disease (ESRD). Cytomegalovirus (CMV) infection was analysed among symptomatic and asymptomatic post-renal-transplant recipients (PRTRs). A total of 30 PRTRs were enrolled. DNA was extracted and quantitative real-time PCR for CMV (CMV R-Gene, France) targeting ppUL83 gene was performed on whole blood, urine and saliva. The detection rate of CMV was found to be 27% (n = 8) in different samples, including whole blood, urine and saliva. Among 30 PRTRs, 53% (n = 16) of the PRTRs did not shed virus in saliva. About 7% of CMV was detected only in saliva among PRTRs who were symptomatic.

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.

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.

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.

Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung.

Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, Western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of pulmonary artery pressure (mean pulmonary artery pressure/mm Hg: 35.9±1.8 versus 14.8±2.0, control; P<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary artery pressure to 22.6±0.8 mm Hg (P<0.001). Substantially higher levels of peroxynitrite and significant loss of PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF.

Biventricular Mechanical Circulatory Support Does Not Prevent Delayed Myocardial Ventricular Rupture following Myocardial Infarction.

Cardiogenic shock and myocardial rupture can complicate an acute myocardial infarction (AMI). A case is reported in which a 58-year-old male with an acute inferior myocardial infarction required placement of biventricular assist device for hemodynamic support eight days after the onset of his AMI; eleven days after his AMI, the patient developed abrupt onset of hemodynamic instability with massive bleeding from his chest tube due to delayed free wall myocardial rupture that was discovered when he was taking emergently to the operating room. Myocardial rupture in patients with a ventricular assist device should be considered in the differential diagnosis in the event of acute hemodynamic compromise. A high level of suspicion for such a complication should prompt aggressive and emergent actions including surgery. We present a case of delayed free wall myocardial rupture following an acute inferior wall myocardial infarction in a patient with biventricular mechanical circulatory support.

Patients with low compared with high body mass index gain more weight after implantation of a continuous-flow left ventricular assist device.

BACKGROUND: Patterns of weight change after implantation of a continuous-flow left ventricular assist device (CF-LVAD) can affect transplant candidacy and may influence outcomes. We evaluated changes in weight over a 24-month period from a national LVAD clinical trial database. METHODS: A retrospective analysis was performed of 896 patients enrolled into the HeartMate II Clinical trials for bridge-to-transplant and destination therapy from March 2005 to January 2009. The patients were divided into 4 groups: underweight (body mass index [BMI] <18.5 [kg/m(2)]); normal (BMI 18.5 to 29.9); obese (BMI 30 to 34.9); and extremely obese (BMI ≥ 35). Baseline BMI was compared with BMI at 6 months and 24 months after implant. BMI change >10% of baseline was considered clinically significant. RESULTS: At 6 months, underweight and normal-weight patients had significant increases in BMI, with effects sustained up to 24 months (p < 0.01). Underweight patients gained weight most often, with 75% showing clinically meaningful weight gain at 24 months. Obese and extremely obese patients, in contrast, did not experience weight change over the same period. Pre-albumin levels improved from baseline to 6 months in all patients. CONCLUSIONS: Underweight and normal-weight patients had an increase in BMI after LVAD implantation, and these changes persisted through 24 months. The BMIs of obese and extremely obese patients remained unchanged. Nutritional status improved in all groups.

Dysregulation of PTEN in cardiopulmonary vascular remodeling induced by pulmonary hypertension.

Pulmonary hypertension (PH) is a disorder of lung vasculature characterized by arterial narrowing. Phosphatase-and-tensin homolog on chromosome 10 (PTEN), associated in the progression of multiple cancers, is implicated in arterial remodeling. However, the involvement of PTEN in PH remains unclear. The objective of the present study was to determine the role of PTEN in pulmonary vascular remodeling using established models of PH. The study used rat models of PH, induced by monocrotaline (MCT) administration (60 mg/kg) or continuous hypoxic exposure (10% oxygen) for 3 weeks. Pulmonary artery smooth muscle cells (SMCs) were used for in vitro confirmation. Development of PH was verified by hemodynamic, morphological and histopathology analyses. PTEN and key downstream proteins in pulmonary and cardiac tissues were analyzed by western blotting and RT-PCR. PTEN was significantly decreased (MCT, 53%; Hypoxia, 40%), pAkt was significantly increased (MCT, 42%; Hypoxia, 55%) in tissues of rats with PH. Similar results were observed in SMCs exposed to hypoxia (1% oxygen) for 48 h. Ubiquitination assay showed that PTEN degradation occurs via proteasomal degradation pathway. Western blotting demonstrated a significant downregulation of cell-cycle regulatory proteins p53 and p27, and upregulation of cyclin-D1 in the lungs of both models. The results showed that PTEN-mediated modulation of PI3K pathway was independent of the focal adhesion kinase and fatty acid synthase. The study, for the first time, established that PTEN plays a key role in the progression of pulmonary hypertension. The findings may have potential for the treatment of pulmonary hypertension using PTEN as a target.

Extremes of body mass index do not impact mid-term survival after continuous-flow left ventricular assist device implantation.

BACKGROUND: Extremes of body mass index (BMI) are often considered contraindications to use of a left ventricular assist device (LVAD), but data regarding outcomes across the spectrum of BMI are limited. We sought to assess the association of BMI with survival and major morbidity after continuous-flow (CF) LVAD implantation. METHODS: Patients (n = 896) enrolled in the HeartMate II LVAD bridge-to-transplantation and destination therapy trials were divided into 4 BMI groups: underweight (<18.5 kg/m(2)); normal (18.5 kg/m(2) ≤ BMI < 30 kg/m(2)); obese (30 kg/m(2) ≤ BMI < 35 kg/m(2)); and extremely obese (≥35 kg/m(2)). The association of BMI with survival was tested using Kaplan-Meier analysis and proportional hazards regression. Major adverse events were compared using Poisson's regression and chi-square tests. RESULTS: At implantation, 48 (5%) patients were underweight, 596 (67%) normal weight, 164 (18%) obese and 88 (10%) extremely obese. BMI extremes were associated with differences in creatinine, albumin, age, central venous pressure and etiology. BMI was not associated with survival in the univariate analysis (p = 0.83) or in adjusted models (extremely obese: hazard ratio [HR] 1.29, p = 0.231; obese: HR 0.94, p = 0.723; underweight: HR 1.23, p = 0.452). Underweight patients were more likely to have bleeding events (p < 0.001), whereas extremely obese patients had higher rates of device-related infection (p = 0.041) and rehospitalization (p = 0.014). CONCLUSIONS: Overall survival in patients receiving CF LVAD is similar across BMI categories. Carefully selected patients at both extremes of BMI have good mid-term survival after LVAD and should be considered for LVAD implantation relative to overall risk profile.

Mechanical circulatory support for the visually impaired: is it appropriate?

Long-term mechanical circulatory support devices, especially left ventricular assist devices, are being increasingly utilized in the management of end-stage heart failure either as bridge to heart transplantation, recovery or as destination therapy. However, current technology for controllers and alarm systems for left ventricular assist devices does not permit their implantation in eligible patients with visual impairment. We report two patients in whom the decrease in visual acuity was a significant factor in determining eligibility for long-term mechanical circulatory support.