Twenty-year survival following orthotopic heart transplantation in the United States.

BACKGROUND: This study evaluated 20-year survival after adult orthotopic heart transplantation (OHT). METHODS: The United Network of Organ Sharing Registry database was queried to study adult OHT recipients between 1987 and 1998 with over 20-year posttransplant follow-up. The primary and secondary outcomes were 20-year survival and cause of death after OHT, respectively. Multivariable logistic regression was used to identify significant independent predictors of long-term survival, and long-term survival was compared among cohorts stratified by number of predictors using Kaplan Meier survival analysis. RESULTS: 20,658 patients undergoing OHT were included, with a median follow-up of 9.0 (IQR, 3.2-15.4) years. Kaplan-Meier estimates of 10-, 15-, and 20-year survival were 50.2%, 30.1%, and 17.2%, respectively. Median survival was 10.1 (IQR, 3.9-16.9) years. Increasing recipient age (>65 years), increasing donor age (>40 years), increasing recipient body mass index (>30), black race, ischemic cardiomyopathy, and longer cold ischemic time (>4 h) were adversely associated with a 20-year survival. Of these 6 negative predictors, presence of 0 risk factors had the greatest 10-year (59.7%) and 20-year survival (26.2%), with decreasing survival with additional negative predictors. The most common cause of death in 20-year survivors was renal, liver, and/or multisystem organ failure whereas graft failure more greatly impacted earlier mortality. CONCLUSIONS: This study identifies six negative preoperative predictors of 20-year survival with 20-year survival rates exceeding 25% in the absence of these factors. These data highlight the potential for very long-term survival after OHT in patients with end-stage heart failure and may be useful for patient selection and prognostication.

Direct bridging to cardiac transplantation with the surgically implanted Impella 5.0 device.

This study evaluated outcomes of direct bridging to orthotopic heart transplantation (OHT) with the Impella 5.0 device. Adult recipients in the United Network for Organ Sharing registry bridged to OHT with the Impella 5.0 device between 2010 to 2018 were included. Outcomes included waitlist and post-transplant survival. A total of 236 patients were wait-listed with Impella 5.0 support, and 24% (n = 57) underwent bridge to OHT. Early and late post-transplant survival was excellent at 96.5% at 30 day, 93.8% at 90-day, and 90.3% at 1-year follow-up. Post-transplant complications were infrequent, but the most common were renal failure requiring dialysis (8.8%, n = 5), cerebrovascular accidents (1.8%, n = 1), and pacemaker implant (1.8%, n = 1). The rate of waitlist removal for death or clinical deterioration was 20.0% (n = 47); however, the majority of patients were bridged to OHT (24%, n = 57) or durable continuous-flow left ventricular assist device (37.0%, n = 87). The median time supported on the device, while waitlisted was 13 days (Interquartile range [IQR] 7, 20 days). The Impella 5.0 device can be used as a direct bridge to OHT with excellent survival and minimal post-transplant morbidity. Overall, these data support the utilization of Impella 5.0 as a bridge to OHT in select patients with refractory cardiogenic shock.

Left ventricular assist device implantation in patients with a history of malignancy.

BACKGROUND: This study evaluates the impact of a history of malignancy on outcomes of left ventricular assist device (LVAD) implantation. METHODS: Adult patients with a preimplant history of malignancy who underwent LVAD implantation between 2006 and 2018 were included. The primary outcome was post-LVAD survival. RESULTS: A total of 250 patients underwent LVAD implant during the study period, including 37 (14.8%) patients with a history of malignancy. Of these 37 patients, five (13.5%) had active malignancy at the time of LVAD implantation, and seven had more than one type of cancer. The median disease-free duration before LVAD was 3.5 years (interquartile range [IQR] 1.0-7.75 years). The most common types of malignancy included urologic (n = 20; 45.5%), skin (n = 7, 15.9%), and leukemia or lymphoma (n = 6; 13.6%). Median follow-up was 244 (IQR, 126-571) days and 313 (IQR 127-738) days for those with and without a history of malignancy, respectively (P = .49). Unadjusted post-LVAD survival was reduced in those with a malignancy history (2-year survival 53.4% vs 66.9%; P = .01), a finding that persisted after risk-adjustment (hazard ratio 1.89, 95% confidence interval, 1.13-3.14; P = .01). Only one (2.7%) patient died post-LVAD from their cancer. CONCLUSIONS: Although a history of malignancy is associated with reduced survival after LVAD implantation, more than half of the patients are alive at 2 years. This combined with the fact that most do not die from causes directly related to their cancer suggest that LVAD implantation is reasonable to perform in carefully selected patients with a history of malignancy.

Temporary left ventricular assist devices as a bridge to heart transplantation.

BACKGROUND: To create equitable access to donor organs for the highest mortality patients, the cardiac transplant allocation system now prioritizes patients with surgically implanted temporary left ventricular assist devices (T-LVADs). The outcomes following a direct bridge from a T-LVAD to orthotopic heart transplant (OHT) are not well delineated. AIM: This study investigates the T-LVAD waitlist outcomes and compares the posttransplant outcomes in patients bridged to OHT with surgically implanted T-LVADs to patients bridged with durable continuous-flow left ventricular assist devices (CF-LVADs). METHODS: Adults recorded in the United Network for Organ Sharing registry bridged to OHT with a durable CF-LVAD and T-LVADs, with or without temporary right ventricular assist devices (T-RVADs), between 2010 and 2018 were included. Propensity matching and multivariable Cox regression were utilized to compare outcomes. RESULTS: Of 504 patients waitlisted with T-LVADs, the majority were transplanted (50%), bridged to CF-LVAD (17%), or recovered (9%). A total of 9047 recipients were bridged to OHT during the study period with 8875 CF-LVADs and 172 T-LVADs. Early survival in propensity-matched T-LVAD ± T-RVAD patients was similar to CF-LVAD ± T-RVAD patients but reduced at a 1-year follow-up. This difference in survival at 1-year follow-up was attributable to significantly reduced survival in patients with combined T-LVAD + T-RVAD support when compared with CF-LVAD, isolated T-LVAD and combined CF-LVAD + T-RVAD support (80% vs 90% vs 90% vs 91%; P = .005). CONCLUSIONS: This study demonstrates that most patients waitlisted with a T-LVAD are successfully bridged to durable therapy or recover, and those bridged to OHT have acceptable posttransplant outcomes, particularly when T-RVADs are not required.

Nationwide variability in the use of induction immunosuppression for adult heart transplantation.

BACKGROUND: Institutional factors have been shown to impact outcomes following orthotopic heart transplantation (OHT). This study evaluated center variability in the utilization of induction therapy for OHT and its implications on clinical outcomes. METHODS: Adult OHT patients between 2010 and 2018 were identified from the United Network for Organ Sharing registry. Transplant centers were stratified based on their rates of induction therapy utilization. Mixed-effects logistic regression models were created with drug-treated rejection within 1 year as primary endpoint and individual centers as a random parameter. Risk-adjusted Cox regression was used to evaluate patient-level mortality outcomes. RESULTS: In 17,524 OHTs performed at 100 centers, induction therapy was utilized in 48.6% (n = 8411) with substantial variability between centers (interquartile range, 21.4%-79.1%). There were 36, 30, and 34 centers in the low (<29%), intermediate (29%-66%), and high (>67%) induction utilization terciles groups, respectively. Induction therapy did not account for the observed variability in the treated rejection rate at 1 year among centers after adjusting for donor and recipient factors (p = .20). No differences were observed in postoperative outcomes among induction utilization centers groups (all, p > .05). Furthermore, there was a weak correlation between the percentage of induction therapy utilization at the center-level and recipients found to have moderate (r = .03) or high (r = .04) baseline risks for acute rejection at 1 year. CONCLUSIONS: This analysis demonstrates that there is substantial variability in the use of induction therapy among OHT centers. In addition, there was a minimal correlation with baseline recipient risk or 1-year rejection rates, suggesting a need for better-standardized practices for induction therapy use in OHT.

Pulmonary vascular resistance determines mortality in end-stage renal disease patients with pulmonary hypertension.

The multifactorial etiology of pulmonary hypertension (PH) in end-stage renal disease (ESRD) includes patients with and without elevated pulmonary vascular resistance (PVR). We explored the prognostic implication of this distinction by evaluating pretransplant ESRD patients who underwent right heart catheterization and echocardiography. Demographics, clinical data, and test results were analyzed. All-cause mortality data were obtained. Median follow-up was 4 years. Of the 150 patients evaluated, echocardiography identified 99 patients (66%) with estimated pulmonary artery (PA) systolic pressure > 36 mm Hg, which correlated poorly with mortality (HR = 1.28, 95% CI 0.72-2.27, P = .387). Right heart catheterization identified 88 (59%) patients with mean PA pressure ≥ 25 mm Hg. Of these, 70 had PVR ≤ 3 Wood units and 18 had PVR > 3 Wood units. Survival analysis demonstrated a significant prognostic effect of an elevated PVR in patients with high mean PA pressures (HR = 2.26, 95% CI 1.07-4.77, P = .03), while patients with high mean PA pressure and normal PVR had equivalent survival to those with normal PA pressure. Despite the high prevalence of PH in ESRD patients, elevated PVR is uncommon and is a determinant of prognosis in patients with PH. Patients with normal PVR had survival equivalent to those with normal PA pressures.

Pulmonary Hypertension in the Intensive Care Unit.

Pulmonary hypertension occurs as the result of disease processes increasing pressure within the pulmonary circulation, eventually leading to right ventricular failure. Patients may become critically ill from complications of pulmonary hypertension and right ventricular failure or may develop pulmonary hypertension as the result of critical illness. Diagnostic testing should evaluate for common causes such as left heart failure, hypoxemic lung disease and pulmonary embolism. Relatively few patients with pulmonary hypertension encountered in clinical practice require specific pharmacologic treatment of pulmonary hypertension targeting the pulmonary vasculature. Management of right ventricular failure involves optimization of preload, maintenance of systemic blood pressure and augmentation of inotropy to restore systemic perfusion. Selected patients may require pharmacologic therapy to reduce right ventricular afterload by directly targeting the pulmonary vasculature, but only after excluding elevated left heart filling pressures and confirming increased pulmonary vascular resistance. Critically-ill patients with pulmonary hypertension remain at high risk of adverse outcomes, requiring a diligent and thoughtful approach to diagnosis and treatment.

Prognostic Value of Pericardial Effusion on Serial Echocardiograms in Pulmonary Arterial Hypertension.

BACKGROUND: Pericardial effusion in pulmonary arterial hypertension (PAH) is an indicator of right heart failure and poor prognosis; its significance on serial transthoracic echocardiograms (TTE) is not clear. METHODS: Baseline and follow-up TTE (1.0 ± 0.5 years), clinical parameters, and outcomes were studied (N = 200) in consecutive patients with PAH who underwent TTE at our center between October 1999 and November 2007. Study baseline TTE was 2.8 ± 4.0 years from initial PAH diagnosis. RESULTS: Over median follow-up of 3.6 ± 2.6 years from baseline TTE, 106 patients (53%) died. Pericardial effusion was present in 20% at baseline, and at any time during the study in 29%. Patients with any pericardial effusion during follow-up were more likely to have underlying connective tissue disease. They also had significantly higher mean right atrial pressure and pulmonary vascular resistance, had lower cardiac output by invasive hemodynamic studies, had higher serum creatinine, and were more likely to be treated with prostanoids. Patients were also significantly likely to have more echocardiographic right atrial dilation and right ventricular dilation and dysfunction, and worse tricuspid regurgitation with higher peak velocity. During follow-up, there was significantly increased use of prostanoids (58% vs. 28%) and combination therapy (8% vs. 2%) compared to baseline. Persistence of pericardial effusion on both baseline and follow-up TTE was associated with worse outcome, and an independent predictor of survival after adjusting for age, creatinine, functional class, and hemodynamics (P < 0.01). CONCLUSION: Persistence of pericardial effusion in PAH despite vasoactive therapy predicts worse outcomes; absence or resolution of pericardial effusion with therapy suggests better prognosis.

[Treatment goals of pulmonary hypertension]. / Pulmoner hipertansiyonda tedavi hedefleri.

With significant therapeutic advances in the field of pulmonary arterial hypertension, the need to identify clinically relevant treatment goals that correlate with long-term outcome has emerged as 1 of the most critical tasks. Current goals include achieving modified New York Heart Association functional class I or II, 6-min walk distance >380 m, normalization of right ventricular size and function on echocardiograph, a decreasing or normalization of B-type natriuretic peptide (BNP), and hemodynamics with right atrial pressure <8 mm Hg and cardiac index >2.5 L/dk/m2. However, to more effectively prognosticate in the current era of complex treatments, it is becoming clear that the "bar" needs to be set higher, with more robust and clearer delineations aimed at parameters that correlate with long-term outcome; namely, exercise capacity and right heart function. Specifically, tests that accurately and noninvasively determine right ventricular function, such as cardiac magnetic resonance imaging and BNP/N-terminal pro-B-type natriuretic peptide, are emerging as promising indicators to serve as baseline predictors and treatment targets. Furthermore, studies focusing on outcomes have shown that no single test can reliably serve as a long-term prognostic marker and that composite treatment goals are more predictive of long-term outcome. It has been proposed that treatment goals be revised to include the following: modified New York Heart Association functional class I or II, 6-min walk distance 380 to 440 m, cardiopulmonary exercise test-measured peak oxygen consumption >15 ml/min/kg and ventilatory equivalent for carbon dioxide <45 l/min/l/min, BNP level toward "normal," echocardiograph and/or cardiac magnetic resonance imaging demonstrating normal/near-normal right ventricular size and function, and hemodynamics showing normalization of right ventricular function with right atrial pressure <8 mm Hg and cardiac index >2.5 to 3.0 l/min/m2. (J Am Coll Cardiol 2013;62:D73-81) ©2013 by the American College of Cardiology Foundation.

Improved waitlist and comparable post-transplant outcomes in simultaneous heart-kidney transplantation under the 2018 heart allocation system.

OBJECTIVE: This study aimed to investigate the clinical trends and the impact of the 2018 heart allocation policy change on both waitlist and post-transplant outcomes in simultaneous heart-kidney transplantation in the United States. METHODS: The United Network for Organ Sharing registry was queried to compare adult patients before and after the allocation policy change. This study included 2 separate analyses evaluating the waitlist and post-transplant outcomes. Multivariable analyses were performed to determine the 2018 allocation system's risk-adjusted hazards for 1-year waitlist and post-transplant mortality. RESULTS: The initial analysis investigating the waitlist outcomes included 1779 patients listed for simultaneous heart-kidney transplantation. Of these, 1075 patients (60.4%) were listed after the 2018 allocation policy change. After the policy change, the waitlist outcomes significantly improved with a shorter waitlist time, lower likelihood of de-listing, and higher likelihood of transplantation. In the subsequent analysis investigating the post-transplant outcomes, 1130 simultaneous heart-kidney transplant recipients were included, where 738 patients (65.3%) underwent simultaneous heart-kidney transplantation after the policy change. The 90-day, 6-month, and 1-year post-transplant survival and complication rates were comparable before and after the policy change. Multivariable analyses demonstrated that the 2018 allocation system positively impacted risk-adjusted 1-year waitlist mortality (sub-hazard ratio, 0.66, 95% CI, 0.51-0.85, P < .001), but it did not significantly impact risk-adjusted 1-year post-transplant mortality (hazard ratio, 1.03; 95% CI, 0.72-1.47, P = .876). CONCLUSIONS: This study demonstrates increased rates of simultaneous heart-kidney transplantation with a shorter waitlist time after the 2018 allocation policy change. Furthermore, there were improved waitlist outcomes and comparable early post-transplant survival after simultaneous heart-kidney transplantation under the 2018 allocation system.

Impact of post-transplant stroke and subsequent functional independence on outcomes following heart transplantation under the 2018 United States heart allocation system.

BACKGROUND: This study evaluates the clinical trends, risk factors, and effects of post-transplant stroke and subsequent functional independence on outcomes following orthotopic heart transplantation under the 2018 heart allocation system. METHODS: The United Network for Organ Sharing registry was queried to identify adult recipients from October 18, 2018 to December 31, 2021. The cohort was stratified into 2 groups with and without post-transplant stroke. The incidence of post-transplant stroke was compared before and after the allocation policy change. Outcomes included post-transplant survival and complications. Multivariable logistic regression was performed to identify risk factors for post-transplant stroke. Sub-analysis was performed to evaluate the impact of functional independence among recipients with post-transplant stroke. RESULTS: A total of 9,039 recipients were analyzed in this study. The incidence of post-transplant stroke was higher following the policy change (3.8% vs 3.1%, p = 0.017). Thirty-day (81.4% vs 97.7%) and 1-year (66.4% vs 92.5%) survival rates were substantially lower in the stroke cohort (p < 0.001). The stroke cohort had a higher rate of post-transplant renal failure, longer hospital length of stay, and worse functional status. Multivariable analysis identified extracorporeal membrane oxygenation, durable left ventricular assist device, blood type O, and redo heart transplantation as strong predictors of post-transplant stroke. Preserved functional independence considerably improved 30-day (99.2% vs 61.2%) and 1-year (97.7% vs 47.4%) survival rates among the recipients with post-transplant stroke (p < 0.001). CONCLUSIONS: There is a higher incidence of post-transplant stroke under the 2018 allocation system, and it is associated with significantly worse post-transplant outcomes. However, post-transplant stroke recipients with preserved functional independence have improved survival, similar to those without post-transplant stroke.

Impact of a Medication Optimization Clinic on Heart Failure Hospitalizations.

Efforts to optimize guideline-directed medical therapy (GDMT) through team-based care may affect outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This study evaluated the impact of an innovative medication optimization clinic (MOC) on GDMT and outcomes in patients with HFrEF. Patients with HFrEF who are not receiving optimal GDMT are referred to MOC and managed by a team comprised of a nurse practitioner or physician assistant, clinical pharmacist, and HF cardiologist. We retrospectively evaluated the impact of MOC (n = 206) compared with usual care (n = 412) with a 2:1 propensity-matched control group. The primary clinical outcome was the incidence of HF hospitalizations at 3 months after the index visit. Kaplan-Meier cumulative event curves and Cox proportional hazards regression models with adjustment were conducted. A significantly higher proportion of patients in MOC received quadruple therapy (49% vs 4%, p <0.0001), angiotensin receptor neprilysin inhibitor (60% vs 27%, p <0.0001), mineralocorticoid receptor antagonist (59% vs 37%, p <0.0001), and sodium-glucose cotransporter-2 inhibitor (60% vs 10%, p <0.0001). The primary outcome was significantly lower in the MOC versus the control group (log-rank, p = 0.0008). Cox regression showed that patients in the control group were more than threefold more likely to be hospitalized because of HF than those in the MOC group (p = 0.0014). In conclusion, the MOC was associated with improved GDMT and lower risk of HF hospitalizations in patients with HFrEF.

Left ventricular assist device bridging to heart transplantation: Comparison of temporary versus durable support.

BACKGROUND: Since the revision of the United States heart allocation system, increasing use of mechanical circulatory support has been observed as a means to support acutely ill patients. We sought to compare outcomes between patients bridged to orthotopic heart transplantation (OHT) with either temporary (t-LVAD) or durable left ventricular assist devises (d-LVAD) under the revised system. METHODS: The United States Organ Network database was queried to identify all adult OHT recipients who were bridged to transplant with either an isolated t-LVAD or d-LVAD from 10/18/2018 to 9/30/2020. The primary outcome was 1-year post-transplant survival. Predictors of mortality were also modeled, and national trends of LVAD bridging were examined across the study period. RESULTS: About 1,734 OHT recipients were analyzed, 1,580 (91.1%) bridged with d-LVAD and 154 (8.9%) bridged with t-LVAD. At transplant, the t-LVAD cohort had higher total bilirubin levels and greater prevalence of pre-transplant intravenous inotrope usage and mechanical ventilation. Median waitlist time was also shorter for t-LVAD. At 1 year, there was a non-significant trend of increased survival in the t-LVAD cohort (94.8% vs 90.1%; p = 0.06). After risk adjustment, d-LVAD was associated with a 4-fold hazards for 1-year mortality (hazard ratio 3.96, 95% confidence interval 1.42-11.03; p = 0.009). From 2018 to 2021, t-LVAD bridging increased, though d-LVAD remained a more common bridging strategy. CONCLUSIONS: Since the 2018 allocation change, there has been a steady increase in t-LVAD usage as a bridge to OHT. Overall, patients bridged with these devices appear to have least equivalent 1-year survival compared to those bridged with d-LVAD.

Clinical trends, risk factors, and temporal effects of post-transplant dialysis on outcomes following orthotopic heart transplantation in the 2018 United States heart allocation system.

BACKGROUND: This study evaluated the current clinical trends, risk factors, and temporal effects of post-transplant dialysis on outcomes following orthotopic heart transplantation after the 2018 United States adult heart allocation policy change. METHODS: The United Network for Organ Sharing (UNOS) registry was queried to analyze adult orthotopic heart transplant recipients after the October 18, 2018 heart allocation policy change. The cohort was stratified according to the need for post-transplant de novo dialysis. The primary outcome was survival. Propensity score-matching was performed to compare the outcomes between 2 similar cohorts with and without post-transplant de novo dialysis. The impact of post-transplant dialysis chronicity was evaluated. Multivariable logistic regression was performed to identify risk factors for post-transplant dialysis. RESULTS: A total of 7,223 patients were included in this study. Out of these, 968 patients (13.4%) developed post-transplant renal failure requiring de novo dialysis. Both 1-year (73.2% vs 94.8%) and 2-year (66.3% vs 90.6%) survival rates were lower in the dialysis cohort (p < 0.001), and the lower survival rates persisted in a propensity-matched comparison. Recipients requiring only temporary post-transplant dialysis had significantly improved 1-year (92.5% vs 71.6%) and 2-year (86.6 % vs 52.2%) survival rates compared to the chronic post-transplant dialysis group (p < 0.001). Multivariable analysis demonstrated low pretransplant estimated glomerular filtration (eGFR) and bridge with extracorporeal membrane oxygenation (ECMO) were strong predictors of post-transplant dialysis. CONCLUSIONS: This study demonstrates that post-transplant dialysis is associated with significantly increased morbidity and mortality in the new allocation system. Post-transplant survival is affected by the chronicity of post-transplant dialysis. Low pretransplant eGFR and ECMO are strong risk factors for post-transplant dialysis.

Recent Changes in Durable Left Ventricular Assist Device Bridging to Heart Transplantation.

This study evaluates the impact of the recent United Network for Organ Sharing (UNOS) allocation policy change on outcomes of patients bridged with durable left ventricular assist devices (LVADs) to orthotopic heart transplantation (OHT). Adults bridged to OHT with durable LVADs between 2010 and 2019 were included. Patients were stratified based on the temporal relationship of their OHT to the UNOS policy change on October 18, 2018. The primary outcome was early post-OHT survival. In total, 9,628 OHTs were bridged with durable LVADs, including 701 (7.3%) under the new policy. Of all OHTs performed during the study period, the proportion occurring following durable LVAD bridging decreased from 45% to 34% (p < 0.001). The more recent cohort was higher risk, including more extracorporeal membrane oxygenation bridging (2.6% vs. 0.3%, p < 0.001), more mechanical right ventricular support (9.7% vs. 1.4%, p < 0.001), greater pretransplant ICU admission (22.8% vs. 8.7%, p < 0.001) more need for total functional assistance (62.8% vs. 53.0%, p < 0.001), older donor age (33.3 vs. 31.7 years, p < 0.001), and longer ischemic times (3.38 vs. 3.13 hours, p < 0.001). Despite this, early post-OHT survival was comparable at 30 days (96.1% vs. 96.0%, p = 0.89), 90 days (93.7% vs. 94.0%, p = 0.76), and 6 months (91.0% vs. 93.0%, p = 0.96), findings that persisted after risk-adjustment. In this early analysis, OHT following bridging with durable LVADs is performed less frequently and in higher risk recipients under the new allocation policy. Despite this, short-term posttransplant outcomes appear to be unaffected in this patient cohort in the current era.

Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase-dependent nitric oxide generation.

BACKGROUND: Pulmonary arterial hypertension is a progressive proliferative vasculopathy of the small pulmonary arteries that is characterized by a primary failure of the endothelial nitric oxide and prostacyclin vasodilator pathways, coupled with dysregulated cellular proliferation. We have recently discovered that the endogenous anion salt nitrite is converted to nitric oxide in the setting of physiological and pathological hypoxia. Considering the fact that nitric oxide exhibits vasoprotective properties, we examined the effects of nitrite on experimental pulmonary arterial hypertension. METHODS AND RESULTS: We exposed mice and rats with hypoxia or monocrotaline-induced pulmonary arterial hypertension to low doses of nebulized nitrite (1.5 mg/min) 1 or 3 times a week. This dose minimally increased plasma and lung nitrite levels yet completely prevented or reversed pulmonary arterial hypertension and pathological right ventricular hypertrophy and failure. In vitro and in vivo studies revealed that nitrite in the lung was metabolized directly to nitric oxide in a process significantly enhanced under hypoxia and found to be dependent on the enzymatic action of xanthine oxidoreductase. Additionally, physiological levels of nitrite inhibited hypoxia-induced proliferation of cultured pulmonary artery smooth muscle cells via the nitric oxide-dependent induction of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). The therapeutic effect of nitrite on hypoxia-induced pulmonary hypertension was significantly reduced in the p21-knockout mouse; however, nitrite still reduced pressures and right ventricular pathological remodeling, indicating the existence of p21-independent effects as well. CONCLUSIONS: These studies reveal a potent effect of inhaled nitrite that limits pathological pulmonary arterial hypertrophy and cellular proliferation in the setting of experimental pulmonary arterial hypertension.

Ruptured cerebral mycotic aneurysm in a left ventricular assist device patient with bacteremia.

A 50-year-old male with a history of nonischemic dilated cardiomyopathy presented in cardiogenic shock and ultimately underwent durable left ventricular assist device implantation. He recovered well initially but developed persistent bacteremia. His indwelling pacemaker leads were extracted due to evidence of vegetation. Shortly thereafter, around 3 months post-left ventricular assist device, he succumbed to a massive intracranial hemorrhage due to ruptured cerebral mycotic aneurysm. This case highlights the potential importance of brain imaging in left ventricular assist device patients with persistent bacteremia to avoid this likely catastrophic complication.

Pre-implant left ventricular dimension is not associated with worse outcomes after left ventricular assist device implantation.

BACKGROUND: Left ventricular dimension has the potential to impact clinical outcomes following implantation of left ventricular assist devices (LVAD). We investigated the effect of pre-implant left ventricular end-diastolic diameter (LVEDD) on outcomes following LVAD implantation. METHODS: Patients implanted with a continuous-flow LVAD between 2004 and 2018 at a single institution were included. The primary outcome was death while on LVAD support. Secondary outcomes included adverse event rates such as renal failure requiring dialysis, device thrombosis, and right ventricular failure. The LVEDD measurements were dichotomized using restricted cubic splines and threshold regression. Survival was determined using Kaplan-Meier estimates. Multivariable logistic regression was used to determine risk-adjusted mortality based on LVEDD. RESULTS: A total of 344 patients underwent implantation of a continuous flow LVAD during the study period. The optimal cut point for LVEDD was 65 mm, with 126 (36.6%) subjects in the <65 mm group and 165 (48.0%) in the >65 mm group. The LVEDD <65 mm group was older, had more females, higher incidence of diabetes, more pre-implant mechanical ventilation, and more admissions for acute myocardial infarctions (all, P<0.05). Importantly, post-implant adverse events were similar between the groups (all, P>0.05). Risk-adjusted survival at 1-year (OR 1.3, 95% CI: 0.6-2.5, P=0.53) was also comparable between the groups. Furthermore, incremental increases in LVEDD when modeled as a continuous variable did not impact overall mortality (OR 0.98, 95% CI: 0.9-1.0, P=0.09). CONCLUSIONS: Preoperative LVEDD was not associated with rates of major morbidities or mortality following LVAD implantation.

Evolving Trends in Adult Heart Transplant With the 2018 Heart Allocation Policy Change.

Importance: The US heart allocation policy was changed on October 18, 2018. The association of this change with recipient and donor selection and outcomes remains to be elucidated. Objective: To evaluate changes in patient characteristics, wait list outcomes, and posttransplant outcomes after the recent allocation policy change in heart transplant. Design, Setting, and Participants: In this cohort study, all 15 631 adults undergoing heart transplants, excluding multiorgan transplants, in the US as identified by the United Network for Organ Sharing multicenter, national registry were reviewed. Patients were stratified according to prepolicy change (October 1, 2015, to October 1, 2018) and postpolicy change (October 18, 2018 or after). Follow-up data were available through March 31, 2020. Exposures: Heart transplants after the policy change. Main Outcomes and Measures: Competing risk regression for wait list outcomes was performed. Posttransplant survival was compared using the Kaplan-Meier method, and risk adjustment was performed using multivariable Cox proportional hazards regression analysis. Results: In this cohort study, of the 15 631 patients undergoing transplant, 10 671 (mean [SD] age, 53.1 [12.7] years; 7823 [73.3%] male) were wait listed before and 4960 (mean [SD] age, 52.7 [13.0] years; 3610 [72.8%] male) were wait listed after the policy change. Competing risk regression demonstrated reduced likelihood of mortality or deterioration (subhazard ratio [SHR], 0.60; 95% CI, 0.52-0.69; P < .001), increased likelihood of transplant (SHR, 1.38; 95% CI, 1.32-1.45; P < .001), and reduced likelihood of recovery (SHR, 0.54; 95% CI, 0.40-0.73; P < .001) for wait listed patients after the policy change. A total of 6078 patients underwent transplant before and 2801 after the policy change. Notable changes after the policy change included higher frequency of bridging with temporary mechanical circulatory support and lower frequency of bridging with durable left ventricular assist devices. Posttransplant survival was reduced after the policy change (1-year: 92.1% vs 87.5%; log-rank P < .001), a finding that persisted after risk adjustment (HR, 1.29; 95% CI, 1.07-1.55; P = .008). Conclusions and Relevance: Substantial changes have occurred in adult heart transplant in the US after the policy change in October 2018. Wait list outcomes have improved, although posttransplant survival has decreased. These data confirm findings from earlier preliminary analyses and demonstrate that these trends have persisted to 1-year follow-up, underscoring the importance of continued reevaluation of the new heart allocation policy.