INTRODUCTION:Observational studies provide a signal that phosphodiesterase-5 inhibitors such as sildenafil are associated with lower mortality and ischaemic stroke during durable left ventricular assist device (LVAD) support. This study aims to determine the causal effects of sildenafil on platelet activation and circulating mediators of vascular remodelling during LVAD support. METHODS:We conducted a double-blind, randomized, placebo-controlled study to determine the effect of sildenafil on platelet activation and circulating mediators of vascular remodelling. Stable participants on LVAD support were assigned to sildenafil or placebo every 8 h for a 15-day period. Three primary endpoints were percent change in platelet activation by collagen, thromboxane (Tx) A2, and adenosine diphosphate (ADP). Secondary endpoints included changes in circulating mediators of vascular remodelling. RESULTS:Twenty participants were randomized. On day 15, those on sildenafil had lower collagen (-41%, -60 to -24, vs. -7%, -18 to 79, P = .038), but not TxA2 (-24%, -45 to -14 vs. 3%, -15 to 87, P = .112), and ADP (-5%, -70 to 25 vs. 31%, -29 to 242, P = .122) induced platelet activation compared to placebo. Endothelin-1 changed by -30% (-53 to 4) in the sildenafil group vs. -3% (-18 to 22) with placebo (P = .041). Angiopoietin (ang)-2 changed by -5% (-11 to -4) with sildenafil compared to 3% (-5 to 15) with placebo (P = .039), while ang-1 increased by 24% (17-54) with sildenafil and was -4% (-19 to -2) with placebo (P = .001), leading to a change in the ang-2/ang-1 ratio by -23% (-45 to -15) with sildenafil compared to 8% (-3 to 24) with placebo (P = .001). Hs-CRP and fibrinogen were unchanged between the groups. CONCLUSION:Fifteen days of sildenafil exposure modifies platelet activation and lowers mediators of vascular remodelling on LVAD support.

Introduction Thrombocytopenia is a common complication in patients requiring temporary mechanical circulatory support (tMCS), likely due to shearing forces. However, its clinical significance remains poorly understood. This study investigates risk factors for thrombocytopenia development and the relationship between thrombocytopenia severity and clinical outcomes. Hypothesis We hypothesize that severe thrombocytopenia while on tMCS is associated with increased mortality and bleeding complications. Methods We conducted a retrospective analysis of adults admitted to a tertiary care hospital from January to December 2021. Patients requiring tMCS for >24 hours were included, while those with preexisting thrombocytopenia were excluded. Thrombocytopenia was defined as a platelet count <150K/uL, categorized as moderate (nadir 50-150K/uL) or severe (nadir <50K/uL). Chi-square tests assessed relationships between patient/device characteristics and thrombocytopenia severity. Associations with mortality, hemorrhage, and blood product transfusions were also evaluated. Results A total of 125 patients were included (68% male). Mean platelet count was 98K/uL ± 64K/uL. Of these, 25 had normal platelet counts (206K/uL ± 46K/uL), 67 had moderate thrombocytopenia (88K/uL ± 26K/uL), and 33 had severe thrombocytopenia (36K/uL ± 10K/uL). tMCS type was significantly associated with thrombocytopenia severity (χ² = 30.43, p < 0.001). Extracorporeal membrane oxygenation (ECMO) and multiple-device use were more frequently associated with severe thrombocytopenia, whereas patients with intra-aortic balloon pump (IABP) alone had a lower incidence. No significant associations were found between thrombocytopenia severity and patient age, sex, race, ethnicity, admission diagnosis, or tMCS duration (p > 0.05 for all). Severe thrombocytopenia was associated with in-hospital mortality (χ² = 15, p < 0.001), hemorrhage (χ² = 15, p < 0.001), and receipt of blood products (χ² = 42, p < 0.001). Among patients suspected of heparin-induced thrombocytopenia, none had positive serotonin release assays. Conclusion tMCS type is significantly associated with thrombocytopenia severity, with ECMO and multiple-device use posing the highest risk. Thrombocytopenia severity correlated with increased in-hospital mortality, hemorrhage, and transfusion. Further studies are needed to identify patients most at risk for thrombocytopenia while on tMCS and clarify its clinical implications.

Endomyocardial biopsy is routinely performed to detect rejection following heart transplantation (HTx). During endomyocardial biopsy, a bioptome catheter is serially advanced under fluoroscopy across the tricuspid valve to the interventricular septum. The tricuspid valve is at risk of iatrogenic chordal severing from the catheter bioptome which can result in flail tricuspid valve leaflets, tricuspid regurgitation (TR) and right ventricular failure. Twenty-eight (28) patients with prior HTx and severe TR were enrolled the TRILUMINATE Pivotal trial and treated TriClip transcatheter edge-to-edge repair (TEER). The TRILUMINATE Pivotal trial was designed to evaluate the safety and effectiveness of TEER in patients with severe TR, who remained symptomatic despite medical therapy. Key inclusion criterion for prior HTx patients included medical stability with no planned endomyocardial biopsies within 2 years of TEER. A retrospective analysis to assess the safety and effectiveness of TEER in patients with prior HTx was performed on the TRILUMINATE Pivotal population. The trial consented 64 patients with prior HTx, of whom 28 subjects underwent tricuspid TEER. Five (5) patients screen failed for further medical optimization and two (2) failed due to potential future intracardiac biopsies. Other screen failure reasons were unrelated to the prior HTx. The average patient age was 60 ± 14 yrs and 75% were male. Common co-morbidities included hypertension (82%), renal disease (82%), dyslipidemia (57%) and atrial fibrillation (32%). The average time between the HTx and TEER was 11 ± 10 years with a median of 6.4 years. All HTx patients had severe (32%), massive (20%), or torrential (48%) TR at baseline. The average baseline KCCQ score was 59 ± 23 and 43% of patients were categorized as NYHA class III/IV. The tricuspid TEER procedure was on average 136 ± 54 minutes with an average of 1.9 ± 0.6 clips deployed. Adverse events were low with one (1) non-cardiovascular death and one (1) patient with heart failure hospitalization prior to 30-day follow-up. There were no instances of major bleeding, cardiogenic shock, or new onset renal failure. No single-leaflet device attachments were observed through 30-day follow-up. TR was reduced to moderate or less in 91% of patients and mild or less in 55% of patients at 30-day follow-up. Thirty-day quality of life improvement was observed with an average KCCQ score improvement of 12 ± 19 points with most patients categorized as NYHA class I/II (84%). Tricuspid TEER is a safe and effective treatment option for patients with prior HTx and severe TR.

Despite a plethora of pharmacological therapies for heart failure (HF), reducing the symptomatic burden in patients with advanced HF remains an unmet clinical need. Over the past decade, atrial shunting has emerged as a novel therapy for those with symptomatic HF despite optimal guideline-directed medical therapy. Initially thought of as a therapy reserved for those with diastolic HF, the field now spans the entire HF spectrum. In this review, we explore the physiology, devices, and trials that have shaped the field of atrial shunting. We detail how device-based interatrial shunts, no-implant interatrial shunts, and coronary sinus shunts aim to provide clinical benefit in specific patient populations and the limitations associated with their use.

Abstract Background Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that frequently coexists with inflammatory bowel disease (IBD). Data comparing the paediatric- and adult-onset PSC-IBD are lacking. We compared disease characteristics and the clinical course of PSC-IBD between Canadian children and adults. Methods This was a multi-center retrospective cohort study including eight paediatric centers from different provinces across Canada including (Ontario, Alberta, Nova Scotia, Manitoba) and four adult centers from the province of Ontario, including patients diagnosed with PSC-IBD from 1985-2023. Patient and disease characteristics and outcome data were extracted from the clinical charts. We compared patient demographics, disease course, laboratory and imaging results, and complications including liver transplant among paediatric- and adult-onset PSC-IBD. Continuous data were reported as median (Q1-Q3) and compared with the Wilcoxon Rank Sum test, and categorical data were reported as number (%) and compared with chi-square or Fisher exact tests. We compared the time to transplant with the log-rank test. Results We included 521 patients (228 children, median follow-up 3.3 (Q1-Q3 1.5-5.8) years; 293 adults, median follow-up 9.8 (Q1-Q3 4.3-16.0) years (Table-1). The interval between PSC and IBD diagnosis was longer in adults. Small duct disease and PSC with autoimmune hepatitis (AIH) features were more common in children, with corresponding higher ALT and more frequently positive autoantibodies. Rates of portal hypertension at PSC diagnosis were similar in both groups. Ulcerative colitis predominated in both groups with more IBD-unclassified in children. Colitis was most severe in the right colon in a third of children and adults. Children were more often treated with ursodeoxycholic acid, vancomycin, corticosteroids and immunomodulators. Adult patients experienced a higher proportion of adverse liver events over the entire follow-up duration, but time to event analysis showed similar rates of progression to liver transplant (log-rank p=0.075; 2- and 5-year survival with native liver in paediatric vs. adult: 97% and 90% vs. 94% and 84%). (Figure-1) Conclusion In this large Canadian multi-center cohort of PSC-IBD, paediatric-onset disease was characterized by more frequent small duct disease and features of AIH. The interval between IBD and PSC diagnosis was far longer in adults. Although a greater proportion of adult-onset patients experienced adverse liver outcomes overall, rates of transplant at 2 and 5 years were similar between groups, suggesting that PSC progression may in fact be similar.

BACKGROUND:Heart transplantation (HT) following donation after circulatory death (DCD) has grown substantially in recent years. However, the effects of functional ischemic injury during procurement on exercise capacity remain unknown. We compared exercise performance parameters between DCD and donation after brain death (DBD) recipients. METHODS:We conducted a single-center, retrospective, case-control study of adults with isolated HT between January 2022 and April 2024 and completed a treadmill cardiopulmonary exercise test (CPET) post-transplant. DCD-HT recipients (cases) were matched to DBD-HT recipients (controls) based on major demographics and CPET timing. The primary outcome was peak oxygen consumption (pVO2). Secondary outcomes included additional exercise capacity parameters and echocardiographic indices at peak exercise. RESULTS:Cases (DCD-HT: n = 10, 20% female) and controls (DBD-HT: n = 10, 20% female) had similar baseline characteristics. Total ischemic time was longer in the DCD group (6.9 [interquartile range (IQR): 6.4-7.1] vs. 4.6 [IQR: 3.94.8] h; p = 0.002). Time from HT to CPET did not differ. DCD and DBD-HT recipients had similar pVO2 (17.1 [IQR: 15.2-19.7] vs. 19.7 [IQR: 13.3-21.2] mL/kg/min; p = 0.545). Respiratory exchange ratio (RER) was slightly lower in the DCD group (1.1 [IQR: 1.0-1.2] vs. 1.2 [IQR: 1.21.3]; p = 0.031). Ventilatory efficiency (VE/VCO2) at anaerobic threshold, left ventricular ejection fraction, and E/e' at peak exercise were comparable between groups. CONCLUSION:DCD and DBD heart transplant recipients demonstrate similar exercise performance. Overall, exercise capacity remains limited after HT, highlighting the need for further studies to identify underlying mechanisms and potential therapeutic interventions.

Although there has been considerable momentum in the field of pulmonary arterial hypertension (PAH) over the past few decades, it remains an incurable disease. Sotatercept is a novel agent that favors pro-apoptotic pathways within the pulmonary artery by way of complex signaling. This unique remodeling mechanism is distinct from traditional vasodilator therapy, as it attempts to address the underpinning pathophysiology of PAH. It was recently approved as an adjunct to traditional vasodilator therapies in non-low risk patients. We describe our early hemodynamic experience with Sotatercept in a series of patients implanted with a pulmonary artery sensor system (CardioMEMS™). Through weekly remote transmissions, we describe the rapid hemodynamic improvement observed in our cohort.

BACKGROUND:Trimethoprim/sulfamethoxazole (TMP/SMX) is commonly used after orthotopic heart transplant (OHT) for opportunistic infection (OI) prophylaxis, but its contribution to hyperkalemia is uncertain. Whether switching to atovaquone (ATQ), which has a narrower antimicrobial spectrum, affects infection risk and improves hyperkalemia has not been investigated. This study evaluated whether transitioning from TMP/SMX to ATQ in the setting of post-OHT hyperkalemia is beneficial in lowering risk of recurrent hyperkalemia while maintaining OI prophylaxis efficacy. METHODS:A single-center retrospective review of OHT patients (January 2011-April 2022) compared those maintained on TMP/SMX with those switched to ATQ due to side effects, specifically hyperkalemia. The primary endpoint was the resolution of hyperkalemia, and the secondary endpoint was the combined infection rate. RESULTS:Among 321 OHT recipients, 76% were switched to ATQ. Patients switched to ATQ had higher rates of severe and recurrent hyperkalemia and experienced numerically higher overall infection rates compared to TMP/SMX patients (27% vs. 52%; p < 0.001). However, in a Poisson regression model adjusted for immortal time bias, the incidence rate ratio (IRR) for infections with ATQ versus TMP/SMX was 1.32 (95% CI: 0.93-1.86; p = 0.119). Multivariable analyses excluding chronic kidney disease patients confirmed TMP/SMX's association with lower hyperkalemia rates (initial/recurrent). Age and diabetes independently predicted initial hyperkalemia. CONCLUSIONS:Transitioning from TMP/SMX to ATQ did not decrease hyperkalemia rates and was associated with a numerically higher incidence of infections, though this difference was not statistically significant. Hyperkalemia is likely multifactorial and often unresolved by switching from TMP/SMX.

BACKGROUND:Cardiac surgery, particularly cardiac transplantation, is considered high risk in patients with sickle cell hemoglobinopathies and rarely reported in the literature. CASE SUMMARY:We present a case of a 33-year-old woman with sickle cell β+ thalassemia and peripartum cardiomyopathy, who presented with sickling crisis and cardiogenic shock requiring temporary mechanical support. The patient ultimately successfully underwent heart transplantation. DISCUSSION:This case illustrates how careful use of mechanical circulatory support, appropriate perisurgical planning including preoperative exchange transfusion and avoidance of hypothermia, allowed for successful orthotopic heart transplantation in a woman with sickle cell hemoglobinopathy and cardiogenic shock in the postpartum setting. TAKE-HOME MESSAGES:Cardiac transplantation in patients with hemoglobinopathies is rare but achievable. A tailored perioperative approach, developed by a collaborative multidisciplinary team, can optimize outcomes and lead to successful transplantation in these complex cases.

Abstract Background Primary sclerosing cholangitis (PSC) is present in up to 8% of individuals with inflammatory bowel disease (IBD). Characteristics of this population are unique and data are limited. Aims To describe the demographic and clinical characteristics of all individuals with PSC-IBD managed at The Ottawa Hospital (TOH). Methods A chart review was performed for 132 patients with PSC-IBD followed at TOH between January 1998 and July 2023. Results Of 132 individuals with PSC-IBD identified at TOH, 26.5% had Crohn’s disease (CD), 68.2% had ulcerative colitis (UC) and 5.3% had IBD-unclassified. Median age at diagnosis were 25.3 (IQR 20.94) for IBD and 33.84 (IQR 23.98) for PSC, and 66.7% of all patients were male. More than 17% had a co-morbid autoimmune disease other than IBD or PSC. Of those with CD, roughly 15% had fibrostenotic or penetrating complications and 17% had perianal disease at the time of IBD diagnosis. Only 28% ever had a liver biopsy, whereas the majority were diagnosed with PSC by cholangiography. PSC distribution was isolated intrahepatic in 47%, isolated extra-hepatic in 5.1% and mixed intra/extra-hepatic in 38.5%. Clinically significant portal hypertension was present in 11.5% at PSC diagnosis, while 27.3% and 16.7% developed cirrhosis and liver decompensation, respectively by last follow-up. 17.4% underwent liver transplant, of which 30.4% developed PSC recurrence post-transplant. Conclusions Our study showed that the majority of PSC-IBD patients are young males with UC. Co-morbid autoimmune diseases are common while isolated extra-hepatic PSC is uncommon. Cirrhosis, liver decompensation and liver transplant are frequent occurrences in this population. PSC recurrence post-transplant is observed in more than 30% of patients. Funding Agencies None

Purpose: Iron Deficiency (Fe-def) in heart failure (HF) correlates with disease severity and progression, regardless of anemia. Current definition is based on thresholds for iron therapy rather than clinical outcomes and optimal treatment effectiveness. In the present study we sought to better characterize Fe-def in advanced HF.

Using proton-proton collision data corresponding to an integrated luminosity of 140 fb$^{-1}$ collected by the CMS experiment at $\sqrt{s}$ = 13 TeV, the $\Lambda_\text{b}^0$ $\to$ J/$\psi\Xi^-$K$^+$ decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the $\Lambda_\text{b}^0$ $\to$ $\psi$(2S)$\Lambda$ decay, is measured to be $\mathcal{B}$($\Lambda_\text{b}^0$ $\to$ J/$\psi\Xi^-$K$^+$)/$\mathcal{B}$( $\Lambda_\text{b}^0$ $\to$ $\psi$(2S)$\Lambda$) = [3.38 $\pm$ 1.02 $\pm$ 0.61 $\pm$ 0.03]%, where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in $\mathcal{B}$($\psi$(2S) $\to$ J/$\psi\pi^+\pi^-$) and $\mathcal{B}$($\Xi^-$ $\to$ $\Lambda\pi^-$).

Purpose: DCD-donors have become an important source of organs for HT, but there is limited data regarding their use for multi-organ HT. We evaluated the trend and early outcomes of DCD-donor use in multi-organ HT.