BACKGROUND:Invasive hemodynamics may facilitate outpatient identification of ambulatory advanced heart failure. We analyzed cardiac failure risk stratified by four hemodynamic profiles recorded during implantation of the pulmonary artery pressure sensor, CardioMEMS heart failure system. METHODS AND RESULTS:This multicenter, retrospective cohort study included patients with heart failure with reduced ejection fraction who underwent pulmonary artery pressure sensor implantation from 2015 to 2022. Hemodynamic profiles were categorized using the Stevenson heart failure classification, defining cold (impaired systemic perfusion) as a cardiac index of <2.2 L/min/m2; and wet (hemodynamic congestion) as a pulmonary capillary wedge pressure of ≥18 mm Hg. The primary end point was 1-year cardiac failure, including all-cause mortality, inotrope dependence, and the need for durable ventricular assist device or heart transplantation. Among 512 patients (median age 71 years, 28% female, 77% New York Heart Association functional class III, median N-terminal pro-B-type natriuretic peptide 2554 pg/mL), the hemodynamic profiles were as follows: 30% warm-dry, 22% warm-wet, 21% cold-dry, and 27% cold-wet. Overall, 118 patients (23%) experienced cardiac failure, of whom 57 required chronic inotrope, durable ventricular assist device implantation, or heart transplantation; 61 died despite medical therapy. The 1-year event-free survival rate differed across the profiles: warm-dry (90%), warm-wet (74%), cold-dry (80%), and cold-wet (61%) (P < 0.001). Multivariable analysis (reference: warm-dry) showed increased cardiac failure risk in cold-wet (adjusted hazard ratio [HR] 4.4, 95% confidence interval [CI] 2.4-7.8, P < 0.001), cold-dry (adjusted HR 2.2, 95% CI 1.1-4.2; P = 0.019), and warm-wet (adjusted HR 2.8, 95% CI 1.5-5.4; P = 0.001). CONCLUSIONS:At the time of pulmonary artery pressure sensor placement, an abnormal hemodynamic profile-especially a cold-wet profile-was associated with increased cardiac failure risk, indicating subgroups who might have already progressed to ambulatory advanced heart failure.

AIMS:Following HeartMate 3 (HM3) LVAD implantation, acute right heart failure necessitating temporary right ventricular assist device (tRVAD) support has not been extensively described. We examined clinical outcomes in patients with HM3 LVAD stratified by the need for tRVAD support. METHODS AND RESULTS:This was a single-centre, retrospective study of patients who underwent primary HM3 implantation from 2018 to 2022. Patients were placed on tRVAD (concomitant or delayed) support due to clinical deterioration. The primary outcome was 1-year all-cause mortality following HM3 implantation using competing risk analysis with heart transplantation acting as the competing event. A matched cohort analysis was also performed to evaluate the primary outcome of patients with and without tRVAD support. Secondary outcomes included an analysis of risk of LVAD-related adverse events stratified by the presence of tRVAD. Of the 192 patients (median age 60 [49-68] years, 74% male, 37% white), 51 (26%) required tRVAD support. Compared with those with HM3 alone, the tRVAD group had a higher percentage of INTERMACS profile 1 or 2 (49% vs. 27%, P = 0.0005) and had higher rates of pre-operative VA-ECMO (28% vs. 5%, P < 0.0001). The tRVAD group had a higher 1-year all-cause mortality (33% vs. 3%, adjusted HR [95%CI]: 32.4 [9.51-110], P < 0.0001) compared with the HM3 alone group. In-hospital mortality for patients with tRVAD was 26% compared with 1% in patients with HM3 alone (P < 0.0001). In the matched cohort analysis, significantly higher risk of both stroke (HR [95% CI]: 5.75 [1.55-21.3], P = 0.009) and dialysis (HR [95% CI]: 13.4 (3.96-45.5), P < 0.0001) was observed in the tRVAD cohort. Compared with concomitant tRVAD support, the delayed tRVAD group did not have a significantly higher risk of adverse events. CONCLUSIONS:In this large single-centre experience, patients undergoing HM3 LVAD requiring tRVAD support had significantly higher risks of adverse clinical outcomes.

Managing refractory cardiogenic shock is individualized, with few aspects considered routine or universally contraindicated. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a temporary mechanical circulatory support strategy, providing hemodynamic stabilization and gas exchange for patients with severe cardiogenic shock. It is increasingly used as salvage therapy for advanced cardiopulmonary failure and serves as a bridge to myocardial recovery, heart transplantation, or durable mechanical support such as a left ventricular assist device. Over the past decade, VA-ECMO utilization has risen, even though robust clinical trial evidence supporting its use remains limited. Furthermore, consensus is lacking on key aspects of care, including patient selection, cannulation strategy, weaning protocols, and complication management. This review outlines a structured approach to daily VA-ECMO care, emphasizing multidisciplinary coordination and individualized patient support to optimize outcomes and mitigate complications. We also address the implications of limited trial data and highlight the need for evidence-based frameworks to guide clinical decision-making.

AbstractAimsIntra‐aortic balloon pump (IABP) devices are commonly used in patients with heart failure related cardiogenic shock (HF‐CS), including those with out‐of‐proportion right ventricular (RV) dysfunction. Pulmonary artery pulsatility index (PAPi) is a haemodynamic surrogate for RV performance. We aimed to assess short‐term haemodynamic changes in patients with HF‐CS following IABP support stratified by baseline PAPi.Methods and resultsThis is a single‐centre study of 67 consecutive patients with HF‐CS who underwent IABP placement between 2020 and 2022. The primary aim was haemodynamic changes of specific variables on pulmonary artery catheter monitoring over 72 h following IABP placement. Secondary aims were clinically significant changes in diuretic regimens, changes in inotropes or vasopressors at 72 h following IABP, along with clinical outcomes. Prior to IABP placement, 57% of the total cohort (median age 59 years [48, 69], 31% female) had Society of Cardiovascular Angiography and Interventions Stage C HF‐CS. Thirty‐eight (56%) patients had a PAPi <2.0. Following 72 h of IABP support, the PAPi <2.0 group had an observed significant decrease in central venous pressure (CVP; 20 to 12 mmHg, P < 0.001) and mean pulmonary artery pressure (mPAP; 37.5 to 28.5 mmHg, P = 0.001), and an increase in PAPi (1 to 1.6, P = 0.001). No significant change in cardiac index (CI; 2 to 2.1 L/min/m2, P = 0.31) was observed. The PAPi ≥2.0 group (N = 29) had no observed significant change in CVP (10 to 8 mmHg, P = 0.47), or PAPi (2.6 to 2.8, P = 0.92), but there was a significant improvement in CI (1.9 to 2.5 L/min/m2, P = 0.004) along with reduction in mPA (37 to 29 mmHg, P = 0.03). The PAPi <2.0 group had a significant increase in diuretic requirement (52.6% vs. 20.7%, P = 0.01) and numerically greater addition of inotropes/vasopressors (47.3% vs. 34.4%, P = 0.07) compared with the PAPi ≥2.0 group at 72 h following IABP placement. Significantly more patients in the PAPi ≥2.0 group underwent left ventricular assist device (55.2% vs. 26.3%, P = 0.02), with no overall significant differences observed in escalation to veno‐arterial extracorporeal membrane oxygenation, 30‐day mortality, renal replacement therapy post‐IABP, or rates of heart transplantation.ConclusionsIABP devices in those with HF‐CS and low or abnormal PAPi may provide modest short‐term haemodynamic benefits without significant improvement in CI, along with greater need for adjustment in medical therapeutics to achieve haemodynamic optimization.

Introduction: Eculizumab (ECU) is utilized in desensitization strategies in both kidney (KT) and heart transplantation (HT). Due to its ability to prevent the formation of membrane attack complexes, the complement inhibitor could be an ideal agent to limit the immune response to circulating donor specific antibodies (DSAs). Data regarding the efficacy and treatment in the setting of antibody mediated rejection (AMR) for HT is limited. We present our multi-modal approach when treating severe acute AMR in HT recipients.

Purpose of review The goal of this review is to describe the current evidence available for remote monitoring devices available for patients with chronic heart failure, and also detail practical clinical recommendations for implementing these tools in daily clinical practice. Recent findings Several devices ranging from sophisticated multiparametric algorithms in defibrillators, implantable pulmonary artery pressure sensors, and wearable devices to measure thoracic impedance can be utilized as important adjunctive tools to reduce the risk of heart failure hospitalization in patients with chronic heart failure. Pulmonary artery pressure sensors provide the most granular data regarding hemodynamic status, while alerts from wearable devices for thoracic impedance and defibrillator-based algorithms increase the likelihood of worsening clinical status while also having high negative predictive value when values are within normal range. Summary Multiple device-based monitoring strategies are available to reduce longitudinal risk in patients with chronic heart failure. Further studies are needed to best understand a practical pathway to integrate multiple signals of data for early clinical decompensation risk prediction Video abstract: http://links.lww.com/HCO/A95.

BACKGROUND:Left ventricular assist device (LVAD) outflow graft obstruction can result in severe clinical deterioration. Underlying mechanisms may vary depending on the location. Outflow graft tamponade due to external compression can be under recognized. Management of this complication varies across institutions and a uniform approach has yet to be elucidated. OBJECTIVES:Report a single center experience with outflow graft tamponade in patients with LVAD with the purpose of developing an optimal algorithm for the diagnosis and treatment of LVAD-related outflow graft tamponade. METHODS AND RESULTS:Retrospective chart review between July 2011 and July 2020. A total of 351 LVADs were implanted at our center, with outflow graft tamponade identified in 26 patients with LVAD. Fourteen (53.8%) had HeartMate II™, 8 (30.8%) had HeartMate3™ and 4 (15.4%) had HeartWare™. Individuals presented with heart failure symptoms, an audible precordial murmur and LVAD alarms after a median duration of 862 days of support (IQR 327 - 1455). Of the 26 patients, 15 (57.7%) underwent mini thoracotomy with outflow graft relief, 4 had percutaneous balloon dilatation and stenting, 2 were bridged directly to transplant and 1 had a pump exchange. No intervention was made on the remaining due to mild symptoms (n = 4). CONCLUSIONS:Conclusions: Outflow graft tamponade is a form outflow graft obstruction with a variable presentation that can result in significant hemodynamic compromise. It is amenable to both surgical and percutaneous interventions that restore LVAD function.

Purpose: Left ventricular assist device (LVAD) patients who require temporary right ventricular assist device (tRVAD) support have increased morbidity and mortality. Limited data exists predicting which patients will require tRVAD support following HeartMate 3 (HM3) LVAD implantation. We examined the utility of established risk scores and hemodynamic surrogates in predicting right heart failure (RHF) requiring tRVAD among HM3 patients.

Purpose: Right ventricular failure occurs in approximately 30% of patients following a HeartMate 3 (HM3) left ventricular assist device, with nearly 10% requiring a temporary right ventricular assist device (tRVAD). We present our outcomes in HM3 patients with a tRVAD compared to HM3 alone.

Purpose: Tacrolimus (FK) nephrotoxicity can occur in heart transplant (HT) recipients, but the effect of time to therapeutic tacrolimus trough (TTT-FK) on renal function is not well studied. We examined the impact of TTT-FK on estimated glomerular filtration rate (eGFR) from baseline to 12 weeks post HT.

Background:Patient selection for real-world use of HeartMate 3 left ventricular assist device (HM3 LVAD) differs from that of clinical trials. We assessed adverse-event rates between "nontrial like" (NTL) and "trial like" (TL) patients who underwent commercial HM3 implantation. Methods:We conducted a multicenter, retrospective cohort study of 231 consecutive patients who underwent primary HM3 implant from October 2017 to December 2021. Patients were identified as NTL if they met ≥1 exclusion criteria from the Mulitcenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial and TL if they had no exclusion criteria. The primary outcome was freedom from death, heart failure hospitalization, LVAD-related infection, and hemocompatibility-related adverse events including major gastrointestinal bleed, all-cause stroke, and pump thrombosis. Results:Of the 231 patients (median age 59 years, 24% female), 105 (45%) were categorized as NTL, most commonly due to low albumin and/or prealbumin levels alone (n = 48) followed by the use of temporary mechanical circulatory support alone (n = 10) and having ≥2 exclusion criteria (n = 26). Compared to the TL group, the NTL group had a lower 1-year event-free survival (34% vs 48%, adjusted hazard ratio (HR) [95% confidence interval (CI)]: 1.5[1.01-2.0], p = 0.043). One-year overall survival was 82% in NTL group vs 95% in TL group (adjusted HR [95%CI]: 3.3[1.1-8.7], p = 0.013). Post-HM3 adverse events were associated with the presence of ≥2 exclusion criteria (adjusted HR [95%CI]: 1.8[1.06-3.1], p = 0.028); and veno-arterial extracorporeal membrane oxygenation support prior to HM3 (adjusted HR [95%CI]: 1.9[1.08-3.4], p = 0.026). Conclusions:In this multicenter cohort of HM3 patients, those outside of traditional clinical trial eligibility had a significantly lower 1-year event-free survival.

PurposeThe utilization of guideline directed medical therapy (GDMT) in left ventricular assist device (LVAD) patients has not been well studied. We evaluated the use of GDMT in patients following HeartMate 3 LVAD implantation stratified by severe initial right ventricular failure requiring temporary right ventricular assist device (tRVAD).MethodsWe retrospectively analyzed a single-center convenience sample of patients from 2018-2021 who required both LVAD with tRVAD (N=23) or LVAD alone (N=58). We compared rates of GDMT implementation at 6 months post-implant. GDMT implementation was at the discretion of the provider. GDMT doses were expressed as daily total mg equivalents of valsartan (ARB), metoprolol (beta-blocker), spironolactone (MRA), hydralazine, and furosemide (diuretic), then compared using Mann-Whitney test and proportions by Fischer's exact test.ResultsAt 6 month visit, median age (64 vs. 53 yrs), female sex (24% vs. 43%), creatinine (1.3 vs. 1.0 mg/dL), and mean arterial pressure (89 vs. 87 mmHg) were reported in LVAD alone versus LVAD-tRVAD, respectively. No significant differences in doses of ARB (52 vs. 80 mg, P=0.36), MRA (25 vs. 25 mg, P=0.93) and diuretic (60 vs. 50 mg, P=0.76) were observed in LVAD alone compared to LVAD-tRVAD (Figure). Significantly greater beta-blocker dosage and utilization was observed in the LVAD alone group (50 vs. 25 mg, 53% vs. 17%, P<0.05 for both). Hydralazine was utilized more in LVAD alone group (56% [N=33] vs. 26% [N=6], P=0.02), though did not significantly differ by dose (100 vs 65 mg, P=0.43). Significantly greater digoxin utilization was observed in the LVAD-tRVAD group (65% vs 24%, P=0.005).ConclusionSignificant differences in GDMT utilization were observed between LVAD patients with and without tRVAD post implant. The longitudinal impact of these findings on clinical outcomes needs further investigation. The utilization of guideline directed medical therapy (GDMT) in left ventricular assist device (LVAD) patients has not been well studied. We evaluated the use of GDMT in patients following HeartMate 3 LVAD implantation stratified by severe initial right ventricular failure requiring temporary right ventricular assist device (tRVAD). We retrospectively analyzed a single-center convenience sample of patients from 2018-2021 who required both LVAD with tRVAD (N=23) or LVAD alone (N=58). We compared rates of GDMT implementation at 6 months post-implant. GDMT implementation was at the discretion of the provider. GDMT doses were expressed as daily total mg equivalents of valsartan (ARB), metoprolol (beta-blocker), spironolactone (MRA), hydralazine, and furosemide (diuretic), then compared using Mann-Whitney test and proportions by Fischer's exact test. At 6 month visit, median age (64 vs. 53 yrs), female sex (24% vs. 43%), creatinine (1.3 vs. 1.0 mg/dL), and mean arterial pressure (89 vs. 87 mmHg) were reported in LVAD alone versus LVAD-tRVAD, respectively. No significant differences in doses of ARB (52 vs. 80 mg, P=0.36), MRA (25 vs. 25 mg, P=0.93) and diuretic (60 vs. 50 mg, P=0.76) were observed in LVAD alone compared to LVAD-tRVAD (Figure). Significantly greater beta-blocker dosage and utilization was observed in the LVAD alone group (50 vs. 25 mg, 53% vs. 17%, P<0.05 for both). Hydralazine was utilized more in LVAD alone group (56% [N=33] vs. 26% [N=6], P=0.02), though did not significantly differ by dose (100 vs 65 mg, P=0.43). Significantly greater digoxin utilization was observed in the LVAD-tRVAD group (65% vs 24%, P=0.005). Significant differences in GDMT utilization were observed between LVAD patients with and without tRVAD post implant. The longitudinal impact of these findings on clinical outcomes needs further investigation.

IntroductionAmong heart transplant (HT) recipients, anti-angiotensin II type 1 receptor antibodies (AT1R-Ab) have been implicated in non-HLA antibody-mediated rejection (AMR). Donor-derived cell free DNA (dd-cfDNA) is increasingly being used to detect both subclinical and overt cardiac allograft injury. We present a case of using dd-cfDNA in suspected AT1R-Ab-associated cardiac allograft dysfunction.Case ReportA 38-year-old male with a history of HVAD implantation complicated by driveline infection and pump thrombosis underwent an uncomplicated HT. He received standard immunosuppression: basiliximab induction, mycophenolate mofetil (MMF 1000mg BID), tacrolimus (goal trough 10-12 ng/ml), and prednisone taper. Three months post-HT, right heart catheterizations revealed normal filling pressures and persistently low cardiac indices (3-5-month post-HT mean thermodilution, TDCI = 1.9 L/min/m2). Serial transthoracic echocardiograms showed normal function. Biopsies were repeatedly negative for both acute cellular rejection (grade 0) and pathologic AMR. Donor-specific antibodies were negative. Non-HLA antibody testing showed elevated AT1R-Ab titers (12 U/ml, normal <10). Due to the unrevealing work-up, dd-cfDNA was checked and found to be elevated (0.66%, normal <0.12%). Given his clinical stability, we opted to increase MMF to 1250mg BID and initiated losartan 50mg daily. Though AT1R-Ab titers remained elevated, his TDCI significantly improved (6-9-month post-HT mean = 2.4 L/min/m2), and dd-cfDNA normalized (Fig. 1).SummaryOur case raises the possibility that among certain HT recipients, AT1R-Ab may cause subclinical dysfunction whose etiology eludes traditional testing methods. In cases of suspected AT1R-associated graft dysfunction, dd-cfDNA may have utility in 1) detecting allograft injury and 2) monitoring for treatment response. Further study is necessary to understand AT1R-Ab-associated injury and the use of dd-cfDNA in these cases.

PurposePatient selection for real-world use of HeartMate 3 left ventricular assist devices (HM3) differs from that of clinical trials. We assessed adverse-event rates between "non-trial like" (NTL) and "trial like" (TL) patients who underwent commercial HM3 implantation.MethodsWe conducted a multicenter, retrospective cohort study of 197 consecutive patients who underwent primary HM3 implant from 10/2017 to 6/2021 with ≥1-year follow-up. Patients were identified as NTL if they met ≥1 exclusion criteria from the MOMENTUM 3 clinical trial and TL if they had no exclusion criteria. The primary outcome was freedom from composite events of death, LVAD-related infection (LVADI), and hemocompatibility related adverse events (HRAE) including major gastrointestinal bleed, all-cause stroke, and pump thrombosis.ResultsOf the 197 patients (median age 58 years, 24% female), 84 (43%) were categorized as NTL due to low albumin and/or prealbumin levels (n=38), temporary MCS (tMCS) prior to HM3 (n=10), elevated bilirubin (n=5), psychosocial reasons (n=5), severe PAD (n=3), elevated creatinine (n=2), hematological reasons (n=1), severe COPD (n=1), or having ≥2 exclusion criteria (n=19). Both NTL and TL patients were statistically similar in age, sex, and race. Compared to the TL group, the NTL group had a lower 1-year event-free survival (43% vs 62%, adjusted HR [95% CI]: 1.6 [1.04-2.4], p=0.034; Fig1A&B). One-year overall survival was 84% in NTL group vs. 95% in TL group (adjusted HR [95% CI]: 3.3 [1.1-9.6], p=0.028). There was more use of post-operative RVAD in the NTL group (25% vs 10%, respectively, p=0.0058). In an adjusted analysis, post-LVAD adverse events were associated with the presence of ≥2 exclusion criteria (adjusted HR [95% CI]: 2.2 [1.1-4.3], p=0.016) and the use of tMCS prior to HM3 (adjusted HR [95% CI]: 2.0 [1.04-3.9], p=0.037).ConclusionIn this multicenter experience of HM3 patients, those outside of traditional clinical trial eligibility had a significantly lower event-free survival. Patient selection for real-world use of HeartMate 3 left ventricular assist devices (HM3) differs from that of clinical trials. We assessed adverse-event rates between "non-trial like" (NTL) and "trial like" (TL) patients who underwent commercial HM3 implantation. We conducted a multicenter, retrospective cohort study of 197 consecutive patients who underwent primary HM3 implant from 10/2017 to 6/2021 with ≥1-year follow-up. Patients were identified as NTL if they met ≥1 exclusion criteria from the MOMENTUM 3 clinical trial and TL if they had no exclusion criteria. The primary outcome was freedom from composite events of death, LVAD-related infection (LVADI), and hemocompatibility related adverse events (HRAE) including major gastrointestinal bleed, all-cause stroke, and pump thrombosis. Of the 197 patients (median age 58 years, 24% female), 84 (43%) were categorized as NTL due to low albumin and/or prealbumin levels (n=38), temporary MCS (tMCS) prior to HM3 (n=10), elevated bilirubin (n=5), psychosocial reasons (n=5), severe PAD (n=3), elevated creatinine (n=2), hematological reasons (n=1), severe COPD (n=1), or having ≥2 exclusion criteria (n=19). Both NTL and TL patients were statistically similar in age, sex, and race. Compared to the TL group, the NTL group had a lower 1-year event-free survival (43% vs 62%, adjusted HR [95% CI]: 1.6 [1.04-2.4], p=0.034; Fig1A&B). One-year overall survival was 84% in NTL group vs. 95% in TL group (adjusted HR [95% CI]: 3.3 [1.1-9.6], p=0.028). There was more use of post-operative RVAD in the NTL group (25% vs 10%, respectively, p=0.0058). In an adjusted analysis, post-LVAD adverse events were associated with the presence of ≥2 exclusion criteria (adjusted HR [95% CI]: 2.2 [1.1-4.3], p=0.016) and the use of tMCS prior to HM3 (adjusted HR [95% CI]: 2.0 [1.04-3.9], p=0.037). In this multicenter experience of HM3 patients, those outside of traditional clinical trial eligibility had a significantly lower event-free survival.

Background:We describe our clinical experience performing device exchange from a HeartMate II (HM2) or HVAD to a HeartMate 3 (HM3) left ventricular assist device. Methods:A single-center retrospective study was performed of all patients (N = 14) who underwent a left ventricular assist device exchange from HM2 (n = 7) or HVAD (n = 7) to HM3 between October 2018 and October 2021. The primary outcome was 1-year overall survival, and secondary outcomes included adverse events through discharge. Results:All patients (median age, 59 years; 29% female) were destination therapy and required urgent device exchange because of pump failure. Although statistically insignificant, the 1-year overall survival was worse in the HVAD to HM3 group compared with the HM2 to HM3 cohort (57% vs 100%, respectively; P = .19). The HVAD to HM3 group also experienced significantly more acute right-sided heart failure requiring right ventricular assist device support (71% vs 0%; P = .02), ventilator days (11 days vs 1 day; P = .001), and reoperation (100% vs 14%; P = .004). Conclusions:Patients being considered for device exchange from HVAD to HM3 may have a more complicated clinical course compared with HM2 to HM3 patients.

Purpose The implications of the development of restrictive hemodynamics (RH) in the absence of overt graft dysfunction post heart transplantation (OHT) are unclear. We sought to determine the incidence of patients with post-OHT RH profiles and the respective clinical outcomes associated with this pathophysiologic state. Methods We retrospectively analyzed 164 (2008-2020) patients who underwent OHT at our institution. Hemodynamics were obtained during scheduled endomyocardial biopsies. Right atrial pressure ≥ 12, pulmonary capillary wedge pressure > 15, and cardiac index > 2.2 L/min/m2 in the absence of graft dysfunction by echocardiography and without evidence of rejection met criteria for a RH profile. We sought to identify if RH profiles persisted at 12 months in addition to rate of heart failure admissions, change in renal function (glomerular filtration rate, GFR), and calcineurin inhibitor protocol deviation (decreases in dosing) compared to controls who did not have primary graft dysfunction or abnormal hemodynamics. Results Of 164 patients, 39 had RH profiles at week 4. There was an increased risk of heart failure admissions in those with RH profiles (incident rate ratio 1.81, 95% CI 1.78-1.85, P<0.001) (Panel A). The weekly diuretic dose at 9 months in the RH group was 308 mg/week compared to 127 mg/week in controls (P=0.005) (Panel B). Lower GFR was observed in those with RH at 4 weeks compared to controls, though no significant decline in GFR was observed longitudinally (Panel C). Calcineurin inhibitor protocol deviation occurred in 15 of 39 patients with RH and in 23 of 125 patients without RH (P=0.02). RH persisted at one year in 25.6% of patients (10/39). Conclusion Post-OHT patients who develop a RH profile are more likely to experience heart failure hospitalizations, decreases in calcineurin-inhibitor dosing, and have higher loop diuretic doses. The majority tend to normalize their hemodynamic profile at 1 year. Further studies are required to elucidate what factors contribute to the development of this phenotype. The implications of the development of restrictive hemodynamics (RH) in the absence of overt graft dysfunction post heart transplantation (OHT) are unclear. We sought to determine the incidence of patients with post-OHT RH profiles and the respective clinical outcomes associated with this pathophysiologic state. We retrospectively analyzed 164 (2008-2020) patients who underwent OHT at our institution. Hemodynamics were obtained during scheduled endomyocardial biopsies. Right atrial pressure ≥ 12, pulmonary capillary wedge pressure > 15, and cardiac index > 2.2 L/min/m2 in the absence of graft dysfunction by echocardiography and without evidence of rejection met criteria for a RH profile. We sought to identify if RH profiles persisted at 12 months in addition to rate of heart failure admissions, change in renal function (glomerular filtration rate, GFR), and calcineurin inhibitor protocol deviation (decreases in dosing) compared to controls who did not have primary graft dysfunction or abnormal hemodynamics. Of 164 patients, 39 had RH profiles at week 4. There was an increased risk of heart failure admissions in those with RH profiles (incident rate ratio 1.81, 95% CI 1.78-1.85, P<0.001) (Panel A). The weekly diuretic dose at 9 months in the RH group was 308 mg/week compared to 127 mg/week in controls (P=0.005) (Panel B). Lower GFR was observed in those with RH at 4 weeks compared to controls, though no significant decline in GFR was observed longitudinally (Panel C). Calcineurin inhibitor protocol deviation occurred in 15 of 39 patients with RH and in 23 of 125 patients without RH (P=0.02). RH persisted at one year in 25.6% of patients (10/39). Post-OHT patients who develop a RH profile are more likely to experience heart failure hospitalizations, decreases in calcineurin-inhibitor dosing, and have higher loop diuretic doses. The majority tend to normalize their hemodynamic profile at 1 year. Further studies are required to elucidate what factors contribute to the development of this phenotype.

BACKGROUND:Hydrogen sulfide (H2S) exerts mitochondria-specific actions that include the preservation of oxidative phosphorylation, biogenesis, and ATP synthesis, while inhibiting cell death. 3-MST (3-mercaptopyruvate sulfurtransferase) is a mitochondrial H2S-producing enzyme whose functions in the cardiovascular disease are not fully understood. In the current study, we investigated the effects of global 3-MST deficiency in the setting of pressure overload-induced heart failure. METHODS:Human myocardial samples obtained from patients with heart failure undergoing cardiac surgeries were probed for 3-MST protein expression. 3-MST knockout mice and C57BL/6J wild-type mice were subjected to transverse aortic constriction to induce pressure overload heart failure with reduced ejection fraction. Cardiac structure and function, vascular reactivity, exercise performance, mitochondrial respiration, and ATP synthesis efficiency were assessed. In addition, untargeted metabolomics were utilized to identify key pathways altered by 3-MST deficiency. RESULTS:Myocardial 3-MST was significantly reduced in patients with heart failure compared with nonfailing controls. 3-MST KO mice exhibited increased accumulation of branched-chain amino acids in the myocardium, which was associated with reduced mitochondrial respiration and ATP synthesis, exacerbated cardiac and vascular dysfunction, and worsened exercise performance following transverse aortic constriction. Restoring myocardial branched-chain amino acid catabolism with 3,6-dichlorobenzo1[b]thiophene-2-carboxylic acid (BT2) and administration of a potent H2S donor JK-1 ameliorates the detrimental effects of 3-MST deficiency in heart failure with reduced ejection fraction. CONCLUSIONS:Our data suggest that 3-MST derived mitochondrial H2S may play a regulatory role in branched-chain amino acid catabolism and mediate critical cardiovascular protection in heart failure.

Purpose Intra-aortic balloon pump (IABP) support is a commonly used strategy in patients with heart failure related cardiogenic shock (HF-CS), however its efficacy in those with out-of-proportion right ventricular (RV) failure is unknown. We aim to assess the hemodynamic response of IABP support for HF-CS over a spectrum of RV function as defined by pulmonary artery pulsatility index (PAPi). Methods This is a single center, retrospective study assessing IABP support in consecutive HF-CS patients. We analyzed patients who underwent IABP support with or without baseline inotropic support and excluded patients with acute coronary syndromes or mechanical support devices. We stratified the cohort by PAPi ([pulmonary artery systolic pressure - pulmonary artery diastolic pressure] / central venous pressure) below or above 2. Hemodynamics were compared pre and 48 hours post IABP insertion. Results 46 patients were included with median age 61 yrs and left ventricular ejection fraction 19%, 32.6% women, and 91% on inotropes. 22 patients had PAPi > 2 and 24 had < 2. No significant differences in baseline characteristics were observed except for greater age in patients with PAPi > 2 (61 vs 51 yr). Within 48 hours of IABP insertion, patients with PAPi < 2 had significant improvement in central venous pressure, mean pulmonary artery pressure, and cardiac index (P < 0.05 for all, Figure). Although baseline hemodynamics were better optimized in patients with PAPi > 2, only CI improved significantly post IABP (Figure). No significant change in diuretic or inotrope dosing was observed in patients post-IABP irrespective of PAPi (P > 0.05). No significant change in 30-day survival was observed between patients with PAPi < 2 (n=3, 12.5%) versus PAPi > 2 (n=1, 4.5%; P=0.34). Conclusion In patients with HF-CS with baseline PAPi <2, we observed a positive hemodynamic response which may infer treatment benefit in patients with out-of-proportion RV dysfunction.