Impact of type of mechanical circulatory support before transplant on postorthotopic heart transplantation infections.

BACKGROUND: Infections after orthotopic heart transplantation (OHT) cause significant morbidity and mortality. Concurrent with increased pre-OHT temporary mechanical circulatory support (MCS), there have been recent concerns of a perceived increase in infections post-OHT. We examined the association between pre-OHT temporary versus durable MCS and post-OHT infection. METHODS: We performed a single-center retrospective review of patients who received OHT at Tufts Medical Center between January 2014 and April 2022. Our composite outcome was the occurrence of bacteremia, invasive fungal infections, opportunistic infections, or skin/soft tissue infections of device sites within 1-year post-OHT. We used Cox proportional hazards models to assess the relationship between the type of pre-OHT MCS and time to the first infection, treating death from other causes as a competing risk. We addressed confounding with 2 statistical methods: propensity score (PS) with inverse probability weighting (IPW) and an instrumental variable (IV) analysis. RESULTS: Of the 320 OHT recipients, 268 required MCS before OHT; 192 were managed with durable MCS and 76 with temporary MCS. Patients receiving pre-OHT temporary MCS had no difference in time to first infection (unadjusted hazard ratio [HR] 0.77, 95% CI 0.41-1.44) compared to durable MCS. Results were similar in the model employing PS with IPW (HR 0.61, 95% CI 0.29-1.27) and the IV analysis (HR 0.28, 95% CI 0.26-2.36). CONCLUSIONS: Pre-OHT temporary MCS was not associated with the composite outcome of bacteremia, invasive fungal infections, opportunistic infections, or skin/device site infections post-OHT compared to durable MCS in this single-center cohort.

The Association Between Pulmonary Vascular Resistance and Posttransplant Outcomes Differs by Left Ventricular Assist Device Status.

Elevated pulmonary vascular resistance (PVR) is a risk factor for mortality after heart transplantation (HT), but whether this association differs for patients with and without left ventricular assist device (LVAD) support before HT is unknown. We analyzed adult first-time HT recipients from the United Network for Organ Sharing (UNOS) registry transplanted between 2010 and 2021. We quantified the association between PVR and the outcomes of 30 day graft failure and 1 year mortality using multivariable logistic regression, stratified by LVAD support status at the time of HT. Pulmonary vascular resistance was modeled using restricted cubic splines to identify clinically relevant risk thresholds. We also examined the association with 10 year survival using multivariable Cox proportional hazards regression. For PVR values less than approximately 2 WU, higher PVR was independently associated with a higher risk of early graft failure (odds ratio [OR] = 1.58, 95% CI: 1.06-2.36) and a higher risk of 1 year mortality (OR = 1.32, 95% CI: 1.10-1.59) among LVAD patients only (interaction p = 0.023 and 0.03, respectively). However, for patients surviving at least 1 year, PVR was not associated with long-term mortality among either subgroup. Whether more aggressive reduction of PVR among HT candidates supported with LVADs can mitigate these risks requires further study.

Increased Spironolactone Dosing in Acute Heart Failure Alters Potassium Homeostasis but Does not Enhance Decongestion.

BACKGROUND: The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. METHODS: We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. RESULTS: Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. CONCLUSIONS: Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

Mechanical Preload Reduction: Harnessing a Cornerstone of Heart Failure Management to Improve Clinical Outcomes.

Decongestion is a cornerstone therapeutic goal for those presenting with decompensated heart failure. Current approaches to clinical decongestion include reducing cardiac preload, which is typically limited to diuretics and hemofiltration. Several new technologies designed to mechanically reduce cardiac preload are in development. In this review, we discuss the pathophysiology of decompensated heart failure; the central role of targeting cardiac preload; emerging mechanical preload reduction technologies; and potential application of these devices.

Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

PROMIS: Physical, Mental and Social Health Outcomes Improve From Before to Early After LVAD Implant: Findings From the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study.

Study participants (n = 272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months postimplant. All but 1 PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.

High- versus low-dose losartan and uric acid: An analysis from HEAAL.

BACKGROUND: Serum uric acid (SUA) is activated in catabolic, hypoxic, and inflammatory conditions characteristic of heart failure (HF) and is a source of reactive oxygen species. Losartan is unique among other angiotensin receptor blockers in reducing SUA. OBJECTIVES: To study the patient characteristics and outcome associations by SUA levels, as well as the effect of high- vs. low-dose losartan on SUA levels in HF. METHODS: HEAAL was a double-blind trial, comparing the effect of two doses of losartan 150 (high dose) vs. 50 (low dose) mg/day among 3834 patients with symptomatic HF, a left ventricular ejection fraction≤40 %, and known intolerance to angiotensin-converting enzyme inhibitors. In the present study, we studied the associations of SUA with outcomes and the effect of high- vs. low-dose losartan on SUA levels, incident hyperuricemia, and gout. RESULTS: Patients with higher SUA had more comorbidities, worse renal function, were more symptomatic, used diuretics more frequently, and were 1.5- to 2-fold more likely to experience HF hospitalizations and cardiovascular death. The benefit of high-dose losartan to improve HF outcomes was not influenced by baseline SUA levels (interaction p > 0.1). Compared with low-dose, high-dose losartan reduced SUA by -0.27 (-0.34 to -0.21) mg/dL, p < 0.001. The incidence of hyperuricemia was reduced with high-dose losartan, but the incidence of gout was not. CONCLUSIONS: In HEAAL, hyperuricemia was associated with worse outcomes. High-dose losartan reduced SUA and hyperuricemia more than low-dose and the cardiovascular benefits of high-dose losartan were not modified by SUA levels.

The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review.

Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

High- Versus Low-dose Losartan and Serum Potassium: An Analysis From HEAAL.

BACKGROUND: Patients with heart failure (HF) experience frequent alterations of serum potassium. Despite the high risk of events associated with hypokalemia, hyperkalemia is feared by clinicians and often leads to interruption or discontinuation of renin-angiotensin-aldosterone system inhibitors. Data on serum potassium of patients treated with different doses of renin-angiotensin-aldosterone system inhibitors are scarce. METHODS AND RESULTS: The effects of high-dose vs low-dose losartan on clinical outcomes in patients with heart failure (HEAAL) trial randomized 3834 patients with HFrEF intolerant to angiotensin-converting enzyme inhibitors to losartan 150 mg/d (high dose) vs 50 mg/d (low dose). We studied the associations of serum potassium (baseline and time updated) with study outcomes and the effect of the randomized treatment on serum potassium. Patients with higher baseline potassium were older, had diabetes, poorer renal function, and used mineralocorticoid receptor antagonists more frequently. In time-updated models, hyperkalemia (>5.0 or ≥5.5 mmol/L) was not associated with cardiovascular death or the composite of cardiovascular death or HF hospitalization. Hypokalemia (serum potassium of ≤3.5 mmol/L, in particular) was associated with a higher risk of the composite of cardiovascular death or HF hospitalization (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.19-2.08), all-cause death (HR 1.68, 95% CI 1.26-2.24), and sudden cardiac death or resuscitated cardiac arrest (HR 1.74, 95% CI 1.11-2.73). High-dose losartan decreased the risk of hypokalemia (HR 0.77, 95% CI 0.63-0.92) and increased the risk of hyperkalemia (HR 1.21, 95% CI 1.05-1.39). High-dose losartan decreased the composite of cardiovascular death or HF hospitalizations consistently across the full spectrum of serum potassium at baseline (interaction P = .85). CONCLUSIONS: In patients with HF with reduced ejection fraction intolerant to angiotensin-converting enzyme inhibitors and treated with either high- or low-dose losartan, incident hypokalemia had a stronger association with poor outcomes than incident hyperkalemia. High-dose losartan reduced the incidence of hypokalemia, and its benefits were maintained across the full spectrum of serum potassium.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

BACKGROUND: While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined. METHODS: We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling. RESULTS: Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk. CONCLUSIONS: Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.

A Multicenter Study of Left Ventricular Assist Device-Related Gastrointestinal Bleeding.

INTRODUCTION: Continuous left ventricular assist devices (LVADs) offer hemodynamic support in advanced and decompensated heart failure but are often complicated by gastrointestinal bleeding (GIB) in medically fragile patients. METHODS: We performed a retrospective analysis of 475 consecutive patients who underwent LVAD implantation at the Massachusetts General Hospital and Tufts Medical Center from 2008 to 2019 and identified 128 patients with clinically significant GIB. Clinical characteristics of each bleeding event, including procedures and interventions, were recorded. We examined LVAD patients with overt and occult presentations to determine diagnostic endoscopic yield and analyzed predictors of recurrent GIB. RESULTS: We identified 128 unique patients with LVAD implantation complicated by GIB. No significant difference was observed based on study center, underlying cardiomyopathy, race/ethnicity, serum indices, and medications used. Overt bleeders presented more commonly during LVAD implantation admission ( P = 0.001) than occult bleeders. Occult bleed presentations had only 1 lower and no middle GI bleed source identified, despite similar workups to overt bleeds. Destination therapy (e.g., among nontransplant candidates) LVAD implantation (odds ratio 2.38, 95% confidence interval 1.05-5.58) and a history of GIB (odds ratio 3.85, 95% confidence interval 1.29-12.7) were independently associated with an increased risk of recurrent GIB-related hospitalization. DISCUSSION: Our findings confirm a high rate of GIB, especially in destination LVAD patients, and show a low diagnostic yield for colonoscopy and middle GI bleed assessments in LVAD patients with occult bleeds. Overt bleeding was more common and associated with vascular malformations. Although endoscopic interventions stopped active hemorrhage, GIB often recurred.

Percutaneous Decommissioning of a Left Ventricular Assist Device in a Patient With Myocardial Recovery.

A 37-year-old man was referred for consideration of percutaneous decommissioning of a left ventricular assist device (LVAD). Following careful hemodynamic monitoring during pump turn-down and temporary outflow graft occlusion, the LVAD was permanently decommissioned by using a vascular plug to induce thrombosis of the outflow graft. (Level of Difficulty: Advanced.).

Skeletal Muscle Mass Recovery Early After Left Ventricular Assist Device Implantation in Patients With Advanced Systolic Heart Failure.

BACKGROUND: Patients with advanced systolic heart failure are at risk of unintentional weight loss and muscle wasting. It has been observed that left ventricular assist device (LVAD) recipients gain weight after device implantation, although it is unknown whether this represents skeletal muscle mass gains. We aimed to determine whether skeletal muscle mass increases early during LVAD support. METHODS: We prospectively recruited 30 adults with systolic heart failure ±21 days from LVAD implantation. Participants underwent whole-body dual X-ray absorptiometry to measure fat free mass, appendicular lean mass (ALM, lean mass in the arms and legs) and fat mass. Dual X-ray absorptiometry imaging was repeated at 3 and 6 months after LVAD implantation, with participation ending after the 6-month visit or heart transplantation, whichever occurred first. Changes in body composition were evaluated using mixed effects linear regression models. RESULTS: The cohort was 87% male, with mean age 56±12 (SD) years, and mean body mass index 26.4±5.4 kg/m2. Per sarcopenia ALM criteria, 52% of participants had muscle wasting at baseline. At baseline, mean fat free mass and ALM were 56.4±11.7 and 21.0±5.3 kg, respectively. Both measures increased significantly (P<0.001) over 6 months of LVAD support: mean fat free mass change at 3 and 6 months: 2.3 kg (95% CI, 1.0-3.5) and 4.2 kg (95% CI, 2.2-6.1); mean ALM change at 3 and 6 months: 1.5 kg (95% CI, 0.7-2.3) and 2.3 kg (95% CI, 0.9-3.6). CONCLUSIONS: Among LVAD recipients with advanced systolic heart failure and high baseline prevalence of muscle wasting, there were significant gains in skeletal muscle mass, as represented by dual X-ray absorptiometry fat free mass and ALM, over the first 6 months of LVAD support.

Outcomes With Phosphodiesterase-5 Inhibitor Use After Left Ventricular Assist Device: An STS-INTERMACS Analysis.

BACKGROUND: Elevated right ventricular afterload following continuous-flow left ventricular assist device (CF-LVAD) may contribute to late right heart failure (LRHF). PDE5i (phosphodiesterase-5 inhibitors) are used to treat pulmonary hypertension and right heart dysfunction after CF-LVAD, but their impact on outcomes is uncertain. METHODS: We queried Interagency Registry for Mechanically Assisted Circulatory Support from 2012 to 2017 for adults receiving a primary CF-LVAD and surviving ≥30 days from index discharge. Patients receiving early PDE5i (ePDE5i) at 1 month were propensity-matched 1:1 with controls. The primary outcome was the cumulative incidence of LRHF, defined using prevailing Interagency Registry for Mechanically Assisted Circulatory Support criteria; secondary outcomes included all-cause mortality and major bleeding. RESULTS: Among 9627 CF-LVAD recipients analyzed, 2463 (25.6%) received ePDE5i and 1600 were propensity-matched 1:1 with controls. Before implant, ePDE5i patients had more severe RV dysfunction (13.1% versus 9.6%) and higher pulmonary vascular resistance (2.8±2.7 versus 2.2±2.4 WU), both P<0.001, but clinical factors were well-balanced after propensity-matching. In the unmatched cohort, ePDE5i patients had a higher 3-year cumulative incidence of LRHF, mortality, and major bleeding, but these differences were attenuated in the propensity-matched cohort: LRHF 40.8% versus 35.7% (hazard ratio, 1.14 [95% CI, 0.99-1.32]; P=0.07); mortality 38.6% versus 35.8% (hazard ratio, 0.99 [95% CI, 0.86-1.15]; P=0.93); major bleeding 51.2% versus 46.0% (hazard ratio, 1.12 [95% CI, 0.99-1.27]; P=0.06). CONCLUSIONS: Compared with propensity-matched controls, adult CF-LVAD patients receiving ePDE5i had similar rates of LRHF, mortality, and major bleeding. While intrinsic patient risk factors likely account for more adverse outcomes with ePDE5i in the unmatched cohort, there is no obvious benefit of ePDE5i in the LVAD population.