Aims Therapy with phosphodiesterase-5 inhibitors (PDE5Is) after left ventricular assist device (LVAD) implantation has been associated with lower mortality and device thrombosis but increased risk for post-operative and gastrointestinal bleeding. We aimed to evaluate the impact of long-term PDE5Is on the overall bleeding risk after LVAD implantation. Methods and resultsWe retrospectively included patients who received a continuous-flow LVAD at our site and were prescribed with long-term oral PDE5Is after discharge from the index hospitalization. The primary endpoint was the occurrence of bleeding at 12 month follow-up. Secondary endpoints were all-cause death and the combination of bleeding and all-cause death. Our analysis included 109 patients of whom 75 (69%) received long-term PDE5Is. Mean age was 56 years, and 85% were male. At 12 months, 19 (17%) patients experienced at least one bleeding event. Patients on PDE5Is had higher bleeding rates (23% vs. 6%, P = 0.03) and more bleeding events per patient-year (0.32 vs. 0.06, P = 0.03) compared with patients not on PDE5Is. While overall bleeding incidence was excessively higher in the PDE5I group, there were no significant differences in the incidence of major bleeding (19% vs. 6%, P = 0.08) and gastrointestinal bleeding (11% vs. 3%, P = 0.18). Kaplan-Meier analysis revealed higher cumulative incidence of bleeding for the PDE5I group (log rank = 0.04) with no difference on all-cause death (log rank = 0.67) and the combination of bleeding and all-cause death (log rank = 0.13). Hospitalizations for bleeding and their duration were numerically higher in the PDE5I group (0.28 vs. 0.03, P = 0.07 and 2.4 vs. 0.2, P = 0.07, respectively). Conclusions Phosphodiesterase-5 inhibitor treatment after LVAD implantation is associated with increased bleeding risk after LVAD implantation. The safety of long-term PDE5Is in LVAD patients remains unclear and needs to be further clarified in prospective studies with randomized study design.

AimsThe study aimed to investigate the prevalence, phenotypic characteristics, and predictors of atrial fibrillation (AF) in patients presenting with cardiac amyloidosis (CA) of light-chain (AL) or transthyretin (ATTR) type. Methods and resultsClinical, biochemical, and echocardiographic data of patients presenting with CA between 2005 and 2020 were retrospectively collected. CA staging was based on established biomarker systems. Binomial logistic regression was run to analyse the effects of clinical variables on the likelihood of AF. The study included 133 patients [53% AL, 41% wild-type (wt) ATTR-CA, & 6% hereditary ATTR-CA]. Mean age was 71 years, and 80% were male patients. AF was diagnosed in 64 (48%) patients (28% in AL-CA, 80% in wtATTR, 13% in hATTR, P < 0.001). Patients with AF were older (74 vs. 69 years, P < 0.001), more likely to have wtATTR-CA (67 vs. 16%, P < 0.001), exhibited more often New York Heart Association ≥ III symptoms (66 vs. 45%, P = 0.02) and carried a higher burden of comorbidities. AF patients had lower left ventricular ejection fraction (47 vs. 53%, P < 0.005), higher left atrial volume index (54 vs. 46 mL/m 2 , P = 0.007), higher pulmonary artery pressure (42 vs. 31 mmHg, P = 0.008), and worse tricuspid annular plane systolic excursion values (17 vs. 20 mm, P = 0.01). Mitral regurgitation ≥ Grade 2 was more frequent in AF (56 vs. 25%, P < 0.001). Higher ATTR-CA stage was associated with higher AF prevalence (47% vs. 74% vs. 94%, P < 0.001, for Stages I, II, & III, respectively). Higher AL-CA stage was associated with lower AF prevalence (0% vs. 40% vs. 31% vs. 18%, P < 0.001, for Stages I, II, IIIa, & IIIb, respectively). Three independent predictors for AF were identified in a multivariate logistic regression model with 81.5% classification accuracy: AL type [odds ratio (OR) 0.1, confidence interval (CI) 0.01-0.29, P = 0.001], estimated glomerular filtration rate (OR 0.9, CI 0.93-0.99, P = 0.03), and body mass index (OR 1.3, CI 1.07-1.66, P = 0.01). ATTR amyloidosis was associated with a 10-fold higher risk of AF. During 1 year follow-up, only one episode of ischaemic stroke was reported. Conclusions Atrial fibrillation affects nearly half of all patients with CA. Patients presenting with AF have more severe symptoms and higher burden of comorbidities. ATTR type of amyloidosis is the strongest predictor of AF. Prospective screening for occult AF may be considered in ATTR-CA.

Cardiac transthyretin amyloidosis is an infiltrative cardiomyopathy with high mortality. To date, there are no specific biomarkers to directly assess disease activity and response to specific treatments. Our aim was to evaluate scintigraphic changes after treatment with the transthyretin stabilizer tafamidis. Methods: We included patients who had undergone 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ( 99m Tc-DPD) scintigraphy before tafamidis initiation and after at least 9 mo. Tracer activity was assessed visually and quantitatively as SUV max . Results: The study included 14 patients who were on tafamidis for 44 6 14 mo. We observed regression of Perugini grade in 5 patients, unchanged grade in 9 patients, and regression of mean heart-to-contralateral-lung ratio (P 5 0.015) and SUV max (P 5 0.005). There were no changes in N-terminal pro-B-type natriuretic peptide or echocardiographic measures. Conclusion: Treatment with tafamidis results in regression of myocardial 99m Tc-DPD uptake. 99m Tc-DPD scintigraphy may provide useful imaging biomarkers to assess response to treatment.

Aims Phosphodiesterase‐5 inhibitors (PDE5I) are frequently implemented after left ventricular assist device (LVAD) implantation to improve haemodynamics in patients with early postoperative right ventricular (RV) failure. It is unknown if long‐term PED5I therapy beyond the early post‐operative period provides any clinical benefit in stable outpatients, who have recovered from post‐operative RV failure under univentricular device support. This study aimed to investigate the impact of PDE5I discontinuation on RV function and cardiopulmonary exercise capacity in patients on durable LVAD support. Methods and results We enrolled 31 clinically stable LVAD recipients on long‐term oral PDE5I therapy. The mean age was 53 years, and 90% were male. Patients discontinued PDE5I and underwent cardiopulmonary exercise testing, echocardiography, LVAD interrogation, and biomarker analysis at baseline and 4 weeks after PDE5I withdrawal. At 4 weeks, no significant changes were observed in echocardiographic indices of RV morphology and function but an increase in peak tricuspid regurgitation velocity (2.1 vs. 2.4 m/s, P = 0.01). Peak oxygen consumption (11.4 vs. 11.8 mL/min/kg, P = 0.52), minute ventilation/carbon dioxide production slope (33 vs. 35, P = 0.56), N‐terminal pro‐brain natriuretic peptide (1455 vs. 1399 pg/mL, P = 0.55), flow and power readings of the device, and quality of life (Kansas City Cardiomyopathy Questionnaire score 78.3% vs. 77.5%, P = 0.62) exhibited no significant changes. We observed an increase in 6‐min walking distance (346 vs. 364 m, P = 0.03). Two patients were hospitalized for non‐cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation. Conclusions In LVAD patients with a history of early post‐operative RV failure, discontinuation of long‐term PDE5I therapy was not associated with deterioration of RV function, exercise capacity, and quality of life. PDE5I should be critically evaluated until more evidence regarding the net clinical benefit of this pharmacologic intervention becomes available.

Background Long-term therapy with oral phosphodiesterase-5 inhibitors (PDE5I) is frequently implemented after left ventricular assist-device (LVAD) implantation to improve hemodynamics and prevent late-onset right ventricular (RV) failure or to facilitate listing for heart transplantation in individuals with persistent pulmonary hypertension. The safety and efficacy of this appoach has not been prospectively studied. Recent analyses of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) demonstrated improved survival for patients under long-term PDE5I after 48 months but higher incidence of early postoperative RV failure as well as a higher risk for gastrointestinal bleeding. Purpose To evaluate the impact of discontinuation of PDE5I in patients on LVAD support. Methods In this prospective, single-arm, interventional study we enrolled LVAD recipients on oral PDE5I (sildenafil or tadalafil) after at least 1 month post-implant who were clinically stable on optimal medical therapy. The patients underwent physical examination, ECG, 6-minute walking test, cardiopulmonary exercise testing, transthoracic echocardiography, LVAD interrogation, questionnaire based evaluation of quality of life and testing of serum biomarkers at baseline and 4 weeks after discontinuation of oral PDE5I therapy. Results From 10/2019 to 02/2021 thirty patiens were included in the study and completed the follow-up. Mean age was 54 years, 90% were male. Destination therapy was the primary treatment goal in 13% of this cohort while 87% received LVAD as a bridge to transplant. Mean dosis of tadalafil was 24.6 mg, of sildenafil 42.5 mg. At follow-up no significant changes were elicited in echocardiographic markers of RV function, peak oxygen consumption, VE/VCO2 slope, eGFR, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, quality of life and average flow and power readings of the device but mild increase in walking distance (Table 1). Two patients were hospitalized for non-cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation. Conclusion Discontinuation of PDE5I was not associated with deterioration of RV function, exercise capacity and quality of life after 4 weeks. The risk/benefit profile of PDE5I in LVAD patients needs to be further investigated in context of randomized controlled trials. FUNDunding Acknowledgement Type of funding sources: None. Table 1