Aims
The LION‐HEART study was a multicentre, double‐blind, randomised, parallel‐group, placebo‐controlled trial evaluating the efficacy and safety of intravenous administration of intermittent doses ...of levosimendan in outpatients with advanced chronic heart failure.
Methods and results
Sixty‐nine patients from 12 centres were randomly assigned at a 2:1 ratio to levosimendan or placebo groups, receiving treatment by a 6‐hour intravenous infusion (0.2 μg/kg/min without bolus) every 2 weeks for 12 weeks. The primary endpoint was the effect on serum concentrations of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) throughout the treatment period in comparison with placebo. Secondary endpoints included evaluation of safety, clinical events and health‐related quality of life (HRQoL). The area under the curve (AUC, pg.day/mL) of the levels of NT‐proBNP over time for patients who received levosimendan was significantly lower than for the placebo group (344 × 103 95% Confidence Interval (CI) 283 × 103−404 × 103 vs. 535 × 103 443 × 103−626 × 103, p = 0.003). In comparison with the placebo group, the patients on levosimendan experienced a reduction in the rate of heart failure hospitalisation (hazard ratio 0.25; 95% CI 0.11–0.56; P = 0.001). Patients on levosimendan were less likely to experience a clinically significant decline in HRQoL over time (P = 0.022). Adverse event rates were similar in the two treatment groups.
Conclusions
In this small pilot study, intermittent administration of levosimendan to ambulatory patients with advanced systolic heart failure reduced plasma concentrations of NT‐proBNP, worsening of HRQoL and hospitalisation for heart failure. The efficacy and safety of this intervention should be confirmed in larger trials.
Background
In Spain, listing for high‐urgent heart transplantation is allowed for critically ill candidates not weanable from temporary mechanical circulatory support (T‐MCS). We sought to analyse ...the clinical outcomes of this strategy.
Methods and results
We conducted a case‐by‐case, retrospective review of clinical records of 291 adult patients listed for high‐urgent heart transplantation under temporary devices from 2010 to 2015 in 16 Spanish institutions. Survival after listing and adverse clinical events were studied. At the time of listing, 169 (58%) patients were supported on veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO), 70 (24%) on temporary left ventricular assist devices (T‐LVAD) and 52 (18%) on temporary biventricular assist devices (T‐BiVAD). Seven patients transitioned from VA‐ECMO to temporary ventricular assist devices while on the waiting list. Mean time on T‐MCS was 13.1 ± 12.6 days. Mean time from listing to transplantation was 7.6 ± 8.5 days. Overall, 230 (79%) patients were transplanted and 54 (18.6%) died during MCS. In‐hospital postoperative mortality after transplantation was 33.3%, 11.9% and 26.2% for patients bridged on VA‐ECMO, T‐LVAD and T‐BiVAD, respectively (P = 0.008). Overall survival from listing to hospital discharge was 54.4%, 78.6% and 55.8%, respectively (P = 0.002). T‐LVAD support was independently associated with a lower risk of death over the first year after listing (hazard ratio 0.52, 95% confidence interval 0.30–0.92). Patients treated with VA‐ECMO showed the highest incidence rate of adverse clinical events associated with T‐MCS.
Conclusion
Temporary devices may be used to bridge critically ill candidates directly to heart transplantation in a setting of short waiting list times, as is the case of Spain. In our series, bridging with T‐LVAD was associated with more favourable outcomes than bridging with T‐BiVAD or VA‐ECMO.
Abstract Background Pulmonary arterial hypertension (PAH) is common in patients with congenital heart disease (CHD). Although Eisenmenger syndrome may be on decline, other types of PAH–CHD are ...increasing and little is known on long-term outcome of this population. We report the PAH–CHD population of Spain via a national registry with focus on long-term survival. Methods and results A total of 240 consecutive patients (age 37.7 ± 14.1 years, 67.9% females) with PAH–CHD included in the REHAP registry were analysed. Patients were classified into 3 groups: 1) Eisenmenger syndrome, 2) postoperative-PAH and 3) PAH associated with small defects. Over a median follow-up time of 4.5 1.6–7.1 years, 50 patients (20.8%) died or underwent lung/heart-lung transplantation. Patients with Eisenmenger syndrome had better survival than postoperative-PAH (HR 0.1 95% CI: 0.2–0.9, p = 0.048) but no advantage compared to small defects (HR 4.4, 95% CI 0.6–31.4, p = 0.15). In the overall PAH–CHD population, patients in NYHA functional class III–IV had a 3-fold increased risk of death (HR 3.0, 95% CI: 1.5–5.9, p = 0.001). Amongst patients with Eisenmenger syndrome, a pre-tricuspid shunt had a 2.6-fold increase risk of death (HR 2.6, 95% CI: 1.2–5.6, p = 0.03). There was no significant difference in survival between patients with postoperative-PAH and patients with iPAH (HR 0.99 95% CI: 0.6–1.7, p = 0.97). Conclusion PAH–CHD is associated with mid to long-term mortality. Outcome relates closely to functional class, type of PAH–CHD and within the Eisenmenger cohort, with location of the shunt. Adults with postoperative-PAH have the worse prognosis in the PAH–CHD cohort, reinforcing the need for lifelong close follow-up of such patients.
Aims
Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre‐ and ...post‐capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre‐ and post‐capillary PH (CpcPH).
Methods and results
The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE‐HF) trial is a multicentre, randomized, parallel, placebo‐controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo‐corrected mean difference of 0.62 Wood units, 95% confidence interval CI −0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo‐corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre‐specified secondary outcomes.
Conclusions
SPHERE‐HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre‐specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.
Summary of the study outline, flowchart, and results of the primary and secondary outcomes. The β3 selective agonist mirabegron did not improve pulmonary haemodynamics in adult patients with combined pre‐ and post‐capillary pulmonary hypertension associated with symptomatic heart failure. On secondary outcomes, a significant improvement in right ventricular ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life. PP, per protocol population.
Introduction
It is recommended to assess frailty prior to heart transplantation (HT). Our objective was to assess the prevalence of frailty in patients listed for HT.
Methods
The FELICITAR registry ...(Frailty Evaluation after List Inclusion, Characteristics and Influence on TrAnsplantation And Results) is a prospective registry that includes patients listed for HT in three centers, from January 2017 to April 2019. We assessed the presence of frailty, depression, cognitive impairment, and quality of life when included.
Results
Ninety‐nine patients were included. Of this group, 30.6% were frail, 55 (56.1%) had depression (treated only in nine patients), and 51 (54.8%) had cognitive impairment. Compared with non‐frail patients, frail patients were more frequently hospitalized when included in HT waiting list (P = .048), had a lower upper‐arm circumference (P = .026), had a lower Barthel index (P = .001), more anemia (P = .010), higher rates of depression (P = .001), poorer quality of life (P = .001), and lower hand‐grip strength (P < .001). In multivariate analysis hand‐grip strength (odds ratio .91; 95% confidence interval .87–.96, P < .001) and Barthel index (odds ratio .90; 95% confidence interval .82–.99, P = .024) were associated with frailty.
Conclusions
Frailty, depression, and cognitive impairment are common in patients included in HT waiting list. Frailty is strongly associated with hand‐grip strength.
Background
Pulmonary arterial hypertension (PAH) is an independent predictor of death in patients with human immunodeficiency virus (HIV) infection. HIV is the leading cause of PAH (HIV‐PAH) ...worldwide.
Aims
We described the characteristics, treatment patterns, and prognosis of a cohort of HIV‐PAH patients and compared them with those of an equivalent cohort of patients with idiopathic/familial PAH (IPAH/FPAH).
Methods
We retrospectively analysed and compared the demographic, clinical, and treatment data from patients with HIV‐PAH and those with IPAH/FPAH in the Spanish PAH registry (REHAP) from 1998 to 2018. The HIV‐PAH overall survival (OS) rate up to 5 years was compared to the age‐ and sex‐matched IPAH/FPAH population. Changes in treatment patterns in patients with HIV‐PAH after 2010 and their effects on OS were also analysed.
Results
Compared to those with IPAH/FPAH (n = 739), patients with HIV‐PAH (n = 132) were younger, mainly men, and had a better functional status. The clinical presentation, haemodynamics, and respiratory function were similar between the groups. Parenteral drug use was the most common mode of HIV transmission. Approximately 11% of patients with HIV‐PAH did not receive PAH‐targeted therapy. The age‐ and sex‐adjusted 5‐year OS rate from diagnosis was 74.0% for patients with HIV‐PAH and 68.7% for those with IPAH (p < 0.159). During/after 2010, 23% of patients with IPAH/FPAH received upfront dual oral combination, while oral monotherapy remained the main first‐line treatment in patients with HIV‐PAH. The overall OS rate remained stable.
Conclusions
Patients with HIV‐PAH were predominantly young men. The short‐term prognosis is similar to that of age‐ and sex‐matched patients with IPAH/FPAH, despite a better functional status. Oral monotherapy remains the preferred first‐line treatment in the current cohorts.
Background
Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin ...inhibitor, is increasingly used for anticoagulation in patients with non‐valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab.
Aim
To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT.
Methods
Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery.
Results
Fifty‐three patients were included (81.1% male). 7.5% required re‐operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30‐day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post‐HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post‐HT death was associated with bleeding.
Conclusions
These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
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