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.
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.
Background—
Postoperative outcomes of patients with advanced heart failure undergoing ventricular assist device implantation are strongly influenced by their preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles. We sought to investigate whether a similar association exists in patients undergoing emergency heart transplantation.
Methods and Results—
By means of the Spanish National Heart Transplant Registry database, we identified 704 adult patients treated with emergency heart transplantation in 15 Spanish centers between 2000 and 2009. Post-transplant outcomes were analyzed pertaining to patient preoperative INTERMACS profiles, which were retrospectively assigned by 2 blinded cardiologists. Before transplantation, INTERMACS profile 1 (critical cardiogenic shock) was present in 207 patients, INTERMACS profile 2 (progressive decline) in 291, INTERMACS profile 3 (inotropic dependence) in 176, and INTERMACS profile 4 (resting symptoms) was present in 30 patients. In-hospital postoperative mortality rates were, respectively, 43%, 26.8%, and 18% in patients with profiles 1, 2, and 3 to 4 (
P
<0.001). INTERMACS 1 patients also presented the highest incidence of primary graft failure (1: 31.3%, 2: 22.3%, 3–4: 21.8%;
P
=0.03) and postoperative need for dialysis (1: 33.2%, 2: 18.9%, 3–4: 21.5%;
P
<0.001). Adjusted odds-ratios for in-hospital postoperative mortality were 4.38 (95% confidence interval, 2.51–7.66) for profile 1 versus 3 to 4, 2.49 (95% confidence interval, 1.56–3.97) for profile 1 versus 2, and 1.76 (95% confidence interval, 1.02–3.03) for profile 2 versus 3 to 4. Long-term survival after hospital discharge was not influenced by preoperative INTERMACS profiles.
Conclusions—
Preoperative INTERMACS profiles determine outcomes after emergency heart transplantation. Results call for a change in policies related to the management of heart transplant candidates presenting with INTERMACS profiles 1 and 2.
BackgroundTGF-β1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-β1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-β1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function.Methodology/Principal FindingsThe subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-β1 was determined by ELISA. Under pressure overload, TGF-β1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-β1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-β1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, β-myosin heavy chain) remodelling targets of TGF-β1, in TAC mice and in AS patients.Conclusions/SignificanceA circulating TGF-β1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-β1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts.
SummaryThe results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 AE 4.1 vs. 24.3 AE 3.7; P < 0.01), and male donors were younger than female donors (33.4 AE 12.7 vs. 38.2 AE 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with longterm mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.
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