Marta Farrero

Pulmonary Hypertension Is Related to Peripheral Endothelial Dysfunction in Heart Failure With Preserved Ejection Fraction

Background—Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF.; Methods and Results—Flow-mediated dilation of the brachial artery, matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C-terminal propeptide of type I procollagen were determined in 28 patients with HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery pressure >35 mm Hg on echocardiogram underwent a right heart catheterization. Patients with HFpEF had more severe PED than controls: flow-mediated dilation 1.95% (−0.81 to 4.92) versus 5.02% (3.90 to 10.12), P=0.002. Twenty patients with PH underwent right heart catheterization: mean pulmonary artery pressure 38 (27–52) mm Hg, wedge capillary pressure 18 (16–22) mm Hg, pulmonary vascular resistance 362 (235–603) dyn s cm-5. There was a significant inverse correlation between flow-mediated dilation and pulmonary vascular resistance in patients with HFpEF and PH (r=−0.679; P=0.002). Patients with HFpEF showed higher matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide of type I procollagen values also had higher mean pulmonary artery pressure (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary vascular resistance (r=0.626; P=0.004). Conclusions—In patients with HFpEF, there is a significant correlation between PED and pulmonary vascular resistance. Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify patients with HFpEF at risk of developing PH.

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: Calcineurin-inhibitors conversion or minimization?

BACKGROUNDnIn the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i.nnnMETHODSnIn a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences.nnnRESULTSnOverall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07).nnnCONCLUSIONnIn terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Bosentan in heart transplantation candidates with severe pulmonary hypertension: efficacy, safety and outcome after transplantation

Increased pulmonary vascular resistance (PVR) is associated with increased right ventricular failure and mortality after heart transplantation.

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long‐term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient‐years) was significantly higher than that observed on CNI therapy in the pre‐conversion period (2.2 per 100 patient‐years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post‐conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow‐up. Conversion to a CNI‐free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post‐conversion rejection could help to refine the current PSI conversion strategies.

Primary immunosuppression and outcome differences after heart transplantation: tacrolimus versus cyclosporine.

BACKGROUNDnThe superiority of tacrolimus (Tac) as primary immunosuppression for heart transplantation (HT) compared with cyclosporine (CsA) is still under debate. Outcomes of comparison studies are not consistent; the duration of these studies has been limited. The aim of this study was to evaluate long-term outcomes of patients undergoing HT based on primary immunosuppression regime.nnnMETHODS AND RESULTSnWe analyzed a single-center registry of all HT patients between 1998 and 2009, comparing outcomes based on primary immunosuppressions (Tac or CsA). Patients who died before starting immunosuppression were excluded. A total of 197 patients entered the study; 103 received Tac and 94 CsA. There were no differences between groups in baseline characteristics, United Network for Organ Sharing status 1A or ventricular assist device use, except for ischemia time (195 ± 50 min in Tac group vs 182 ± 55 min in CsA; P = .08) and days on waiting list (164 ± 155 vs 100 ± 73; P < .001). After mean follow-ups of 4.5 ± 2.3 years in the Tac group and 6.3 ± 4.3 years in the CsA group, there were 19 and 36 deaths, respectively. Kaplan-Meier analysis showed increased survival for the Tac group (log rank P = .04). Tac also was significantly superior to CsA regarding mortality (relative risk 0.55; 95% confidence interval, 0.31-0.98; P = .04).nnnCONCLUSIONSnIn our series the use of tacrolimus resulted in improved long-term survival compared with cyclosporine. At 1-year follow-up, there were no differences in acute rejection episodes or the appearance of vasculopathy.