Felix Perez-Villa

Preoperative INTERMACS Profiles Determine Postoperative Outcomes in Critically Ill Patients Undergoing Emergency Heart Transplantation: Analysis of the Spanish National Heart Transplant Registry

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.

Initial experience with bosentan therapy in patients considered ineligible for heart transplantation because of severe pulmonary hypertension

Abstract: Background: Pre‐operative elevated pulmonary vascular resistance (PVR) has been associated with increased right ventricular failure and mortality after heart transplantation. The aim of this study was to assess the efficacy of bosentan, an oral endothelin‐receptor antagonist, to reduce PVR in patients considered ineligible for heart transplantation because of severe pulmonary hypertension.

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.

Valor pronóstico de los niveles de citocinas y neurohormonas en la insuficiencia cardíaca severa

Background and objetives. The screening of candidates for heart transplantation continues to present difficulties. High plasma levels of cytokines and neurohormones have been associated with a poor prognosis in heart failure but their usefulness for identifying candidates for heart transplantation is still not established. Methods. In 83 patients (59 ± 11 years old), with systolic left ventricular dysfunction and New York Heart Association functional class III-IV, we assessed levels of aldosterone, atrial natriuretic peptide, plasma renin activity, angiotensin II, norepinephrine, endothelin, interleukin-6 and tumor necrosis factor-α . Results. Over the following year, 13 patients died and 26 received heart transplantation. Mean ejection fraction was 23 ± 6%, end-diastolic and end-systolic diameters were 73 ± 10 and 60 ± 10 mm, respectively. Univariate analysis identified the following variables to be associated with poor prognosis: angiotensin II (p = 0.001), norepinephrine (p = 0.003), plasma renin activity (p = 0.02), systolic blood pressure (p = 0.006), end-diastolic diameter (p = 0.02) and end-systolic diameter (p = 0.04). Multivariate regression analysis identified the following variables to be independent predictors of death or need for heart transplantation: a low cardiac index (p = 0.007), plasma angiotensin II (p = 0.001) and pulmonary capillary wedge pressure (p = 0.04) The sensitivity and specificity of angiotensin II for predicting poor outcome was only moderate according to interpretation of the receiver operating curves. Conclusions. Although plasma angiotensin II was the best neurohormone for identifying patients with severe heart failure and the worst prognosis, its sensitivity and specificity for predicting death or the need for heart transplantation was limited. The decision to transplant should continue to be based on clinical and hemodynamic parameters.

Heart transplantation using allografts from older donors: Multicenter study results

BACKGROUND The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors. METHODS We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors. RESULTS There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs. 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18-1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22-2.27; p = 0.001). CONCLUSIONS There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.

Withdrawal of proliferation signal inhibitors due to adverse events in the maintenance phase of heart transplantation

BACKGROUND The increasing use of proliferation signal inhibitors (PSIs) has raised the issue of their risk profile. We sought to determine the causes, incidence, risk factors, and consequences of withdrawal due to adverse events of PSIs in maintenance heart transplantation. METHODS This was a retrospective study from 9 centers of the Spanish Registry for Heart Transplantation. Demographic, clinical, analytic, and evolution data were obtained for patients in whom a PSI (sirolimus or everolimus) was used between October 2001 and March 2009. RESULTS In the first year, 16% of 548 patients could not tolerate PSIs. This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%), pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis, withdrawal of PSI was related to the absence of statin therapy (p = 0.006), concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug discontinuation was associated with a decline in renal function (p = 0.045) but not with an excess in mortality (p = 0.42). CONCLUSIONS In this large cohort of maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in the first year, and 25% had stopped PSI due to severe adverse events by the fourth year. This high rate of toxicity-related PSI withdrawal could limit the clinical utility of this otherwise novel class of immunosuppressive agents.

Low Troponin-I Levels on Admission Are Associated With Worse Prognosis in Patients With Fulminant Myocarditis

BACKGROUND The clinical outcomes of patients with fulminant acute myocarditis (FAM) range from death to complete recovery. We sought to identify clinical, biological, and echocardiographic characteristics of prognostic value for this population. METHODS AND RESULTS We prospectively included 185 patients with the diagnosis of acute myocarditis who were admitted to our institution between 2000 and 2007, selecting 15 who displayed FAM, namely, severe congestive heart failure or cardiogenic shock, requiring inotropic and/or mechanical circulatory support. Their mean age was 27.9 +/- 12.4 years (range, 12-52) and mean left ventricular ejection fraction (LVEF) was 22 +/- 8.4% (range, 10-35). Seven subjects had poor outcomes, defined as death (n = 4), urgent transplantation (x = 2), or persistent left ventricular dysfunction (n = 3). The other 6 individuals experienced complete recovery of ventricular function. Troponin-I values below 1 ng/mL on admission were significantly associated with greater in-hospital (P = .05) and mid-term poor outcomes (P = .001). Additionally, patients with poor outcomes showed significantly lower LVEF (17.6 +/- 6.2% vs 28.8 +/- 6.9%; P = .006). CONCLUSION Among patients with FAM, normal or minimal elevation of troponin-I and low LVEF on admission were associated with worse in-hospital and mid-term prognosis.

Effects of cyclosporine, tacrolimus and sirolimus on vascular changes related to immune response.

BACKGROUND Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation. METHODS Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts. RESULTS At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p < 0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods. CONCLUSIONS SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.

Idiopathic Restrictive Cardiomyopathy Is Primarily a Genetic Disease.

Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular physiology in the presence of normal diastolic volume and normal ventricular wall thickness [(1)][1]. RCM is the least common cardiomyopathy and its prevalence is unknown [(1,2)][1]. Furthermore, its etiology could be

Impact of short-term mechanical circulatory support with extracorporeal devices on postoperative outcomes after emergency heart transplantation: Data from a multi-institutional Spanish cohort

OBJECTIVES We sought to investigate the potential impact of preoperative short-term mechanical circulatory support (MCS) with extracorporeal devices on postoperative outcomes after emergency heart transplantation (HT). METHODS We conducted an observational study of 669 patients who underwent emergency HT in 15 Spanish hospitals between 2000 and 2009. Postoperative outcomes of patients bridged to HT on short-term MCS (n=101) were compared with those of the rest of the cohort (n=568). Short-term MCS included veno-arterial extracorporeal membrane oxygenators (VA-ECMOs, n=23), and both pulsatile-flow (n=53) and continuous-flow (n=25) extracorporeal ventricular assist devices (VADs). No patient underwent HT on intracorporeal VADs. RESULTS Preoperative short-term MCS was independently associated with increased in-hospital postoperative mortality (adjusted odds-ratio 1.75, 95% CI 1.05-2.91) and overall post-transplant mortality (adjusted hazard-ratio 1.60, 95% CI 1.15-2.23). Rates of major surgical bleeding, cardiac reoperation, postoperative infection and primary graft failure were also significantly higher among MCS patients. Causes of death and survival after hospital discharge were similar in MCS and non-MCS candidates. Increased risk of post-transplant mortality affected patients bridged on pulsatile-flow extracorporeal VADs (adjusted hazard-ratio 2.21, 95% CI 1.48-3.30) and continuous-flow extracorporeal VADs (adjusted hazard-ratio 2.24, 95% CI 1.20-4.19), but not those bridged on VA-ECMO (adjusted hazard-ratio 0.51, 95% CI 0.21-1.25). CONCLUSIONS Patients bridged to emergency HT on short-term MCS are exposed to an increased risk of postoperative complications and mortality. In our series, preoperative bridging with VA-ECMO resulted in comparable post-transplant outcomes to those of patients transplanted on conventional support.