Alfredo Cuppoletti

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.

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.

Assessment of Peripheral Endothelial-Dependent Vasodilatation Within the First Year After Heart Transplantation

BACKGROUND Peripheral endothelial dysfunction (ED) has been found in patients with severe heart failure. Whether ED improves after heart transplantation (HTx) is still a matter of controversy. METHODS Forearm endothelium-dependent vasoreactivity was assessed in 40 patients after HTx. Flow-mediated vasodilatation (FMD) was measured by high-resolution brachial artery ultrasound to assess endothelial function at 1, 6, and 12 months after HTx. Cardiac allograft vasculopathy (CAV) was assessed by coronary angiography at 1 and 12 months and by intravascular ultrasound (IVUS) at 1 year. RESULTS Mean FMD at 1 month was 1.9% +/- 2.6%, improving to 3.3% +/- 3.2% at 6 months (p < 0.005) and to 5.1% +/- 3.4% at 1 year (p < 0.0001). FMD was significantly impaired in 33 patients (82%) at 1 month, in 27 (67%) at 6 months, and in 19 (47%) at 1 year after HTx. CAV was diagnosed by IVUS in 19 patients (63%) at 1 year. Patients without peripheral ED at 1 month had lower incidence of increased intimal thickness of 0.5 mm or more at 1 year after HTx (20% vs 75%, p < 0.01). CONCLUSIONS Impairment of peripheral FMD was highly prevalent soon after HTx and was present in nearly 50% of patients at 1 year. Patients without peripheral ED at 1 month were associated with lower probability of CAV. Although more studies are needed, the evaluation of peripheral endothelial function at 1 month after HTx could be potentially useful to identify patients at lower risk of CAV.

Specialized Care Program for End-Stage Heart Failure Patients. Initial Experience in a Heart Failure Unit

INTRODUCTION AND OBJECTIVES End-stage heart failure is associated with very high morbidity and mortality. Palliative care has been little studied in affected patients. PATIENTS AND METHOD Between January 1998 and December 2004, 61 patients with end-stage heart failure participated in a specialized advanced heart failure care program. The program included patient education on advanced heart failure, with day-care and home-care elements, and involved intravenous drug administration when necessary. RESULTS The mean age of the study population was 64 (13) years (range 32-87 years), with 92% being male. Their mean ejection fraction was 23 (6%), mean systolic blood pressure 100 (16) mm Hg, mean blood sodium level 137 (4) mEq, mean creatinine level 1.7 (0.8) mg/dL, and mean hemoglobin level 12 (2) mg/dL. The number of hospitalizations, number of days in hospital per admission, and number of emergency room visits in the year before inclusion in the specialized heart failure care program were 5.7 (0.5), 53 (5), and 8.3 (1.1), respectively. After inclusion, these figures decreased significantly to 1.9 (0.2) (P=.0001), 19 (3) (P=.0001), and 1.2 (0.2) (P=.0001), respectively. During a mean follow-up period of 11 (10) months, 28 patients died (47%) and 23 (38%) underwent heart transplantation. In addition, use of the program led to a reduction in healthcare costs. CONCLUSIONS Although mortality in end-stage heart failure patients remained very high, use of a specialized advanced heart failure care program decreased the number of hospitalizations, days per hospitalization, and emergency room visits, and reduced the cost of care.

Activación neurohormonal en la insuficiencia cardíaca congestiva: ¿se normaliza después del trasplante cardíaco?

Introduccion y objetivo En los pacientes con insuficiencia cardiaca congestiva, la activacion neurohormonal desempena un papel importante en la progresion de la enfermedad y en el pronostico. El objetivo de este estudio fue determinar la evolucion de la activacion neurohormonal despues del trasplante cardiaco. Pacientes y metodo Se incluyo en el estudio a 37 pacientes en lista de espera para trasplante cardiaco. Se determinaron las concentraciones plasmaticas de angiotensina II, aldosterona, endotelina, peptido natriuretico auricular (PNA) y adrenomedulina antes y 1, 4, 9 y 12 meses despues del trasplante cardiaco. Las concentraciones plasmaticas de noradrenalina y renina se determinaron antes y 1 mes despues del trasplante. Resultados Las concentraciones de angiotensina II, noradrenalina y renina mostraron una tendencia no significativa hacia la reduccion. Las concentraciones de aldosterona no se modificaron, mientras que se produjo un incremento en las de endotelina a los 9 y 12 meses tras el trasplante. Las concentraciones plasmaticas de PNA y de adrenomedulina disminuyeron significativamente 1, 4, 9 y 12 meses despues del trasplante, comparadas con los valores previos al trasplante. Conclusiones Durante los primeros meses posteriores al trasplante cardiaco, no se producen reducciones significativas en las concentraciones plasmaticas de angiotensina II, aldosterona y endotelina, mientras que se reducen significativamente las concentraciones de peptidos con un efecto predominante vasodilatador (PNA y adrenomedulina). Este perfil neurohormonal desfavorable podria contribuir al desarrollo de complicaciones postrasplante, tales como edemas, hipertension arterial y disfuncion endotelial.

Neurohormonal Activation in Congestive Heart Failure: Does it Normalize After Heart Transplantation?

Introduction and objective In patients with congestive heart failure, neurohormonal activation plays an important role in disease progression and prognosis. The aim of this study was to document the evolution of neurohormonal activation after heart transplantation. Patients and method Thirty-seven patients on the waiting list for heart transplantation were included in the study. Plasma levels of angiotensin II, aldosterone, endothelin, atrial natriuretic peptide and adrenomedullin were measured before heart transplantation and again 1, 4, 9 and 12 months afterwards. Plasma levels of norepinephrine and renin were measured before and 1 month after heart transplantation. Results The levels of angiotensin II, norepinephrine and renin showed a nonsignificant trend towards reduction. The levels of aldosterone were unchanged, and an increase in endothelin levels was seen 9 and 12 months after transplantation. Plasma levels of atrial natriuretic peptide and adrenomedullin were significantly lower 1, 4, 9 and 12 months after heart transplantation compared to pretransplant levels. Conclusions During the first several months after heart transplantation there were no significant reductions in plasma levels of angiotensin II, aldosterone and endothelin, and there were significant reductions soon after surgery in peptides with a predominantly vasodilator effect (atrial natriuretic peptide and adrenomedullin). This unfavorable neurohormonal profile may contribute to the development of posttransplant complications such as edema, arterial hypertension and endothelial dysfunction.