Christiano Pereira Silva

Mychophenolate Mofetil Increased Chagas Disease Reactivation in Heart Transplanted Patients: Comparison Between Two Different Protocols

Heart transplantation (HT) remains the treatment of choice for advanced chagasic cardiomyopathy. New immunosuppression protocols have provided better control of rejection (RJ) and cardiac allograft vasculopathy. However, their influence on infection and Chagas disease reactivation (CDR) is not well established. The aim of this study was to compare the CDR rate in patients under two different immunosuppression protocols. We studied 39 chagasic patients who had undergone orthotopic HT between April, 1987 and June, 2004. They were divided into two groups, one taking azathioprine (group 1 = 24 patients) and the other taking mycophenolate mofetil (group 2 = 15 patients), in the standard doses (2 mg/kg/day and 2 g/day, respectively), beside prednisone and cyclosporine, in equivalent doses. The number of CDR and RJ episodes were analyzed in the first and second years after HT. CDR rates were 8%± 5% at 1 year and 12%± 6% at 2 years of follow‐up in group 1. Otherwise, patients in group 2 presented CDR rates of 75%± 10% and 81%± 9% at the same periods, respectively (p < 0.0001, hazard ratio = 6.06). When comparing RJ rates in the first year after HT, both groups had similar behavior under both immunosuppression protocols (p = 0.88). These data show that current prescribed doses of mycophenolate mofetil increase the early risk of CDR without changing RJ incidence in this period.

Insuficiência cardíaca descompensada na unidade de emergência de hospital especializado em cardiologia

FUNDAMENTO: Estudos nacionais em insuficiencia cardiaca descompensada (ICD) sao fundamentais para o entendimento dessa afeccao em nosso meio. OBJETIVO: Determinar as caracteristicas dos pacientes com ICD em uma unidade de emergencia. METODOS: Examinamos prospectivamente 212 pacientes com o diagnostico de insuficiencia cardiaca descompensada, os quais foram admitidos em uma unidade de emergencia (UE) de hospital especializado em cardiologia. Estudaram-se variaveis clinicas, apresentacao e causas de descompensacao. Em 100 pacientes, foram analisados exames complementares, prescricao de drogas vasoativas, tempo de internacao e letalidade. RESULTADOS: Entre os pesquisados houve predominio de homens (56%) e a etiologia isquemica foi a mais frequente (29,7%), apesar da elevada frequencia de valvares (15%) e chagasicos (14,7%). A forma de apresentacao e a causa de descompensacao mais comuns foram, respectivamente, congestao (80,7%) e ma adesao/medicacao inadequada (43,4%). Na subanalise dos 100 pacientes, a disfuncao sistolica foi a mais frequente (55%), uso de drogas vasoativas ocorreu em 20% e a letalidade foi de 10%. Analise comparativa entre os pacientes que receberam alta e faleceram durante a internacao ratificou alguns criterios de mau prognostico: pressao arterial sistolica reduzida, baixo debito associado a congestao, necessidade de droga vasoativa, fracao de ejecao do ventriculo esquerdo reduzida, diâmetro diastolico do ventriculo esquerdo (DDVE) aumentado e hiponatremia. CONCLUSAO: Este trabalho apresenta dados sobre o perfil da populacao com insuficiencia cardiaca descompensada atendida na unidade de emergencia de um hospital especializado em cardiologia da regiao sudeste do Brasil. Na avaliacao inicial destes pacientes dados clinico-hemodinâmicos e de exames complementares fornecem subsidios para estratificacao de risco, auxiliando na decisao de internacao e estrategias terapeuticas mais avancadas.

Transplantation for Chagas' disease: an overview of immunosuppression and reactivation in the last two decades.

Bacal F, Silva CP, Pires PV, Mangini S, Fiorelli AI, Stolf NG, Bocchi EA. Transplantation for Chagas’ disease: an overview of immunosuppression and reactivation in the last two decades.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2009.01202.x.
© 2010 John Wiley & Sons A/S.

Por que os portadores de cardiomiopatia chagásica têm pior evolução que os não-chagásicos?

BACKGROUND: Heart failure is a highly prevalent disease, the prognosis of which depends on different predictive factors. OBJECTIVE: Chagas disease is a predictor of poor prognosis in patients with chronic heart failure (HF). The purpose of this study is to investigate whether this condition also predicts poor outcome in acutely decompensated patients. METHODS: Four hundred and seventeen patients admitted for decompensated heart failure were studied. Mean age was 51.8 years, and 291 (69.8%) were male. They were divided into two groups: 133 (31.9%) patients with Chagas heart disease (CH) and 284 patients with heart failure of other etiologies. Cytokine and norepinephrine plasma levels were measured in a subgroup of 63 patients (15.1% with Chagas disease). RESULTS: At admission, 24.6% of the patients needed inotropic support, and one-year mortality was 54.7%. Mortality rates were higher in the CH group (69.2% vs. 47.9%, p < 0.001). When data were compared, patients with Chagas disease were younger (47.6 vs. 53.8 years, p < 0.001) and, on average, showed lower systolic blood pressure (96.7 vs. 111.2 mmHg, p < 0,001), ejection fraction (32.7 vs. 36.4%, p < 0.001), and serum Na (134.6 vs. 136.0, p = 0.026), in addition to higher TNF-α levels (33.3 vs. 14.8, p = 0.001). The presence of hypotension requiring inotropic support, left ventricular (LV) diastolic diameter, renal function findings, and interleukin-6 and norepinephrine plasma levels did not differ between both groups. CONCLUSION: Chagas disease patients admitted with decompensated heart failure had worse prognoses than patients with heart failure of other etiologies. This may be owing to a greater degree of cardiac impairment (lower ejection fraction) and hemodynamic instability (lower systolic blood pressure and heart rate), increased activation of the renin-angiotensin system (lower sodium), and increased cytokine levels (TNF-α).

Impact of sublingual sildenafil on pulmonary hypertension in patients with heart failure

BACKGROUND Pulmonary hypertension (PH) is a factor of poor prognosis in the postoperative period of heart transplant (HT) and thus, the study of the degree of reversibility to vasodilators is mandatory during the preoperative assessment. OBJECTIVE To evaluate the pulmonary and systemic hemodynamic effects of sildenafil as a vasodilator during the PH reversibility test in patients that are candidates to HT. METHODS Patients awaiting HT were submitted to the measurement of systemic and pulmonary hemodynamic variables before and after the administration of a single sublingual dose of 100 mg of sildenafil during right heart catheterization. RESULTS Fourteen patients (age: 47+/-12 years, 71.4% men) with advanced heart failure Ejection Fraction (EF) 25 +/- 7%, Functional Class (FC - NYHA) FC III - 6 and FC IV - 8, were evaluated in this study. The acute administration of sildenafil showed to be effective in decreasing the systolic (62.4 +/- 12.1 vs 51.5 +/- 9.6 mmHg, CI=95%, p<0.05) and mean (40.7 +/- 7.3 vs 33.8 +/- 7.6 mmHg, CI=95%, p <0.05) pressures of the pulmonary artery. There was also a significant decrease in the pulmonary (4.2 +/- 3 vs 2.0 +/- 0.9 uWood, CI=95%, p<0.05) and systemic vascular resistance (22.9 +/- 6.8 vs 18.6 +/- 4.1 Wood, CI=95%, p<0.05), associated to an increase in the cardiac output (3.28 +/- 0.79 vs 4.12 +/-1.12 uWood, CI=95%, p<0.05) without, however, significantly interfering in the systemic arterial pressure (87.8 +/- 8.2 vs 83.6 +/- 9.1 mmHg, CI=95%, p=0.3). CONCLUSION The sublingual administration of sildenafil is an effective and safe alternative as a vasodilator during the PH reversibility test in patients with heart failure and awaiting a HT.FUNDAMENTO: La hipertension pulmonar (HP) se muestra factor de mal pronostico en el postoperatorio de transplante cardiaco (TC) y, de esta forma, el estudio del grado de reversibilidad a vasodilatadores se vuelve obligatorio durante evaluacion preoperatoria. OBJETIVO: Evaluar los efectos hemodinamicos pulmonares y sistemicos del Sildenafil como droga vasodilatadora durante la prueba de reversibilidad de la HP en candidatos a transplante cardiaco. METODOS: Pacientes en fila para TC fueron sometidos a la medicion de variables hemodinamicas sistemicas y pulmonares, antes y luego de la administracion de 100mg en dosificacion unica y sublingual de Sildenafil, durante cateterizacion cardiaca derecha. RESULTADOS: Se evaluaron en este estudio a 14 pacientes (edad: 47±12 anos, el 71,4% varones) con insuficiencia cardiaca avanzada, fraccion de eyeccion (FE) 25 ± 7%, clase funcional (CF-NYHA) CF III - 6 y CF IV - 8. La administracion aguda de Sildenafil se mostro eficaz en la reduccion de las presiones sistolica (62,4 ± 12,1 vs 51,5 ± 9,6 mmHg, IC=95%, p<0,05) y media (40,7 ± 7,3 vs 33,8 ± 7,6 mmHg, IC=95%, p <0,05) de la arteria pulmonar. Hubo tambien una reduccion significativa de la resistencia vascular pulmonar (4,2 ± 3 vs 2,0 ± 0,9 uWood, IC=95%, p<0,05) y sistemica (22,9 ± 6,8 vs 18,6 ± 4,1 Wood, IC=95%, p<0,05), asociada a una elevacion del debito cardiaco (3,28 ± 0,79 vs 4,12 ±1,12 uWood, IC=95%, p<0,05) sin, con todo, interferir de manera significativa en la presion arterial sistemica (87,8 ± 8,2 vs 83,6 ± 9,1 mmHg, IC=95%, p=0,3). CONCLUSION: El Sildenafil sublingual resulta una alternativa eficaz y segura como droga vasodilatadora durante la prueba de reversibilidad de la HP en portadores de insuficiencia cardiaca y en fila para transplante cardiaco.

VO2 pico e inclinação VE/VCO2 na era dos betabloqueadores na insuficiência cardíaca: uma experiência brasileira

Methods: We studied 391 patients with heart failure, aged 49 ± 14 years and presenting a left ventricular ejection fraction of 38 ± 10%. The total number of patients that used (Group I - GI) or did not use (Group II - GII) betablockers was 229 and 162, respectively. All patients were submitted to a cardiopulmonary stress test on a treadmill, using the Naughton protocol. Results: A peak VO 2 16 ml.kg-1.min-1 categorizes patients with a better mid- term prognosis. Peak VO2 values between > 10 and < 16 ml.kg -1 .min -1 indicated moderate risk for cardiac event in four years of follow up. The betablocker use significantly reduced the VE/VCO 2 slope in patients with HF. The prognostic value of the VE/VCO 2 slope < 34 in the group using betablocker can reflect the impact of the drug on this cardiorespiratory variable. Conclusion: A low peak VO2 and an elevated VE/VCO2 slope are strong and independent predictors of cardiac events in HF. Thus, both variables remain important survival predictors in patients with HF, especially at the age of betablockers. (Arq Bras Cardiol 2007;88(6):624-628)

Reduction of central sleep apnea in heart failure patients with beta-blockers therapy

BACKGROUND Sleep apneas are frequent in patients with heart failure (HF). Estimate of the pre-beta blocker age (BB) point out to 45% of central apneas in these patients. OBJECTIVE Assess the influence of BB in central apneas and their interference in the quality of sleep and life of patients with heart failure. METHODS 65 patients with heart failure underwent diagnostic polysomnography. Polysomnography have been assessed according to the use or not of BB. On the day of examination, the patients answered the Minnesota questionnaire for quality of life with HF. After 6 and 12 months from the polysomnography date, all patients were contacted by phone, in order to repeat the Minnesota questionnaire. RESULTS The prevalence of sleep apnea (IAH > 15/h) hit 46.1% in the total population, however, central sleep apnea was identified in 18.4% of patients. The use of BB, in a multivariate analysis, was the only predictor of a minor index of central apnea and hypopnea (IAH) (p=0.002), greater saturation (p=0.02) and smaller average desaturation of oxygen (p=0.03). Additionally, the use of BB could predict a better quality of life after 6 and 12 months (p=0.002 and 0.001 respectively) and a smaller number admissions in these periods (p=0.001 and p=0.05 respectively). CONCLUSION The use BB reduced the rate of central sleep apnea in total population, if we compare to literature data. Additionally, the BB improved parameters of quality of sleep and life of patients with heart failure.FUNDAMENTO: As apneias do sono sao doencas frequentes em portadores de insuficiencia cardiaca (IC). Estimativas da era pre-betabloqueador (BB) apontam para uma prevalencia de 45% de apneias centrais nestes pacientes. OBJETIVO: Avaliar a influencia dos BB na prevalencia das apneias centrais e sua interferencia na qualidade do sono e de vida de portadores de IC. METODOS: 65 pacientes portadores de IC foram submetidos a polissonografia diagnostica.Os resultados da polissonografia foram avaliados de acordo com o uso ou nao de BB. No dia do exame os pacientes responderam ao questionario de Minessota para qualidade de vida com IC. Apos 6 e 12 meses da data da polissonografia, houve contato telefonico com todos os pacientes, para a repeticao do questionario de Minessota. RESULTADOS: A prevalencia de apneia do sono (IAH > 15/h) foi de 46,1% na populacao total, porem a apneia central foi identificada em apenas 18,4% dos pacientes. O uso de BB, em analise multivariada, foi o unico preditor de ocorrencia de menor indice de apneia e hipopneia (IAH) central (p=0,002), maior saturacao (p=0,02) e menor dessaturacao media de oxigenio (p=0,03). Alem disso, o uso de BB foi preditor de melhor qualidade de vida apos 6 e 12 meses (p=0,002 e 0,001 respectivamente) e de menor numero de hospitalizacoes nestes periodos (p=0,001 e p=0,05 respectivamente). CONCLUSAO: O uso de BB reduziu a incidencia de apneia central na populacao total, se compararmos com os dados da literatura. Alem disto, os BB melhoraram parâmetros da qualidade do sono e de vida de portadores de IC.

Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores

OBJECTIVES The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. METHODS A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. RESULTS Most of the patients were Functional Class II (42.3%) and evolution stage C (94.9%). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor--enalapril and captopril--or angiotensin receptor antagonist--losartan), whereas 85% of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. CONCLUSION Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

Sildenafil vs. Nitroprussiato de Sódio durante Teste de Reatividade Pulmonar pré-transplante cardíaco

BACKGROUND: Pulmonary hypertension is associated with a worse prognosis after cardiac transplantation. The pulmonary hypertension reversibility test with sodium nitroprusside (SNP) is associated with a high rate of systemic arterial hypotension, ventricular dysfunction of the transplanted graft and high rates of disqualification from transplantation. OBJECTIVE: This study was aimed at comparing the effects of sildenafil (SIL) and SNP on hemodynamic, neurohormonal and echocardiographic variables during the pulmonary reversibility test. METHODS: The patients underwent simultaneously right cardiac catheterization, echocardiography, BNP measurement, and venous blood gas analysis before and after receiving either SNP (1 - 2 µg/kg/min) or SIL (100 mg, single dose). RESULTS: Both drugs reduced pulmonary hypertension, but SNP caused a significant systemic hypotension (mean blood pressure - MBP: 85.2 vs. 69.8 mm Hg; p < 0.001). Both drugs reduced cardiac dimensions and improved left cardiac function (SNP: 23.5 vs. 24.8%, p = 0.02; SIL: 23.8 vs. 26%, p < 0.001) and right cardiac function (SIL: 6.57 ± 2.08 vs. 8.11 ± 1.81 cm/s, p = 0.002; SNP: 6.64 ± 1.51 vs. 7.72 ± 1.44 cm/s, p = 0.003), measured through left ventricular ejection fraction and tissue Doppler, respectively. Sildenafil, contrary to SNP, improved venous oxygen saturation, measured on venous blood gas analysis. CONCLUSION: Sildenafil and SNP are vasodilators that significantly reduce pulmonary hypertension and cardiac geometry, in addition to improving biventricular function. Sodium nitroprusside, contrary to SIL, was associated with systemic arterial hypotension and worsening of venous oxygen saturation.

Desmin-related restrictive cardiomyopathy

Restrictive cardiomyopathies may have different etiologies, among which we can point out storage diseases by accumulation of different materials such as desmin. Desminopathies are uncommon diseases that progress with conduction abnormalities, peripheral myopathies, and ventricular dysfunction. The present report describes a patient with complete atrioventricular block as the initial event; he later developed skeletal muscle alterations and heart failure. The investigation led to the diagnosis of restrictive cardiomyopathy due to desmin accumulation.