Sandrigo Mangini

Cardiomyopathy, adult valve disease and heart failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas’ disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas’ disease and rheumatic fever in South American countries.

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.

Exhaled Acetone as a New Biomarker of Heart Failure Severity

BACKGROUND Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. METHODS Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. RESULTS The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). CONCLUSIONS EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity.

Mode of Death on Chagas Heart Disease: Comparison with Other Etiologies. A Subanalysis of the REMADHE Prospective Trial

Background Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. Methods and results We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34–5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04–1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97–0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47–6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01–1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34–0.94; p = 0.014) were independently associated with sudden death mortality. Conclusions In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. Trial Registration ClinicalTrails.gov NCT00505050 (REMADHE)

Stress-induced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases.

Cardiac complications after liver transplantation are a common cause of death. Stress-induced cardiomyopathy, also called takotsubo cardiomyopathy, is a special form of cardiomyopathy that is precipitated by a stress situation. It can occur after a surgical procedure that results in acute heart failure. Herein we have presented 2 cases of reversible stress-induced cardiac dysfunction early in the period after liver transplantation. Before surgery, cardiac evaluation was normal, with both patients classified as low risk for cardiovascular events during the proposed procedure. Both patients experienced cardiac arrest after graft reperfusion with return of spontaneous circulation after resuscitation. Their early periods after transplantation were characterized by cardiogenic shock secondary to important ventricular dysfunction requiring vasoactive drugs. Subsequent investigations excluded coronary disease. The diagnosis of takotsubo cardiomyopathy was established based on the clinical features and ancillary tests, particularly echocardiography showing apical ballooning. In both cases, ventricular function recovered completely. In conclusion, stress-induced cardiomyopathy, an underestimated cause of heart complications, should be considered as a possible cause of cardiac failure in liver transplant patients.

Solução salina hipertônica para prevenção de insuficiência renal em pacientes com insuficiência cardíaca descompensada e hiponatremia

BACKGROUND: Hyponatremia and congestive phenomena indicate a bad prognosis in decompensated heart failure. The occurrence of renal failure is associated to an increased death risk. OBJECTIVE: To evaluate the safety and efficacy of the hypertonic saline solution in patients with decompensated heart failure for renal failure prevention. METHODS: Patients with decompensated heart failure, congestion and hyponatremia participated in the study. In addition to the standard treatment, the patients received hypertonic saline solution and were submitted to clinical as well as laboratory assessment. RESULTS: Nine patients were enrolled in the study. Mean age was 55 + 14.2 years, being 5 male (55.5%) and 4 (44.5%) female patients. All of them presented functional class III-IV of the New York Heart Association (NYHA), and 5 (55.5%) received dobutamine. All of them presented initial creatinine > 1.4 mg/dl. The mean tonicity of the solution was 4.39% + 0.018% (2.5% to 7.5%) and the duration of treatment was 4.9 days + 4.1 days (1-15 days). There were no severe adverse effects; none of the patients presented clinical worsening or neurologic disorders; hypokalemia occurred in 4 cases (44.5%). The comparison of the variables before and after treatment showed a decrease in urea (105 mg/dl + 74.8 mg/dl vs. 88 mg/dl + 79.4 mg/dl; p = 0.03) and increase in the urinary volume (1,183 ml/day vs. 1,778 ml/day; p = 0.03); there was no tendency to creatinine decrease (2.0 mg/dl + 0.8 mg/dl vs. 1.7 mg/dl + 1.0 mg/dl; p = 0.08). Despite the elevation in sodium levels (131 mEq/l + 2.8 mEq/l vs. 134 mEq/l + 4.9 mEq/l) and weight decrease (69.5 kg + 18.6 kg vs. 68.2 kg + 17.1 kg), there was no statistically significant difference. CONCLUSION: The use of hypertonic saline solution in patients with decompensated heart failure can be a safe therapeutic method and potentially related to clinical improvement and renal failure prevention.

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.

Validation of a cutoff value on echo Doppler analysis to replace right heart catheterization during pulmonary hypertension evaluation in heart transplant candidates.

BACKGROUND Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. OBJECTIVES Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. METHODS One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >or= 60 mm Hg; a mean transpulmonary gradient >or= 15; or pulmonary vascular resistance >or= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. RESULTS A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. CONCLUSIONS The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Heart transplantation: review

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.