Zika Virus Meningoencephalitis in an Immunocompromised Patient.

The World Health Organization considers the Zika virus (ZIKV) outbreak in the Americas a global public health emergency. The neurologic complications due to ZIKV infection comprise microcephaly, meningoencephalitis, and Guillain-Barré syndrome. We describe a fatal case of an adult patient receiving an immunosuppressive regimen following heart transplant. The patient was admitted with acute neurologic impairment and experienced progressive hemodynamic instability and mental deterioration that finally culminated in death. At autopsy, a pseudotumoral form of ZIKV meningoencephalitis was confirmed. Zika virus infection was documented by reverse trancriptase-polymerase chain reaction, immunohistochemistry, and immunofluorescence and electron microscopy of the brain parenchyma and cerebral spinal fluid. The sequencing of the viral genome in this patient confirmed a Brazilian ZIKV strain. In this case, central nervous system involvement and ZIKV propagation to other organs in a disseminated pattern is quite similar to that observed in other fatal Flaviviridae viral infections.

Short-term and long-term models of doxorubicin-induced cardiomyopathy in rats: A comparison of functional and histopathological changes.

OBJECTIVES: Doxorubicin (DXR), an anthracyclic antineoplastic agent, is one of the most commonly drug utilized to induce dilated cardiomyopathy (DCM) and heart failure (HF), but the well optimized protocol for cardiomyopathy induction leading to development of cardiac systolic dysfunction is unclear. This study aims to critically compare short-term and long-term DXR injection protocols for the induction of DCM in rats. METHODS: Animals were allocated into 3 experimental groups: a ST (short-term DXR injection) group, in which animals received 6 intraperitoneal (i.p.) injections of DXR (2.5mg/kg per dose) over a period of 2 weeks (cumulative dose of 15mg/kg); a LT (long-term DXR injection) group in which animals received weekly i.p. injections of DXR (2mg/kg per dose) over a period of 9 weeks (cumulative dose of 18mg/kg); and a control group in which animals received an appropriate volume of 0.9% saline i.p. All animals were submitted to echocardiography analysis at baseline and after completion treatment. Afterwards, the hearts were collected for conventional light microscopy and collagen quantification. RESULTS: Morphological myocardial analysis of both DXR-treated groups showed an identical pattern of swollen and vacuolated cardiomyocytes and disorganization of myofibrils. There was pronounced interstitial fibrosis in both groups of DXR-treated hearts as compared to controls, as assessed by the interstitial collagen volume fraction. There was no difference in interstitial fibrosis between the ST and LT groups. The echocardiography analysis of the LT group showed structural and functional findings compatible with DCM, including increased left ventricular systolic (5.02±0.96mm) and diastolic (7.68±0.96mm) dimensions and reduction of ejection fraction (69.40±8.51%) as compared to the ST group (4.10±0.89mm, 7.32±0.84, and 79.68±7.23%, respectively) and control group (4.07±0.72mm, 7.17±0.68mm and 80.08±4.71%, respectively), ANOVA p<0.01. CONCLUSIONS: These results indicate that LT injection of DXR is more effective than ST injection in inducing left ventricular dysfunction and structural cardiac changes resembling those found in dilated cardiomyopathy.

Calpain-mediated dystrophin disruption may be a potential structural culprit behind chronic doxorubicin-induced cardiomyopathy.

The critical importance of dystrophin to cardiomyocyte contraction and sarcolemmal and myofibers integrity, led us to test the hypothesis that dystrophin reduction/loss could be involved in the pathogenesis of doxorubicin-induced cardiomyopathy, in order to determine a possible specific structural culprit behind heart failure. Rats received total cumulative doses of doxorubicin during 2 weeks: 3.75, 7.5, and 15 mg/kg. Controls rats received saline. Fourteen days after the last injection, hearts were collected for light and electron microscopy, immunofluorescence and western blot. The cardiac function was evaluated 7 and 14 days after drug or saline. Additionally, dantrolene (5 mg/kg), a calcium-blocking agent that binds to cardiac ryanodine receptors, was administered to controls and doxorubicin-treated rats (15 mg/kg). This study offers novel and mechanistic data to clarify molecular events that occur in the myocardium in doxorubicin-induced chronic cardiomyopathy. Doxorubicin led to a marked reduction/loss in dystrophin membrane localization in cardiomyocytes and left ventricular dysfunction, which might constitute, in association with sarcomeric actin/myosin proteins disruption, the structural basis of doxorubicin-induced cardiac depression. Moreover, increased sarcolemmal permeability suggests functional impairment of the dystrophin-glycoprotein complex in cardiac myofibers and/or oxidative damage. Increased expression of calpain, a calcium-dependent protease, was markedly increased in cardiomyocytes of doxorubicin-treated rats. Dantrolene improved survival rate and preserved myocardial dystrophin, calpain levels and cardiac function, which supports the opinion that calpain mediates dystrophin loss and myofibrils degradation in doxorubicin-treated rats. Studies are needed to further elucidate this mechanism, mainly regarding specific calpain inhibitors, which may provide new interventional pathways to prevent doxorubicin-induced cardiomyopathy.

Discinergia ventricular esquerda reversível identificada por potenciação pós-extrassistólica em miocardiopatia chagásica crônica não é causada por hibernação miocárdica / Reversible dysynergy identified by post-extrasystolic potentiation in chronic chagas cardiomyopathy is not caused by myocardial hibernation

A alteração regional da mobilidade segmentar do ventrículo esquerdo é marcador precoce de miocardiopatia chagásica crônica. Demonstramos recentemente que a discinergia em algumas regiões ventriculares pode ser revertida pela potenciação pós-extrassistólica. Apesar de angiografia coronária normal, pacientes com miocardiopatia chagásica apresentam falhas de perfusão, corroborando a hipótese de que a hibernação miocárdica pode ser responsável pelas anormalidades de mobilidade segmentar revertidas durante a potenciação pós-extrassistólica. Método: Vinte e dois pacientes consecutivos portadores de miocardiopatia chagásica foram submetidos a angiografia coronária, ventriculografia e cintilografia miocárdica com tálio-201 com o protocolo estresse-redistribuição-reinjeção para avaliação da perfusão dos segmentos do ventrículo esquerdo...

Background: Regional left ventricular segmental wall motion impairment is an early marker of chronic Chagas cardiomyopathy. We have recently shown that dysynergy may be reversed in some ventricular regions by post-extrasystolic potentiation. Despite normal epicardial coronary arteries, patients with Chagas cardiomyopathy have perfusion defects, raising the possibility that myocardial hibernation could be responsible for the wall motion abnormalities reversed during post-extrasystolic potentiation. Methods: Twentytwo consecutive patients with chronic Chagas cardiomyopathy underwent coronary angiography, left ventricular contrast angiography and stress-redistribution-reinjection thallium-201 myocardial scintigraphy for the assessment of the perfusion status in left ventricular segments showing the presence of post-extrasystolic potentiation...

Persistência de distúrbios perfusionais miocárdicos após intervenção coronária percutânea com êxito: dependência de fatores microcirculatórios / Myocardial perfusion disturbances persisting after successful percutaneous coronary angioplasty: relationship to microcirculatory derangements

Introdução: A persistência transitória de defeitos perfusionais imediatamente após intervenção coronária percutânea bem sucedida para correção de estenoses coronárias é bem documentada. Método: Para testar a hipótese de que tais anormalidades perfusionais sejam associadas a distúrbios microcirculatórios causados por microembolização coronária, comparou-se a intensidade e extensão desses defeitos perfusionais detectados com cintilografia miocárdica em grupos randomicamente constituídos de pacientes tratados com angioplastia coronária por balão (AB) ou submetidos a aterectomia rotacional complementada por balão (AR + B). As características clínicas e angiográficas foram comparáveis nos dois grupos, assim como o sucesso do procedimento de angioplastia coronária. Resultados: Antes da intervenção coronária percutânea, o índice de defeito miocárdico, englobando a extensão e a gravidade da hipoperfusão, foi comparável nos dois grupos, na condição de estresse (AB = 7,72±1,91 vs AR + B = 8,61±3,38) e de repouso (AB = 3,11±1,22 vs AR + B = 2,40±1,63). Após o procedimento, o índice de defeito perfusional decresceu em ambos os grupos durante o estresse, mas com significância estatística apenas no grupo AB = 3,96±1,40 vs AR + B = 3,71 ±1,89. O contraste entre os dois grupos se acentuou na condição de repouso após a intervenção coronária: o índice de defeito decresceu de forma marginalmente significante no grupo AB para 1,46±0,66 e aumentou, embora sem significância estatística, no grupo AR + B, para 3,47±1,92. Conclusão: Esses resultados são compatíveis com o conceito de que a persistência transitória de defeitos perfusionais após angioplastia coronária bem sucedida seja dependente de distúrbios microcirculatórios associados à microembolização durante o procedimento.

Introduction: The transitory persistence of perfusion defects immediately after successful percutaneous coronary interventions to correct coronary stenosis is well known. Methods: To test the hypothesis that such perfusion abnormalities are associated with microcirculatory disorders caused by coronary microembolization we compared the intensity and extent of these perfusion defects detected using myocardial scintigraphy in groups of patients randomly assigned to coronary balloon angioplasty (BA) or to rotational atherectomy plus balloon angioplasty (RA + B). The clinical and angiography characteristics were comparable in both groups, as well as the successof the coronary angioplasty procedure. Results: Before the percutaneous coronary intervention the myocardium defect index, related to the extent and severity of hypoperfusion, was comparable for the two groups, both under stress (AB =7.72±1.91 vs. RA + B = 8.61±3.38) and at rest (AB = 3.11±1.22vs. RA + B = 2.40±1.63). After the procedure, the perfusion defect index decreased for both groups during stress, but with statistical significance only in the AB Group = 3.96±1.40 vs. RA + B = 3.71±1.89. The difference between the two groups was greater at rest after the coronary intervention procedure: the defect index decreased with marginal significance for the AB Group to 1.46±0.66 and increased, though without statistical significance, for the RA + B Group to 3.47±1.92. Conclusion: These results are compatible with the notion that transitory persistence of perfusion defects after successful coronary angioplasty are dependent on microcirculatory disorders associated to microembolization during the procedure

Myocardial kinetics of reporter probe 124I-FIAU in isolated perfused rat hearts after in vivo adenoviral transfer of herpes simplex virus type 1 thymidine kinase reporter gene.

UNLABELLED: Reporter gene imaging holds promise for noninvasive monitoring of cardiac gene therapy. We recently demonstrated that (124)I-labeled 2'-fluoro-2'-deoxy-5'-iodo-1beta-d-arabinofuranosyluracil ((124)I-FIAU) is suitable for PET of myocardial expression of herpes simplex virus type 1 thymidine kinase reporter gene (HSV1-tk). In contrast to previous studies in tumors, early specific uptake was followed by rapid washout. Myocardial kinetics of (124)I-FIAU are still poorly understood. This study aimed at a further investigation under controlled conditions using an isolated heart perfusion model. METHODS: Male Wistar rats underwent transthoracic regional injection of replication-defective adenovirus (2.5 x 10(9) plaque-forming units) containing either HSV1-tk (n = 16) or LacZ reporter gene (n = 15) into the inferior wall. Nonmanipulated rats (n = 5) served as further controls. Hearts were excised 2 d later and perfused according to the Langendorff technique with (124)I-FIAU-containing buffer (15 min, followed by 30 min of nonradioactive perfusion). Experiments were performed under baseline conditions and in the presence of thymidine (competitive substrate) or fludarabine (in vitro inhibitor of 5'-nucleotidase). Time-activity curves were acquired by external coincident detectors. The myocardial rate of (124)I-FIAU uptake (K(i)), clearance rate (K(o)), and volume of distribution (V(d) = K(i)/K(o)) were calculated. Subsequently, hearts were subjected to gamma-counting, followed by microtome slicing and autoradiography. RESULTS: The V(d) from Langendorff perfusion significantly correlated with final whole-heart tracer retention (r = 0.88, P = 0.019) and the autoradiographic area of regional myocardial activity (r = 0.89, P = 0.016). HSV1-tk hearts showed higher K(i) and V(d) of (124)I-FIAU compared with that of controls (P < 0.001) and detectable but slower washout compared with that of the LacZ group (P < 0.01). Addition of thymidine to the perfusate inhibited myocardial uptake of (124)I-FIAU by reducing V(d) and K(i) in HSV1-tk and LacZ hearts compared with the baseline. Addition of fludarabine did not result in the expected reduction of washout in HSV1-tk hearts due to inhibition of 5'-nucleotidases (which may dephosphorylate (124)I-FIAU monophosphate). It acted as an uptake inhibitor similar to thymidine, reducing V(d) in HSV1-tk hearts. CONCLUSION: Assessment of specific reporter probe kinetics after regional in vivo reporter gene transfer is feasible using the isolated perfused rat heart preparation. This model allows one to study the effects of pharmacologic interventions and may refine understanding of the reporter probe signal for in vivo imaging. Different nucleoside analogs significantly inhibit (124)I-FIAU uptake, emphasizing the importance of transporter mechanisms for reporter probe kinetics.

PET of cardiac transgene expression: comparison of 2 approaches based on herpesviral thymidine kinase reporter gene.

UNLABELLED: PET of reporter gene expression holds promise for noninvasive monitoring of gene therapy. Previously, 2 approaches based on the herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) have been successfully applied to the heart. Wild-type HSV1-tk was imaged with (124)I-labeled 2'-fluoro-2'-deoxy-5-iodo-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU), and a mutant HSV1-tk (HSV1-sr39tk) was imaged with (18)F-labeled 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine (FHBG). The aim of this study was to compare these 2 combinations with regard to specificity, imaging contrast, and reporter probe kinetics using dynamic PET in small and large animals. METHODS: Similar titers of adenovirus-expressing wild-type HSV1-tk (Ad(tk)), mutant HSV1-sr39tk (Ad(sr39tk)), or control genes were directly injected into the myocardium of 24 rats and 8 pigs. Two days later, dynamic PET was performed with a clinical scanner during the 120 min after injection of (124)I-FIAU (Ad(tk) animals and controls) or (18)F-FHBG (Ad(sr39tk) animals and controls). Imaging with (13)N-ammonia was performed to identify cardiac regions of interest. RESULTS: In rats, significant cardiac (124)I-FIAU accumulation occurred in images obtained early (10-30 min) after Ad(tk) injection. Because of tracer washout, however, no difference between Ad(tk)-injected animals and controls was seen in the images obtained later. For (18)F-FHBG, specific myocardial accumulation greater than background levels was detected in Ad(sr39tk)-injected animals at early imaging and, in contrast to (124)I-FIAU accumulation, increased over time until the latest imaging (105-120 min). At maximum, cardiac (18)F-FHBG concentration showed a 4.15 +/- 1.65-fold increase compared with controls (105-120 min), and cardiac (124)I-FIAU concentration reached a maximal increase of 1.34 +/- 0.38-fold compared with controls (10-30 min, P = 0.0014). Global cardiac reporter probe kinetics in rats were confirmed by regional myocardial analysis in pig hearts. Transgene expression was specifically visualized by both approaches. The highest target-to-background ratio of (124)I-FIAU in Ad(tk)-infected pig myocardium was 1.50 +/- 0.20, versus 2.64 +/- 0.49 for (18)F-FHBG in Ad(sr39tk)-infected areas (P = 0.01). In vivo results were confirmed by ex vivo counting and autoradiography. CONCLUSION: Both reporter gene/probe combinations were feasible for noninvasive imaging of cardiac transgene expression in different species. Specific probe kinetics suggest different myocardial handling of pyrimidine (FIAU) and acycloguanosine (FHBG) derivatives. The results favor (18)F-FHBG with mutant HSV1-sr39tk because of continuous accumulation over time and higher imaging contrast.

Noninvasive imaging of transgene expression by use of positron emission tomography in a pig model of myocardial gene transfer.

BACKGROUND: Radionuclide imaging of reporter gene expression may be useful for noninvasive monitoring of clinical cardiac gene therapy. Experience until now, however, has been limited to small animals. METHODS AND RESULTS: To evaluate feasibility in a clinically applicable setting, pigs were studied by conventional positron emission tomography (PET) 2 days after regional intramyocardial injection of control adenovirus or adenovirus carrying herpesviral thymidine kinase reporter gene (HSV1-tk). Myocardial blood flow was quantified by use of [13N]ammonia. Subsequently, kinetics of the reporter substrate [124I]-2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabino-furanosyluracil (FIAU) were assessed over a period of 2 hours. Areas infected with adenovirus expressing HSV1-tk showed significantly elevated FIAU retention during the first 30 minutes after injection. At later times, washout was observed, and retention was not different from that in areas infected with control virus or remote myocardium. Early in vivo FIAU uptake correlated with ex vivo images, autoradiography, and immunohistochemistry for reporter gene product after euthanasia. After intramyocardial injection of both adenoviruses, myocardial blood flow was mildly elevated compared with that in remote areas, consistent with histological signs of regional inflammation. CONCLUSIONS: In vivo quantification of regional myocardial transgene expression is feasible with clinical PET methodology, the radioiodinated reporter probe FIAU, and the HSV1-tk reporter gene. Radioactivity efflux after specific initial uptake was not observed previously in tumor studies, suggesting that tissue-specific differences in nucleoside metabolism influence reporter probe kinetics. By coregistering reporter gene expression with additional biological parameters such as myocardial blood flow, PET allows for noninvasive characterization of the success of cardiac gene transfer along with its functional correlates.

Perfil clínico, cinecoronariográfico e evolutivo precoce de pacientes jovens com infarto agudo do miocárdio na era trombolítica / Clinical Profile, Early Outcome and Coronary Angiography Findings in Young Patients with Acute Myocardial Infarction in the Thrombolytic Era

PURPOSE: To assess the clinical, angiographic and early follow-up findings of young patients suffering an acute myocardial infarction, in comparison with older patients with infarction, in the thrombolytic era. METHODS: A retrospective analysis of the medical records of 46 patients < 40 years-old (group I) at the time of an acute myocardial infarction was compared with that of 46 older patients, randomly selected, presenting with this syndrome between february, 1991 and february, 1996 (group II). In both groups a comparison was conducted regarding the proportions of gender, risk factors, type of infarction (Q vs non-Q), left ventricular function, coronary anatomy and early mortality (1 month). The medical treatment was comparable for both groups, including the utilization of thrombolytics. RESULTS: The groups were discriminated only by: higher prevalence of smoking, of angiographically normal coronary arteries, and of non-critical (< 75reduction of luminal diameter) coronary stenosis in group I; in the older group a higher proportion of patients had multivessel disease. Although not reaching statistical significance, a trend was observed to a more benign early course of the infarction in the patients less than < 40 years-old. CONCLUSION: The present findings are similar to those described in the pre-thrombolytic era, for young patients suffering an acute myocardial infarction.

Studies of the coronary circulation in Chagas' heart disease

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually tree of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be a causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.

Reagudizaçäo de cardite chagásica provocando insuficiência ventricular direita exclusiva / Reactivation of Myocarditis in Chagas' Disease Inducing Isolated Right Ventricular Failure

Woman, 42 years-old, receiving immunosuppressive therapy for a lymphoma, presented reagudization of Chagas' disease, from its indeterminate phase. Intense inflammatory visceral aggression, due to extensive intracellular proliferation of the Trypanosoma cruzi, was the likely mechanism for acute myocarditis leading to severe right ventricular failure. Antiparasite chemotherapy was effective in the control of visceral involvement and for the remission of cardiac failure. The clinical course in this case is compatible with the hypothesis of early right ventricular damage in Chagas' disease

A circulaçäo coronária na cardiopatia chagásica crônica / Coronary circulation in chronic Chagas' heart disease

Anormalidades anatômicas e funcionais da circulaçäo coronária têm sido descritas e englobadas na teoria vascular da patogênese da cardiopatia chagásica crônica. Neste artigo foram criticamente revistos resultados de estudos em humanos e modelos experimentais da infecçäo como o T.Cruzi sobre aspectos anatômicos e funcionais da circulaçäo coronária, no epicárdio e na microcirculaçäo. por evidências necroscópicas e cinecoronariográficas, as artérias epicárdicas näo exibem, em geral, lesöes obstrutivas consideradas capazes de induzir isquemia miocárdica. Constituem exceçäo aqueles pacientes chagásicos estudados após episódio de infarto agudo do miocárdio, que apresentam frequência de obstruçöes coronarianas superponível à encontrada na populaçäo näo-chagásica com infarto agudo do miocárdio. Distúrbios prefusionais, compatíveis com as alteraçöes microvasculares experimentalmente documentadas, säo observados em pacientes chagásicos crônicos com coronárias angiograficamente normais. Essas alteraçöes podem ter relaçäo causal com a disfuncçäo contrátil regional detectada em regioöes com hipoperfusäo crônica, sugerindo a ocorrência de possíveis áreas de hibernaçäo miocárdica, análoga à que se verifica na cardiopatia isquêmica aterosclerótica. Investigaçöes recentes em cardiopatas chagásicos com precordialgia sugerem anormalidades no controle vasomotor coronariano, havendo atenuaçäo das respostas arteriais epicárdicas aos estímulos constritor e dilatador.

Detecção de isquemia miocárdica em chagásicos crônicos com precordialgia atípica pelos testes de esforço e Holter / Detection of Myocardial Ischemia in Chagas' Disease Patients with Angina-Like Symptoms by the Effort Test and Holter Monitoring

Objetivo - Investigar a freqüência e as características de alteraçöes isquêmicas miocárdicas detectadas pela eletrocardiografia de esforço e monitorizaçäo eletrocardiográfica contínua (Holter) em pacientes chagásicos com dor precordial. Métodos - Trinta e um pacientes com diagnósticos clínicos e sorológico de doença de Chagas (54,4 ñ 9,6 anos, 51// homens) foram investigados para esclarecimento causal de angina de peito intensa e preocupante a ponto de afetar o padräo de vida e exigir exploraçäo agressiva. A detecçäo de isquemia miocárdica consistiu de 1 teste de esforço máximo e 2) Holter de 24h. Todos os pacientes foram submetidos a cinecoronariografia, ocasiäo em que se executava manobra de hiperventilaçäo controlada para constataçäo de espasmo arterial coronário. Os resultados obtidos com os dois testes (esforço e Holter) foram correlacionados e confrontados com os obtidos durante a cinecoronariografia. Resultados - alteraçöes basais do eletrocardiograma (ECG) impediram a análise do segmento ST em 11 pacientes. Dos restantes, 7(35//) apresentaram angina no teste de esforço. Dois deles (10//) tiveram isquemia miocárdica concomitante, detectando-se coronariopatia orgânica/funcional em ambos (associaçäo positiva, p=0,03): lesöes de 90// na artéria circunflexa e de 50// no trajeto intramiocárdico da descendente anterior esquerda. Nesta última, após hiperventilaçäo, ocorreu espasmo que reduziu em mais de 30// o diâmetro luminal do segmento estenótico, com dor precordial e elevaçäo de ST, que reverteram com nitrato. Durante o Holter (16 pacientes com traçados aproveitáveis), 25// dos indivíduos apresentaram angina do peito, sem qualquer distúrbio arrítmico ou isquêmico concomitante. Isquemia silente ocorreu em 1 paciente (5//) durante o esforço e, em outros (18//), durante o Holter. Sua presença näo foi preditiva de alteraçöes coronárias orgânicas ou funcionais. Näo foram documentadas lesöes significativas nos 11 pacientes cujo ECG näo era passível de análise. Conclusäo - Observou-se importante limitaçäo da aplicabilidade geral dos métodos eletrocardiográficos para detecçäo de isquemia miocárdica nos pacientes chagásicos em decorrência das alteraçöes basais do ECG. Contudo, quando o ECG basal é adequado, o teste de esforço positivo (ST isquêmico, acompanhado de dor precordial) apresentou 100// de valor preditivo para doença arterial coronária orgânica/funcional. Isto ocorreu em pequena, porém näo desprezivel proporçäo desta populaçäo chagásica específica (10//). O teste de Holter näo contribuiu para elucidaçäo da origem da angina do peito em qualquer um dos doentes estudados. Ante a inconsistência dos resultados, o significado o significado clínico e fisiopatológico da isquemia silente na cardiopatia chágasica demanda investigaçäo ulterior

Purpose - To determine the incidence and characteristics of myocardial ischemia, as detected by stress electrocardiography and Holter monitoring in Chagus' patients whose main complaint was precordial pain. Methods - Thirty-one consecutive patients with Chagas' disease diagnosed on the basis of clinical and serological tests, and precordial pain severe enough to warrant cardiac catheterization were studied. Mean age was 54.4 ± 9.6 years, and 51% were males. EKG changes indicative of myocardial ischemia were sought during maximul exercise and also during 24-hour Holter monitoring. The detection of myocardial ischemia by each one of these tests was compared by Fischer exact test, and also correlated to anatomical and functional results of coronary angiography at rest and after standardized hyperventilation for detecting coronary vasospasm. Results - Baseline EKG changes mainly associated with ventricular conduction defects precluded the analysis of the ST segment in 11 patients. Among the other 20 patients, 7(35%) had angina during the exercice test, of whom only 2(10%) showed concomitant ischemic ST changes: one had 90% stenosis in the circumflex branch and the other 50% reduction of luminal diameter in a intramyocardial segment of the leit anterior descending coronary artery, undergoing further 30% constriction after hyperventilation, with pain and ST-elevation that responded to nitrate administration. Thus, a positive correlation between a positive EKG exercise test with accompanying symptoms, and organic/functional coronary artery disease was found (p = 0.03). Holter tracings of good quality were obtained in 16 patients. Angina-like symptoms occurred in 25% of these patients, without concomitant ischemic or dysrhythmic EKG changes. Conversely, silent ischemia was detected in 1 (5%) patient during exercice and in 3 (18%) patients during the Holter monitoring None of these patients had any evidence of organic or functional alterations in the coronary arteries. The absence of significant (> 50%) narrowing of the coronary arteries, t baseline and after hyperventilation, was also documented in the 11 patients in whom no valid EKG tracings were obtained for analysis. Conclusion - EKG-based methods for detecting myocardial eschemia are of limited value in the general population with Chagas' disease presenting with precordial pain, due to the high prevalence of baseline ST changes. The overall incidence of significant coronary artery disease, as detected by angiography, was low but not negligible in this population of Chagas' patients with precordial pain (4%). Nevertheless, a positive EKG test based on ST changes and accompanying pain has a 100% positive predictive accuracy for the presence of organic or functional coronary abnormalities. No additional yield was obtained with Holter monitoring, for the elucidution of the pathophysiology of the precordial pain in Chagas' patients with atypical angina. The significance of episodes of silent ischemia in some of these patients, with angiographically normal coronary arteries, remains to be determined

Protocolo para o atendimento da parada cárdio-respiratória / Guidelines for cardiopulmonary resuscitation

Os autores apresentam de forma sintética e prática os passos para o atendimento da Parada Cárdio-Respiratória (PCR), estabelecidos como rotina pela Divisäo de Cardiologia do HC-FMRPUSP. Säo revistos, à luz das contribuiçöes mais recentes da literatura médica, os conceitos que fundamentam os procedimentos preconizados em cada uma das fases do atendimento da PCR