Estudio sobre la miocardiopatía hipertrófica: aspectos clínicos, ecocardiográficos, hemodinámicos y angiocardiográficos en una serie de treinta pacientes / Hypertronic mycardiopathy study: clinical, ecocardiographic, ecographic, hemodynamic and angiographic aspects in series of thirty patients

Se hace la descripción clínica de la miocardiopatía hipertrófica en el medio venezolano. El estudio versó sobre los aspecto clínicos, ecocardiográficos, hemodinámicos y angiocardiográficos de esta entidad, el cual fue realizado en una serie de treinta pacientes, observados durante el lapso de 7 años (1978-1985) en nuestro país. El espectro clínico de la afección fue muy amplio, el cual abarcó desde formas asintomáticas hasta formas con sintomatología de severidad progresiva. El diagnóstico clínico se fundamentó en una historia clínica sugestiva, a veces de carácter familiar, con una signología en la que sobresalen las alteraciones del pulso, el hallazgo de un choque apexiano anormal (bífido o trífido), el latido presistólico y los soplos relacionados con la obstrucción del tracto de salida y la insufiencia valvular mitral. La enfermedad se caracterizó por un cuadro clínico de evolución progresiva. El diagnóstico clínico fue corroborado por la presencia de dos alteraciones ecocardiográficas significativas: 1) la hipertrofia septal asimétrica, 2) el movimiento sistólico anterior de la valva anterior de la válvula mitral o de ambos. En el estudio hemodinámico por la presencia de un gradiente de presión intraventricular en reposo o provocado y en la angiocardiografía por la constatación de la hipertrofia septal y de los músculos papilares. Se desconoce la prevalencia de la afección en escala mundial y nacional. Es necesario realizar estudios sobre el aspecto familiar y las alteraciones genéticas que presenta la afección en nuestro medio. Los estudios patológicos, realizados en el Instituto de Anatomía Patológica, UCV, han permitido corroborar las alteraciones estructurales características de la afección en el material patológico de nuestro medio

HLA-C(*)03 is a risk factor for cardiomyopathy in Chagas disease.

Previous studies have shown the effect of class 1 as detected by serology or class 2 HLA genes by oligotyping upon susceptibility or resistance to the cardiomyopathy that develops in approximately one third of the Trypanosoma cruzi chronically infected patients. Low and intermediate resolution DNA typing of class 1 alleles was performed in a sample of 113 serologically positive individuals with and without cardiomyopathy. A polymerase chain reaction-sequence-specific oligonucleotide probe method using primers and probes from the British Society of Histocompatibility and Immunogenetics as modified for the VII Latin American Histocompatibility Workshop by D. Middleton, and LiPA kits from Innogenetics were used. Several alleles (A(*)11, A(*)31, B(*)15, B(*)35, B(*)45, B(*)49, B(*)51, and C(*)03) showed increased frequencies among patients with cardiac damage versus the asymptomatic group, but only the last one remained significant after correction of the p value (OR = 5.8, p(c) = 0.03). HLA-C(*)03 showed linkage disequilibrium with B(*)40 and B(*)15 and although both haplotypes were increased in cardiopathic patients compared with asymptomatic individuals, the difference is not significant. These results suggest that the HLA-C*03 allele could confer susceptibility to the development of cardiomyopathy among Venezuelan T. cruzi seropositive individuals and contrast with the protective effect conferred by the HLA B40 Cw3 haplotype among Chilean chagasic patients. Further studies will be needed to confirm the role of this allele on the cardiomyopathy of Chagas disease.

[Dilated cardiomyopathy: recent advances and current treatment]. / Miocardiopatía dilatada: avances recientes y tratamiento actual.

The combination of dilatation and systolic dysfunction of the left or both ventricles from idiopathic or specific origin define dilated cardiomyopathy (DC). It is an important cause of cardiac morbidity through congestive heart failure (CHF) or arrhythmias. Prevalence studies estimate a rate of left ventricular systolic dysfunction of 2% to 3% or more, and of 1.5% of CHF among the general population. Genetic studies on familial DC have identified at least 5 genetic locus. In addition, the role of virus, genetic abnormalities, immunologic responses and increased myocardial apoptosis are factors recognized factors that play a significant role in the pathogenesis of idiopathic DC. Mortality in severe CHF may reach 50% at 2 years after diagnosis. The introduction of "triple" therapy combining diuretics, digoxin and angiotensin converting enzyme inhibitors (ACEI) has significantly decreased this high mortality. Recent large, multicentric clinical trials on drugs aimed to diminish the neuroendocrine hyperactivity of patients in stable chronic CHF (betablockers and spirolactone) have resulted in an additional reduction in total mortality of about 35% in relation with control groups. Betablockers, compared to ACEI, also diminish the rate of sudden death prompting their almost mandatory indication in the absence of contraindications. Cardiac transplantation presently offers a survival rate of 66% at 5 years but donor scarcity has stabilized the number of procedures. In patients resuscitated from malignant arrhytmias the implantation of defibrillators offers a better survival than drugs. Future advances in the knowledge of the pathogenesis and especially of genetic mechanisms, may substantially change the understanding and treatment of these disorders.

HLA class II DRB1, DQB1, DPB1 polymorphism and cardiomyopathy due to Trypanosoma cruzi chronic infection.

Trypanosomiasis is an important cause of cardiomyopathy in endemic rural areas of Latin America. Previous studies have suggested participation of HLA molecules in the immune response regulation of T. cruzi infection, and association of HLA antigens with heart damage. One hundred and eleven unrelated T. cruzi antigen-seropositive individuals were tested for HLA class II alleles by the polymerase chain reaction and sequence specific oligonucleotide (PCR-SSO) method. Patients were classified in 3 groups according to clinical and electrocardiographic characteristics: asymptomatics (group A), with arrhythmia (group B), and with overt congestive heart failure (group C). Statistical analysis confirmed the significant increment of the DRB1*01 DQB1*0501 haplotype (p = 0.03) previously reported by our laboratory in patients with cardiomyopathy. The DPB1*0401 allele frequency is also significantly increased in patients with heart disease (groups B + C) (p = 0.009) while DPB1*0101 frequency is higher among the asymptomatic group (p = 0.04) compared with individuals of group C. The DPB1*0401 allele in homozygous form or in combination with allele DPB1*2301 or 3901, was found present more often in patients of groups B and C. Thus, the combination of two of these three alleles, sharing specific sequence motifs in positions 8, 9, 76, and 84-87 confers a relative risk of 6.55 to develop cardiomyopathy in seropositive patients (p = 0.041). Furthermore, 32% of the cardiomyopathics have either DRB1*01 DQB1*0501 and/or DPB1*0401/*0401, 0401/*2301, or* 0401/*3901 compared with 9% of the seropositive asymptomatics (OR = 5.0; p = 0.006).

Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas' disease: assessment by dobutamine stress echocardiography.

OBJECTIVES: To determine whether dobutamine stimulation in patients with Chagas' disease may uncover abnormal contractile responses as seen in ischemic myocardium. BACKGROUND: Segmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas' heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas' disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors. METHODS: Two groups of patients with Chagas' disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation. RESULTS: Patients with Chagas' disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas' group 1 (54.7+/-6.6%; SD) and in group 2 (35.1+/-12.1%) were significantly lower than control group (66.7+/-2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas' disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001). CONCLUSIONS: Thus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.

Influence of the HLA class II polymorphism in chronic Chagas' disease.

Chagas' disease or American trypanosomiasis due to Trypanosoma cruzi has existed at least since the time of the Inca empire and contributes significantly to cardiovascular morbidity and mortality in several countries of this continent. Due to the fundamental role of human class II molecules polymorphic residues in the control of the immune response, a study was designed to define by DNA typing HLA class II alleles in a sample of 67 serologically positive individuals with and without cardiomyopathy and in 156 healthy controls of similar ethnic origin. Genomic DNA extraction, PCR amplification of the HLA-DRB1 and DQB1 second exon regions and hybridization to labelled specific probes were carried out following the 11th International Histocompatibility Workshop reference protocol. Comparison of DRB1 and DQB1 allele frequencies among the patients and control subjects showed a decreased frequency of DRB1*14 and DQB1*0303 in the patients, suggesting independent protective effects to the chronic infection in this population. Allele frequencies comparison between patients with and without cardiomyopathy showed a higher frequency of DRB1*01, DRB1*08 and DQB1*0501 and a decreased frequency of DRB1*1501 in the patients with arrhythmia and congestive heart failure. The results suggest that HLA Class II genes may be associated with the development of a chronic infection and with heart damage in Chagas' disease.

[Heart pathology of extracardiac origin (V). Recent advances in chagasic cardiomyopathy]. / Patología del corazón de origen extracardíaco (V). Avances recientes en miocardiopatía chagásica.

INTRODUCTION AND OBJECTIVES: Chronic Chagas' heart disease is an important public health problem in Latin America. Rural migration from endemic to nonendemic countries has aroused widespread interest (United States, Spain) because of the possibility of observing affected patients. METHODS: Review of recent literature. RESULTS: The diagnosis of Chagas' cardiomyopathy is based on the triad of epidemiological history, positive serology and the clinical Chagas' syndrome. About 75% of asymptomatic seropositive subjects had no or almost no heart damage but the disease could be transmitted by blood donation. The other 25% may develop arrhythmias, heart failure and/or embolisms. Specific parasiticidal drugs are mainly used in the acute phase. CONCLUSIONS: In countries where Chagas' disease is infrequent, patients may be inadvertently diagnosed as having primary dilated or ischemic cardiomyopathy. Disease reactivation in immunodepressed patients due to AIDS, chemotherapy for cancer or for organ transplantation constitutes a formidable clinical challenge. Sanitary prophylactic measures are the strategies of choice.

Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans.

BACKGROUND: Ionizing radiation has been shown to reduce neointimal formation after balloon angioplasty in experimental models of restenosis. This study was designed to evaluate the feasibility, safety, and effectiveness of intracoronary radiation therapy (ICRT) after percutaneous transluminal coronary angioplasty (PTCA) for preventing restenosis in human coronary arteries. METHODS AND RESULTS: Twenty-one patients (22 arteries) with unstable angina underwent standard balloon angioplasty. ICRT was performed with the use of an 192Ir source wire that was hand delivered to the angioplasty site. Angiographic follow-up was performed at 24 hours, between 30 and 60 days, and at 6 months. Angioplasty was successful in 19 of 22 lesions, and insertion of the radioactive source wire was successful at all treated sites. Angiographic study at 24 hours demonstrated early late loss of the luminal diameter from 1.92+/-0.55 to 1.40+/-0.27 mm. Between 30 and 60 days, repeat angiography demonstrated total occlusion in 2 arteries, a new pseudoaneurysm in 1 artery, and significant dilatation at the treatment site in 2 additional vessels. At > or = 6 months' follow-up, all remaining arteries (n=20) maintained patent, with a mean lumen diameter of 1.65+/-0.8 mm. The calculated late lumen loss was 0.27+/-0.56 mm, and the late loss index was 0.19. Clinical events at 1 year included myocardial infarction in 1 patient, repeat angioplasty to the treated site in 3 patients, and persistent angina in 7 patients. CONCLUSIONS: These preliminary results demonstrate that ICRT after coronary intervention is feasible and is associated with an acceptable degree of complications and lower rates of angiographic restenosis indexes.

Coronary vascular reactivity is abnormal in patients with Chagas' heart disease.

Symptoms of myocardial ischemia, such as chest pain (sometimes with anginal features), acute myocardial infarction, and segmental wall motion abnormalities (including left ventricular apical aneurysm), frequently occur in patients with Chagas' heart disease. Because these clinical findings occur in the presence of normal coronary arteries, it is possible that an abnormality of the coronary vascular reactivity could be present in these patients. Therefore the current study was undertaken to determine whether endothelium-dependent coronary vasodilation is abnormal in Chagas' heart disease. Coronary endothelial function was assessed by infusing the endothelium-dependent vasodilator acetylcholine (10(-8) to 10(-6) mol/L) and the endothelium-independent vasodilator adenosine (10(-4) mol/L) into the left anterior descending coronary artery of nine patients (age 43 +/- 4 years) with Chagas' heart disease. Coronary blood flow was measured with a Doppler flow velocity catheter and by quantitative coronary cineangiography. The left ventricular ejection fraction was 39% +/- 5%; eight patients had a left ventricular apical aneurysm; and one had an area of anteroapical hypokinesis. An impairment of the endothelium-dependent coronary vasodilation was demonstrated by a reduction in coronary blood flow of 41.2% +/- 12.8% produced by the infusion of acetylcholine at 10(-6) mol/L and by a blunted but preserved increase in coronary blood flow of 114.6% +/- 65.0% with the infusion of adenosine at 10(-4) mol/L (p = 0.03). In conclusion, patients with Chagas' heart disease have an abnormality of the coronary endothelium-dependent vasodilation, and this abnormality may play a role in their chest pain syndrome and in the development of segmental wall motion abnormalities.

Unusual sequelae after percutaneous mitral valvuloplasty: a Doppler echocardiographic study.

Percutaneous mitral valvuloplasty is a promising new technique for the treatment of mitral stenosis, with a relatively low complication rate reported to date. To assess the sequelae of this procedure, Doppler echocardiographic studies were prospectively performed before and after percutaneous mitral valvuloplasty in a series of 172 patients (mean age 53 +/- 17 years). After balloon dilation, mitral valve area increased from 0.9 +/- 0.3 to 2 +/- 0.8 cm2 (p less than 0.0001), mean gradient decreased from 16 +/- 6 to 6 +/- 3 mm Hg (p less than 0.0001) and mean left atrial pressure decreased from 24 +/- 7 to 14 +/- 6 mm Hg (p less than 0.0001). Although most patients were symptomatically improved, six (4%) were identified who had unusual sequelae evident on Doppler echocardiographic examination immediately after percutaneous mitral valvuloplasty. These included rupture of a posterior mitral valve leaflet, producing a flail distal leaflet portion with severe mitral regurgitation detected on Doppler color flow mapping (n = 1); asymptomatic rupture of the chordae tendineae attached to the anterior mitral valve leaflet with systolic anterior motion of the ruptured chordae into the left ventricular outflow tract (n = 1); a double-orifice mitral valve (n = 1); and evidence of a tear in the anterior mitral valve leaflet (n = 3), producing on both pulsed Doppler ultrasound and color flow mapping a second discrete jet of mitral regurgitation in addition to regurgitation through the main mitral valve orifice. All six patients made a satisfactory recovery and none has required mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiography in dilated and restrictive cardiomyopathies.

Dilated cardiomyopathy is characterized by systolic dysfunction and cardiac enlargement of unknown origin. Various Doppler modalities are useful to detect and quantitate atrioventricular regurgitation, which is common and contributes to clinical symptoms. Pulsed Doppler assessment of mitral and tricuspid inflow velocities shows a spectrum of findings indicative of abnormal diastolic function and hemodynamic status. When mitral regurgitation is more than moderate and heart failure is severe, the ratio between early inflow E wave to atrial inflow A wave peak velocities is increased. Mitral deceleration time may be short. When mitral regurgitation is trivial and left atrial pressure is not increased, abnormal relaxation may be detected as a low E:A ratio. Mitral deceleration time and isovolumic relaxation time are prolonged. In restrictive cardiomyopathy, there is an abrupt limitation in early ventricular filling due to abnormal compliance of endocardial or endomyocardial origin. Mitral and tricuspid inflow velocities show normal to increased early peak velocity, rapid deceleration time, low peak atrial velocity, and an increased E:A ratio. Differentiation between restriction and constriction might be possible by the demonstration in pericardial constriction of inspiratory decreases in mitral early inflow peak velocities and in prolongation of isovolumic relaxation time, with reciprocal changes on tricuspid inflow velocity profiles. In constriction, these respiratory variations are caused by the ventricular limitation to accommodate changes in venous return due to the pericardial shell. Doppler abnormalities and two-dimensional echocardiographic assessment of ventricular and atrial size and ejection fraction provide the practicing physician with valuable diagnostic information.

Echocardiographic recognition of Chagas' disease and endomyocardial fibrosis.

Chagas' heart disease and endomyocardial fibrosis are common medical conditions in Central and South America but are only rarely encountered in North America. In the small number of patients who have these conditions, recognition is frustrating because of a lack of familiarity with their characteristic echocardiographic pattern. In Chagas' heart disease a left ventricular apical aneurysm is characteristic, but in contrast to coronary artery disease, septal involvement is minimal. In endomyocardial fibrosis apical obliteration with a small inwardly moving left ventricular cavity, large atria, and atrioventricular valvular insufficiency are typical features. It is the aim of this article to present the characteristic echocardiographic findings with these conditions and thereby facilitate the recognition when they appear in nonendemic areas.

Long-term control of Chagas disease in Venezuela: effects on serologic findings, electrocardiographic abnormalities, and clinical outcome.

To evaluate the long-term effects (20 years) of a Chagas control program (CCP) in Venezuela, a prospective serologic evaluation was carried out from 1981 to 1984 on 5771 inhabitants (8%) of Roscio county. This region was selected as a representative area where the national CCP was implemented effectively. Comparison with a serologic survey performed in the same region before the CCP disclosed a reduction in seropositive subjects from 47.8% to 17.1% (p less than .001), most marked amongst children and teenagers from 29.9% to 1.9%, suggesting that transmission of the disease had diminished. Similar seropositivity changes after the CCP were observed nationwide. Because decreased superinfection would also be expected to occur, we tried to ascertain whether the clinical outcome of seropositive individuals living in Roscio county had improved. The mean age of seropositive subjects between both surveys increased significantly from 34.9 +/- 17.3 to 46.7 +/- 15.1 years (p less than .001). Additionally, we examined clinically and obtained electrocardiograms from 775 seropositive subjects. They were classified as asymptomatic (group A, n = 614) or as symptomatic, having mild-to-moderate heart symptoms (group B, n = 99) or having advanced congestive heart failure (group C, n = 62). Their electrocardiograms were compared with those of 923 seronegative subjects collected simultaneously and with published data obtained before the CCP. Comparison of the age-related rates of electrocardiographic abnormalities of seropositive individuals before and after the CCP showed that they did not differ significantly by linear regression analysis, by the Kruskal-Wallis test, or by the normal approximation to the binomial distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained ventricular tachycardia in chronic chagasic myocarditis: electrophysiologic and pharmacologic characteristics.

Sustained ventricular tachycardia (VT) develops in many patients with chronic Chagasic myocarditis. Programmed stimulation was used to study the electrophysiologic characteristics of VT in 15 patients with Chagas' cardiomyopathy. Nine patients were in New York Heart Association functional class I, 5 were in class II and 1 patient was in class III. The average ejection fraction was 56 +/- 7%, which is somewhat better than that reported in patients with VT owing to idiopathic cardiomyopathy. In 11 patients VT could be reproducibly initiated and terminated by programmed stimulation. Intravenous mexilitene prevented induction of VT in 7 of 8 patients; amiodarone did not prevent induction in 3 of 4 patients. Our data indicate that the mechanism of VT is likely to be reentrant in many patients, and therefore VT can be produced by extrastimuli. Electrophysiologic study is therefore useful for establishing the diagnosis of sustained VT and may be useful for guiding initial therapy in selected cases of Chagas' disease.

Echocardiographic features of impaired left ventricular diastolic function in Chagas's heart disease.

To study left ventricular diastolic function in Chagas's disease, simultaneous echocardiograms, phonocardiograms, and apexcardiograms were recorded in 20 asymptomatic patients with positive Chagas's serology and no signs of heart disease (group 1), 12 with Chagas's heart disease and symptoms of ventricular arrhythmia but no heart failure (group 2), 20 normal subjects (group 3), and 12 patients with left ventricular hypertrophy (group 4). The recordings were digitised to determine left ventricular isovolumic relaxation time and the rate and duration of left ventricular cavity dimension increase and wall thinning. In groups 1 and 2 (a) aortic valve closure (A2) and mitral valve opening were significantly delayed relative to minimum dimension and were associated with prolonged isovolumic relaxation, (b) left ventricular cavity size was abnormally increased during isovolumic relaxation and abnormally reduced during isovolumic contraction, and (c) peak rate of posterior wall thinning and dimension increase were significantly reduced and duration of posterior wall thinning was significantly prolonged; both of these abnormalities occurred at the onset of diastolic filling. These abnormalities were more pronounced in group 2 and were accompanied by an increase in the height of the apexcardiogram "a" wave, an indication of pronounced atrial systole secondary to end diastolic filling impairment due to reduced left ventricular distensibility. Group 4, which had an established pattern of diastolic abnormalities, showed changes similar to those in group 2; however, the delay in aortic valve closure (A2) and in mitral valve opening and the degree of dimension change were greater in the latter group. Thus early isovolumic relaxation and left ventricular abnormalities were pronounced in the patients with Chagas's heart disease and may precede systolic compromise, which may become apparent in later stages of the disease. The digitised method is valuable in the early detection of myocardial damage.

Radionuclide evaluation of left-ventricular function in chronic Chagas' cardiomyopathy.

Left-ventricular ejection fraction (LVEF) and abnormalities of regional wall motion (WMA) were studied by means of radionuclide ventriculography in 41 patients prospectively diagnosed as having chronic Chagas' disease. Thirteen patients were asymptomatic (ASY), 16 were arrhythmic (ARR), and 12 had congestive heart failure (CHF). Mean LVEF was normal in ASY (0.64 +/- 0.06) but markedly depressed in CHF (0.28 +/- 0.08). Regional WMAs were minimal in ASY and their severity increased in ARR. Most CHFs (75%) had diffuse hypokinesia of the left ventricle. The region most frequently affected was the infero-apical (63%). Seven patients had a distinct apical aneurysm. Correlation between radionuclide and contrast ventriculography data was good in 17 patients. For LVEF, r = 0.90. For WMA there was agreement between the two techniques in 77% of 65 segments compared. Best agreement occurred with infero-apical lesions (88%), and worst with septal (69%). Selective coronary arteriography showed normal arteries in all patients. Therefore, chronic Chagas' heart disease joins ischemic heart disease as a cause of regional WMA.