Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis (MF) occurs in up to 80% of subjects with asymptomatic or mildly symptomatic hypertrophic cardiomyopathy (HCM) and can constitute an arrhythmogenic substrate for re-entrant, life-threatening ventricular arrhythmias in predisposed persons. OBJECTIVE: The aim was to investigate whether MF detected by delayed enhancement cardiac CT is predictive of ventricular tachycardia (VT) and fibrillation (VF) that require appropriate therapy by an implantable cardioverter defibrillator (ICD) in patients with HCM. METHODS: Twenty-six patients with HCM with previously (for at least 1 year) implanted ICD underwent MF evaluation by cardiac CT. MF was quantified by myocardial delayed enhanced cardiac CT. Data on ICD firing were recorded every 3 months after ICD implantation. Risk factors for sudden cardiac death in patients with HCM were evaluated in all patients. RESULTS: MF was present in 25 of 26 patients (96%) with mean fibrosis mass of 20.5 ± 15.8 g. Patients with appropriate ICD shocks for VF/VT had significantly greater MF mass than patients without (29.10 ± 19.13 g vs 13.57 ± 8.31 g; P = .01). For a MF mass of at least 18 g, sensitivity and specificity for appropriate ICD firing were 73% (95% CI, 49%-88%) and 71% (95% CI, 56%-81%), respectively. Kaplan-Meier curves indicated a significantly greater VF/VT event rate in patients with MF mass ≥18 g than in patients with MF <18 g (P = .02). In the Cox regression analysis, the amount of MF was independently associated with VF/VT in ICD-stored electrograms. CONCLUSION: The mass of MF detected by cardiac CT in patients with HCM at high risk of sudden death was associated with appropriate ICD firings.

Ativação adrenérgica intramiocárdica na cardiomiopatia chagásica e doença arterial coronariana / Intramyocardial adrenergic activation in chagasic cardiomyopathy and coronary artery disease / Activación adrenérgica intramiocárdica en la cardiomiopatía chagásica y enfermedad arterial coronaria

FUNDAMENTO: A norepinefrina miocárdica está alterada na disfunção ventricular esquerda. Em pacientes com cardiomiopatia chagásica (CC), essa questão ainda não foi discutida. OBJETIVO: Determinar o nível de norepinefrina (NE) miocárdica em pacientes com CC e compará-la em pacientes com doença arterial coronariana (DAC) e relacionar NE miocárdica com a fração de ejeção do ventrículo esquerdo (FEVE). MÉTODOS: Estudamos 39 pacientes com CC, divididos em grupo 1: 21 indivíduos com FEVE normal e grupo 2: 18 com FEVE diminuída. Dezessete pacientes com DAC foram divididos em grupo 3: 12 indivíduos com FEVE normal e grupo 4: 5 indivíduos com FEVE diminuída. Ecocardiografia bidimensional foi usada para medir a FEVE. A NE miocárdica foi determinada através de Cromatografia Líquida de Alta Eficiência (HPLC). RESULTADOS: A NE miocárdica na CC com e sem disfunção ventricular foi 1,3±1,3 e 6,1±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001); na DAC com e sem disfunção ventricular, foi 3,3±3,0 e 9,8±4,2 pg/μg de proteína não-colagenosa, respectivamente (p<0,0001). Uma correlação positive foi observada entre a FEVE e a concentração de NE miocárdica em pacientes com CC (p<0,01; r = 0,57) e também naqueles com DAC (p<0,01; r=0,69). Uma diferença significante foi demonstrada entre as concentrações de NE em pacientes com FEVE normal (grupos 1 e 3; p = 0,0182), mas nenhuma diferença foi observada em pacientes com FEVE diminuída (grupos 2 e 4; p = 0,1467). CONCLUSÃO: Pacientes com CC e fração de ejeção global normal apresentam uma denervação cardíaca precoce, quando comparados à pacientes com doença arterial coronariana.

BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment. In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed. OBJECTIVE: To determine the level of myocardial norepinephrine in patients with CC and compare it in patients with coronary artery disease, and to relate myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS: We studied 39 patients with CC, divided into group 1: 21 individuals with normal LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with coronary artery disease were divided into group 3: 12 individuals with normal LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional echocardiography was used to measure LVEF. Myocardial norepinephrine was determined by high-performance liquid chromatography. RESULTS: Myocardial norepinephrine in CC with and without ventricular dysfunction was 1.3±1.3 and 6.1±4.2 pg/μg noncollagen protein, respectively (p<0.0001); in coronary artery disease with and without ventricular dysfunction, it was 3.3±3.0 and 9.8±4.2 pgμg noncollagen protein, respectively (p<0.0001). A positive correlation was found between LVEF and myocardial norepinephrine concentration in the patients with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary artery disease (p<0.01, r=0.69). A significant difference was demonstrated between norepinephrine concentrations in patients with normal LVEF (groups 1 and 3; p = 0.0182), but no difference was found in patients with decreased LVEF (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy and normal global ejection fraction there is an early cardiac denervation, when compared to coronary artery disease patients.

FUNDAMENTO: La norepinefrina miocárdica está alterada en la disfunción ventricular izquierda. En pacientes con cardiomiopatía chagásica (CC), esa cuestión aun no fue discutida. OBJETIVO: Determinar el nivel de norepinefrina (NE) miocárdica en pacientes con CC y compararla en pacientes con enfermedad arterial coronaria (EAC) y relacionar NE miocárdica con la fracción de eyección del ventrículo izquierdo (FEVI). MÉTODOS: 39 pacientes con CC, divididos en grupo 1: 21 individuos con FEVI normal y grupo 2: 18 con FEVI disminuida. Diecisiete pacientes con EAC fueron divididos en grupo 3: 12 individuos con FEVI normal y grupo 4: 5 individuos con FEVI disminuida. Ecocardiografía bidimensional fue usada para medir la FEVI. La NE miocárdica fue determinada a través de Cromatografía Líquida de Alta Eficiencia (HPLC). RESULTADOS: La NE miocárdica en la CC con y sin disfunción ventricular fue 1,3±1,3 y 6,1±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001); en la EAC con y sin disfunción ventricular, fue 3,3±3,0 y 9,8±4,2 pg/µg de proteína no colagenosa, respectivamente (p<0,0001). Una correlación positiva fue observada entre la FEVI y la concentración de NE miocárdica en pacientes con CC (p<0,01; r=0,57) y también en aquellos con EAC (p<0,01; r=0,69). Una diferencia significativa fue demostrada entre las concentraciones de NE en pacientes con FEVI normal (grupos 1 y 3; p = 0,0182), pero ninguna diferencia fue observada en pacientes con FEVI disminuida (grupos 2 y 4; p = 0,1467). CONCLUSIONES: Pacientes con CC y fracción de eyección global normal presentan una denervación cardíaca precoz, cuando son comparados a pacientes con enfermedad arterial coronaria.

Intramyocardial adrenergic activation in chagasic cardiomyopathy and coronary artery disease.

BACKGROUND: Myocardial norepinephrine is altered in left ventricular impairment. In patients with Chagas' cardiomyopathy (CC), this issue has not been addressed. OBJECTIVE: To determine the level of myocardial norepinephrine in patients with CC and compare it in patients with coronary artery disease, and to relate myocardial norepinephrine to left ventricular ejection fraction (LVEF). METHODS: We studied 39 patients with CC, divided into group 1: 21 individuals with normal LVEF and group 2: 18 individuals with decreased LVEF. Seventeen patients with coronary artery disease were divided into group 3: 12 individuals with normal LVEF and group 4: 5 individuals with decreased LVEF. Two-dimensional echocardiography was used to measure LVEF. Myocardial norepinephrine was determined by high-performance liquid chromatography. RESULTS: Myocardial norepinephrine in CC with and without ventricular dysfunction was 1.3±1.3 and 6.1±4.2 pg/µg noncollagen protein, respectively (p<0.0001); in coronary artery disease with and without ventricular dysfunction, it was 3.3±3.0 and 9.8±4.2 pg/µg noncollagen protein, respectively (p<0.0001). A positive correlation was found between LVEF and myocardial norepinephrine concentration in the patients with Chagas' cardiomyopathy (p<0.01, r = 0.57) and also in those with coronary artery disease (p<0.01, r=0.69). A significant difference was demonstrated between norepinephrine concentrations in patients with normal LVEF (groups 1 and 3; p = 0.0182), but no difference was found in patients with decreased LVEF (groups 2 and 4; p = 0.1467). CONCLUSION: In patients with Chagas' cardiomyopathy and normal global ejection fraction there is an early cardiac denervation, when compared to coronary artery disease patients.

Sleep quality and quality of life in patients with hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate clinical predictors of poor sleep quality and quality of life (QOL) in patients with hypertrophic cardiomyopathy (HCM). METHODS: Consecutive stable patients with HCM were evaluated for the risk of obstructive sleep apnea (OSA) by the Berlin Questionnaire, daytime sleepiness by the Epworth Sleepiness Scale, sleep quality by the Pittsburgh Sleep Questionnaire Index and QOL by the Minnesota Living with Heart Failure Questionnaire. Asymptomatic subjects without HCM were used as controls. RESULTS: We studied 84 patients with HCM and 42 controls who were similar with regard to gender (49 vs. 50% males), age [52 (38-62) vs. 47 (33-58) years] and body mass index (27 ± 4 vs. 27 ± 5). HCM diagnosis, high risk for OSA and female gender were independently associated with poor sleep quality in the entire population. Among patients with HCM, poor QOL was independently associated with poor sleep quality, New York Heart Association functional class and diuretic therapy. CONCLUSION: Poor sleep quality is very common in patients with HCM and may have a negative impact on the QOL, which in turn is an important marker of prognosis in patients with cardiomyopathies.

[Study of mutations causing hypertrophic cardiomyopathy in a group of patients from Espirito Santo, Brazil]. / Estudo de mutações causadoras de cardiomiopatia hipertrófica em um grupo de pacientes no Espírito Santo, Brasil.

BACKGROUND: Hypertrophic cardiomyopathy (HC) is the most frequent cardiac hereditary disease, caused by mutations in sarcomere protein coding genes. Although more than 430 mutations have been identified in several continents and countries, there have been no reports of mutations in Brazil. OBJECTIVE: To carry out a genetic study to identify genetic mutations that cause HC in a group of patients in Espirito Santo, Brazil. METHODS: Using the SSCP technique, 12 exons from the three main genes involved in HC were studied: exons 15, 20, 21, 22 and 23 of the beta-myosin heavy chain gene (MYH7), exons 7, 16, 18, 22 and 24 of the myosin binding protein C gene (MYBPC3) and exons 8 and 9 of troponin T gene (TNNT2). RESULTS: 16 alterations were found, including two mutations, one of them possibly pathogenic in the MYBPC3 gene (p. Glu441Lys) and another pathogenic one, previously described in the TNNT2 gene (p.Arg92Trp), 8 rare sequence variations and 6 sequence variations with allelic frequency higher than 1% (polymorphisms). CONCLUSION: These data allow the conclusion that the genotyping of patients is feasible in our country. It is possible that the isolated p.Glu441Lys variant identified in exon 16 of the MYBPC3 gene is pathogenic, promoting a milder phenotype than that found when in association with other mutations. The p.Arg92Trp variant in the exon 9 of TNNT2 gene does not promote such a homogeneous phenotype as previously described and it can lead to severe hypertrophy.

Fibrose miocárdica em pacientes com cardiomiopatia hipertrófica com alto risco para morte súbita cardíaca / Myocardial fibrosis in patients with hypertrophic cardiomyopathy and high risk for sudden death

FUNDAMENTO: A estratificação de risco para morte súbita na cardiomiopatia hipertrófica (CMH), continua a ser um verdadeiro desafio devido à grande heterogeneidade da sua apresentação, em que a maioria dos indivíduos permanecem assintomáticos por toda sua vida e outros apresentam a morte súbita como primeiro sintoma. Recentes trabalhos vêm sugerindo que a fibrose miocárdica pode constituir-se em um importante substrato para as arritmias ventriculares malignas, responsáveis pela morte súbita nesta doença. OBJETIVO: Avaliação da prevalência e quantificação da fibrose miocárdica (FM), em pacientes com CMH com alto risco ou recuperados de morte súbita, portadores de cardiodesfibrilador implantável (CDI). MÉTODOS: Vinte e oito pacientes com CMH portadores de CDI foram submetidos à tomografia computadorizada com múltiplos detectores, para realização da técnica de realce tardio, e avaliação da fibrose miocárdica. RESULTADOS: 96 por cento dos pacientes apresentavam fibrose miocárdica (20,38 ± 15,55 gramas) correspondendo a 15,96 ± 10,20 por cento da massa miocárdica total. A FM foi significativamente mais prevalente que os demais fatores de risco clássicos para morte súbita. CONCLUSÃO: Concluímos que existe uma alta prevalência de fibrose miocárdica em pacientes com cardiomiopatia hipertrófica de alto risco ou recuperados de morte súbita, como neste grupo - portadores de cardiodesfibrilador implantável. A maior prevalência da fibrose miocárdica comparada aos fatores de risco de pior prognóstico levantam a hipótese de que a fibrose miocárdica possa ser um importante substrato potencialmente necessário na gênese das arritmias desencadeadoras da morte súbita.

BACKGROUND: The stratification of risk for sudden death in hypertrophic cardiomyopathy (HCM) continues to be a true challenge due to the great heterogeneity of this disease's presentation, as most individuals remain asymptomatic during their entire lives and others present sudden death as first symptom. Recent studies have suggested that myocardial fibrosis may represent an important substrate for the malignant ventricular arrhythmias, that are responsible for the cases of sudden death related to this disease. OBJECTIVE: To assess the prevalence and quantification of myocardial fibrosis (MF) in hypertrophic cardiomyopathy (HCM) patients with implantablecardioverter - defibrillator (ICD) indicated due to their high risk or recovered from cardiac sudden death. METHODS: Twenty-eight HCM patients with ICD were submitted to multidetector computed tomography to assess myocardial fibrosis by delayed enhancement technique. RESULTS: Myocardial fibrosis was present in 96 percent of these HCM patients with (20.38 ± 15.55 g) comprising 15.96 ± 10.20 percent of the total myocardial mass. MF was observed in a significantly higher prevalence as compared to other classical risk factors for sudden death. CONCLUSION: It is possible to conclude that there is a high prevalence of myocardial fibrosis in hypertrophic cardiomyopathy patients with high-risk or recovered from cardiac sudden death, like those with clinical indication to implantable cardioverter -defibrillator. The higher prevalence of myocardial fibrosis in comparison to classical risk factors of worse prognosis raise the hypothesis that the myocardial fibrosis may be an important substrate in the genesis of lifethreatening arrhythmias in these high risk HCM population.

[Myocardial fibrosis in patients with hypertrophic cardiomyopathy and high risk for sudden death]. / Fibrose miocárdica em pacientes com cardiomiopatia hipertrófica com alto risco para morte súbita cardíaca.

BACKGROUND: The stratification of risk for sudden death in hypertrophic cardiomyopathy (HCM) continues to be a true challenge due to the great heterogeneity of this disease's presentation, as most individuals remain asymptomatic during their entire lives and others present sudden death as first symptom. Recent studies have suggested that myocardial fibrosis may represent an important substrate for the malignant ventricular arrhythmias, that are responsible for the cases of sudden death related to this disease. OBJECTIVE: To assess the prevalence and quantification of myocardial fibrosis (MF) in hypertrophic cardiomyopathy (HCM) patients with implantablecardioverter - defibrillator (ICD) indicated due to their high risk or recovered from cardiac sudden death. METHODS: Twenty-eight HCM patients with ICD were submitted to multidetector computed tomography to assess myocardial fibrosis by delayed enhancement technique. RESULTS: Myocardial fibrosis was present in 96% of these HCM patients with (20.38 +/- 15.55 g) comprising 15.96 +/- 10.20% of the total myocardial mass. MF was observed in a significantly higher prevalence as compared to other classical risk factors for sudden death. CONCLUSION: It is possible to conclude that there is a high prevalence of myocardial fibrosis in hypertrophic cardiomyopathy patients with high-risk or recovered from cardiac sudden death, like those with clinical indication to implantable cardioverter -defibrillator. The higher prevalence of myocardial fibrosis in comparison to classical risk factors of worse prognosis raise the hypothesis that the myocardial fibrosis may be an important substrate in the genesis of lifethreatening arrhythmias in these high risk HCM population.

Obstructive sleep apnea is common and independently associated with atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated with arrhythmias and cardiovascular death. Left atrial enlargement and atrial fibrillation (AF) are considered markers for death due to heart failure in patients with HCM. Obstructive sleep apnea (OSA) is independently associated with heart remodeling and arrhythmias in other populations. We hypothesized that OSA is common and is associated with heart remodeling and AF in patients with HCM. METHODS: We evaluated 80 consecutive stable patients with a confirmed diagnosis of HCM by sleep questionnaire, blood tests, echocardiography, and sleep study (overnight respiratory monitoring). RESULTS: OSA (apnea-hypopnea index [AHI] > 15 events/h) was present in 32 patients (40%). Patients with OSA were significantly older (56 [41-64] vs 38.5 [30-53] years, P < .001) and presented higher BMI (28.2 +/- 3.5 vs 25.2 +/- 5.2 kg/m(2), P < .01) and increased left atrial diameter (45 [42-52.8] vs 41 [39-47] mm, P = .01) and aorta diameter (34 [30-37] vs 29 [28-32] mm, P < .001), compared with patients without OSA. Stepwise multiple linear regression showed that the AHI (P = .05) and BMI (P = .06) were associated with left atrial diameter. The AHI was the only variable associated with aorta diameter (P = .01). AF was present in 31% vs 6% of patients with and without OSA, respectively (P < .01). OSA (P = .03) and left atrial diameter (P = .03) were the only factors independently associated with AF. CONCLUSIONS: OSA is highly prevalent in patients with HCM and it is associated with left atrial and aortic enlargement. OSA is independently associated with AF, a risk factor for cardiovascular death in this population.

Estudo de mutações causadoras de cardiomiopatia hipertrófica em um grupo de pacientes no Espírito Santo, Brasil / Study of mutations causing hypertrophic cardiomyopathy in a group of patients from Espirito Santo, Brazil / Estudio de mutaciones causadoras de cardiomiopatía hipertrófica en un grupo de pacientes en Espírito Santo, Brasil

Fundamento: A cardiomiopatia hipertrófica (CH) é a doença cardíaca hereditária mais frequente, causada por mutações nos genes codificadores para proteínas do sarcômero. Embora mais de 430 mutações tenham sido identificadas em vários continentes e países, não há relato de que isso tenha sido estudado no Brasil. Objetivo: Conduzir um estudo genético para identificar mutações genéticas que causam a CH em um grupo de pacientes no estado do Espírito Santo, Brasil. Métodos: Usando a técnica SSCP, 12 exons dos três principais genes envolvidos com a CH foram estudados: exons 15, 20, 21, 22 e 23 do gene da cadeia pesada da β-miosina (MYH7), exons 7, 16, 18, 22 e 24 do gene da proteína C ligada à miosina (MYBPC3) e exons 8 e 9 do gene da troponina T (TNNT2). Resultados: 16 alterações foram encontradas, incluindo duas mutações, uma delas possivelmente patogênica no gene MYBPC3 gene (p. Glu441Lys) e a outra patogênica já descrita no gene TNNT2 (p.Arg92Trp); 8 variações de seqüência raras e 6 variações de seqüência com frequência alélica maior do que 1 por cento (polimorfismos). Conclusão: Com esses dados, é possível concluir que a genotipagem dos pacientes é factível em nosso meio. É possível que a variante p.Glu441Lys no exon 16 do gene MYBPC3 seja patogênica, resultando em um fenótipo mais leve do que o encontrado em associação com outras mutações. A variante p.Arg92Trp no exon 9 do gene TNNT2 não resulta em um fenótipo tão homogêneo como descrito anteriormente e pode levar à hipertrofia grave.

Background: Hypertrophic cardiomyopathy (HC) is the most frequent cardiac hereditary disease, caused by mutations in sarcomere protein coding genes. Although more than 430 mutations have been identified in several continents and countries, there have been no reports of mutations in Brazil. Objective: To carry out a genetic study to identify genetic mutations that cause HC in a group of patients in Espirito Santo, Brazil. Methods: Using the SSCP technique, 12 exons from the three main genes involved in HC were studied: exons 15, 20, 21, 22 and 23 of the β-myosin heavy chain gene (MYH7), exons 7, 16, 18, 22 and 24 of the myosin binding protein C gene (MYBPC3) and exons 8 and 9 of troponin T gene (TNNT2). Results: 16 alterations were found, including two mutations, one of them possibly pathogenic in the MYBPC3 gene (p. Glu441Lys) and another pathogenic one, previously described in the TNNT2 gene (p.Arg92Trp), 8 rare sequence variations and 6 sequence variations with allelic frequency higher than 1 percent (polymorphisms). Conclusion: These data allow the conclusion that the genotyping of patients is feasible in our country. It is possible that the isolated p.Glu441Lys variant identified in exon 16 of the MYBPC3 gene is pathogenic, promoting a milder phenotype than that found when in association with other mutations. The p.Arg92Trp variant in the exon 9 of TNNT2 gene does not promote such a homogeneous phenotype as previously described and it can lead to severe hypertrophy.

Fundamento: La cardiomiopatía hipertrófica (CH) es la enfermedad cardíaca hereditaria más frecuente, causada por mutaciones en los genes codificadores para proteínas del sarcómero. Aunque se hayan identificado más de 430 mutaciones en varios continentes y países, no hay relato de que esto se haya estudiado en Brasil. Objetivo: Conducir un estudio genético para identificar mutaciones genéticas que causan la CH en un grupo de pacientes en el estado de Espírito Santo, Brasil. Métodos: Usando la técnica SSCP, se estudiaron 12 exones de los tres principales genes involucrados con la CH: exones 15, 20, 21, 22 y 23 del gen de la cadena pesada de la β-miosina (MYH7), exones 7, 16, 18, 22 y 24 del gen de la proteína C unida a la miosina (MYBPC3) y exones 8 y 9 del gen de la troponina T (TNNT2). Resultados: Se encontraron 16 alteraciones, incluyendo dos mutaciones, una de ellas posiblemente patogénica en el gen MYBPC3 gen (p. Glu441Lys) y otra patogénica ya descrita en el gen TNNT2 (p. Arg92Trp); 8 variaciones de secuencia raras y 6 variaciones de secuencia con frecuencia alélica mayor que el 1 por ciento (polimorfismos). Conclusiones: Con estos datos, es posible concluir que el genotipaje de los pacientes es factible en nuestro medio. Es posible que la variante p.Glu441Lys en el exón 16 del gen MYBPC3 sea patogénica, resultando en un fenotipo más leve que el encontrado en asociación con otras mutaciones. La variante p.Arg92Trp en el exón 9 del gen TNNT2 no resulta en un fenotipo tan homogéneo como el descrito anteriormente y puede llevar a hipertrofia grave.

Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death.

We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD) for primary prevention.

Síndrome Leopard e miocardiopatia hipertrófica: uma associação relacionada à morte súbita / Síndrome leopard y miocardiopatía hipertrófica: una asociación relacionada a la muerte súbita / Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death

Relatamos a rara associação entre síndrome Leopard e miocardiopatia hipertrófica em mulher de 27 anos, pouco sintomática, que veio para estratificação e prevenção de risco de morte súbita. Portadora de uma síndrome rara, que se manifesta com pequenas máculas disseminadas pelo corpo, além de alterações oculares, genitais, cardíacas e de crescimento. A associação de miocardiopatia hipertrófica com fatores de risco de morte súbita determinou a indicação do implante de cardiodesfibrilador (CDI) para prevenção primária.

We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD) for primary prevention.

Relatamos la rara asociación entre síndrome Leopard y miocardiopatía hipertrófica en una mujer de 27 años, poco sintomática, que vino para estratificación y prevención de riesgo de muerte súbita. Portadora de un síndrome raro, que se manifiesta con pequeñas manchas diseminadas por el cuerpo, además de alteraciones oculares, genitales, cardíacas y de crecimiento. La asociación de miocardiopatía hipertrófica con factores de riesgo de muerte súbita determinó la indicación del implante de cardiodesfibrilador (CDI) para prevención primaria.

Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE: To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61% (p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF < or =6.19% and CVF> 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

Valor prognóstico da fração de volume de colágeno na cardiomiopatia hipertrófica / Prognostic value of the collagen volume fraction in hypertrophic cardiomyopathy / Valor pronóstico de la fracción de volumen de colágeno en la cardiomiopatía hipertrófica

FUNDAMENTO: Na cardiomiopatia hipertrófica (CMH), a fibrose miocárdica intersticial é uma importante alteração histológica que tem sido associada com morte súbita e evolução para dilatação. OBJETIVO: Avaliar, prospectivamente, o valor prognóstico da fração de colágeno na CMH. MÉTODOS: Biópsia endomiocárdica do ventrículo direito foi realizada com sucesso em 21 pacientes sintomáticos com CMH. A fração de volume de colágeno (FVC) miocárdico foi determinada por histologia. A FVC também foi determinada em fragmentos de nove corações normais de indivíduos falecidos por causas não-cardíacas. Os pacientes foram divididos em grupos supra e infra-medianos em relação à FVC, sendo comparadas as características clínico-ecocardiográficas e as curvas de sobrevida. RESULTADOS: Entre os pacientes, a FVC variou de 1,86% a 29,9%, mediana 6,19%; nos corações normais, de 0,13% a 1,46%, mediana 0,36% (p<0,0001 entre CMH e controle). Não foram observadas correlações significativas entre FVC e medidas ecocardiográficas basais. Pacientes com FVC<6,19% e FVC>6,19% foram comparados e não foram observadas diferenças basais. Entretanto, após um período de seguimento médio de 110 meses, quatro mortes ocorreram (duas súbitas, duas por insuficiência cardíaca) no grupo com FVC maior, enquanto os pacientes do grupo com FVC menor estavam vivos ao final do período (p=0,02). CONCLUSÃO: Pela primeira vez, a fibrose miocárdica foi prospectivamente associada a um pior prognóstico em pacientes com CMH. Esforços devem ser direcionados para quantificação da fibrose miocárdica na CMH, assumindo que a associação com o prognóstico pode auxiliar na estratificação de risco para implante de desfibrilador e na prescrição de fármacos potencialmente reparadores miocárdicos.

BACKGROUND: In hypertrophic cardiomyopathy (HCM), interstitial myocardial fibrosis is an important histological modification that has been associated with sudden death and evolution toward myocardial dilation. OBJECTIVE:To prospectively evaluate the prognostic value of the collagen volume fraction in HCM. METHODS: An endomyocardial biopsy of the right ventricle was successfully performed in 21 symptomatic patients with HCM. The myocardial collagen volume fraction (CVF) was determined by histology. The CVF was also determined in fragments of nine normal hearts from subjects deceased from non-cardiac causes. The patients were divided into above-median CVF and below-median CVF groups, and their clinical and echocardiographic characteristics and survival curves were compared. RESULTS: Among the patients, the CVF ranged from 1.86% to 29.9%, median 6.19%; in normal hearts, from 0.13% to 1.46%, median 0.61%(p <0.0001 between HCM and control). There were no significant correlations between CVF and baseline echocardiographic measures. Patients with CVF < 6.19% and CVF> 6.19% were compared and no baseline differences were observed. However, after an average follow-up period of 110 months, four deaths occurred (two sudden, two due to heart failure) in the group with increased CVF, whereas the patients of the group with lower CVF were all alive at the end of the period (p = 0.02). CONCLUSION: For the first time, myocardial fibrosis was prospectively associated with a worse prognosis in patients with HCM. Efforts should be directed to the quantification of myocardial fibrosis in HCM, on the premise that its association with the prognosis can aid in the stratification of risk for defibrillator implantation, and in the prescription of drugs that potentially promote myocardial repair.

FUNDAMENTO: En la cardiomiopatía hipertrófica (CMH), la fibrosis miocárdica intersticial es una importante alteración histológica, que ha sido asociada con muerte súbita y evolución hacia dilatación. OBJETIVO:Evaluar, prospectivamente, el valor pronóstico de la fracción de colágeno en la CMH. MÉTODOS:Se realizó, con éxito, biopsia endomiocárdica del ventrículo derecho en 21 pacientes sintomáticos con CMH. La fracción de volumen de colágeno (FVC) miocárdico se determinó por medio de histología. Se determinó la FVC también en fragmentos de nueve corazones normales de individuos fallecidos por causas no cardiacas. Respecto a la FVC, se dividieron a los pacientes en grupos supra e inframedianos (FVC elevada y FVC baja, respectivamente), y se compararon las características clínicas y ecocardiográficas y las curvas de sobrevida. RESULTADOS: Entre los pacientes, la FVC tuvo variación del 1,86% al 29,9%, con mediana en el 6,19%. Ya en los corazones normales, del 0,13% al 1,46%, mediana en el 0,36% (p<0,0001 entre CMH y control). No se verificaron correlaciones significativas entre FVC y medidas ecocardiográficas basales. Se compararon a pacientes con FVC<6,19 por ciento y FVC>6,19%, sin que se observara diferencias basales. Sin embargo, tras un período de seguimiento promedio de 110 meses, cuatro muertes ocurrieron (dos súbitas, y otras dos por insuficiencia cardiaca) en el grupo con FVC mayor, mientras que los pacientes del grupo con FVC menor estaban vivos al final del período (p=0,02). CONCLUSIÓN: Por primera vez, se asoció prospectivamente la fibrosis miocárdica a un peor diagnóstico en pacientes con CMH. Se deben encaminar esfuerzos hacia la cuantificación de la fibrosis en la CMH, al aceptar que la asociación con el pronóstico puede auxiliar tanto en la estratificación de riesgo para implante de desfibrilador, como en la prescripción de fármacos potencialmente reparadores...

Cardiomiopatia hipertrófica: atualização / Hypertrophic cardiomyopathy: a review

São relatados conhecimentos recentes sobre a cardiomiopatia hipertrófica nas áreas de etiologia genética, métodos diagnósticos como ecocardiografia, ressonância magnética cardíaca e tomografia computadorizada com múltiplas colunas de detetores, assim como as relacionadas ao tratamento clínico com novas drogas e prevenção da morte súbita com o desfibrilador implantável. Em 2008, a cardiomiopatia hipertrófica completou 50 anos de sua descrição por Donald Teare, patologista londrinio e, apesar do tempo decorrido, em que houve grande avanço no conhecimento, ainda há muito por conhecer.

Serum NT pro-BNP: relation to systolic and diastolic function in cardiomyopathies and pericardiopathies.

BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD)--14 patients; 2) hypertrophic cardiomyopathy (HCM)--71 patients; 3) endomyocardial fibrosis (EMF)--26 patients; 4) pericardial effusion (PE)--18 patients; and 5) constrictive pericarditis (CP)--16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.

Níveis séricos de NT pro-BNP: relação com função sistólica e diastólica nas miocardiopatias e pericardiopatias / Serum NT pro-BNP: relation to systolic and diastolic function in cardiomyopathies and pericardiopathies

FUNDAMENTO: O NT pro-BNP é marcador de disfunção sistólica e diastólica. OBJETIVO: Determinar os níveis de NT pro-BNP em pacientes com cardiopatia chagásica, hipertrófica, restritiva e afecções pericárdicas, e sua relação com medidas ecocardiográficas de disfunção sistólica e diastólica. MÉTODOS: Cento e quarenta e cinco pacientes foram divididos nos respectivos grupos: 1) cardiopatia chagásica (CCh) - 14 pacientes; 2) miocardiopatia hipertrófica (CMH) - 71 pacientes; 3) endomiocardiofibrose (EMF) - 26 pacientes; 4) derrame pericárdico (DP) - 18 pacientes; 5) e pericardite constritiva (PC) - 16 pacientes. Foi constituído um grupo-controle de 40 indivíduos sem doença cardíaca. O grau de acometimento miocárdico e o derrame pericárdico foram avaliados pelo ecocardiograma bidimensional e a restrição pelo Doppler pulsátil do fluxo mitral. O diagnóstico de PC foi confirmado por meio da ressonância magnética. Os níveis de NT pro-BNP foram medidos por imunoensaio com detecção por eletroquimioluminescência. RESULTADOS: O NT pro-BNP esteve aumentado (p < 0,001) na CCh (mediana 513,8 pg/ml), CMH (mediana 848 pg/ml), EMF (mediana 633 pg/ml), PC (mediana 568 pg/ml), DP (mediana 124 pg/ml), quando comparados ao grupo-controle (mediana 28 pg/ml). Não foram observadas diferenças estatisticamente significativas entre PC e EMF (p = 0,14). No grupo hipertrófico, o NT pro-BNP correlacionou-se com tamanho de átrio esquerdo (r = 0,40; p < 0,001) e relação E/Ea (p < 0,01). No grupo restritivo, houve uma tendência de correlação com pico de velocidade de onda E (r = 0,439; p = 0,06). CONCLUSÃO: O NT pro-BNP encontra-se aumentado nas diversas miocardiopatias e afecções pericárdicas, e apresenta relação com o grau de disfunção sistólica e diastólica.

BACKGROUND: NT pro-BNP is a marker of systolic and diastolic dysfunction. OBJECTIVE: To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction. METHODS: A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD) - 14 patients; 2) hypertrophic cardiomyopathy (HCM) - 71 patients; 3) endomyocardial fibrosis (EMF) - 26 patients; 4) pericardial effusion (PE) - 18 patients; and 5) constrictive pericarditis (CP) - 16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay. RESULTS: NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06). CONCLUSION: NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.

Value of real time three-dimensional echocardiography in patients with hypertrophic cardiomyopathy: comparison with two-dimensional echocardiography and magnetic resonance imaging.

UNLABELLED: Real time three-dimensional echocardiography (RT3DE) has been demonstrated to be an accurate technique to quantify left ventricular (LV) volumes and function in different patient populations. We sought to determine the value of RT3DE for evaluating patients with hypertrophic cardiomyopathy (HCM), in comparison with cardiac magnetic resonance imaging (MRI). METHODS: We studied 20 consecutive patients with HCM who underwent two-dimensional echocardiography (2DE), RT3DE, and MRI. Parameters analyzed by echocardiography and MRI included: wall thickness, LV volumes, ejection fraction (LVEF), mass, geometric index, and dyssynchrony index. Statistical analysis was performed by Lin agreement coefficient, Pearson linear correlation and Bland-Altman model. RESULTS: There was excellent agreement between 2DE and RT3DE (Rc = 0.92), 2DE and MRI (Rc = 0.85), and RT3DE and MRI (Rc = 0.90) for linear measurements. Agreement indexes for LV end-diastolic and end-systolic volumes were Rc = 0.91 and Rc = 0.91 between 2DE and RT3DE, Rc = 0.94 and Rc = 0.95 between RT3DE and MRI, and Rc = 0.89 and Rc = 0.88 between 2DE and MRI, respectively. Satisfactory agreement was observed between 2DE and RT3DE (Rc = 0.75), RT3DE and MRI (Rc = 0.83), and 2DE and MRI (Rc = 0.73) for determining LVEF, with a mild underestimation of LVEF by 2DE, and smaller variability between RT3DE and MRI. Regarding LV mass, excellent agreement was observed between RT3DE and MRI (Rc = 0.96), with bias of-6.3 g (limits of concordance = 42.22 to-54.73 g). CONCLUSION: In patients with HCM, RT3DE demonstrated superior performance than 2DE for the evaluation of myocardial hypertrophy, LV volumes, LVEF, and LV mass.