High muscle sympathetic nerve activity is associated with left ventricular dysfunction in treated hypertensive patients.

BACKGROUND: The presence of asymptomatic left ventricular diastolic dysfunction (LVDD) in hypertensive patients can be associated with the development of cardiac events. The increase in sympathetic activity may be 1 of the mechanisms that predisposes to this outcome. In this study, we analyzed 2 hypotheses: (i) whether sympathetic activity is higher in the presence of LVDD, independent of blood pressure control and (ii) whether different classes of LVDD have a different effect on sympathetic activity. METHODS: After analyzing left ventricular function using echo Doppler cardiography, 45 hypertensive patients receiving treatment were allocated into 3 groups: normal function (LV-NF, n = 15), impaired relaxation (LV-IR, n = 15), and pseudonormal or restrictive (LV-P/R, n = 15). An age-, sex-, and body mass index-matched control group of normotensive volunteers (N, n = 14) was included. Muscle sympathetic nerve activity (MSNA), heart rate, and systolic blood pressure variabilities and baroreflex sensitivity were evaluated while the patient was in a supine position. RESULTS: Blood pressure and antihypertensive drug use were similar among the hypertensive groups. The LV-IR and LV-P/R groups had similar MSNA (33±1 and 32±1 bursts/min, respectively), which was significantly higher than that of the LV-NF and N groups (26±3 and 15±2 bursts/min, respectively). The LV-IR and LV-P/R groups had significantly higher LF-systolic blood pressure variability and significantly lower baroreflex sensitivity compared with the N group. CONCLUSIONS: The presence of asymptomatic LVDD is associated with increased MSNA, independent of blood pressure control. The sympathetic hyperactivity associated with LVDD is similar in the different patterns of LVDD studied.

Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure.

BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3+/-10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.

Polimorfismo genético, terapia farmacológica e função cardíaca seqüencial em pacientes com insuficiência cardíaca / Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure

FUNDAMENTO: Variantes funcionais do gene da enzima conversora da angiotensina (ECA) podem estar associados com a resposta à terapia em portadores de insuficiência cardíaca (IC). OBJETIVO: Testar a hipótese de diferenças na avaliação ecocardiográfica seqüencial da fração de ejeção do ventrículo esquerdo de pacientes com IC em tratamento farmacológico, inclusive com inibidores da ECA, em relação ao polimorfismo de inserção (I) e deleção (D) do gene da ECA. MÉTODOS: Estudamos 168 pacientes (média de idade 43,3±10,1 anos), 128 (76,2 por cento) dos quais homens, com IC e ecocardiogramas seqüenciais. O polimorfismo I/D foi determinado por reação em cadeia da polimerase. A fração de ejeção do ventrículo esquerdo (FEVE) foi analisada comparativamente aos genótipos. Mais de 90 por cento dos pacientes estavam tomando inibidores da ECA. RESULTADOS: Houve um aumento significantemente maior na FEVE média em pacientes com o alelo D, em comparação com pacientes com genótipo II (p = 0,01) após um seguimento médio de 38,9 meses. O alelo D foi associado com aumento de 8,8 por cento na FEVE média no mesmo período. Além disso, observou-se uma tendência para um efeito do "número de cópias" do alelo D sobre o aumento da FEVE média com o tempo: uma diferença de 3,5 por cento na variação da FEVE entre os pacientes com genótipos II e ID (p = 0,03) e de 5 por cento entre os pacientes com genótipos II e DD (p = 0,02). CONCLUSÃO: O polimorfismo de deleção do gene da ECA pode estar associado com a resposta ao tratamento farmacológico com inibidores da ECA em portadores de IC. Outros estudos controlados poderão contribuir para uma melhor compreensão das influências genéticas sobre a resposta à terapia.

BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3±10.1 years), 128 (76.2 percent) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90 percent of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8 percent in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5 percent difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5 percent difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.

Angiotensin-converting enzyme gene deletion polymorphism modulation of onset of symptoms and survival rate of patients with heart failure.

BACKGROUND: Angiotensin-converting enzyme is involved in the pathophysiology of heart failure. We hypothesized that clinical characteristics as well as survival rate in patients with heart failure of different etiologies may be modulated by functional variants DD, ID and II of the angiotensin-converting enzyme gene. METHODS: We studied 333 patients with heart failure, aged 43.3 +/- 10.5 years, 262 (78.7%) men and 71 (21.3%) women. Heart failure was ascribed to idiopathic dilated cardiomyopathy in 125 patients. Heart failure was caused by ischemic heart disease in 63 patients, Chagas' disease in 58, hypertensive heart disease in 41, alcoholic cardiomyopathy in 24, and was due to other etiologies in 22 patients. Statistical analysis was performed with the chi(2) test, Student's t-test, analysis of variance, Kaplan-Meier and Cox proportional hazards methods. RESULTS: The DD genotype was associated with increased systolic left ventricular diameter (p = 0.031). Earlier onset of symptoms was observed in patients with alcoholic cardiomyopathy and DD genotype (p = 0.033, codominant D) and in patients with hypertensive cardiomyopathy and DD genotype (p = 0.048, codominant D; p = 0.024, recessive D). Mortality was higher in patients older than 50 years with DD genotype (p = 0.007, codominant D; p = 0.002, recessive D). Variables independently associated with higher mortality in patients older than 50 years were age, diabetes mellitus, Chagas' disease etiology and DD genotype. CONCLUSIONS: These results add evidence for an association of the DD genotype of the angiotensin-converting enzyme gene with earlier onset of symptoms and decreased survival rate of selected patients with heart failure.

Análise do bloqueio do ramo esquerdo pelo mapeamento eletrocardiográfico de superfície. Comparação com os achados eletro-vetorcardiográficos / Left bundle branch block analysis by body surface mapping. Comparison with electrocardiographic and vectocardiographic findings

PURPOSE: To compare the correlation between the departure areas (DA), negative or positive, in patients whose electrocardiogram showed left bundle branch block (LBBB) and association with left ventricular hipertrophy (LVH) and myocardial infarction (MI), to the electrocardiographic (ECG) and vectocardiographic (VCG) classic criteria. METHODS: The study was carried out with 46 patients (27 males) with LBBB. These patients had hypertension (19.5), coronary heart disease (34.7) and 21 patients with no heart disease (45.8). RESULTS: The statistic analysis using the Cluster method divided the patients in two groups. Group I (22 patients) showed an average rate for the DA (-2 SD) of 1091 for QRS and of 640 for ST-T. For the DA (+2 SD), the average rate was 618 for QRS and 881 for ST-T; group II (24 patients) showed an averaged for the DA (-2 SD) of 1063 for QRS and of 225 for ST-T. For the DA (+2 SD), the averaged rate was 428 for QRS and 600 for ST-T. CONCLUSION: In general the current ECG/VCG findings, can not differentiate the presence of the association of LBBB to LVH and MI. The DA of ST-T, mainly negative was the most efficient to separate the two groups and help in the differential diagnosis.