Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.

Epidemiologic studies have shown an important increase in the high mortality of patients with congestive heart failure (CHF) despite optimal medical management. Ventricular arrhythmia was recognized as the most common cause of death in this population. Electrolyte imbalance, myocardial fibrosis, left ventricular dysfunction, and inappropriate neurohumoral activation are presumed responsible for sudden cardiac death. In this study, we focused on the deleterious effects of the overproduction of aldosterone that occurs in patients with CHF. Secondary hyperaldersteronism can be part of several factors thought to be responsible for sudden cardiac death. We randomized 35 patients (32 men, aged 48 +/- 9 years) with systolic dysfunction (ejection fraction 33 +/- 5%) and New York Heart Association class III CHF secondary to dilated or ischemic cardiomyopathy into 2 groups. The treatment group received spironolactone, an aldosterone receptor antagonist, along with standard medical management using furosemide, angiotensin-converting enzyme inhibitors, and digoxin. The control group received only the standard medical treatment. Holter monitoring was used to assess the severity of ventricular arrhythmia. After 20 weeks, patients who received spironolactone had a reduced hourly frequency of ventricular premature complexes (VPCs) (65 +/- 18 VPCs/hour at week 0 and 17 +/- 9 VPCs/hour at week 16) and episodes of nonsustained ventricular tachycardia (VT) (3.0 +/- 0.8 episodes of VT/24-hour period at week 0, and 0.6 +/- 0.3 VT/24-hour period at week 16). During monitored treadmill exercise, a significant improvement in ventricular arrhythmia was found in the group receiving spironolactone (39 +/- 10 VPCs at week 0, and 6 +/- 2 VPCs at week 16). These findings suggest that aldosterone may contribute to the incidence of ventricular arrhythmia in patients with CHF, and spironolactone helps reduce this complication.

Left ventricular hypertrophy predicts outcome of hypertension regardless of the type of ventricular arrhythmia present.

Left ventricular hypertrophy is associated with an increased cardiovascular mortality in hypertension. A potential role of ventricular arrhythmias is debated but not yet determined. The purpose of this study was to evaluate whether the presence of arrhythmias would ascribe any additional risk to cardiovascular mortality beyond that related to the presence of left ventricular hypertrophy. From November 1988 to February 1991, 40 mild to severe hypertensive patients (mean SBP, DBP 183/117 mm Hg) were submitted to clinical, echocardiographic and electrocardiographic evaluations complemented by 24-h Holter monitoring and then followed until November 1996. The Kaplan-Meier method supplemented by the Cox multiple regression model were performed to identify the variable(s) associated with fatal cardiovascular outcome. Twelve cardiovascular fatalities occurred as a consequence of sudden death (n = 4), stroke (n = 4), heart failure (n = 2) and myocardial infarction (n = 2). In comparison with patients who survived, those dying from cardiovascular causes had a greater percentage of electrocardiographic left ventricular hypertrophy (83 vs 36%, P = 0. 0037) and couplets of ventricular ectopic beats (58 vs 18%, P = 0. 0467). In addition, they showed larger left ventricular diastolic diameter (60 +/- 10 vs 53 +/- 8 mm), mass index (248 +/- 67 vs 154 +/- 57 g/m2) and posterior wall thickness (12 +/- 2 vs 10 +/- 2 mm), as well as shorter left ventricular fractional shortening (0.23 +/- 0.8 vs 0.32 +/- 0.9). Univariate analysis showed that electrocardiographic left ventricular hypertrophy and strain, mass index, end-systolic wall stress, fractional shortening and the presence of couplets were significantly related to cardiovascular mortality. However, only mass index was shown to be independently associated with cardiovascular death. In conclusion, left ventricular hypertrophy predicts cardiovascular outcome, regardless of the presence of other signs of cardiac damage, including ventricular arrhythmia.

Blood pressure and the risk of complex arrhythmia in renal insufficiency, hemodialysis, and renal transplant patients.

Complex arrhythmia is frequent in hemodialysis patients but it is not clear if this is a consequence of dialysis or uremia or is secondary to the hemodynamic and cardiovascular alterations often associated with chronic renal failure. The incidence of complex ventricular arrhythmia (frequent multiform premature beats, couplets, and runs) in 31 subjects who had their uremic status recently corrected by renal transplant (Group 1) and in 23 predialysis (Group 2) and 73 hemodialysis (Group 3) chronic renal failure patients were studied with 24-h Holter monitoring. Patients were not receiving antiarrhythmic drugs or digitalis and significant coronary artery disease was excluded by clinical and noninvasive methods. Complex arrhythmia was two times more frequent in dialysis patients but the difference did not reach statistical significance (Group 1: 16%; Group 2: 17%; Group 3: 34%; chi2 4.9, P = .086). The stepwise model of logistic regression analysis identified systolic blood pressure (odds ratio 1.015, 95% confidence interval [CI] 1.001-1.027, P = .03) and left ventricular systolic dysfunction (odds ratio 7.04, 95% CI 1.3-36.7, P = .02) as the only factors that independently influenced the probability of complex arrhythmia. Age, gender, race, diabetes, smoking status, body mass index, diastolic blood pressure, serum creatinine, hematocrit, left ventricular mass index, and use of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatolytics, and calcium channel blockers did not influence the occurrence of complex arrhythmia. The data indicate that blood pressure and myocardial dysfunction are more important determinants of complex arrhythmia than dialysis or uremia in chronic renal disease patients.

[The role of hypertrophy and left ventricular function on the occurrence of ventricular arrhythmias in arterial hypertension]. / Papel da hipertrofia e da função ventricular esquerda sobre a ocorrência de arritmias ventriculares na hipertensão arterial.

PURPOSE: To evaluate the role of left ventricular hypertrophy (LVH), left ventricular systolic function an other clinical parameters on prevalence and complexity of ventricular arrhythmias in hypertension. METHODS: Ventricular arrhythmias were studied in 39 hypertensives by 24 hours ambulatory electrocardiographic monitoring. Frequency and complexity of ventricular arrhythmias were compared among 3 groups: A and B, respectively without and with LVH, both with normal left ventricular function; and C with LVH and systolic dysfunction. LVH and systolic dysfunction were established echocardiographically. Linear regression analysis was performed in order to identify an independent correlation between clinical parameters and presence of arrhythmias. RESULTS: Group C patients were older and had significantly higher systolic and diastolic blood pressures, greater mass index, diastolic posterior wall thickness and end-systolic stress and increased prevalence of electrocardiographic strain. Left ventricular diastolic diameter in C group patients was increased only when compared to A group. Frequencies of cases with more than 10 ectopic ventricular beats/hour, pairs and nonsustained ventricular tachycardia episodes were all significantly increased in C when compared to B and to A. However, only left ventricular mass index or diastolic posterior wall thickness identified independently patients with ventricular arrhythmias. CONCLUSION: Left ventricular hypertrophy is the main predictor of potential high risk rhythm disturbances in hypertension.

[Hypertension and complex ventricular arrhythmias. Evolution following a long-term blood pressure treatment]. / Hipertensão arterial e arritmias ventriculares complexas. Evolução após tratamento de longo prazo da pressão arterial.

PURPOSE: To evaluate the effects of long-term antihypertensive treatment in the frequency as well as in the complexity of ventricular arrhythmias in arterial hypertension. METHODS: Twenty three patients, 14 males and 11 whites, with mean age of 46 years, were submitted to 24 hours ambulatory electrocardiographic monitoring and echocardiographic studies before and 9 months after antihypertensive treatment. RESULTS: There was no significant serum potassium level alteration, but significant reductions of both systolic (from 192 +/- 29mmHg to 161 +/- 25mmHg) and diastolic (from 122 +/- 17mmHg to 99 +/- 16mmHg) blood pressure. Left ventricular percent of fiber shortening significantly increased, even though only from 26 +/- 9% to 30 +/- 9%, and end-systolic wall stress did not change at all (before 258 +/- 94 10(3) dyn/cm2, after 255 +/- 101 10(3) dyn/cm2). Left ventricular mass index showed significant but also a discrete reduction from 211 +/- 75g/m2 to 196 +/- 70g/m2. Ambulatory electrocardiographic monitoring did not show any significant decrease in neither ventricular ectopic beats nor in couplets. Non-sustained ventricular tachycardia episodes remained unchanged too. Four out of 8 patients with more than 30 ventricular ectopic beats per hour reduced it by more than 70%. On the other hand, the number of patients with couplets was reduced from 10 to 8 whilst those with non-sustained ventricular tachycardia increased from 5 to 7. Furthermore, in 7 patients reevaluated 24 months thereafter results were not expressively dissimilar. CONCLUSION: In hypertensive patients with either severe degree of left ventricular hypertrophy or myocardial dysfunction, long-term blood pressure treatment that produce no impressive changes in these abnormalities also do not modify complex ventricular arrhythmias, in spite of a great reduction in the increase blood pressure.

[Beneficial effects of enalapril on the diastolic ventricular function in Chagas myocardiopathy]. / Ação benéfica do enalapril sobre a função diastólica ventricular na miocardiopatia da doença de Chagas.

PURPOSE: To verify the effect of enalapril on ventricular function and on the incidence of ventricular arrhythmias in patients with Chagas' disease with congestive heart failure. METHODS: We studied 20 patients with Chagas' disease, aged between 24 to 64 (mean 44) years. There were 17 male. All patients have positive serologic blood tests for Chagas' disease (immunofluorescence and Machado-Guerreiro test), left ventricular diastolic diameter superior to 55mm and ejection fraction less than 0.60. The patients were divided aleatory in two groups: control group (CG) with 9 patients receiving conventional treatment (digital and diuretics) and enalapril group (EG), with 11 patients where enalapril was added to conventional treatment. The treatment was maintained during two months and the patients were evaluated at the beginning and at the end, when they were submitted to clinical examination, echo-doppler-cardiogram, stress test and 24h Holter monitoring. At two dimensional echocardiographic study we evaluate left ventricular and left atrial diameters, at doppler study the E/A relations, the systolic volume and cardiac index. At the stress test and Holter monitoring we evaluate the incidence of ventricular arrhythmias. RESULTS: The comparison between initial and final evaluations, showed that there was a significant improvement of diastolic function (p = 0.04) and a trend to improvement of systolic function (great systolic volume and cardiac index) at EG. The incidence of non sustained ventricular tachycardia was the same in the two groups. CONCLUSION: In Chagas' disease enalapril improves significantly diastolic dysfunction in patients with heart failure. After two months of treatment we observed tendency to improvement of systolic dysfunction and the incidence of arrhythmias induced by stress test.

Prognostic significance of silent myocardial ischemia after a first uncomplicated myocardial infarction.

Forty asymptomatic patients were studied after a first uncomplicated myocardial infarction. They were 36 men and 4 women, with a mean age of 52.6 yr; the location of myocardial infarction was in the anterior wall in 18 (45%) patients and in the inferior wall in 22 (55%). The patients were submitted to: (1) 48-h Holter monitoring, during the 2nd and 8th weeks after the acute event; (2) exercise testing during the same periods; (3) cardiac catheterization and coronary arteriography. Patients with clinical conditions associated with cardiac rhythm disturbances or repolarization abnormalities were excluded. The electrocardiographic methods identified 11 (27.5%) patients with silent myocardial ischemia. Patients with and without silent ischemia were similar in relation to sex, age, coronary risk factors, arrhythmias, left ventricular function and follow-up. Patients with silent ischemia had more inferior wall myocardial infarctions, but the difference was not statistically significant. Patients with silent ischemia had significantly more extensive coronary artery disease (45.5% multivessel disease) when compared to those without ischemia (14.8% multivessel disease) (p < 0.05). After a 2-yr follow-up, 4 (36.4%) patients with and 1 (3.4%) without silent ischemia had a coronary event (p < 0.05). Kaplan-Meier analysis demonstrated a significantly higher cumulative probability of not experiencing a new coronary event for the patients without silent ischemia (96.5%) as compared to those with silent ischemia (62.3%) (p < 0.01). Our results suggest that silent myocardial ischemia after a first uncomplicated myocardial infarction carries an adverse prognosis and should be routinely investigated.

[Variability of the heart rate and silent ischemia after myocardial infarction]. / Variabilidade da freqüência cardíaca e isquemia silenciosa após infarto do miocárdio.

PURPOSE: To show a possible relation between heart rate and silent myocardial ischemia. METHODS: Forty-nine ischemic episodes were registered in six patients during a total period of 576-hour Holter monitoring. Those patients were selected from a group of 40 asymptomatic individuals after a first uncomplicated myocardial infarction; 11 (27.5%) showed ischemia during daily activities or exercise, the six selected patients had myocardial ischemia on Holter monitoring. RESULTS: The silent episodes consisted 92% of the total ischemic burden; they lasted from 1 min 30 s to 20 min and the ST-segment depression varied from -1.1 mm to 3.3 mm. Thirty-five (72%) episodes occurred at rest or during light physical activities; nine (18.5%) occurred between 7:00 AM and 12:00 PM; eight (16.5%), between 12:00 PM and 6:00 PM; 17 (35%) between 6:00 PM and 12:00 AM and 15 (30%), between 12:00 AM and 7:00 AM. There was no significant change (more than 20%) in heart rate at the onset of ischemic episodes in relation to the heart rate 1 minute before (94.63 +/- 9.79 bpm and 99.47 +/- 10.99 bpm, respectively). Complex ventricular arrhythmias occurred in all patients and only one of them had an episode of nonsustained ventricular tachycardia related to silent ischemia. CONCLUSION: Our results suggest that there is no relation between heart rate, arrhythmias and silent ischemia.

Efeitos eletrocardiográficos e hemodinâmicos do cloridrato de amiodarona por via venosa / Electrocardiographic and hemodynamic effects of amiodarone hydrochloride by intravenous route

Quatorze pacientes portadores de cardiomiopatia chagasica cronica, com arritmias ventriculares persistentes e insuficiencia miocardica, foram submetidos a avaliacao eletrocardiografica continua por periodo de 24 horas (em 12 pacientes) e a estudo hemodinamico, antes (condicao de controle) e apos (condicao 20, 40 e 60 minutos) a administracao de 5 mg/kg de peso seguida por infusao venosa continua de 900 a 1050 mg de cloridrato de amiodarona (AM) por periodo de 24 horas. Houve reducao porcentual media de 73,5% no numero de extra-sistoles ventriculares sem modificacoes apreciaveis nos episodios de taquicardia ventricular. Entre as condicoes 20 e 60 minutos, ocorreu diminuicao significativa da frequencia cardiaca (FC) e do indice cardiacao e aumento nas pressoes media do atrio direito (AD), na diastolica final do ventriculo esquerdo e nas resistencias arterial pulmonar e vascular sistemica. Com excecao dos valores da FC e da AD, as demais variaveis hemodinamicas retornaram aos valores de controle 24 horas a infusao venosa continua de AM. Em vista da depressao da funcao cardiaca que persistiu ate 60 minutos, concluiu-se que o AM deve ser cuidadosamente administrado principalmente em pacientes con insuficiencia miocardica

Tratamento cirúrgico da anomalia de Ebstein associada à síndrome Wolff - Parkinson-White / Surgical treatment of Ebstein's anomaly associated with Wolff-Parkinson-White syndrome

Os autores relatam o caso de paciente masculino, 19 anos, portador de anomalia de Ebstein associada a pre-excitacao direta, manifestada somente por crises frequentes de taquicardias, limitadoras e resistentes a terapeutica convencional. O estudo eletrofisiologico, realizado por ocasiao de estudo hemodinamico completo, demonstrou haver pre-excitacao ventricular por conexao anomala postero-septal direita participando no circuito de taquicardia. O paciente foi submetido a troca valvar por bio-protese de dura-mater e a interrupcao da via anomala. Houve desaparecimento da pre-excitacao, nao se demonstrando conducao retrograda e/ou anterograda, atraves dos testes de estimulacao artificial. Com base no resultado obtido, os autores concluem pela eficacia do tratamento cirurgico na interrupcao funcional da conexao anomala e propoem, como procedimento de rotina nesta anomalia,a investigacao eletrofisiologica e a seccao dos feixes anomalos quando presentes, mesmo em ausencia de arritmia previa