Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure

Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.     

Nifedipine tablet vs. hydralazine in patients with persisting hypertension who receive combined diuretic and beta-blocker therapy

The antihypertensive effects of a 20 mg tablet of nifedipine were compared with those of hydralazine in a randomized, double-blind, placebo-controlled study. Nineteen patients with a diastolic blood pressure (BP) between 95 and 120 mm Hg despite combined diuretic and beta-blocker therapy completed the protocol. After 2 weeks of placebo each subject received increasing doses of nifedipine (20, 40, and 60 mg b.i.d.) and hydralazine (25, 50, and 100 mg b.i.d.) if tolerated or until goal BP (supine and standing diastolic BP less than 85 mm Hg) was achieved. Both nifedipine and hydralazine significantly lowered supine BP from placebo baseline (146 +/- 3/96 +/- 2 mm Hg) to 119 +/- 3/80 +/- 2 and 129 +/- 2/81 +/- 2 mm Hg, respectively. The decrease in systolic BP with nifedipine was significantly lower than that with hydralazine at 9 weeks. Neither drug significantly altered heart rate. Mean left ventricular ejection fractions were similar for nifedipine (67% +/- 2%), hydralazine (69% +/- 3%), and placebo (66% +/- 2%). The nifedipine tablet appears to be an effective antihypertensive agent in patients whose BP remains high despite combined diuretic and beta-blocker therapy.     

Augmentation of diastolic function with phosphodiesterase inhibition in congestive heart failure

Phosphodiesterase inhibition promotes both cellular uptake and release of calcium, which should thus facilitate both myocardial relaxation and myocardial contraction. To test the hypothesis that phosphodiesterase inhibition augments both diastolic and systolic ventricular function, parameters of left ventricular ejection and filling were measured in patients with dilated cardiomyopathy before and after therapy with the phosphodiesterase inhibitor enoximone. Baseline radionuclide ventriculography was performed in all subjects with derivation of left ventricular ejection fraction and peak diastolic filling rate. These parameters were again assessed after 3 months of therapy with either placebo (six patients) or enoximone (seven patients). Ejection fraction increased significantly (p less than 0.05) in the enoximone group (change from baseline = 11 +/- 14 ejection fraction units) but did not change in the placebo group (0.2 +/- 5 ejection fraction units). Enoximone administration was associated with a significant (p less than 0.05) increase in peak filling rate, from 0.9 +/- 0.5 to 1.4 +/- 0.5 end-diastolic volumes per second, which was noted in the placebo group (1.2 +/- 0.6 to 1.4 +/- 0.9 end-diastolic volumes per second; p = not significant). Thus, in comparison with placebo, exoximone augmented both diastolic and systolic function in dilated cardiomyopathy. This identifies an additional influence of this class of inotropic agent on the function of the intact ventricle that is consistent with previously described cellular mechanisms and that may significantly contribute to a restoration of normal hemodynamic status in dilated cardiomyopathy.     

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.     

Efficacy of valsartan in patients aged > or =65 years with systolic hypertension

OBJECTIVE: This randomized, double-blind, placebo-controlled, parallel-group, multicenter trial investigated the effects of valsartan, an angiotensin II receptor blocker, on systolic blood pressure (SBP) in patients aged > or =65 years with systolic hypertension, with or without diastolic hypertension. BACKGROUND: Hypertension in older persons is a public health problem of epidemic proportions. SBP, which increases with age, is a better predictor of cardiovascular morbidity and all-cause mortality than is diastolic blood pressure (DBP). SBP is now thought to be a major modifiable risk factor for cardiovascular disease. METHODS: The study population consisted of 146 outpatients (74 female and 72 male) with a mean (+/- SD) age of 73.0+/-6.7 years and a trough mean sitting SBP > or =160 mm Hg; 88.4% were white. Patients with clinically relevant cardiac valvular disease, documented or suspected renal artery stenosis, and a serum creatinine level >2.5 mg/dL were excluded from the study. After a 2- to 4-week, single-blind, placebo run-in period, patients were randomly assigned to receive valsartan 80 mg or placebo once daily for 4 weeks and were then force-titrated to valsartan 160 mg or matching placebo once daily for an additional 4 weeks. Median DBP was 90 mm Hg, and >50% of the patients had isolated systolic hypertension. RESULTS: For the primary efficacy variable, the change from baseline to end point in trough mean sitting SBP, treatment with valsartan was superior to placebo, with reductions of 19.2 mm Hg compared with 8.8 mm Hg, respectively (P < 0.001, 95% CI -15.7, -5.5). Valsartan also produced superior reductions in trough mean sitting DBP (5.2 mm Hg and 1.2 mm Hg for valsartan and placebo, respectively; P < 0.001, 95% CI -6.4, -2.3). The tolerability of valsartan was comparable to that of placebo, with adverse events occurring in 31 (42.5%) valsartan-treated patients compared with 28 (38.4%) patients who received placebo. CONCLUSIONS: In this patient population of hypertensive patients aged > or =65 years, valsartan was effective and well tolerated and offers a promising new approach to the treatment of systolic hypertension.     

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.     

A pilot study to assess the use of protein a immunoadsorption for chronic dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a leading cause of end-stage heart failure and cardiac transplantation. Anticardiac antibodies are common and removal of these through immunoadsorption (IA) is associated with improvement in global cardiac function. The effect of IA on regional function and quality of life (QOL) without intravenous immunoglobulin (IVIG) substitution has not been described. We performed a pilot trial using Immunosorba columns in four patients with chronic DCM and NYHA Class II-III congestive heart failure. Subjects were followed for 6 months with serial echocardiograms and validated QOL assessments. Regional and global left ventricular (LV) end-systolic deformations were assessed by two-dimensional strain echocardiography. Total IgG decreased 95% (from 1,210 +/- 274 mg/dl to 57 +/- 16 mg/dl, P = 0.003) and IgG3 decreased 61% (from 33 +/- 16 mg/dl to 13 +/- 7 mg/dl, P = 0.024). QOL improved from baseline to 6 months as assessed by the Living with Heart Failure questionnaire (from 54 +/- 18 to 19 +/- 7, P = 0.029). Mean LV ejection fraction improved from 35 to 40% at Day 5 and to 44% at 6 months (P = NS). The LV end diastolic and end systolic volumes decreased (220-202 ml, 159-130 ml, P = NS) at 6 months. Global end-systolic strain improved from -7.3% at baseline to -8.5% at Day 5 and -8.8% at 6 months (P = NS). Regional LV function and response to IA was not uniform. Even without IVIG substitution, IA for the treatment of chronic DCM is associated with improved QOL up to 6 months after treatment. A randomized, sham-controlled trial is required to confirm the benefits of IA for DCM.     

Dual chamber pacemaker therapy for mid-cavity obstructive hypertrophic cardiomyopathy

Intracavitary LV obstruction is an important determinant of clinical outcome in hypertrophic cardiomyopathy (HCM). In a minority of patients the obstruction is at the level of the papillary muscles. Mid-cavity obstructive HCM may be associated with a distal LV aneurysm and a worse prognosis. It is often not amenable to standard cardiac surgeryfor LV outflow obstruction. The long-term effects (mean follow-up 4.8+/-2.9 years) of dual chamber (DDD) pacemaker therapy in 14 patients with mid-cavity obstructive HCM (mean age 34+/-16 years, range 15-65 years) were studied. Patients were evaluated by cardiac catheterization at baseline and 6 months to 1 year after receiving DDD pacemakers off all drug therapy. Symptoms were improved in all patients and NYHA functional class reduced from 2.8+/-0.1 to 1.9+/-0.4 (P < 0.0005). Intracavitary LV pressure gradients was reduced significantly (43+/-36 vs 84+/-31 mmHg at baseline, P < 0.0005). There was a significant associated reduction in apical LV systolic pressure (152+/-37 vs 188+/-34 mmHg, P < 0.001). In addition, there was a trend towards increased exercise tolerance (445+/-123 vs 396+/-165). Cardiac output and LV filling pressures were unchanged. In conclusion, chronic DDD pacing results in significant symptomatic and hemodynamic improvement in this uncommon but important subset of patients with obstructive HCM in whom the role of cardiac surgery is less well defined compared with the more typical outflow tract location of LV obstruction.     

Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome

BACKGROUND: Hypercholesterolemic patients with metabolic syndrome (MS) are at high risk for coronary heart disease. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines provide the option of aggressively lowering low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients with MS. OBJECTIVE: The lipid-modifying efficacy of simvastatin and atorvastatin in hypercholesterolemic patients with MS as defined by NCEP ATP III was assessed. METHODS: A post hoc subgroup analysis was performed on data from a 36-week, multicenter (54 sites worldwide), randomized, double-blind, parallel-group, dose-escalation (forced-titration) study designed to assess the effects of simvastatin (40-80 mg) and atorvastatin (20-80 mg) on high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels in patients with LDL-C > or = 160 mg/dL. Patients were classified as having MS if they met >/=3 of the following criteria: (1) triglyceride (TG) level > or =150 mg/dL; (2) HDL-C <40 mg/dL (men) or <50 mg/dL (women); (3) secondary diagnosis of type 2 diabetes mellitus and/or taking antidiabetic medication and/or fasting serum glucose (FSG) level > or =110 mg/dL; (4) secondary diagnosis of hypertension and/or taking antihypertensive medication and/or systolic blood pressure (SBP)/diastolic blood pressure (DBP) > or =130/ > or =85 mm Hg; and (5) body mass index (BMI) > or =30 kg/m(2) (surrogate for waist circumference). RESULTS: Of 808 evaluable patients, 212 (26.2%) were classified as having MS at baseline. Compared with the non-MS subgroup, MS patients were slightly older and more likely to be female. They also had higher BMI, SBP/DBP, FSG, and TG levels, and lower HDL-C and apo A-I levels than non-MS patients. The simvastatin group contained 99 patients; the atorvastatin group, 113 patients. Both drugs produced large reductions in total cholesterol, LDL-C, non-HDL-C, TG, and apo B, with atorvastatin producing slightly greater reductions in TG. However, simvastatin consistently produced larger increases in HDL-C and apo A-I than atorvastatin, especially at higher doses. After 36 weeks of treatment, 47.7% and 48.5% in the simvastatin and atorvastatin groups, respectively, no longer met > or =3 of the MS criteria. CONCLUSIONS: In hypercholesterolemic patients with characteristics of MS, simvastatin and atorvastatin had comparable beneficial effects on apo B-containing atherogenic lipids and lipoproteins, and MS status was effectively modified by both drugs. However, although atorvastatin produced slightly larger decreases in TG, simvastatin produced larger increases in HDL-C.     

Antihypertensive activity of isradipine in humans: a new dihydropyridine calcium channel antagonist

Isradipine (Sandoz PN 200-110), a new dihydropyridine calcium channel antagonist, was evaluated in a randomized, double-blind, placebo-controlled trial for antihypertensive efficacy in 24 patients with essential hypertension. Two groups were studied: one received placebo throughout the entire study (n = 12) and the other received isradipine (n = 12), 2.5 mg b.i.d., for the first week, 5 mg b.i.d. the second week, and 10 mg b.i.d. the third week after an initial 3-week baseline placebo period. Blood pressure was measured approximately 3 hours after dosing. Isradipine, at a total daily dose of 10 mg, lowered average supine diastolic blood pressure 11.8 mm Hg, with only a 3.5 mm Hg decrease in systolic blood pressure compared with baseline. At a total daily dose of 20 mg, average supine diastolic blood pressure decreased 14.8 mm Hg and supine systolic blood pressure declined 13.9 mm Hg; both were significantly decreased compared with placebo or baseline. Heart rate was increased only minimally by isradipine. Renin level activity was increased slightly by isradipine. No serious adverse clinical or laboratory experiences were noted. Isradipine appears to be effective in lowering blood pressure without reflex tachycardia.     

Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy.

Previous reports have shown that increases in heart rate may result in enhanced left ventricular (LV) systolic and diastolic performance. To assess whether this phenomenon occurs in the presence of depressed LV function, the effects of pacing on LV pressure and volume were compared in seven patients with dilated cardiomyopathy (LV ejection fraction 0.19 +/- 0.11) and six patients with no or minimal coronary artery disease (LV ejection fraction 0.69 +/- 0.11). Patients with normal LV function demonstrated significant increases in LV peak-positive dP/dt, LV end-systolic pressure-volume ratio, LV peak filling rate, and a progressive leftward and downward shift of their pressure-volume diagrams, compatible with increased contractility and distensibility in response to pacing tachycardia. There was no change in LV peak-negative dP/dt or tau. Patients with dilated cardiomyopathy, in contrast, demonstrated no increase in either LV peak-positive dP/dt or the end-systolic pressure-volume ratio, and absence of a progressive leftward shift of their pressure-volume diagrams. Moreover, cardiomyopathy patients demonstrated no increase in LV peak-negative dP/dt or LV peak filling rate and a blunted downward shift of the diastolic limb of their pressure-volume diagrams. Tau, as determined from a derivative method, became abbreviated although never reaching control values. We conclude that patients with dilated cardiomyopathy may demonstrate little or no significant enhancement in systolic and diastolic function during atrial pacing tachycardia, suggesting a depression of both inotropic and lusitropic reserve.     

Enalapril in low-renin essential hypertension

The antihypertensive efficacy of N-[(S)-1-(ethoxycarbonyl)-3-phenyl-propyl]-L-alanyl-L-proline (enalapril maleate) was evaluated in a randomized, double-blind trial in 23 patients with mild low-renin essential hypertension ranging in age from 32 to 70 yr (20 were black and 3 were white). All underwent a 4-wk washout-placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily, 5 mg enalapril twice daily, or placebo twice daily for 12 wk. Conditional on diastolic pressure, the dose was increased at 4-wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached. At the end of the 12-wk titration phase, there was a follow-up period during which measurements were made after discontinuation of the medication. Mean supine diastolic pressure decreased from baseline (98.5 +/- 2.6 mm Hg) during the titration phase (86.3 +/- 4.6 mm Hg) in the group taking enalapril once daily. In three of the eight patients in the once-daily group and five of eight in the twice-daily group, supine diastolic pressures fell below 90 mm Hg. Neither supine nor standing systolic pressure nor standing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily. Heart rates measured after 5 min supine rest were not altered by enalapril. Enalapril induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules. No adverse effect attributable to enalapril occurred during the study. The data indicate that once-daily enalapril is safe and effective treatment for mild low-renin essential hypertension.     

Clinical Efficacy and Safety of Lower-Dose Indapamide Therapy in the Treatment of Patients with Mild to Moderate Hypertension

Previous clinical studies with indapamide, an indoline antihypertensive drug with diuretic and vasodilating activities, have shown a dose relationship associated with potassium loss. Two placebo-controlled, randomized, double-blind, parallel clinical studies were, therefore, done to evaluate the safety and efficacy of a low dose (1.25 mg) of indapamide and to determine if an improved safety profile could be produced while maintaining efficacy with a 1.25-mg dose in patients with mild to moderate essential hypertension. Four hundred seventeen (417) adult patients with mild to moderate essential hypertension (sitting diastolic blood pressure greater-than-or-equal 95 mmHg and less-than-or-equal 110 mmHg) were enrolled in two clinical studies; 209 patients were randomized to indapamide 1.25 mg and 208 patients to placebo. Patients received single-blind placebo for a 4-week washout period followed by an 8-week double-blind treatment period during which patients received either indapamide 1.25 mg or placebo. The primary efficacy endpoint was the mean change from baseline to week 8 in sitting diastolic blood pressure. Secondary efficacy variables were the proportion of patients whose sitting diastolic blood pressure had decreased greater-than-or-equal 10 mmHg and/or had a sitting diastolic blood pressure of less-than-or-equal 90 mmHg (treatment success) at all visits and at endpoint, mean changes from baseline in sitting diastolic blood pressure at designated timepoints and at endpoint, and mean changes from baseline in standing diastolic blood pressure and in sitting and standing systolic blood pressure at all visits and at endpoint. Results of these trials were pooled in order to have a larger patient population in an attempt to detect trends not readily apparent with a smaller sample size. In the primary analysis, indapamide produced statistically significantly (p = 0.0001) greater reductions in sitting diastolic blood pressure than placebo after 8 weeks of therapy. In the secondary analysis, the percentage of indapamide-treated patients who achieved treatment success after 8 weeks of therapy was statistically significantly (p < 0.0001) higher compared to placebo-treated patients. In addition, indapamide produced a statistically significantly (p = 0.0001) superior reduction compared to placebo in sitting systolic and standing systolic and diastolic blood pressure after 8 weeks of therapy. The incidence of drug-related adverse events between patients in the indapamide and placebo groups was similar. There were no clinically meaningful differences in laboratory values, including serum potassium, between the patients in the indapamide and placebo groups. Low-dose (1.25 mg) indapamide proved to be safe and effective in the treatment of mild to moderate hypertension.     

An integrated measure of left ventricular diastolic function based on relative rates of mitral E and A wave propagation.

BACKGROUND AND OBJECTIVES: The mitral E wave propagation inside the left ventricle is slowed in patients with abnormal left ventricular (LV) relaxation with a prolongation of its transit time to the LV outflow tract (T(e)). On the contrary, the mitral A wave propagation is faster in those with elevated LV end-diastolic stiffness, resulting in a shortening of its transit time (T(a)). We hypothesized that the T(e)/T(a) ratio may serve an integrated measure of global LV diastolic function. METHODS AND RESULTS: The T(e)/T(a) ratio was measured with Doppler echocardiography in 94 subjects: 25 normal subjects, 38 patients with LV hypertrophy (18 with secondary LV hypertrophy and 20 with hypertrophic cardiomyopathy), and 31 patients undergoing left heart catheterization for clinical indications. The T(e)/T(a) ratio was 1. 98 +/- 0.61 in the normal subjects, 3.32 +/- 0.93 in patients with secondary LV hypertrophy (P <.0001 vs normal), and 3.18 +/- 1.36 in patients with hypertrophic cardiomyopathy (P =.0003 vs normal). In the invasive group the T(e)/T(a) ratio (range 0.56 to 3.60) correlated significantly with Tau (r = 0.76, P <.0001), peak negative dP/dt (r = -0.46, P =.01), the LV late diastolic stiffness index (r = 0.57, P =.0013), LV pre-A wave pressure (r = 0.46, P =. 0096), LV end-diastolic pressure (r = 0.58, P =.0007), and the amount of LV pressure rise with atrial systole (r = 0.52, P =.0032) but not with the heart rate. Tau and LV stiffness were its sole determinants by stepwise multiple regression (R = 0.82). CONCLUSIONS: The ratio of mitral E and A wave transit times inside the LV (T(e)/T(a) ratio) is closely related to LV relaxation, its late diastolic stiffness, and filling pressures and gives valuable insights into LV diastolic performance.     

Dual chamber pacing in hypertrophic cardiomyopathy: long-term effects on diastolic function

To assess the effects of chronic dual chamber pacing (DDD) on LV diastolic function in obstructive hypertrophic cardiomyopathy (HCM), 21 patients with obstructive HCM paced for refractory symptoms were studied at baseline and at 3 and 12 months. HCM patients were matched to 21 patients with obstructive HCM on conventional treatment. Left atrial fractional shortening was calculated by M-mode echocardiography; this index reflects LV end-diastolic pressure. LV outflow tract gradient decreased 65 +/- 21% with DDD pacing and the NYHA class improved (P = 0.033). Left atrial fractional shortening worsened with DDD pacing (P < 0.001). Patients with abnormal baseline left atrial fractional shortening (< 16%) were older, had a higher NYHA class, and had more severe mitral regurgitation. In this subgroup, left atrialfractional shortening did not worsen with DDD pacing and the NYHA class improved more than in patients with normal left atrialfractional shortening (P = 0.033). In conclusion, chronic DDD pacing reduces obstruction but impairs diastolic function in HCM. In patients with normal diastolic function, the untoward effects of pacing on diastolic function are more evident than in patients with abnormal diastolic function at baseline. This suggests that DDD pacing might be beneficial in a subgroup of patients with obstructive HCM and abnormal diastolic function.     

The effect of ruboxistaurin on nephropathy in type 2 diabetes

OBJECTIVE: Ruboxistaurin selectively inhibits protein kinase C-beta and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons (n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated. RESULTS: At baseline, urinary ACR was 764 +/- 427 mg/g (means +/- SD), and eGFR was 70 +/- 24 ml/min per 1.73 m2. Systolic and diastolic blood pressures were 135 +/- 14 and 75 +/- 9 mmHg, respectively. HbA(1c) was 8.0 +/- 1.2%. After 1 year, urinary ACR decreased significantly (-24 +/- 9%) in participants treated with ruboxistaurin (P = 0.020) and nonsignificantly (-9 +/- 11%) in the placebo group (P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (-2.5 +/- 1.9 ml/min per 1.73 m2) (P = 0.185), whereas the placebo group lost significant eGFR over 1 year (-4.8 +/- 1.8 ml/min per 1.73 m2) (P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences. CONCLUSIONS: In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.     

Determinants of coronary flow abnormalities in obstructive type hypertrophic cardiomyopathy: noninvasive assessment by transthoracic Doppler echocardiography.

We aimed to visualize the coronary flow velocities (CFV) of patients with hypertrophic obstructive cardiomyopathy by using transthoracic Doppler echocardiography, and to determine the relationship between abnormal CFV patterns and conventional echocardiography indices. Guided by 2-dimensional echocardiography and Doppler color flow mapping, CFV in the distal left anterior descending coronary artery were measured in 21 patients with hypertrophic obstructive cardiomyopathy using a 3.5-MHz transducer. The results were compared with those of 18 control subjects. Abnormal systolic flow patterns were observed in 15 (71%) patients (11 systolic-reversal flow and 4 no systolic flow). For patients and control subjects, peak diastolic velocity and velocity-time integral obtained from distal left anterior descending coronary artery were higher (63 +/- 21 cm/s and 18.5 +/- 4 cm vs 41 +/- 11 cm/s and 14.2 +/- 5 cm, respectively; P <.01 for both) whereas peak systolic velocity and velocity-time integral were significantly lower (-17 +/- 10 cm/s and 4.5 +/- 6 cm vs 24 +/- 9 cm/s and 9.5 +/- 4 cm, respectively; P <.001 for both). Significant positive and negative correlations between diastolic CFV and septal thickness index (r = 0.79, P <.0001), and between systolic CFV and septal thickness index (r = -0.65, P <.005), have been observed. CFV abnormalities that could easily be recorded by a standard Doppler echocardiographic study seem to be related to septal thickness rather than the degree of obstruction in hypertrophic obstructive cardiomyopathy.     

The importance of ventricular septal morphology in the effectiveness of dual chamber pacing in hypertrophic obstructive cardiomyopathy

It has been reported that older patients with hypertrophic obstructive cardiomyopathy (HOCM) benefited the most from dual chamber (DDD) pacing. Since in older patients the distribution of septal hypertrophy and left ventricular (LV) cavity shape differs from that in younger patients, we decided to study the efficacy of DDD pacing on the reduction of LV outflow tract (LVOT) gradient in different patterns of septal hypertrophy. We compared HOCM patients with nonreversed septal curvature, thus preserving the elliptical LV cavity contour (common in the elderly), (group I) versus patients with reversed septal curvature, deforming the LV cavity to a crescent shape (common in the young), (group II). Eighteen HOCM patients were studied (11 patients in group I and 7 patients in group II). After implantation of a DDD pacemaker, the LVOT gradient was measured using Doppler echocardiography at various programmed AV delay intervals to determine the maximal percentage decrease of LVOT gradient from baseline. The measurement was repeated after at least a 6-month follow-up (chronic DDD pacing). The baseline LVOT gradient was comparable between groups (79 +/- 28 vs 81 +/- 25 mmHg, P = 0.92). The LVOT gradient reduction at acute DDD pacing was significantly greater in group I than group II (61 +/- 18% vs 23 +/- 10%, P = 0.0001). This difference in favor of the patients from group I was maintained at midterm follow-up (69 +/- 17% vs 40 +/- 17% P = 0.0076). In conclusion, patients with normal septal curvature and preserved elliptical LV cavity shape had a greater reduction of LVOT gradient after DDD pacing than patients with reversed septal curvature deforming LV cavity. The proposed criterion assessing the septal curvature may be useful to predict the efficacy of DDD pacing in the reduction of LVOT gradient.     

A double-blind ambulatory blood pressure monitoring study of the efficacy and tolerability of once-daily telmisartan 40 mg in comparison with losartan 50 mg in the treatment of mild-to-moderate hypertension in Taiwanese patients

Ambulatory blood pressure monitoring (ABPM) was used to compare the efficacy and tolerability of once-daily telmisartan 40 mg and once-daily losartan 50 mg in Taiwanese patients with mild-to-moderate essential hypertension in a randomised, double-blind, double-dummy, parallel-group study. The initial 2-week placebo run-in phase was followed by randomisation to treatment with telmisartan 40 mg (n = 31) or losartan 50 mg (n = 30) for 6 weeks. The reduction in 18- to 24-h mean (SE) ambulatory diastolic blood pressure (DBP) from baseline was significantly greater with telmisartan 40 mg (-12.1 +/- 1.6 mmHg, p = 0.036) than with losartan 50 mg (-7.0 +/- 1.8 mmHg). The reduction in 18- to 24-h mean (SE) ambulatory systolic blood pressure (SBP) from baseline was also greater with telmisartan 40 mg (-16.0 +/- 2.4 mmHg) than with losartan 50 mg (-11.8 +/- 2.7 mmHg), but did not achieve statistical significance. Telmisartan was well tolerated; no serious adverse events occurred.     

Antihypertensive and cardiovascular effects of nitrendipine: a controlled study vs. placebo

The antihypertensive and cardiovascular effects of nitrendipine, a calcium entry blocker similar to nifedipine, have been evaluated in a double-blind, placebo-controlled study in 20 patients with hypertension. At baseline and at the end of the 8-week period (nitrendipine, 20 mg once a day, or placebo, 1 tablet once a day) the following parameters were measured: systolic and diastolic blood pressure (BP) and heart rate (HR) at rest by an automatic recorder; BP, HR, and cardiac workload (systolic BP X HR) during exercise testing on a bicycle; left ventricular mass (LVMe according to the method of Devereux) and cross-sectional area (CSA), and main parameters of systolic function (end diastolic volume, end systolic volume [ESV], and ejection fraction [EF]) by M mode echocardiography. There was a significant decrease in BP at rest (163/108 vs. 144/92 mm Hg; P less than 0.001) and during exercise in subjects receiving nitrendipine, while placebo did not modify these parameters. LVMe (from 195 to 188 gm; P less than 0.01) and CSA (from 20.2 to 19.8 cm2; P less than 0.05) were reduced by nitrendipine, which also improved cardiac performance (ESV fell from 44 to 38 ml [P less than 0.001] and EF fell from 62% to 66% [P less than 0.01]). No effect was observed in the placebo group. Our results indicate that nitrendipine is a powerful antihypertensive agent that also improves cardiac performance and slightly but significantly reduces left ventricular mass.