Relation of impaired left ventricular filling to systolic midwall mechanics in hypertensive patients with normal left ventricular systolic chamber function: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study

Background

Patients with hypertensive left ventricular (LV) hypertrophy commonly have diastolic dysfunction with preserved LV ejection fraction. LV systolic midwall shortening (MWS) may be impaired in hypertensive patients with normal LV ejection fraction. However, it is unclear whether impaired LV filling is related to depressed systolic midwall mechanics.

Methods

Echocardiographic measures of LV diastolic filling and systolic performance were compared in 632 unmedicated patients with stage II or III hypertension and LV hypertrophy determined by electrocardiogram, with LV ejection fraction >55% and <2+ mitral regurgitation.

Results

Stress-corrected LV MWS, an index of myocardial contractility, was lower in patients with abnormal as opposed to normal LV filling patterns (98% ± 12% vs 102% ± 10%, P < .001) and in patients with prolonged as opposed to normal isovolumic relaxation time (IVRT) (98% ± 13% vs 101% ± 12%, P = .014). Stress-corrected MWS was <85% of predicted levels in more patients with abnormal LV filling patterns (11.8% vs 6.3%) or with long IVRT (≥105 msec) (34% vs 21%, both P < .05). In regression analyses, lower stress-corrected MWS and higher LV mass were independent correlates of longer IVRT, while lower stress-corrected MWS was the only independent correlate of prolonged mitral valve deceleration time (P = .017). Higher LV mass had strong, statistically independent relationships to longer IVRT (by 0.3 g/msec) and decreased stress-corrected MWS (by 0.5 g/%; both P < .0001), independent of body size and age.

Conclusion

In patients with moderate hypertension and target organ damage who have normal LV ejection fraction, impaired early diastolic LV relaxation (abnormal E/A ratio, prolonged IVRT and deceleration time) is associated with impaired LV systolic midwall mechanics independent of higher LV mass.     

Limited predictive value of cardiopulmonary exercise indices in patients with moderate chronic heart failure treated with carvedilol

Background

Peak oxygen consumption (VO2) is traditionally used for risk stratification in chronic heart failure (CHF); however, its predictive value is unknown with carvedilol treatment. Therefore, we sought to investigate the prognostic role of gas-exchange parameters obtained from symptom-limited cardiopulmonary exercise testing (CPX) in patients with CHF that is treated with carvedilol.

Methods

A total of 508 consecutive patients (443 men, mean age [± SD] 59 ± 9 years) with a mean left ventricular ejection fraction (LVEF) of 25% ± 7% underwent CPX. The peak VO2 was 13.9 ± 3 mL/kg/min; the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO2 slope) was 32 ± 2. Outcomes (cardiovascular death or urgent heart transplantation) were determined when all patients who survived had been observed for a minimum of 6 months.

Results

Patients were divided into groups according to treatment (carvedilol and non-carvedilol); 236 patients were treated with carvedilol (46%), at a mean dose of 25 ±13 mg. The VE/CO2 slope, LVEF, peak VO2, and carvedilol treatment were revealed by means of multivariate analysis to be independent and additional predictors in the total population; VE/VCO2 slope, LVEF, and peak VO2 were revealed to be independent and additional predictors in the patients in the noncarvedilol group (all P <.001); and only peak VO2 was revealed to be an independent and additional predictor in the patients in the carvedilol group (P <.01). In the carvedilol group, mortality rates were 26%, 11%, 10%, and 4% (P <.05) in patients with peak VO2 ≤10 mL/kg/min, >10 to ≤14 mL/kg/min, >14 to18 mL/kg/min, and ≥18 mL/kg/min, respectively. No difference in mortality rates according to peak VO2 or additional outcome indices were identified in the 212 patients with peak VO2 >10 mL/kg/min.

Conclusions

Peak VO2 provides limited predictive information in patients with CHF that is treated with carvedilol, and no additional gas exchange parameter yields supplementary advice.     

Body weight changes with beta-blocker use: results from GEMINI

Purpose

Patients with type 2 diabetes are commonly overweight, which can contribute to poor cardiovascular outcomes. β-blockers may promote weight gain, or hamper weight loss, and are a concern in high-risk patients. The current analysis of the Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial evaluates the effects of carvedilol and metoprolol tartrate on weight gain in patients with type 2 diabetes and hypertension.

Methods

This prespecified secondary analysis of the GEMINI study (n=1106) evaluated change in body weight after 5 months.

Results

Mean (±SE) baseline weights were 97.5 (±20.1) kg for carvedilol and 96.6 (±20.1) kg for metoprolol tartrate. Treatment difference (c vs m) in mean (±SE) weight change from baseline was −1.02 (±0.21) kg (95% confidence interval [CI], −1.43 to −0.60; P <.001). Patients taking metoprolol had a significant mean (±SE) weight gain of 1.19 (±0.16) kg (P <.001); patients taking carvedilol did not (0.17 [±0.19] kg; P =.36). Metoprolol tartrate-treated patients with body mass index (BMI) >30 kg/m² had a statistically significant greater weight gain than comparable carvedilol-treated patients. Treatment differences (c vs m) in the obese (BMI >30 kg/m²) and morbidly obese groups (BMI >40 kg/m²) were −0.90 kg (95% CI, −1.5 to −0.3; P =.002) and −1.84 kg (95% CI, −2.9 to −0.8; P =.001), respectively. Pairwise correlation analyses revealed no significant associations between weight change and change in HbA_1c, HOMA-IR, or blood pressure.

Conclusions

Metoprolol tartrate was associated with increased weight gain compared to carvedilol; weight gain was most pronounced in subjects with hypertension and diabetes who were not taking insulin therapy.     

Melatonin reduces night blood pressure in patients with nocturnal hypertension

Purpose

Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension.

Patients and Methods

Thirty-eight treated hypertensive patients (22 males, mean age 64 ± 11 years) with confirmed nocturnal hypertension (mean nighttime systolic BP >125 mm Hg), according to repeated 24-hour ambulatory blood pressure monitoring (ABPM), were randomized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks. A 24-hour ABPM was then performed.

Results

Melatonin treatment reduced nocturnal systolic BP significantly from 136 ± 9 to 130 ± 10 mm Hg (P = .011), and diastolic BP from 72 ± 11 to 69 ± 9 mm Hg (P = .002), whereas placebo had no effect on nocturnal BP. The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo (P = .01), and was most prominent between 2:00 am and 5:00 am (P = .002).

Conclusions

Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension. Thus, an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension.     

Response of B-type natriuretic peptide to exercise in hypertensive patients with suspected diastolic heart failure: correlation with cardiac function, hemodynamics, and workload

Background

Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF.

Methods

Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (Sa) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios.

Results

Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 ± 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 ± 19/88 ± 8 to 191 ± 22/ 90 ± 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P < .05) and peak heart rate (r = −0.40, P < .05). BNP increased with exercise (from 48 ± 57 to 74 ± 97 pg/mL, P = .007), and the increment of BNP with exercise was associated with maximal workload and peak exercise Sa, Ea, and Aa (P < .01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 ± 2.0 to 10.0 ± 4.8, P < .01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 ± 124 vs 45 ± 71 pg/mL, P = .027).

Conclusions

Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.     

Low-dose carvedilol improves left ventricular function and reduces cardiovascular hospitalization in Japanese patients with chronic heart failure: the Multicenter Carvedilol Heart Failure Dose Assessment (MUCHA) trial

Background

The efficacy and optimum dose of β-blockers have not been established in Japanese patients with chronic heart failure (CHF). The efficacy and safety of two doses of carvedilol, a β-blocker with vasodilator and antioxidant actions, were investigated in Japanese patients with CHF.

Methods

After screening and a carvedilol challenge phase, 174 patients with mild to moderate CHF were randomly assigned (double-blinded) to placebo, 2.5 mg of carvedilol twice daily, or 10 mg of carvedilol twice daily. After a 2- to 4-week uptitration phase, maintenance treatment was continued for 24 to 48 weeks. The primary end point was improvement of the global assessment of CHF by the attending physician. Secondary end points were death or hospitalization for cardiovascular disease, cardiovascular hospitalization, hospitalization for heart failure, change of left ventricular ejection fraction, and change in New York Heart Association class.

Results

Carvedilol therapy achieved dose-dependent improvement of all end points (P for linear trend, range .002 to <.001). Both carvedilol groups showed marked risk reduction (71% to 91%) for cardiovascular and CHF hospitalization and for death or cardiovascular hospitalization (P range, .024 to <.001 for pairwise comparisons with placebo). No significant differences were observed for noncardiovascular hospitalization or adverse events.

Conclusions

In Japanese patients with mild or moderate CHF, carvedilol achieved dose-related improvement of CHF and left ventricular ejection fraction; cardiovascular hospitalization was markedly reduced. At 5 mg/d, carvedilol conferred an important patient benefit, less than at 20 mg/d.     

Effects of oral amino acid supplementation on myocardial function in patients with type 2 diabetes mellitus

Background

Diabetes mellitus is associated with an increased rate of cardiac amino acid catabolism that could interfere with cardiac function.

Methods

We assessed the effects of an oral amino acids mixture (AAM) on myocardial function in patients with type 2 diabetes mellitus (DM2). We studied 65 consecutive patients with DM2 who had normal resting left ventricular ejection fraction (LVEF) and did not have obstructive coronary artery disease (CAD). After baseline evaluations, patients were randomized to receive, in a single-blinded fashion, AAM (12 grams/day) or placebo for 12 weeks, after which, treatment was crossed over for another similar period. At baseline and at the end of each treatment, 2-dimensional ecocardiography at rest and during isometric exercise (handgrip) was performed, as were biochemical assays. Twenty adults, matched for age, sex, and body mass index served as control subjects.

Results

At baseline and during AAM or placebo treatment, resting left ventricular dimensions and LVEF in patients with DM2 did not differ from those of control subjects. In patients with DM2, at baseline and during placebo treatment, peak handgrip LVEF decreased significantly in comparison with the resting value (63% ± 9% vs 56% ± 9%, P <.001; and 62% ± 6% vs 55% ± 8%, P <.001). During AAM treatment, peak handgrip LVEF did not differ from resting value (66% ± 11% vs 64% ± 9%, P = not significant). Thus, exercise LVEF was higher during AAM treatment than both baseline and placebo treatment (66% ± 11% vs 56% ± 9% and vs 55% ± 8%, P <.001). In contrast to placebo treatment, after the AAM supply, a decreased glycated hemoglobin level was observed (7.0% ± 1.3% vs 7.6% ± 1.8%, P <.05).

Conclusions

Myocardial dysfunction is easily inducible with isometric exercise in patients with DM2 who have normal resting LV function and do not have CAD. An increased amino acid supply prevents this phenomenon and improves metabolic control.     

Effects of Exenatide Combined with Lifestyle Modification in Patients with Type 2 Diabetes

Objective

To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylurea.

Methods

In this 24-week, multicenter, randomized, double-blind, placebo-controlled study, 194 patients participated in a lifestyle modification program, consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week. Participants were randomized to 5 μg exenatide twice daily injection + lifestyle modification program (n = 96) or placebo + lifestyle modification program (n = 98), and after 4 weeks increased their exenatide dose to 10 μg twice daily or volume equivalent of placebo.

Results

Baseline characteristics: (mean ± standard deviation) age, 54.8 ± 9.5 years; weight, 95.5 ± 16.0 kg; hemoglobin A_1c, 7.6 ± 0.8%. At 24 weeks (least squares mean ± standard error), treatments showed similar decreases in caloric intake (−378 ± 58 vs −295 ± 58 kcal/day, exenatide + lifestyle modification program vs placebo + lifestyle modification program, P = .27) and increases in exercise-derived energy expenditure. Exenatide + lifestyle modification program showed greater change in weight (−6.16 ± 0.54 kg vs −3.97 ± 0.52 kg, P = .003), hemoglobin A_1c (−1.21 ± 0.09% vs −0.73 ± 0.09%, P <.0001), systolic (−9.44 ± 1.40 vs −1.97 ± 1.40 mm Hg, P <.001) and diastolic blood pressure (−2.22 ± 1.00 vs 0.47 ± 0.99 mm Hg, P = .04). Nausea was reported more for exenatide + lifestyle modification program than placebo + lifestyle modification program (44.8% vs 19.4%, respectively, P <.001), with no difference in withdrawal rates due to adverse events (4.2% vs 5.1%, respectively, P = 1.0) or rates of hypoglycemia.

Conclusions

When combined with lifestyle modification, exenatide treatment led to significant weight loss, improved glycemic control, and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and/or sulfonylurea treatment.     

Aortic root dysfunctioning and its effect on left ventricular function in Ross procedure patients assessed with magnetic resonance imaging

Background

This study evaluated the diameters and distensibility of the aortic root as well as the degree of aortic regurgitation (AR) and its effect on left ventricular (LV) function in patients 8.2 ± 3.1 years after they underwent the Ross procedure, with a comparison of these parameters between patients and matched healthy subjects.

Methods

Eighteen Ross procedure patients (16 male patients, age [mean ± SD] 19.2 ± 3.8 years) and 18 matched healthy subjects (16 male patients, age [mean ± SD] 19.7 ± 4.2 years) underwent magnetic resonance imaging. Measurements for diameters (at 4 levels) and the distensibility of the aortic root were performed using a steady-state free precession sequence. Aortic flow was assessed with a velocity-encoded phase-contrast sequence. Left ventricular systolic function was assessed with a gradient-echo sequence in the short-axis plane. Comparison of parameters was performed using the Mann-Whitney U test. Correlations between diameters, distensibility, AR fraction, and LV systolic function were expressed with Spearman rank correlation coefficients. Linear regression analysis was used to identify predictors of LV systolic dysfunction.

Results

Aortic root diameters were increased in Ross procedure patients as compared with healthy subjects (mean difference 6.3-11.6 mm, P ≤ .02 at all 4 levels). Distensibility of the aortic root was lower in patients (1.9 ± 1.1 vs 7.8 ± 3.3 mm Hg⁻¹, P < .01). An AR fraction >5% was present in 14 of the 18 patients (mean AR fraction 8% ± 5% vs 1% ± 1%, P < .01). Left ventricular ejection fraction was lower in patients (50% ± 6% vs 57% ± 6%, P < .01). Dilatation, decreased distensibility, and AR fraction were correlated with impaired LV systolic function (P < .05 for all). The AR fraction predicted impaired LV systolic function (P < .01).

Conclusions

Magnetic resonance imaging shows dilatation and decreased distensibility of the aortic root, AR, and consequent impaired LV systolic function in patients after the Ross procedure.     

Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy

Background

Mitral annular velocities derived from tissue Doppler imaging (TDI) provide information about left ventricular (LV) long-axis function and allow for the assessment of LV filling pressures in selected subsets of patients. It was the aim of this study to assess the usefulness of TDI in patients with moderate to severe aortic valve stenosis (AS).

Methods

Twenty-three patients with moderate to severe AS (mean aortic valve area 0.8 ± 0.4 cm²), in whom coronary artery disease had been ruled out, and 36 asymptomatic age-matched control subjects underwent assessment of ejection fraction, fractional shortening, and mitral inflow (E, A, E/A ratio). TDI velocities (S', E', A') were derived from the septal mitral annulus. In patients with AS, LV pressure before atrial contraction (LV pre-A pressure), LV end-diastolic pressure, and cardiac index were measured during cardiac catheterization.

Results

In patients with AS, systolic (S') and early diastolic mitral annular velocities (E') were significantly reduced in comparison to control subjects (systolic, 5.5 ± 1.2 vs 8.3 ± 1.3 cm/s; early diastolic, 5.6 ± 1.6 vs 10.2 ± 3.0 cm/s, P < .001 for both comparisons), but ejection fraction, fractional shortening, and cardiac index were normal. In patients with AS, LV pre-A pressures (14 ± 4 mm Hg) and end-diastolic pressures were high (19 ± 7 mm Hg). In such patients, the mitral E/E' ratio was significantly related to LV pre-A pressure (r = 0.75, P < .001) and to LV end-diastolic pressure (r = 0.78, P < .001). In patients with AS, an E/E' ratio ≥13 identified an LV end-diastolic pressure >15 mm Hg, with a sensitivity of 93% and a specificity of 88%.

Conclusions

In patients with moderate to severe AS, TDI allows for a reliable, noninvasive estimation of filling pressures. In such patients, systolic long-axis function is impaired even in the presence of normal ejection fraction and cardiac index. Thus, TDI integrates information about systolic and diastolic performance and may be a useful addition in the echocardiographic workup and care of patients with AS.     

Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction

Background

The effects of physical training on ventricular remodeling after extensive anterior acute myocardial infarction (AMI) have not yet been defined. This randomized controlled study examines whether exercise aggravates left ventricular (LV) remodeling in patients with extensive anterior AMI.

Methods

Forty-eight consecutive patients with a first extensive anterior AMI and an LV ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3 days of onset were randomly allocated to a training group (n = 24) or a control group (n = 24). Exercise intensity was determined by the heart rate of each patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was performed, followed by a supervised exercise program at VT for 12 weeks. The LVG was reassessed after the exercise program. We then calculated the global LV volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and systolic expansion volume index (SEVI), a new parameter for measuring the infarction site expansion at the end-systolic phase.

Results

Both EDVI and ESVI significantly decreased in the control group from 1 to 4 months after onset (91.2 ± 26.1 to 83.3 ± 24.0 mL/m², P <.05; 52.4 ± 22.5 to 45.7 ± 18.8mL/m², P <.01, respectively), but not in the exercise group. The SEVI also significantly decreased in the control group from 1 to 4 months (33.1 ± 16.9 to 25.7 ± 13.9 mL/m², P <.05), but not in the training group (34.2 ± 12.9 to 36.5 ± 15.5 mL/m², P = not significant).

Conclusion

Exercise while healing in patients with extensive anterior AMI, even at the VT level, induces LV enlargement and thus might aggravate LV remodeling. Therefore, in these patients, clinicians should consider withholding exercise training for at least 8 weeks, versus the 3-week period used in this trial.     

Echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction: role of mitral regurgitation

Introduction and objectives

Patients with heart failure and similar left ventricular systolic dysfunction have differing exercise capacity. The aim of this study was to identify echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction.

Methods

We included 150 patients with class II (70%) or III (30%) heart failure with left ventricular ejection fraction below 40%. Six-minute walking test and cardiac color Doppler-echo, including tissue Doppler of mitral and tricuspid rings, were performed. Moderate and severe mitral regurgitation were considered as significant. Two groups were divided according to the median walking distance (290 m): Group 1, <290 m and Group 2, ≥290 m.

Results

Mitral regurgitation was detected in 112 patients (75%), which was significant in 40 (27%). Group 1 showed more significant mitral regurgitation (35 vs 18%), increased left atrium area (27±1 vs 24±1 cm²), mitral E amplitude (88±5 vs 72±3 cm/s) and systolic pulmonary pressure (37±1 vs 32±1 mmHg, all P<.05). By logistic regression analysis, only the presence of significant mitral regurgitation was independently associated with less walked distance (odds ratio: 3.44 95% confidence interval 1.02-11.66, P<.05). By multiple linear regression, the only independent predictor of walked distance was left atrium area (r=0.25, beta coefficient: −6.52 ± 2, P<.01).

Conclusions

In patients with class II-III heart failure and left ventricular systolic dysfunction, the main echocardiographic predictors of exercise capacity are related to the presence of significant mitral regurgitation.Full English text available from:www.revespcardiol.org     

Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy

Background

Trimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy.

Methods

Sixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated.

Results

Both in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 ± 7 vs 41 ± 9 and 45 ± 8 vs 36 ± 8%, P < .001 for both) and M value (4.0 ± 1.8 vs 3.3 ± 1.6, P = .003, and 3.5 ± 1.5 vs 2.7 ± 1.6 mg/kg body weight/min, P < .01) increased, while fasting blood glucose (121 ± 30 vs 136 ± 40, P = .02 and 125 ± 36 vs 140 ± 43, P = .19) and endothelin-1 (8.8 ± 3.8 vs 10.9 ± 3.8, P < .001 and 6.2 ± 2.4 vs 9.2 ± 4.3 pg/mL, P = .03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ (P = .019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved (P = .018 vs placebo).

Conclusions

In a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.     

Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors

Background

Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs.

Methods

This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning.

Results

At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 ± 180 nmol/L), which tended to be small (19.9 ± 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 ± 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 ± 0.58 mmol/L). FMD was impaired (4.5% ± 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P = .030), a 26.7% reduction in small LDL (P = .100), and a 44.9% reduction in small VLDL (P = .023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% ± 0.6%); however, the difference between treatment phases was not statistically significant (P = .080).

Conclusions

This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.     

Pulsed-wave tissue Doppler quantification of systolic and diastolic function of viable and nonviable myocardium in patients with ischemic cardiomyopathy

Background

Detection of myocardial viability is crucial for clinical treatment of patients with ischemic cardiomyopathy. Currently, quantitative information for the evaluation of systolic and diastolic function of viable tissue is limited. Our aim was to compare quantitatively systolic and diastolic function in viable and nonviable dysfunctional myocardium in patients with ischemic cardiomyopathy.

Methods

A total of 93 patients (mean age, 62 ± 10 years) underwent dobutamine stress echocardiography to assess myocardial viability. Pulsed-wave tissue Doppler imaging (TDI) was used to assess systolic ejection velocity (V_S) and early (V_E) and late (V_A) diastolic velocities at rest and at low-dose dobutamine infusion (10 μg/kg per minute) in viable and nonviable dysfunctional regions. Analysis was repeated after dividing study population in patients ≥65 years old (n = 40) and <65 years old (n = 53).

Results

Pulsed-wave TDI demonstrated that V_S was comparable in dysfunctional viable and nonviable regions at rest (V_S, 6.3 ± 1.9 cm/s vs 6.3 ± 2.0 cm/s, respectively, P = .93). However, at low-dose dobutamine challenge, V_S was significantly higher in viable regions (8.5 ± 2.7 cm/s vs 7.8 ± 2.4 cm/s, P = .002). Viable regions had higher V_E at rest compared with nonviable regions (8.4 ± 2.5 cm/s vs 7.5 ± 2.8 cm/s, P = .003). Myocardial velocities were significantly higher in patients ≥65 years old, both in viable and nonviable regions.

Conclusions

Quantification of myocardial motion by pulsed-wave TDI demonstrates that at low-dose dobutamine stress, systolic velocity is markedly improved in viable myocardium, indicating the presence of contractile reserve in viable regions. A superior early diastolic filling at rest can also differentiate viable from nonviable myocardium.     

Dilatation of the aorta in pure, severe, bicuspid aortic valve stenosis

Background

Aortic complications are more frequent after bicuspid aortic valve (BAV) replacement (AVR), than tricuspid aortic valve replacement. We studied the size of the proximal thoracic aorta in patients with BAV undergoing AVR for pure, severe aortic stenosis, looking for dilatation in comparison with patients with a matched tricuspid aortic valve (TAV) and normograms of aortic size.

Methods

Aortic root and ascending aortic diameter measurements were taken at 3 levels, from electrocardiographic-gated multidetector row computed tomograms, in 28 patients with pure, severe aortic stenosis before AVR. The patients were divided in 2 groups (BAV, n = 10; TAV, n = 18). Patients with greater than mild aortic regurgitation or who were scheduled for aortic root replacement were excluded.

Results

Although patients in the BAV group were younger (P <.0001) and less likely to have hypertension (P <.005), their aortic diameters were larger than those of patients in the TAV group at all levels measured (aortic sinus, 41.1 ± 8.1 mm vs 33.8 ± 3.3 mm; sino-tubular junction, 39.0 ± 7.8 mm vs 31.1 ± 3.8 mm; right pulmonary artery level, 42.8 ± 7.1 mm vs 33.7 ± 4.3 mm; P <.005 for all). Whereas 60% (6/10) of patients in the BAV group had ≥1 aortic diameter measurements greater than the 95th age-adjusted percentile, 0% (0/18) of patients in the TAV group did.

Conclusions

Patients with BAV undergoing AVR with pure, severe aortic stenosis commonly have moderate dilatation of the thoracic aorta, whereas matched patients with a TAV do not. This finding may contribute to the increased frequency of aortic complications seen in follow up of patients with a BAV after AVR.     

Tissue Doppler atrial conduction times and electrocardiogram interlead P-wave durations with varying severity of obstructive sleep apnea

Objectives

Obstructive sleep apnea (OSA) has been reported to be associated with an increased risk of atrial fibrillation. The aim of this study was to investigate atrial electromechanical couplings in patients with OSA and the relationship between these parameters and P-wave dispersion (Pd).

Methods

One hundred twenty-six patients were enrolled in this study. All patients underwent polysomnographic examination. The apnea-hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep. An AHI score of 5 or more was diagnosed as OSA, and an AHI score of less than 5 was diagnosed as OSA (−). Thirty-nine of the patients had an AHI score of less than 5 (group 1), 42 of the patients had AHI score between 5 and 30 (mild and moderate, group 2), 45 of the patients had an AHI score more than 30 (severe, group 3). Atrial electromechanical coupling (PA), intra-atrial, and interatrial electromechanical delay were measured with tissue Doppler imaging. P-wave dispersion was calculated from 12-lead electrocardiogram.

Results

Maximum P-wave duration was higher in group 3 compared with groups 2 and 1 (126.0 ± 16.7 vs 111.0 ± 12.5 [P < .001] and 126.0 ± 16.7 vs 99.9 ± 10.0 [P < .001], respectively). Maximum P-wave duration was higher in group 2 than in group 1 (111.0 ± 12.5 vs 99.9 ± 10.0, P < .001). P-wave dispersion was higher in group 3 compared with groups 2 and 1 (50.9 ± 11.5 vs 37.0 ± 8.6 [P < .001] and 50.9 ± 11.5 vs 27.9 ± 6.8 [P < .001], respectively). P-wave dispersion was higher in group 2 than in group 1 (37.0 ± 8.6 vs 27.9 ± 6.8, P < .001). Minimum P-wave duration did not differ between the groups. Atrial PA at the left lateral mitral annulus (lateral PA), septal mitral annulus (septal PA), and right ventricular tricuspid annulus (RV PA) were significantly higher in group 3 than in group 2 (P < .001, P = .001, and P = .009, respectively). Lateral PA, septal PA, and RV PA were higher in group 2 compared with group 1 (P < .001, P = .003, and P = .009, respectively). Interatrial electromechanical delay (lateral PA − RV PA) was significantly longer in group 3 compared with groups 2 and 1 (33.6 ± 12.1 vs 22.4 ± 9.4 [P < .001] and 33.6 ± 12.1 vs 14.9 ± 9.2 [P < .001], respectively). Interatrial electromechanical delay was longer in group 2 than in group 1 (22.4 ± 9.4 vs 14.9 ± 9.2, P = .001). There was a positive correlation between AHI and Pd, lateral PA, septal PA, RV PA, interatrial electromechanical delay, and left-sided intra-atrial electromechanical delay.

Conclusion

Prolongation of electromechanical delay and increased Pd are associated with apnea-hypopnea index (AHI) and hence the severity of disease.     

Changes in systemic sympathetic nervous system activity after mitral valve surgery and their relationship to changes in left ventricular size and systolic performance in patients with mitral regurgitation

Background

We have shown that the systemic sympathetic nervous system (SNS) is activated in patients with chronic mitral regurgitation (MR). However, the fate of systemic SNS activity after surgical correction of MR is currently unknown.

Methods

We examined 14 patients with MR who had normal sinus rhythm with an investigational, preoperative cardiac catheterization, including arterial norepinephrine (NE) sampling and [³H]-NE infusions and arterial blood sampling to determine NE kinetic parameters using a 2-compartment modeling analysis. The arterial NE and NE kinetic parameters were determined in all patients after mitral valve surgery (MVS) at a mean of 12 months. A 2-dimensional echocardiographic examination was also performed before and after MVS.

Results

The average extravascular NE release rates (NE₂) before and after MVS were 1.89 ± 0.66 and 2.26 ± 0.82 μg/min/m² (P = .24), respectively. The average left ventricular (LV) end-diastolic dimension, fractional shortening, and ejection fraction decreased, whereas the mean LV end-systolic dimension did not change between the pre- and post-MVS echocardiographic studies. However, these group averages were comprised of patients with MR in whom the NE₂ and echocardiographic values both increased and decreased. This lack of homogeneity was a reflection of our new observation that the pre- to post-MVS changes in NE₂ were directly proportional to the changes in LV end-systolic dimension (r = 0.91, P <.001) and inversely related to the changes in LV fractional shortening (r = −0.82, P <.001) and ejection fraction (r = −0.78, P <.001).

Conclusions

The response in systemic SNS activity in patients with MR after MVS is not homogeneous, and these changes are concordant with the post-MVS changes in LV size and systolic performance. These data further support our earlier observations and extend them to suggest that systemic SNS activation in patients with chronic MR is related to LV remodeling and impaired systolic performance.     

Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention

Background

Diabetes mellitus (DM) is predictive of increased mortality for patients with coronary artery disease (CAD). To what extent this risk extends below the diabetic threshold (fasting glucose level [FG] <126 mg/dL) is uncertain.

Methods

The study objective was to determine the risk associated with FG in a prospectively assembled cohort of 1612 patients with CAD who were undergoing percutaneous coronary intervention (PCI) and had a FG measured or a clinical diagnosis of DM (CDM). Patients were grouped as: CDM; no CDM, but FG ≥126 mg/dL (ADA-DM); impaired FG, 110-125 mg/dL (IFG); or normal FG, <110 mg/dL (NFG). Survival was assessed for 2.8 ± 1.2 years.

Results

The average patient age was 62 ± 12 years; 74% of the patients were men. Diagnostic frequencies were: CDM, 24%; ADA-DM , 18%; IFG, 19%; and NFG, 39%. Mortality rates were greater for patients in the CDM (44/394 [11.2%], P <.0001), ADA-DM (27/283 [9.5%], P <.001), and IFG (20/305 [6.6%], P = .04) groups than patients in the NFG group(12/630 [1.9%]). Independent receiver operating characteristic analysis chose FG ≥109 mg/dL as the best cutoff for increased risk (sensitivity, 81%; specificity, 51%). After adjustment with Cox regression analysis, CDM (hazard ratio [HR] = 5.0; 95% CI, 2.6-9.6; P <.001), ADA-DM (HR, 4.1; 95% CI, 2.1-8.2; P <.001), and IFG status (HR, 3.2; 95% CI, 1.5-6.5; P = .002) remained independent predictors of mortality.

Conclusions

Prognostically significant abnormalities of FG are much more prevalent (61%) than expected in patients with CAD who are undergoing PCI. Despite revascularization, the associated mortality risk of even mild elevations in FG is substantial, emphasizing the importance of early detection and treatment of glycemia-related risk.     

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

Background

Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR.

Methods

Exercise echocardiography was performed in 86 patients (20 women, age 53 ± 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by ≥5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis.

Results

CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% ± 11% versus 54% ± 15% (P < .0001). CR could not be predicted by resting EF, volumes or sphericity, and DTI measurement of base-apex function was the only resting echocardiographic parameter to distinguish between patients with and without CR (10 ± 2 vs 8 ± 2 cm/s, P < .03). This parameter showed greater differences after stress (14 ± 4 vs 11 ± 3 cm/s, P < .001). Patients with CR showed lower peak DTI than controls, as well as lower exercise capacity and EF response to exercise. In a multiple linear regression model, rest DTI (P = .03) was an independent correlate of contractile reserve. The other correlates were age (P < .0001), resting (P < .0001) and peak end-systolic volume (P = .01), and resting (P < .0001) and peak end-diastolic volume (P < .0001); the model r² was 0.93 (P < .001).

Conclusion

In the absence of regional LV dysfunction, measurement of longitudinal axis function by DTI may be a marker of CR.