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.     

Intensive Lifestyle Intervention Improves Cardiometabolic and Exercise Parameters in Metabolically Healthy Obese and Metabolically Unhealthy Obese Individuals

Background

The effects of an intensive lifestyle intervention including Mediterranean diet nutritional counselling and high-intensity interval training (HIIT) on body composition, cardiometabolic, and exercise parameters were studied in metabolically unhealthy obese (NMHO) and metabolically healthy but obese (MHO) subjects.

Methods

Fifty-five MHO (51 ± 8 years; waist circumference, 109 ± 13 cm) and 79 NMHO subjects (54 ± 9 years; waist circumference, 112 ± 13 cm) participated in an intensive lifestyle modification program based on Mediterranean diet nutritional counselling and HIIT 2-3 times per week. Body composition, cardiometabolic, and exercise parameters were measured at baseline and after 9 months.

Results

Initially, MHO patients had a lower blood pressure (BP), fasting glycemia, triglycerides, and a higher high-density lipoprotein cholesterol and peak oxygen uptake (VO₂ peak) (P < 0.05) vs NMHO patients. Body mass (P < 0.05), waist circumference (P < 0.0001), total and trunk fat mass (P < 0.001), systolic and diastolic BP (P < 0.001), fasting glucose (P < 0.0001), insulin sensitivity (P < 0.05), VO₂ peak and muscle endurance (P < 0.0001) were similarly improved in both groups after the program. Prevalence of NMHO was reduced by 17.91% (P < 0.01) after the program. Similar improvements in body composition, BP, and exercise parameters were found for MHO and NMHO men and women (P < 0.05). In all patients, improvement of VO₂ peak was negatively correlated with improvements in body composition, systolic blood pressure, and resting heart rate (HR) (R = −0.61 to −0.24; P < 0.05).

Conclusions

A long-term intensive lifestyle program including Mediterranean diet nutritional counselling and HIIT is an appropriate intervention in MHO and NMHO subjects with similar potential clinical health benefits including an improved body composition, BP, fasting glycemia, insulin sensitivity, VO₂ peak, and muscle endurance.     

Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison

Background

Exercise testing with ventilatory expired gas analysis has proven to be a valuable tool for assessing patients with heart failure (HF). Peak oxygen consumption (peak VO₂) continues to be considered the gold standard for assessing prognosis in HF. The minute ventilation − carbon dioxide production relationship (VE/VCO₂ slope) has recently demonstrated prognostic significance in patients with HF, and in some studies, it has outperformed peak VO₂.

Methods

Two hundred thirteen subjects, in whom HF was diagnosed, underwent exercise testing between April 1, 1993, and October 19, 2001. The ability of peak VO₂ and VE/VCO₂ slope to predict cardiac-related mortality and hospitalization was examined.

Results

Peak VO₂ and VE/VCO₂ slope were demonstrated with univariate Cox regression analysis both to be significant predictors of cardiac-related mortality and hospitalization (P <.01). Multivariate analysis revealed that peak VO₂ added additional value to the VE/VCO₂ slope in predicting cardiac-related hospitalization, but not cardiac mortality. The VE/VCO₂ slope was demonstrated with receiver operating characteristic curve analysis to be significantly better than peak VO₂ in predicting cardiac-related mortality (P <.05). Although area under the receiver operating characteristic curve for the VE/VCO₂ slope was greater than peak VO₂ in predicting cardiac-related hospitalization (0.77 vs 0.73), the difference was not statistically significant (P = .14).

Conclusions

These results add to the present body of knowledge supporting the use of cardiopulmonary exercise testing in HF. Consideration should be given to revising clinical guidelines to reflect the prognostic importance of the VE/VCO₂ slope in addition to peak VO₂.     

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.     

Evaluation of the dofetilide risk-management program

Background

Dose-dependent torsades de pointes has been shown to occur with dofetilide (Tikosyn) and sotalol HCl (Betapace AF); thus, detailed dosing and monitoring recommendations to minimize this risk are included in the product labeling for both drugs. Only dofetilide, however, has a mandated risk-management program that restricts distribution of the drug and requires prescriber education on the drug. We investigated whether this program improved adherence to dosing and monitoring recommendations for dofetilide as compared with sotalol.

Methods

Charts for 47 patients taking dofetilide and 117 patients taking sotalol were reviewed.

Results

The recommended starting dose was prescribed more frequently in the dofetilide group than in the sotalol group (79% vs 35%, P <.001). A higher number of patients in the dofetilide group compared with the sotalol group received the recommended baseline tests for potassium (100% vs 82%, P <.001), magnesium (89% vs 38%, P <.001), serum creatinine (100% vs 82%, P <.001), and electrocardiography (94% vs 67%, P <.001). A significantly greater proportion of patients in the dofetilide group received recommended electrocardiograms obtained after the first dose (94% for dofetilide vs 43% for sotalol, P <.001) and subsequent doses (80% for dofetilide vs 3.5% for sotalol, P <.001).

Conclusion

Better adherence to several dosing and monitoring recommendations in the dofetilide group may be caused by the presence of the risk-management program. However, low usage of dofetilide during the study period may signify an unintended, negative consequence of the risk-management program.     

Oxygen uptake efficiency slope, a new submaximal parameter in evaluating exercise capacity in chronic heart failure patients

Background

The oxygen uptake efficiency slope (OUES) is a new submaximal parameter which objectively predicts the maximal exercise capacity in children and healthy subjects. However, the usefulness of OUES in adult patients with and without advanced heart failure remains undetermined. The present study investigates the stability and the usefulness of OUES in adult cardiac patients with and without heart failure.

Methods

Forty-five patients with advanced heart failure (group A) and 35 patients with ischemic heart disease but normal left ventricular ejection fraction (group B) performed a maximal exercise test. PeakVO₂ and percentage of predicted peakVO₂ were markers of maximal exercise capacity, whereas OUES, ventilatory anaerobic threshold (VAT), and slope VE/VCO₂ were calculated as parameters of submaximal exercise.

Results

Group A patients had lower peakVO₂ (P < .001), lower percentage of predicted peakVO₂ (P = .001), lower VAT (P < .05), steeper slope VE/VCO₂ (P < .001), and lower OUES (P < .02). Within group A, significant differences were found for VAT, slope VE/VCO₂, and OUES (all P < .01) between patients with peakVO₂ above and below 14 mL O₂/kg/min. Of all the submaximal parameters, VAT correlated best with peakVO₂ (r =.814, P < .01) followed by OUES/kg (r = .781, P < .01), and slope VE/VCO₂ (r = −.492, P < .001). However, VAT could not be determined in 18 (23%) patients.

Conclusions

OUES remains stable over the entire exercise duration and is significantly correlated with peakVO₂ in adult cardiac patients with and without impaired LVEF. Therefore, OUES could be helpful to assess exercise performance in advanced heart failure patients unable to perform a maximal exercise test. Further studies are needed to confirm our hypothesis.     

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.     

The Obesity Paradox, Weight Loss, and Coronary Disease

Purpose

Because obesity is a cardiovascular risk factor but is associated with a more favorable prognosis among cohorts of cardiac patients, we assessed this “obesity paradox” in overweight and obese patients with coronary heart disease enrolled in a cardiac rehabilitation and exercise training (CRET) program, making this assessment in patients classified as overweight/obese using both traditional body mass index (BMI) and percent body fat assessments. Additionally, we assessed the efficacy and safety of purposeful weight loss in overweight and obese coronary patients.

Patients and Methods

We retrospectively studied 529 consecutive CRET patients following major coronary events before and after CRET, and compared baseline and post program data in 393 overweight and obese patients (body mass index [BMI] ≥25 kg/m²) divided by median weight change (median = −1.5%; mean +2% vs −5%, respectively). In addition, we assessed 3-year total mortality in various baseline BMI categories as well as compared mortality in those with high baseline percent fat (>25% in men and >35% in women) versus those with low baseline fat.

Results

Following CRET, the overweight and obese with greater weight loss had improvements in BMI (−5%; P <.0001), percent fat (−8%; P <.0001), peak oxygen consumption (+16%; P <.0001), low-density lipoprotein cholesterol (−5%; P <.02), high-density lipoprotein cholesterol (+10%; P <.0001), triglycerides (−17%; P <.0001), C-reactive protein (−40%; P <.0001), and fasting glucose (−4%; P = .02), as well as marked improvements in behavioral factors and quality-of-life scores. Those with lower weight loss had no significant improvements in percent fat, low-density lipoprotein cholesterol, triglycerides, C-reactive protein, and fasting glucose. During 3-year follow-up, overall mortality trended only slightly lower in those with baseline overweightness/obesity who had more weight loss (3.1% vs 5.1%; P = .30). However, total mortality was considerably lower in the baseline overweight/obese (BMI ≥25 kg/m²) than in 136 CRET patients with baseline BMI <25 kg/m² (4.1% vs 13.2%; P <.001), as well as in those with high baseline fat compared with those with low fat (3.8% vs 10.6%; P <.01).

Conclusions

Purposeful weight loss with CRET in overweight/obese coronary patients is associated with only a nonsignificant trend for lower mortality but is characterized by marked improvements in obesity indices, exercise capacity, plasma lipids, and inflammation, as well as behavioral factors and quality of life. Although an “obesity paradox” exists using either baseline BMI or baseline percent fat criteria, these results support the safety and potential long-term benefits of purposeful weight loss in overweight and obese patients with coronary heart disease.     

Measures of exercise capacity in adults with congenital heart disease

Background

Exercise capacity in grown-ups with congenital heart disease (GUCH) is mostly reported by peak oxygen consumption (peak VO₂). Our aim was to evaluate the maximal character of exercise tests, and to investigate submaximal measures of exercise capacity.

Methods

Adults with Coarctation of the Aorta (COA, n = 155), Tetralogy of Fallot (TOF, n = 98), dextro-Transposition of the Great Arteries (dTGA, n = 68) and Univentricular Heart (UVH, n = 10), and 122 healthy adults performed cardiopulmonary exercise testing until exhaustion. Gas exchange was measured breath by breath. The maximal performance of the test was evaluated by respiratory exchange ratio (RER), ventilatory equivalent for oxygen and Borg scale. Oxygen uptake efficiency slope (OUES), VE/VCO₂ slope and VO₂/WR slope were calculated and ventilatory anaerobic threshold (VAT) was defined. Correlations of these measures with peak VO₂ were calculated.

Results

GUCH showed significantly lower peak VO₂ than controls (p < 0.001), declining from 80% in COA, 74% in TOF, 64% in dTGA, to 55% in UVH. Compared to suggested criteria, mean peak RER and median Borg scale indicated a maximal effort in GUCH, however these results were significantly lower than controls (p < 0.05). OUES, VO₂/WR slope and VAT were significantly lower in patients compared to controls. OUES (r = 0.853) and VAT (r = 0.840) correlated best with peak VO₂; VO₂/WR slope (r = 0.551) and VE/VCO₂ slope (r = −0.421) correlated to a lesser degree (p < 0.001).

Conclusion

The investigated GUCH show reduced exercise tolerance compared to controls, related to the underlying heart defect. Different expressions of exercise tolerance clearly reveal the same differences in exercise capacity across groups of GUCH.     

Obesity paradox in patients with hypertension and coronary artery disease

Purpose

An obesity paradox, a “paradoxical” decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known.

Methods

A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66 ± 9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m² (thin), 20 to 25 kg/m² (normal weight), 25 to 30 kg/m² (overweight), 30 to 35 kg/m² (class I obesity), and 35 kg/m² or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke.

Results

With patients of normal weight (BMI 20 to <25 kg/m²) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P <.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P <.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (−17.5 ± 21.9 mm Hg/−9.8 ± 12.4 mm Hg vs −20.7 ± 23.1 mm Hg /−10.6 ± 12.5 mm Hg, P <.001).

Conclusion

In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention.     

Determinants of ST-segment level in lead aVR in anterior wall acute myocardial infarction with ST-segment elevation

Background

This study aimed to clarify the determinants of ST-segment level in lead aVR in anterior wall acute myocardial infarction (AAMI).

Methods

We analyzed ST-segment levels in all 12 leads on admission and emergency coronary angiographic findings in 261 patients with a first AAMI with ST-segment elevation. The length of the left anterior descending coronary artery (LAD) was classified as follows: short = not reaching the apex; medium = perfusing less than 25% of the inferior wall; long = perfusing 25% or more of the inferior wall.

Results

The ST-segment level in lead aVR correlated significantly with the ST-segment levels in leads I, II, III, aVF, V₁, and V_3-6, especially with those in leads II and V₆ (r = −0.63, P < .001; r = −0.61, P < .001; respectively). Patients with a proximal LAD occlusion had a greater ST-segment level in lead aVR than those with a distal LAD occlusion (P < .001). Patients with a long LAD had a lower ST-segment level than those with a short or medium LAD (P < .05).

Conclusions

The ST-segment levels, especially in leads II and V₆, the site of the LAD occlusion, and the length of the LAD affect the ST-segment level in lead aVR in ST-segment elevation AAMI.     

Exercise training program characteristics and magnitude of change in functional capacity of heart failure patients

Background

Intuitively higher exercise program volume may be the primary stimulus for physical adaptation. We sought to establish if aerobic exercise training program characteristics produced different effect sizes for change in cardiorespiratory fitness in heart failure patients.

Methods

We conducted a MEDLINE search (1966 to 2012), for exercise based rehabilitation trials in heart failure, using the search terms ‘exercise training, left ventricular dysfunction, peak VO₂, cardio-myopathy and systolic heart dysfunction’. Forty seven studies were included, producing 54 intervention groups; 3 (6%) were high-, 29 (54%) vigorous-, 20 (37%) moderate- and 2 (3%) low- intensity groups, providing a total of 2285 exercising subjects and 2098 control subjects, totaling 4383 participants.

Results

Peak VO₂ increased by a mean difference of 3.3 ml kg^− 1 min^− 1 [95% CI 0.53 to 6.13, p = 0.02] with high intensity training in exercise groups versus control, equating to a 23% improvement from baseline. The corresponding data for vigorous, moderate and low intensity were 8%, 13%; and 7% respectively. Weekly exercise energy expenditure > 460 kcal was associated with a mean difference in peak VO₂ of 2.6 ml kg^− 1 min^− 1 [95% CI 1.88 to 3.28, p < 0.00001].

Conclusions

Our data suggest that high-intensity exercise, achieving at least 460 kcal weekly energy expenditure may elicit the greatest changes in cardiorespiratory fitness.     

Multivariable analysis of heart rate recovery after cycle ergometry in heart failure: exercise in heart failure

Purpose

The purpose of this study was to investigate the association between impairment in heart rate recovery (HR_rec) after cycle ergometry and prognostic markers in patients with heart failure (HF) compared with healthy controls.

Methods

Fifty patients with chronic HF (systolic HF, N = 30; diastolic HF, N = 20; mean age = 62 ± 12 years) and 50 healthy controls (N = 50; mean age = 66 ± 13 years) underwent 2-dimensional and M-mode echocardiography followed by cardiopulmonary exercise testing. Independent predictors of HR_rec at 1 and 2 minutes after exercise were analyzed by univariable and multivariable regression analyses, and receiver operating characteristics were performed to obtain area under the curve.

Results

In HF, left ventricular end-diastolic diameter (millimeters), left ventricular ejection fraction (%), N-terminal pro-brain natriuretic peptide (picograms/milliliter), peak oxygen uptake (VO₂peak [milliliters/kilogram/min]), and peak heart rate (HR_peak) showed a significant association with HR_rec (beats/min) in univariate regression analyses (P < .001), but only VO₂peak remained independently predictive of both HR_rec1 (P = .034) and HR_rec2 (P = .008) in the multivariable regression analyses. In controls, VO₂peak (P = .035) and HR_peak (P = .032) were significantly associated with HR_rec2 in univariate analyses only. Optimal cutoff values for discriminating HF versus non-HF based on HR_rec were 17.5 beats/min (sensitivity 92%; specificity 74%) for HR_rec1 and 31.5 beats/min (sensitivity 94%; specificity 86%) for HR_rec2. Optimal cutoff values for discriminating systolic HF versus diastolic HF were 12.5 beats/min (sensitivity 78%; specificity 80%) for HR_rec1 and 24.5 beats/min (sensitivity 82%; specificity 90%) for HR_rec2.

Conclusion

Impairment in after exercise HR_rec is significantly and independently associated with VO2peak in HF and thus might constitute a useful tool for assessing the degree of functional status during exercise rehabilitation.     

Relation between P-wave dispersion and left ventricular geometric patterns in newly diagnosed essential hypertension

Aim

P-wave durations and P-wave dispersion (PD) are considered to reflect the heterogeneous conduction in atria. The aim of this study was to investigate PD and P-wave duration in different left ventricle geometric patterns of hypertensive patients.

Methods

One hundred forty-nine consecutive patients with newly diagnosed essential hypertension and 29 healthy control groups were included in the study. The maximum and minimum P-wave duration (P_max and P_min, respectively) and PD were measured from the 12-lead surface electrocardiogram. Echocardiographic examination was also performed in all subjects. Four different geometric patterns were identified in hypertensive patients according to left ventricular mass index (LVMI) and relative wall thickness.

Results

P-wave dispersion was longer in concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH) groups when compared with the control group (P = .009, P < .001, P < .001, respectively). P-wave dispersion of normal left ventricle (NLV) geometric pattern was not different from that of the control group. Patients with NLV geometric pattern had shorter PD than patients who had CH and EH (NLV vs CH, P < .001; NLV vs EH, P = .025). P-wave dispersion of the NLV group was not different from that of the CR group. Patients with CR had also shorter PD than patients who had CH (P = .002). In bivariate analysis, there was a significant correlation between PD with left ventricle geometry, body surface area, LVMI, and relative wall thickness. In multiple linear regression analysis, PD was independently correlated only with LVMI (β = .425, P < .001).

Conclusions

P-wave dispersion is independently associated with LVMI rather than left ventricle geometry and relative wall thickness in hypertensive patients. Thus, it is increased particularly in patients with CH and EH.     

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.     

The effect of comprehensive lifestyle intervention or metformin on obesity in young women

Background and aim

Young women are at high risk of weight gain but few weight management interventions have been investigated in this group. This study aimed to determine the effect of metformin on body weight, body composition, metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention.

Methods and results

203 overweight or obese young women (BMI 33.2+/−0.3 kg/m2, age 28+/−0.3 years) were randomised to 1500 mg/day metformin (M) plus general lifestyle advice, placebo (P) plus general lifestyle advice or comprehensive lifestyle intervention including structured diet, exercise and behavioural therapy (L) for 12-weeks. At 12-weeks, linear mixed models found that L group had greater weight loss (−4.2+/−0.4 kg) compared to M (−1.0+/−0.4 kg) and P groups (−0.2+/−0.3 kg) (P < 0.0001). Weight loss between M and P groups were not significantly different. Attrition rate was 48% for L, 34% for M and 29% for P (P = 0.08). Intention-to-treat analysis showed that 10% (8/79) of the subjects in P group had gained weight (>3%), compared to 3% (2/65) from M group and none (0/59) from L group (P < 0.001). The L group had the greatest decrease in waist circumference (−5.2+/−0.7 cm) and fat mass (−5.4+/−0.7 kg) compared to the other groups (P < 0.05). No significant time-by-group effects were seen in plasma lipids, SHBG, testosterone, blood pressure, serum folate, serum ferritin and serum vitamin B12. Conclusion: Lifestyle intervention was more effective in reducing body weight and improving body composition compared to metformin among healthy overweight or obese young women.     

Mortality trends for 23,505 Medicare patients hospitalized with heart failure in Northeast Ohio, 1991 to 1997

Background

Clinical trials have identified major therapeutic advances for heart failure (HF), but the degree to which survival has improved among the general population of patients with HF is not known. This study analyzed mortality trends from 1991 to 1997 for 23,505 Medicare patients hospitalized with a first admission for HF at 29 Northeast Ohio hospitals.

Methods

We linked databases from the Cleveland Health Quality Choice (CHQC) program and Medicare to allow identification of first admissions for HF and death date. We adjusted for changes in admission illness severity using chart data from CHQC (eg, vital signs, do-not-resuscitate status, comorbid conditions, and laboratory results). Logistic regression was used to analyze trends in risk-adjusted mortality.

Results

At baseline (1991), crude inhospital, 30-day and 1-year mortality rates were 6.4%, 8.6% and 36.5%, respectively. Between 1991 and 1997, mean length of stay declined steeply from 9.2 days to 6.6 days (P < .001 for trend). Risk-adjusted inhospital mortality also declined markedly (absolute-decline −3.7%, 95% CI −4.3 to −3.0), a 52.8% relative decrease. However, the decline in 30-day mortality was only −1.4% (95% CI −2.5 to −0.1, P < .05), a 15.3% relative decrease. The 1-year mortality declined −5.3% (95% CI −3.2 to −7.4, P < .001), a 14.6% relative decrease.

Conclusions

Long-term mortality for patients hospitalized with HF improved from 1991 to 1997, although mortality remains very high. The 30-day mortality declined far less than inhospital mortality, indicating that mortality shortly after discharge increased. This raises concerns that the marked reduction in length of stay is causing adverse consequences.     

Depression and Clinical Outcomes in Heart Failure: An OPTIMIZE-HF Analysis

Background

Depression is a risk factor of excessive morbidity and mortality in heart failure. We examined in-hospital treatment and postdischarge outcomes in hospitalized heart failure patients with a documented history of depression from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure.

Methods

We identified patient factors associated with depression history and evaluated the association of depression with hospital treatments and mortality, and early postdischarge mortality, emergency care, and rehospitalization.

Results

In 48,612 patients from 259 hospitals, depression history was present in 10.6% and occurred more often in females, whites, and those with common heart failure comorbidities, including chronic pulmonary obstructive disease (36% vs 27%), anemia (27% vs 16.5%), insulin-dependent diabetes mellitus (20% vs 16%), and hyperlipidemia (38% vs 31%), all P <.001. Patients with depression history were less likely to receive coronary interventions and cardiac devices, all P <.01; or be referred to outpatient disease management programs, P <.001. Length of hospital stay was longer with depression history (7.0 vs 6.4 days, P <.001). In 5791 patients followed-up at 60-90 days postdischarge, those with depression history had higher mortality (8.8% vs 6.4%; P = .025). After multivariable modeling, depression history remained a predictor of length of hospital stay, P <.001 and postdischarge mortality, P = .02.

Conclusions

Depression history at heart failure hospitalization may be a predictor of prolonged length of hospital stay, less use of cardiac procedures and postdischarge disease management, and increased 60-90 day mortality. Patients with depression might represent a vulnerable group in which improved use of evidence-based treatment should be considered.     

Diagnostic and Prognostic Value of Uric Acid in Patients with Acute Dyspnea

Background

Uric acid was shown to predict outcome in patients with stable chronic heart failure. Its impact in patients admitted in the Emergency Department with acute dyspnea, however, remains unknown.

Methods

We prospectively investigated the diagnostic and prognostic value of uric acid in 743 unselected patients presenting to the Emergency Department with acute dyspnea.

Results

Uric acid at admission was higher in patients with acute decompensated heart failure (51% of the cohort) as compared with patients with noncardiac causes of dyspnea (median, 447 μmol/L vs 340 μmol/L, P <.001). The area under the receiver operating characteristic curve for the accuracy to detect acute decompensated heart failure was inferior for uric acid (0.70) than for B-type natriuretic peptide (area under the receiver operating characteristic curve 0.91, P <.001). Patients in the highest uric acid tertile more often required admission to the hospital (92% vs 74% in the first tertile, P <.001) and had higher in-hospital mortality (13% vs 4% in the first tertile, P <.001). Cumulative 24-month mortality rates were 28% in the first, 31% in the second, and 50% in the third tertile (P <.001). After adjustment in multivariable Cox proportional hazard analysis, uric acid predicted 24-month mortality independently of B-type natriuretic peptide (P = .003).

Conclusions

Our study first shows that uric acid, measured at Emergency Department admission or hospital discharge, is a powerful predictor of long-term outcome in dyspneic patients.     

Combination of B-type natriuretic peptide and peak oxygen consumption improves risk stratification in outpatients with chronic heart failure

Background

Peak oxygen consumption is a cornerstone for prognostic determination in patients with congestive heart failure. The purpose of this study was to assess whether plasma B-type natriuretic peptide (BNP) provided any additional prognostic information.

Methods

Plasma concentrations of atrial natriuretic peptide, N terminal pro-atrial natriuretic peptide, BNP, endothelin-1, norepinephrine, and peak VO₂ were measured in 250 consecutive outpatients with mild to moderate heart failure (96% in New York Heart Association [NYHA] class II or III) and left ventricular ejection fraction (LVEF) <45%.

Results

During a median follow-up of 584 days, 42 patients died (19 from sudden death) and 5 underwent urgent heart transplantation. Multivariate stepwise regression analysis showed that, among 13 variables including NYHA and LVEF, plasma BNP (χ² = 11.9, P = .0001) was the strongest independent predictor of death or urgent transplantation, followed by serum sodium (χ² = 8, P = .0046), resting heart rate (χ² = 7.5, P = .0062), plasma endothelin-1 (χ² = 7.2, P = .007), and peak VO₂ (χ² = 6.2, P = .012). Patients with plasma BNP above the upper quartile value (260 pg/mL) had a 1-year rate of death or urgent transplantation of 31%. The 1- and 2-year survival rates without urgent transplantation in patients with a peak VO₂ ≤14 mL × kg⁻¹ × min⁻¹ were 71% and 59%, respectively, when plasma BNP was >137 pg/mL (median value), compared with 100% and 89%, respectively, when plasma BNP was ≤137 pg/mL (P = .008). Furthermore, plasma BNP was the only independent predictor of sudden death (χ² = 19.9, P = .00001).

Conclusions

Plasma BNP provides additive independent prognostic information compared to peak VO₂ alone in outpatients with mild to moderate heart failure.