First-Phase Ejection Fraction Is a Powerful Predictor of Adverse Events in Asymptomatic Patients With Aortic Stenosis and Preserved Total Ejection Fraction

Objectives

This study investigated the prognostic value of first-phase ejection fraction (EF1) in patients with aortic stenosis (AS), a condition in which left ventricular dysfunction as measured by conventional indices is an indication for valve replacement.

The Natural History of Left Ventricular Geometry in the Community: Clinical Correlates and Prognostic Significance of Change in LV Geometric Pattern

ObjectivesThis study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow-up period.BackgroundIt is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance.MethodsThis study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years. Four groups were defined on the basis of the sex-specific distributions of left ventricular mass (LVM) and relative wall thickness (RWT) (normal: LVM and RWT <80th percentile; concentric remodeling: LVM <80th percentile but RWT ≥80th percentile; eccentric hypertrophy: LVM ≥80th percentile but RWT <80th percentile; and concentric hypertrophy: LVM and RWT ≥80th percentile).ResultsAt baseline, 2,874 of 4,492 observations (64%) had normal LVM and RWT. Participants with normal geometry or concentric remodeling progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change from eccentric to concentric hypertrophy was uncommon (8%). Among participants with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4-year period. Among participants with abnormal LV geometry at baseline, a significant proportion (29% to 53%) reverted to normal geometry within 4 years. Higher blood pressure, greater body mass index (BMI), advancing age, and male sex were key correlates of developing an abnormal geometry. Development of an abnormal LV geometric pattern over 4 years was associated with increased CVD risk (140 events) during a subsequent median follow-up of 12 years (adjusted-hazards ratio: 1.59; 95% confidence interval: 1.04 to 2.43).ConclusionsThe longitudinal observations in the community suggest that dynamic changes in LV geometric pattern over time are common. Higher blood pressure and greater BMI are modifiable factors associated with the development of abnormal LV geometry, and such progression portends an adverse prognosis.     

The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease – A systematic literature review by a European panel of experts

BackgroundHeterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients.MethodsA comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease. The review included all original articles that presented ERT outcomes data on patients with Fabry disease, irrespective of the study type.ResultsClinical evidence for the efficacy of ERT in female patients was available from 67 publications including six clinical trial publications, and indicates significant reductions in plasma and urine globotriaosylceramide (GL-3) accumulation (in female patients with elevated pre-treatment levels) and improvements in cardiac parameters and quality of life (QoL). To date, data are insufficient to conclude on the effects of ERT on the nervous system, gastrointestinal manifestations, and pain in female patients with Fabry disease.ConclusionsThis review of available literature data demonstrates that ERT in adult female patients with Fabry disease has a beneficial effect on GL-3 levels and cardiac outcomes. The current evidence also suggests that ERT may improve QoL in this patient population, though further studies are needed to examine these results.     

The renin‐angiotensin system,blood pressure,and heart structure in patients with hereditary vitamin D–resistance rickets (HVDRR)

Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin‐angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25‐dihydroxyvitamin D–resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age‐ and gender‐matched healthy subjects. Serum calcium, phosphorous, creatinine, 25‐hydroxyvitamin D [25(OH)D],1,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT‐II), and angiotensin‐converting enzyme (ACE) levels were determined. Ambulatory 24‐hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)₂D₃ and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT‐II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6‐ to 36‐year‐old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT‐II, normal aldosterone levels, and no hypertension or gross heart abnormalities. © 2011 American Society for Bone and Mineral Research     

Reduced left ventricular mass after treatment of obese patients with sibutramine: An echocardiographic multicentre study

AIM: In obesity, left ventricular hypertrophy is frequently observed, especially in the presence of hypertension. Following body weight reduction, the left ventricular mass (LVM) is reduced. It is not known to which extent this occurs after treatment with sibutramine. METHODS: In this multicentre trial, 195 male and female patients (18-65 years of age, body mass index 30-40 kg/m2) were treated for 12 weeks with either 15 mg/day sibutramine or placebo. They were advised to follow mildly hypocaloric reducing diets. Exclusion criteria were blood pressure values >180/110 mmHg and tachycardia (heart rate > or =100 beats/min). Echocardiography in M-mode was performed to determine LVM as well as systolic function. RESULTS: Body weight was reduced by 6.9 +/- 0.3 kg under sibutramine and by 2.1 +/- 0.6 kg under placebo; body fat was reduced by 5.2 +/- 0.4 kg and 1.6 +/- 0.7 kg respectively. In the sibutramine group, LVM was reduced by 10.9 +/- 24.2 g; LVM indexed for body surface area was reduced by 2.3 +/- 11.8 g/m2 and LVM indexed for body height was reduced by 2.5 +/- 6.0 g/m(2.7). In the placebo group, LVM and LVM indices were not significantly changed. Changes in LVM correlated with reductions in body weight and initial LVM but not with changes in blood pressure or heart rate. CONCLUSIONS: After 3 months of treatment with sibutramine, obese patients lost about three times as much of body weight and LVM than patients treated with placebo. Therefore, sibutramine may be recommended not only to reduce body weight but also to obtain a regression of the LVM in obese patients with and without hypertension.