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Hwang S.-J.,Mayo Medical School | Hwang S.-J.,Gyeongsang National University | Melenovsky V.,Mayo Medical School | Melenovsky V.,Institute of Clinical and Experimental Medicine IKEM | Borlaug B.A.,Mayo Medical School
Journal of the American College of Cardiology | Year: 2014

Objectives This study investigated the characteristics, evaluation, prognostic impact, and treatment of coronary artery disease (CAD) in patients with heart failure and preserved ejection fraction (HFpEF). Background CAD is common in patients with HFpEF, but it remains unclear how CAD should be categorized, evaluated for, and treated in HFpEF. Methods Clinical, hemodynamic, echocardiographic, treatment, and outcome characteristics were examined in consecutive patients with previous HFpEF hospitalizations who underwent coronary angiography. Results Of the 376 HFpEF patients examined, 255 (68%) had angiographically-proven CAD. Compared with HFpEF patients without CAD, patients with CAD were more likely to be men, to have CAD risk factors, and to be treated with anti-ischemic medications. However, symptoms of angina and heart failure were similar in patients with and without CAD, as were measures of cardiovascular structure, function, and hemodynamics. Compared with patients without CAD, HFpEF patients with CAD displayed greater deterioration in ejection fraction and increased mortality, independent of other predictors (hazard ratio: 1.71, 95% confidence interval: 1.03 to 2.98; p = 0.04). Complete revascularization was associated with less deterioration in ejection fraction and lower mortality compared with patients who were not completely revascularized, independent of other predictors (hazard ratio: 0.56, 95% confidence interval: 0.33 to 0.93; p = 0.03). Conclusions CAD is common in patients with HFpEF and is associated with increased mortality and greater deterioration in ventricular function. Revascularization may be associated with preservation of cardiac function and improved outcomes in patients with CAD. Given the paucity of effective treatments for HFpEF, prospective trials are urgently needed to determine the optimal evaluation and management of CAD in HFpEF. © 2014 by the American College of Cardiology Foundation. Published by Elsevier Inc. Source

Melenovsky V.,Mayo Medical School | Melenovsky V.,Institute of Clinical and Experimental Medicine IKEM | Hwang S.-J.,Mayo Medical School | Lin G.,Mayo Medical School | And 2 more authors.
European Heart Journal | Year: 2014

Aim Right heart function is not well characterized in patients with heart failure and preserved ejection fraction (HFpEF). The goal of this study was to examine the haemodynamic, clinical, and prognostic correlates of right ventricular dysfunction (RVD) in HFpEF. Methods and results Heart failure and preserved ejection fraction patients (n = 96) and controls (n = 46) underwent right heart catheterization, echocardiographic assessment, and follow-up. Right and left heart filling pressures, pulmonary artery (PA) pressures, and right-sided chamber dimensions were higher in HFpEF compared with controls, while left ventricular size and EF were similar. Right ventricular dysfunction (defined by RV fractional area change, FAC <35%) was present in 33% of HFpEF patients and was associated with more severe symptoms and greater comorbidity burden. Right ventricular function was impaired in HFpEF compared with controls using both load-dependent (FAC: 40 ± 10 vs. 53 ± 7%, P < 0.0001) and load-independent indices (FAC adjusted to PA pressure, P = 0.003), with enhanced afterload-sensitivity compared with controls (steeper FAC vs. PA pressure relationship). In addition to haemodynamic load, RVD in HFpEF was associated with male sex, atrial fibrillation, coronary disease, and greater ventricular interdependence. Over a median follow-up of 529 days (IQR: 143-1066), 31% of HFpEF patients died. In Cox analysis, RVD was the strongest predictor of death (HR: 2.4, 95% CI: 1.6-2.6; P < 0.0001). Conclusion Right heart dysfunction is common in HFpEF and is caused by both RV contractile impairment and afterload mismatch from pulmonary hypertension. Right ventricular dysfunction in HFpEF develops with increasing PA pressures, atrial fibrillation, male sex, and left ventricular dysfunction, and may represent a novel therapeutic target. © 2014 Published on behalf of the European Society of Cardiology. Source

Abudiab M.M.,Mayo Medical School | Redfield M.M.,Mayo Medical School | Melenovsky V.,Mayo Medical School | Melenovsky V.,Institute of Clinical and Experimental Medicine IKEM | And 4 more authors.
European Journal of Heart Failure | Year: 2013

AimsExercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF), yet its mechanisms remain unclear. The current study sought to determine whether increases in cardiac output (CO) during exercise are appropriately matched to metabolic demands in HFpEF.Methods and resultsPatients with HFpEF (n = 109) and controls (n = 73) exercised to volitional fatigue with simultaneous invasive (n = 96) or non-invasive (n = 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO2) during upright or supine exercise. At rest, HFpEF patients had higher LV filling pressures but similar heart rate, stroke volume, EF, and CO. During supine and upright exercise, HFpEF patients displayed lower peak VO2 coupled with blunted increases in heart rate, stroke volume, EF, and CO compared with controls. LV filling pressures increased dramatically in HFpEF patients, with secondary elevation in pulmonary artery pressures. Reduced peak VO2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO2 was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O2, P = 0.0005). While absolute increases in arterial-venous O2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial-venous O2 difference relative to VO2 was greater in HFpEF patients (8.9 ± 3.4 vs. 5.5 ± 2.0 min/dL, P < 0.0001). These differences were observed in the total cohort and when upright and supine exercise modalities were examined individually.ConclusionWhile diastolic dysfunction promotes congestion and pulmonary hypertension with stress in HFpEF, reduction in exercise capacity is predominantly related to inadequate CO relative to metabolic needs. © 2013 The Author. Source

Lejskova M.,Institute for Postgraduate Medical Education | Alusi S.,Institute for Postgraduate Medical Education | Valenta Z.,Academy of Sciences of the Czech Republic | Adamkova S.,Thomayer Hospital and Outpatient Clinic | Pitha J.,Institute of Clinical and Experimental Medicine IKEM
Physiological Research | Year: 2012

Cardiovascular disease, while rare in women of reproductive age, is the main cause of mortality in menopause. The purpose of our study was to determine the association of natural menopause with cardiovascular risk factors, including their clustering into metabolic syndrome (MS). A random 5 % representative population sample of women aged 45-54 years was examined. In 575 women, we were able to determine their natural reproductive aging status. Multiple regression analysis was used to calculate the association between age, menopausal status, and risk factors under study. After adjustment for age, there was an increase in the odds ratio of developing MS, as defined by NCEP (OR=2.0; 95 % CI [1.1; 3.7]), and an increase in plasma lipid ratios (total cholesterol/HDL-C, LDL-C/HDL-C, apolipoprotein-B/ apolipoprotein-A1; p<0.05 for all) in postmenopausal women. Age, but not menopausal status, was associated with some single components of MS; only waist circumference significantly increased after menopause, independently of age. Clustering of risk factors in MS and lipid ratios (combined factors) was strongly associated with menopause whereas worsening of single components of MS was strongly associated with age. In conclusion, based on our results, the menopause may pose a risk to women through clustering of cardiovascular risk factors beyond simple aging. © 2012 Institute of Physiology v.v.i. Source

Reichenbach A.,Institute for Clinical and Experimental Medicine IKEM | Al-Hiti H.,Institute for Clinical and Experimental Medicine IKEM | Malek I.,Institute for Clinical and Experimental Medicine IKEM | Pirk J.,Institute of Clinical and Experimental Medicine IKEM | And 3 more authors.
International Journal of Cardiology | Year: 2013

Background: The goal was to examine the hemodynamic and clinical effects of long-term therapy with PDE5 inhibitor sildenafil (SILD) in patients with advanced, pre-transplant heart failure (HF) and severe pulmonary hypertension (PH), in comparison to a similar control group (CON). Methods: In this non-randomized, retrospective case-control study, 32 middle-aged patients (81% males) with advanced systolic HF (80% ≥ NYHA III, 56% ischemic) and severe pre-capillary PH (transpulmonary pressure gradient > 15 mm Hg) were studied before and after initiation of SILD (dose 73 ± 25 mg/day) and were compared to 15 CON patients, matched for key clinical characteristics (including PH severity, age and co-morbidities), not exposed to SILD. Changes at 3 months and the long-term outcome were compared between groups. Results: SILD significantly reduced pulmonary vascular resistance (- 32% vs. baseline), transpulmonary gradient (- 25%) and increased cardiac output (+ 15%) compared to controls, without affecting systemic or ventricular filling pressures. SILD-treated subjects experienced an improvement in NYHA class and had a steady body weight which contrasted with significant weight loss in the CON group (by - 4.8%, absolutely by 4.3 ± 6 kg). During follow-up (median 349 days from baseline), 60% of patients underwent heart transplantation. Two patients in CON group had severe post-transplant failure of the right ventricle, none in SILD group. Overall pre- and peritransplant survival (censored 30 days after transplantation) was significantly better in SILD than CON group (93.7 vs 60%, p = 0.0048). Conclusions: In patients with advanced HF and severe PH, SILD therapy has beneficial effects on hemodynamics, clinical status, cardiac cachexia, and contributes to improved peri-transplant survival. © 2012 Elsevier Ireland Ltd. All rights reserved. Source

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