6 research outputs found
The UPHILL study: A nutrition and lifestyle intervention to improve quality of life for patients with pulmonary arterial hypertension
Abstract The aim of the UPHILL study (a nutrition and lifestyle intervention in patients with pulmonary arterial hypertension [PAH]: effect on quality of life [QoL]), was to determine the effect of innovative nutritional interventions on adjustments in nutritional intake and QoL. In this study a group of prevalent PAH patients at a single center in Amsterdam (the Netherlands) was informed about healthy nutrition using a newly designed video eâlearning. They were subsequently instructed to follow a healthy diet during dietary intervention. Nutritional intake was assessed using a food frequency questionnaire (HELIUS) and QoL by the shortâform (SF)â36 questionnaire. Nutritional parameters were determined in blood samples. Seventeen patients stable under treatment, who had been diagnosed with PAH 7.0 [3.0â14.0] years before, started and completed the intervention (2 males, 15 females; 45.35â±â13.57 years). Since all patients in the intervention group made behavioral changes in nutritional intake, during study and followâup, nutritional and lifestyle adaptations persisted. Despite the fact that patients had already high mean scores at baseline for both mental (74.10 [60.51â84.25]) and physical QoL (66.46 [50.21â73.84]), scores improved further during eâlearning. Furthermore, patients who realized most nutritional adaptations, had the best improvement in QoL. This pilot study showed that eâlearning modules on nutrition provide an unique opportunity to change nutritional intake in PAH patients and by that improve QoL
Nutritional status in pulmonary arterial hypertension
Abstract Nutritional deficiencies have been described in patients with pulmonary arterial hypertension (PAH), such as in iron and vitamin D. However, an extensive description of vitamin and mineral status is lacking and until now there is no data on dietary intake in PAH patients. We analyzed blood samples and determined nutritional intake using a food frequency questionnaire (HELIUS) in a cohort of prevalent PAH patients at a single center in Amsterdam, the Netherlands. Quality of life (QoL) was assessed by the SFâ36 questionnaire. In total, 37 patients were included (6 males, 31 females; 48â±â16 years). The dietary intake of sugar was above 25âg in 87% of the patients and fluid intake was above 1500âml in 78% of the patients. Sodium intake was below 1800âmg in the majority (56%) of the patients. Sugar and fluid intake were linear related. We confirm previously observed deficiencies of iron and vitamin D in our study population. In addition, we observed a functional vitamin B12 deficiency in 29% of patients, which coincided with an increased expression of methylmalonic acid. 60% of patients had a low vitamin K1 status (<0.8ânmol/L). Finally, 40% of patients had selenium levels below <100âÎŒg/L and low selenium levels associated with reduced vitality in these patients. Besides the known deficiencies in iron and vitamin D levels, we observed in a subset of patients signs of vitamin B12, vitamin K1 and selenium deficiencies. There is room for improving dietary intake. Future research aims to demonstrate the clinical importance and reveal the effect of nutritional interventions
Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled crossâover trial
Abstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results The DoPINGâHFpEF trial was a phase II singleâcentre, doubleâblind, placeboâcontrolled, randomized crossâover trial. Patients were randomized to trimetazidine treatment or placebo for 3Â months and switched after a 2âweek washâout period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorusâ31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI â2, 2] mmHg over multiple levels of exercise, PÂ =Â 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], PÂ =Â 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6âmin walking distance (mean change of â6 [95% CI â18, 7] m vs. â5 [95% CI â22, 22] m, respectively, PÂ =Â 0.93), Nâterminal proâBâtype natriuretic peptide (5 (â156, 166) ng/L vs. â13 (â172, 147) ng/L, PÂ =Â 0.70), overall qualityâofâlife (KCCQ and EQâ5Dâ5L, PÂ =Â 0.78 and PÂ =Â 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF
Geranylgeranylacetone reduces cardiomyocyte stiffness and attenuates diastolic dysfunction in a rat model of cardiometabolic syndrome
Abstract Titinâdependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressureâoverload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown. Our objective was to investigate whether oral GGA treatment lowers cardiomyocyte stiffness and attenuates LV diastolic dysfunction in a rat model of the cardiometabolic syndrome. Twentyâoneâweekâold male lean (nâ=â10) and obese (nâ=â20) ZSF1 rats were studied, and obese rats were randomized to receive GGA (200âmg/kg/day) or vehicle by oral gavage for 4âweeks. Echocardiography and cardiac catheterization were performed before sacrifice at 25âweeks of age. Titinâbased stiffness (Fpassive) was determined by force measurements in relaxing solution with 100ânM [Ca2+] in permeabilized cardiomyocytes at sarcomere lengths (SL) ranging from 1.8 to 2.4âÎŒm. In obese ZSF1 rats, GGA reduced isovolumic relaxation time of the LV without affecting blood pressure, EF or LV weight. In cardiomyocytes, GGA increased myofilamentâbound HSPB5 and HSPB1 expression. Vehicleâtreated obese rats exhibited higher cardiomyocyte stiffness at all SLs compared to lean rats, while GGA reduced stiffness at SL 2.0âÎŒm. In obese ZSF1 rats, oral GGA treatment improves cardiomyocyte stiffness by increasing myofilamentâbound HSPB1 and HSPB5. GGA could represent a potential novel therapy for the early stage of diastolic dysfunction in the cardiometabolic syndrome
EXPRESS: Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients
Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.
Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the in vivo environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs. Specific recommendations were provided, including a call to incorporate precision medicine and innovations in prognosis, diagnosis, and novel RV therapeutics for patients with pulmonary vascular disease