Background: Diastolic function (DF) guidelines have been simplified but lack extensive outcome data. Using a rural university heart failure (HF) database, we assessed whether DF grading could predict HF, HF readmission, and all-cause mortality (ACM). Methods: In this single-center retrospective study that included 613 patients in sinus rhythm hospitalized for HF (HF with preserved—254 patients, with mid-range—216 patients, and reduced ejection fraction—143 patients), we recorded demographics, Doppler-echo, Framingham HF score, laboratories, HF readmission, and ACM with follow-up to 2167 days. Results: Diastolic dysfunction (Ddys) parameters (left atrial volume index [LAVI] > 34 ml/m2, tricuspid regurgitation [TR] velocity > 2.8 m/sec, and E/e’ > 14) had moderate sensitivity (46.2%–65.0%) for predicting HF among all phenotypes combined with DF grading having moderate predictability and additive to a clinical composite for HF prediction (AUC =.677, P < 0.0001; difference =.043, P < 0.001) for combined phenotypes. Ddys parameters and Ddys severity (2016 ASE criteria: grade II and III) were significantly associated with HF readmission for decompensated HF within 60–2167 days of follow-up (LAVI > 34 ml/m2: HR 1.56 [1.26–2.19]; E/e’ > 14: HR 1.44 [1.21–1.99]; TR > 2.8 m/sec: H1.43 [1.19–1.88]; LV Dys grade II: HR 2.12 [1.42–2.96]; LV Ddys grade III: HR 2.39 [1.57–4.82]). Conclusion: The findings of this study highlight the clinical and prognostic relevance of determining the severity of LV Ddys in patients with HF with regard to HF verification and HF readmission.

Patients with severe heart failure (HF) are often excluded from exercise training studies due to their potentially unstable nature and severe exercise intolerance. Steady state cycling and walking have been the most common interventions and it is unknown whether these training modalities are appropriate and safe for patients with severe HF as they can produce significant cardiovascular stress. Body-weight supported treadmill (BWST) training may be beneficial in patients with severe HF by improving the periphery while minimizing cardiac loading. The purpose of this study was to: 1) assess the safety and feasibility of BWST training in severe HF patients and 2) to evaluate the effect of BWST training on functional capacity, health-related quality of life (HRQL ), cardiopulmonary function, and blood vessel function. Three male patients with severe HF participated in the study. On study entry and at the end of 24 sessions of physician supervised BWST training, patients completed a cardiopulmonary exercise test, two HRQL questionnaires, a 6-Minute Walk Test (6-MWT), and a Doppler ultrasound study. Although there were no study-related adverse events, only one subject (Patient 1) was able to complete post-testing. However, all three patients seemed to demonstrate a general trend towards increased exercise tolerance. By the seventeenth exercise session, the BWS was reduced to zero for Patient 1. In addition, Patient 1 achieved an average walking speed of2.0 km/hr and was completing 34 minutes ofwalking with minimal rest periods by the end of the training program. Patients 2 and 3 also responded to the training as evidenced by a slight increase in exercise duration. However due to fluctuations in their health status, they did not have any substantial improvement. Patient 1 experienced substantial increases in functional capacity: a 64% increase in V02 peak (7.2 to 11.7 ml/kg/min); a 33% increase in peak power output (300 to 400 kpm/min); a 37% increase in VE peak (28 to 39 L/min); and a 28% increase in 6-MWT distance (223. 5 to 286m). In addition, Patient 1 's NYHA-FC improved after training from class III to II. A significant training effect was also evident by reductions in HR at rest (96 to 79 bpm) and during submaximal exercise (100 kpm/min) (105 to 84 bpm). HRQL also tended to improve for Patient 1. Based on these findings and observations, two conclusions can be made. First, patients with severe HF can safely participate in BWST training and may derive considerable benefits. Second, the feasibility of training patients with severe HF is highly dependent on their cardiac condition and other co-morbidities remaining stable enough to allow consistent training. / Thesis / Master of Science (MS)

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Cartas al editor

Heart failure (HF) is a common cause of hospitalisation and mortality across industrialised countries. The number of hospitalisations and deaths attributed to heart failure is increasing, and this trend is predicted to continue. Numerical and in-vitro simulations of the human cardiovascular system constitute the basic tools for enhancing diagnostic and therapeutic technologies for HF and this would in turn, have significant effects on morbidity,mortality, and healthcare expenditure. Mechanical Circulatory Support (MCS) as a destination therapy for HF is rising significantly as it provides a cost-effective alternative to long-term treatment and cardiac transplantation. However, long-term versatility is far from ideal and incidence of transient and permanent neurological events is still high. To this end, evolution of MCS devices calls for more sophisticated design and evaluation methods. The purpose of this work is to develop a numerical model and to implemented a novel in-vitro model of the cardiovascular system with the intention of evaluating the performance characteristics of a purposely selected centrifugal pump impeller for the treatment of both Class III and IV HF conditions when placed in series with the heart at two different anatomic locations: Ascending Aorta and Descending Aorta. An existing lumped-parameter model of the CV system, that included models for the heart, the pulmonary and the systemic circulatory loops by adapting a modified version of the fourth-element Windkessel model was enhanced by dividing the systemic circulation into six parallel vascular beds, and by including an autoregulatory system to control both pressures and volumes throughout the system. As part of the novelty of the present work, a volume reflex loop was included with the purpose of simulating volume overload conditions, as commonly found in HF conditions, and obtaining a more realistic analysis of volume displacement, while using a MCS device. The in-vitro model implemented in this work adopted most of the features included in the mathematical counterpart with the purpose of validating the numerical results. As a result of the combination of models and proper optimisation of the system parameters, predictions of pathophysiological trends and MCS usage are satisfactorily obtained. The models implemented in this work offer a valuable tool for the selection and performance evaluation of MCS devices for the treatment of HF conditions.

Heart failure is the leading cause of morbidity and mortality in the world. It is an incurable disease and most treatment strategies aim to treat the symptoms or slow the progression of the condition. Cardiac contractility is governed by calcium homeostasis within cardiac myocytes and is modulated by the sympathetic nervous system. Both mechanisms are detrimentally altered in heart failure. An important group of enzymes, phosphodiesterases, are fundamental to the sympathetic (beta-adrenergic) modulation of calcium cycling in cardiac myocytes. The selective inhibition of phosphodiesterase 5 (PDE5) has recently been considered as a potential therapy for heart failure; having beneficial effects in human and animal models of the disease. The present study employs a large animal model of tachypacing induced heart failure to test the effect of PDE5 inhibition on myocyte and whole heart contractility and beta-adrenergic function, to assess the molecular mechanisms by which PDE5 inhibition is beneficial to the failing myocardium. In initial experiments the PDE5 inhibitor sildenafil was applied acutely to voltage clamped ventricular myocytes from uninstrumented sheep. PDE5 inhibition reduced baseline L-type calcium current and systolic calcium transient amplitude, suggesting it is negatively inotropic. Furthermore, the positive inotropic effects of beta-adrenergic stimulation were somewhat reversed by acute PDE5 inhibition. Interestingly, such negative inotropic effects of acute PDE5 inhibition were not observed in failing ventricular myocytes, which have dysfunctional calcium homeostasis and beta-adrenergic reserve. When delivered chronically over 3 weeks to tachypaced animals, PDE5 inhibition restored and augmented the systolic calcium transient and beta-adrenergic responsiveness at both the whole heart and myocyte level. These effects were associated with changes to the expression and phosphorylation status of the proteins that control calcium homeostasis in left ventricular tissue. In vivo, PDE5 inhibition prolonged longevity and reduced the onset of clinical signs of heart failure in sheep, as well as arresting cardiac dilatation and wall thinning. Chronic PDE5 inhibition however had no effect on cardiac contractility or heart failure induced changes in cardiac electrophysiology. This study presents a novel mechanism by which PDE5 inhibition may be beneficial in a large animal model of heart failure by restoring calcium homeostasis and beta-adrenergic responsiveness. This study may have important implications for the management of heart failure in clinical practice.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 48-54).

Background: Heart failure and diabetes are common coexisting diseases. Elevated levels of glucose in the blood caused by insulin resistance can damage blood vessels and nerves, and eventually lead to heart disease. A poor diet and obesity can also contribute to the progression of diabetes and heart disease. Objective: The purpose of this study was to determine if diet and lifestyle factors between adult heart failure patients with and without diabetes who are participating in the EducatioN, and Supportive Partners Improving Self-CaRE (ENSPIRE) study are associated with comorbidities such as diabetes, and if so then how current dietary recommendations in this population should be modified based on diabetes status. Methods: Using data collected from the EducatioN and Supportive Partners Improving Self-CaRE (ENSPIRE) study from 2006 to 2009 which was a prospective, randomized, controlled clinical trial, a secondary data analysis was conducted. Daily dietary intake of calories, sodium, carbohydrate, fat, sugar, and fiber was assessed via a 3-day food record. Differences in anthropometric measures, smoking history, education level and health literacy score between the two groups were also assessed. 117 heart failure patients were included in the analysis. Of these, 39% had diabetes. Statistical analysis: Statistical analyses included the t-test, Chi-square analysis, and Mann Whitney U test used to compare anthropometric data, lifestyle factors, and disease states. Results: Weight was higher in heart failure patients with vs. without diabetes (104.9 vs. 92.6 kg, respectively; P Conclusion: Weight was significantly higher in heart failure patients with diabetes and they consumed fewer carbohydrates than their non-diabetic counterparts. We recommend encouraging these individuals to closely monitor their macronutrient intake, specifically limiting fat in the diet. Meeting with a dietitian to ensure adequate nutrient intake is strongly recommended.