No abstract

Background Hemodynamic assessment after volume challenge has been proposed as a way to identify heart failure with preserved ejection fraction (HFpEF). However, the normal hemodynamic response to a volume challenge and how age and sex affect this relationship remains unknown. Methods and Results Sixty healthy subjects underwent right heart catheterization to measure age- and sex-related normative responses of pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (MPAP) to volume loading with rapid saline infusion (100-200 ml/min). Hemodynamic responses to saline infusion in HFpEF (n=11) were then compared to healthy young (<50yrs) and older-aged (≥50yrs) subjects. In healthy subjects, PCWP increased from 10±2 to 16±3 mmHg after ~1L and to 20±3 mmHg after ~2L of saline infusion. Older women displayed a steeper increase in PCWP relative to volume infused (16±4mmHg·L−1·m2) than the other 3 groups (p≤0.019). Saline infusion resulted in a greater increase in MPAP relative to cardiac output in women compared to men, irrespective of age. Subjects with HFpEF exhibited a steeper increase in PCWP relative to infused volume (25±12 mmHg·L−1·m2) than healthy young and older subjects (p≤0.005). Conclusions Filling pressures rise significantly with volume loading, even in normal volunteers. Older women and patients with HFpEF exhibit the largest increases in PCWP and MPAP.

Objectives The aim of this study was to determine the relative contribution of the muscle and ventilatory pumps to stroke volume in patients without a subpulmonic ventricle. Background In patients with Fontan circulation, it is unclear how venous return is augmented to increase stroke volume and cardiac output during exercise. Methods Cardiac output (acetylene rebreathing), heart rate (electrocardiography), oxygen uptake (Douglas bag technique), and ventilation were measured in 9 patients age 15.8 ± 6 years at 6.1 ± 1.8 years after Fontan operation and 8 matched controls. Data were obtained at rest, after 3 min of steady-state exercise (Ex) on a cycle ergometer at 50% of individual working capacity, during unloaded cycling at 0 W (muscle pump alone), during unloaded cycling with isocapnic hyperpnea (muscle and ventilatory pump), during Ex plus an inspiratory load of 12.8 ± 1.5 cm water, and during Ex plus an expiratory load of 12.8 ± 1.6 cm water. Results In Fontan patients, the largest increases in stroke volume and stroke volume index were during zero-resistance cycling. An additional increase with submaximal exercise occurred in controls only. During Ex plus expiratory load, stroke volume indexes were reduced to baseline, non-exercise levels in Fontan patients, without significant changes in controls. Conclusions With Fontan circulation increases in cardiac output and stroke volume during Ex were due to the muscle pump, with a small additional contribution by the ventilatory pump. An increase in intrathoracic pressure played a deleterious role in Fontan circulation by decreasing systemic venous return and stroke volume.

Background-Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. However, it is unclear whether a strategy of exercise combined with alagebrium would improve LV stiffness in sedentary older humans. Methods and Results-Sixty-two healthy subjects were randomized into 4 groups: sedentary+placebo; sedentary+alagebrium (200 mg/d); exercise+placebo; and exercise+alagebrium. Subjects underwent right heart catheterization to define LV pressurevolume curves; secondary functional outcomes included cardiopulmonary exercise testing and arterial compliance. A total of 57 of 62 subjects (67±6 years; 37 f/20 m) completed 1 year of intervention followed by repeat measurements. Pulmonary capillary wedge pressure and LV end-diastolic volume were measured at baseline, during decreased and increased cardiac filling. LV stiffness was assessed by the slope of LV pressure-volume curve. After intervention, LV mass and end-diastolic volume increased and exercise capacity improved (by ≈8%) only in the exercise groups. Neither LV mass nor exercise capacity was affected by alagebrium. Exercise training had little impact on LV stiffness (training×time effect, P=0.46), whereas alagebrium showed a modest improvement in LV stiffness compared with placebo (medication×time effect, P=0.04). Conclusions-Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01014572.(Circ Heart Fail. 2013;6:1155-1164.)Key Words: aging ◼ alagebrium ◼ cardiac function tests ◼ hemodynamics Received April 25, 2013; accepted October 8, 2013. no study that invasively evaluated the effect of alagebrium on LV stiffness in healthy aged individuals. Moreover, it is unclear whether a concurrent pharmacological therapy is required to observe an exercise effect in LV stiffness when significant AGE accumulation and AGE crosslinks are likely to have occurred. Thus, we hypothesized that a combination of alagebrium and exercise training for 1 year would be the optimal strategy to reverse age-associated LV stiffening and atrophy compared with alagebrium or exercise alone in healthy older individuals. To investigate this hypothesis, we performed comprehensive and detailed measurements of hemodynamics and LV structure and function in healthy older individuals before and after 1 year of alagebrium combined with exercise training. Methods Subject Population and Study DesignThis study was a prospective, controlled, randomized (for all subjects), double-blind placebo (alagebrium only) study for 1 year evaluating the efficacy of the combination of alagebrium o...

No abstract

Background: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore,

No abstract

No abstract