Invasive Hemodynamics of Pulmonary Disease and the Right Ventricle.

Pulmonary hypertension (PH) falls into 5 groups, as defined by the World Health Organization. Swan-Ganz catheters determine precapillary versus postcapillary PH. The hemodynamic values of PH at rest and with vasodilatory challenge categorize the etiology of PH and guide treatment. RV maladaptations to increased pulmonary vascular resistance (PVR) and the chronicity of the right ventricle's (RV) response to increased PH and/or increased PVR can be understood with pressure-volume (PV) loops constructed with use of conductance catheters. These PV loops demonstrate the RV's ability to increase stroke volume in acutely and chronically increased PVR.

Relative importance of errors in left ventricular quantitation by two-dimensional echocardiography: insights from three-dimensional echocardiography and cardiac magnetic resonance imaging.

BACKGROUND: The accuracy of left ventricular (LV) volumes and ejection fraction (EF) on two-dimensional echocardiography (2DE) is limited by image position (IP), geometric assumption (GA), and boundary tracing (BT) errors. METHODS: Real-time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR) were used to determine the relative contribution of each error source in normal controls (n = 35) and patients with myocardial infarctions (MIs) (n = 34). LV volumes and EFs were calculated using (1) apical biplane disk summation on 2DE (IP + GA + BT errors), (2) biplane disk summation on RT3DE (GA + BT errors), (3) 4-multiplane to 8-multiplane surface approximation on RT3DE (GA + BT errors), (4) voxel-based surface approximation on RT3DE (BT error alone) and (5) CMR. By comparing each method with CMR, the absolute and relative contributions of each error source were determined. RESULTS: IP error predominated in LV volume quantification on 2DE in normal controls, whereas GA error predominated in patients with MIs. Underestimation of volumes on 2DE was overcome by increasing the number of imaging planes on RT3DE. Although 4 equidistant image planes were acceptable, the best results were achieved with voxel-based RT3DE. For EF estimation, IP error predominated in normal controls, whereas BT error predominated in patients with MIs. Nevertheless, one third of the EF estimation error in patients with MIs was due to a combination of IP and GA errors, both of which may be addressed using RT3DE. CONCLUSIONS: The relative contribution of each source of LV quantitation error on 2DE was defined and quantified. Each source of error differed depending on patient characteristics and LV geometry.

Sildenafil improves exercise hemodynamics and oxygen uptake in patients with systolic heart failure.

BACKGROUND: Heart failure (HF) is frequently associated with dysregulation of nitric oxide-mediated pulmonary vascular tone. Sildenafil, a type 5 phosphodiesterase inhibitor, lowers pulmonary vascular resistance in pulmonary hypertension by augmenting intracellular levels of the nitric oxide second messenger, cyclic GMP. We tested the hypothesis that a single oral dose of sildenafil (50 mg) would improve exercise capacity and exercise hemodynamics in patients with chronic systolic HF through pulmonary vasodilation. METHODS AND RESULTS: Thirteen patients with New York Heart Association class III HF underwent assessment of right heart hemodynamics, gas exchange, and first-pass radionuclide ventriculography at rest and with cycle ergometry before and 60 minutes after administration of 50 mg of oral sildenafil. Sildenafil reduced resting pulmonary arterial pressure, systemic vascular resistance, and pulmonary vascular resistance, and increased resting and exercise cardiac index (P<0.05 for all) without altering mean arterial pressure, heart rate, or pulmonary capillary wedge pressure. Sildenafil reduced exercise pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary vascular resistance/systemic vascular resistance ratio, which indicates a selective pulmonary vasodilator effect with exercise. Peak VO2 increased (15+/-9%) and ventilatory response to CO2 output (VE/VCO2 slope) decreased (16+/-5%) after sildenafil treatment. Improvements in right heart hemodynamics and exercise capacity were confined to patients with secondary pulmonary hypertension (rest pulmonary arterial pressure >25 mm Hg). CONCLUSIONS: The present study shows that in patients with systolic HF, type 5 phosphodiesterase inhibition with sildenafil improves peak VO2, reduces VE/VCO2 slope, and acts as a selective pulmonary vasodilator during rest and exercise in patients with HF and pulmonary hypertension.

Dissociation between improvement in left ventricular performance and functional class in patients with chronic heart failure.

Resting left ventricular ejection fraction (LVEF) and functional capacity do not correlate in chronic heart failure patients treated with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. We sought to determine whether substantial improvement in LVEF, as may occur during long-term beta-blockade or after coronary artery bypass graft (CABG) surgery, leads consistently to improvement in functional class. Doppler echocardiogram and assessment of functional class were obtained at baseline and 12 months after initiation of beta-blockade (87 patients) or CABG surgery (51 patients). At 12 months the effects of beta-blockade were variable: LVEF increased greatly by >or=11% (median value) in 45 patients (52%) and by <11% in 19 (22%), but it decreased or remained unchanged in 23 patients (26%). In contrast, functional class was unchanged or worsened in 59 patients (68%) and improved in only 28 (32%). Similarly, surgery had variable effects on LVEF. LVEF increased by >or=12% (median) in 28 patients (55%) and by <12% in 14 (27%), whereas it decreased or remained unchanged in 9 patients (18%). Functional class was unchanged or worsened in 41 patients (80%) and improved in only 10 (20%). Changes in functional class and LVEF were unrelated for both interventions. Both beta-blockade and CABG surgery improve LVEF in the majority of patients. However, significant improvement in LVEF does not enhance functional capacity consistently in chronic heart failure.

Endothelial cell activation in patients with decompensated heart failure.

BACKGROUND: Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state. METHODS AND RESULTS: Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation. CONCLUSIONS: Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.

Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium.

Limited availability of endothelial tissue is a major constraint when investigating the cellular mechanisms of endothelial dysfunction in patients with metabolic and cardiovascular diseases. We propose a novel approach that combines collection of 200-1,000 endothelial cells from a superficial forearm vein or the radial artery, with reliable measurements of protein expression by quantitative immunofluorescence analysis. This method was validated against immunoblot analysis in cultured endothelial cells. Levels of vascular endothelial cell activation, oxidative stress, and nitric oxide synthase expression were measured and compared in five patients with severe chronic heart failure and in four healthy age-matched subjects. In summary, vascular endothelial biopsy coupled with measurement of protein expression by quantitative immunofluorescence analysis provides a novel approach to the study of the vascular endothelium in humans.