Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction
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Abstract:
Importance
Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, yet there are no specific therapies, possibly due to phenotypic heterogeneity. The development of pulmonary hypertension (PH) in patients with HFpEF is considered a high-risk phenotype in need of targeted therapies, but there have been limited hemodynamic and outcomes data.Objective
To identify the hemodynamic characteristics and outcomes of PH-HFpEF.Design, Setting, and Participants
Cohort study of participants who had a right heart catheterization from January 2005 to September 2012 (median [interquartile range] follow-up time, 1578 [554-2513] days) were analyzed. Hemodynamic catheterization data was linked to the clinical data repository of all inpatient and outpatient encounters across a health system. Single tertiary referral center for heart failure and PH within a large health care network using a common clinical data repository was studied. There were 19 262 procedures in 10 023 participants.Exposures
Participants were classified as having no PH, precapillary PH, or PH in the setting of left heart disease (reduced or preserved ejection fraction). Pulmonary hypertension associated with HFpEF was defined as mean pulmonary artery pressure of 25 mm Hg or more, pulmonary artery wedge pressure of 15 mm Hg or more, and left ventricular ejection fraction of 45% or more. Pulmonary hypertension severity was quantified by the hemodynamic parameters transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient.Main Outcomes and Measures
The primary outcome was time to all-cause mortality. Secondary outcomes were time to acute hospitalization and cardiovascular hospitalization.Results
The mean (SD) of all study individuals was 65 (38) years. Of 10 023 individuals, 2587 (25.8%) had PH-HFpEF. Mortality was 23.6% at 1 year and 48.2% at 5 years. Cardiac hospitalizations occurred in 28.1% at 1 year and 47.4% at 5 years. The frequency of precapillary PH using clinically defined cut-offs for transpulmonary gradient (>12 mm Hg), pulmonary vascular resistance (3 Woods units), and diastolic pulmonary gradient (≥7 mm Hg) were 12.6%, 8.8%, and 3.5%, respectively. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pressure gradient were predictive of mortality and cardiac hospitalizations.Conclusions and Relevance
In a large cohort referred for invasive hemodynamic assessment, PH-HFpEF was common. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient are all associated with mortality and cardiac hospitalizations.Keywords:
Pulmonary wedge pressure
Interquartile range
Pulmonary wedge pressure
Cardiac catheterization
Pathophysiology of hypertension
Right heart catheterization
Hypoxia
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Pulmonary wedge pressure
Cardiac catheterization
Pathophysiology of hypertension
Right heart catheterization
Hypoxia
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Abstract Correlations between pulmonary artery and pulmonary vein wedge pressures were investigated in 13 patients with atrial septal defect and 1 patient with Tetralogy of Fallot. Pulmonary vein wedge pressure wave form resembled that of pulmonary artery pressure, and the former lagged behind the latter by 70 to 110 msec (mean 88 ± 14) as observed by the fluid‐filled catheter system. Diastolic pulmonary artery and diastolic pulmonary vein wedge pressures were nearly identical. Although systolic and mean pulmonary artery pressures correlated well with respective pulmonary vein wedge pressures, there were discrepancies when systolic and mean pulmonary artery pressure exceeded 35 and 20 mm Hg, respectively. However, systolic and mean pulmonary artery pressures could be estimated by adding the difference between the diastolic pulmonary vein wedge pressure and the mean left atrial pressure to corresponding systolic or mean pulmonary artery pressure. In conclusion, pulmonary artery pressures can be estimated by measuring pulmonary vein wedge pressures and the mean left atrial pressure.
Pulmonary wedge pressure
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The effects of endotoxin on pulmonary hemodynamics were studied in seven intact dogs. The distribution of pulmonary vascular resistance was estimated by the effective pulmonary capillary pressure, which was derived from the pressure transient recorded while the pulmonary artery catheter was rapidly wedged. After the injection of endotoxin, cardiac output and aortic pressure consistently fell. Pulmonary artery occlusion (wedge) pressure also decreased, but not significantly. Although pulmonary artery pressure did not necessarily rise, total pulmonary vascular resistance increased in every dog. The absolute increase in pulmonary artery resistance was greater (142 mm Hg/L X min/kg); than in venous resistance (111 mm Hg/L X min/kg); however, the relative increase in venous resistance was higher (410% for venous resistance vs. 220% for pulmonary artery resistance). As a result of venoconstriction, there was a consistent increase in effective pulmonary capillary pressure (from 2.5 to 6.3 mm Hg). Our data indicate that the pulmonary vascular response to endotoxin injection is characterized by constriction of both pulmonary arteries and pulmonary veins. The capillary wedge pressure did not reflect the pulmonary microvascular pressure, since it varied in the opposite direction to the effective capillary pressure.
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To clarify the importance of pulmonary hypertension in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF).Pulmonary hypertension is frequently present in HFpEF because of both elevated pulmonary venous pressure and some element of pulmonary vasoconstriction. HFpEF may be the most common cause of pulmonary hypertension in the elderly. The noninvasive detection of pulmonary hypertension can distinguish patients with HFpEF from those with diastolic dysfunction without heart failure. Pulmonary hypertension may be an important target for treatment of HFpEF. Phosphodiesterase-5 inhibitors are a promising method to treat pulmonary hypertension because of HFpEF.Pulmonary hypertension is an important contributor to the pathophysiology of HFpEF, can be used to recognize HFpEF and may be an important target for therapy.
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Wedge (geometry)
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We reviewed cardiac catheterization data and the medical records of 30 patients with systemic hypertension to establish their pulmonary hemodynamic profiles and the relationship between certain clinical and demographic variables and increased pulmonary vascular resistance. Mean systemic arterial pressure ranged from 110 to 210 mm Hg, and systemic vascular resistance ranged from 17.6 to 47.0 units. Seven patients had normal pulmonary wedge pressure and normal pulmonary vascular resistance, one had elevated pulmonary wedge pressure and normal pulmonary vascular resistance, five had elevated pulmonary wedge pressure and increased pulmonary vascular resistance, and 17 had normal pulmonary wedge pressure and increased pulmonary vascular resistance. There were significant positive correlations between systemic vascular resistance and pulmonary vascular resistance and between mean systemic arterial pressure and mean pulmonary artery pressure, but there was no correlation between mean pulmonary wedge pressure and pulmonary vascular resistance. Of the 17 patients with normal pulmonary wedge pressure and increased pulmonary vascular resistance, seven had clinical or radiologic evidence of prior left ventricular failure. We conclude that increased pulmonary vascular resistance occurs commonly in patients with systemic hypertension. Although some cases of increased pulmonary vascular resistance relate to active or preexistent left ventricular failure, the majority remain unexplained, suggesting that neurohumoral or other factors may produce a hypertensive response in both the systemic and pulmonary arterial circuit.
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BACKGROUND: Despite demonstrated benefits of lateral positioning, critically ill patients may require prolonged supine positioning to obtain reproducible hemodynamic measurements. OBJECTIVES: TO determine the effect of 30 degree right and left lateral positions on pulmonary artery and pulmonary artery wedge pressures after cardiac surgery in critically ill adult patients. METHODS: An experimental repeated-measures design was used to study 35 patients with stable hemodynamics after cardiac surgery. Subjects were randomly assigned to 1 of 2 position sequences. Pulmonary artery and pulmonary artery wedge pressures were measured in each position. RESULTS: Measurements obtained from patients in the 30 degree left lateral position differed significantly (all Ps < .05) from measurements obtained from patients in the supine position for pulmonary artery systolic, end-diastolic, and mean pressures. Pulmonary artery wedge pressures did not differ significantly; however, data were available from only 17 subjects. The largest mean difference in pressures between the 2 positions was 2.0 +/- 2.1 mm Hg for pulmonary artery systolic pressures, whereas maximum differences for end-diastolic and pulmonary artery wedge pressures were 1.4 +/- 2.7 mm Hg and 1.6 +/- 2.4 mm Hg, respectively. Clinically significant position-related changes in pressure occurred in 12 (2.1%) of 581 pressure pairs. Clinically significant changes occurred in end-diastolic pressure in 2 subjects and in pulmonary artery wedge pressure in 1 subject. CONCLUSiONS: In patients with stable hemodynamics during the first 12 to 24 hours after cardiac surgery, measurements of pulmonary artery and pulmonary artery wedge pressures obtained in the 30 degree lateral and supine positions are clinically interchangeable.
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