Pulmonary Hypertension in Patients with Heart Failure with Preserved Ejection Fraction. Where to Draw the Line.
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ABSTRACT:
SUBMITTER: Simon MA
PROVIDER: S-EPMC6680312 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The most common cause of pulmonary hypertension (PH) due to left heart disease (LHD) was previously rheumatic mitral valve disease. However, with the disappearance of rheumatic fever and an aging population, nonvalvular LHD is now the most common cause of group 2 PH in the developed world. In this review, we examine the challenge of investigating patients who have PH and heart failure with preserved ejection fraction (HF-pEF), where differentiating between pulmonary arterial hypertension (PAH) and PH-LHD can be difficult, and also discuss the entity of combined precapillary and postcapillary PH. Given the proven efficacy of targeted therapy for the treatment of PAH, there is increasing interest in whether these treatments may benefit selected patients with PH associated with HF-pEF, and we review current trial data.
| S-EPMC4860544 | biostudies-literature
Project description:AimsPulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve.Methods and resultsPlasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001).ConclusionSubjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype.Clinical trial registrationNCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.
| S-EPMC7963136 | biostudies-literature
Project description:AimsWhile right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV).Methods and resultsWe prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm2 in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04).ConclusionsDiffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.
| S-EPMC7083501 | biostudies-literature
Project description:AimsThe presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF.Methods and resultsThe phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by -0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred.ConclusionThe vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.
| S-EPMC9492239 | biostudies-literature
Project description:BackgroundWe hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF.MethodsPatients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter.ResultsThe average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (P<0.0001 for all) but lower than PVOD (P≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50-70]) than in PVOD (median, 91 [interquartile range, 82-103]). PASP correlated with arterial percent medial thickness (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (P<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs.ConclusionsIn HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.
| S-EPMC5915920 | biostudies-literature
Project description:BACKGROUND:Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth-line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown. METHODS:We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs. placebo. We evaluated the effects of spironolactone vs. placebo on BP reduction in this group and related this to the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure. RESULTS:We identified 403 participants in the Americas with RHTN. Compared to people without RHTN, those with RHTN were more frequently women, non-White, diabetics, with a higher left ventricular ejection fraction and body mass index, and a lower hemoglobin concentration. In the RHTN group, spironolactone resulted in a decrease of SBP: -6.1 (-8.9, -3.3); P < 0.001 and diastolic BP: -2.9 (-4.6, -1.2); P = 0.001 mm Hg during the first 8 months. BP became controlled after 4 weeks in 63% of patients receiving spironolactone vs. 46% receiving placebo (P = 0.003), with similar responses at 8 weeks, 4 and 8 months. Patients with RHTN derived similar overall benefit from spironolactone on the primary outcomes as those without. CONCLUSIONS:In HFpEF patients with RHTN, spironolactone lowered BP substantially and was associated with similar benefit as those without RHTN. CLINICAL TRIALS REGISTRATION:Trial Number NCT00094302 (ClinicalTrials.gov identifier).
| S-EPMC5861580 | biostudies-literature
Project description:Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous collection of conditions that are unified by the presence of a left ventricular ejection fraction ≥50%, evidence of impaired diastolic function and elevated natriuretic peptide levels, all within the context of typical heart failure signs and symptoms. However, while HFpEF is steadily becoming the predominant form of heart failure, disease-modifying treatment options for this population remain sparse. This review provides an overview of the diagnosis, management and prevention of HFpEF for general physicians.
| S-EPMC6334030 | biostudies-literature
Project description:Iloprost, an inhaled synthetic prostacyclin analogue, improves hemodynamic and clinical status with minimal systemic adversity in patients with pulmonary arterial hypertension. Our single-site, prospective case series aimed to determine the effects of iloprost in subjects with group 2 pulmonary hypertension and heart failure with preserved ejection fraction. Patients referred to Boston Medical Center for initial evaluation of suspected pulmonary hypertension received a test dose of 2.5 μg inhaled iloprost, followed by two subsequent doses of 5 μg. Hemodynamic measurements were recorded for each inhalation after 15, 30, 60, and 90 minutes. Results were analyzed via paired t test and signed-rank test. Eight subjects fulfilled criteria and elected to enter the study. There was a reduction of pulmonary arterial pressure (by an average of 7.0 mmHg [P = 0.005] and 4.7 mmHg [P = 0.021] with the first and second 5-μg inhalations, respectively) and pulmonary vascular resistance (by an average of 161.9 dyn·s/cm(5) [P = 0.019] and 95.0 dyn·s/cm(5) [P = 0.014] with the first and second 5-μg inhalations, respectively). There were trends for increased cardiac output and decreased oxygen saturation. There were no changes in other vital or hemodynamic parameters, including pulmonary capillary wedge pressure. All patients completed each cycle of iloprost administration without preestablished termination criteria. In patients with pulmonary hypertension and heart failure with preserved ejection fraction, inhaled iloprost resulted in acute reduction of pulmonary arterial pressure and pulmonary vascular resistance. Further evaluation of iloprost in this subset of patients is warranted.
| S-EPMC4405721 | biostudies-other
Project description: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.
| S-EPMC5875307 | biostudies-literature
Project description:AimsDiastolic stress testing (DST) is recommended to confirm heart failure with preserved ejection fraction (HFpEF) in patients with exertional dyspnea, but current algorithms do not detect all patients. We aimed to identify additional echocardiographic markers of elevated pulmonary arterial wedge pressure during exercise (exPAWP) in patients referred for DST.Methods and resultsWe identified candidate parameters in 22 patients referred for exercise right heart catheterization with simultaneous echocardiography. Elevated exPAWP (≥25 mmHg) was present in 14 patients, and was best identified by peak septal systolic annular velocity <9.5 cm/s [exS', area under the receiver operating characteristic curve (AUC) 0.97, 95% confidence interval 0.92-1.0] and mean pulmonary artery pressure/cardiac output slope ≥3.2 mmHg/L [mPAP/CO, AUC 0.88 (0.72-1.0)]. We propose a decision tree to identify patients with elevated exPAWP. Applying this decision tree to 326 patients in an independent non-invasive DST cohort showed that patients labeled as "high probability of HFpEF" (n = 85) had reduced peak oxygen uptake [13.0 (10.7-15.1) mL/kg/min, p < 0.001 vs. intermediate/low probability], high H2FPEF score [53 (40-72) %, p < 0.001 vs. intermediate/low probability], and typical clinical characteristics. The diagnostic yield of DST increased from 11% using exercise E/e', to 62% using the decision tree.ConclusionIn DST for suspected HFpEF, exS' was the most accurate echocardiographic parameter to identify elevated PAWP. We propose a decision tree including exS' and mPAP/CO for interpretation of DST. Application of this decision tree revealed typical HFpEF characteristics in patients labeled as high probability of HFpEF, and substantially reduced the number of inconclusive results.
| S-EPMC8863971 | biostudies-literature