Pulmonary Hypertension in Heart Failure Patients

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Abstract

The development of pulmonary hypertension (PH) in patients with heart failure is associated with increased morbidity and mortality. In this article, the authors examine recent changes to the definition of PH in the setting of left heart disease (PH-LHD), and discuss its epidemiology, pathophysiology and prognosis. They also explore the complexities of diagnosing PH-LHD and the current evidence for the use of medical therapies, promising clinical trials and the role of left ventricular assist device and transplantation.

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Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial.

William T. Abraham, Philip B. Adamson, Robert Bourge … (2011)

Results of previous studies support the hypothesis that implantable haemodynamic monitoring systems might reduce rates of hospitalisation in patients with heart failure. We undertook a single-blind trial to assess this approach. Patients with New York Heart Association (NYHA) class III heart failure, irrespective of the left ventricular ejection fraction, and a previous hospital admission for heart failure were enrolled in 64 centres in the USA. They were randomly assigned by use of a centralised electronic system to management with a wireless implantable haemodynamic monitoring (W-IHM) system (treatment group) or to a control group for at least 6 months. Only patients were masked to their assignment group. In the treatment group, clinicians used daily measurement of pulmonary artery pressures in addition to standard of care versus standard of care alone in the control group. The primary efficacy endpoint was the rate of heart-failure-related hospitalisations at 6 months. The safety endpoints assessed at 6 months were freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00531661. In 6 months, 83 heart-failure-related hospitalisations were reported in the treatment group (n=270) compared with 120 in the control group (n=280; rate 0·31 vs 0·44, hazard ratio [HR] 0·70, 95% CI 0·60-0·84, p<0·0001). During the entire follow-up (mean 15 months [SD 7]), the treatment group had a 39% reduction in heart-failure-related hospitalisation compared with the control group (153 vs 253, HR 0·64, 95% CI 0·55-0·75; p<0·0001). Eight patients had DSRC and overall freedom from DSRC was 98·6% (97·3-99·4) compared with a prespecified performance criterion of 80% (p<0·0001); and overall freedom from pressure-sensor failures was 100% (99·3-100·0). Our results are consistent with, and extend, previous findings by definitively showing a significant and large reduction in hospitalisation for patients with NYHA class III heart failure who were managed with a wireless implantable haemodynamic monitoring system. The addition of information about pulmonary artery pressure to clinical signs and symptoms allows for improved heart failure management. CardioMEMS. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.

Margaret M. Redfield, Horng Chen, Barry Borlaug … (2013)

Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF). To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction ≥50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012. Sildenafil (n = 113) or placebo (n = 103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks. Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e' (16), left atrial volume index (44 mL/m2), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (-0.20 [IQR, -0.70 to 1.00]) or sildenafil (-0.20 [IQR, -1.70 to 1.11]) were not significantly different (P = .90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, -0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P = .85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P = .92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status. clinicaltrials.gov Identifier: NCT00763867.

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Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction.

Barry Borlaug, Rick A. Nishimura, Paul Sorajja … (2010)

When advanced, heart failure with preserved ejection fraction (HFpEF) is readily apparent. However, diagnosis of earlier disease may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and hemodynamic indicators of volume overload may be absent at rest. Patients with exertional dyspnea and ejection fraction >50% were referred for hemodynamic catheterization. Those with no significant coronary disease, normal brain natriuretic peptide assay, and normal resting hemodynamics (mean pulmonary artery pressure <25 mm Hg and pulmonary capillary wedge pressure [PCWP] <15 mm Hg) (n=55) underwent exercise study. The exercise PCWP was used to classify patients as having HFpEF (PCWP ≥25 mm Hg) (n=32) or noncardiac dyspnea (PCWP <25 mm Hg) (n=23). At rest, patients with HFpEF had higher resting pulmonary artery pressure and PCWP, although all values fell within normal limits. Exercise-induced elevation in PCWP in HFpEF was confirmed by greater increases in left ventricular end-diastolic pressure and was associated with blunted increases in heart rate, systemic vasodilation, and cardiac output. Exercise-induced pulmonary hypertension was present in 88% of patients with HFpEF and was related principally to elevated PCWP, as pulmonary vascular resistances dropped similarly in both groups. Exercise PCWP and pulmonary artery systolic pressure were highly correlated. An exercise pulmonary artery systolic pressure ≥45 mm Hg identified HFpEF with 96% sensitivity and 95% specificity. Euvolemic patients with exertional dyspnea, normal brain natriuretic peptide, and normal cardiac filling pressures at rest may have markedly abnormal hemodynamic responses during exercise, suggesting that chronic symptoms are related to heart failure. Earlier and more accurate diagnosis using exercise hemodynamics may allow better targeting of interventions to treat and prevent HFpEF progression.

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Author and article information

Journal

Journal ID (nlm-ta): Card Fail Rev

Journal ID (iso-abbrev): Card Fail Rev

Journal ID (publisher-id): CFR

Title: Cardiac Failure Review

Publisher: Radcliffe Cardiology

ISSN (Print): 2057-7540

ISSN (Electronic): 2057-7559

Publication date (Electronic): 09 April 2020

Publication date Collection: March 2020

Volume: 6

Electronic Location Identifier: e05

Affiliations

[1. ] Advanced Heart Failure/Transplantation Programme, Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania Philadelphia, PA, US

[2. ] Department of Medicine, Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania Philadelphia, PA, US

[3. ] Pulmonary Hypertension Programme, Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania Philadelphia, PA, US

Author notes

Disclosure: The authors have no conflicts of interest to declare.

Correspondence: Jeremy A Mazurek, Advanced Heart Failure/Cardiac Transplantation and Pulmonary Hypertension, Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine, South Pavilion, 11th Floor, Suite 11–179, 3400 Civic Center Boulevard, Philadelphia, PA 19104, US. E: jeremy.mazurek@ 123456pennmedicine.upenn.edu

Article

DOI: 10.15420/cfr.2019.09

PMC ID: 7199161

SO-VID: d91d5d65-42de-4ac7-9cef-452995f3a836

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This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

History

Date received : 12 August 2019

Date accepted : 13 December 2019

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Pages: 7

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Pulmonary Hypertension in Heart Failure Patients

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Cardiovascular Innovations and Applications

Most cited references 58

Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial.

Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.

Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction.

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