Mechanisms of Right Ventricular Adaptation in Patients With Heart Failure With Preserved Ejection Fraction

NCT ID: NCT04154657

Last Updated: 2020-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-15
• Study Completion Date: 2022-06-30

Brief Summary

Biventricular PV-loop studies and advanced imaging to assess left-to-right ventricular interaction in HFpEF: In a group of 30 HFpEF patients with clinical indication for LH/RH catheter investigation, we will perform biventricular PV loop assessment in combination with extensive imaging (MRI, echo) for in-depth analysis of left-to-right ventricular interaction in the different HFpEF categories, both under baseline and stress (volume challenge and exercise) conditions.

Detailed Description

The right ventricle is the main determinant of prognosis in pulmonary hypertension . The response of the right ventricle to the structural alterations and increasing afterload in the pulmonary circulation is a complex process. The interplay between neuroendocrine and paracrine signalling and increased afterload may lead to myocardial ischemia and inflammation, resulting in loss of myocytes, myocardial fibrosis and RV-arterial uncoupling. Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (HFpEF-PH) is a frequent complication which is associated with impaired prognosis. HFpEF-PH is defined by a high mean pulmonary artery pressure (> 20 mm Hg), high left ventricular end-diastolic pressure (LVEDP > 15 mm Hg) and a normal systolic left ventricular function with impaired diastolic function. However, not all HFpEF patients develop pulmonary vascular remodelling with a high transpulmonary pressure gradient, and increased pulmonary vascular resistance leading to adverse right ventricular remodelling. Ageing, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, including obesity, diabetes and hypertension, are recognized as clinical risk factors for HFpEF-PH. A main and emerging question in that context is the interplay between the right and left ventricle in HFpEF-PH, and whether diastolic left ventricular failure is the driving force of the hemodynamic and right ventricular functional changes. Recent studies have shown that HFpEF-PH patients demonstrate haemodynamic limitations during exercise, including impaired recruitment of LV preload due to excessive right heart congestion and blunted RV systolic reserve compared to HFpEF without PH . However, up to now, no data exist about the mechanism of interplay between RV, LV and pulmonary haemodynamics in HFpEF and HFpEF-PH. Whereas in patients with HFpEF, PV loop analysis has demonstrated that increased end-diastolic pressure at rest is associated with higher end-diastolic stiffness, and a consistently upwards and leftwards shifted pressure volume relationship during exercise and volume challenge, Gortner et al suggest that reduced LV preload (measured by LV transmural pressure gradient) due to excessive RV congestion, is a major driver for reduced cardiac output in HFpEF-PH. However, preliminary own data in 21 patients with HFpEF demonstrate a more complex relationship with approximately one third of patients not showing an increase of (RV and LV ) end-diastolic pressure volume relation during exercise.

Thus, a simultaneous PV loop-catheterization of LV and RV, in addition to right heart catheter, would therefore provide an enormous gain of knowledge about the interaction of RV and LV and would contribute to a better understanding of the pathophysiology of HFpEF-PH and HFpEF.

Conditions

Heart Failure, Diastolic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

biventricular conductance catheter

patients with indication for invasive assessment receive right and left heart catheter and parallel biventricular conductance catheter at rest and stress

Group Type: EXPERIMENTAL

conductance catheter measurement

Intervention Type: PROCEDURE

biventricular parallel conductance catheter measurement at rest and stress conditions, + CMR at rest and stress

Interventions

conductance catheter measurement

biventricular parallel conductance catheter measurement at rest and stress conditions, + CMR at rest and stress

Intervention Type: PROCEDURE

Other Intervention Names

pressure volume loop catheter measurement

Eligibility Criteria

Inclusion Criteria

Diagnosis of HFpEF as follows

• Heart failure NYHA II or NYHA III
• LVEF ≥ 50%
• HFA-PEFF score ≥ 5 OR HFA-PEFF score 2-4 with one of the following criteria:
• baseline PCWP ≥ 15 mm Hg OR PCWP increase ≥ 10 mm Hg with exercise (~20 Watt)
• stable medical therapy for last 4 weeks

Exclusion Criteria

• Significant coronary stenosis > 50% or valvular heart disease requiring intervention
• coronary or cardiac valvular intervention < 3 months
• uncontrolled rate of atrial fibrillation
• Severe chronic kidney disease (MDRD eGFR < 30 ml/min)
• Life expectancy < 12 months
• Contraindication to MRI or other planned investigations

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Giessen

OTHER

Sponsor Role: collaborator

Johann Wolfgang Goethe University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Birgit Assmus

Director Heart Failure Department, Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Goethe University Hospital

Frankfurt am Main, Hesse, Germany

Site Status: RECRUITING

University Hospital Justus-Liebig University

Giessen, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Birgit Assmus, MD

Role: CONTACT

birgit.assmus@innere.med.uni-giessen.de

+49641985 ext. 42637

Khodr Tello, MD

Role: CONTACT

khodr.tello@innere.med.uni-giessen.de

+49641985 ext. 56087

Facility Contacts

Eike Nagel, MD

Role: primary

eike.nagel@kgu.de

+49696301 ext. 84491

Valentina M Puntmann, MD

Role: backup

valentina.puntmann@kgu.de

+49696301 ext. 84491

Birgit Assmus, MD

Role: primary

birgit.assmus@innere.med.uni-giessen.de

+49 641 985 ext. 42637

Khodr Tello, MD

Role: backup

khodr.tello@innere.med.uni-giessen.de

+49 641 985 ext. 56087

Other Identifiers

Interact_HFpEF

Identifier Type: -

Identifier Source: org_study_id