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

Heart Failure, Diastolic Clinical Trial

— INTERACT-HFpEF  

Official title:

Disclosing Mechanisms of Right Ventricular Adaptation in Patients With Heart Failure With Preserved Ejection Fraction With and Without Pulmonary Hypertension - Insights From Invasive Hemodynamic and Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04154657
• Other study ID #: Interact_HFpEF
• Status: Recruiting
• Phase: N/A
• Start date: February 15, 2020
• Est. completion date: June 2022

Study information

• Verified date: July 2020
• Source: Johann Wolfgang Goethe University Hospital
• Contact: Birgit Assmus, MD
• Phone: +49641985
• Email: birgit.assmus[@]innere.med.uni-giessen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic

Intervention

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

Locations

Country	Name	City	State
Germany	Goethe University Hospital	Frankfurt	Hessen
Germany	University Hospital Justus-Liebig University	Gießen

Sponsors (2)

Lead Sponsor	Collaborator
Johann Wolfgang Goethe University Hospital	University of Giessen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	delta Eed	RV stiffness measured by conductance catheter is reduced alreday in early HFpEF stages	immediate after procedure
Primary	delta RV volume	homeometric followed by teterometric adaptation with consecutive dilation of the RV occurs with disease progression from HFpEF-Non-PH ti ICC-PH_HFpEF to cpc-PH-HFpEFprogressive H, impacting position and motion of the septum with stress	immediate after procedure
Secondary	correlation of delta RV longitudinal strain with Eed	RV longitudinal strain (related to RV EDV) is the best predictor of RV diastolic stiffness (Eed) in HFpEF-PH (correlation analysis)	immediate after procedure
Secondary	delta transmural septal pressure	acute change of the transmural pressure gradients from rest to stress conditions, adversly impacts LV filling	immediate after procedure