ASPIRE: Arrhythmias in Pulmonary Hypertension Assessed by Continuous Long-term Cardiac Monitoring

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Recruiting

CT.gov ID

NCT04554160

Collaborator

Actelion (Industry)

Enrollment

Location

54.2

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Arrhythmias are considered a prominent phenomenon in pulmonary hypertension (PH) as the disease progresses. According primarily to retrospective studies with up to 24 hours of monitoring, supraventricular tachycardias (SVT) can be found in 8-35% of patients, with significant impact on survival.

Furthermore, a few prospective studies to date deploying short-term monitoring (10 minutes-24 hours) have revealed lower heart rate variability (HRV) in patients with pulmonary arterial hypertension (PAH).

In ASPIRE arrhythmias and heart rate variability is being assessed via long term monitoring.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension Arrhythmias, Cardiac Heart Rate Variability	Device: Loop recorder implantation

Detailed Description

In general there is a lack of evidence of the arrhythmic burden in PH. The present study is the first to apply continuous long-term cardiac monitoring in patients with PH to describe the prevalence of arrhythmias in PH by continuous long-term cardiac monitoring. Furthermore, the correlation between heart rate variability and risk assessment parameters including WHO functional class (FC), NT-proBNP, 6MWT, cardiac parameters and cardiac function will be studies.

A few prospective studies have demonstrated lower HRV in PH than in healthy individuals, however only based on short-term monitoring (20 minutes to 24 hour) and only in a few patients. In retrospective studies, a higher mortality in children with PAH and low HRV has been shown with 24 hour Holter monitoring. Consequently, there is a lack of evidence regarding right heart failure and the prognostic value of HRV.

Risk assessment in PH is essential in the selection of treatment in PH and for prognosis in the study ASPIRE the investigators will assess the use of heart rate variability in pulmonary hypertension.

In conclusion the ASPIRE study will:

Assess the incidence and prevalence of arrhythmias using long term cardiac monitoring via a reveal LINQ loop recorder (Medtronic). Furthermore, the investigators will assess; Change in cardiac index, right atrial size, RV size, fibrosis and stroke volume.
The investigators will assess the arrhythmic burden in relation to:

Change in 6 MWT
Hemodynamic changes with RHC
Hemodynamic changes in echocardiography
The number of patients progressing one FC (Modified NYHA class)
Changes in NT-proBNP.
Hospital admission for any reason
Death or transplantation

Monitor heart rate variability and address a comparison to known risk markers and CMR and echocardiography.

The study specifically seeks to investigate following:

The incidence and type of supraventricular and ventricular arrhythmias in PH by continuous long-term monitoring
The predictive value of both right and left ventricular cardiac magnetic resonance (CMR) imaging parameters for arrhythmogenesis in PAH, heart rate variability, and heart rate.
Optimization of specific therapy in PAH using continuous long-term arrhythmia monitoring

Study Design

Study Type:

Observational

Anticipated Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

ArrhythmiaS in Pulmonary arterIal hypeRtEnsion and Right Heart Failure Assessed by Continuous Long-term Cardiac Monitoring

Actual Study Start Date :

Sep 24, 2018

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Outcome Measures

Primary Outcome Measures

The incidence and prevalence of arrhythmias in pulmonary hypertension [2022]
Assessed throughout continuous cardiac monitoring
Heart rate variability [2022]
Throughout continuous cardiac monitoring heart rate variability will be assessed as a clinical marker. It will be compared with already known clinical markers in pulmonary hypertension and compared with echocardiography and cardiac MR scans.
Arrhythmias and their impact on heart function assessed with echocardiography [2022]
Change in function of the right and left heart chambers in the patients' with and without arrhythmias assessed with echocardiography.
Heart rate variability and heart function assessed with CMR scans. [2022]
The patients' heart rate variability will be compared to the function of the right and left ventricle (LVEF, RVEF)
Heart rate variability and chamber sizes assessed CMR scans [2022]
The patients' heart rate variability will be compared to the size of the right and left ventricle (ml)
Change in heart function when having arrhythmias, assessed with CMR scans. [2022]
The patients' arrhythmic burden will be compared to the function of the right and left ventricle (LVEF, RVEF)
Heart size in the group with and without arrhythmias, assessed with CMR scans. [2022]
The patients' arrhythmic burden will be compared to the size of the right and left ventricle (ml).
Chamber sizes in patients with and without arrhythmias assessed with echocardiography. [2022]
Change in echocardiography parameters assess by the size of the right and left heart chambers (ml and cm2) in the patients with and without arrhythmias.

Secondary Outcome Measures

Arrhythmias and their impact on WHO functional class [2022]
Modified WHO functional class when having arrhythmias

Other Outcome Measures

Arrhythmias and their impact on death or transplantation [2022]
Do any patients die because of the arrhythmias and will any patients need a transplantation because of terminal PH and arrhythmias.
Arrhythmias impact on specific PAH therapy [2022]
How many patients will need escalation in PAH therapy when having arrhythmia and how much of an increase.
Arrhythmias impact on six minute walking tests [2022]
Arrhythmias impact on reduction in number of meters performed in a six minute walking test during the study period.
Arrhythmias and their impact on NT-proBNP [2022]
NT-proBNP change during the study period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Inclusion Criteria:

Pulmonary hypertension patients >18 years of age
Voluntary participation after giving informed verbal and written consent
Patients naïve to PAH-specific treatments
Patients on current PAH specific medication independent of duration of therapy
Patients can be in WHO group 1 classified by one of the following subgroups:
Idiopathic pulmonary arterial hypertension (IPAH)
Heritable pulmonary arterial hypertension (HPAH)
Drugs and toxins
Associated with (APAH): specifically, connective tissue disease (CTD), HIV infection and congenital heart disease
Diagnosis of PAH confirmed by right heart catheterization
WHO/NYHA functional class II to IV symptoms
6MWT distances of ≥50 meters and within 15% of each other on 2 consecutive tests preferably performed on different days during Screening.

Exclusion Criteria:

Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction at Screening: BMI >30 kg/m2; diabetes mellitus of any type; systemic hypertension, significant coronary artery disease; or left atrial volume index (LAVi)

30 mL/m2.

Evidence or history of left-sided heart disease and/or clinically significant cardiac disease.
Acutely decompensated heart failure within 30 days prior to Screening
Evidence of significant parenchymal lung disease
Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (SBP) >160 mmHg or sitting diastolic blood pressure (DBP) >100 mmHg at Screening. • Systolic blood pressure >160 mmHg or < 90 mmHg; or diastolic blood pressure > 100 mgHg at Screening
Male subjects with a corrected QT interval using Fridericia's formula (QTcF) >450 msec, and female subjects with QTcF >470 msec on ECG measured at Screening or Baseline.
Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or that would confound study analysis or impair study participation or cooperation