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.

Currently the the loop-recorder is considered the gold standard for long-term continuous cardiac montoring. A non-invasive continuous monitoring could be of a great benefit for the patients, and could potentially contribute to treatment optimization.

The study will assess apple watches as a non-invasive tool compared to to the loop recorder, which is considered as the current gold standard.

Additionally, the study seeks to assess apple watches for monitoring as an independent wearable for risk assessment in PH.

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:

1. 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.

2. 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

3. 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

4. Monitor patients using smart watches (apple watches) to evaluate the applicability of long-term monitoring via apple watches in patients with pulmonary hypertension for irsk asessment.

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
  • Patients with chronic thromboembolic pulmonary hypertension
  • 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

Patients diagnosed with pulmonary hypertension:

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