Arrhythmias in Pulmonary Hypertension
Research type
Research Study
Full title
Investigation into conductive and arrhythmogenic properties of the right atrium and ventricle in patients with pulmonary hypertension
IRAS ID
273093
Contact name
Claire Martin
Contact email
Sponsor organisation
Royal Papworth Hospital NHS Foundation Trust
Clinicaltrials.gov Identifier
P02594, Papworth Study number
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Research Summary
Pulmonary Hypertension (PH) is a common and important clinical condition with a significant degree of associated morbidity and mortality. Much of this is due to the high incidence of cardiac arrhythmias in these patients, the presence of which have been shown to correlate with worse prognosis.
Very little is understood about the mechanisms underlying these arrhythmias however. We plan to study the heart muscle conduction characteristics of patients with PH undergoing ablation procedures as part of their clinical care. Firstly, using wires (catheters) inserted peripherally via the femoral vein and passed up to the heart we can create a 3 dimensional map of the heart using specialised software. These catheters are also capable of measuring local electrical activation in heart tissue with which they are in contact. We can thus create a model of electrical activation and map areas of scar in the heart chambers of interest.
Secondly, a group of PH patients undergoing MRI scans of the heart for clinical purposes will be identified for non-invasive mapping using novel Electrocardiographic Imaging (ECGI) technology. This involves wearing a multi-electrode vest for the duration of the MRI scan and a short period before or after. Using anatomical information gleaned from the scan and electrical information gleaned from the multi-electrode vest a similar 3 dimensional map of the heart can be created without the need for invasive catheter manipulation.
By identifying and characterising arrhythmia mechanisms in patients with PH we hope to better understand how these arrhythmias arise, how they correlate to prognosis and how to target therapy appropriately.
Lay summary of study results
Background Raised blood pressure in the lungs, known as pulmonary arterial hypertension (PAH), affects about 1 in 100 people. One of the consequences of this condition is to increase strain on the right sided chambers of the heart, which are responsible for pumping blood to the lungs.
Eventually this can lead to weakening and stretching of the heart muscle much like a balloon being overinflated, resulting in pump failure and generation of heart rhythm abnormalities (arrhythmias).Arrhythmias can cause the heart to beat less efficiently. Patients with PAH are more vulnerable and sensitive to arrhythmias, and their presence has been shown to correlate with worse prognosis. Furthermore, PAH patients can often be intolerant of some of the main medications used to treat arrhythmias. Waiting to treat these arrhythmias until after they have become clinically manifest therefore can lead to significant illness and poor quality of life.
Aim of the research
Very little is understood about the mechanisms underlying arrhythmias in PAH patients. By identifying and characterising this we hope to better understand how arrhythmias arise, how they correlate to prognosis and how to target therapy appropriately.In a cross-sectional study, we quantified the speed of electrical impulse conduction, scar burden, and size and function of the right heart chambers in a group of patients with PAH. In one group of patients this was done invasively, with wires inserted in a blood vessel in the groin and passed up to the heart. These are used to create a 3-dimensional map of the heart and gather information on electrical conduction and scar using specialised software. From this, a model of electrical activation and areas of scar can be mapped in the heart chambers.
In a second group, the electrical activation was measured non-invasively using a 256-electrode vest worn around the torso. This was coupled to a 3-dimensional map of the heart acquired via magnetic resonance imaging (MRI). Patients in this group were monitored over a two-year period to see if they experienced any heart rhythm problems
An informal pre-study patient survey was favourable for the rationale and design of the trial.
What’s new?
10 PAH patients from a specialist Pulmonary Hypertension centre in Cambridge underwent invasive mapping and 30 underwent non-invasive mapping. The majority of patients were female with an average age of 58 years. 11 (36.7%) of the patients undergoing non-invasive mapping suffered an arrhythmia during follow up.
The study found that:
• Patients with dilatation of the top chamber of the heart (the right atrium) were more prone to arrhythmia.
• Dilatation was associated with disordered electrical activity in the right atrium, specifically:
o slower conduction of electrical impulses across the atrium
o slower transmission of impulses through the atrium into the bottom chamber of the heart (the right ventricle)
• Right atrial size was not directly related to severity of pulmonary hypertension.Why is this important?
The findings identify right atrial dilatation as a potential predictor of arrhythmia incidence and present a plausible mechanism for how arrhythmias may occur. The research team expect this to influence risk stratification for patients with PAH, and may identify a subgroup of patients in whom more active screening for arrhythmia may be beneficial.What’s next?
Research into this area is ongoing. The initial study was carried out in a small number of patients, and the team are exploring expanding this into all subgroups of pulmonary hypertension to determine whether this finding is translatable across the disease spectrum.
Further research may aim to find out whether reducing right atrial size reverses the electrical changes identified and restore arrhythmia risk to normal.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
20/EE/0177
Date of REC Opinion
29 Jul 2020
REC opinion
Favourable Opinion