The Effect of CRT on the Frank Starling Mechanism

The investigators are examining a scientific principle called the Frank Starling Mechanism and how it relates to Cardiac Resynchronisation Therapy (CRT), a form of pacemaker therapy used in the treatment of heart failure.

The Frank Starling Mechanism is an established biological principle. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction, when all other factors remain constant. In other words, the law states that the more blood enters the heart, the more blood is pumped out of the heart with any given beat.

There is some evidence that in some patients with chronic heart conditions, the Frank Starling Mechanism is LESS EFFECTIVE, meaning that the heart is less able to cope with a reduction in heart pumping function over time. There is also evidence that treatment with CRT may IMPROVE the Frank Starling Mechanism - evidence for this has been shown in dog and mice hearts, however, has never been shown in humans.

The investigators aim to conduct a study where subjects undergo an ultrasound scan of the heart (echocardiogram) whilst the participants pacemaker settings are temporarily changed. This allows the investigators to measure the pumping function of the heart as more blood enters the heart. The investigators will perform this test on 20 participants before and after CRT, as well as 20 participants who have pacemakers, but no heart failure. This study aims to test 3 hypotheses.

1. In participants with pacemakers, a REDUCED Frank Starling Mechanism predicts which participants go on to develop heart failure.
2. Treatment with CRT IMPROVES the Frank Starling Mechanism in participants with pacemakers and heart failure.
3. The degree of improvement of the Frank Starling Mechanism after treatment with CRT predicts which participants will respond to this treatment.

The primary research investigation in this study is a non-invasive test of the Frank Starling mechanism, which involves performing a transthoracic echocardiogram (ultrasound scan of the heart) whilst temporarily changing pacemaker settings to mimic conditions such as faster heart rates or increased blood flow to the heart. Measurements taken from the echocardiogram during these changes in pacemaker settings will be used to determine the effectiveness of the heart's Starling Mechanism. This test will last between 20-40 minutes. No special preparation is needed and participants will be able to go home immediately afterwards. Pacemaker settings will be returned to normal once the test is completed.

Eligibility Criteria:
Inclusion Criteria:

* • Ability to provide informed consent to participate and willing to comply with the clinical investigation plan and follow-up schedule.

  * Existing dual chamber pacemaker or ICD including atrial lead and RV lead.
  * RV pacing percentage \>40%.
  * CRT group - Severe left ventricular systolic impairment (LVEF≤35%). Clinical symptoms of heart failure despite optimum medical therapy (NYHA class II-IV).
  * Control group - LVEF \>50%.

Exclusion Criteria:

* • Previous treated with CRT (existing LV lead/His-Bundle lead/Left Bundle Branch Area lead).

  * Persistent atrial fibrillation
  * Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
  * Participation in other studies with active treatment / investigational arm