Hypertrophic Obstructive Cardiomyopathy (HOCM) is an inherited cardiac condition which causes the heart muscle to become abnormally thick causing obstruction of blood flow in the heart. This causes debilitating symptoms including shortness of breath, blackouts and chest pain. Current treatments are not ideal as the medication is often poorly tolerated or ineffective.

People with HOCM can often have an Implantable Cardioverter Defibrillator (ICD) to shock them out of dangerous arrhythmias. ICD's can also be used as pacemakers and are a promising treatment option, since they can alter the sequence of the heart muscle contraction thereby relieving the obstruction to the blood flow, making it easier for the heart to pump.

The study will recruit patients who already have an ICD/pacemaker or who are scheduled to have an ICD / pacemaker implanted. For patients who are due to have a device implanted high precision haemodynamic, echocardiographic and electrical measurement techniques will be used to assess whether adjusting the position of the pacing lead (at the time of implant) can bring about changes in LVOT gradient and blood pressure. These patients with a new device and also patients who already have a device in situ will then go on to have atrioventricular delay (AV Delay) optimisation so we can assess what the optimum AV delay should be programmed at in order to bring about the most improvement in LVOT gradient and blood pressure.

Patients will then be recruited into a medium term double blinded randomised crossover study. They will have optimum RV pacing settings turned on for 3 months. They will then return and be crossed over and have optimum RV pacing turned off for a further 3 months. The primary outcome will be to see if optimum RV pacing being turned on is effective in improving symptoms and quality of life.

1. To test the impact of changing the pacing site and how it affects intra-ventricular delay and the amount of dyssynchrony.

   At the time of device implant, the RV lead will be positioned temporarily in the RV apex, low septum, high septum, RV free wall and coronary sinus. Non-invasive blood pressure will be measured by a Finometer device and Echo will assess LVOT gradient whilst pacing is turned on at each site. Ultra-high frequency ECG will be used to assess intraventricular dyssynchrony at each site. Haemodynamic measurements will also be made of aortic pressure and flow using a Combowire (with temporary heparinisation) to assess if non-invasively measured beat-by-beat finometer blood pressure are consistent with invasively measured changes in aortic flow. Combining these measurements will further assess the relationship between level of dyssynchrony, blood pressure and LVOT gradient change. The RV lead will then be implanted in a conventional position.

2. To use high-precision techniques to assess the impact of adjusting the AV Delay and how it affects blood pressure and LVOT gradient change.

   After patients have had their device implanted & those patients who already have a device in situ will then undergo an AV optimisation protocol (paced alternations of AV delay will be made from 40ms in 40ms increments up to 200ms / fusion). Non-invasive blood pressure will be measured (using a Finometer) along with LVOT gradient change with Echo at each AV delay and allow to identify the optimum AV Delay that brings about the most benefit in these acute parameters.

3. To follow patients over a period of 6 months in a double blinded randomised crossover trial. Patients will have active optimum RV pacing for 3 months. After this point they will then be crossed over for a further 3 months to optimum RV pacing off. Patient and assessor will remain blinded throughout. Patients will have the following assessed at baseline, 3 months and then at 6 months:

   • A symptom questionnaire (Kansas City Questionnaire + EQ5D5L Questionnaire). A smart phone symptom application will also record their daily symptoms during the 6 months follow up.
   • A blood test for BNP
   • A 6 Minute Walk Test & Cardiopulmonary Exercise test (MVOT)
   • An Echo scan
   • Device interrogation

Through simulation of a mixed-effects model to analyse the cross-over design, 60 patients would provide approximately 83% power.

Inclusion criteria:

• All patients will have a clinical diagnosis of HOCM with an LVOT gradient of at least 30 mmHg, at rest or provoked.
• Symptomatic patients
• Can have co-existing mid-cavity obstruction.
• HOCM patients referred for Dual Chamber Pacemaker / ICD Implantation.
• Adults willing to take part (ages 18 - 100 years old)
• Able to give consent.

Exclusion criteria:

• Unable to give consent
• Children age < 18 years or adults > 100 years old
• Pregnant patient
• Patients with persistent Atrial Fibrillation or high grade Atrio-Ventricular Block