paced dyssynchrony and myocardial perfusion in apical hcm

Conditions: Hypertrophic Cardiomyopathy

Summary: hypertrophic cardiomyopathy (hcm) is the most common inherited heart disease. a relatively common subgroup of hcm patients have apical hcm - a type of heart muscle disease that causes abnormal muscle thickening towards the tip (apex) of the heart. this can impair the heart's own blood flow through the thickened heart muscle. we think this is one of the causes for symptoms such as shortness of breath and chest pain. if medications are ineffective at treating symptoms, there are few further options available, limited to invasive heart surgery. this study aims to determine if it is possible to improve the blood flow within by altering the settings of patients' permanent pacemakers, dynamic microvascular obstruction is an important cause of perfusion abnormalities in hcm and whether introducing localized dyssynchrony with ventricular pacing improves this. this phased study will include patients with apical hcm that already have implanted pacemaker devices to remove risks associated with device implantation. the study may provide insights into novel mechanisms for symptoms in hcm and provide new methods for treating a patient group in whom therapeutic options can be extremely limited.

the treatments for people with apical hcm and symptoms are limited but include medicines. the use of a pacemaker in this situation is an experimental treatment which has not yet been fully explored. we believe symptoms are linked with abnormalities in blood flow through the heart muscle at the tip / apex of the heart and wish to see if using a pacemaker can improve such abnormalities. we want to test if this treatment works using a clinical trial to help us decide whether this is a viable treatment option that may be offered to other patients with the condition. the null hypothesis states that there will be no difference in blood flow through the heart muscle with pacing. the alternative hypothesis states that there will be a significant difference in blood flow through the heart muscle with pacing. this was chosen based upon our current knowledge that abnormal blood flow in the heart muscle in apical hcm is linked with abnormal squeeze at the apex / tip and symptoms. echocardiography pilot data has demonstrated a reduction in squeeze at the apex of the heart when using the pacemaker to cause the heart muscle to contract in a different way. our alternative hypothesis therefore is that we can use the pacemaker to reduce squeeze at the apex and improve blood flow through the heart muscle. this is a single centre, prospective pilot study. because data on acute changes in perfusion with pacing in apical hcm are extremely limited, the most ethical methodology is to perform a two-phase study. phase a of the study assesses acute changes in blood flow through the heart muscle during different pacemaker settings (active and back-up), looking for potential efficacy of the intervention. secondary outcomes of phase a include recruitment rate and proportion of patients willing to proceed to phase b. phase b of the study consists of entering those same patients into a randomised double-blind cross-over 6-month follow-up pilot to collect baseline statistical data and assess acceptability of study protocol to design a future study. here, assessment of further secondary outcomes will allow establishment of baseline statistical data for the design of an outcomes-based clinical trial. patients will only be entered into phase b of the study if an improvement is seen in myocardial perfusion with pacing during phase a.

Eligibility criteria:
inclusion criteria: 1. male or female, \>18 years. 2. hcm patients with apical hcm defined as apical hypertrophy with apical lv systolic obliteration and the presence of characteristic ecg changes. participants with a mixed cardiac phenotype will be considered if they also meet these criteria and do not have resting outflow tract obstruction. 3. a programmable intracardiac pacing device with a right atrial lead and an apically / low septal located right ventricular lead. 4. willing and able to provide informed consent. exclusion criteria: 1. outflow tract obstruction \>50 mmhg at rest due to systolic anterior mitral movement. 2. evidence of high-grade heart block. 3. moderate or severe primary valvular disease. 4. unrevascularised, known, significant coronary disease: the significance of any known coronary disease will be determined after discussion with an independent clinician. 5. atrial fibrillation at the time of randomisation. 6. inability to undergo cmr with adenosine stress and gadolinium contrast imaging. 7. pregnancy.

Keywords: apical hypertrophic cardiomyopathy pacemaker perfusion