Effect of Personalized Accelerated Pacing in Symptomatic Patients With Non-Obstructive Hypertrophic Cardiomyopathy

Change in NT-proBNP concentration from baseline to 3-month follow-up will be summarized by study arm using basic descriptive statistics and subsequently compared between groups. Samples will be obtained by venipuncture and submitted to a local laboratory for analysis. While normal NT-proBNP levels vary by age, the normal threshold for those under 50 years of age is 450 pg/mL, while it is 900 pg/mL for those greater than 50 years of age. Higher than normal NT-proBNP levels may be indicative of heart failure. As part of an exploratory analysis for this trial a \>29% decrease in NT-proBNP concentration from baseline will be considered a "clinically meaningful threshold"

Change in pVO2 and predicted pVO2 from baseline to 3-month follow-up will be measured by cardiopulmonary exercise testing (CPET). CPET is a functional assessment that helps to detect disorders affecting the system involved in oxygen transport and utilization through the analysis of gas exchange during exercise. Change in pVO2 uptake from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios. An increase in pVO2 \>1.5mL/kg/min from baseline will be considered a "clinically meaningful threshold" as part of an exploratory analysis for this trial.

Change in pacemaker-detected atrial arrhythmia burden from baseline to 3-month follow-up will be assessed by interrogation of the pacemaker. Pacemaker-detected data will be continuously collected and stored by the pacemaker. Atrial arrhythmia burden is quantified as the percentage of time per day the patient is in atrial fibrillation (AF). Change in percentage over time will be summarized by study arm using basic descriptive statistics and analyzed by win ratios. Pacemaker-detected arrhythmia burden is associated with more adverse cardiac outcomes including increased risk of stroke or thromboembolism.

Change in pacemaker-detected patient activity levels from baseline to 3-month follow-up will be assessed using the pacemaker's built-in accelerometer. This accelerometer can measure a patient's physical activity levels by detecting the frequency and amplitude of a patient's motion. The device measures the number of hours/minutes the patient is active, based on a threshold for the number and magnitude of accelerometer signal deflections. Change in pacemaker-detected patient activity levels from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios. As part of an exploratory analysis for this trial an increase in pacemaker detected daily activity \>0.5 hour/day from baseline will be considered a "clinically meaningful threshold".

Change in LA strain from baseline to 3-month follow-up will be assessed using TTE. Strain is a measure of deformation of the myocardium during the cardiac cycle in multiple directions; lengthening, shortening and thickening and is expressed as a fractional length change, where shortening is a negative value and lengthening a positive value. The difference between length at the reference point (end-diastole) and the current length (end-systole) will be calculated in accordance with American Society of Echocardiography (ASE) January 2015 guidelines related to strains. This is then divided by original reference length and then expressed as a percentage for the given timepoint. Change in this percentage from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios. LA strain is an earlier marker of underlying cardiovascular pathology than many conventional echocardiographic parameters given the relatively thinner walls of the atria.

Change in LV strain from baseline to 3-month follow-up will be assessed using transthoracic echocardiogram (TTE). Strain is a measure of deformation of the myocardium during the cardiac cycle in multiple directions; lengthening, shortening and thickening and is expressed as a fractional length change, where shortening is a negative value and lengthening a positive value. The difference between length at the reference point (end-diastole) and the current length (end-systole) will be calculated in accordance with (ASE) January 2015 guidelines related to strain. This is then divided by original reference length and then expressed as a percentage for the given timepoint. Change in this percentage from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios. LV Strain can be used for the early detection of left ventricular dysfunction by detecting subtle changes in deformation of heart muscle, which can lead to earlier diagnosis/prognosis.

Change in echocardiographic E/e' ratio from baseline to 3-month follow-up will be assessed using transthoracic echocardiogram (TTE). E/e' ratio is a measure of diastolic function that is calculated by dividing the peak E wave velocity (early filling velocity, or E) by the peak e' wave velocity (or the early relaxation velocity, e') and will be calculated in accordance with (ASE) January 2015 guidelines. Elevated E/e' ratios are a key indicator of left ventricular end-diastolic pressure and, as such, are often used to assess the severity of diastolic dysfunction. Change in E/e' ratios will be summarized by study arm using basic descriptive statistics and analyzed by win ratios.

Change LVMT from baseline to 3-month follow-up will be evaluated using motion-mode echocardiography in accordance with (ASE) January 2015 guidelines. This one-dimensional view allows for digitized, linear measurements of LV thickness in the parasternal long-axis view. Increased LV myocardial wall thickness can lead to Left ventricular hypertrophy (LVH), making it more difficult for the heart to pump blood and increase the risk of unfavorable cardiovascular outcomes. Change in LV myocardial thickness will be summarized by study arm using basic descriptive statistics and analyzed by win ratios.

Change in LA chamber size from baseline to 3-month follow-up will be evaluated using transthoracic echocardiogram (TTE) in accordance with (ASE) January 2015 guidelines. An enlarged left atrium, known as Left Atrial Enlargement (LAE), is a result of increased left atrial pressure over a prolonged period and can be a predictor of clinically significant cardiovascular diseases and heart failure. Change in LA chamber size from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios.

Change in LV chamber size from baseline to 3-month follow-up will be evaluated using transthoracic echocardiogram (TTE) in accordance with (ASE) January 2015 guidelines. An increased left ventricular chamber size is caused by elevated blood pressure over a prolonged period and can lead to Left Ventricular Hypertrophy (LVH) complications of which can lead to heart failure or sudden cardiac death. Change in LV chamber size from baseline will be summarized by study arm using basic descriptive statistics and analyzed by win ratios.