Association of Septal Myectomy With Quality of Life in Patients With Left Ventricular Outflow Tract Obstruction From Hypertrophic Cardiomyopathy

This cohort study assesses the association of septal myectomy with quality of life in patients with left ventricular outflow tract obstruction from hypertrophic cardiomyopathy.


172
There are no specific benefits to the patient. 173

174
The primary aim of this study is to examine change in quality of life as measured by the 175 KCCQ following septal myectomy in patients with obstructive hypertrophic cardiomyopathy as 176 compared to prior to surgery. Secondary aims include the assessing change in functional 177 capacity utilizing six-minute walk test distance, and quality of life as measured by the PROMIS 178 and DASI following septal myectomy in patients with obstructive hypertrophic cardiomyopathy 179 as compared to prior to surgery. The aim of the substudy is to examine change in exercise 180 capacity by cardiometabolic exercise testing in a subset of patients who underwent 181 cardiometabolic exercise testing prior to septal myectomy as part of their routine clinical care. 182 The study will be powered to detect a mild change in Kansas City Cardiomyopathy 183 Questionnaire summary score since this disease-specific health-related quality of life 184 assessment tool has been well studied and changes in clinical status have been validated within 185 a heart failure population. A substudy will also be powered to detect an absolute increase in 186 peak oxygen uptake on cardiometabolic exercise testing. Additional secondary end-points will 187 include change in score on the • A medical history will be obtained including a complete family history 236 • A limited physical examination will be performed including heart rate and blood pressure 237 • Results of testing prior to septal myectomy available at the baseline visit will be recorded 238 including ECG, exercise testing, Holter monitoring, and echocardiography. 239 • ECG and echocardiography per standard of care at follow up visits 240 241 •

Study-specific Testing 242
Six-minute walk test at baseline and follow-up visit 243

Quality of Life Assessments (KCCQ, PROMIS, and DASI) at baseline and follow-up visit 244
Cardiometabolic exercise testing at follow up in the substudy patients who had undergone 245 cardiometabolic exercise testing prior to septal myectomy as part of their routine care 246 247

248
Compensation for parking for required visits for the study protocol will be compensated. 249 Patients enrolled in the substudy may also receive compensation for a meal on the day 250 of the cardiometabolic stress test. Testing performed outside of the scope of normal 251 clinical practice including 6-minute walk test and quality of life assessments (KCCQ, 252 PROMIS and DASI) at baseline and follow up visit, and cardiometabolic exercise testing 253 at follow up visit in the substudy will be covered in full by the study. 254 6 STUDY SCHEDULE 255 6.1 Screening 256 Informed consent must be obtained by a member of the study team prior to any study-related 257 procedures. Patient's medical records will be reviewed to be certain of diagnosis and eligibility. 258 Patients will be identified for eligibility for the substudy evaluating change in performance on 259 cardiometabolic exercise testing simultaneously. 260 261

263
Initial encounter for the research protocol will involve a six-minute walk test and quality of life 264 assessments prior to septal myectomy. Clinical data regarding the baseline visit (history,  265 physical exam, echocardiogram, cardiometabolic stress test, etc) will be obtained by the 266 individual physician per standard of care. 267

268
Follow up visit will be scheduled at a mean of 12±6 months post-septal myectomy for a six-269 minute walk test and quality of life assessments will be administered for a second time. For the 270 subset of patients who underwent cardiometabolic exercise testing prior to septal myectomy 271 who are enrolled in the substudy, they will undergo repeat cardiometabolic exercise testing 272 again at this point. Post-operative clinical follow up data will be obtained from the outpatient visit 273 per standard of care, and data collection regarding outcomes (atrial fibrillation, stroke, ICD 274 discharge etc.) will terminate at the time of the follow up visit. 275 For the substudy, assuming an average maximal oxygen uptake (peak VO2) of 19.4 ± 6.4 317 ml/kg/min based on prior studies in patients with obstructive hypertrophic cardiomyopathy prior 318

ASSESSMENT OF OUTCOME MEASURES
to septal myectomy (20) and an alpha error rate of 5%, 32 patients provides over 90% power to 319 detect an absolute change of 2 ml/kg/min. An additional 3 patients (35 total) will be enrolled in 320 the substudy to compensate for an absolute dropout rate of 10%. 321

Participant Enrollment and Follow-Up
322 175 patients will be followed through follow up visit at 12±6 months post-septal myectomy. 323

324
Overall statistical analysis should be straightforward and involve paired t-tests comparing the 325 change in scores on quality of life assessments, and distance walked on six-minute walk tests. 326 Additionally the incidence of other outcomes including atrial fibrillation, hospitalization for heart 327 failure, repeat septal myectomy, sudden cardiac death or appropriate ICD discharge will be 328 noted. For patients in the substudy, paired t-tests will also be used to compare peak oxygen 329 uptake prior to and following septal myectomy. Additional analyses examining the correlation of 330 scores on various quality of life assessments to performance on exercise testing as measured 331 by distance walked on six-minute walk test and peak oxygen uptake in the substudy patients 332 may also yield valuable information regarding the performance of these assessments in the 333 HCM population. 334 335 9 DATA HANDLING AND RECORD KEEPING 336 9.1 Data Capture Methods

337
All clinical and intake data will be captured on electronic data collection forms (RedCap). 338