Rasputniak O. Pathogenic substantiation of the clinical efficiency of permanent dual chamber pacing in the treatment of hypertrophic obstructive cardiomyopathy.

The left ventricular outfow tract (LV OT) obstruction is an important clinical index of obstructive hypertrophic cardiomyopathy (HCM) patients. The true significance of systolic pressure gradient (SPG) in the LV outflow tract (OT) and functional mitral regurgitation (MR) in hypertrophic cardiomyopathy (HCM) has been controversial. The LVOT gradient was correlated with the systolic anterior motion (SAM) of anterior mitral leaflet. SAM is a primary systolic event in obstructive HCM and a trigger of OT obstruction. The severe SAM and prolonged mitral-septal apposition are known to go not only with substantial OT SPG but also with functional mitral regurgitation. Both the systolic gradient, and mitral regurgitation appear during the moment of systolic pull-up or the anterior mitral leaflet to the hypertrophied basal part interventricular septum (IVS). Yet little is known about the actual SAM mechanism. The mechanism of DDD pacing benefit in obstructive HCM still is not well understood. This thesis is a study of the formation of hemodynamic obstruction of the left ventricular outflow tract (systolic pressure gradient and mitral regurgitation) and application of permanent dual chamber pacing in treatment of hypertrophic obstructive cardiomyopathy. A total of 94 HCM consecutive patients (mean age 31.7±3.2 yrs) underwent the following investigations: ECG with 12 standard leads; phonocardiography, sphygmography; M-mode, two-dimensional and Doppler echocardiography with SPG determination, mitral regurgitation assessment, and short distance (h, cm) between IVS and MV anterior leaflet in systole measurement; cardiac catheterization with direct LVOT SPG measurement. Systolic pressure gradient (SPG) on LV OT in 72 patients was 72.8±9.0 mmHg (range: 30-150 mmHg), in 32 patients SPG on LV OT was < 30 mmHg (mean 13.0±3.3mmHg). Endocardial mapping of LV excitation sequence in relation to His potential registered in the AV node region was performed in 59 patients. 33 patients with LV OT obstruction underwent acute hemodynamic and Echo-Doppler study with temporary AAI and DDD pacing mode with a variable A-V delays. 18 obstructive HCM patients with severe unresponsiveness to medical therapy and with not less than 30% SPG decrease of initial value during temporary pacing test received permanent dual chamber pacemakers. LV activation sequence mapping was performed in a retrograde manner through aorta with the use of a steerable electrophysiological catheter; the process should be correlated with the His potential registered in the AV node region. We compared the LVapex excitation onset time with the same for the hypertrophied part of IVS and calculated the difference in ms (DT) between the LVA excitation initiation and the same for LVOT. Depending on the difference in ms (DT) between the HV intervals in LVA area and in IVS hypertrophied part three groups of patients were determined. In 10 patients there was 10-30 ms previous excitation of the LV apex in relation to the area of hypertrophy of the interventricular septum, in 15 patients there was simultaneous contraction of the LV apex and zone of IVS hypertrophy, and 34 patients had 10-40 ms LV apex activation delay in relation to the area of IVS hypertrophy. It has been established that the most expressed hemodynamic disturbances (LV OT systolic pressure gradient, mitral regurgitation) appeared in patients with the more expressed delay of LV apex (LVA) activation in relation to the IVS hypertrophied area. The development of LV excitation sequence disturbances was accompanied by the signs of LV remodeling (LV posterior wall thickening, lower end-diastolic and end-systolic dimensions indices, lower end-diastolic volume, end-systolic volume and stroke volume indices). In the acute hemodynamic study during temporal DDD pacing 33 patients with LV OT obstruction showed a decrease of SPG and mitral regurgitation immediately after the pre-excitation reached the LVA and lasted till the moment of the loss of atrial input with the wedging of the MV and made over 50% of the initial value. The ultrasound assessment of DDD pacing efficiency in all 18 patients showed both a drop of systolic pressure gradient and a decrease of mitral regurgitation (follow-up from 3 month to 4 years). Conclusions: The LV outflow tract systolic pressure gradient and mitral regurgitation in HOCM are conditioned by the LV activation asynchrony caused by LV apex and papillary muscles activation delay relatively to the hypertrophied part of IVS.The development of LV activation asynchrony is accompanied by LV remodeling in HCM patients.The DDD pacing with optimized AV delay (AVD) modifies the LV apex and papillary muscles activation. The LVA preexcitation with DDD pacing leads to earlier excitation of papillary muscles keeping MV front cusp from floating and intrusion in the LVOT lumen which prevents the occurrence of SAM of the mitral valve at IVS and its consequences-SPG and MR.