Right-to-Left Ventricular Diastolic Delay in Chronic Thromboembolic Pulmonary Hypertension Is Associated With Activation Delay and Action Potential Prolongation in Right Ventricle

Abstract

Background-Delayed left ventricle (LV)-to-right ventricle (RV) peak shortening results in cardiac output reduction in patients with chronic thromboembolic hypertension (CTEPH) and other types of pulmonary arterial hypertension. Why the synchrony between LV and RV is lost is unknown. We hypothesized that RV electrophysiological remodeling, notably, conduction slowing and action potential prolongation, contribute to this loss in synchrony. Methods and Results-We conducted epicardial mapping during pulmonary endarterectomy in 26 patients with CTEPH and compared these findings with clinical, hemodynamic, and echocardiographic variables. We consecutively placed a multielectrode grid on the epicardium of the RV free wall and LV lateral wall. These regions corresponded to RV and LV areas where echocardiographic Doppler sample volumes were placed to measure RV-to-LV diastolic interventricular delay. RV and LV epicardial action potential duration was assessed by measuring activation-recovery interval. Onset of diastolic relaxation of RV free wall with respect to LV lateral wall (diastolic interventricular delay) was delayed by 38Ϯ31 ms in patients with CTEPH versus Ϫ12Ϯ13 ms in control subjects (PϽ0.001), because, in patients with CTEPH, RV completed electric activation later than LV (65Ϯ20 versus 44Ϯ7 ms, PϽ0.001) and epicardial action potential duration, as assessed by activation-recovery interval measurement, was longer in RV free wall than in LV lateral wall (253Ϯ29 versus 240Ϯ22 ms, PϽ0.001). Conclusion-Additive effects of electrophysiological changes in RV, notably, conduction slowing and action potential prolongation, assessed by epicardial activation-recovery interval, contribute to diastolic interventricular delay in patients with CTEPH. (Circ Arrhythmia Electrophysiol. 2009;2:555-561.)

Impaired Left Ventricular Mechanics in Pulmonary Arterial Hypertension

“…Other groups have also noted similar findings of LV diastolic dysfunction in patients with PAH, as demonstrated by impaired LV relaxation. 30 Proposed mechanisms include an early diastolic left-to-right septal displacement with reduced LV compliance, 39,40 decreased LV torsion with delayed diastolic untwisting, 18 increased RV tension leading to prolonged myocardial shortening with impairment of RV systole and LV diastole, 19,41 RV conduction slowing and action potential prolongation with resultant ventricular dyssynchrony and diastolic delay, 42 and impaired LV filling through preload reduction. 43 Indeed, patients tended to have a reduction in the early peak diastolic tissue velocities of the mitral annulus (E), although neither E′ velocity nor E/E′ ratio was different between those with or without severe LV systolic strain reduction.…”

“…dyssynchrony and diastolic delay, 42 and impaired LV filling through preload reduction. 43 Indeed, patients tended to have a reduction in the early peak diastolic tissue velocities of the mitral annulus (E), although neither E′ velocity nor E/E′ ratio was different between those with or without severe LV systolic strain reduction.…”

Is Cardiac Resynchronization Therapy for Right Ventricular Failure in Pulmonary Arterial Hypertension of Benefit?

“…TDI echocardiography in these patients revealed that mechanical diastolic interventricular delay correlated with the RV to LV activation delay. 25 This evidence underscores the importance of electrophysiologic remodeling and its role in undermining electromechanical coupling and promoting disturbances due to anisotropic conduction, even in instances in which the surface ECG does not indicate gross conduction delay.…”

“…As noted above, epicardial mapping in patients with chronic thromboembolic pulmonary hypertension has demonstrated delayed activation of the RV free wall compared with the LV lateral wall. 25 Studies in both MRI and TDI echocardiography have revealed RV delay to peak strain compared with the LV in patients with pulmonary hypertension. 37 MRI strain imaging suggests that this delay in RV peak strain represents a functionally unproductive RV postsystolic isovolumetric contraction period that is followed by a normal relaxation phase.…”

“…The RV was also found to complete activation and repolarization later than the LV in these patients. 24 Hardziyenka et al 25 performed epicardial mapping in a similar group of patients undergoing pulmonary endarterectomy and showed that epicardial activation was later in the RV free wall than LV lateral wall due to significantly slower longitudinal and transverse conduction velocities in the RV. TDI echocardiography in these patients revealed that mechanical diastolic interventricular delay correlated with the RV to LV activation delay.…”