View metadata, citation and similar papers at core.ac.uk brought to you by CORE Journal of the American College of Cardiology providedVol. by Elsevier 42, No. - 3,Publisher 2003 Connector © 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00 Published by Elsevier Inc. doi:10.1016/S0735-1097(03)00709-5 Cardiac Resynchronization Therapy Can Reverse Abnormal Myocardial Strain Distribution in Patients With Heart Failure and Left Bundle Branch Block Ole-A. Breithardt, MD,*† Christoph Stellbrink, MD, FESC,* Lieven Herbots, MD,† Piet Claus, PHD,† Anil M. Sinha, MD,* Bart Bijnens, PHD,† Peter Hanrath, MD, FESC, FACC,* George R. Sutherland, MD, FESC† Aachen, Germany; and Leuven, Belgium OBJECTIVES We studied the effects of cardiac resynchronization therapy (CRT) on regional myocardial strain distribution, as determined by echocardiographic strain rate (SR) imaging. BACKGROUND Dilated hearts with left bundle branch block (LBBB) have an abnormal redistribution of myocardial fiber strain. The effects of CRT on such abnormal strain patterns are unknown. METHODS We studied 18 patients (12 males and 6 females; mean age 65 Ϯ 11 years [range 33 to 76 years]) with symptomatic systolic heart failure and LBBB. Doppler myocardial imaging studies were performed to acquire regional longitudinal systolic velocity (cm/s), systolic SR Ϫ (s 1), and systolic strain (%) data from the basal and mid-segments of the septum and lateral wall before and after CRT. By convention, negative SR and strain values indicate longitudinal shortening. RESULTS Before CRT, mid-septal peak SR and peak strain were lower than in the mid-lateral wall (peak SR: Ϫ0.79 Ϯ 0.5 [septum] vs. Ϫ1.35 Ϯ 0.8 [lateral wall], p Ͻ 0.05; peak strain: Ϫ7 Ϯ 5 [septum] vs. Ϫ11 Ϯ 5 [lateral wall], p Ͻ 0.05). This relationship was reversed during CRT (peak SR: Ϫ1.35 Ϯ 0.8 [septum] vs. Ϫ0.93 Ϯ 0.6 [lateral wall], p Ͻ 0.05; peak strain: Ϫ11 Ϯ 6 [septum] vs. Ϫ7 Ϯ 6 [lateral wall], p Ͻ 0.05). Cardiac resynchronization therapy reversed the septal–lateral difference in mid-segmental peak strain from Ϫ46 Ϯ 94 ms (LBBB) to 17 Ϯ 92 ms (CRT; p Ͻ 0.05). CONCLUSIONS Left bundle branch block can lead to a significant redistribution of abnormal myocardial fiber strains. These abnormal changes in the extent and timing of septal–lateral strain relationships can be reversed by CRT. The noninvasive identification of specific abnormal but reversible strain patterns should help to improve patient selection for CRT. (J Am Coll Cardiol 2003; 42:486–94) © 2003 by the American College of Cardiology Foundation Cardiac resynchronization therapy (CRT) is a new treat- gration of the regional strain rate (SR) curve enables the ment option for patients with heart failure and left bundle computation of myocardial shortening and lengthening (i.e., branch block (LBBB). Several controlled clinical trials have estimation of myocardial strain [⑀]) (6). In a healthy demonstrated both the acute hemodynamic and long-term ventricle, regional peak SR values correlate well with inva- functional benefit of CRT in selected patients (1–3). Ex- sive indexes of global systolic function, such as peak elas- perimental studies based on tagged magnetic resonance tance and a peak positive rate of rise in left ventricular (LV) imaging have suggested that asynchronous activation leads pressure (ϩdP/dt) (7,8). In diseased ventricles, SRI is able to a pronounced redistribution of regional fiber shortening to identify regional changes associated with a range of (4,5). These phenomena might contribute to the reduction pathologies and can allow the differentiation between in ventricular function in patients with cardiomyopathies healthy, ischemic and viable segments (9). Thus, we hy- and LBBB. Thus, the identification of specific abnormal pothesized that SRI might provide the optimal noninvasive patterns in regional myocardial fiber strain redistribution approach to determine the nature of baseline regional might help to select those patients who are likely to benefit contractile asynchrony and to assess the changes with pacing from CRT. to define better patient selection criteria for CRT. For this Myocardial deformation can be quantified by echocardio- purpose, we studied the regional deformation patterns in graphic strain rate imaging (SRI), a technique based on LBBB and evaluated the acute effects of CRT by echocar- processing of velocity data on color Doppler myocardial diographic SRI. imaging (CDMI, or tissue Doppler imaging). The rate of regional myocardial deformation is measured by SRI. Inte- METHODS Patients. Twenty consecutive heart failure patients were From the *Department of Cardiology, University Hospital Aachen, Aachen, Germany; and the †Department of Cardiology, University Hospital Gasthuisberg, studied. Two patients were subsequently excluded from Katholic University Leuven, Leuven, Belgium. Dr. Breithardt was supported as a analysis because of poor transthoracic image quality. Thus, research fellow (2001–2002) by a scholarship from the Katholic University Leuven, data on 18 patients (12 males and 6 females; mean age 65 Ϯ Belgium. Manuscript received January 6, 2003; revised manuscript received April 13, 2003, 11 years [range 33 to 76 years]) with New York Heart accepted April 17, 2003. Association functional class III/IV heart failure were ana- JACC Vol. 42, No. 3, 2003 Breithardt et al. 487 August 6, 2003:486–94 Longitudinal Strain in LBBB and CRT majority of patients due to either a poor signal-to-noise Abbreviations and Acronyms ratio or poor alignment of the Doppler beam with the CDMI ϭ color Doppler myocardial imaging longitudinal motion of the wall. The image sector width was CRT ϭ cardiac resynchronization therapy set as narrow as possible to achieve the highest possible ⑀ ϭ Ϫ strain acquisition frame rates (Ͼ140 fps 1), and the pulse repeti- ICM ϭ ischemic cardiomyopathy IVCT ϭ isovolumic contraction time tion frequency was set to avoid aliasing. For each myocardial IVRT ϭ isovolumic relaxation time wall, CDMI cine loops containing three consecutive cardiac LBBB ϭ left bundle branch block cycles were stored digitally for post-processing. ϭ LV left ventricle/ventricular Image analysis. A detailed description of the SR acquisi- NICM ϭ nonischemic dilated cardiomyopathy RV ϭ right ventricle/ventricular tion procedure has previously been presented by our group, SR ϭ strain rate with a reproducibility for regional longitudinal SR and SRI ϭ strain rate imaging strain measurements ranging from 11% to 14% (10). In ϭ Vmax peak positive velocity brief, we analyzed CDMI data clips off-line on a PC workstation using customized software (SPEQLE, Katholic University Leuven, Belgium) to derive regional velocity profiles from the basal and mid-segments of each wall. A lyzed. Echocardiography was performed after implantation semi-automatic tracking algorithm was applied to maintain of the CRT device and before initiation of active CRT. All the sample volume in the region of interest throughout the patients received a biventricular pacing system with a right cardiac cycle. ventricular (RV) apical lead and LV pacing electrodes Regional SR was estimated from the spatial gradient of implanted through the coronary sinus and positioned in a the myocardial velocity profile over a user-defined sample LV epicardial vein. This coronary sinus lead was placed in a volume with a computational area of 10 mm. By conven- lateral position in 11 (61%) of 18 patients, in a posterior tion, SR is expressed as a positive parameter when the position in 6 patients (33%), and in an anterior position in segment thickens/lengthens and as a negative parameter 1 patient (6%). when the segment thins/shortens. In normal myocardium, Nine patients had presented with nonischemic cardiomy- longitudinal directional changes from the apical views are opathy (NICM), and nine had evidence of underlying characterized by systolic shortening (negative SR) and coronary artery disease by coronary angiography and were diastolic lengthening (positive SR). An increase in the rate classified as having ischemic cardiomyopathy (ICM). None of longitudinal systolic shortening will result in a more of them had any evidence of myocardial ischemia at rest or negative SR value and is expressed as an increased/higher an indication for revascularization. Six of nine patients with peak SR, and vice versa. ICM had a previous transmural myocardial infarction (two anterior and four inferior). Velocity and SR profiles were averaged over three con- All patients had LBBB with a mean QRS width of 167 Ϯ secutive cycles (spatial processing: 5 radial pixels, 3 lateral 22 ms (range 120 to 196 ms) and a mean PR interval of 200 pixels [median averages]). The regional SR profiles were Ϯ 38 ms (range 140 to 260 ms). Echocardiography docu- integrated over time to obtain the natural systolic strain mented LV dilation in all patients with a mean LV profiles. This curve was then used to define the extent of end-diastolic diameter of 75 Ϯ 10 mm (range 61 to 95 mm) systolic shortening (negative strain) or lengthening (positive and a mean biplane ejection fraction of 23 Ϯ 9% (range 9% strain). An increase in the extent of systolic shortening (i.e., to 37%). Exercise capacity was reduced, with a mean peak more negative strain) is expressed as increased/higher strain, and vice versa. oxygen consumption (VO2max) of 11.9 ml/kg/min (range 9.9 to 15.5 ml/kg/min). We incorporated data from anatomic M-mode record- Protocol. All patients underwent a standard echocardio- ings on aortic and mitral valvular opening and closure to graphic examination at rest both during “pacing off” and identify the duration of LV isovolumic contraction time during CRT with the permanent programmed atrioventric- (IVCT), ejection, and isovolumic relaxation time (IVRT). ular delay (mean 117 Ϯ 18 ms). Reprogramming of the These data were obtained from parasternal CDMI cine pacemakers to “no pacing” and CRT were performed during loops from cycles with identical R-R intervals.