Rutger J. van Bommel

Optimal Left Ventricular Lead Position Predicts Reverse Remodeling and Survival After Cardiac Resynchronization Therapy

OBJECTIVES The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position. BACKGROUND A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT. METHODS The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest X-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. RESULTS Significant LV reverse remodeling (reduction in LV end-systolic volume from 189 +/- 83 ml to 134 +/- 71 ml, p < 0.001) was noted in the group of patients with a concordant LV lead position (n = 153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32 +/- 16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, p = 0.004). CONCLUSIONS Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up.

Assessment of left ventricular dyssynchrony by speckle tracking strain imaging comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy.

OBJECTIVES The objective of this study was to assess the usefulness of each type of strain for left ventricular (LV) dyssynchrony assessment and its predictive value for a positive response after cardiac resynchronization therapy (CRT). Furthermore, changes in extent of LV dyssynchrony for each type of strain were evaluated during follow-up. BACKGROUND Different echocardiographic techniques have been proposed for assessment of LV dyssynchrony. The novel 2-dimensional (2D) speckle tracking strain analysis technique can provide information on radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). METHODS In 161 patients, 2D echocardiography was performed at baseline and after 6 months of CRT. Extent of LV dyssynchrony was calculated for each type of strain. Response to CRT was defined as a decrease in LV end-systolic volume >/=15% at follow-up. RESULTS At follow-up, 88 patients (55%) were classified as responders. Differences in baseline LV dyssynchrony between responders and nonresponders were noted only for RS (251 +/- 138 ms vs. 94 +/- 65 ms; p < 0.001), whereas no differences were noted for CS and LS. A cut-off value of radial dyssynchrony >/=130 ms was able to predict response to CRT with a sensitivity of 83% and a specificity of 80%. In addition, a significant decrease in extent of LV dyssynchrony measured with RS (from 251 +/- 138 ms to 98 +/- 92 ms; p < 0.001) was demonstrated only in responders. CONCLUSIONS Speckle tracking radial strain analysis constitutes the best method to identify potential responders to CRT. Reduction in LV dyssynchrony after CRT was only noted in responders.

Comparison of Aortic Root Dimensions and Geometries Before and After Transcatheter Aortic Valve Implantation by 2- and 3-Dimensional Transesophageal Echocardiography and Multislice Computed Tomography

Background—3D transesophageal echocardiography (TEE) may provide more accurate aortic annular and left ventricular outflow tract (LVOT) dimensions and geometries compared with 2D TEE. We assessed agreements between 2D and 3D TEE measurements with multislice computed tomography (MSCT) and changes in annular/LVOT areas and geometries after transcatheter aortic valve implantations (TAVI). Methods and Results—Two-dimensional circular (&pgr;×r2), 3D circular, and 3D planimetered annular and LVOT areas by TEE were compared with “gold standard” MSCT planimetered areas before TAVI. Mean MSCT planimetered annular area was 4.65±0.82 cm2 before TAVI. Annular areas were underestimated by 2D TEE circular (3.89±0.74 cm2, P<0.001), 3D TEE circular (4.06±0.79 cm2, P<0.001), and 3D TEE planimetered annular areas (4.22±0.77 cm2, P<0.001). Mean MSCT planimetered LVOT area was 4.61±1.20 cm2 before TAVI. LVOT areas were underestimated by 2D TEE circular (3.41±0.89 cm2, P<0.001), 3D TEE circular (3.89±0.94 cm2, P<0.001), and 3D TEE planimetered LVOT areas (4.31±1.15 cm2, P<0.001). Three-dimensional TEE planimetered annular and LVOT areas had the best agreement with respective MSCT planimetered areas. After TAVI, MSCT planimetered (4.65±0.82 versus 4.20±0.46 cm2, P<0.001) and 3D TEE planimetered (4.22±0.77 versus 3.62±0.43 cm2, P<0.001) annular areas decreased, whereas MSCT planimetered (4.61±1.20 versus 4.84±1.17 cm2, P=0.002) and 3D TEE planimetered (4.31±1.15 versus 4.55±1.21 cm2, P<0.001) LVOT areas increased. Aortic annulus and LVOT became less elliptical after TAVI. Conclusions—Before TAVI, 2D and 3D TEE aortic annular/LVOT circular geometric assumption underestimated the respective MSCT planimetered areas. After TAVI, 3D TEE and MSCT planimetered annular areas decreased as it assumes the internal dimensions of the prosthetic valve. However, planimetered LVOT areas increased due to a more circular geometry.

Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up.

OBJECTIVES The aim of the current study was to evaluate the relation between the extent of left ventricular (LV) reverse remodeling and clinical/echocardiographic improvement after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome. BACKGROUND Despite the current selection criteria, individual response to CRT varies significantly. Furthermore, it has been suggested that reduction in left ventricular end-systolic volume (LVESV) after CRT is related to outcome. METHODS A total of 302 CRT candidates were included. Clinical status and echocardiographic evaluation were performed before implantation and after 6 months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. RESULTS Based on different extents of LV reverse remodeling, 22% of patients were classified as super-responders (decrease in LVESV > or =30%), 35% as responders (decrease in LVESV 15% to 29%), 21% as nonresponders (decrease in LVESV 0% to 14%), and 22% negative responders (increase in LVESV). More extensive LV reverse remodeling resulted in more clinical improvement, with a larger increase in LV function and more reduction in mitral regurgitation. In addition, more LV reverse remodeling resulted in less heart failure hospitalizations and lower mortality during long-term follow-up (22 +/- 11 months); 1- and 2-year hospitalization-free survival rates were 90% and 70% in the negative responder group compared with 98% and 96% in the super-responder group (log-rank p value <0.001). CONCLUSIONS The extent of LV reverse remodeling at midterm follow-up is predictive for long-term outcome in CRT patients.

Cardiac Sympathetic Denervation Assessed With 123-Iodine Metaiodobenzylguanidine Imaging Predicts Ventricular Arrhythmias in Implantable Cardioverter-Defibrillator Patients

OBJECTIVES The purpose of this study was to evaluate whether 123-iodine metaiodobenzylguanidine (123-I MIBG) imaging predicts ventricular arrhythmias causing appropriate implantable cardioverter-defibrillator (ICD) therapy (primary end point) and the composite of appropriate ICD therapy or cardiac death (secondary end point). BACKGROUND Although cardiac sympathetic denervation is associated with ventricular arrhythmias, limited data are available on the predictive value of sympathetic nerve imaging with 123-I MIBG on the occurrence of arrhythmias. METHODS Before ICD implantation, patients underwent 123-I MIBG and myocardial perfusion imaging. Early and late 123-I MIBG (planar and single-photon emission computed tomography [SPECT]) imaging was performed to assess cardiac innervation (heart-to-mediastinum ratio, cardiac washout rate, and 123-I MIBG SPECT defect score). Stress-rest myocardial perfusion imaging was performed to assess myocardial infarction and perfusion abnormalities (perfusion defect scores). During follow-up, appropriate ICD therapy and cardiac death were documented. RESULTS One-hundred sixteen heart failure patients referred for ICD therapy were enrolled. During a mean follow-up of 23 +/- 15 months, appropriate ICD therapy (primary end point) was documented in 24 (21%) patients and appropriate ICD therapy or cardiac death (secondary end point) in 32 (28%) patients. Late 123-I MIBG SPECT defect score was an independent predictor for both end points. Patients with a large late 123-I MIBG SPECT defect (summed score >26) showed significantly more appropriate ICD therapy (52% vs. 5%, p < 0.01) and appropriate ICD therapy or cardiac death (57% vs. 10%, p < 0.01) than patients with a small defect (summed score </=26) at 3-year follow-up. CONCLUSIONS Cardiac sympathetic denervation predicts ventricular arrhythmias causing appropriate ICD therapy as well as the composite of appropriate ICD therapy or cardiac death.

Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

Background— The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study. Methods and Results— In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters. Conclusions— Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

Strain analysis in patients with severe aortic stenosis and preserved left ventricular ejection fraction undergoing surgical valve replacement

AIMS To evaluate myocardial multidirectional strain and strain rate (S-and-SR) in severe aortic stenosis (AS) patients with preserved left ventricular (LV) ejection fraction (EF), using two-dimensional speckle-tracking strain imaging (2D-STI). The long-term effect of aortic valve replacement (AVR) on S-and-SR was also evaluated. METHODS AND RESULTS Changes in LV radial, circumferential, and longitudinal S-and-SR were evaluated in 73 severe AS patients (65 +/- 13 years; aortic valve area 0.8 +/- 0.2 cm2) with preserved LVEF (61 +/- 11%), before and 17 months after AVR. Strain and strain rate data were compared with data from 40 controls (20 healthy individuals and 20 patients with LV hypertrophy) matched by age, gender, body surface area, and LVEF. Compared with controls, severe AS patients had significantly decreased values of LV S-and-SR in the radial (33.1 +/- 14.8%, P = 0.2; 1.7 +/- 0.5 s(-1), P = 0.003), circumferential (-15.2 +/- 5.0%, P = 0.001; -0.9 +/- 0.3 s(-1), P < 0.0001), and longitudinal (-14.6 +/- 4.1%, P < 0.0001; -0.8 +/- 0.2 s(-1), P < 0.0001) directions. At 17 months after AVR, LV S-and-SR significantly improved in all the three directions, whereas LVEF remained unchanged (60 +/- 12%, P = 0.7). CONCLUSION In severe AS patients, impaired LV S-and-SR existed although LVEF was preserved. After AVR, a significant S-and-SR improvement in all the three directions was observed. These subtle changes in LV contractility can be detected by 2D-STI.

Characteristics of heart failure patients associated with good and poor response to cardiac resynchronization therapy: a PROSPECT (Predictors of Response to CRT) sub-analysis

AIMS Predictors of Response to Cardiac Resynchronization Therapy (CRT) (PROSPECT) was the first large-scale, multicentre clinical trial that evaluated the ability of several echocardiographic measures of mechanical dyssynchrony to predict response to CRT. Since response to CRT may be defined as a spectrum and likely influenced by many factors, this sub-analysis aimed to investigate the relationship between baseline characteristics and measures of response to CRT. METHODS AND RESULTS A total of 286 patients were grouped according to relative reduction in left ventricular end-systolic volume (LVESV) after 6 months of CRT: super-responders (reduction in LVESV > or =30%), responders (reduction in LVESV 15-29%), non-responders (reduction in LVESV 0-14%), and negative responders (increase in LVESV). In addition, three subgroups were formed according to clinical and/or echocardiographic response: +/+ responders (clinical improvement and a reduction in LVESV > or =15%), +/- responders (clinical improvement or a reduction in LVESV > or =15%), and -/- responders (no clinical improvement and no reduction in LVESV > or =15%). Differences in clinical and echocardiographic baseline characteristics between these subgroups were analysed. Super-responders were more frequently females, had non-ischaemic heart failure (HF), and had a wider QRS complex and more extensive mechanical dyssynchrony at baseline. Conversely, negative responders were more frequently in New York Heart Association class IV and had a history of ventricular tachycardia (VT). Combined positive responders after CRT (+/+ responders) had more non-ischaemic aetiology, more extensive mechanical dyssynchrony at baseline, and no history of VT. CONCLUSION Sub-analysis of data from PROSPECT showed that gender, aetiology of HF, QRS duration, severity of HF, a history of VT, and the presence of baseline mechanical dyssynchrony influence clinical and/or LV reverse remodelling after CRT. Although integration of information about these characteristics would improve patient selection and counselling for CRT, further randomized controlled trials are necessary prior to changing the current guidelines regarding patient selection for CRT.

Analysis of Ventricular Activation Using Surface Electrocardiography to Predict Left Ventricular Reverse Volumetric Remodeling During Cardiac Resynchronization Therapy

Background— Cardiac resynchronization therapy for heart failure with left bundle branch block reduces left ventricular (LV) conduction delay, contraction asynchrony, and LV end-systolic volume (“reverse remodeling”). Up to one third of patients do not improve, and the electric requirements for reverse remodeling are unclear. We hypothesized that reverse remodeling is predicted by the left bundle branch block ventricular activation sequence, the paced activation sequence, and interactions between these 2 conditions. Methods and Results— Twelve-lead ECGs during left bundle branch block and cardiac resynchronization therapy were analyzed in 202 consecutive patients (New York Heart Association class III to IV heart failure, ejection fraction ≤35%) for predictors of reverse remodeling (≥10% reduction in end-systolic volume) at 6 months. Greater longest baseline LV activation time predicted increased odds of reverse remodeling (odds ratio [confidence interval]=1.30 [1.11, 1.52] per 10-ms increase), whereas higher QRS scores for LV scar predicted reduced reverse remodeling (odds ratio [confidence interval]=0.49 [0.27, 0.88] for each 1-point increase from 0 to 4; 0.92 [0.83, 1.01] for each 1-point increase >4). After cardiac resynchronization therapy, increasing R amplitudes in leads V1 through V2 (odds ratio [confidence interval]=2.76 [1.01, 7.51] for each 1× increase over [baseline R×4.5]) and left→right frontal axis shift (odds ratio [confidence interval]=2.00 [0.99, 4.02]), indicators of ventricular activation wavefront fusion, were positive predictors of reverse remodeling. Predicted probability of reverse remodeling ranged from <20% for patients with adverse predictors to 99% for those with positive predictors. Conclusions— Ventricular activation with the use of the ECG accurately predicts LV reverse remodeling during cardiac resynchronization therapy. Greater longest baseline LV activation time and smaller scar volume combined with wavefront fusion on the paced ECG, anticipate higher probability of reverse remodeling.

Alterations in multidirectional myocardial functions in patients with aortic stenosis and preserved ejection fraction: a two-dimensional speckle tracking analysis

AIMS To identify changes in multidirectional strain and strain rate (SR) in patients with aortic stenosis (AS). METHODS AND RESULTS A total of 420 patients (age 66.1 ± 14.5 years, 60.7% men) with aortic sclerosis, mild, moderate, and severe AS with preserved left ventricular (LV) ejection fraction [(EF), ≥50%] were included. Multidirectional strain and SR imaging were performed by two-dimensional speckle tracking. Patients were more likely to be older (P < 0.001) and at a worse New York Heart Association functional class (P < 0.001) with increasing AS severity. There was a progressive stepwise impairment in longitudinal, circumferential, and radial strain and SR with increasing AS severity (all P < 0.001). The myocardial dysfunction appeared to start in the subendocardium with mild AS, to mid-wall dysfunction with moderate AS, and eventually transmural dysfunction with severe AS. Aortic valve area, as a measure of AS severity, was an independent determinant of multidirectional strain and SR on multiple linear regressions. CONCLUSIONS Patients with AS have evidence of subclinical myocardial dysfunction early in the disease process despite normal LVEF. The myocardial dysfunction appeared to start in the subendocardium and progressed to transmural dysfunction with increasing AS severity. Symptomatic moderate and severe AS patients had more impaired multidirectional myocardial functions compared with asymptomatic patients.