Biventricular pacing-induced acute response in baroreflex sensitivity has predictive value for midterm response to cardiac resynchronization therapy

2009 ◽  
Vol 297 (1) ◽  
pp. H233-H237 ◽  
Author(s):  
Maaike G. J. Gademan ◽  
Rutger J. van Bommel ◽  
C. Jan Willem Borleffs ◽  
SumChe Man ◽  
Joris C. W. Haest ◽  
...  

In a previous study we demonstrated that the institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after the institution of cardiac resynchronization therapy (CRT) has predictive value for midterm response. One day after implantation of a CRT device in 33 CHF patients (27 male/6 female; age, 66.5 ± 9.5 yr; left ventricular ejection fraction, 28 ± 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). Echocardiography was performed before implantation (baseline) and 6 mo after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end-systolic volume at follow-up had decreased by ≥15%. Responders (69.7%) and nonresponders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% ( P = 0.03); this differed significantly ( P = 0.02) from the average BRS change (−2%) in the nonresponders. CRT also increased HRV by 30% in responders ( P = 0.02), but there was no significant difference found compared with the increase in HRV (8%) in the nonresponders. Receiver-operating characteristic curve analysis revealed that the percent BRS increase had predictive value for the discrimination of responders and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.51–0.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodeling.

Author(s):  
Marta Sitges ◽  
Genevieve Derumeaux

Cardiac imaging techniques have an important role in the follow-up of patients undergoing cardiac resynchronization therapy (CRT) as they provide objective evidence of changes in cardiac dimensions and function. The role of echocardiography is well established in the assessment of left ventricular reverse remodelling and the evaluation of secondary (functional) mitral regurgitation. Additionally, echocardiography might be used for optimizing the programming of atrio-ventricular (AV) and inter-ventricular (VV) delays of current CRT devices. Acute benefits from this optimization have been demonstrated, but longer follow-up studies have failed to show a clear benefit of optimized CRT on top of simultaneous biventricular pacing on the outcome of patients with CRT. This chapter reviews the role of imaging in assessing follow-up and outcome of patients undergoing CRT, as well as the rationale, the methods used, and the clinical impact of optimization of the programming of CRT devices.


Author(s):  
Marta Sitges ◽  
Erwan Donal

Cardiac imaging techniques have an important role in the follow-up of patients undergoing cardiac resynchronization therapy (CRT) as they provide objective evidence of changes in cardiac dimensions and function. The role of echocardiography is well established in the assessment of left ventricular reverse remodelling and the evaluation of secondary (functional) mitral regurgitation. Additionally, echocardiography might be used for optimizing the programming of atrioventricular (AV) and interventricular (VV) delays of current CRT devices. Acute benefit from this optimization has been demonstrated, but longer follow-up studies have failed to show a clear benefit of optimized CRT on top of simultaneous biventricular pacing on the outcome of patients with CRT. This chapter reviews the role of imaging in assessing follow-up and outcome of patients undergoing CRT as well as the rationale, the methods used, and the clinical impact of optimization of the programming of CRT devices.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
N Yamamoto ◽  
M Nakano ◽  
H Hayashi ◽  
Y Hasebe ◽  
N Ueda ◽  
...  

Abstract Background For cardiac resynchronization therapy (CRT), patients with chronic heart failure (HF) and wide (>150msec) QRS duration (QRSd) received class I/A indication. However, its beneficial effect seemed to be limited for those with mid- (120–150msec) QRSd. Recent studies demonstrated that QRSd normalized to left ventricular end-diastolic volume (QRSd/ LVEDV) improved prediction of clinical outcome in patients with CRT. Therefore, we sought to investigate predictive value of QRSd/LVEDV for responding to CRT in patients with mid-QRSd. Methods This was retrospective multi-center observational cohort study. A total 506 consecutive patients who underwent CRT implantation in Tohoku University Hospital and National Cerebral and Cardiovascular Center were evaluated. Exclusion criteria were QRSd less than 120ms, upgrade procedures from other implanted non-CRT devices and bradycardia requiring pacing. We evaluated clinical variables, data of electrocardiogram and transthoracic echocardiography at baseline and 6 months after CRT implantation. Primary endpoint was a HF hospitalization after CRT implantation. Distribution of free from HF hospitalization during follow-up was calculated using Kaplan-Meier curves, and the effects of covariate on the time to endpoint were investigated using a Cox proportional hazards model. Results After 199 patients were excluded based on exclusion criterion, remaining 307 patients were included for the analysis. Mean age was 62±14 [SD] years, and 238 (77%) were male. Mean LVEF and LVEDV were 25±9% and 234±82ml, respectively, and 24% of patients had ischemic etiology of HF. During the median 948 days of follow-up, CRT patients with mid QRSd (n=126; 136±10msec), as compared with those with wide QRSd (n=181; 174±17msec), tended to have higher incidence of HF hospitalization (Wilcoxon p=0.03). Multivariate analysis showed that QRSd and QRSd/LVEDV were significant predictors for HF hospitalization in CRT patients with mid QRSd, and cut-off values (137msec of QRSd and 0.65 of QRSd/LVEDV), which was calculated by receiver operative curve analysis, was used for risk stratification. QRSd<137msec was significant negative predictors for HF hospitalization (p=0.005), and Mid-QRSd patients with QRSd≥137msec demonstrated equivalent clinical outcome with those with wide QRSd. Moreover, patients with QRSd/LVEDV≥0.65 tended to have lower incidence of HF hospitalization as compared with those without it among patients with QRSd<137msec (n=64, Figure). Conclusion The present study demonstrates that QRSd normalized to left ventricular end-diastolic volume (QRSd/ LVEDV) could be clinical value in predicting outcome in CRT patients with mid-QRSd. These findings indicate normalized QRSd reflects myocardial conduction properties and contribute to risk stratification. FUNDunding Acknowledgement Type of funding sources: None.


2021 ◽  
Vol 11 (11) ◽  
pp. 1176
Author(s):  
Patrick Leitz ◽  
Julia Köbe ◽  
Benjamin Rath ◽  
Florian Reinke ◽  
Gerrit Frommeyer ◽  
...  

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4–12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p < 0.01), Δ LV paced–right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p < 0.01), CHA2DS2-Vasc score (p < 0.01), glomerular filtration rate (p < 0.01), coronary artery disease (p < 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p < 0.01), NT-proBNP (p < 0.01), and clinical response to CRT (p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Villegas-Martinez ◽  
HH Odland ◽  
OJ Sletten ◽  
F Khan ◽  
A Wajdan ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Background There is no consensus on which haemodynamic marker should be used to quantify acute response to cardiac resynchronization therapy (CRT) during implantation of the device. CRT has been shown to acutely reduce left ventricular (LV) end systolic as well as end-diastolic volume (EDV), precluding the use of preload dependent markers such as LV maximum pressure rise (dP/dtmax). Purpose As resynchronization will abolish the uncoordinated regional early systolic contractions of the LV, it will shorten the time to maximal pressure rise and aortic valve opening. For this reason, the purpose of this study was to investigate if duration from the time-point of ventricular pacing to dP/dtmax is less preload dependent and a better marker of acute response to CRT than dP/dtmax by comparing how the 2 markers reflected LV function during different CRT configurations. Methods LV pressure by micromanometer and volume by sonomicrometry were measured in 6 anaesthetized canines with left bundle branch block. Transient caval constrictions were performed to vary preload. Preload dependency of the 2 markers was compared by normalizing their values and calculating their relations to EDV. In 4 of the animals, biventricular pacing was performed at 3 different pacing sites with variations in atrioventricular delays that provided a range of response to CRT. To correct for acute changes in preload by CRT, stroke volume (SV) at identical EDV found from transient caval constrictions, were assessed and used as reference to grade improved LV function. Linear regression analysis was used to assess the correlation of both the duration of the preejection phase and dP/dtmax with SV. Results The duration of the preejection phase varied less with changes in preload compared to dP/dtmax: the slopes of their relation to EDV were -0.6 ± 0.7 %/ml and 4.8 ± 2.1 %/ml (p = 0.004), respectively. Turning CRT on, acutely reduced EDV from 74 ± 16 to 69 ± 17 ml (p &lt; 0.001) at the best pacing configuration. For the different pacing sites and settings, there was a consistent relation in all animals where the preejection phase shortened as SV increased (average r2 = 0.75) (Figure A). dP/dtmax showed no clear relation to SV (average r2 = 0.22) and included cases with both negative and positive slopes (Figure B). Conclusions The duration of the preejection phase correlated with changes in LV function induced by CRT while dP/dtmax performed poorly as preload was changed. Hence, the novel timing parameter was less preload dependent and may be a better marker for assessing acute response to CRT. Abstract Figure.


2021 ◽  
Vol 26 (9) ◽  
pp. 4500
Author(s):  
L. M. Malishevsky ◽  
V. A. Kuznetsov ◽  
V. V. Todosiychuk ◽  
N. E. Shirokov ◽  
D. S. Lebedev

Aim. To analyze the prognostic value of 18 electrocardiographic (ECG) markers of left bundle branch block (LBBB) in predicting left ventricular (LV) reverse remodeling in patients receiving cardiac resynchronization therapy (CRT).Material and methods. The study included 98 patients. Depending on the presence of reverse remodeling during CRT, defined as a decrease in LV endsystolic volume ≥15%, the patients were divided into two groups: non-responders (n=33) and responders (n=65). We selected and analyzed 18 ECG markers included in 9 LBBB criteria.Results. Among the ECG markers significantly associated with reverse remodeling during CRT, the absence of q wave in leads V5-V6 demonstrated the highest sensitivity (92,31%), a negative predictive value (70,59%) and overall accuracy (73,47%). Normal internal deviation interval of the R wave in leads V1-V3 was also associated with the best sensitivity (92.31%), while QS with a positive T in lead aVR — the best specificity (69,7%). Discordant T wave demonstrated the highest positive predictive value (80,33%). Multivariate analysis revealed following ECG signs independently associated with reverse remodeling during CRT: QRS complex duration (odds ratio (OR)=1,022; 95% confidence interval (CI): 1,001-1,043; p=0,040); absence of q wave in leads V5-V6 (OR=4,076; 95% CI: 1,071-15,51; p=0,039); discordant T wave (OR=4,565; 95% CI: 1,708-12,202; p=0,002). These ECG findings were combined into a mathematical model that demonstrated high predictive power (AUC=0,81 [0,722-0,898], p<0,001). Once the cut-off point was determined, a binary variable was obtained that showed higher sensitivity, negative predictive value, and overall accuracy when compared with the actual LBBB criteria. The 5-year survival rate among patients with a model value above the cut-off point was 84,4%, while in patients with a value below the cut-off point — 50% (Log-rank test, p=0,001). To improve usability of the model, a mobile application was developed.Conclusion. For the first time, the diagnostic value of ECG markers of LBBB were analyzed and a mathematical model with ECG signs was proposed to predict reverse remodeling in patients receiving CRT.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andrea M Thelen ◽  
Christopher L Kaufman ◽  
Kevin V Burns ◽  
Daniel R Kaiser ◽  
Aaron S Kelly ◽  
...  

Background: Previous large studies on the effects of cardiac resynchronization therapy (CRT) in patients with heart failure have generally excluded patients previously paced from the right ventricle (RV). Previously RV paced patients (RVp) can exhibit an iatrogenic cause of dyssynchrony and reduced systolic function and thus, may respond differently to CRT than patients not previously RV paced (nRVp). The purpose of this study was to test the hypothesis that RVp patients have greater improvements in left ventricular systolic function, volumes, and dyssynchrony in response to CRT than nRVp. Methods: Standard echocardiograms with tissue Doppler imaging were performed before and after chronic CRT in RVp (n = 21, 16 male) and nRVp (n = 70, 54 male) heart failure patients. Ejection fraction (EF), left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were calculated using the biplane Simpson’s method. Longitudinal dyssynchrony was calculated as the standard deviation of time to peak displacement (TT-12) of 12 segments in the apical views. Using mid-ventricular short axis views and speckle-tracking methods, radial dyssynchrony (Rad dys ) was calculated as the maximal time difference between six myocardial segments for peak radial strain. Echo response was defined as ≥ 15% reduction in LVESV. Results are reported as mean ± SD. Results: Significant baseline differences (p < 0.05) were observed between groups (RVp vs. nRVp) for age (74 ± 13 vs. 67 ± 13 year), follow-up time (6.1 ± 1.8 vs. 4.6 ± 2.1 months), LVEDV (154.3±50.8 vs.185.3±56.9 mL), and a trend for LVESV (112.4 ± 40.6 vs. 134.9 ± 47 mL, p = 0 .05). No differences were observed for EF, etiology of heart failure, and dyssynchrony measures between groups at baseline. Echo response rate was significantly ( p < 0.05) greater in RVp (76%) than nRVp (57%). After adjusting for baseline differences, RVp had greater improvement in EF (14 ± 9 vs. 8 ± 7%, p < 0.05) and LVESV (−33 ± 18 vs. −20 ± 21%, p < 0.05). After adjustment for follow-up time, no difference was observed for change in dyssynchrony between groups. Conclusion: RVp patients upgraded to CRT exhibit greater improvements in systolic function and ventricular remodeling as compared to nRVp patients.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Jedrzejczyk-Patej ◽  
M Mazurek ◽  
W Kowalska ◽  
M Bugajski ◽  
A Konieczny-Kozielska ◽  
...  

Abstract Background Over a quarter of all cardiac resynchronization therapy (CRT) implants are upgrades from previous devices, mainly from implantable cardioverter-defibrillator (ICD). In comparison to CRT with defibrillator (CRT-D) de novo implantation, upgrade from ICD to CRT-D carries higher risk of complications. Limited number of studies evaluated predictors of death in patients undergoing upgrade from ICD to CRT-D. Aim To determine mortality predictors and outcome in patients undergoing upgrade from ICD to CRT-D in comparison to subjects with CRT-D de novo implantation. Methods Study population consisted of 595 consecutive patients with CRT-D implanted between 2002 and 2015 in tertiary care university hospital, in a densely inhabited, urban region of Poland (480 subjects [84.3%] with CRT-D de novo implantation; 115 patients [15.7%] upgraded from ICD to CRT-D). Results The median follow-up was 1692 days (range: 457–3067). All-cause mortality in patients upgraded from ICD was significantly higher than in subjects with CRT-D implanted de novo (43.5% vs. 35.5%, P=0.045). On multivariable regression analysis, left ventricular end-systolic diameter (HR 1.07, 95% CI 1.02–1.11, P=0.002), creatinine level at baseline (HR 1.01, 95% CI 1.00–1.02, P=0.01), NYHA IV class at baseline (HR 2.36, 95% CI 1.00–5.53, P=0.049) and cardiac device-related infective endocarditis (CDRIE) during follow up (HR 2.42, 95% CI 1.02–5.75, P=0.046) were identified as independent predictors of higher mortality in patients with CRT-D upgraded from ICD. Conclusions Mortality rate in patients upgraded from ICD is higher in comparison to CRT-D de novo implanted subjects, and reaches almost 45% within 4.5 years. Left ventricular dimensions, creatinine level, high NYHA class at baseline and infective endocarditis during follow up are independent mortality predictors in patients with CRT-D upgraded from ICD.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V A Kuznetsov ◽  
T N Enina ◽  
A M Soldatova ◽  
T I Petelina ◽  
N E Shirokov ◽  
...  

Abstract Background Superresponders to cardiac resynchronization therapy (CRT) demonstrate significant reverse remodeling, improvement in cardiac function, decrease in inflammatory mediators and markers of cardiac fibrosis. It is not clear if superresponse (SR) can be early or late and if the time of SR to CRT is associated with different degree of biochemical improvement. Aim To assess structural and functional heart parameters, sympathetic activity, levels of biomarkers of myocardial fibrosis, inflammatory and neurohormonal mediators in patients with various time of SR to CRT. Methods The study enrolled 82 superresponders to CRT (decrease in left ventricular end-systolic volume (LVESV) >30%) (mean age 60.4±9.3 years; 80.5% men, 19.5% women; 54.9% with ischemic etiology of heart failure). Patients were divided into two groups: group 1 (n=19) – SR was achieved within 24 months (14.0 [8.0; 21.0] months); group 2 (n=63) - SR was achieved after 24 months (59 [43.0; 84.0] months). Echocardiographic parameters, plasma levels of epinephrine, norepinephrine, NT-proBNP, interleukin (IL) 1β, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), metalloproteinase (MMP) 9, tissue inhibitors of metalloproteinase (TIMP) 1 and 4 were evaluated. Results At baseline there were no differences in demographic, clinical and echocardiographic characteristics between the groups. Levels of epinephrine (1.1 [0.1; 2.2] ng/ml vs 2.1 [0.7; 3.4] ng/ml; p=0.049) and IL-10 (1.8 [1.5; 3.5] pg/ml vs 3.9 [2.7; 5.1] pg/ml; p=0.019) were significantly higher in group 2. Both groups demonstrated significant improvement in echocardiographic parameters. On follow-up left ventricular (LV) end-systolic dimension (p=0.041), LV end-diastolic dimension (p=0.049), LVESV (p=0.014), LV end-diastolic volume (p=0.045) were lower in group 2. In group 1 IL-6 (p=0.047), TNF-α (p=0.047) decreased significantly and there was a tendency for IL-1β (p=0.064) and norepinephrine (p=0.069) levels to increase. In group 2 levels of IL-1β (p<0.001), IL-6 (p=0.030), IL-10 (p=0.003), TNF-α (p<0.001), TIMP-1 (p=0.010) and epinephrine (p=0.024) decreased significantly while MMP-9/TIMP-1 (p=0.023) increased as compared to baseline levels. Additionally there was a tendency for NT-proBNP level to decrease in group 2 (p=0.069). Follow-up level of norepinephrine (7.8 [2.9; 17.2] ng/ml vs 1.1 [0.2; 8.7] ng/ml; p=0.011 was lower and MMP-9/TIMP-4 level was higher (0.058 [0.044; 0.091] vs 0.092 [0.064; 0.111]; p=0.013) in group 2. Diverse trends were observed in IL-10 (0.4 [−0.6; 1.2] pg/ml in group 1 vs −2.3 [−3.4; −0.5] pg/ml in group 2; p=0.007) and norepinephrine (4.0 [−5.2; 14.3] ng/ml in the group 1 vs −1.2 [−11.6; 4.0] ng/ml in the group 2; p=0.015) between the groups. Conclusion CRT modulates sympathetic, neurohumoral, immune and fibrotic activity. Late SR to CRT is associated with decrease of sympathetic and inflammatory activity and more pronounced LV reverse remodeling.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R San Antonio ◽  
M Pujol-Lopez ◽  
R Jimenez-Arjona ◽  
A Doltra ◽  
F Alarcon ◽  
...  

Abstract Funding Acknowledgements Cardiac Pacing Scholarship from the Spanish Society of Cardiology (SEC) Background Electrocardiogram-based optimization of cardiac resynchronization therapy (CRT) using the fusion-optimized intervals (FOI) method has demonstrated to improve both acute hemodynamic response and left ventricle (LV) reverse remodeling compared to nominal programming of CRT. FOI optimizes the atrioventricular (AV) and ventriculo-ventricular (VV) intervals to achieve the shortest paced-QRS duration. The recent development of multipoint pacing (MPP) enables the activation of the LV from 2 locations, also shortening the QRS duration compared to conventional biventricular pacing. Purpose To determine if MPP reduces the paced-QRS duration compared to FOI optimization.  Methods This prospective clinical study included 25 consecutive patients who successfully received a CRT with MPP pacing capability. All patients were in sinus rhythm and had an PR interval below 250 ms. The QRS duration was measured with a 12-lead digital electrocardiography (screen speed of 200 mm/s) at baseline and using 3 different configurations: MPP, FOI and a combined FOI-MPP strategy. In MPP, the intervals were (based on previous studies): 1) AV 130 ms, 2) Right ventricular (RV)-LV2 (Δ1) 5 ms, and 3) LV1-LV2 (Δ2) 5 ms. In FOI, AV and VV intervals were optimized to achieve fusion between intrinsic conduction and biventricular pacing. In FOI-MPP, the Δ2 was set at 5 ms, while AV and Δ1 intervals were optimized using the FOI method. The CRT device was programmed with the configuration that achieved a greater paced-QRS shortening. After 45 days, battery life was estimated. Results   Mean age was 65 ± 10 years, 20 were men (80%) and baseline QRS duration was 177 ± 17 ms. The FOI method bested nominal MPP (QRS shortened by 58 ± 16 ms vs 43 ± 16 ms, respectively, p = 0.002). Adding MPP to the narrowest QRS by FOI did not result in further shortening (FOI: 58 ± 16 ms vs FOI-MPP: 59 ± 13 ms, p = 0.81). The final configuration was FOI method alone in most cases (n = 16, 64%) and FOI-MPP in all others (n = 9, 36%; figure). In total, 10 out of 25 patients (40%) were not candidates to MPP due to: 1) pacing thresholds exceeding 3.5 V/0.4 ms at the distal or proximal electrode (8, 32%), and 2) phrenic stimulation (2, 8%). Estimated battery longevity was longer in patients receiving FOI as compared to MPP (8.3 ± 2.1 years vs. 6.2 ± 2.2 years, p = 0.04). Conclusion In CRT, the FOI method is not improved by coupling with MPP.  Up to 40% of patients are not candidates for MPP due to high thresholds or phrenic stimulation. The use of MPP in unselected patients would result in a decrease of battery longevity, without any additional benefit over FOI. Abstract Figure.


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