Pilot study to evaluate left-to-right ventricular offset in biventricular pacing-comparison of electrocardiographic imaging and ECG.

INTRODUCTION: Biventricular pacing (BiVp) improves outcomes in systolic heart failure patients with electrical dyssynchrony. BiVp is delivered from epicardial left ventricular (LV) and endocardial right ventricular (RV) electrodes. Acute electrical activation changes with different LV-RV stimulation offsets can help guide individually optimized BiVp programming. We sought to study the BiVp ventricular activation with different LV-RV offsets and compare with 12-lead ECG. METHODS: In five patients with BiVp (63 ± 17-year-old, 80% male, LV ejection fraction 27 ± 6%), we evaluated acute ventricular epicardial activation, varying LV-RV offsets in 20 ms increments from -40 to 80 ms, using electrocardiographic imaging (ECGI) to obtain absolute ventricular electrical uncoupling (VEUabs, absolute difference in average LV and average RV activation time) and total activation time (TAT). For each patient, we calculated the correlation between ECGI and corresponding ECG (3D-QRS-area and QRS duration) with different LV-RV offsets. RESULTS: The LV-RV offset to attain minimum VEUabs in individual patients ranged 20-60 ms. In all patients, a larger LV-RV offset was required to achieve minimum VEUabs (36 ± 17 ms) or 3D-QRS-area (40 ± 14 ms) than that for minimum TAT (-4 ± 9 ms) or QRS duration (-8 ± 11 ms). In individual patients, 3D-QRS-area correlated with VEUabs (r 0.65 ± 0.24) and QRS duration correlated with TAT (r 0.95 ± 0.02). Minimum VEUabs and minimum 3D-QRS-area were obtained by LV-RV offset within 20 ms of each other in all five patients. CONCLUSIONS: LV-RV electrical uncoupling, as assessed by ECGI, can be minimized by optimizing LV-RV stimulation offset. 3D-QRS-area is a surrogate to identify LV-RV offset that minimizes LV-RV uncoupling.

Different methods of 3D QRS area calculation from vectorcardiographic X, Y, and Z Leads.

3DQRSarea is a strong marker for cardiac resynchronization therapy and can be obtained by taking the (i) summation or the (ii) difference of the areas subtended by positive and negative deflections in X, Y, Z vectorcardiographic electrocardiogram (ECG) leads. We correlated both methods with the instantaneous-absolute-3D-voltage-time-integral (VTIQRS-3D). 3DQRSarea consistently underestimated the VTIQRS -3D, but the summation method was a closer and more reliable approximation. The dissimilarity was less apparent in left bundle branch block (r2 summation .996 vs. difference .972) and biventricular paced ECGs (r2 .996 vs. .957) but was more apparent in normal ECGs (r2 .988 vs. .653).

Electrocardiographic Z-axis QRS-T voltage-time-integral in patients with typical right bundle branch block - Correlation with echocardiographic right ventricular size and function.

BACKGROUND: Right bundle branch block (RBBB) can be benign or associated with right ventricular (RV) functional and structural abnormalities. Our aim was to evaluate QRS-T voltage-time-integral (VTI) compared to QRS duration and lead V1 R' as markers for RV abnormalities. METHODS: We included adults with an ECG demonstrating RBBB and echocardiogram obtained within 3 months of each other, between 2010 and 2020. VTIQRS and VTIQRST were obtained for 12 standard ECG leads, reconstructed vectorcardiographic X, Y, Z leads and root-mean-squared (3D) ECG. Age, sex and BSA-adjusted linear regressions were used to assess associations of QRS duration, amplitudes, VTIs and lead V1 R' duration/VTI with echocardiographic tricuspid annular plane systolic excursion (TAPSE), RV tissue Doppler imaging S', basal and mid diameter, and systolic pressure (RVSP). RESULTS: Among 782 patients (33% women, age 71 ± 14 years) with RBBB, R' duration in lead V1 was modestly associated with RV S', RV diameters and RVSP (all p ≤ 0.03). QRS duration was more strongly associated with RV diameters (both p < 0.0001). AmplitudeQRS-Z was modestly correlated with all 5 RV echocardiographic variables (all p ≤ 0.02). VTIR'-V1 was more strongly associated with TAPSE, RV S' and RVSP (all p ≤ 0.0003). VTIQRS-Z and VTIQRST-Z were among the strongest correlates of the 5 RV variables (all p < 0.0001). VTIQRST-Z.√BSA cutoff of ≥62 µVsm had sensitivity 62.7% and specificity 65.7% for predicting ≥3 of 5 abnormal RV variables (AUC 0.66; men 0.71, women 0.60). CONCLUSION: In patients with RBBB, VTIQRST-Z is a stronger predictor of RV dysfunction and adverse remodeling than QRS duration and lead V1 R'.

Electrocardiogram-based deep learning improves outcome prediction following cardiac resynchronization therapy.

AIMS: This study aims to identify and visualize electrocardiogram (ECG) features using an explainable deep learning-based algorithm to predict cardiac resynchronization therapy (CRT) outcome. Its performance is compared with current guideline ECG criteria and QRSAREA. METHODS AND RESULTS: A deep learning algorithm, trained on 1.1 million ECGs from 251 473 patients, was used to compress the median beat ECG, thereby summarizing most ECG features into only 21 explainable factors (FactorECG). Pre-implantation ECGs of 1306 CRT patients from three academic centres were converted into their respective FactorECG. FactorECG predicted the combined clinical endpoint of death, left ventricular assist device, or heart transplantation [c-statistic 0.69, 95% confidence interval (CI) 0.66-0.72], significantly outperforming QRSAREA and guideline ECG criteria [c-statistic 0.61 (95% CI 0.58-0.64) and 0.57 (95% CI 0.54-0.60), P < 0.001 for both]. The addition of 13 clinical variables was of limited added value for the FactorECG model when compared with QRSAREA (Δ c-statistic 0.03 vs. 0.10). FactorECG identified inferolateral T-wave inversion, smaller right precordial S- and T-wave amplitude, ventricular rate, and increased PR interval and P-wave duration to be important predictors for poor outcome. An online visualization tool was created to provide interactive visualizations (https://crt.ecgx.ai). CONCLUSION: Requiring only a standard 12-lead ECG, FactorECG held superior discriminative ability for the prediction of clinical outcome when compared with guideline criteria and QRSAREA, without requiring additional clinical variables. End-to-end automated visualization of ECG features allows for an explainable algorithm, which may facilitate rapid uptake of this personalized decision-making tool in CRT.

Association of vectorcardiographic T-wave area with clinical and echocardiographic outcomes in cardiac resynchronization therapy.

AIMS: Data on repolarization parameters in cardiac resynchronization therapy (CRT) are scarce. We investigated the association of baseline T-wave area, with both clinical and echocardiographic outcomes of CRT in a large, multi-centre cohort of CRT recipients. Also, we evaluated the association between the baseline T-wave area and QRS area. METHODS AND RESULTS: In this retrospective study, 1355 consecutive CRT recipients were evaluated. Pre-implantation T-wave and QRS area were calculated from vectorcardiograms. Echocardiographic response was defined as a reduction of ≥15% in left ventricular end-systolic volume between 3 and 12 months after implantation. The clinical outcome was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Left ventricular end-systolic volume reduction was largest in patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs compared with QRS area ≥ 109 µVs and T-wave area < 66 µVs (P = 0.004), QRS area < 109 µVs and T-wave area ≥ 66 µVs (P < 0.001) and QRS area < 109 µVs and T-wave area < 66 µVs (P < 0.001). Event-free survival rate was higher in the subgroup of patients with QRS area ≥ 109 µVs and T-wave area ≥ 66 µVs (n = 616, P < 0.001) and QRS area ≥ 109 µVs and T-wave area < 66 µVs (n = 100, P < 0.001) than the other subgroups. In the multivariate analysis, T-wave area remained associated with echocardiographic response (P = 0.008), but not with the clinical outcome (P = 0.143), when QRS area was included in the model. CONCLUSION: Baseline T-wave area has a significant association with both clinical and echocardiographic outcomes after CRT. The association of T-wave area with echocardiographic response is independent from QRS area; the association with clinical outcome, however, is not.

Electrocardiographic prediction of left ventricular hypertrophy in women and men with left bundle branch block - Comparison of QRS duration, amplitude and voltage-time-integral.

BACKGROUND: Standard ECG criteria for left ventricular (LV) hypertrophy rely on QRS amplitudes. However, in the setting of left bundle branch block (LBBB), ECG correlates of LV hypertrophy are not well established. We sought to evaluate quantitative ECG predictors of LV hypertrophy in the presence of LBBB. METHODS: We included adult patients with typical LBBB having ECG and transthoracic echocardiogram performed within 3 months of each other in 2010-2020. Orthogonal X, Y, Z leads were reconstructed from digital 12­lead ECGs using Kors's matrix. In addition to QRS duration, we evaluated QRS amplitudes and voltage-time-integrals (VTIs) from all 12 leads, X, Y, Z leads and 3D (root-mean-squared) ECG. We used age, sex and BSA-adjusted linear regressions to predict echocardiographic LV calculations (mass, end-diastolic and end-systolic volumes, ejection fraction) from ECG, and separately generated ROC curves for predicting echocardiographic abnormalities. RESULTS: We included 413 patients (53% women, age 73 ± 12 years). All 4 echocardiographic LV calculations were most strongly correlated with QRS duration (all p < 0.00001). In women, QRS duration ≥ 150 ms had sensitivity/specificity 56.3%/64.4% for increased LV mass and 62.7%/67.8% for increased LV end-diastolic volume. In men, QRS duration ≥ 160 ms had a sensitivity/specificity 63.1%/72.1% for increased LV mass and 58.3%/74.5% for increased LV end-diastolic volume. QRS duration was best able to discriminate eccentric hypertrophy (area under ROC curve 0.701) and increased LV end-diastolic volume (0.681). CONCLUSIONS: In patients with LBBB, QRS duration (≥ 150 in women and ≥ 160 in men) is a superior predictor of LV remodeling esp. eccentric hypertrophy and dilation.

QRS area as a predictor of cardiac resynchronization therapy response: A systematic review and meta-analysis.

BACKGROUND: QRS area, a three-dimensional QRS complex, is a novel vectorcardiography method of measuring the magnitude of electrical forces in the heart. Hypothetically, a greater QRS area denotes higher dyssynchrony and indicates potential benefits from cardiac resynchronization therapy (CRT). Previous studies suggest a positive correlation between QRS area and the degree of response to CRT, but its clinical use remains unclear. We performed a meta-analysis of the relationship between QRS area and survival benefit following CRT. METHODS: We comprehensively searched the MEDLINE, EMBASE, and Cochrane databases from inception to August 2021. We included studies with prospective and retrospective cohort designs that reported QRS area before CRT and total mortality. Data from each study were analyzed using a random-effects model. The results were reported as a hazard ratio (HR) and 95% confidence intervals. RESULTS: Five observational studies including 4931 patients were identified. The cut-off values between large and small QRS areas ranged from 102 to 116 µVs. Our analysis showed a larger QRS area was statistically associated with increased 5-year survival in patients implanted with CRT (HR pooled 0.48, 95% CI 0.46-0.51, I2  = 54%, p < .0001). Greater QRS area reduction (pre- and post-implantation) were associated with a lower total mortality rate (HR pooled 0.45, 95% CI 0.38-0.52, I2  = 0%, p < .0001). CONCLUSION: Larger pre-implantation QRS area was associated with increased survival after CRT. QRS area reduction following CRT implantation was also associated with lower mortality. QRS area may potentially become an additional selection criterion for CRT implantations.

Reduction in the QRS area after cardiac resynchronization therapy is associated with survival and echocardiographic response.

INTRODUCTION: Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response. METHODS AND RESULTS: Electrocardiograms (ECG) obtained before and 2-12 months after CRT from 1299 patients in a multi-center CRT-registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12-lead ECGs. The primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end-systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut-off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33-0.56, p < .001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4-4.6, p < .0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p < .0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967-0.994, p = .006). CONCLUSION: ∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome.

Association between vectorcardiographic QRS area and incident heart failure diagnosis and mortality among patients with left bundle branch block: A register-based cohort study.

BACKGROUND: QRS duration and morphology including left bundle branch block (LBBB) are the most widely used electrocardiogram (ECG) markers for assessing ventricular dyssynchrony and predicting heart failure (HF). However, the vectorcardiographic QRS area may more accurately identify delayed left ventricular activation and HF development. OBJECTIVE: We investigated the association between QRS area and incident HF risk in patients with LBBB. METHODS: By crosslinking data from Danish nationwide registries, we identified patients with a first-time digital LBBB ECG between 2001 and 2015. The vectorcardiographic QRS area was derived from a 12­lead ECG using the Kors transformation method and grouped into quartiles. The endpoint was a composite of HF diagnosis, filled prescriptions for loop diuretics, or death from HF. Cause-specific multivariable Cox regression was used to compute hazard ratios(HR) with 95% confidence intervals(CI). RESULTS: We included 3316 patients with LBBB free from prior HF-related events (median age, 72 years; male, 40%). QRS area quartiles comprised Q1, 36-98 µVs; Q2, 99-119 µVs; Q3, 120-145 µVs; and Q4, 146-295 µVs. During a 5-year follow-up, 31% of patients reached the composite endpoint, with a rate of 39% in the highest quartile Q4. A QRS area in quartile Q4 was associated with increased hazard of the composite endpoint (HR:1.48, 95%CI:1.22-1.80) compared with Q1. CONCLUSIONS: Among primary care patients with newly discovered LBBB, a large vectorcardiographic QRS area (146-295 µVs) was associated with an increased risk of incident HF diagnosis, filling prescriptions for loop diuretics, or dying from HF within 5-years.

Sequential His bundle and left ventricular pacing for cardiac resynchronization.

INTRODUCTION: Fusion of left ventricular pacing with intrinsic conduction provides superior resynchronization compared to biventricular pacing. His bundle pacing (HBP) preserves intrinsic conduction and allows for constant fusion with left ventricular pacing. This study evaluated sequential His bundle and left ventricular pacing for cardiac resynchronization therapy (CRT). METHODS: In patients referred for CRT, sequential His bundle and left ventricular pacing was performed when HBP did not correct the QRS. At implant, QRS duration and area were compared between biventricular pacing and His bundle and left ventricular pacing. Devices were programmed for His and left ventricular pacing. Functional status and echocardiography were evaluated in follow up. RESULTS: Twenty-one patients, seven female, 70.7 ± 9.9 years, 57% with nonischemic cardiomyopathy were included. Baseline QRS duration was 170 ± 21 ms and was 157 ± 16 ms with HBP. Biventricular pacing resulted in a QRS duration of 141 ± 15 ms and decreased to 110 ± 14 ms with His bundle and left ventricular pacing (p < .0005). His bundle and left ventricular pacing resulted in a smaller paced QRS area (38.5 ± 22.6 µVs) compared to biventricular pacing (67.5 ± 24.0 µVs) and baseline (78.1 ± 28.1 µVs; p < .0005). Left ventricular ejection fraction increased from 27.6 ± 6.4% to 41.1 ± 12.5 (at 25 mean months, p = .001) and functional class improved from 3.1 ± 0.5 to 2.1 ± 0.8 (at mean 32 months, p < .001). CONCLUSIONS: Sequential His bundle and left ventricular pacing results in superior electrical synchrony in patients with indication for CRT when HBP does not correct the QRS and resulted in promising clinical and echocardiographic response rates.

Fully automated QRS area measurement for predicting response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and conduction abnormalities. However, a significant number of patients do not respond to CRT. Currently employed criteria for selection of patients for this therapy (QRS duration and morphology) have several shortcomings. QRS area was recently shown to provide superior association with CRT response. However, its assessment was not fully automated and required the presence of an expert. OBJECTIVE: Our objective was to develop a fully automated method for the assessment of vector-cardiographic (VCG) QRS area from electrocardiographic (ECG) signals. METHODS: Pre-implantation ECG recordings (N = 864, 695 left-bundle-branch block, 589 men) in PDF files were converted to allow signal processing. QRS complexes were found and clustered into morphological groups. Signals were converted from 12­lead ECG to 3­lead VCG and an average QRS complex was built. QRS area was computed from individual areas in the X, Y and Z leads. Practical usability was evaluated using Kaplan-Meier plots and 5-year follow-up data. RESULTS: The automatically calculated QRS area values were 123 ±â€¯48 µV.s (mean values and SD), while the manually determined QRS area values were 116 ±â€¯51 ms; the correlation coefficient between the two was r = 0.97. The automated and manual methods showed the same ability to stratify the population (hazard ratios 2.09 vs 2.03, respectively). CONCLUSION: The presented approach allows the fully automatic and objective assessment of QRS area values. SIGNIFICANCE: Until this study, assessing QRS area values required an expert, which means both additional costs and a risk of subjectivity. The presented approach eliminates these disadvantages and is publicly available as part of free signal-processing software.

Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes.

INTRODUCTION: Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). METHODS AND RESULTS: VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl , and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 µVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 µVs, IQR:10;57) and YArea (44 µVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl , Δ3DAmpl , ZArea, ΔZArea , Δ3DArea , and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement. CONCLUSION: Of all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method might be an easy, noninvasive tool to guide CRT implantation and optimization.

Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy.

BACKGROUND: QRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection. METHODS: VCG (Frank orthogonal lead system) was recorded prior to CRT device implantation in 81 consecutive patients. VCG parameters, including QRSAREA, were assessed, and compared to QRS duration and morphology. Three LBBB definitions were used, differing in requirement of mid-QRS notching. Responders to CRT (CRT-R) were defined as patients with ≥15% reduction in left ventricular end systolic volume after 6months of CRT. RESULTS: Fifty-seven patients (70%) were CRT-R. QRSAREA was larger in CRT-R than in CRT non-responders (140±42 vs 100±40 µVs, p<0.001) and predicted CRT response better than QRS duration (AUC 0.78 vs 0.62, p=0.030). With a 98µVs cutoff value, QRSAREA identified CRT-R with an odds ratio (OR) of 10.2 and a 95% confidence interval (CI) of 3.4 to 31.1. This OR was higher than that for QRS duration >156ms (OR=2.5; 95% CI 0.9 to 6.6), conventional LBBB classification (OR=5.5; 95% CI 0.9 to 32.4) or LBBB classification according to American guidelines (OR=4.5; 95% CI 1.6 to 12.6) or Strauss (OR=10.0; 95% CI 3.2 to 31.1). CONCLUSION: QRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB. CONDENSED ABSTRACT: In 81 candidates for cardiac resynchronization therapy (CRT) we measured the area of the QRS complex (QRSAREA) using 3-dimensional vectorcardiography. QRSAREA was larger in echocardiographic responders than in non-responders and predicted CRT response better than QRS duration and than simple LBBB criteria. QRSAREA is a promising electrophysiological predictor of CRT response.

Exploring QRS Area beyond Patient Selection in CRT-Can It Guide Left Ventricular Lead Placement?

Vectorcardiographic QRS area is a promising tool for patient selection and implantation guidance in cardiac resynchronization therapy (CRT). Research has mainly focused on the role of QRS area in patient selection for CRT. Recently, QRS area has been proposed as a tool to guide left ventricular lead placement in CRT. Theoretically, vector-based electrical information of ventricular fusion pacing, calculated from the basic 12-lead ECG, can give real-time insight into the extent of resynchronization at any LV lead position, as well as any selected electrode on the LV lead. The objective of this review is to provide an overview of the background of vectorcardiographic QRS area and its potential in optimizing LV lead location in order to optimize the benefits of CRT.

Does mechanical dyssynchrony in addition to QRS area ensure sustained response to cardiac resynchronization therapy?

AIMS: Judicious patient selection for cardiac resynchronization therapy (CRT) may further enhance treatment response. Progress has been made by using improved markers of electrical dyssynchrony and mechanical discoordination, using QRSAREA, and systolic rebound stretch of the septum (SRSsept) or systolic stretch index (SSI), respectively. To date, the relation between these measurements has not yet been investigated. METHODS AND RESULTS: A total of 240 CRT patients were prospectively enrolled from six centres. Patients underwent standard 12-lead electrocardiography, and echocardiography, at baseline, 6-month, and 12-month follow-up. QRSAREA was derived using vectorcardiography, and SRSsept and SSI were measured using strain-analysis. Reverse remodelling was measured as the relative decrease in left ventricular end-systolic volume, indexed to body surface area (ΔLVESVi). Sustained response was defined as ≥15% decrease in LVESVi, at both 6- and 12-month follow-up. QRSAREA and SRSsept were both strong, multivariable adjusted, variables associated with reverse remodelling. SRSsept was associated with response, but only in patients with QRSAREA ≥ 120 µVs (AUC = 0.727 vs. 0.443). Combined presence of SRSsept ≥ 2.5% and QRSAREA ≥ 120 µVs significantly increased reverse remodelling compared with high QRSAREA alone (ΔLVESVi 38 ± 21% vs. 22 ± 21%). As a result, 92% of left bundle branch block (LBBB)-patients with combined electrical and mechanical dysfunction were 'sustained' volumetric responders, as opposed to 51% with high QRSAREA alone. CONCLUSION: Parameters of mechanical dyssynchrony are better associated with response in the presence of a clear underlying electrical substrate. Combined presence of high SRSsept and QRSAREA, but not high QRSAREA alone, ensures a sustained response after CRT in LBBB patients.

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population.

PURPOSE: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. METHODS: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated. RESULTS: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109µVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 µVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 µVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. CONCLUSIONS: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.

Left Ventricular Lead Placement Guided by Reduction in QRS Area.

Background: Reduction in QRS area after cardiac resynchronization therapy (CRT) is associated with improved long-term clinical outcome. The aim of this study was to investigate whether the reduction in QRS area is associated with hemodynamic improvement by pacing different LV sites and can be used to guide LV lead placement. Methods: Patients with a class Ia/IIa CRT indication were prospectively included from three hospitals. Acute hemodynamic response was assessed as the relative change in maximum rate of rise of left ventricular (LV) pressure (%∆LVdP/dtmax). Change in QRS area (∆QRS area), in QRS duration (∆QRS duration), and %∆LVdP/dtmax were studied in relation to different LV pacing locations within a patient. Results: Data from 52 patients paced at 188 different LV pacing sites were investigated. Lateral LV pacing resulted in a larger %∆LVdP/dtmax than anterior or posterior pacing (p = 0.0007). A similar trend was found for ∆QRS area (p = 0.001) but not for ∆QRS duration (p = 0.23). Pacing from the proximal electrode pair resulted in a larger %∆LVdP/dtmax (p = 0.004), and ∆QRS area (p = 0.003) but not ∆QRS duration (p = 0.77). Within patients, correlation between ∆QRS area and %∆LVdP/dtmax was 0.76 (median, IQR 0.35; 0,89). Conclusion: Within patients, ∆QRS area is associated with %∆LVdP/dtmax at different LV pacing locations. Therefore, QRS area, which is an easily, noninvasively obtainable and objective parameter, may be useful to guide LV lead placement in CRT.

Effect of QRS area reduction and myocardial scar on the hemodynamic response to cardiac resynchronization therapy.

BACKGROUND: Vectorcardiographic QRS area (QRSarea) predicts clinical outcomes after cardiac resynchronization therapy (CRT). Myocardial scar adversely affects clinical outcomes after CRT. OBJECTIVE: The purpose of this study in patients with an ideally deployed quadripolar left ventricular (LV) lead (QUAD) was to determine whether reducing QRSarea leads to an acute hemodynamic response (AHR) and whether scar affects this interaction. METHODS: Patients (n = 26; age 69.2 ± 9.12 years [mean ± SD]) underwent assessment of the maximum rate of change of LV pressure (ΔLV dP/dtmax) during CRT using various left ventricular pacing locations (LVPLs). Cardiac magnetic resonance (CMR) scan was used to localize LV myocardial scar. RESULTS: Interindividually, ΔQRSarea (area under the receiver operating characteristic curve [AUC] 0.81; P <.001) and change in QRS duration (ΔQRSd) (AUC 0.76; P <.001) predicted ΔLV dP/dtmax after CRT. Scar burden correlated with ΔQRSarea (r = 0.35; P = .003), ΔQRSarea (r = 0.35; P = .003), and ΔQRSd (r = 0.46; P <.001). A reduction in QRSarea was observed with LVPLs remote from scar (-3.28 ± 38.1 µVs) or in LVPLs in patients with no scar at all (-43.8 ± 36.8 µVs), whereas LVPLs over scar increased QRSarea (22.2 ± 58.4 µVs) (P <.001 for all comparisons). LVPLs within 1 scarred LV segment were associated with lower ΔLV dP/dtmax (-2.21% ± 11.5%) than LVPLs remote from scar (5.23% ± 10.3%; P <.001) or LVPLs in patients with no scar at all (10.2% ± 7.75%) (both P <.001). CONCLUSION: Reducing QRSarea improves the AHR to CRT. Myocardial scar adversely affects ΔQRSarea and the AHR. These findings may support the use of ΔQRSarea and CMR in optimizing CRT using QUAD.

Changes in QRS Area and QRS Duration After Cardiac Resynchronization Therapy Predict Cardiac Mortality, Heart Failure Hospitalizations, and Ventricular Arrhythmias.

Background Predicting clinical outcomes after cardiac resynchronization therapy (CRT) and its optimization remain a challenge. We sought to determine whether pre- and postimplantation QRS area (QRSarea) predict clinical outcomes after CRT. Methods and Results In this retrospective study, QRSarea, derived from pre- and postimplantation vectorcardiography, were assessed in relation to the primary end point of cardiac mortality after CRT with or without defibrillation. Other end points included total mortality, total mortality or heart failure (HF) hospitalization, total mortality or major adverse cardiac events, and the arrhythmic end point of sudden cardiac death or ventricular arrhythmias with or without a shock. In patients (n=380, age 72.0±12.4 years, 68.7% male) undergoing CRT over 7.7 years (median follow-up: 3.8 years [interquartile range 2.3-5.3]), preimplantation QRSarea ≥102 µVs predicted cardiac mortality (HR: 0.36; P<0.001), independent of QRS duration (QRSd) and morphology (P<0.001). A QRSarea reduction ≥45 µVs after CRT predicted cardiac mortality (HR: 0.19), total mortality (HR: 0.50), total mortality or heart failure hospitalization (HR: 0.44), total mortality or major adverse cardiac events (HR: 0.43) (all P<0.001) and the arrhythmic end point (HR: 0.26; P<0.001). A concomitant reduction in QRSarea and QRSd was associated with the lowest risk of cardiac mortality and the arrhythmic end point (both HR: 0.12, P<0.001). Conclusions Pre-implantation QRSarea, derived from vectorcardiography, was superior to QRSd and QRS morphology in predicting cardiac mortality after CRT. A postimplant reduction in both QRSarea and QRSd was associated with the best outcomes, including the arrhythmic end point.

Vectorcardiographic QRS area is associated with long-term outcome after cardiac resynchronization therapy.

BACKGROUND: Recent studies have suggested that vectorcardiographic measures predict left ventricular (LV) reverse remodeling and clinical outcome in patients receiving cardiac resynchronization therapy (CRT). OBJECTIVES: The objectives of this study were to compare predictive abilities of different vectorcardiographic measures (QRS area and sum absolute QRS-T integral) and transformation methods (Kors and inverse Dower) and to assess the independent association between the best predictor and outcomes in CRT recipients. METHODS: This retrospective study included CRT recipients with a digital baseline electrocardiogram, QRS duration ≥120 ms, and ejection fraction ≤35%. The end point was a composite of heart transplantation, LV assist device implantation, or all-cause death. Analyses were performed for the overall cohort and for a prespecified subgroup of patients with left bundle branch block (LBBB). RESULTS: Of 705 included patients with a mean age of 66.6 ± 11.5 years, 492 (70%) were men, 374 (53%) had ischemic heart disease, and 465 (66%) had LBBB. QRS area from vectorcardiograms derived via the Kors transformation demonstrated the best predictive value. In multivariable Cox regression, patients with a smaller QRS area (≤ 95 µVs) had an increased hazard in the overall cohort (adjusted hazard ratio 1.65; 95% CI 1.25-2.18 P < .001) and in the LBBB subgroup (adjusted hazard ratio 1.95; 95% CI 1.38-2.76 P < .001). QRS area was associated with outcome in patients with QRS duration <150 ms (unadjusted hazard ratio 3.85; 95% CI 2.02-7.37 P < .001) and in patients with QRS duration ≥150 ms (unadjusted hazard ratio 1.76; 95% CI 1.32-2.34 P < .001). CONCLUSION: Vectorcardiographic QRS area is associated with survival free from heart transplantation and LV assist device implantation in CRT recipients.