Quantification of abnormal QRS peaks predicts response to cardiac resynchronization therapy and tracks structural remodeling.
ABSTRACT: BACKGROUND:Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response. METHODS:Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT. RESULTS:Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ?150ms, QRSp ?7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ?7 responded than those with QRSp <7 (75 vs. 0%, p<0.05). CONCLUSIONS:Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms.
Project description:Background: Little is known about electrical remodeling of the native conduction systems, particularly how the PR interval changes, after cardiac resynchronization therapy (CRT). We investigated the effects of CRT on the intrinsic PR interval (i-PRi) and QRS duration (i-QRSd). Methods and results: In 100 consecutive CRT recipients with sinus rhythm and long-term follow-up (>1 year), the i-PRi and i-QRSd were measured at baseline and at the last echocardiographic follow-up (33.4 ± 17.9 months) with biventricular pacing temporarily withdrawn. The relative decrease in the left ventricular end-systolic volume (LVESV) was measured to define CRT-responders (?15%) and super-responders (?30%). Following CRT, the left ventricular (LV) ejection fraction increased significantly (p < 0.001). In CRT-responders (n = 71), the LVESV and i-QRSd decreased markedly (170 ± 39 to 159 ± 24 ms, p = 0.012). However, the i-PRi was not shortened with CRT response and was actually likely to increase, even in the super-responder group (n = 33). Moreover, lengthening of the i-PRi was observed consistently irrespective of the CRT response status, beta-blocker use, or amiodarone use. CRT non-responders were associated with a remarkable PR prolongation (p = 0.005) and QRS widening (p = 0.001), along with positive ventricular remodeling. Conclusion: LV volume and i-QRSd decreased markedly with CRT response. However, the i-PRi was not shortened, but rather increased regardless of the degree of CRT response. CRT non-response was associated with a considerable increase in the i-PRi and i-QRSd, along with positive ventricular remodeling. CRT-induced electrical reverse remodeling might occur preferentially in the intraventricular, but not the atrioventricular, conduction system.
Project description:Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown.In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics.Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177 ms (IQR: 160-192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: -6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 ± 2.7%, TomTec: -7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors.Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.
Project description:Background:Trials using echocardiographic mechanical dyssynchrony (MD) parameters in narrow QRS patients have shown a negative response to CRT. We hypothesized MD in these patients may relate to myocardial scar rather than electrical dyssynchrony. Methods:We determined the prevalence of cardiac magnetic resonance (CMR) derived measures of MD in 130 systolic heart failure patients with both broad (? 130 ms - BQRS) and narrow QRS duration (< 130 ms - NQRS). We assessed whether late gadolinium enhancement derived scar might explain the presence of MD amongst narrow QRS patients. Dyssynchrony was calculated on the basis of a systolic dyssynchrony index (SDI). Results:Fifty-nine patients (45%) had a NQRS and the remaining had QRS ? 130 ms (BQRS group). 25% of NQRS patients had MD based on SDI. In all narrow and broad QRS patients with MD there was a significantly lower scar volume than those without MD (7.4 ± 10.5% vs 13.7 ± 13.3% vs. p < 0.01). This was the case in the BQRS group with a significantly lower scar burden in patients with MD (5.0 ± 7.7% vs 15.4 ± 15.6%, p < 0.01). Notably in the NQRS group this difference was absent with an equal scar burden in patients with MD 13.3 ± 13.9% and without MD 12.5 ± 11%, p = 0.92. Conclusions:25% of patients with systolic heart failure and a NQRS (< 130 ms) have CMR derived mechanical dyssynchrony. Our findings suggest MD in this group may be secondary to myocardial scar rather than electrical dyssynchrony and therefore not amenable to correction by CRT. This may give insight into non-response and potential harm from CRT in this group.
Project description:AIM:The goal of this study was to compare associations between clinical and ECG predictors of cardiac resynchronization therapy (CRT) response with electrical dyssynchrony. METHODS:Body-surface potentials were recorded using a 120-lead system in 4 patients (age 62 ± 12 y, left ventricular ejection fraction (LVEF) 29 ± 5 %; QRS duration 154 ± 19 ms) with post-myocardial infarction scar and left bundle branch block before CRT implantation. A patient-specific heart-torso model derived from MRI with 291 heart-surface nodes was developed. Electrical dyssynchrony index (EDI) was computed as the standard deviation of activation times on the epicardium while uncoupling index (UI) was measured as the difference between the activation times. RESULTS:QRS duration correlated with mean activation time (r = 0.977; P = 0.023), but did not correlate with EDI or UI. LVEF inversely correlated with activation time at the lowest 20th percentile (r = -0.960; P = 0.040). Sum absolute QRST integral (SAI QRST), measured on orthogonal XYZ ECG, correlated with EDI (r = 0.955; P = 0.045), and characterized late-activated area of the left ventricle. CONCLUSION:SAI QRST is a measure of electrical dyssynchrony on ECG.
Project description:Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50-100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9-13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9-13 ms lower QRSd thresholds for female CRT guidelines.
Project description:Response to cardiac resynchronization therapy (CRT) is commonly assessed after 6 or 12 months. We evaluated subsequent echocardiographic changes, serial QRS duration, and clinical outcomes in patients showing delayed responses to CRT after 12 months.Among all patients who received CRT in Seoul St. Mary's Hospital, 36 one-year survivors were enrolled. Indicators of a positive CRT response were ≥ 15% reduction in left ventricular end-systolic volume (LVESV) or ≥ 10% increase in left ventricular ejection fraction (LVEF) on any follow up echocardiogram. We defined the early responders as patients responding before one year, the late responders as patients responding after one year, and the non-responders as patients who did not respond on any follow-up echocardiogram.We identified 17 early responders, 10 late responders, and 9 non-responders. The late responders showed modest improvement in LVESV and LVEF at two years after CRT. QRS duration was shortened the day after CRT in all three groups. Narrowed QRS was maintained for two years in early and late responders, whereas it was continuously prolonged over time in non-responders. Incidence of all-cause death or heart failure hospitalization was comparable between early and late responders, while non-responders showed worst prognosis.Patients responding to CRT after one year show modest echocardiographic improvement but clinical outcome is similar to early responders. Shorter baseline QRS duration and long-term maintenance of QRS duration shortening are important features of the late responders to CRT.
Project description:Background:Conventional complete left bundle branch block (CLBBB) criteria sometimes result in a false-positive diagnosis that does not represent dyssynchrony. Recently, true CLBBB criteria have been proposed to detect responders to cardiac resynchronization therapy (CRT), although their correlation with severity of dyssynchrony or natural prognosis is unclear. Methods:Ninety-four consecutive patients (74 ± 9 years, 63 men) with conventional CLBBB during sinus rhythm underwent semiconductor SPECT. They were divided into two groups: patients with true CLBBB and others. True CLBBB was characterized by the mid-QRS notching/slurring and wide QRS duration (male, ≥140 milliseconds; female, ≥130 milliseconds). Multivariate analysis was performed to detect left ventricular dyssynchrony (LVD), defined as bandwidth ≥145° and/or phase standard deviation (SD) ≥43°. Primary endpoints (hospitalization for heart failure or cardiac death) were evaluated. Results:True CLBBB had wider bandwidth (145 ± 83° vs 110 ± 64°, P = 0.024) and higher phase SD (48 ± 26° vs 35 ± 19°, P = 0.007). Ejection fraction (EF), end-diastolic volume (EDV), summed rest score (SRS), and the presence of ischemic heart disease (IHD) showed no differences between groups (P = 0.401, 0.591, 0.165, and 0.212, respectively). Multivariate analysis revealed that true CLBBB, EF, and EDV were significant predictors of LVD (odds ratio, 12.6, 0.90, 1.03; P = 0.003, 0.002, 0.022, respectively). At 3-year follow-up (median 667 days), primary endpoints were comparable in both groups (log-rank, P = 0.92). Conclusions:Patients with true CLBBB had more severe dyssynchrony on single-photon emission computed tomography than patients with nontrue CLBBB. On the other hand, the two groups showed no differences in EF, EDV, the presence of IHD, hospitalization for heart failure, and cardiac death.
Project description:BACKGROUND:Numerous studies have illustrated the association of QRS width with the incidence of echocardiographic response to cardiac resynchronization therapy (CRT). This study aimed to summarize the observational studies regarding the magnitude of change in QRS width between responders and nonresponders to CRT. METHODS:The PubMed, Embase, and the Cochrane Library were systematically searched for relevant studies investigating the changes of QRS width with the incidence of echocardiographic response to CRT from inception till May 2019. The pooled weighted mean difference (WMD) with 95% confidence interval (CI) was calculated through random-effects model. RESULTS:Five prospective and 6 retrospective studies with a total of 1524 patients were selected for final analysis. The reduction of QRS width in responders was significantly greater than nonresponders (WMD: -20.54 ms; 95% CI: -26.78 to -14.29; P?<?.001). Moreover, responders were associated with greater percentage reduction in QRS width when compared with nonresponders (WMD: -8.80%; 95% CI: -13.08 to -4.52; P?<?.001). Finally, the mean change in QRS width between responders and nonresponders differed when stratified by country, study design, mean age, percentage male, ejection fraction, measuring time of postimplanted QRS, ischemic cardiomyopathy, atrial fibrillation, and study quality. CONCLUSIONS:These findings indicated that shortening QRS width after CRT device implantation showed association with greater incidence of echocardiographic responses to CRT. Further prospective studies should be conducted to evaluate the prognostic values of QRS width on the incidence of echocardiographic response to CRT.
Project description:Previous methods to quantify dyssynchrony could not determine regional 3-dimensional (3-D) strain. We hypothesized that a novel 3-D speckle tracking strain imaging system can quantify left ventricular (LV) dyssynchrony and site of latest mechanical activation. We studied 64 subjects; 54 patients with heart failure were referred for cardiac resynchronization therapy (CRT) with an ejection fraction 25 +/- 6% and QRS interval 165 +/- 29 ms and 10 healthy volunteer controls. The 3-D speckle tracking system determined radial strain using a 16-segment model from a pyramidal 3-D dataset. Dyssynchrony was quantified as maximal opposing wall delay and SD in time to peak strain. The 3-D analysis was compared to standard 2-dimensional (2-D) strain datasets and site of 3-D latest mechanical activation, not possible by 2D was quantified. As expected, dyssynchrony in patients on CRT was significantly greater than in controls (maximal opposing wall delay 316 +/- 112 vs 59 +/- 12 ms and SD 124 +/- 48 vs 28 +/- 11 ms, p <0.001 vs normal). The 3-D opposing wall delay was closely correlated with 3-D 16-segment SD (r = 0.95) and 2-D mid-LV strain (r = 0.83) and SD (r = 0.85, all p values <0.001). The 3-D site of the latest mechanical activation was most commonly midposterior (26%), basal posterior (22%), midlateral (20%), and basal lateral (17%). Eleven patients studied after CRT demonstrated improvements in 3-D synchrony (300 +/- 124 to 94 +/- 37 ms) and ejection fraction (24 +/- 6% to 31 +/- 7%, p <0.05). In conclusion, 3-D speckle tracking can successfully quantify 3-D dyssynchrony and site the latest mechanical activation. This approach may play a clinical role in management of patients on CRT.
Project description:<h4>Background</h4>Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure, but still 30% of patients failed to respond to such therapy. This lack of response may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on acute response following CRT implantation.<h4>Methods</h4>Fifty-one consecutive patients with heart failure (LV ejection fraction 27% +/- 5%, 67% ischemic cardiomyopathy) underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve (improvement in LV ejection fraction) and local contractile reserve in the region of the LV pacing lead (assessed by radial strain using speckle tracking analysis). Responders were defined by an increase in stroke volume > or = 15% after CRT.<h4>Results</h4>Compared with nonresponders, responders (25 patients) showed a greater exercise-induced increase in LV ejection fraction, a higher degree of mitral regurgitation and a significant extent of LV dyssynchrony. The presence of contractile reserve was directly related to the acute increase in stroke volume (r = 0.48, p < 0.001). Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders during exercise than in nonresponders (p < 0.0001).<h4>Conclusion</h4>The present study showed that response to CRT largely depends not only on the extent of LV dyssynchrony and the severity of mitral regurgitation but also on the presence of contractile reserve.