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:AimsTo evaluate the effects of cardiac resynchronization therapy (CRT) on long-term survival of patients without baseline left ventricular (LV) mechanical dyssynchrony.Methods and resultsA total of 290 heart failure patients (age 67 ± 10 years, 77% males) without significant baseline LV dyssynchrony (<60 ms as assessed with tissue Doppler imaging) were treated with CRT. Patients were divided according to the median LV dyssynchrony measured after 48 h of CRT into two groups. All-cause mortality was compared between the subgroups. In addition, the all-cause mortality rates of these subgroups were compared with the all-cause mortality of 290 heart failure patients treated with CRT who showed significant LV dyssynchrony (≥60 ms) at baseline. In the group of patients without significant LV dyssynchrony, median LV dyssynchrony increased from 22 ms (inter-quartile range 16-34 ms) at baseline to 40 ms (24-56 ms) 48 h after CRT. The cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with LV dyssynchrony ≥40 ms 48 h after CRT implantation were significantly higher when compared with patients with LV dyssynchrony <40 ms (10, 17, and 23 vs. 3, 8, and 10%, respectively; log-rank P< 0.001). Finally, the cumulative mortality rates at 1-, 2-, and 3-year follow-up of patients with baseline LV dyssynchrony were 3, 8, and 11%, respectively (log-rank P= 0.375 vs. patients with LV dyssynchrony <40 ms). Induction of LV dyssynchrony after CRT was an independent predictor of mortality (hazard ratio: 1.247; P= 0.009).ConclusionIn patients without significant LV dyssynchrony, the induction of LV dyssynchrony after CRT may be related to a less favourable long-term outcome.
Project description:AimsJudicious 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 resultsA 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.ConclusionParameters 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.
Project description:BackgroundAdaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear.ObjectiveCompare effects of aCRT and conventional CRT on electrical dyssynchrony.MethodsA prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times.ResultsWe randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups.ConclusionThe effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.
Project description:Over the past two decades, cardiac resynchronization therapy (CRT) became an established treatment option for patients with symptomatic heart failure [...].
Project description:BackgroundApproximately 20-40% of recipients of cardiac resynchronization therapy (CRT) do not respond to it based on the current patient selection criteria. The purpose of this study was to identify baseline parameters that can predict CRT response and to evaluate the effect of those predictive parameters on long-term prognosis.MethodsThis was a retrospective, nonrandomized, noncontrolled cohort study. Patients who received CRT in our centre were divided into responders and nonresponders by the definition of CRT response (an increase in left ventricular ejection fraction (LVEF) of ≥5% and improvement of ≥1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up).ResultsOf the 101 patients, 68 were responders and 33 were nonresponders. Left ventricular end-diastolic diameter (LVEDD; OR: 0.88, 95% CI: 0.81-0.95, P=0.001) and QRS duration (OR: 1.07, 95% CI: 1.04-1.10, P < 0.001) were independent predictors of CRT response. The combination of LVEDD and QRS duration was more valuable for predicting CRT response (AUC 0.836; 95% CI: 0.76-0.91; P < 0.001). Moreover, the combination of LVEDD ≤ 71 mm and QRS duration ≥ 170 ms had a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. In addition, baseline LVEDD had a positive correlation with QRS duration (R=0.199, P=0.046). Responders to CRT had better LV reverse remodeling.ConclusionThe combination of LVEDD and QRS duration provided more robust prediction of CRT response. Moreover, the combination of LVEDD ≤ 71 mm and QRS duration ≥ 170 ms was associated with a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. Our results may be useful to provide individualized patient selection for CRT.
Project description:Cardiac dyssynchrony arises from conduction abnormalities during heart failure and worsens morbidity and mortality. Cardiac resynchronization therapy (CRT) re-coordinates contraction using bi-ventricular pacing, but the cellular and molecular mechanisms involved remain largely unknown. The aim is to determine how dyssynchronous heart failure (HFdys ) alters the phospho-proteome and how CRT interacts with this unique phospho-proteome by analyzing Ser/Thr and Tyr phosphorylation. Phospho-enriched myocardium from dog models of Control, HFdys , and CRT is analyzed via MS. There were 209 regulated phospho-sites among 1761 identified sites. Compared to Con and CRT, HFdys is hyper-phosphorylated and tyrosine phosphorylation is more likely to be involved in signaling that increased with HFdys and was exacerbated by CRT. For each regulated site, the most-likely targeting-kinase is predicted, and CK2 is highly specific for sites that are "fixed" by CRT, suggesting activation of CK2 signaling occurs in HFdys that is reversed by CRT, which is supported by western blot analysis. These data elucidate signaling networks and kinases that may be involved and deserve further study. Importantly, a possible role for CK2 modulation in CRT has been identified. This may be harnessed in the future therapeutically to compliment CRT, improving its clinical effects.
Project description:BackgroundTo evaluate the impact of changes in the filtered QRS duration (fQRS) on signal-averaged electrocardiograms (SAECGs) from pre- to postimplantation on the clinical outcomes in nonischemic heart failure (HF) patients under cardiac resynchronization therapy (CRT).MethodsWe studied 103 patients with nonischemic HF and sinus rhythm who underwent CRT implantation. SAECGs were obtained within 1 week before and 1 week after implantation and narrowing fQRS was defined as a decrease in fQRS from pre- to postimplantation. Echocardiography was performed before and 6 months after CRT implantation. The primary outcome was death from any cause. The secondary outcomes were hospitalization due to worsened HF and occurrence of ventricular tachyarrhythmias.ResultsOf the 103 CRT patients, 53 (51%) showed narrowing fQRS. Left ventricular end-diastolic volume and end-systolic volume were significantly reduced (both p < .001), and the left ventricular ejection fraction was significantly increased (p < .001) after CRT in patients with narrowing fQRS, but not in patients with nonnarrowing fQRS. During a median follow-up period of 33 months, patients with narrowing fQRS exhibited better survival than patients with nonnarrowing fQRS (p = .007). A lower incidence of hospitalization due to worsened HF (p < .001) and a lower occurrence of ventricular tachyarrhythmias (p = .071) were obtained in patients with narrowing fQRS. After adjusting for confounding variables, narrowing fQRS was associated with a low risk of mortality (HR 0.27, p = .006).ConclusionOur results suggested that narrowing fQRS on SAECG after CRT implantation predicts LV reverse remodeling and long-term outcomes in nonischemic HF patients.
Project description:BackgroundThe systolic and diastolic dyssynchrony is physiologically related, but measure different left ventricular mechanisms. Left ventricular systolic mechanical dyssynchrony (systolic LVMD) has shown significant clinical values in improving cardiac resynchronization therapy (CRT) response in the heart failure patients with dilated cardiomyopathy (DCM). Our recent study demonstrated that LV diastolic dyssynchrony (diastolic LVMD) parameters have important prognostic values for DCM patients. However, there are a limited number of studies about the clinical value of diastolic LVMD for CRT. This study aims to explore the predictive values of both systolic LVMD and diastolic LVMD for CRT in DCM patients.MethodsEighty-four consecutive CRT patients with both DCM and complete left bundle branch block (CLBBB) who received gated resting SPECT MPI at baseline were included in the present study. The phase analysis technique was applied on resting gated short-axis SPECT MPI images to measure systolic LVMD and diastolic LVMD, characterized by phase standard deviation (PSD) and phase histogram bandwidth (PBW). CRT response was defined as ≥ 5% improvement of LVEF at 6-month follow-up. Variables with P < 0.10 in the univariate analysis were included in the multivariate cox analysis.ResultsDuring the follow-up period, 59.5% (50 of 84) patients were CRT responders. The univariate cox regression analysis showed that at baseline QRS duration, non-sustained ventricular tachycardia (NS-VT), systolic PSD, systolic PBW, diastolic PSD, diastolic PBW, scar burden and LV lead in the scarred myocardium were statistically significantly associated with CRT response. The multivariate cox regression analysis showed that QRS duration, NS-VT, systolic PSD, systolic PBW, diastolic PSD, and diastolic PBW were independent predictive factors for CRT response. Furthermore, the rate of CRT response was 94.4% (17 of 18) in patients whose LV lead was in the segments with both the first three late contraction and the first three late relaxation; by contrast, the rate of CRT response was only 6.7% (1 of 15, P < 0.000) in patients whose LV lead was in the segments with neither the first three late contraction nor the first three late relaxation.ConclusionBoth systolic LVMD and diastolic LVMD from gated SPECT MPI have important predictive values for CRT response in DCM patients. Pacing at LV segments with both late contraction and late relaxation has potential to increase the CRT response.
Project description:BACKGROUND:QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. METHODS AND RESULTS:Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [P<0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. CONCLUSIONS:Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm.