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Aim: Cardiac resynchronization therapy (CRT) is a cornerstone in the management of chronic heart failure in patients with a broad or paced QRS. However, data on long-term outcome after upgrade to CRT are scarce., Methods and Results: This international, multicentre retrospective registry included 2275 patients who underwent a de novo or upgrade CRT implantation with a mean follow-up of 3.6 ± 2.7 years. The primary composite endpoint included all-cause mortality, heart transplantation, or ventricular assist device implantation. The secondary endpoint was first heart failure admission. Multivariable Cox regression and propensity score matching (PSM) analyses were performed. Patients who underwent CRT upgrade (n = 605, 26.6%) were less likely female (19.7% vs. 28.8%, p < 0.001), more often had ischeemic cardiomyopathy (49.8% vs. 40.2%, p < 0.001), and had worse renal function (median estimated glomerular filtration rate 50.3 ml/min/1.73 m 2 [35.8-69.5] vs. 59.9 ml/min/1.73 m 2 [43.0-76.5], p < 0.001). The incidence rate of the composite endpoint was 10.8%/year after CRT upgrade versus 7.1%/year for de novo implantations (p < 0.001). PSM for the primary endpoint resulted in 488 pairs. After propensity score matching, upgrade to CRT was associated with a higher chance to reach the composite endpoint (multivariable hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.08-1.70), for both upgrade from pacemaker (multivariable HR 1.33, 95% CI 1.03-1.70) and implantable cardioverter-defibrillator (ICD) (multivariable HR 1.40, 95% CI 1.01-1.95). PSM for the secondary endpoint resulted in 277 pairs. After PSM, upgrade to CRT was associated with a higher chance for heart failure admission (HR 1.74, 95% CI 1.26-2.41)., Conclusion: In this retrospective analysis, the outcome of patients who underwent upgrades to CRT differed significantly from patients who underwent de novo CRT implantation, particularly for upgrades from ICD. Importantly, this difference in outcome does not imply a causal relation between therapy and outcome but rather a difference between two different patient populations., (© 2023 European Society of Cardiology.)

Aims: The contribution of adverse ventricular interdependence remains undervalued in heart failure or pulmonary vascular disease, and not much is known about its dynamic nature during exercise and respiration. In this study, we evaluated ventricular interaction during exercise in patients with heart failure with preserved ejection fraction (HFpEF) and patients with chronic thromboembolic pulmonary hypertension (CTEPH) as compared with healthy controls., Methods and Results: Forty-six subjects (10 controls, 19 CTEPH patients, and 17 HFpEF patients) underwent cardiac magnetic resonance imaging during exercise. Ventricular interaction was determined through analysis of the septal curvature (SC) of a mid-ventricular short-axis slice at end-diastole, end-systole, and early-diastole, both in expiration and inspiration. Exercise amplified ventricular interaction in CTEPH patients and to a lesser extent in HFpEF patients (P < 0.05 for decrease in SC with exercise). Adverse interaction was most profound in early-diastole and most pronounced in CTEPH patients (P < 0.05 interaction group * exercise) because of a disproportionate increase RV afterload (P < 0.05 to both controls and HFpEF) and diastolic pericardial restraint (P < 0.001 for interaction group * exercise) during exercise. Inspiration enhanced diastolic interdependence in CTEPH and HFpEF patients (P < 0.05 vs. expiration). Both at rest and during exercise, SC strongly correlated with RV volumes and pulmonary artery pressures (all P < 0.05)., Conclusions: Exercise amplifies adverse right-left ventricular interactions in CTEPH, while a more moderate effect is observed in isolated post-capillary HFpEF. Given the strong link with RV function and pulmonary hemodynamic, assessing ventricular interaction with exCMR might be valuable from a diagnostic or therapeutic perspective., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Cardiac output limitation is a fundamental feature of heart failure with preserved ejection fraction (HFpEF) but the relative contribution of its determinants in symptomatic vs. asymptomatic stages are not well characterized. We aimed to gain insight into disease mechanisms by performing comprehensive comparative non-invasive exercise imaging in patients across the disease spectrum., Methods and Results: We performed bicycle stress echocardiography in 10 healthy controls, 13 patients with hypertensive left ventricular (LV) concentric remodelling and asymptomatic diastolic dysfunction (HTDD), 15 HFpEF patients, and 15 subjects with isolated right ventricular (RV) dysfunction secondary to chronic thromboembolic pulmonary hypertension (CTEPH). During exercise, ventricular performance differed across the groups (all P ≤ 0.01 for interaction). Notably in controls, LV and RV function significantly increased (all P < 0.05) while both LV systolic and diastolic reserve were significantly reduced in HFpEF patients. Likewise, RV systolic reserve was also impaired in HFpEF but not to the extent of CTEPH patients (P < 0.001 between groups). HTDD patients behaved as an intermediary group with borderline LV systolic and diastolic reserve and reduced RV systolic reserve. The increased pulmonary vascular (PV) load in HFpEF and CTEPH patients in combination with impaired RV reserve resulted in RV-pulmonary artery uncoupling during exercise., Conclusion: The multifaceted decline of cardiac and PV function accompanying disease progression in HFpEF is unmasked by exercise and already emerges in preclinical disease. The revelation of these subtle abnormalities during exercise illustrates the benefit of exercise imaging and creates new prospects for early diagnosis and management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Aims: Identifying early right ventricular (RV) dysfunction and impaired vasodilator reserve is challenging in heart failure with preserved ejection fraction (HFpEF). We hypothesized that cardiac magnetic resonance (CMR)-based exercise imaging and serial cyclic guanosine monophosphate (cGMP) measurements can identify dynamic RV-arterial uncoupling and responsiveness to pulmonary vasodilators at early stages of the HFpEF syndrome., Methods and Results: Patients with HFpEF (n = 16), impaired left ventricular relaxation due to concentric remodelling (LVCR, n = 7), and healthy controls (n = 8) underwent CMR at rest and during supine bicycle exercise with simultaneous measurements of central haemodynamics and circulating cGMP levels, before and after oral administration of 50 mg sildenafil. At rest, mean pulmonary artery pressures (mPAP) were higher in HFpEF, compared with LVCR and controls (27 ± 2, 18 ± 1, and 11 ± 1, respectively; P = 0.01), whereas biventricular volumes, heart rate, and stroke volume were similar. During exercise, LVCR and HFpEF had a greater increase in the ratio of mPAP over cardiac output than controls (5.50 ± 0.77 and 6.34 ± 0.86 vs. 2.24 ± 0.55 in controls, P = 0.005). The ratio of peak exercise to rest RV end-systolic pressure-volume, a surrogate of RV contractility, was significantly reduced in LVCR and HFpEF (2.32 ± 0.17 and 1.56 ± 0.08 vs. 3.49 ± 0.35 in controls, P < 0.001) and correlated with peak exercise VO 2 (R 2  = 0.648, P < 0.001). cGMP levels increased with exercise across the HFpEF spectrum (P < 0.05 vs. baseline), except when postcapillary pulmonary hypertension was present at rest (P = 0.73 vs. baseline). A single sildenafil administration failed to increase circulating cGMP levels and did not improve RV performance., Conclusion: Exercise CMR identifies impaired RV-arterial coupling at an early stage of HFpEF. Circulating cGMP levels phenocopy the haemodynamic spectrum in HFpEF but fail to increase after phosphodiesterase type 5 inhibition, endorsing the need for alternative interventions to increase cGMP signalling in HFpEF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain., Purpose: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT., Methods: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18 F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent., Results: We evaluated 88 patients (67 ± 10 years, 72% males). 18 F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively., Conclusions: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

This subanalysis of the Euro-CRT survey II specifically focus on Belgian practice for CRT implantation. It explores Belgian adherence with the guidelines but also benchmark CRT practice in Belgium against the other European countries. Overall, Belgian management of CRT implantation is performed with great agreement with guidelines. This report could be used to provide guidance for both practical and economical approaches.

Background: Myocardial scarring from infarction or nonischemic fibrosis forms an arrhythmogenic substrate. The Selvester QRS score has been developed to estimate myocardial scar from the 12-lead electrocardiogram., Objective: We aimed to assess the value of an automated version of the Selvester QRS score for the prediction of implantable cardioverter-defibrillator (ICD) therapy and death in patients undergoing primary prevention ICD implantation., Methods: Unselected patients undergoing primary prevention ICD implantation were included in this retrospective, observational, multicenter study. The QRS score was calculated automatically from a digital standard preimplantation 12-lead electrocardiogram and was correlated to the occurrence of death and appropriate and inappropriate shocks during follow-up. Analyses were performed in groups defined by QRS duration < 130 ms vs ≥ 130 ms., Results: Overall, 1047 patients (872 [83%] men; median age 64 years IQR [55-71]) with ischemic (648, 62%) or nonischemic (399, 38%) cardiomyopathy were included. The median QRS duration was 123 ms (interquartile range [IQR] 111-157 ms), and the median QRS score was 5 (IQR 2-8). The QRS duration was <130 ms in 59% and ≥130 ms in 41%. During a median follow-up of 45 months (IQR 24-72 months), a QRS score of ≥5 was independently associated with a significantly higher risk of mortality (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.05-2.66; P = .031) and appropriate (HR 1.83; 95% CI 1.07-3.14; P = .028) and inappropriate (HR 2.32; 95% CI 1.04-5.17; P = .039) shocks in patients with QRS duration ≥ 130 ms. No association of the QRS score and outcome was observed in patients with QRS duration < 130 ms (P > .05)., Conclusion: The automatically calculated Selvester QRS score, an indicator of myocardial scar burden, predicts mortality and appropriate and inappropriate shocks in patients undergoing primary prevention ICD implantation with a prolonged QRS duration., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Setting up a randomized trial to assess the association of mechanical dyssynchrony (MD) and the success of cardiac resynchronization therapy (CRT) in heart failure with a wide QRS complex is ethically challenging. We therefore investigated this association in a retrospective cohort study observing different treatment strategies which were chosen based on the availability of health care resources. The survival of 500 patients from six Western European centers treated with CRT was compared to their 137 Eastern European counterparts not treated with CRT, with regard to the presence of MD. MD was visually assessed and was defined as the presence of apical rocking and/or septal flash. Patients were followed for a mean of 26 ± 8 months for the occurrence of death of any cause. As compared with medical therapy alone, CRT was associated with a more favorable survival (hazard ratio (HR), 0.53; 95% confidence interval (CI) 0.35-0.79; P = 0.002). Patients with MD treated by CRT had better survival than patients belonging to all other groups-they showed 72%, 66% and 56% reduction in all-cause mortality, respectively, compared to patients with MD not treated by CRT (HR 0.28; 95% CI 0.17-0.44), patients without MD treated by CRT (HR 0.34; 95% CI 0.22-0.52) and patients without MD not treated by CRT (HR 0.44; 95% CI 0.25-0.76). Patients with wide QRS complex who are treated with CRT have a significantly better survival when MD is present.

Background: The necessity of neurohumoral blockers in patients with heart failure who demonstrate normalized ejection fractions after cardiac resynchronization therapy remains unclear., Objectives: The aim of this study was to investigate the feasibility and safety of neurohumoral blocker withdrawal in patients with normalized ejection fractions after cardiac resynchronization therapy., Methods: In this prospective, open-label, randomized controlled pilot trial with a 2 × 2 factorial design, subjects were randomized to withdrawal of renin-angiotensin-aldosterone system inhibitors and/or beta-blockers versus continuation of treatment. The primary endpoint was a recurrence of negative remodeling, defined as an increase in left ventricular end-systolic volume index of >15% at 24 months. The secondary endpoint was a composite safety endpoint of all-cause mortality, heart failure-related hospitalizations, and incidence of sustained ventricular arrhythmias at 24 months., Results: Eighty subjects were consecutively enrolled and randomized among 4 groups (continuation of neurohumoral blocker therapy, n = 20; withdrawal of renin-angiotensin-aldosterone system inhibitors, n = 20; withdrawal of beta-blockers, n = 20; and withdrawal of renin-angiotensin-aldosterone system inhibitors and beta-blockers, n = 20). Of the 80 subjects, 6 (7.5%) met the primary and 4 (5%) the secondary endpoint. However, re-initiation of neurohumoral blockers occurred in 17 subjects because of hypertension or supraventricular arrhythmias., Conclusions: The incidence of the primary and secondary endpoints over a follow-up period of 2 years was low in both the control group and in the groups in which neurohumoral blockers were discontinued. However, neurohumoral blocker withdrawal was hampered by cardiac comorbidities. (Systematic Withdrawal of Neurohumoral Blocker Therapy in Optimally Responding CRT Patients [STOP-CRT]; NCT02200822)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aim: To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines., Methods and Results: Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37-86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P < 0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P = 0.02). Comparable results were observed using the latest American Guidelines., Conclusion: Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony.

Background: Sudden cardiac death (SCD) results from a complex interplay of abnormalities in autonomic function, myocardial substrate and vulnerability. We studied whether a combination of noninvasive risk stratification tests reflecting these key players could improve risk stratification., Methods: Patients implanted with an ICD in whom 24-hr holter recordings were available prior to implant were included. QRS fragmentation (fQRS) was selected as measure of myocardial substrate and a high ventricular premature beat count (VPB >10/hr) for arrhythmic vulnerability. From receiver operating characteristics analysis, detrended fluctuation analysis (DFA), turbulence slope, and deceleration capacity were selected for autonomic function. Adjusted Cox regression analysis with comparison of C-statistics was performed to predict first appropriate shock (AS) and total mortality., Results: A total of 220 patients were included in the analysis with an overall follow-up of 4.3 ± 3.1 years. A model including VPB >10/hr, inferior fQRS, and abnormal nonedited DFA was the best for prediction of AS after 1 year of follow-up with a trends toward improvement of the C-statistics compared to baseline (p = 0.055). The risk increased significantly with every abnormal test (HR 1.793, 95%CI 1.255-2.564). A model including fQRS in any region and abnormal edited DFA was the best for prediction of mortality after 3 years of follow-up with significant improvement of the C-statistics (p = 0.023). Each abnormal test was associated with a significant increase in mortality (HR 5.069, 95%CI 1.978-12.994)., Conclusion: Combining noninvasive risk stratification tests according to their physiological background can improve the risk prediction of SCD and mortality., (© 2018 Wiley Periodicals, Inc.)

Objectives There is conflicting evidence concerning the role of right ventricular (RV) systolic dysfunction in the long-term clinical outcome after cardiac resynchronization therapy (CRT). Therefore we aimed to assess evolution of RV systolic function during CRT, covariates associated with its improvement, and its impact on outcome. Methods and results All CRT device implantations (Jan 2009-Dec 2011) in our institution were reviewed. Records of 69 patients (25% female, mean age 62.8 ± 9.2 years, mean left ventricular (LV) ejection fraction 27 ± 8%) were analyzed. Baseline RV fractional area change (FAC) < 35% was present in 37 patients (54%). At one year, 24 of them (65%) improved in RV FAC. LV remodeling and mitral regurgitation were significantly associated with the likelihood of RV FAC improvement (OR 4.80, 95% CI 1.13-20.46, P = 0.034 and OR 0.32, 95% CI 0.12-0.89, P = 0.029, respectively). The composite endpoint of death or heart transplantation occurred in 23 patients (33%) over a mean follow-up of 2.8 ± 1.4 years. RV FAC at one year (HR 0.90, 95% CI 0.86-0.94, P < .001) was, independently of NYHA class and LV remodeling, associated with clinical outcome. Conclusions RV systolic function might improve during CRT. This seems mainly due to changed left-sided hemodynamics and LV remodeling. Good RV systolic function is independently related with better outcome.

Aims: Apical rocking (ApRock) and septal flash (SF) are often observed phenomena in asynchronously contracting ventricles. We investigated the relationship of visually assessed ApRock and SF, reverse remodelling, and long-term survival in cardiac resynchronization therapy (CRT) candidates., Methods and Results: A total of 1060 patients eligible for CRT underwent echocardiographic examinations before and 12 ± 6 months after device implantation. Three blinded physicians were asked to visually assess the presence of ApRock and SF before device implantation and also their correction by CRT 12 ± 6 months post-implantation. Patients with a left ventricular (LV) end-systolic volume decrease of ≥15% during the first year of follow-up were regarded as responders. Patients were followed for a median period of 46 months (interquartile range: 27-65 months) for the occurrence of death of any cause. If corrected by CRT, visually assessed ApRock and SF were associated with reverse remodelling with a sensitivity of 84 and 79%, specificity of 79 and 74%, and accuracy of 82 and 77%, respectively. ApRock (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.30-0.53, P < 0.0001) and SF (HR 0.45 [CI 0.34-0.61], P < 0.001) were independently associated with lower all-cause mortality after CRT and had an incremental value over clinical variables and QRS width for identifying CRT responders. Both the absence of ApRock/SF and unsuccessful correction of ApRock/SF despite CRT were associated with a high risk for non-response and an unfavourable long-term survival., Conclusion: A specific LV mechanical dyssynchrony pattern, characterized by ApRock and SF, is associated with a more favourable long-term survival after CRT. Both parameters are also indicators of an effective therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objective: The choice between a resynchronization pacemaker (CRT-P) or defibrillator (CRT-D) is still a matter of debate. We hypothesised that when selecting patients based on co-morbidities and age as proposed by the ESC-guidelines, there would be no long-term survival benefit of CRT-D compared to CRT-P., Methods: We performed a retrospective analysis of patients who received a CRT device at the University Hospitals Leuven between 2001 and 2007. For the analysis of the association between predictors and outcome, uni- and multivariate Cox regression analyses were performed. We present data from three multivariate models., Results: A total of 144 CRT devices were implanted (CRT-D n=98, CRT-P n=46). Patients who received a CRT-P were older and had a higher prevalence of co-morbidities. Patients who received a CRT-D had a significant lower mortality. When applying incremental multivariate analysis using 1st variables with a P < 0.05 in univariate analysis, 2nd variables with a P < 0.10 and 3rd adding on top all the baseline variables that were significantly different between the two groups, the significance of a possible survival benefit for CRT-D over CRT-P disappeared: risk model 1, hazard ratio 2.21 (P = 0.008), risk model 2, HR 1.81 (P = 0.069), and risk model 3, HR 1.85 (P = 0.091). The use of amiodarone and the presence of COPD or renal insufficiency remained associated with a significant, higher mortality risk, while the use of beta blockers was protective in all three models., Conclusion: The choice of a CRT-D seemed a predictor of improved survival in simple but not in more complex multivariable analyses. The fact that the survival benefit strongly depended on the number of co-variables suggests that it is at most marginal.

Aims: Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction (LVEF) and the response to cardiac resynchronization therapy (CRT). Using apical rocking (ApRock) as surrogate dyssynchrony parameter, we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular (LV) dyssynchrony and LVEF and their potential pathophysiological interdependence., Methods and Results: Fifty-eight guideline-selected CRT candidates were prospectively enrolled for low-dose DSE. Dyssynchrony was quantified by the amplitude of ApRock. An LVEF increase during stress of >5% was regarded significant. Scar burden was assessed by magnetic resonance imaging. Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death. ApRock during DSE predicted CRT response (AUC 0.88, 95% CI 0.77-0.99, P < 0.001) and correlated inversely with changes in EF (r = -0.6, P < 0.001). Left-ventricular ejection fraction changes during DSE were not associated with CRT response (P = 0.082). Linear regression analysis revealed an inverse association of LVEF changes during DSE with both, total scar burden (B = -2.67, 95CI -3.77 to -1.56, P < 0.001) and the DSE-induced change in ApRock amplitude (B = -1.23, 95% CI -1.53 to -0.94, P < 0.001). Kaplan-Meier analysis revealed that DSE-induced increase in ApRock, but not LVEF, was associated with improved long-term survival., Conclusion: During low-dose DSE in CRT candidates with baseline dyssynchrony, myocardial contractile reserve predominantly results in more dyssynchrony, but less in an increase in LVEF. Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT.

Aims: Current attempts of improving patient selection in cardiac resynchronization therapy (CRT) are mainly based on echocardiographic timing of myocardial velocity peaks. Regional myocardial function is neglected. Apical transverse motion (ATM) is a new parameter to quantify apical rocking as an integrative surrogate of both temporal and functional inhomogeneities within the left ventricle. In this study, we tested the predictive value of apical rocking for response to CRT., Methods and Results: Sixty-nine patients eligible for CRT were assessed by echocardiography before and 11 ± 5 months after pacemaker implantation. Response was defined as left ventricular (LV) end-systolic volume decrease >15%. Rocking was quantified (ATM) and visually assessed by four blinded readers. Predictive value for CRT response of both assessments was compared with conventional dyssynchrony parameters. ATM in the four-chamber view plane differentiated best between responders and non-responders (2.2 ± 1.5 vs. 0.06 ± 1.9 mm, P< 0.0001). Quantified ATM predicted reverse remodelling with a sensitivity, specificity, and accuracy of 75, 96, and 83% whereas visual rocking assessment resulted in 89, 75, and 83%, respectively. The accuracy of conventional parameters was significantly lower., Conclusion: Apical rocking is a new marker to assess LV dyssynchrony and predict CRT response. It is superior to conventional parameters. Even its simple visual assessment may be sufficiently accurate in the clinical setting.

Background: Heart failure is associated with a reduction in left ventricular (LV) contractility as evidenced by a blunted force-frequency response (FFR) and downregulation of contractility regulating genes., Objective: This study sought to investigate whether cardiac resynchronization therapy (CRT) is capable of reversing the blunted FFR and the downregulation of contractility regulating genes., Methods: Twenty heart failure patients underwent echocardiographic examination during incremental AAI and DDD-CRT pacing at 70, 90, and 110 beats/min, immediately after and 4 months after CRT implantation. The FFR was determined from the ratio of the LV systolic pressure/end systolic volume index at given heart rate. In a subgroup of 6 patients with idiopathic dilated cardiomyopathy, serial LV dP/dtmax was invasively measured during both pacing modes and serial LV endomyocardial biopsies were taken to measure sarcoplasmatic reticulum calcium ATPase 2alpha (SERCA2alpha), phospholamban (PLN), sarcolemmal sodium calcium exchanger (NCX), beta1-adrenoreceptor (beta1-AR), and apelin (APL) gene expression using reverse-transcriptase polymerase chain reaction., Results: Acutely, DDD-CRT pacing was associated with a decrease in dyssynchrony (P <.01) and increase in diastolic filling time (P <.01) at all heart rates paralleled by an upward shift of the FFR (P <.01) without force-frequency amplification. A greater upward shift of the FFR was noticed during DDD-CRT as compared with AAI (P <.01) after 4 months. In addition, CRT was associated with a significant force-frequency amplification at follow-up as evidenced from the steeper slope of the FFR relationship (P = .039). This was associated with a significant upregulation of SERCA2alpha P = .01), PLN (P = .01), their ratio (P = .01), ratio of SERCA/NCX (P = .02), beta1-AR (P = .03), and APL (P = .01) mRNA levels., Conclusion: CRT is associated with an acute upward shift in the FFR without force-frequency amplification related to restored synchronicity and increased filling time of the LV. Only chronic CRT is associated with force-frequency amplification in parallel to upregulation of contractility regulating genes.

An abstract of the article "Restoration of the Force-Frequency Relationship by Chronic Cardiac Resynchronization Therapy Is Paralleled by Upregulation of Contractility Regulating Genes," by W. Mullens and colleagues is presented.