Combination prophylaxis in CMV high risk heart transplant recipients: A single center experience.

INTRODUCTION: Cytomegalovirus (CMV) is the most clinically relevant infectious agent following heart transplantation (HTX). Data on the beneficial effects of prophylactic use of CMV immunoglobulins (CMVIG) are scarce. METHODS: In this single-center, retrospective study, we reported patient outcomes following cardiac transplantation using prophylactic CMV treatment, including CMVIG. Distinct clinically relevant outcomes were compared across different CMV risk groups (CMV D-/R-, CMV D-/R+, CMV D+/R+, and CMV D+/R- or CMV high risk group). RESULTS: We included 272 heart transplant procedures, performed between 1/1/2009 and 1/11/2020. Sixty-one (22%) procedures belonged to the CMV high risk group, while 96 (35%), 50 (18%), and 65 (24%) were CMV D-/R-, CMV D-/R+, and CMV D+/R+, respectively. Baseline donor and recipient characteristics (sex, age, body mass index, cause of death, indication for HTX), ischemia times and baseline immunosuppressive regimens were similar across the different CMV risk groups, yet fewer patients were bridged with a mechanical circulatory support in the CMV D+/R- group. CMV disease following cardiac transplantation was more common in the CMV D+/R- risk group (n = 40 or 66.7%; p < .001), yet mortality and re-transplantation rates, cardiac allograft vasculopathy (CAV) severity, rejection episodes, and development of donor-specific antibodies (DSA), post-transplant lymphoproliferative diseases (PTLD), and EBV infections were similar across all four CMV risk groups. CONCLUSION: High risk CMV D+/R- patients had a similar survival compared to low and intermediate CMV risk groups using a prophylactic strategy combining CMVIG and viral DNA polymerase inhibitors. This may be related to a number of factors unrelated to prophylaxis strategy as two out of three CMV D+/R- recipients developed CMV primary infection after prophylaxis was discontinued.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

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 18F-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). 18F-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.

Exercise capacity, muscle strength and objectively measured physical activity in patients after heart transplantation.

Maximal exercise capacity of patients after heart transplantation (HTX) remains limited, affecting their quality of life. Evidence on the evolution of muscle strength and physical activity (PA) post-HTX is lacking, but a prerequisite to tailor cardiac rehabilitation programmes. Forty-five consecutive patients were evaluated every 3 months during the first year post-HTX. Functional exercise capacity (Six minutes walking distance test (6MWD)), peripheral (Quadriceps strength (QF)) and respiratory (Maximal inspiratory strength (MIP)) muscle strength were evaluated. PA (number of steps (PAsteps), active time (PAactive) and sedentary time (PAsed)) was objectively measured. 6MWD, QF, MIP, PAsteps and PAactive significantly improved over time (P < 0.001). No change in PAsed was noticed (P = 0.129). Despite improvements in 6MWD and QF, results remained substantially below those of age-and gender-matched healthy subjects. One year post-HTX, 30% of patients presented with peripheral muscle weakness. Baseline levels of 6MWD and QF were significantly higher in patients with pretransplant LVAD-implantation and this difference was maintained during follow-up. cardiac rehabilitation, combining aerobic exercise training and peripheral muscle strength training, is mandatory in patients post-HTX. Inspiratory muscle training should be implemented when respiratory muscle weakness is present. Programmes improving physical activity and reducing sedentary time post-HTX are essential.

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

AIMS: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively. CONCLUSION: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

The evolution and benefit of device therapy in patients listed for heart transplant.

Aims: The latest 2015 ESC Guidelines on the prevention of sudden cardiac death make a Class IIa recommendation for ICD implantation in patients listed for heart transplantation. This recommendation was based on expert consensus in view of the sparsity of data. Methods and results: All patients listed for heart transplantation at the University Hospitals of Leuven from 2002 until 2014 were studied retrospectively. Exclusion criteria were age <16 years, cardiac disease other than ischaemic or dilated cardiomyopathy and re-transplantation. A total of 286 patients were included, of which 140 (49.0%) received an ICD. There was a historical increase of the time on the waiting list before transplantation (P < 0.001) together with an increase of the use of ICDs (P < 0.001) and left ventricular assist devices (LVADs) (P < 0.001). The proportion of patients reaching heart transplant remained unchanged (P = 0.700). The annual appropriate shock rate in patients with ICD was 28.0%/y on the active waiting list. Patients with ICD showed a trend to improved survival (P = 0.070). Independent predictors of mortality or removal from the transplant list because of clinical deterioration were the need for LVAD (HR 4.38, 95%CI 2.11-9.01), a history of stroke (HR 2.95, 95%CI 1.61-5.40), older age (HR 1.03, 95%CI 1.01-1.05) and a worse renal function (HR 1.15, 95%CI 1.00-1.33). Conclusion: The time on the waiting list for heart transplantation significantly increased together with an increased use of device therapy in this population. The proportion of patients reaching transplant remained unchanged. This patient group is prone to life-threatening arrhythmias and the use of an ICD may improve survival.

Monocentric experience of leadless pacing with focus on challenging cases for conventional pacemaker.

AIM: Leadless cardiac pacemaker has been developed to reduce complications related to cardiac pacing and is considered as an alternative to conventional pacemaker although safety and efficacy data in clinical practice are limited. The purpose of this study was to investigate the safety and efficacy profile of Micra Transcatheter Pacing System (TPS) used in daily clinical activity with a focus on challenging cases for conventional pacing. METHODS: A total of 66 patients (46 men, 79.1 ± 9.7 years) having a Class I or II indication for ventricular pacing underwent a Micra TPS implant procedure. All patients were enrolled in a prospective registry. Follow-up visits were scheduled at discharge and after 1, 3, 6 and 12 months. RESULTS: Primary indication for pacing was third degree atrioventricular block (30.3%), sinus node dysfunction (21.2%) or permanent atrial fibrillation with bradycardia (45.5%). The device was successfully implanted in 65 patients (98.5%). During follow-up of 10.4 ± 6.1 months (range 1-23 months), electrical measurements remained stable. Mean pacing capture threshold, pacing impedance and R-wave sensing were respectively 0.57 ± 0.32 V, 580 ± 103 Ohms, 10.62 ± 4.36 mV at the last follow-up. One major (loss of function) and three minor adverse events occurred. Pericardial effusion, dislodgement, device related infection or pacemaker syndrome were not observed. Micra TPS implantation was straightforward for patients with congenital or acquired cardiac and/or vascular abnormalities, previous tricuspid surgery and after heart transplantation. CONCLUSION: Our experience confirms that implantation of Micra is safe and efficient in a real world population including patients who present a challenging condition for conventional pacing.

The impact of changes in LVEF and renal function on the prognosis of ICD patients after elective device replacement.

BACKGROUND: A proportion of patients with an implantable cardioverter-defibrillator (ICD) in prevention of sudden cardiac death will only receive their first appropriate ICD therapy (AT) after device replacement. Clinical reassessment at the time of replacement could be helpful to guide the decision to replace or not in the future. METHODS: All patients with an ICD for primary or secondary prevention in ischemic (ICM) or nonischemic cardiomyopathy were included in a single-center retrospective registry. The association of changes in left ventricular ejection fraction (LVEF; cut-off at 35%), worsening renal function (decrease in estimated glomerular filtration rate > 15 mL/min), and worsening New York Heart Association class at elective device replacement with mortality and AT was analyzed using adjusted Cox regression analysis. RESULTS: A total of 238 (33%) out of 727 patients received elective device replacement (86.1% male, 74.4% ICM, 42.9% primary prevention). During this replacement 20.2% received a device upgrade. The mean time to replacement was 6.4 ± 2.0 years and mean follow-up after replacement was 3.4 ± 3.0 years. Of patients who did not receive AT before replacement 23.1% received their first AT after replacement. Worsening renal function (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.50-5.18) and a consistently LVEF ≤35% compared to a consistently LVEF >35% (HR 2.15, 95% CI 1.10-4.19) at the time of replacement were independent predictors of mortality. Independent predictors of first AT after replacement could not be identified. CONCLUSION: Although reassessment of LVEF and renal function at replacement can be helpful in predicting total mortality, the clinical utility to guide reimplantation seemed limited. Our experience indicates that approximately 25% of patients received their first AT only after replacement.

Prognostic significance of improvement in right ventricular systolic function during cardiac resynchronization therapy.

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.

Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter Defibrillators over Time in Ischemic and Dilated Cardiomyopathy Patients.

BACKGROUND: Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality. METHODS: All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014. RESULTS: A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 ± 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality. CONCLUSION: These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort.

Dynamic relationship of left-ventricular dyssynchrony and contractile reserve in patients undergoing cardiac resynchronization therapy.

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.

Leptin-adiponectin ratio in pre-diabetic patients undergoing percutaneous coronary intervention.

BACKGROUND: The obesity-related hormones leptin and adiponectin are independently and oppositely associated with insulin resistance, which is an important risk factor for coronary artery disease (CAD) and restenosis after coronary intervention. In this report, we set out to determine the role of the leptin-adiponectin ratio (LAR) in non-diabetic patients with or without impaired glucose tolerance undergoing a percutaneous coronary intervention. METHODS: 300 PCI patients were enrolled in this prospective single-centre study. Patients with known diagnosis of diabetes (n = 50) and newly diagnosed diabetes (2h OGTT > 200 mg/dL, n = 25) were excluded. In both stable and acute subjects, assessment was done on the day of discharge and included a fasting glucose level, leptin, adiponectin and an oral glucose tolerance test (OGTT). RESULTS: LAR was significantly higher in diabetic (7.2 ± 0.7) than in non-diabetic patients (3.9 ± 0.3, P = 0.001), and even higher in newly diagnosed diabetics (9.8 ± 1.5, P < 0.001). Likewise, among non-diabetic patients, LAR was significantly higher in patients with impaired glucose tolerance. LAR was significantly higher in pre-diabetic (4.57 ± 0.48) versus normoglycaemic patients (3.45 ± 0.33, P = 0.05). LAR was found to be numerically higher in pre-diabetic versus normoglycaemic patients with two- and three-vessel disease (VD), but not in patients with single VD. In pre-diabetic patients, LAR was found to be significantly increased with more advanced CAD (P = 0.021), independent of stable versus unstable presentation. CONCLUSIONS: LAR is related to the extent of CAD in pre-diabetic patients but not in normoglycaemic patients. This finding might in part explain the poorer outcome in revascularized patients with impaired glucose tolerance compared to normoglycaemic patients.

How to choose between a pacemaker or defibrillator for resynchronization therapy?

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.

Left bundle branch pacing better preserves ventricular mechanical synchrony than right ventricular pacing: a two-centre study.

AIMS: Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP. METHODS AND RESULTS: Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02). CONCLUSION: LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP.

Long-term outcome after upgrade to cardiac resynchronization therapy: A propensity score-matched analysis.

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 m2 [35.8-69.5] vs. 59.9 ml/min/1.73 m2 [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.

Landmark Evolutions in Time and Indication for Cardiac Resynchronization Therapy: Results from a Multicenter Retrospective Registry.

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12-2.03; atrial fibrillation: HR 2.08, 95% CI 1.30-3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29-2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics.

Mechanical dyssynchrony as a selection criterion for cardiac resynchronization therapy: Design of the AMEND-CRT trial.

AIMS: One third of patients do not improve after cardiac resynchronization therapy (CRT). Septal flash (SF) and apical rocking (ApRock) are deformation patterns observed on echocardiography in most patients eligible for CRT. These markers of mechanical dyssynchrony have been associated to improved outcome after CRT in observational studies and may be useful to better select patients. The aim of this trial is to investigate whether the current guideline criteria for selecting patients for CRT should be modified and include SF and ApRock to improve therapy success rate, reduce excessive costs and prevent exposure to device-related complications in patients who would not benefit from CRT. METHODS: The AMEND-CRT trial is a multicentre, randomized, parallel-group, double-blind, sham-controlled trial with a non-inferiority design. The trial will include 578 patients scheduled for CRT according to the 2021 ESC guidelines who satisfy all inclusion criteria. The randomization is performed 1:1 to an active control arm ('guideline arm') or an experimental arm ('echo arm'). All participants receive a device, but in the echo arm, CRT is activated only when SF or ApRock or both are present. The outcome of both arms will be compared after 1 year. The primary outcome measures are the average change in left ventricular end-systolic volume and patient outcome assessed using a modified Packer Clinical Composite Score. CONCLUSIONS: The findings of this trial will redefine the role of echocardiography in CRT and potentially determine which patients with heart failure and a prolonged QRS duration should receive CRT, especially in patients who currently have a class IIa or class IIb recommendation.

Lateral QRS amplitude is independently associated with outcome after cardiac resynchronization therapy: advancing patient selection?

BACKGROUND: Cardiac resynchronization therapy (CRT) is a cornerstone in the treatment of selected heart failure patients. However, a relevant proportion of patients does not show beneficial response. Identification of simple, additive, and outcome-relevant selection criteria may improve patient selection. OBJECTIVE: We sought to determine whether baseline QRS amplitude is associated with outcome in CRT. METHODS: Quantification of intrinsic, pre-CRT-implantation QRS amplitude in an observational multinational two-center retrospective cohort analysis (derivation cohort Zurich, n=178, 2000-2015; validation cohort Leuven, n=183, 1999-2016) with a composite endpoint of all-cause mortality, ventricular assist device implantation or heart transplantation at 5 years. RESULTS: Higher baseline-to-peak amplitude in lateral leads (lead I and V6) was associated with a lower risk of reaching the composite endpoint (lead I: HR 0.86 [95%CI 0.78-0.95] per mV, p=0.002, lead V6: HR 0.94 [95%CI 0.88-1.00] per mV, p=0.043). Concordance index-based comparison of quartile-, spline-, and ROC curve analysis suggested cut-off values of 6mV for lead I and 3mV for V6 for optimal discrimination of outcome. External validation confirmed the cut-off of 3mV in lead V6 as highly significant discriminator of outcome (p<0.001), associated with a risk reduction of 65%. CONCLUSIONS: Low QRS amplitude in lateral ECG leads is associated with higher risk of poor outcome in CRT patients. A cut-off of 3mV in lead V6 proved highly discrimitative. Further studies need to confirm the additive value of QRS amplitude in patient selection for CRT and to assess whether CRT may be made available to more patients.

Is it feasible to outsource the remote monitoring of implantable cardiac defibrillators in a large tertiary hospital?

AIM: To provide a detailed description of the workflow at our telecardiology centre and to analyse the workload of real-world remote monitoring with the aim to assess the feasibility to outsource this service. METHODS: A retrospective analysis was conducted on the telecardiology service provided at the University Hospitals of Leuven by extracting patient demographic data, general time usage and detailed information about the type of remote contacts. 10,869 contacts in 948 patients have been included. A 2-week prospective study was conducted on the same service by documenting and monitoring every action performed by specialised nurses when analysing and solving remote monitoring transmissions. 337 contacts in 262 patients were collected during this period. RESULTS: Both analyses indicated similar numbers of events and interventions. Unplanned transmissions were more challenging and required more interventions than planned transmissions. Relatively little time (retrospective median: 1.83 min; prospective median: 1.56 min, per event) was spent on incoming non-actionable 'normal' transmissions (retrospective: 46%; prospective: 40% of all events). Retrospectively 54% and prospectively 60% of transmissions showed abnormalities and were responsible for most of the time expended. Disease-related issues were the most frequent cause for these 'abnormal' alerts. Contacting patients and physicians were key interventions undertaken. Interaction initiated by patients mainly involved the installation process (42%) and bedside monitoring problems (32%). CONCLUSION: External data centres could deal with 40% of the transmissions, but the decline in workload would be negligible for the in-hospital remote monitoring team, because very little time is spent dealing with the many 'non-event' transmissions whereas most of the time is spent solving clinical problems. Providing sufficient resources and optimising communication protocols is necessary to aid in managing the workload of the remote monitoring team.Implications for practiceContacting patients and physicians are key interventions for specialist nurses in remote monitoring centres.Detailed timing confirmed that most time was spent on relevant disease-related clinical problems.Despite dealing with ∼40% of transmissions, outsourcing to external data centres would decrease the workload only by 15-25%.Patient initiated contacts with questions concerning remote monitoring form a high burden and should be countered by scaling the service and creating communication protocols.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.