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Aims Bi-atrial remodelling in patients with atrial fibrillation (AF) is rarely assessed and data on the presence of right atrial (RA) fibrosis, the relationship between RA and left atrial (LA) fibrosis, and possible association of RA remodelling with AF recurrence after ablation in patients with AF is limited. Methods and results A total of 110 patients with AF undergoing initial pulmonary vein isolation (PVI) were included in the present study. All patients were in sinus rhythm during cardiac magnetic resonance (CMR) imaging performed prior to ablation. LA and RA volumes and function (volumetric and feature tracking strain) were derived from cine CMR images. The extent of LA and RA fibrosis was assessed from 3D late gadolinium enhancement images. AF recurrence was followed up for 12 months after PVI using either 12-lead electrocardiograms or Holter monitoring. Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (interquartile range: 122–286) days. RA remodelling parameters were not significantly different between patients with and without AF recurrence after ablation, whereas LA remodelling parameters were different (volume, emptying fraction, and strain indices). LA fibrosis had a strong correlation with RA fibrosis (r = 0.88, P < 0.001). Both LA and RA fibrosis were not different between patients with and without AF recurrence. Conclusions This study shows that RA remodelling parameters were not predictive of AF recurrence after AF ablation. Bi-atrial fibrotic remodelling is present in patients with AF and moreover, the amount of LA fibrosis had a strong correlation with the amount of RA fibrosis.

Pulmonary vein isolation (PVI) by radiofrequency (RF) ablation is an important alternative to antiarrhythmic drugs in the treatment of symptomatic atrial fibrillation. However, the inability to consistently achieve durable isolation of the pulmonary veins hampers the long-term efficacy of PVI procedures. The large number of factors involved in RF lesion formation and the complex interplay of these factors complicate reliable creation of durable and transmural ablation lesions. Various surrogate markers of ablation lesion formation have been proposed that may provide information on RF lesion completeness. Real-time assessment of these surrogates may aid in the creation of transmural ablation lesions, and therefore, holds potential to decrease the risk of PV reconnection and consequent post-PVI arrhythmia recurrence. Moreover, titration of energy delivery until lesions is transmural may prevent unnecessary ablation and subsequent adverse events. Whereas several surrogate markers of ablation lesion formation have been described over the past decades, a ‘gold standard’ is currently lacking. This review provides a state-of-the-art overview of ablation strategies that aim to enhance durability of RF-PVI, with special focus on real-time available surrogates of RF lesion formation in light of the biophysical basis of RF ablation.

Introduction: Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on nonpulmonary vein (PV) target strategies in repeat AF ablation are scarce. Here, we describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. Methods: A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. The ablation strategy for repeat ablation was at the operators' discretion. Non-PV target ablation (n = 140) included PV reisolation, posterior wall isolation, mitral line, roofline, and/or complex fractionated atrial electrogram ablation. PV target ablation (n = 140), included reisolation and/or wide atrium circumferential ablation. Patients' demographics and rhythm outcomes during 12 months follow-up were analyzed. Results: At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p =.001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% vs. 22.1% and 22.9% vs. 10.7%). After adjustment, a significantly higher risk of AT recurrence remained in the non-PV target group. Both groups significantly de-escalated antiarrhythmic drug use; de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs. Conclusion: Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with an increased risk for AT recurrences.

Purpose: The present study assesses different left atrial (LA) strain approaches in relation to atrial fibrillation (AF) recurrence after ablation and compares LA feature tracking (FT) strain to novel rapid LA strain approaches in AF patients. Methods: This retrospective single-center study comprised of 110 prospectively recruited AF patients who underwent cardiac magnetic resonance (CMR) imaging in sinus rhythm prior to their first pulmonary vein isolation ablation. LA rapid strain (long axis strain and atrioventricular (AV)-junction strain), LA FT strain, and LA volumes were derived from 2-chamber and 4-chamber cine images. AF recurrence was followed up for 12 months using either 12‑lead ECGs or rhythm Holter monitoring. Results: Arrhythmia recurrence was observed in 39 patients (36%) after the 90-day blanking period, occurring at a median of 181 (122–286) days. LA long axis strain, AV-junction strain, and FT strain were all more impaired in patients with AF recurrence compared to patients without AF recurrence (long axis strain: P < 0.01; AV-junction strain: P < 0.001; FT strain: P < 0.01, respectively). Area under the curve (AUC) values for LA remodeling parameters in association with AF recurrence were 0.68 for long axis strain, 0.68 for AV-junction strain, 0.66 for FT strain, 0.66 for LA volume index. Phasic FT LA strain demonstrated that contractile strain had the highest AUC (0.70). Conclusion: Both LA rapid strain and LA FT strain are associated with arrhythmia recurrence after ablation in AF patients. LA rapid strain can be a convenient and reproducible alternative for LA FT strain to assess LA function in clinical practice.

Objective: Depression and anxiety in patients with an implantable cardioverter-defibrillator (ICD) are associated with adverse outcomes. This study describes the design of the PSYCHE-ICD study and evaluates the correlation between cardiac status and depression and anxiety in ICD patients. Methods: We included 178 patients. Prior to implantation, patients completed validated psychological questionnaires for depression, anxiety and personality traits. Cardiac status was evaluated by means of left ventricular ejection fraction assessment (LVEF), New York Heart Association (NYHA) functional class, 6-minute walk test (6MWT), and 24-h Holter monitoring for heart rate variability (HRV). A cross-sectional analysis was performed. Follow-up with annual study visits, including repeated full cardiac evaluation, will continue 36 months after ICD implantation. Results: Depressive symptoms were present in 62 (35%) and anxiety in 56 (32%) patients. Values of depression and anxiety significantly increased with higher NYHA class (P < 0.001). Depression symptoms were correlated with a reduced 6MWT (411 ± 128 vs. 488 ± 89, P < 0.001), higher heart rate (74 ± 13 vs. 70 ± 13, P = 0.02), higher thyroid stimulation hormone levels (1.8 [1.3–2.8] vs 1.5 [1.0–2.2], P = 0.03) and multiple HRV parameters. Anxiety symptoms were correlated with higher NYHA class and a reduced 6MWT (433 ± 112 vs 477 ± 102, P = 0.02). Conclusion: A substantial part of patients receiving an ICD have symptoms of depression and anxiety at time of ICD implantation. Depression and anxiety were correlated with multiple cardiac parameters, suggesting a possible biological links between psychological distress and cardiac disease in ICD patients.

Background: The pathogenic missense variant p.G125R in TBX5 (T-box transcription factor 5) causes Holt–Oram syndrome (also known as hand–heart syndrome) and early onset of atrial fibrillation. Revealing how an altered key developmental transcription factor modulates cardiac physiology in vivo will provide unique insights into the mechanisms underlying atrial fibrillation in these patients. Methods: We analyzed ECGs of an extended family pedigree of Holt–Oram syndrome patients. Next, we introduced the TBX5-p.G125R variant in the mouse genome ( Tbx5 G125R ) and performed electrophysiologic analyses (ECG, optical mapping, patch clamp, intracellular calcium measurements), transcriptomics (single-nuclei and tissue RNA sequencing), and epigenetic profiling (assay for transposase-accessible chromatin using sequencing, H3K27ac [histone H3 lysine 27 acetylation] CUT&RUN [cleavage under targets and release under nuclease sequencing]). Results: We discovered high incidence of atrial extra systoles and atrioventricular conduction disturbances in Holt–Oram syndrome patients. Tbx5 G125R/+ mice were morphologically unaffected and displayed variable RR intervals, atrial extra systoles, and susceptibility to atrial fibrillation, reminiscent of TBX5-p.G125R patients. Atrial conduction velocity was not affected but systolic and diastolic intracellular calcium concentrations were decreased and action potentials were prolonged in isolated cardiomyocytes of Tbx5 G125R/+ mice compared with controls. Transcriptional profiling of atria revealed the most profound transcriptional changes in cardiomyocytes versus other cell types, and identified over a thousand coding and noncoding transcripts that were differentially expressed. Epigenetic profiling uncovered thousands of TBX5-p.G125R-sensitive, putative regulatory elements (including enhancers) that gained accessibility in atrial cardiomyocytes. The majority of sites with increased accessibility were occupied by Tbx5. The small group of sites with reduced accessibility was enriched for DNA-binding motifs of members of the SP (specificity protein) and KLF (Krüppel-like factor) families of transcription factors. These data show that Tbx5-p.G125R induces changes in regulatory element activity, alters transcriptional regulation, and changes cardiomyocyte behavior, possibly caused by altered DNA binding and cooperativity properties. Conclusions: Our data reveal that a disease-causing missense variant in TBX5 induces profound changes in the atrial transcriptional regulatory network and epigenetic state in vivo, leading to arrhythmia reminiscent of those seen in human TBX5-p.G125R variant carriers.

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

Background: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications. Methods: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF 2, CAAP-AF, CHADS 2, CHA 2DS 2-VASc, DR-FLASH, HATCH, LAGO and MB-LATER. Results: Median follow-up was 16 (12–31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124–360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553–0.669). CHA 2DS 2-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively). Conclusions: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.

Background The subcutaneous implantable cardioverter-defibrillator (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. Methods and results The PRAETORIAN trial is an international, multicentre, randomized trial in which 849 patients with an indication for ICD therapy were randomized to receive an S- ICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections, and the need for invasive interventions. Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group, 49 complications occurred in 44 patients of which lead dysfunction was most frequent (HR: 0.69; P = 0.11). In both groups, half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared with the TV-ICD group (P < 0.001, P = 0.03, respectively). Significantly more complications required invasive interventions in the TV-ICD group compared with the S-ICD group (8.3% vs. 4.3%, HR: 0.59; P = 0.047). Conclusion This secondary analysis shows that lead-related complications and systemic infections are more prevalent in the TV-ICD group compared with the S-ICD group. In addition, complications in the TV-ICD group were more severe as they required significantly more invasive interventions. This data contributes to shared decision-making in clinical practice.

Aims Various methods and post-processing software packages have been developed to quantify left atrial (LA) fibrosis using 3D late gadolinium-enhancement cardiac magnetic resonance (LGE-CMR) images. Currently, it remains unclear how the results of these methods and software packages interrelate. Methods and results Forty-seven atrial fibrillation (AF) patients underwent 3D-LGE-CMR imaging prior to their AF ablation. LA fibrotic burden was derived from the images using open-source CEMRG software and commercially available ADAS 3D-LA software. Both packages were used to calculate fibrosis based on the image intensity ratio (IIR)-method. Additionally, CEMRG was used to quantify LA fibrosis using three standard deviations (3SD) above the mean blood pool signal intensity. Intraclass correlation coefficients were calculated to compare LA fibrosis quantification methods and different post-processing software outputs. The percentage of LA fibrosis assessed using IIR threshold 1.2 was significantly different from the 3SD-method (29.80 ± 14.15% vs. 8.43 ± 5.42%; P < 0.001). Correlation between the IIR-and SD-method was good (r = 0.85, P < 0.001) although agreement was poor [intraclass correlation coefficient (ICC) = 0.19; P < 0.001]. One-third of the patients were allocated to a different fibrosis category dependent on the used quantification method. Fibrosis assessment using CEMRG and ADAS 3D-LA showed good agreement for the IIR-method (ICC = 0.93; P < 0.001). Conclusions Both, the IIR1.2 and 3SD-method quantify atrial fibrotic burden based on atrial wall signal intensity differences. The discrepancy in the amount of LA fibrosis between these methods may have clinical implications when patients are classified according to their fibrotic burden. There was no difference in results between post-processing software packages to quantify LA fibrosis if an identical quantification method including the threshold was used.

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women. Methods and results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4–4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P

Contains fulltext : 233789.pdf (Publisher’s version ) (Open Access) AIMS: In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated. METHODS AND RESULTS: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction

ObjectiveAtrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.MethodsIn this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.ResultsMean age was 65 (58–71) years, 179 (43%) were female. Follow-up was 2.2 (1.6–2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.ConclusionIn patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed.Trial registration numberNCT02726698.

Aims Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock). Methods and results The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ −15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001). Conclusion SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB. Clinical trial registration The MARC study was registered at clinicaltrials.gov: NCT01519908.

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p

Background Currently, no specific treatment exists for heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) relaxation during diastole is a highly energy-demanding process, while energy homeostasis is known to be compromised in HFpEF. We hypothesise that trimetazidine – a fatty acid β‑oxidation inhibitor – improves LV diastolic function in HFpEF, by altering myocardial substrate use and improving the myocardial energy status. Objectives To assess whether trimetazidine improves LV diastolic function by improving myocardial energy metabolism in HFpEF. Methods The DoPING-HFpEF trial is a randomised, double-blind, placebo-controlled cross-over intervention trial comparing the efficacy of trimetazidine and placebo in 25 patients with stable HFpEF. The main inclusion criteria are: New York Heart Association functional class II to IV, LV ejection fraction ≥50%, and evidence of LV diastolic dysfunction. Patients are treated with one 20-mg trimetazidine tablet or placebo thrice daily (twice daily in the case of moderate renal dysfunction) for two periods of 3 months separated by a 2-week washout period. The primary endpoint is the change in pulmonary capillary wedge pressure during different intensities of exercise measured by right heart catheterisation. Our key secondary endpoint is the myocardial phosphocreatine (PCr)/ATP ratio measured by phosphorus-31 magnetic resonance spectroscopy and its relation to the primary endpoint. Exploratory endpoints are 6‑min walk distance, N-terminal pro-brain natriuretic peptide levels, and quality of life. Conclusion The DoPING-HFpEF is a phase-II trial that evaluates the effect of trimetazidine, a metabolic modulator, on diastolic function and myocardial energy status in HFpEF. [EU Clinical Trial Register: 2018-002170-52; NTR registration: NL7830]

Aims Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational–experimental–clinical study. Methods and results Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy. In a proof-of-principle clinical study, left ventricular (LV) pressure and volume were measured in 22 heart failure (HF) patients (LV ejection fraction 230 ms) and narrow or non-left bundle branch block QRS complex. Computer simulations and animal studies in normal hearts showed that restoring of AV-coupling with unchanged ventricular activation sequence significantly increased LV filling, mean arterial pressure, and cardiac output by 10–15%. In computer simulations of failing hearts and in HF patients, reducing PR interval by biventricular (BiV) pacing (patients: from 300 ± 61 to 137 ± 30 ms) resulted in significant increases in LV stroke volume and stroke work (patients: 34 ± 40% and 26 ± 31%, respectively). However, worsening of ventricular dyssynchrony by using right ventricular (RV) pacing abrogated the benefit of restoring AV-coupling. In model simulations, animals and patients, the increase of LV filling and associated improvement of LV pump function coincided with both larger mitral inflow (E- and A-wave area) and reduction of diastolic mitral regurgitation. Conclusion Restoration of AV-coupling by BiV pacing in normal and failing hearts with prolonged AV conduction leads to considerable haemodynamic improvement. These results indicate that BiV or physiological pacing, but not RV pacing, may improve cardiac function in patients with HF and prolonged PR interval.

PURPOSE: To determine whether the distance between the descending aorta and left atrial (LA) wall correlates with the amount of fibrosis quantified in the posterior left inferior pulmonary vein (LIPV) area of the LA in patients with atrial fibrillation (AF). MATERIALS AND METHODS: In this retrospective study, patients with AF underwent cardiac MRI in sinus rhythm prior to a pulmonary vein isolation procedure (July 2018 to February 2020). The mean distance (distance(mean)) and shortest distance (distance(short)) between the descending aorta and the LA wall were measured on three-dimensional (3D) contrast-enhanced MR angiograms; distance(mean) was defined as the average of five measurements at different levels between the descending aorta and the LA wall. The extent of LA fibrosis, both global fibrosis and regional fibrosis within the LIPV area, was derived from postprocessed, 3D, late gadolinium–enhanced images. Associations between the extent of fibrosis and the proximity of the descending aorta were analyzed by using correlative and multivariable analyses. RESULTS: A total of 47 (mean age, 60 years ± 8 [standard deviation]; 31 men) patients were included for analysis. The extent of fibrosis in the posterior LIPV area was correlated with the distance(mean) (r(s) = −0.48; P < .01) and distance(short) (r(s) = −0.49; P < .01). Patients with a short distance between the descending aorta and LA wall (defined as a distance(short) < 2 mm) had a higher percentage of fibrosis in the posterior LIPV area than patients with a distance(short) greater than 2 mm (38.7% ± 22.7 vs 21.2% ± 17.8; P < .01). CONCLUSION: The distance between the descending aorta and LA was correlated with the extent of quantified fibrosis within the posterior LIPV area. Keywords: MRI, Cardiac, Left Atrium Supplemental material is available for this article. © RSNA, 2022

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT. Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines (n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort (n = 818). Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men (p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % (p > 0.05 for all). Results were comparable in the Belgian cohort. Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT. The MARC study was performed within the framework of the CTMM, the Centre for Translational Molecular Medicine (www.ctmm.nl), project COHFAR (Congestive Heart Failure and Arrhythmias, grant 01C–203), and supported by the Dutch Heart Foundation.

Introduction: Global left atrial (LA) strain is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Recently, novel rapid LA long axis strain has been introduced. Currently, it is unknown whether this fast and simple strain approach can predict AF recurrence after PVI and hence may be a simple alternative for the cumbersome LA feature tracking (FT) strain analysis. Hypothesis: Rapid LA strain is a fast and simple alternative for predicting AF recurrence after PVI as compared to LA FT strain. Methods: A total of 58 AF patients (78% paroxysmal AF, 64% male, mean age 61±7 years) undergoing first PVI ablation were included. Prior to PVI, all patients were in sinus rhythm during cardiac magnetic resonance imaging. LA rapid strain, LA FT strain and LA volumes were derived from 2-chamber and 4-chamber cine CMR images (Figure A). All patients were routinely followed up for arrhythmia recurrence. Results: At one year follow-up, arrhythmia recurrence was observed in 21 patients (36%). Both, rapid LA strain and FT strain were significantly reduced in patients with AF recurrence compared to patients without AF recurrence (rapid strain: -19.96 ± 11.03% vs. -28.18 ± 9.93%, P=0.005; FT strain: -12.54 ± 4.16% vs. -15.94 ± 3.50%, P=0.002, Figure B, and C) while maximal LA volume index (LAVImax) was not different between both groups (16.98 ± 3.70ml/m2 vs. 15.04 ± 2.47ml/m2, P=0.11, Figure D). ROC analysis identified LA FT strain as having the highest area under the curve (AUC) for predicting AF recurrence after PVI (AUC: 0.75 for LA FT strain, 0.71 for LA rapid strain, 0.62 for LAVImax, figure E). Conclusions: Both rapid LA strain and LA FT strain are predictive of AF recurrence after index PVI in AF patients. Moreover, LA mechanical function (strain) may be a more useful marker for predicting AF recurrence than LA volume. Therefore, LA rapid strain can be a more convenient and reproducible parameter for the assessment of LA performance in clinical practice.

Introduction: Radiofrequency (RF) atrial fibrillation (AF) ablation using a catheter dragging technique may shorten procedural duration and improve durability of pulmonary vein isolation (PVI) by creating uninterrupted linear ablation lesions. We compared a novel AF ablation approach guided by Grid annotation allowing for “drag lesions” with a standard point-by-point ablation approach in a single-center randomized study. Methods: Eighty-eight paroxysmal or persistent AF patients were randomized 1:1 to undergo RF-PVI with either a catheter dragging ablation technique guided by Grid annotation or point-by-point ablation guided by Ablation Index (AI) annotation. In the Grid annotation arm, ablation was visualized using 1 mm³ grid points coloring red after meeting predefined stability and contact force criteria. In the AI annotation arm, ablation lesions were created in a point-by-point fashion with AI target values set at 380 and 500 for posterior/inferior and anterior/roof segments, respectively. Patients were followed up for 12 months after PVI using ECGs, 24-h Holter monitoring and a mobile-based one-lead ECG device. Results: Procedure time was not different between the two randomization arms (Grid annotation 71 ± 19 min, AI annotation 72 ± 26 min, p =.765). RF time was significantly longer in the Grid annotation arm compared with the AI annotation arm (49 ± 8 min vs. 37 ± 8 min, respectively, p

Item does not contain fulltext OBJECTIVES: The aim of the present study was to determine the effect of a delayed versus an immediate invasive approach on final infarct size and clinical outcome up to 1 year. BACKGROUND: Up to 24% of patients with acute coronary syndromes present with ST-segment elevation myocardial infarction (STEMI) but show complete resolution of ST-segment elevation and symptoms before revascularization. Current guidelines do not clearly state whether these patients with transient STEMI should be treated with a STEMI-like or non-ST-segment elevation acute coronary syndrome-like intervention strategy. METHODS: In this multicenter trial, 142 patients with transient STEMI were randomized 1:1 to either delayed or immediate coronary intervention. Cardiac magnetic resonance imaging was performed at 4 days and at 4-month follow-up to assess infarct size and myocardial function. Clinical follow-up was performed at 4 and 12 months. RESULTS: In the delayed (22.7 h) and the immediate (0.4 h) invasive groups, final infarct size as a percentage of the left ventricle was very small (0.4% [interquartile range: 0.0% to 2.5%] vs. 0.4% [interquartile range: 0.0% to 3.5%]; p = 0.79), and left ventricular function was good (mean ejection fraction 59.3 +/- 6.5% vs. 59.9 +/- 5.4%; p = 0.63). In addition, the overall occurrence of major adverse cardiac events, consisting of death, recurrent infarction, and target lesion revascularization, up to 1 year was low and not different between both groups (5.7% vs. 4.4%, respectively; p = 1.00). CONCLUSIONS: At follow-up, patients with transient STEMI have limited infarction and well-preserved myocardial function in general, and delayed or immediate revascularization has no effect on functional outcome and clinical events up to 1 year.

Objectives This study evaluated the acute effect of dP/dtmax- versus stroke work (SW)-guided cardiac resynchronization therapy (CRT) optimization and the related acute hemodynamic changes to long-term CRT response. Background Hemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dtmax is used as an index of ventricular performance. Alternatively, SW can be derived from pressure−volume (PV) loops. Methods Forty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms. Results Compared with conventional CRT, dP/dtmax-guided optimization resulted in a one-third additional dP/dtmax increase (17 ± 11% vs. 12 ± 9%; p Conclusions PV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dtmax optimization favored LV contractility. Ultimately, acute changes in SW showed larger predictive value for long-term CRT response compared with dP/dtmax.

Background: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESS sep ) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESS sep for clinical outcome after CRT. Methods: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESS sep was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization. Results: Two-thirds (65%) of patients had a positive SLICE-ESS sep ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESS sep were at lower risk to reach the primary end point (hazard ratio 0.36; P P =0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; P =0.272). Clinical outcome of class II patients with a positive ESS sep was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66–2.88]; P =0.396). Conclusions: Strain assessment of the septum (SLICE-ESS sep ) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESS sep in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESS sep negative patients have poor prognosis after CRT implantation.

Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1–2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0–3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Background In survivors of sudden cardiac arrest with obstructive coronary artery disease, it remains challenging to distinguish ischemia as a reversible cause from irreversible scar‐related ventricular arrhythmias. We aimed to evaluate the value of implantable cardioverter‐defibrillator (ICD) implantation in sudden cardiac arrest survivors with presumably reversible ischemia and complete revascularization. Methods and Results This multicenter retrospective cohort study included 276 patients (80% men, age 67±10 years) receiving ICD implantation for secondary prevention. Angiography was performed before ICD implantation. A subgroup of 166 (60%) patients underwent cardiac magnetic resonance imaging with late gadolinium enhancement before implantation. Patients were divided in 2 groups, (1) ICD‐per‐guideline, including 228 patients with incomplete revascularization or left ventricular ejection fraction ≤35%, and (2) ICD‐off‐label, including 48 patients with complete revascularization and left ventricular ejection fraction >35%. The primary outcome was time to appropriate device therapy (ADT). During 4.0 years (interquartile range, 3.5–4.6) of follow‐up, ADT developed in 15% of the ICD‐off‐label group versus 43% of the ICD‐per‐guideline group. Time to ADT was comparable in the ICD‐off‐label and ICD‐per‐guideline groups (hazard ratio (HR), 0.46; P =0.08). No difference in mortality was observed (HR, 0.95; P =0.93). Independent predictors of ADT included age (HR, 1.03; P =0.01), left ventricular end‐diastolic volume HR, (1.05 per 10 mL increase; P P =0.04). Conclusions This study demonstrates that sudden cardiac arrest survivors with coronary artery disease remain at high risk of recurrent ventricular arrhythmia, even after complete revascularization and with preserved left ventricular function. Late gadolinium enhancement–cardiac magnetic resonance imaging derived left ventricular volumes and extent of myocardial scar were independently associated with.

The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age = 61 ± 8 years) and 5 age/gender matched controls (age = 56 ± 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities p = 0.01) and (19.3 ± 4.7 cm/s vs. 26.8 ± 5.5 cm/s, p = 0.02), respectively]. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 ± 10.8% vs. 27.8 ± 7.9%, p = 0.01) and in the LA appendage (73.3 ± 5.7% vs. 52.8 ± 16.2%, p = 0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world. Using photoplethysmography (PPG) and software algorithms, AF can be detected with high accuracy using smartphone camera-derived data. However, reports of diagnostic accuracy of standalone algorithms using wristband-derived PPG data are sparse, while this provides a means to perform long-term AF screening and monitoring. This study evaluated the diagnostic accuracy of a well-known standalone algorithm using wristband-derived PPG data. Materials and Methods: Subjects recruited from a community senior care organization were instructed to wear the Wavelet PPG wristband on one arm and the Alivecor KardiaBand one-lead-ECG wristband on the other. Three consecutive measurements (duration per measurement: 60 s for PPG and 30 s for one-lead ECG) were performed with both devices, simultaneously. The PPG data were analyzed by the Fibricheck standalone algorithm and the ECG data by the Kardia algorithm. The results were compared to a reference standard (interpretation of the one-lead ECG by two independent cardiologists). Results: A total of 180 PPGs and one-lead ECGs were recorded in 60 subjects, with a mean age of 70 17. AF was identified in 6 (10%) of the users, two users (3%) were not classifiable by the PPG algorithm and 1 user (2%) was not classifiable by the one-lead ECG algorithm. The diagnostic performance (sensitivity/specificity/positive predictive value/negative predictive value/accuracy) on user level was 100/96/75/100/97% for the PPG wristband and 100/98/86/100/98% for the one-lead ECG wristband. Conclusions: In a small real-world cohort of elderly people, the standalone Fibricheck AF algorithm can accurately detect AF using Wavelet wristband-derived PPG data. Results are comparable to the Alivecor Kardia one-lead ECG device, with an acceptable unclassifiable/bad quality rate. This opens the door for long-term AF screening and monitoring. (C) 2020 The Authors. Published by Elsevier B.V. Seldera, JL (corresponding author), Vrije Univ, Dept Cardiol, Amsterdam UMC, Amsterdam, Netherlands. j.selder@amsterdamumc.nl

Objectives: This study presents a head-to-head comparison of the value of cardiac magnetic resonance (CMR)-derived left-ventricular (LV) function and scar burden and positron emission tomography (PET)-derived perfusion and innervation in predicting ventricular arrhythmias (VAs). Background: Improved risk stratification of VA is important to identify patients who should benefit of prophylactic implantable cardioverter-defibrillator (ICD) implantation. Perfusion abnormalities, sympathetic denervation, and scar burden have all been linked to VA, although comparative studies are lacking. Methods: Seventy-four patients with ischemic cardiomyopathy and left-ventricular ejection fraction (LVEF) ≤35%, referred for primary prevention ICD placement were enrolled prospectively. Late gadolinium-enhanced (LGE) CMR was performed to assess LV function and scar characteristics. [ 15O]H 2O and [ 11C]hydroxyephedrine positron emission tomography (PET) were performed to quantify resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR), and sympathetic innervation. During follow-up of 5.4 ± 1.9 years, the occurrence of sustained VA, appropriate ICD therapy, and mortality were evaluated. Results: In total, 20 (26%) patients experienced VA. CMR and PET parameters showed considerable overlap between patients with VA and patients without VA, caused by substantial heterogeneity within groups. Univariable analyses showed that lower LVEF (hazard ratio [HR]: 0.92; p = 0.03), higher left-ventricular end-diastolic volume index (LVEDVi) (HR 1.02; p < 0.01), and larger scar border zone (HR 1.11; p = 0.03) were related to VA. Scar core size, resting MBF, hyperemic MBF, perfusion defect size, innervation defect size, and the innervation-perfusion mismatch were not found to be associated with VA. Conclusions: In patients with ischemic cardiomyopathy, lower LVEF, higher LVEDVi, and larger scar border zone were related to VA. PET-derived perfusion and sympathetic innervation, as well as CMR-derived scar core size were not associated with VA. These results suggest that improved prediction of VA by advanced imaging remains challenging for the individual patient.

Highlights • Ablation Index-guided ablation allows for ablation lesions of consistent depth. • Ablation Index-guided ablation is limited by ignoring local wall thickness. • Local atrial wall thickness is associated with acute pulmonary vein reconnection. • Wall thickness adjusted Ablation Index targets may improve ablation outcomes., Background Although Ablation Index (AI)-guided ablation facilitates creation of lesions of consistent depth, pulmonary vein (PV) reconnection is still commonly observed after AI-guided pulmonary vein isolation (PVI). The present study aimed to investigate the impact of local left atrial wall thickness on the incidence of acute PV reconnection after AI-guided atrial fibrillation (AF) ablation. Methods and results Seventy patients (63% paroxysmal AF, 67% male, mean age 63 ± 8 years) who underwent preprocedural CT imaging and AI-guided AF ablation were studied. Occurrence of acute PV reconnection after initial PVI was assessed after a 30-minute waiting period. Ablation procedures were retrospectively analyzed and each ablation circle was subdivided into 8 segments. Minimum AI, force-time integral, contact force, ablation duration, power, impedance drop and maximum interlesion distance were determined for each segment. PV antrum wall thickness was assessed for each segment on reconstructed CT images based on patient-specific thresholds in Hounsfield Units. Acute reconnection occurred in 27/1120 segments (2%, 15 anterior/roof, 12 posterior/inferior) in 19/140 ablation circles (14%). Reconnected segments were characterized by a greater local atrial wall thickness, both in anterior/roof (1.87 ± 0.42 vs. 1.54 ± 0.42 mm; p

Background During pulmonary vein isolation (PVI), nonisolation after initial encircling of the pulmonary veins (PVs) may be due to gaps in the initial ablation line, or alternatively, earliest PV activation may occur on the intervenous carina and ablation within the wide‐area circumferential ablation (WACA) circle is needed to eliminate residual conduction. This study investigated prognostic implications and predictors of gap‐related persistent conduction (gap‐RPC) and carina‐related persistent conduction (carina‐RPC) during PVI. Methods and Results Two hundred fourteen atrial fibrillation (AF) patients (57% paroxysmal, 61% male, mean age 62 ± 9 years) undergoing first contact force‐guided radiofrequency PVI were studied. Preprocedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. PVI was assessed directly after initial WACA circle creation, after a minimum waiting period of 30 minutes, and after adenosine infusion. Persistent conduction was targeted for additional ablation and classified as gap‐RPC or carina‐RPC, depending on the earliest activation site. The 1‐year AF recurrence rate was higher in patients with gap‐RPC (47%) compared to patients without gap‐RPC (28%; P = .003). No significant difference in 1‐year recurrence rate was found between patients with carina‐RPC (37%) and patients without carina‐RPC (31%; P = .379). Multivariate analyses identified paroxysmal AF and WACA circumference as independent predictors of gap‐RPC, whereas carina width and WACA circumference correlated with carina‐RPC. Conclusions Gap‐RPC is associated with increased AF recurrence risk after PVI, whereas carina‐RPC does not predict AF recurrence. Moreover, gap‐RPC and carina‐RPC have different correlates and may thus have different underlying mechanisms.

Item does not contain fulltext Aims: This study aims to define an atrioventricular (AV) delay optimization method for cardiac resynchronization therapy (CRT) with a quadripolar left ventricular (LV) lead based on intrinsic conduction intervals. Methods and results: Heart failure patients with a left bundle branch block underwent CRT implantation with a quadripolar LV lead. Invasive LV pressure-volume loops were recorded during four biventricular and three multi-point pacing (MPP) settings, using four patient-specific paced AV delays. Haemodynamic response was defined as change in stroke work (Delta%SW) compared to intrinsic rhythm and was related to the following conduction intervals: right atrial pacing to right ventricular sensing interval (RAp-RVs), Q to LV sensing interval normalized to QRS duration (QLV/QRSd), PR-interval, and P-wave duration. In 44 patients, the largest Delta%SW (104 +/- 76%) occurred at a paced AV delay of 128 +/- 32 ms, at 47 +/- 9% of RAp-RVs. Optimal AV delay of biventricular pacing (126 +/- 26 ms) did not differ from MPP (126 +/- 21 ms, P = 0.29). Intra-class correlation coefficient between optimal AV delays of different pacing configurations was 0.64 (0.45-0.78, P < 0.001). Although not statistically significant, Delta%SW at 50% of RAp-RVs (98 +/- 74%) was closer to the maximal achievable Delta%SW increase than a fixed interval of 120 ms (96 +/- 73%, P = 0.60). RAp-RVs, QLV/QRSd, PR interval, and P-wave duration were associated with the optimal AV delay in univariate analysis, but only RAp-RVs remained significantly associated in multivariate analysis (R = 0.69). Conclusion: The AV delay that provides highest haemodynamic response is similar for various LV pacing configurations and for MPP. An AV delay approximately 50% of RAp-RVs creates an acute haemodynamic response close to the maximal patient-specific response.