Post-implantation CMR imaging to study biventricular pacing effects on the right ventricle in left bundle branch block patients.

Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT-off during follow-up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT.

Assessment of ICD eligibility in non-ischaemic cardiomyopathy patients: a position statement by the Task Force of the Dutch Society of Cardiology.

International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.

Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.

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 (Tbx5G125R) 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. Tbx5G125R/+ 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 Tbx5G125R/+ 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.

Efficacy and Safety of Appropriate Shocks and Antitachycardia Pacing in Transvenous and Subcutaneous Implantable Defibrillators: Analysis of All Appropriate Therapy in the PRAETORIAN Trial.

BACKGROUND: The PRAETORIAN trial (A Prospective, Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy) showed noninferiority of subcutaneous implantable cardioverter defibrillator (S-ICD) compared with transvenous implantable cardioverter defibrillator (TV-ICD) with regard to inappropriate shocks and complications. In contrast to TV-ICD, S-ICD cannot provide antitachycardia pacing for monomorphic ventricular tachycardia. This prespecified secondary analysis evaluates appropriate therapy and whether antitachycardia pacing reduces the number of appropriate shocks. METHODS: The PRAETORIAN trial was an international, investigator-initiated randomized trial that included patients with an indication for implantable cardioverter defibrillator (ICD) therapy. Patients with previous ventricular tachycardia <170 bpm or refractory recurrent monomorphic ventricular tachycardia were excluded. In 39 centers, 849 patients were randomized to receive an S-ICD (n=426) or TV-ICD (n=423) and were followed for a median of 49.1 months. ICD programming was mandated by protocol. Appropriate ICD therapy was defined as therapy for ventricular arrhythmias. Arrhythmias were classified as discrete episodes and storm episodes (≥3 episodes within 24 hours). Analyses were performed in the modified intention-to-treat population. RESULTS: In the S-ICD group, 86 of 426 patients received appropriate therapy, versus 78 of 423 patients in the TV-ICD group, during a median follow-up of 52 months (48-month Kaplan-Meier estimates 19.4% and 17.5%; P=0.45). In the S-ICD group, 83 patients received at least 1 shock, versus 57 patients in the TV-ICD group (48-month Kaplan-Meier estimates 19.2% and 11.5%; P=0.02). Patients in the S-ICD group had a total of 254 shocks, compared with 228 shocks in the TV-ICD group (P=0.68). First shock efficacy was 93.8% in the S-ICD group and 91.6% in the TV-ICD group (P=0.40). The first antitachycardia pacing attempt successfully terminated 46% of all monomorphic ventricular tachycardias, but accelerated the arrhythmia in 9.4%. Ten patients with S-ICD experienced 13 electrical storms, versus 18 patients with TV-ICD with 19 electrical storms. Patients with appropriate therapy had an almost 2-fold increased relative risk of electrical storms in the TV-ICD group compared with the S-ICD group (P=0.05). CONCLUSIONS: In this trial, no difference was observed in shock efficacy of S-ICD compared with TV-ICD. Although patients in the S-ICD group were more likely to receive an ICD shock, the total number of appropriate shocks was not different between the 2 groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.

Optimizing patient selection for primary prevention implantable cardioverter-defibrillator implantation: utilizing multimodal machine learning to assess risk of implantable cardioverter-defibrillator non-benefit.

AIMS: Left ventricular ejection fraction (LVEF) is suboptimal as a sole marker for predicting sudden cardiac death (SCD). Machine learning (ML) provides new opportunities for personalized predictions using complex, multimodal data. This study aimed to determine if risk stratification for implantable cardioverter-defibrillator (ICD) implantation can be improved by ML models that combine clinical variables with 12-lead electrocardiograms (ECG) time-series features. METHODS AND RESULTS: A multicentre study of 1010 patients (64.9 ± 10.8 years, 26.8% female) with ischaemic, dilated, or non-ischaemic cardiomyopathy, and LVEF ≤ 35% implanted with an ICD between 2007 and 2021 for primary prevention of SCD in two academic hospitals was performed. For each patient, a raw 12-lead, 10-s ECG was obtained within 90 days before ICD implantation, and clinical details were collected. Supervised ML models were trained and validated on a development cohort (n = 550) from Hospital A to predict ICD non-arrhythmic mortality at three-year follow-up (i.e. mortality without prior appropriate ICD-therapy). Model performance was evaluated on an external patient cohort from Hospital B (n = 460). At three-year follow-up, 16.0% of patients had died, with 72.8% meeting criteria for non-arrhythmic mortality. Extreme gradient boosting models identified patients with non-arrhythmic mortality with an area under the receiver operating characteristic curve (AUROC) of 0.90 [95% confidence intervals (CI) 0.80-1.00] during internal validation. In the external cohort, the AUROC was 0.79 (95% CI 0.75-0.84). CONCLUSIONS: ML models combining ECG time-series features and clinical variables were able to predict non-arrhythmic mortality within three years after device implantation in a primary prevention population, with robust performance in an independent cohort.

Accuracy of a Standalone Atrial Fibrillation Detection Algorithm Added to a Popular Wristband and Smartwatch: Prospective Diagnostic Accuracy Study.

BACKGROUND: Silent paroxysmal atrial fibrillation (AF) may be difficult to diagnose, and AF burden is hard to establish. In contrast to conventional diagnostic devices, photoplethysmography (PPG)-driven smartwatches or wristbands allow for long-term continuous heart rhythm assessment. However, most smartwatches lack an integrated PPG-AF algorithm. Adding a standalone PPG-AF algorithm to these wrist devices might open new possibilities for AF screening and burden assessment. OBJECTIVE: The aim of this study was to assess the accuracy of a well-known standalone PPG-AF detection algorithm added to a popular wristband and smartwatch, with regard to discriminating AF and sinus rhythm, in a group of patients with AF before and after cardioversion (CV). METHODS: Consecutive consenting patients with AF admitted for CV in a large academic hospital in Amsterdam, the Netherlands, were asked to wear a Biostrap wristband or Fitbit Ionic smartwatch with Fibricheck algorithm add-on surrounding the procedure. A set of 1-min PPG measurements and 12-lead reference electrocardiograms was obtained before and after CV. Rhythm assessment by the PPG device-software combination was compared with the 12-lead electrocardiogram. RESULTS: A total of 78 patients were included in the Biostrap-Fibricheck cohort (156 measurement sets) and 73 patients in the Fitbit-Fibricheck cohort (143 measurement sets). Of the measurement sets, 19/156 (12%) and 7/143 (5%), respectively, were not classifiable by the PPG algorithm due to bad quality. The diagnostic performance in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy was 98%, 96%, 96%, 99%, 97%, and 97%, 100%, 100%, 97%, and 99%, respectively, at an AF prevalence of ~50%. CONCLUSIONS: This study demonstrates that the addition of a well-known standalone PPG-AF detection algorithm to a popular PPG smartwatch and wristband without integrated algorithm yields a high accuracy for the detection of AF, with an acceptable unclassifiable rate, in a semicontrolled environment.

Device-related complications in subcutaneous versus transvenous ICD: a secondary analysis of the PRAETORIAN trial.

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.

Strategies for repeat ablation for atrial fibrillation: A multicentre comparison of nonpulmonary vein versus pulmonary vein target 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.

Ablation Index-guided point-by-point ablation versus Grid annotation-guided dragging for pulmonary vein isolation: A randomized controlled trial.

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 < .001). Atrial tachyarrhythmia recurrence was documented in 10 patients (23%) in the Grid annotation arm compared with 19 patients (42%) in the AI annotation arm with time to recurrence not reaching statistical significance (p = .074). CONCLUSIONS: This study shows that a Grid annotation-guided dragging approach provides an alternative to point-by-point RF-PVI using AI annotation.

Radiofrequency ablation to achieve durable pulmonary vein isolation.

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.

Pacing therapy for atrioventricular dromotropathy: a combined computational-experimental-clinical study.

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 <35%) with prolonged PR interval (>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.

Impaired left atrial reservoir and conduit strain in patients with atrial fibrillation and extensive left atrial fibrosis.

BACKGROUND: Atrial fibrillation (AF) is associated with profound structural and functional changes in the atria. In the present study, we investigated the association between left atrial (LA) phasic function and the extent of LA fibrosis using advanced cardiovascular magnetic resonance (CMR) imaging techniques, including 3-dimensional (3D) late gadolinium enhancement (LGE) and feature tracking. METHODS: Patients with paroxysmal and persistent AF (n = 105) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using CMR feature tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy subjects underwent CMR and served as controls (n = 19). RESULTS: Significantly lower LA reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to healthy controls (- 15.9 ± 3.8% vs. - 21.1 ± 3.6% P < 0.001, - 8.7 ± 2.7% vs. - 12.6 ± 2.5% P < 0.001 and - 7.2 ± 2.3% vs. - 8.6 ± 2.2% P = 0.02, respectively). Patients with a high degree of LA fibrosis (dichotomized by the median value) had lower reservoir strain and conduit strain compared to patients with a low degree of LA fibrosis (- 15.0 ± 3.9% vs. - 16.9 ± 3.3%, P = 0.02 and - 7.9 ± 2.7% vs. - 9.5 ± 2.6%, P = 0.01, respectively). In contrast, no difference was found for LA contractile strain (- 7.1 ± 2.4% vs. - 7.4 ± 2.3%, P = 0.55). CONCLUSIONS: Impaired LA reservoir and conduit strain are present in AF patients with extensive atrial fibrosis. Future studies are needed to examine the biologic nature of this association and possible therapeutic implications.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy.

BACKGROUND: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response. METHODS AND RESULTS: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA. CONCLUSION: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

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.

Differences between gap-related persistent conduction and carina-related persistent conduction during radiofrequency pulmonary vein isolation.

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.

Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial.

Aims: Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR). Methods and results: In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography. Conclusion: Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.

Atrioventricular optimization in cardiac resynchronization therapy with quadripolar leads: should we optimize every pacing configuration including multi-point pacing?

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 (Δ%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 Δ%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, Δ%SW at 50% of RAp-RVs (98 ± 74%) was closer to the maximal achievable Δ%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 ∼50% of RAp-RVs creates an acute haemodynamic response close to the maximal patient-specific response.

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling: results from the Markers and Response to CRT (MARC) study.

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. Methods and results: We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. Conclusions: The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908.

Strain analysis in CRT candidates using the novel segment length in cine (SLICE) post-processing technique on standard CMR cine images.

OBJECTIVES: Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates. METHODS: Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated. RESULTS: Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61-0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61). CONCLUSIONS: The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the 'gold standard' CMR-TAG technique, and has the advantage of being widely available. KEY POINTS: • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates.