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Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by chronic organised fibrotic clots, despite adequate anticoagulation. The pulmonary hypertension is also caused by concomitant microvasculopathy which may progress without timely treatment. Timely and accurate diagnosis requires the combination of imaging and haemodynamic assessment. Optimal therapy should be individualised to each case and determined by an experienced multidisciplinary CTEPH team with the ability to offer all current treatment modalities. This report summarises current knowledge and presents key messages from the International CTEPH Conference, Bad Nauheim, Germany, 2021. Sessions were dedicated to 1) disease definition; 2) pathophysiology, including the impact of the hypertrophied bronchial circulation, right ventricle (dys)function, genetics and inflammation; 3) diagnosis, early after acute pulmonary embolism, using computed tomography and perfusion techniques, and supporting the selection of appropriate therapies; 4) surgical treatment, pulmonary endarterectomy for proximal and distal disease, and peri-operative management; 5) percutaneous approach or balloon pulmonary angioplasty, techniques and complications; and 6) medical treatment, including anticoagulation and pulmonary hypertension drugs, and in combination with interventional treatments. Chronic thromboembolic pulmonary disease without pulmonary hypertension is also discussed in terms of its diagnostic and therapeutic aspects.

Abstract We have previously introduced the first generation of C3P3, an artificial system that allows the autonomous in-vivo production of mRNA with m7GpppN-cap. While C3P3-G1 synthesized much larger amounts of capped mRNA in human cells than conventional nuclear expression systems, it produced a proportionately much smaller amount of the corresponding proteins, indicating a clear defect of mRNA translatability. A possible mechanism for this poor translatability could be the rudimentary polyadenylation of the mRNA produced by the C3P3-G1 system. We therefore sought to develop the C3P3-G2 system using an artificial enzyme to post-transcriptionally lengthen the poly(A) tail. This system is based on the mutant mouse poly(A) polymerase alpha fused at its N terminus with an N peptide from the λ virus, which binds to BoxBr sequences placed in the 3′UTR region of the mRNA of interest. The resulting system selectively brings mPAPαm7 to the target mRNA to elongate its poly(A)-tail to a length of few hundred adenosine. Such elongation of the poly(A) tail leads to an increase in protein expression levels of about 2.5–3 times in cultured human cells compared to the C3P3-G1 system. Finally, the coding sequence of the tethered mutant poly(A) polymerase can be efficiently fused to that of the C3P3-G1 enzyme via an F2A sequence, thus constituting the single-ORF C3P3-G2 enzyme. These technical developments constitute an important milestone in improving the performance of the C3P3 system, paving the way for its applications in bioproduction and non-viral human gene therapy.

Introduction Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension (PAH). Although European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines advise assessing PAH severity at baseline and during follow-up, no existing risk assessment methods have been validated for PVOD. This study aimed to identify prognostic factors, examine the impact of treatment strategies and evaluate risk assessment methods for PVOD patients. Methods The study analysed all incident PVOD patients included in the French Pulmonary Hypertension Registry between 2006 and 2021. Survival was assessed based on initial treatment strategy and risk status and compared to a matched (age, sex, pulmonary vascular resistance) PAH group. Six risk assessment methods (number of four low-risk and three noninvasive low-risk variables, ESC/ERS guidelines three-strata and four-strata models, REVEAL 2.0 and Lite 2) were applied at baseline and early follow-up, and their accuracy was compared using Harrell's c-statistic. Results Among the 327 included PVOD patients, survival rates at 1, 3 and 5 years were 86%, 50% and 27%, respectively. Multivariate analysis showed that only 6-min walk distance was associated with survival, with no significant difference based on initial treatment strategy. All six risk assessment methods could discriminate mortality risk, and the ESC/ERS four-strata model was the most accurate at both baseline and follow-up (C-index 0.64 and 0.74). PVOD survival rates were consistently lower than PAH when comparing baseline risk status using the ESC/ERS four-strata model. Conclusion PVOD is associated with poor outcomes, and initial treatment strategies do not significantly affect survival. Risk assessment methods can be useful in predicting survival for PVOD patients.

The Ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and the left cardinal vein, containing a combination of fat, fibrous tissue, blood vessels, muscle bundles, nerve fibers, and ganglia. Various muscular connections exist between the LOM and the left atrium (LA) and the coronary sinus (CS). The LOM is richly innervated by autonomic nerves, with ganglion cells distributed around it. The unique characteristics of the LOM are responsible for generating focal electrical activities and enable it to serve as a substrate for micro- and macro-reentrant circuits. This, in turn, leads to the initiation and perpetuation of atrial fibrillation (AF) and atrial tachycardia (AT). Endocardial ablation in this region does not consistently succeed due to anatomical constraints within the left lateral LA, including the presence of a thicker and longer mitral isthmus (MI), anatomical variations between the MI and epicardial structures such as the CS and vein of Marshall (VOM) and circumflex artery, and the presence of fibrofatty tissue insulating the LOM. Furthermore, epicardial ablation is challenging for inexperienced institutions because of its invasive nature. Ethanol infusion into the VOM (EI-VOM) represents an effective and safe approach that can be employed in conjunction with radiofrequency ablation to eliminate this arrhythmogenic structure.

Abstract Background and objective The automated detection of atrial activations (AAs) recorded from intracardiac electrograms (IEGMs) during atrial fibrillation (AF) is challenging considering their various amplitudes, morphologies and cycle length. Activation time estimation is further complicated by the constant changes in the IEGM active zones in complex and/or fractionated signals. We propose a new method which provides reliable automatic extraction of intracardiac AAs recorded within the pulmonary veins during AF and an accurate estimation of their local activation times. Methods First, two recently developed algorithms were evaluated and optimized on 118 recordings of pulmonary vein IEGM taken from 35 patients undergoing ablation of persistent AF. The adaptive mathematical morphology algorithm (AMM) uses an adaptive structuring element to extract AAs based on their morphological features. The relative-energy algorithm (Rel-En) uses short- and long-term energies to enhance and detect the AAs in the IEGM signals. Second, following the AA extraction, the signal amplitude was weighted using statistics of the AA sequences in order to reduce over- and undersensing of the algorithms. The detection capacity of our algorithms was compared with manually annotated activations and with two previously developed algorithms based on the Teager–Kaiser energy operator and the AF cycle length iteration, respectively. Finally, a method based on the barycenter was developed to reduce artificial variations in the activation annotations of complex IEGM signals. Results The best detection was achieved using Rel-En, yielding a false negative rate of 0.76% and a false positive rate of only 0.12% (total error rate 0.88%) against expert annotation. The post-processing further reduced the total error rate of the Rel-En algorithm by 70% (yielding to a final total error rate of 0.28%). Conclusion The proposed method shows reliable detection and robust temporal annotation of AAs recorded within pulmonary veins in AF. The method has low computational cost and high robustness for automatic detection of AAs, which makes it a suitable approach for online use in a procedural context.

Background Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear. Methods We assessed the proportion and characteristics of patients with “functional respiratory complaints” (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (i.e., symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET). Findings In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9–26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p

Abstract Ultra-high-density (UHD) mapping can improve scar area detection and fast activation mapping in patients undergoing catheter ablation of ventricular tachycardia (VT). The aim of the present study was to compare the outcome after VT ablation guided by UHD and conventional point-by-point 3D-mapping. The acute and long-term ablation outcome of 61 consecutive patients with UHD mapping (64-electrode mini-basket catheter) was compared to 61 consecutive patients with conventional point-by-point 3D-mapping using a 3.5 mm tip catheter. Patients, whose ablation was guided by UHD mapping had an improved 24-months outcome in comparison to patients with conventional mapping (cumulative incidence estimate of the combination of recurrence or disease-related death of 52.4% (95% confidence interval (CI) [36.9–65.7]; recurrence: n = 25; disease-related death: n = 4) versus 69.6% (95% CI [55.9–79.8]); recurrence: n = 31; disease-related death n = 11). In a cause-specific Cox proportional hazards model, UHD mapping (hazard ratio (HR) 0.623; 95% CI [0.390–0.995]; P = 0.048) and left ventricular ejection fraction > 30% (HR 0.485; 95% CI [0.290–0.813]; P = 0.006) were independently associated with lower rates of recurrence or disease-related death. Other procedural parameters were similar in both groups. In conclusion, UHD mapping during VT ablation was associated with fewer VT recurrences or disease-related deaths during long-term follow-up in comparison to conventional point-by-point mapping. Complication rates and other procedural parameters were similar in both groups.

AimsAtrial fibrillation (AF) occurs frequently after mitral valve (MV) surgery. This study aims to evaluate the efficacy and long-term clinical outcomes after the first AF ablation in patients with prior MV surgery.MethodsSixty consecutive patients with a history of MV surgery without MAZE referred to three European centers for a first AF ablation between 2007 and 2017 (group 1) were retrospectively enrolled. They were matched (propensity score match) with 60 patients referred for AF ablation without prior MV surgery (group 2).ResultsAfter the index ablation, 19 patients (31.7%) from group 1 and 24 (40%) from group 2 had no recurrence of atrial arrhythmias (ATa) (p = 0.3). After 62 (48–84) months of follow-up and 2 (2–2) procedures, 90.0% of group 1 and 95.0% of group 2 patients were in sinus rhythm (p = 0.49). In group 1, 19 (31.7%) patients had mitral stenosis, and 41 (68.3%) had mitral regurgitation. Twenty-seven (45.0%) patients underwent mechanical valve replacement and 33 (55.0%) MV annuloplasty. At the final follow-up, 28 (46.7%) and 33 (55.0%) patients were off antiarrhythmic drugs (p = 0.46). ATa recurrence was seen more commonly in patients with prior MV surgery (54 vs. 22%, respectively, p < 0.05). No major complication occurred.ConclusionLong-term freedom of atrial arrhythmias after atrial fibrillation catheter ablation is achievable and safe in patients with a history of mitral valve surgery. In AF patients without a history of mitral valve surgery, repeated procedures are needed to maintain sinus rhythm.

Busulfan is widely used to treat malignant diseases, particularly for therapeutic intensification prior to an autologous stem cell graft. Numerous side effects consecutive to busulfan are described, but few descriptions of pulmonary hypertension exist, while bronchiolitis obliterans remains a rare complication. We report the clinical observations of four patients from the French Pulmonary Hypertension Registry who experienced subacute pulmonary hypertension after receiving busulfan as preparation regimen before an autologous stem cell graft for malignancies (Hodgkin’s disease, Ewing’s sarcoma and primary large B cell lymphoma of the brain). Patients experienced severe pulmonary arterial hypertension 2 to 4.5 months after busulfan administration. Pulmonary hypertension improved after treatment with approved drugs for pulmonary arterial hypertension and/or corticosteroids. During the follow‐up period, two patients developed chronic respiratory insufficiency due to interstitial lung disease, leading to double lung transplantation. The pathological assessment of explanted lungs revealed interstitial lung fibrosis with advanced bronchiolar lesions and severe pulmonary vascular damage. Three of the four patients were still alive after 36 to 80 months and the fourth died unexpectedly and suddenly after 5 months. In conclusion, PAH is a rare but severe complication associated with busulfan chemotherapy in adults. Histological examinations provide evidence for diffuse pulmonary vascular damage combined with interstitial lung injury in most cases.

Abstract Background Cardiovascular magnetic resonance T1ρ mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1ρ mapping method that includes model-based non-rigid motion correction. Methods A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1ρ mapping sequence that collects five T1ρ-weighted (T1ρw) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1ρ fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~ 30 s) and direct visualization of T1ρ maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1ρ maps was scored. In patients, T1ρ mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1ρ values were assessed in remote and injured areas, using LGE as reference. Results Despite breath holds, respiratory motion throughout T1ρw images was much larger in patients than in healthy subjects (5.1 ± 2.7 mm vs. 0.5 ± 0.4 mm, P

Differentiating between atypical atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia utilizing a septal accessory pathway is a complex challenge. The purpose of this study was to describe the "local VA index," a straightforward method based on signals from the coronary sinus catheter, to distinguish between these arrhythmias during tachycardia and entrainment. The ventriculoatrial (VA) interval on the coronary sinus catheter is measured during tachycardia and entrainment, at the site of earliest atrial activity. The difference between these 2 situations defines the "local VA index." We also propose a mechanism to clarify the limitations of historical pacing maneuvers, such as postpacing interval minus tachycardia cycle length (PPI-TCL) and stimulus–atrial interval minus ventriculoatrial interval (SA-VA), by examining nodal decrement and intraventricular conduction delay. In a retrospective study of 75 patients referred for supraventricular tachycardia evaluation, 37 were diagnosed with atrioventricular reentrant tachycardia (AVRT) with orthodromic reciprocating tachycardia, and 38 with AVNRT (27 typical, 11 atypical). In comparison to AVRT patients, AVNRT patients exhibited longer PPI-TCL (176 ± 47 ms vs 113 ± 42 ms; P <.01) and SA-VA (138 ± 47 ms vs 64 ± 28 ms; P <.01). The AVRT group had mean local VA index of –1 ± 13 ms, whereas the AVNRT group had a significantly longer index of 91 ± 46 ms (P <.01). An optimal threshold for differentiation was a local VA index of 40 ms. Importantly, there was no significant correlation between pacing cycle length and nodal decrement as well as intraventricular delay related to pathway location. This interindividual variability might explain misleading interpretations of PPI-TCL and SA-VA. This novel approach is advantageous because of its simplicity and effectiveness, requiring only 2 diagnostic catheters. A local VA interval difference <40 ms provides a clear distinction for AVRT. [ABSTRACT FROM AUTHOR]

Rationale The characteristics of patients with respiratory complaints and/or lung radiologic abnormalities after hospitalisation for coronavirus disease 2019 (COVID-19) are unknown. The objectives were to determine their characteristics and the relationships between dyspnoea, radiologic abnormalities and functional impairment. Methods In the COMEBAC (Consultation Multi-Expertise de Bicêtre Après COVID-19) cohort study, 478 hospital survivors were evaluated by telephone 4 months after hospital discharge, and 177 who had been hospitalised in an intensive care unit (ICU) or presented relevant symptoms underwent an ambulatory evaluation. New-onset dyspnoea and cough were evaluated, and the results of pulmonary function tests and high-resolution computed tomography of the chest were collected. Results Among the 478 patients, 78 (16.3%) reported new-onset dyspnoea, and 23 (4.8%) new-onset cough. The patients with new-onset dyspnoea were younger (56.1±12.3 versus 61.9±16.6 years), had more severe COVID-19 (ICU admission 56.4% versus 24.5%) and more frequent pulmonary embolism (18.0% versus 6.8%) (all p≤0.001) than patients without dyspnoea. Among the patients reassessed at the ambulatory care visit, the prevalence of fibrotic lung lesions was 19.3%, with extent

ObjectiveThe diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is a major challenge as it is a curable cause of pulmonary hypertension (PH). Ventilation/Perfusion (V/Q) lung scintigraphy is the imaging modality of choice for the screening of CTEPH. However, there is no consensus on the criteria to use for interpretation. The aim of this study was to assess the accuracy of various interpretation criteria of planar V/Q scintigraphy for the screening of CTEPH in patients with PH.MethodsThe eligible study population consisted of consecutive patients with newly diagnosed PH in the Brest University Hospital, France. Final diagnosis (CTEPH or non-CTEPH) was established in a referential center on the management of PH, based on the ESC/ERS guidelines and a minimum follow-up of 3 years. A retrospective central review of planar V/Q scintigraphy was performed by three nuclear physicians blinded to clinical findings and to final diagnosis. The number, extent (sub-segmental or segmental) and type (matched or mismatched) of perfusion defects were reported. Sensitivity and specificity were evaluated for various criteria based on the number of mismatched perfusion defects and the number of perfusion defects (regardless of ventilation). Receiver operating characteristic (ROC) curves were generated and areas under the curve (AUC) were calculated for both.ResultsA total of 226 patients with newly diagnosed PH were analyzed. Fifty six (24.8%) were diagnosed with CTEPH while 170 patients (75.2%) were diagnosed with non-CTEPH. The optimal threshold was 2.5 segmental mismatched perfusion defects, providing a sensitivity of 100 % (95% CI 93.6–100%) and a specificity of 94.7% (95%CI 90.3–97.2%). Lower diagnostic cut-offs of mismatched perfusion defects provided similar sensitivity but lower specificity. Ninety five percent of patients with CTEPH had more than 4 segmental mismatched defects. An interpretation only based on perfusion provided similar sensitivity but a specificity of 81.8% (95%CI 75.3–86.9%).ConclusionOur study confirmed the high diagnostic performance of planar V/Q scintigraphy for the screening of CTEPH in patients with PH. The optimal diagnostic cut-off for interpretation was 2.5 segmental mismatched perfusion defects. An interpretation only based on perfusion defects provided similar sensitivity but lower specificity.

Cardiac excitation-contraction coupling can be different between regions of the heart. Little is known at the atria level, specifically in different regions of the left atrium. This is important given the role of cardiac myocytes from the pulmonary vein sleeves, which are responsible for ectopic activity during atrial fibrillation. In this study, we present a new method to isolate atrial cardiac myocytes from four different regions of the left atrium of a large animal model, sheep, highly relevant to humans. Using collagenase/protease we obtained calcium-tolerant atrial cardiac myocytes from the epicardium, endocardium, free wall and pulmonary vein regions. Calcium transients were slower (time to peak and time to decay) in free wall and pulmonary vein myocytes compared to the epicardium and endocardium. This is associated with lower t-tubule density. Overall, these results suggest regional differences in calcium transient and t-tubule density across left atria, which may play a major role in the genesis of atrial fibrillation.

Background and aims: Post-endoscopic retrograde cholangiopancreatography acute pancreatitis (PAP) and post-sphincterotomy hemorrhage are known adverse events of post-endoscopic retrograde cholangiopancreatography. Various electrosurgical currents can be used for endoscopic sphincterotomy. The extent to which this influences adverse events remains unclear. We assessed the comparative safety of different electrosurgical currents, through a Bayesian network meta-analysis of published studies merging direct and indirect comparison of trials. Methods: We performed a Bayesian random-effects network meta-analysis of randomized controlled trials that compared the safety of different electrocautery modes for endoscopic sphincterotomy. Results: Nine studies comparing four electrocautery modes (blended cut, pure cut, endocut, and pure cut followed by blended cut) with a combined enrollment of 1615 patients were included. The pooled results of the network meta-analysis did not show a significant difference in preventing post-sphincterotomy pancreatitis when comparing electrocautery modes. However, pure cut was associated with a statistically significant increased risk of bleeding compared with endocut [relative risk = 4.30; 95% confidence interval (1.53–12.87)]. On the other hand, the pooled results of the network meta-analysis showed no significant difference in prevention of bleeding when comparing blended cut versus endocut, pure cut followed by blended cut versus endocut, pure cut followed by blended cut versus blended cut, pure cut versus blended cut, and pure cut versus pure cut followed by blended cut. The results of rank probability found that endocut was most likely to be ranked the best. Conclusion: No electrocautery mode was superior to another with regard to preventing PAP. Endocut was superior with respect to preventing bleeding. Therefore, we suggest performing endoscopic sphincterotomy with endocut.

Pulmonary arterial hypertension (PAH) is a rare disease characterised by pulmonary vascular remodelling and elevated pulmonary pressure, which eventually leads to right heart failure and death. Registries worldwide have noted a female predominance of the disease, spurring particular interest in hormonal involvement in the disease pathobiology. Several experimental models have shown both protective and deleterious effects of oestrogens, suggesting that complex mechanisms participate in PAH pathogenesis. In fact, oestrogen metabolites as well as receptors and enzymes implicated in oestrogen signalling pathways and associated conditions such as BMPR2 mutation contribute to PAH penetrance more specifically in women. Conversely, females have better right ventricular function, translating to a better prognosis. Along with right ventricular adaptation, women tend to respond to PAH treatment differently from men. As some young women suffer from PAH, contraception is of particular importance, considering that pregnancy in patients with PAH is strongly discouraged due to high risk of death. When contraception measures fail, pregnant women need a multidisciplinary team-based approach. This article aims to review epidemiology, mechanisms underlying the higher female predominance, but better prognosis and the intricacies in management of women affected by PAH.

Abstract Introduction The Memorial Anxiety Scale for Prostate Cancer (MAX-PC, 18 items) was developed to assess anxiety in prostate cancer patients. In the absence of a French version of this scale, we adapted the original English scale and evaluated its psychometric properties in a sample of French men diagnosed with prostate cancer in the previous 12 months. Methods The MAX-PC was translated from English to French and distributed online by two non-profit organizations (Seintinelles and ANAMACaP). The French questionnaire, which also included the Hospital Anxiety and Depression Scale (HADS) and a measure of health-related quality of life (SF12), was intended for adults diagnosed with prostate cancer in the previous 12 months. Factor structure was assessed using exploratory factor analysis (EFA) on data from 56.2% of the sample (n = 104, Seintinelles subsample) and confirmed using confirmatory factor analysis (CFA) on data from the rest of the sample (n = 81, ANAMACaP subsample). The reliability of the scale was measured using Cronbach’s alpha coefficient. Construct validity was assessed by calculating the correlation of the MAX-PC total score and subscale scores with the HADS total score and subscale scores and with the SF12 total score and subscale scores. Results Of the 185 respondents, 168 (90.8%) had complete data on all MAX-PC items. The average age of participants was 65.1 years (SD: 7.7). The three-factor structure defined in the original validation study was very similar in EFA and then confirmed by CFA. The MAX-PC showed good reliability, as Cronbach’s alpha coefficients for the scale and for its three subscales were 0.92, 0.90, 0.68, and 0.87, respectively. It also showed good construct validity. As expected, the MAX-PC total score was positively correlated with the HADS-Anxiety subscale score (r = 0.68, p

The tremendous advancement of cardiac imaging methods, the substantial progress in predictive modelling, along with the amount of new investigative multimodalities, challenge the current technologies in the cardiology field. Innovative, robust and multimodal tools need to be created in order to fuse imaging data (e.g., MR, CT) with mapped electrical activity and to integrate those into 3D biophysical models. In the past years, several cross-platform toolkits have been developed to provide image analysis tools to help build such software. The aim of this study is to introduce a novel multimodality software platform dedicated to cardiovascular diagnosis and therapy guidance: MUSIC. This platform was created to improve the image-guided cardiovascular interventional procedures and is a robust platform for AI/Deep Learning, image analysis and modelling in a newly created consortium with international hospitals. It also helps our researchers develop new techniques and have a better understanding of the cardiac tissue properties and physiological signals. Thus, this extraction of quantitative information from medical data leads to more repeatable and reliable medical diagnoses.

BackgroundVentricular fibrillation (VF) is the main cause of sudden cardiac death, but its mechanisms are still unclear. We propose a noninvasive approach to describe the progression of VF complexity from body surface potential maps (BSPMs).MethodsWe mapped 252 VF episodes (16 ± 10 s) with a 252-electrode vest in 110 patients (89 male, 47 ± 18 years): 50 terminated spontaneously, otherwise by electrical cardioversion (DCC). Changes in complexity were assessed between the onset (“VF start”) and the end (“VF end”) of VF by the nondipolar component index (NDIBSPM), measuring the fraction of energy nonpreserved by an equivalent 3D dipole from BSPMs. Higher NDI reflected lower VF organization. We also examined other standard body surface markers of VF dynamics, including fibrillatory wave amplitude (ABSPM), surface cycle length (BsCLBSPM) and Shannon entropy (ShEnBSPM). Differences between patients with and without structural heart diseases (SHD, 32 vs. NSHD, 78) were also tested at those stages. Electrocardiographic features were validated with simultaneous endocardium cycle length (CL) in a subset of 30 patients.ResultsAll BSPM markers measure an increase in electrical complexity during VF (p < 0.0001), and more significantly in NSHD patients. Complexity is significantly higher at the end of sustained VF episodes requiring DCC. Intraepisode intracardiac CL shortening (VF start 197 ± 24 vs. VF end 169 ± 20 ms; p < 0.0001) correlates with an increase in NDI, and decline in surface CL, f-wave amplitude, and entropy (p < 0.0001). In SHD patients VF is initially more complex than in NSHD patients (NDIBSPM, p = 0.0007; ShEnBSPM, p < 0.0001), with moderately slower (BsCLBSPM, p = 0.06), low-amplitude f-waves (ABSPM, p < 0.0001). In this population, lower NDI (p = 0.004) and slower surface CL (p = 0.008) at early stage of VF predict self-termination. In the NSHD group, a more abrupt increase in VF complexity is quantified by all BSPM parameters during sustained VF (p < 0.0001), whereas arrhythmia evolution is stable during self-terminating episodes, hinting at additional mechanisms driving VF dynamics.ConclusionMultilead BSPM analysis underlines distinct degrees of VF complexity based on substrate characteristics.