Automatic and interpretable prediction of the site of origin in outflow tract ventricular arrhythmias: machine learning integrating electrocardiograms and clinical data.

The treatment of outflow tract ventricular arrhythmias (OTVA) through radiofrequency ablation requires the precise identification of the site of origin (SOO). Pinpointing the SOO enhances the likelihood of a successful procedure, reducing intervention times and recurrence rates. Current clinical methods to identify the SOO are based on qualitative analysis of pre-operative electrocardiograms (ECG), heavily relying on physician's expertise. Although computational models and machine learning (ML) approaches have been proposed to assist OTVA procedures, they either consume substantial time, lack interpretability or do not use clinical information. Here, we propose an alternative strategy for automatically predicting the ventricular origin of OTVA patients using ML. Our objective was to classify ventricular (left/right) origin in the outflow tracts (LVOT and RVOT, respectively), integrating ECG and clinical data from each patient. Extending beyond differentiating ventricle origin, we explored specific SOO characterization. Utilizing four databases, we also trained supervised learning models on the QRS complexes of the ECGs, clinical data, and their combinations. The best model achieved an accuracy of 89%, highlighting the significance of precordial leads V1-V4, especially in the R/S transition and initiation of the QRS complex in V2. Unsupervised analysis revealed that some origins tended to group closer than others, e.g., right coronary cusp (RCC) with a less sparse group than the aortic cusp origins, suggesting identifiable patterns for specific SOOs.

A hybrid clinical and electrocardiographic score to predict the origin of outflow tract ventricular arrhythmias.

BACKGROUND: To predict the outflow tract ventricular arrhythmias (OTVA) site of origin (SOO) before the ablation procedure has important practical implications. The present study sought to prospectively evaluate the accuracy of a clinical and electrocardiographic hybrid algorithm (HA) for the prediction of OTVAs-SOO, and at the same time to develop and to prospectively validate a new score with improved discriminatory capacity. METHODS: In this multicenter study, we prospectively enrolled consecutive patients referred for OTVA ablation (N = 202), and we divided them in a derivation sample and a validation cohort. Surface ECGs during OTVA were analyzed to compare previous published ECG-only criteria and to develop a new score. RESULTS: In the derivation sample (N = 105), the correct prediction rate of HA and ECG-only criteria ranged from 74 to 89%. R-wave amplitude in V3 was the best ECG parameter for discriminating LVOT origin in V3 precordial transition (V3PT) patients, and was incorporated to the novel weighted hybrid score (WHS). WHS correctly classified 99 (94.2%) patients, presenting 90% sensitivity and 96% specificity (AUC 0.97) in the entire population; WHS mantained a 87% sensitivity and 91% specificity (AUC 0.95) in patients with V3PT subgroup. The high discriminatory capacity was confirmed in the validation sample (N = 97): the WHS exhibited an AUC (0.93), and a WHS ≥ 2 allowed a correct prediction of LVOT origin in 87 (90.0%) cases, yielding a sensitivity of 87% and specificity of 90%; moreover, the V3PT subgroup showed an AUC of 0.92, and a punctuation ≥ 2 predicted an LVOT origin with a sensitivity of 94% and specificity of 78%. CONCLUSIONS: The novel hybrid score has proved to accurately anticipate the OTVA's origin, even in those with a V3 precordial transition. A Weighted hybrid score. B Typical examples of the use of the weighted hybrid score. C ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the derivation cohort. D ROC analysis of WHS and previous ECG criteria for prediction of LVOT origin in the V3 precordial transition OTVA subgroup.

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia.

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Immunofluorescent and molecular characterization of effusion tumor cells reveal cancer site-of-origin and disease-driving mutations.

BACKGROUND: Effective cancer treatment relies on precision diagnostics. In cytology, an accurate diagnosis facilitates the determination of proper therapeutics for patients with cancer. Previously, the authors developed a multiplexed immunofluorescent panel to detect epithelial malignancies from pleural effusion specimens. Their assay reliably distinguished effusion tumor cells (ETCs) from nonmalignant cells; however, it lacked the capacity to reveal specific cancer origin information. Furthermore, DNA profiling of ETCs revealed some, but not all, cancer-driver mutations. METHODS: The authors developed a new multiplex immunofluorescent panel that detected both malignancy and pulmonary origin by incorporating the thyroid transcription factor-1 (TTF-1) biomarker. Evaluation for TTF-1-positive ETCs (T-ETCs) was performed on 12 patient samples. T-ETCs and parallel ETCs from selected patients were collected and subjected to DNA profiling to identify pathogenic mutations. All samples were obtained with Institutional Review Board approval. RESULTS: Malignancy was detected in all samples. T-ETCs were identified in 9 of 10 patients who had clinically reported TTF-1 positivity (90% sensitivity and 100% specificity). Furthermore, DNA profiling of as few as five T-ETCs identified pathogenic mutations with equal or greater sensitivity compared with profiling of ETCs, both of which showed high concordance with clinical findings. CONCLUSIONS: The findings suggest that the immunofluorescent and molecular characterization of tumor cells from pleural effusion specimens can provide reliable diagnostic information, even with very few cells. The integration of site-specific biomarkers like TTF-1 into ETC analysis may facilitate better refined diagnosis and improve patient care.

Clinico-pathologic characteristics and prognostic factors of ovarian carcinoma with different histologic subtypes - A benchmark analysis of 482 cases.

PURPOSE: Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis. METHODS: The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis. RESULTS: The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p < 0.001), more frequently diagnosed at an advanced stage >pT3 (78.5% (219/279) versus 42.8% (87/203); p < 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p < 0.02) with a 4.6-fold higher rate of > 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p < 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups. CONCLUSION: OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin.

Reappraisal of electrocardiographic criteria for localization of idiopathic outflow region ventricular arrhythmias.

BACKGROUND: Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria. OBJECTIVE: The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV). METHODS: One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1-3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site. RESULTS: Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites. CONCLUSION: ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

A Novel Use of Noninvasive Registered Electrocardiographic Imaging Map for Localization of VT and PVC.

A 33-year-old woman presented with sustained monomorphic ventricular tachycardia (VT). The 12-lead electrocardiogram, 3-dimensional (3D) picture of chest electrodes, and cardiac magnetic resonance were used to create a noninvasive 3D electrocardiographic imaging map to identify the most likely site of VT origin. This map was integrated with a 3D mapping system to aid in VT ablation. (Level of Difficulty: Advanced.).

Increase of fallopian tube and decrease of ovarian carcinoma: fact or fake?

PURPOSE: Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. METHODS: Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. RESULTS: The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. CONCLUSION: The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

Pathologic Considerations in Gastroenteropancreatic Neuroendocrine Tumors.

This review serves as a primer on contemporary neuroendocrine neoplasm classification, with an emphasis on gastroenteropancreatic well-differentiated neuroendocrine tumors. Topics discussed include general features of neuroendocrine neoplasms, general neuroendocrine marker immunohistochemistry, the distinction of well-differentiated neuroendocrine tumor from pheochromocytoma/paraganglioma and other diagnostic mimics and poorly differentiated neuroendocrine carcinoma from diagnostic mimics, the concepts of differentiation and grade and the application of Ki-67 immunohistochemistry to determine the latter, the various WHO classifications of neuroendocrine neoplasms including the 2019 WHO classification of gastroenteropancreatic tumors, organ-specific considerations for gastroenteropancreatic well-differentiated neuroendocrine tumors, immunohistochemistry to determine site of origin in metastatic well-differentiated neuroendocrine tumor of occult origin, immunohistochemistry in the distinction of well-differentiated neuroendocrine tumor G3 from large cell neuroendocrine carcinoma, and, finally, required and recommended reporting elements for biopsies and resections of gastroenteropancreatic neuroendocrine epithelial neoplasms.

SATB2 in neuroendocrine neoplasms: strong expression is restricted to well-differentiated tumours of lower gastrointestinal tract origin and is most frequent in Merkel cell carcinoma among poorly differentiated carcinomas.

AIMS: Special AT-rich sequence-binding protein 2 (SATB2) is a transcriptional regulator with critical roles in brain, craniofacial and skeletal development. It has emerged as a key marker of lower gastrointestinal (GI) tract columnar epithelial and osteoblastic differentiation. Transcription factor immunohistochemistry is useful in assigning site of origin in well-differentiated neuroendocrine tumours (NETs), and has had a limited role in poorly differentiated neuroendocrine carcinomas (NECs). This study sought to evaluate the role of SATB2 in assigning site of origin in neuroendocrine epithelial neoplasms. METHODS AND RESULTS: Tissue microarrays were constructed from the following: 317 NETs (37 thyroid, 46 lung, 16 stomach, 12 duodenum, 70 pancreas, 106 jejunoileum, 24 appendix, and six rectosigmoid), 44 phaeochromocytomas/paragangliomas, and 79 NECs (29 Merkel cell, 30 lung, and 20 extrapulmonary visceral); nine appendiceal and 19 rectal NETs were examined in whole sections. SATB2 immunohistochemistry was scored for extent (%) and intensity (0-3+), with an H-score being calculated. SATB2 was expressed by 96% of rectosigmoid NETs, 79% of appendiceal NETs, and only 7% of other well-differentiated neoplasms (P < 0.0001). Expression in lower GI tract NETs (median H-score of 255) was stronger than in other positive tumours (median H-score of 7) (P < 0.0001). Any SATB2 expression was 86% sensitive/93% specific for lower GI tract origin. SATB2 was expressed by 79% of Merkel cell carcinomas (median H-score of 300), 33% of lung NECs (median H-score of 23), and 60% of extrapulmonary visceral NECs (median H-score of 110), with stronger expression in Merkel cell carcinoma (P < 0.001). At an H-score cutoff of ≥150, SATB2 was 69% sensitive/90% specific for Merkel cell carcinoma. CONCLUSIONS: SATB2 is frequently and strongly expressed by lower GI tract NETs; we have adopted it as our rectal NET marker. Relatively frequent and strong expression in Merkel cell carcinoma may have value in assigning NEC site of origin.

American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.

This review reflects a collaboration between the American Registry of Pathology (the publisher of the Armed Forces Institute of Pathology Fascicles) and Annals of Diagnostic Pathology. It is part of a series of expert recommendations on topics encountered in daily practice. The authors, three pathologists with expertise in gastrointestinal tract pathology and immunohistochemistry, met on 30 July 2019 tasked with developing expert recommendations for evaluating poorly differentiated and undifferentiated malignant neoplasms encountered on mucosal biopsies of the gastrointestinal tract. We focused on esophageal, gastric, small intestinal, colorectal, and anal (i.e., tubal gut) samples. When faced with diagnostic uncertainty on the initial H&E, it is best to begin by trying to assign the broad tumor class with screening markers such as pankeratin, S100 protein or SOX10, and CD20 or CD45. Once a broad tumor class is established, more specific differentiation markers can be pursued (e.g., lineage-restricted transcription factors for adenocarcinoma; p40 for squamous cell carcinoma; chromogranin A and synaptophysin or INSM1 for neuroendocrine neoplasms). Every small biopsy containing tumor should be considered a potential molecular pathology sample; cutting extra unstained slides with this testing in mind is strongly encouraged.

Leiomyosarcoma: Prognostic outline of a rare head and neck malignancy.

Soft tissue sarcomas (STS) are mesenchymal malignant neoplasms with a broad spectrum of biologic behaviour. Most STS show predilection for extremities with rarity in head and neck. Leiomyosarcoma (LMS) is an extremely rare STS in head and neck due to the paucity of smooth muscles in this anatomical region. Owing to its rarity, diagnosis of LMS is often delayed or is often misdiagnosed. Our study aimed to evaluate clinico-demographic factors determining clinical course of primary head-neck LMS. Further, we also assessed cases of secondary head-neck LMS and LMS due to other causes to compare their clinical outcome with primary head-neck LMS. In primary LMS cases, intraoral LMS showed slightly better prognosis than extraoral LMS. Survival analysis revealed that prognosis of primary LMS was significantly better than secondary LMS. No significant difference in survival was seen between primary LMS and LMS due to other causes. These observations indicate that site of origin appears to determine the clinical behaviour of LMS. Results showed that size, recurrence and metastasis are important prognostic variables. Though large tumor size was associated with poor prognosis, tumor aggressiveness may not be directly proportional to its size. Surgical management with or without adjuvant therapy was associated with favourable outcome. As several factors are associated with prognostic outcome of head-neck LMS, multimodality therapy approach after careful analysis of various prognostic variables in each case on an individual basis is essential.

How to use the 12-lead ECG to predict the site of origin of idiopathic ventricular arrhythmias.

Idiopathic ventricular arrhythmias may arise from anywhere in the heart, and the majority of them can be effectively treated with catheter ablation. The 12-lead electrocardiogram (ECG) is the initial mapping tool to predict the most likely site of origin and is valuable to choose the appropriate ablation strategy. Crucial to ECG interpretation is understanding the attitudinal orientation of the heart within the chest and the relationship between the different cardiac structures. In this review, we provide a stepwise anatomical approach for the localization of idiopathic ventricular arrhythmias based on sequential analysis of the most relevant ECG features.

Localization of Ventricular Arrhythmias for Catheter Ablation: The Role of Surface Electrocardiogram.

The surface ECG is a valuable mapping tool in patients with idiopathic and scar-related ventricular arrhythmias (VAs). A detailed analysis of 12-lead ECG can provide useful information in localizing the VA site of origin. This might help tailoring the ablation strategy to optimize procedural duration, increase the probability of success, and prevent complications. The aim of this article is to review the ECG features of both idiopathic and scar-related VAs and discuss their potential implications for optimizing the ablation strategy.

Single- and dual-site pace mapping of idiopathic septal intramural ventricular arrhythmias.

BACKGROUND: Pace mapping (PM) is used to identify the origin of ventricular arrhythmias (VAs). For intramural VAs, the site of origin often cannot be reached and therefore PM is less accurate. OBJECTIVE: The purpose of this study was to assess the value of single- and dual-site pace maps to differentiate intramural from nonintramural VAs. METHODS: In 18 consecutive patients with idiopathic intramural VAs, pace mapping was performed at 2 breakthrough sites in adjacent anatomic structures. Twelve-lead electrocardiograms of the 2 pace maps were averaged in MATLAB and compared (correlation coefficient [CC]) with the targeted VA. Dual-site pace mapping was performed in a control group of 18 patients with nonintramural VAs at the sites of earliest electrical activation and a breakthrough site in an adjacent anatomic location. RESULTS: Dual-site pace maps had a higher CC than did best single-site pace maps (0.87 ± 0.1 vs 0.81 ± 0.16; P = .02) in patients with intramural VAs. At the site of origin, single-site pace maps had a higher CC than did dual-site pace maps obtained from adjacent anatomic locations (0.93 ± 0.04 vs 0.89 ± 0.05; P = .0004) in patients with nonintramural VAs. Sensitivity, specificity, positive predictive value, and negative predictive value of dual-site pace maps for identifying an intramural VA were 89%, 82%, 84%, 88%, and 86%, respectively. Furthermore, the receiver operating characteristic curve analysis revealed that a CC cutoff value of ≤0.86 for a single-site pace map best differentiated intramural from nonintramural VAs. CONCLUSION: A higher CC value for a dual-site pace map obtained from the earliest breakthrough site as well as a CC cutoff value of ≤0.86 for a single-site pace map obtained from the site of earliest electrical activation can best differentiate intramural from nonintramural VAs.

Problems with the diagnosis of metastatic neuroendocrine neoplasms. Which diagnostic criteria should we use to determine tumor origin and help guide therapy?

Neuroendocrine neoplasms (NENs) can often present with metastatic disease before the primary tumor is discovered. Metastatic lesions are generally classified as well differentiated and poorly differentiated for prognostic and therapeutic purposes. In addition, for well-differentiated neuroendocrine tumors (WDNETs), pathologists are expected to determine the site of origin, if not already known, and grade the tumors. However, it is often difficult for pathologists to provide this information with certainty without knowing the site of tumor origin, as different criteria have been proposed by WHO for classification of gastrointestinal and pulmonary NENs. In this review, we will discuss the current classification and grading schema of NENs and their impact on clinical care, the differential diagnosis of NENs, the use of immunohistochemical stains that help identify tumor site of origin, and a proposed approach for the diagnosis and classification of metastatic NENs.

An easy-to-use, operator-independent, clinical model to predict the left vs. right ventricular outflow tract origin of ventricular arrhythmias.

AIMS: To identify clinical characteristics able to predict a left ventricular outflow tract (LVOT) origin in outflow tract ventricular arrhythmias (OTVAs). METHODS AND RESULTS: We included 117 consecutive patients (training sample) with successful radiofrequency ablation of OTVA in one centre. A predictive model for LVOT origin was obtained using clinical data. The model was prospectively validated in a second population (testing sample) of 143 patients from two additional centres. In training sample, mean age was 54 ± 17 years, 72 patients (61%) were male, and 63 (54%) had cardiovascular risk factors. Sixty (51%) patients had LVOT origin. Independent predictors for LVOT origin were the presence of hypertension [odds ratio (OR) 2.17, confidence interval (CI) 0.91-6.20, P = 0.09], male gender (OR 4.83, 95% CI 1.89-12.33, P < 0.001), and age >50 years (OR 4.46, 95% CI 1.57-12.7, P = 0.005). A simple score was constructed with these three variables to predict LVOT origin (mean predicted probability of 15% for score 0, 26% for score 1, 60% for score 2, and 87% for score 3, P < 0.001) and reached 80% sensitivity and 75% specificity. The score was validated in the testing sample and was not inferior to previously described electrocardiogram algorithms. CONCLUSION: Patients currently referred for OTVA ablation are older, more frequently men, and with a higher probability for LVOT origin than previously described. A LVOT origin is associated with the presence of hypertension, male gender, and older age, and can be anticipated by using a simple clinical score.

Impact of earliest activation site location in the septal right ventricular outflow tract for identification of left vs right outflow tract origin of idiopathic ventricular arrhythmias.

BACKGROUND: The earliest activation site (EAS) location in the septal right ventricular outflow tract (RVOT) could be an additional mapping data predictor of left ventricular outflow tract (LVOT) vs RVOT origin of idiopathic ventricular arrhythmias (VAs). OBJECTIVE: The purpose of this study was to assess the impact of EAS location in predicting LVOT vs RVOT origin. METHODS: Macroscopic and histologic study was performed in 12 postmortem hearts. Electroanatomic maps (EAMs) from 37 patients with outflow tract (OT) VA with the EAS in the septal RVOT were analyzed. Pulmonary valve (PV) was defined by voltage scanning after validation of voltage thresholds by image integration. EAM measurements were correlated with those of macroscopic/histologic study. RESULTS: A cutoff value of 1.9 mV discriminated between subvalvular and supravalvular positions (90% sensitivity, 96% specificity). EAS ≥1 cm below PV excluded RVOT site of origin (SOO). According to anatomic findings (distance PV-left coronary cusp = 5 ± 3 vs PV-right coronary cusp = 11 ± 5 mm), EAS-PV distance was significantly shorter in VAs arising from left coronary cusp than from the other LVOT locations (4.2 ± 5.4 mm vs 9.2 ± 7 mm; P = .034). The 10-ms isochronal longitudinal/perpendicular diameter ratio was higher in the RVOT vs the LVOT SOO group (1.97 ± 1.2 vs 0.79 ± 0.49; P = .001). An algorithm based on EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio predicted LVOT SOO with 91% sensitivity and 100% specificity. CONCLUSION: An algorithm based on the EAS-PV distance and the 10-ms isochronal longitudinal/perpendicular diameter ratio accurately predicts LVOT vs RVOT SOO in outflow tract VAs with EAS in the septal RVOT.

Neurohormonal, structural, and functional recovery pattern after premature ventricular complex ablation is independent of structural heart disease status in patients with depressed left ventricular ejection fraction: a prospective multicenter study.

OBJECTIVES: This study aimed to assess the benefit after ablation of premature ventricular complexes (PVC) in patients with frequent PVC and left ventricular (LV) dysfunction, regardless of previous structural heart disease (SHD) diagnosis, PVC morphology, or estimated site of origin. BACKGROUND: Ablation of PVC in patients with LV dysfunction is usually restricted to patients with suspected PVC-induced cardiomyopathy. METHODS: Consecutive patients with frequent PVC and LV dysfunction accepted for ablation at 4 centers were prospectively included. Of the 80 patients included, 27 (34%) had a diagnosis of SHD. RESULTS: Successful sustained ablation (SSA) was achieved in 53 (66%) patients, and LVEF improved in these patients from 33.7 ± 8% to 43.8 ± 9.4% and 45.8 ± 10.9% at 6 and 12 months, respectively (p < 0.05), without differences related to previous diagnosis of SHD (p = 0.69). BNP decreased from 109 [64 to 242] pg/ml to 60 [25 to 170] pg/ml, 50 [14 to 130] pg/ml, and 60 [19 to 81] pg/ml at 1, 6, and 12 months (p < 0.05). Patients in NYHA class I increased from 12 (23%) to 42 (79%) at 12 months (p < 0.05). A 13% baseline PVC burden had 100% sensitivity and 85% specificity to predict an absolute increase ≥ 5% in LVEF after SSA. Although 20 patients with >13% PVC and SSA had class I indication for cardioverter defibrillator implantation, these indications were absent at 6 months post-ablation. CONCLUSIONS: Independently of the presence of SHD, the SSA of frequent PVC in patients with depressed LVEF induced a progressive clinical and functional improvement. Improvement in heart failure parameters was related to baseline PVC burden and persistence of ablation success.