Editorial: Case reports in heart failure and transplantation: 2022

In this editorial we summarize the most viewed and downloaded contributing articles to the Research Topic “Case Reports in Heart Failure and Transplantation: 2022” of the journal Frontiers in Cardiovascular Medicine

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies

Moderator band and ventricular tachycardia: structural or functional substrate?

The moderator band (MB) is an intracavitary structure of the right ventricle composed of muscular fibers encompassing specialized Purkinje fibers, separated each other by collagen and adipose tissue. In the last decades, premature ventricular complexes originating within the Purkinje network have been implicated in the genesis of life-threatening arrhythmias. However, right Purkinje network arrhythmias have been much less reported in the literature compared to the left counterpart. The MB has unique anatomical and electrophysiological properties, which may account for its arrhythmogenicity and may be responsible for a significant portion of idiopathic ventricular fibrillation. MB embodies autonomic nervous system cells, with important implications in arrhythmogenesis. Some idiopathic ventricular arrhythmias, defined as the absence of any identifiable structural heart disorder, can begin from this site. Due to these complex structural and functional peculiarities strictly interplayed each other, it is arduous to determine the precise mechanism underlying MB arrhythmias. MB-related arrhythmias should be differentiated from other right Purkinje fibers arrhythmias because of the opportunity for intervention and the unusual site for the ablation poorly described in the literature. In the current paper, we report the characteristics and electrical properties of the MB, their involvement in arrhythmogenesis, clinical and electrophysiological peculiarities of MB-related arrhythmias, and current treatment options. © 2023 by the authors

Impact of Vein of Marshall Ethanol Infusion Combined with Anatomical Ablation for the Treatment of Persistent Atrial Fibrillation: A Long-Term Follow-Up Based on Implantable Loop Recorders

Background: The best ablation treatment for persistent atrial fibrillation (PeAF) patients is still debated. The vein of Marshall (VOM) seems to be a promising target for ablation and could be combined with a linear set of ablation lesions. The aim of our study is to evaluate the incidence of AF recurrences in a PeAF population treated with a comprehensive ablation approach consisting of VOM ethanol infusion (EI), pulmonary vein isolation (PVI), a left atrial (LA) roofline, a mitral line (guided by the newly formed lesion after alcohol infusion into the VOM and validated by pacing), and a cavotricuspid isthmus line. Methods: Consecutive patients undergoing the first ablation procedure of catheter ablation (CA) for PeAF were enrolled. All patients underwent VOM-EI, PVI, and ablation lines along the roof of the LA, mitral, and cavotricuspid isthmus. LA voltage mapping before and after VOM-EI was also performed. An implantable loop recorder (ILR) was implanted at the end of the ablation in each patient. Results: Thirty-one consecutive patients (66 ± 8 years and 71% male) affected by PeAF were included in this study. The VOM-EI procedural phase lasted 21.4 ± 10.1 min. PV isolation and lines were validated in all subjects. The ML block was achieved within 10.8 ± 8.7 min. At a mean follow-up of 12 ± 7 months, 27 out of 31 (87%) patients remained free from AT/AF recurrences. Among the patients with recurrences, two (50%) had incomplete ablation lesions and three (75%) had “suboptimal” VOM-EI. In 23/31 patients (74%), antiarrhythmic drugs (AADs) were discontinued after 1 month of follow-up. No significant complications were reported during the follow-up. Conclusions: this single-center experience demonstrates that VOM-EI systematically combined with an anatomical ablation set in patients with PeAF resulted in feasible, safe, and effective freedom from AF/AT recurrences in 87% of the population after a 1-year follow-up period according to an ILR

Tricuspid Regurgitation Velocity and Mean Pressure Gradient for the Prediction of Pulmonary Hypertension According to the New Hemodynamic Definition

Background: The hemodynamic definition of PH has recently been revised with unchanged threshold of peak tricuspid regurgitation velocity (TRV). The aim of this study was to evaluate the predictive accuracy of peak TRV for PH based on the new (>20 mmHg) and the old (>25 mmHg) cut-off value for mean pulmonary artery pressure (mPAP) and to compare it with the mean right ventricular–right atrial (RV–RA) pressure gradient. Methods: Patients with advanced heart failure were screened from 2016 to 2021. The exclusion criteria were absent right heart catheterization (RHC) results, chronic obstructive pulmonary disease, any septal defect, inadequate acoustic window or undetectable TR. The mean RV–RA gradient was calculated from the velocity–time integral of TR. Results: The study included 41 patients; 34 (82.9%) had mPAP > 20 mmHg and 24 (58.5%) had mPAP > 25 mmHg. The AUC for the prediction of PH with mPAP > 20 mmHg was 0.855 for peak TRV and mean RV–RA gradient was 0.811. AUC for the prediction of PH defined as mPAP > 25 mmHg for peak TRV was 0.860 and for mean RV–RA gradient was 0.830. A cutoff value of 2.4 m/s for peak TRV had 65% sensitivity and 100% positive predictive value for predicting PH according to the new definition. Conclusions: Peak TRV performed better than mean RV–RA pressure gradient in predicting PH irrespective of hemodynamic definitions. Peak TRV performed similarly with the two definitions of PH, but a lower cutoff value had higher sensitivity and equal positive predictive value for PH

A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience.

Background: Mitral isthmus (MI) conduction block is a fundamental step in anatomical approach treatment for persistent atrial fibrillation (PeAF). However, MI block is hardly achievable with endocardial ablation only. Retrograde ethanol infusion (EI) into the vein of Marshall (VOM) facilitates MI block. Fluorographic myocardial staining (MS) during VOM-EI could be helpful in predicting procedural alcoholization outcome even if its role is qualitatively assessed in the routine. The aim was to quantitatively assess MS during VOM-EI and to evaluate its association with MI block achievement. Methods: Consecutive patients undergoing catheter ablation for PeAF at Fondazione Toscana Gabriele Monasterio (Pisa, Italy) from February 2022 to May 2023 were considered. Patients with identifiable VOM were included. A proposed index of MS (MSI) was retrospectively calculated in each included patient. Correlation of MSI with low-voltage zones (LVZ) extension after VOM-EI and its association with MI block achievement were assessed. Results: In total, 42 patients out of 49 (85.8%) had an identifiable VOM. MI block was successfully achieved in 35 patients out of 42 (83.3%). MSI was significantly associated with the occurrence of MI block (OR 1.24 (1.03-1.48); p = 0.022). A higher MSI resulted in reduced ablation time (p = 0.014) and reduced radiofrequency applications (p = 0.002) to obtain MI block. MSI was also associated with MI block obtained by endocardial ablation only (OR 1.07 (1.02-1.13); p = 0.002). MSI was highly correlated with newly formed LVZ extension (r = 0.776; p = 0.001). Conclusions: In our study cohort, optimal MSI predicts MI block and facilitates its achievement with endocardial ablation only