Arrhythmic Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity treat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator (ICD) represent the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centered risk stratification approach. A novel risk calculator algorithm estimating the 5 year risk of arrhythmias of patients with ARVC have been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient

Arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity threat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator represents the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centred risk stratification approach. A novel risk calculator algorithm estimating the 5-year risk of arrhythmias of patients with ARVC has been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient

Arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity threat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator represents the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centred risk stratification approach. A novel risk calculator algorithm estimating the 5-year risk of arrhythmias of patients with ARVC has been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient

Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV - Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial

BACKGROUND Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). METHODS SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years. The primary outcome is the proportion with confirmed HIV-RNA ≥50 copies/mL by week 48, estimated by Kaplan-Meier method. Non-inferiority margin was 10%. Registration number for SMILE are: ISRCTN11193709, NCT #: NCT02383108. FINDINGS Between 10th June 2016 and 30th August 2019, 318 participants were enrolled from Africa 53%, Europe 24%, Thailand 15% and Latin America 8%, 158 INSTI + DRV/r [153 Dolutegravir (DTG); 5 Elvitegravir (EVG)], 160 SOC. Median (range) age was 14.7 years (7.6-18.0); CD4 count 782 cells/mm$^{3}$ (227-1647); 61% female. Median follow-up was 64.3 weeks with no loss to follow-up. By 48 weeks, 8 INSTI + DRV/r vs. 12 SOC had confirmed HIV-RNA ≥50 copies/mL; difference (INSTI + DRV/r-SOC) -2.5% (95% CI: -7.6, 2.5%), showing non-inferiority. No major PI or INSTI resistance mutations were observed. There were no differences in safety between arms. By week 48, difference (INSTI + DRV/r-SOC) in mean CD4 count change from baseline was -48.3 cells/mm$^{3}$ (95% CI: -93.4, -3.2; p = 0.036). Difference (INSTI + DRV/r-SOC) in mean HDL change from baseline was -4.1 mg/dL (95% CI: -6.7, -1.4; p = 0.003). Weight and Body Mass Index (BMI) increased more in INSTI + DRV/r than SOC [difference: 1.97 kg (95% CI: 1.1, 2.9; p < 0.001), 0.66 kg/m$^{2}$ (95% CI: 0.3, 1.0; p < 0.001)]. INTERPRETATION In virologically-suppressed children, switching to INSTI + DRV/r was non-inferior virologically, with similar safety profile, to continuing SOC. Small but significant differences in CD4, HDL-cholesterol, weight and BMI were observed between INSTI + DRV/r vs. SOC although clinical relevance needs further investigation. SMILE data corroborate adult findings and provide evidence for this NRTI-sparing regimen for children and adolescents. FUNDING Fondazione Penta Onlus, Gilead, Janssen, INSERM/ANRS and UK MRC. ViiV-Healthcare provided Dolutegravir

Conversion to secondary progressive multiple sclerosis: patient awareness and needs. results from an online survey in Italy and Germany

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified.Methods: Participants were consenting adults with SPMS since &lt;= 5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs.Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany (p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy (p &lt; 0.001).Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients).All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany.Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.Methods and results In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.Conclusion Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

Background and aims: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. Methods: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. Results: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. Conclusions: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs

Different Phases of Disease in a Highly Characterized Cohort of Lymphocytic Myocarditis: Clinical and Electrophysiological Characteristics

Introduzione: la biopsia endomiocardica (BEM) è un esame diagnostico necessario per confermare il sospetto clinico di miocardite linfocitaria (ML) e per identificarne l’eziologia. La BEM fornisce quelle informazioni istologiche ed immunoistochimiche fondamentali per distinguere le varie fasi di malattia. Obiettivi: lo scopo dello studio consiste nella caratterizzazione e comparazione degli aspetti clinici ed elettrofisiologici associati alle varie fasi anatomopatologiche di malattia nei pazienti con diagnosi di ML confermata dalla BEM. Metodi: è stato condotto uno studio prospettico e multicentrico, in cui sono stati inclusi tutti i pazienti con una diagnosi di ML valutati presso tre centri italiani di riferimento per la cura delle aritmie. Sulla scorta delle risultanze anatomopatologiche ed in accordo a quanto presente nella Letteratura, è stata applicata una classificazione che individua le seguenti tre fasi di malattia: ML acuta (MLA), ML cronica attiva (MLCA) e miocardite guarita (MG). I tre gruppi così ottenuti sono stati confrontati in termini di presentazione clinica e risultanze degli accertamenti diagnostici non invasivi ed invasivi. Risultati: nei 122 pazienti inclusi nello studio (MLA, n=44; MLCA, n=42; MG, n= 36), le aritmie ventricolari complesse sono state riscontrate frequentemente in ciascuna fase di malattia (n=109, 89%), ma la fibrillazione ventricolare è risultata essere più comune nella MLA (p=0.028). Alla risonanza magnetica cardiaca, il Late Gadolinium Enhancement (LGE) è stato osservato con maggiore frequenza nei pazienti con MG e MLCA rispetto ai pazienti con MLA (94.4% vs. 92.9% vs. 50%, p&lt;0.002), mentre l’edema miocardico è stato riscontrato più spesso nella MLA che nella MLCA, risultando completamente assente nella MG (90.9% vs. 50% vs. 0%; p&lt;0.001). Pertanto, l’edema miocardico è risultato essere il migliore predittore clinico indipendente dell’infiammazione miocardica confermata dalla BEM. Al mappaggio elettroanatomico, sono state riscontrate meno frequentemente aree di basso voltaggio nella MLA rispetto alla MLCA o alla MG. Inoltre, è stata osservata una associazione regionale significativa tra l’edema in uno specifico segmento miocardico e la presenza di elettrogrammi di normale ampiezza nella medesima sede (OR=0.24 [0.10-0-54]; p&lt;0.01), oltre che tra LGE ed aree di basso voltaggio (OR=2.86 [1.19-6.97]; p=0.019). L’estensione delle aree di basso voltaggio è risultata essere associata all’inducibilità di aritmie ventricolari sostenute mediante stimolazione ventricolare programmata (p=0.03), specialmente nei pazienti con MG. Conclusioni: la ML è una patologia altamente eterogenea e le sue diverse fasi presentano caratteristiche cliniche, morfologiche ed elettrofisiologiche specifiche. Saranno necessari ulteriori studi per identificare potenziali marcatori elettroanatomici dell’infiammazione miocardica.Background: endomyocardial biopsy (EMB) is required to make a definite diagnosis of lymphocytic myocarditis (LM), to identify its etiology, and to classify LM into different phases. Objective: to characterize and compare clinical and electrophysiological characteristics of different biopsy-proven LM phases, namely acute myocarditis (AM), chronic active myocarditis (CAM), and healed myocarditis (HM). Methods: all patients with a diagnosis of LM at three Italian referral centers were prospectively enrolled. According to EMB findings, LM was classified as AM, CAM, or HM; per-group comparisons of clinical presentations, non-invasive, and invasive findings are reported. Results: among the 122 enrolled patients (AM: n=44; CAM: n=42; HM: n=36), complex ventricular arrhythmias were very common overall (n=109, 89%), but ventricular fibrillation was slightly more prevalent in AM (p=0.028). Cardiac magnetic resonance imaging showed late gadolinium enhancement (LGE) in more patients with HM and CAM than AM (94.4% vs. 92.9% vs. 50%; p&lt;0.001), while edema was more common in AM than in CAM, being absent in HM (90.9% vs. 50% vs. 0%; p&lt;0.001). Accordingly, edema was the strongest independent clinical predictor of EMB-proven active inflammation. Electroanatomical mapping revealed a lower prevalence of low-voltage areas (LVAs) in AM than in CAM or HM. We observed a strong association between edema at a specific myocardial segment and normal voltages at that site (OR=0.24 [0.10 – 0.54]; p&lt;0.01), as well as between LGE and LVAs (OR=2.86 [1.19 – 6.97]; p=0.019). The extension of LVAs was linked to inducibility by programmed electrical stimulation (p=0.03), with maximal association in HM. Conclusions: LM is a highly heterogeneous disease, and its different phases are characterized by diverse clinical, morphological, and electrophysiological features. Further research is required to identify electroanatomical markers of inflammation