L’uso di sostanze rappresenta un determinante rilevante ma ancora sottostimato di patologia cardiovascolare, attraverso meccanismi sostanza-specifici e spesso multifattoriali. Il presente lavoro propone il concetto di “malattie cardiovascolari associate all’uso di sostanze d’abuso” (Sr-CVD) come possibile nuova entità nosologica, delineandone le principali implicazioni cliniche. Vengono analizzate le evidenze epidemiologiche ed eziopatogenetiche disponibili e descritte le caratteristiche cliniche, strumentali e terapeutico-gestionali delle principali condizioni cardiovascolari associate all’uso di sostanze. Tali elementi supportano il sospetto diagnostico, la diagnosi differenziale e un approccio di medicina di precisione. Nei casi in cui non sia possibile definire un nesso causale certo, viene proposto il termine “malattie cardiovascolari negli individui che fanno uso di sostanze”, utile per identificare una popolazione a rischio cardiovascolare aumentato con peculiari necessità assistenziali. Le Sr-CVD rappresentano un gruppo eterogeneo di condizioni che richiedono un approccio clinico strutturato e multidisciplinare. L’introduzione di questo framework concettuale può migliorare il riconoscimento, la gestione e la prevenzione del danno cardiovascolare associato all’uso di sostanze.

Abstract Background Late gadolinium enhancement (LGE) quantification by cardiovascular magnetic resonance is central to risk stratification in hypertrophic cardiomyopathy (HCM). Conventional techniques require contour tracing and region-of-interest (ROI) placement, which may reduce reproducibility and increase analysis time. We developed a novel visual approach, the VIsual STAndardized Quantification of LGE (VISTAQ), that does not require myocardial contouring, arbitrary ROI positioning, or dedicated post-processing software. Methods In this multicenter study, LGE images from 400 patients (100 prior myocardial infarction, 250 HCM, 50 other non-ischemic heart diseases) were analyzed. Reproducibility was assessed using the intraclass correlation coefficients (ICC) and Bland–Altman analysis. VISTAQ was compared with conventional methods (mean+2SD, +5SD, +6SD, FWHM, visual thresholding). Prognostic performance was evaluated in 250 HCM patients over a median 5-year follow-up. Results VISTAQ demonstrated excellent intra- and inter-observer reproducibility (ICC up to 0.98 and 0.97, respectively), consistent across disease subtypes. VISTAQ showed similar ICC to FWHM but significantly lower net and absolute inter-observer differences (median absolute difference 1.3%). Mean+2SD markedly overestimated LGE, whereas mean+6SD slightly underestimated LGE compared with VISTAQ, mean+5SD, FWHM, and visual thresholding. Analysis time was shorter with VISTAQ (median 105 vs. 375 seconds, p < 0.0001). During follow-up, 21 hard cardiac events occurred in HCM population. An LGE threshold >10% predicted events with higher accuracy using VISTAQ (AUC 0.90; sensitivity 85%; specificity 94%) compared with mean+6SD (AUC 0.75; sensitivity 57%; specificity 93%). Conclusions VISTAQ provides highly reproducible, time-efficient LGE quantification without dedicated software and demonstrates non-inferior prognostic discrimination in HCM compared with conventional threshold-based techniques.

Left ventricular pseudoaneurysm (LVP) is a rare but severe mechanical complication of myocardial infarction (MI), associated with high risk of rupture and mortality. Accurate diagnosis relies on multimodality imaging, and timely surgical repair remains the mainstay of treatment. We report the case of a 78-year-old man, a former heavy smoker, who presented with progressive exertional dyspnea and bilateral lower limb edema. The electrocardiogram showed sequelae of a prior anterior MI with suspected aneurysmal evolution. Transthoracic echocardiography revealed a dilated left ventricle with severely impaired systolic function (left ventricular ejection fraction [LVEF] -20%) and a dyskinetic, aneurysmal apex. Coronary angiography showed two-vessel disease, while cardiac magnetic resonance confirmed a nonacute transmural infarction of the anterior and septal walls complicated by a large pseudoaneurysm with mural and extramural thrombus. Because of the high risk of progression and embolic complications, the patient underwent elective surgical repair with an endoventricular circular patch plasty (Dor procedure). The postoperative recovery was uneventful. At 2-weeks, echocardiography showed a favorable left ventricular (LV) remodeling, with an important reduction in end-diastolic volume (from 230 to 150 mL), and a marked improvement in systolic function (LVEF from 20% to 39%). This case highlights the critical role of imaging in diagnosing and characterizing LVP, as well as the therapeutic efficacy of surgical ventricular reconstruction. Early surgical intervention can prevent catastrophic rupture and restore LV geometry, improving global systolic performance. Multidisciplinary evaluation is essential to guide management, and less invasive percutaneous approaches may represent future alternatives in high-risk surgical candidates.

BACKGROUND:Spontaneous coronary artery dissection (SCAD) is a major cause of myocardial infarction in young women without traditional cardiovascular risk factors (Hayes et al., 2018; Adlam et al., 2018 [1, 2]). Despite growing awareness, its biological underpinnings remain incompletely understood, and clinical management is largely based on observational evidence rather than mechanistic insight (Saw et al., 2014; Lettieri et al., 2015; Steg et al., 2024 [3-5]). OBJECTIVES:To systematically integrate genomic, epitranscriptomic, proteomic, and metabolomic data in order to characterize the multi-omic architecture of SCAD and identify potential biomarkers and therapeutic targets. METHODS:A systematic review was conducted in accordance with the PRISMA 2020 statement (Arbelo et al., 2023 [6]). PubMed/MEDLINE was searched for original studies investigating genomic and multi-omic features of SCAD. Data were extracted on study design, patient characteristics, identified variants, circulating biomarkers, and implicated biological pathways. Functional enrichment analysis was performed using the DAVID bioinformatics resource (Page et al., 2021 [7]). RESULTS:A total of 16 studies were included. Genome-wide association studies consistently identified susceptibility loci related to arterial structure and extracellular matrix integrity, including ADAMTSL4, PHACTR1/EDN1, LRP1, and FBN1 (Huang et al., 2009; Saw et al., 2020; Turley et al., 2020 [8-10]). Rare variant analyses further supported the role of genes involved in extracellular matrix remodeling and vascular smooth muscle cell function, including COL3A1, COL4A1/2, SMAD3, and TLN1 (Adlam et al., 2023; Turley et al., 2021, 2019; Carss et al., 2020; Zekavat et al., 2022; Wang et al., 2022 [11-16]), while ancestry-specific signals such as TSR1 variants were observed in distinct populations (Turley et al., 2023 [17]). Proteogenomic approaches linked genetic susceptibility loci to circulating proteins involved in matrix remodeling and inflammation, including cathepsin B and ECM1 (Maioli et al., 2010 [18]). Epitranscriptomic analyses identified differential microRNA expression profiles associated with vascular injury and repair pathways (Sun et al., 2019 [19]). CONCLUSIONS:SCAD is characterized by a complex, multi-layered biological architecture involving genetic susceptibility, extracellular matrix dysregulation, and vascular signaling pathways. Integration of multi-omic data provides novel insights into disease mechanisms and highlights potential biomarkers and targets for precision medicine approaches in SCAD.

Cardiac involvement in rheumatoid arthritis (RA) is uncommon and often clinically silent, but may encompass valvular, structural, and conduction system abnormalities. Involvement of the mitral-aortic intervalvular fibrosa (MAIVF) and the membranous interventricular septum is exceptionally rare and has not been previously described in RA. A 61-year-old man with longstanding seropositive RA presented with syncope due to intermittent complete atrioventricular block. Multimodality imaging revealed severe degenerative mitral regurgitation, moderate-to-severe aortic regurgitation, a pseudoaneurysm of the MAIVF extending into the left ventricular outflow tract, and a membranous interventricular septal aneurysm. Infective and congenital etiologies were excluded by repeated negative blood cultures, 18F-FDG PET, and comprehensive imaging. The patient underwent successful surgical mitral and aortic valve replacement. Histopathological analysis demonstrated rheumatoid nodules within both excised valves, confirming immune-mediated valvular involvement. Persistent conduction abnormalities required permanent pacemaker implantation. This report describes the first documented case of a MAIVF pseudoaneurysm in a patient with RA, associated with multivalvular disease and high-grade conduction disturbance. The findings highlight the potential for severe, atypical cardiac manifestations of RA in the absence of active systemic inflammation and underscore the pivotal role of multimodality imaging and multidisciplinary evaluation in establishing diagnosis and guiding management.

AIMS:Hypertrophic cardiomyopathy (HCM) shows variable left ventricular hypertrophy, yet current diagnostic criteria rely on absolute wall thickness (WT) cut-offs that may miss early or subtle phenotypes, particularly in sarcomere mutation carriers. OBJECTIVES:To determine whether wall thickness standard deviation (WTSD), reflecting WT heterogeneity, improves identification of HCM and mutation carriers. METHODS AND RESULTS:Cardiac magnetic resonance was performed in 382 healthy controls, 297 patients with HCM, 82 sarcomere mutation carriers without overt hypertrophy, and 180 patients with other cardiac conditions (75 with and 105 without LV hypertrophy). End-diastolic WT was measured in 16 myocardial segments, and WTSD was computed. Diagnostic performance was compared with other WT-derived parameters using age- and sex-specific thresholds. WTSD was higher in HCM (4.3 ± 1.1 mm) and mutation carriers (2.3 ± 0.3 mm) than in controls (1.3 ± 0.3 mm; P < 0.0001). WTSD identified 97% of HCM and 64% of carriers with 99% specificity. In females, WTSD achieved 98.9% sensitivity and 100% specificity for HCM and detected 74% of carriers. WTSD outperformed demographic-based thresholds and BSA-indexed maximal WT in all subgroups. Mutation carriers showed heterogeneous remodelling with both hypertrophic and thinned segments despite normal absolute WT. WTSD was significantly higher in HCM than in all cardiac conditions with LV hypertrophy and in mutation carriers vs. non-hypertrophic conditions, except post-ischaemic severe LV dysfunction. CONCLUSION:WTSD is a robust imaging biomarker that detects both overt and early sarcomeric HCM with high accuracy. Incorporating WT heterogeneity into diagnostic algorithms may enhance early identification, especially in women and mutation carriers.

INTRODUCTION:The left atrioventricular coupling index (LACI) has emerged as a potential prognostic marker in several clinical settings. This study evaluated the prognostic value of cardiac magnetic resonance (CMR)-derived LACI in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). METHODS:Patients from the multicentre DERIVATE registry with LVEF <50% who underwent CMR were included. LACI was calculated as the ratio between left atrial and left ventricular end-diastolic volumes. Univariable and multivariable Cox regression models estimated hazard ratios (HR) with 95% confidence intervals (CI) for predicting all-cause mortality (ACM), ACM or HF, and HF alone (competing-risk analysis). Time-dependent receiver operating characteristic analysis identified optimal cut-offs for 3-year outcomes. RESULTS:A total of 2170 patients were included (mean age 59.8 ± 13.9 years; 24.7% women; mean LVEF 31.6 ± 11.3%). Median follow-up was 1016 days (580-1609). Median LACI was 19.4% (13.3-28.8). During follow-up, ACM occurred in 191 patients (8.8%), ACM or HF in 565 (26.0%), and HF in 442 (20.4%). After adjustment for clinical and CMR parameters, including LVEF and late gadolinium enhancement (LGE), each 5% increase in LACI was associated with higher risk of ACM (HR 1.06, 95% CI 1.01-1.11; P = .016), ACM or HF (HR 1.09, 95% CI 1.06-1.12; P < .001), and HF (HR 1.09, 95% CI 1.05-1.12; P < .001). The optimal cut-off for ACM was LACI ≥21% (AUC 0.617, 95% CI 0.561-0.673), identifying patients at higher risk of ACM, ACM or HF, and HF (log-rank P < .001 for all). CONCLUSION:CMR-derived LACI independently predicts ACM and HF in patients with reduced LVEF and provides incremental prognostic value beyond LVEF and LGE. A cut-off of ≥21% identifies higher-risk patients and may support clinical risk stratification.

To evaluate the prognostic value of cardiovascular magnetic resonance imaging (MRI)–derived left ventricular filling pressure (MRI-wedge) and pulmonary blood volume index (PBVi), and to assess their association with non-invasive markers of myocardial fibrosis. MRI-wedge pressure was computed from left-atrial volume and left-ventricular mass, and PBVi was measured from first-pass transit analysis. Patients were assigned to one of four MRI haemodynamic stages based on normal or elevated MRI-wedge and PBVi: stage 1 (normal profile), stage 2 (isolated volume overload), stage 3 (isolated pressure overload), and stage 4 (combined overload). Non-invasive myocardial tissue indices and clinical outcomes were compared across stages. The primary endpoint was a composite of cardiovascular death and cardiac hospitalisation. Among 262 participants (mean age 52 ± 17 years; 34

Cocaine abuse is associated with a broad spectrum of cardiovascular complications, including myocardial ischemia, arrhythmias, and cardiomyopathy. However, chronic myocardial injury may remain subclinical, delaying diagnosis until an acute event occurs. We present the case of a 49-year-old man with a history of chronic cocaine use who was admitted following an out-of-hospital cardiac arrest. A post-Return of Spontaneous Circulation Point-of-Care Ultrasound revealed mildly reduced left ventricular systolic function, while coronary angiography excluded obstructive coronary artery disease. Cardiac magnetic resonance (CMR) imaging demonstrated mid-wall late gadolinium enhancement and patchy T1 elevation, consistent with nonischemic myocardial fibrosis and edema. A subcutaneous implantable cardioverter-defibrillator was placed for secondary prevention, and beta-blocker therapy was initiated. Genetic testing for inherited arrhythmogenic and cardiomyopathic conditions was also undertaken. This case underscores the potential for clinically silent cocaine-induced cardiomyopathy and highlights the value of CMR in detecting subclinical myocardial injury.

Cardiac involvement in rheumatoid arthritis (RA) is an uncommon but clinically relevant manifestation that may extend beyond pericardial and valvular disease to involve peri-annular and subvalvular fibrous structures. Aneurysmal and pseudoaneurysmal complications affecting the left ventricular outflow tract (LVOT), aortic root, and adjacent regions are exceptionally rare and largely described in isolated case reports. We performed a systematic review of the reported cases to characterize the clinical, imaging, pathological, and therapeutic features of RA-associated aneurysmal or pseudoaneurysmal cardiac involvement. The review identified a small number of reported cases in which RA-related inflammation involved peri-annular structures, often mimicking infective endocarditis and frequently associated with significant valvular dysfunction. Across cases, multilevel structural involvement, including the aortic root, LVOT, membranous interventricular septum, and cardiac valves, was common. High-grade atrioventricular conduction disturbances were observed in a substantial proportion of patients, reflecting the close anatomical relationship between inflammatory lesions and the cardiac conduction system. Multimodality imaging, combining transthoracic and transesophageal echocardiography with cardiac computed tomography, cardiac magnetic resonance, or FDG-PET/CT, was consistently required to define anatomical extent and guide management. Histopathological examination, when available, proved essential to exclude infection and demonstrated granulomatous inflammation or rheumatoid nodules in autoimmune-mediated cases. Most patients required surgical intervention due to advanced structural disease, while isolated inflammatory involvement without aneurysmal degeneration responded to immunosuppressive therapy. Outcomes were generally favorable. This review underscores that RA-related cardiac inflammation may predispose to aneurysmal degeneration of peri-annular fibrous structures, with complex presentations in which a complete diagnostic pathway, including multimodality imaging and pathological confirmation is critical.

BACKGROUND:Photon-counting computed tomography (PCCT) combines high spatial resolution with spectral imaging and can provide morphologic, functional, and tissue assessment in hypertrophic hearts. OBJECTIVES:The authors investigated whether PCCT characterizes left ventricular hypertrophy (LVH) as accurately as cardiac magnetic resonance (CMR) overall and across hypertrophic phenotypes. METHODS:Consecutive patients with LVH (n = 182; 72 with hypertrophic cardiomyopathy, 47 with amyloid transthyretin cardiomyopathy, and 63 with secondary LVH) underwent PCCT including late iodine enhancement (LIE) and PCCT-derived extracellular volume (ECV). Eighty-three patients (46%) also underwent CMR within ±12 months (median interval: -12 days). Agreement was assessed for morphofunctional indices, ECV, and LIE vs late gadolinium enhancement (LGE). RESULTS:PCCT differentiated etiologies through distinctive tissue patterns. Transthyretin cardiac amyloidosis showed the highest left ventricular mass index (median: 104 g/m2), the greatest LIE extent (median: 17/17 segments), and the highest ECV (median: 47%). Hypertrophic cardiomyopathy showed patchy fibrosis (median 4 enhanced segments) with intermediate ECV (31%), whereas secondary LVH displayed minimal enhancement (median: 0 segments) and the lowest ECV (28%). In paired examinations, PCCT correlated closely with CMR for left ventricular mass index and left ventricular ejection fraction (r = 0.963 and r = 0.947; P < 0.001 for both) and for ECV (r = 0.868; P < 0.001). LIE extent strongly agreed with LGE extent (r = 0.998; P < 0.001); segment-wise LIE/LGE agreement was 99% to 100%, and PCCT detected CMR-LGE with excellent accuracy (AUC: 0.994; sensitivity 99%; specificity 100%). Global PCCT-derived ECV showed excellent inter-reader agreement (ICC: 0.98). CONCLUSIONS:PCCT provides CMR-comparable assessment of ventricular geometry, function, and myocardial fibrosis/ECV while enabling coronary angiography, supporting its use when CMR is contraindicated, impractical, or nondiagnostic.

AIMS:Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy of sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). The aim of current analysis is to evaluate the prognostic impact of late gadolinium enhancement-papillary muscles (LGE-PMs) at cardiovascular magnetic resonance (CMR) and specifically its capability to re-stratify the arrhythmic risk on top to the DERIVATE-ICM Risk Score previously published. METHODS:Eighty-hundred-thirty-nine patients (mean age 65 ± 11 years; males:721[86%]) with ICM and TTE-LVEF <50% were enrolled from the DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy- Ischemic Cardiomyopathy). Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS:During a median follow-up of 1054 days, MAACE occurred in 86 (9.7%). DERIVATE-ICM Risk Score quartiles Q2-Q3 (HR:2.124 [95% CI:1.084-4.162]; p = 0.028), Q4 (HR: 3.865 [95% CI: 1.875-7.970]; p < 0.001) and the involvement of isolated posteromedial (P)PM (HR:1.985 [95% CI:1.073-3.673]; p = 0.029) were independent predictors of MAACE. The Kaplan-Meier survival curves showed a higher event-free rate in absence of LGE-PPM in patients categorized in the DERIVATE-ICM Risk Score quartiles Q2-Q3 (p = 0.018). Finally, adding LGE-PPM involvement on top of the model included TTE LVEF<35% plus DERIVATE-ICM Risk Score quartiles Q2-Q3 provided a significant improvement of prognostic stratification (p = 0.044). CONCLUSION:This study suggests that, in a wide population of ICM patients, LGE-PPM is independently associated with the occurrence of MAACE. In the intermediate quartiles of the DERIVATE-ICM Risk Score, the absence of LGE-PPM, when added to the Score, may contribute to downward re-stratification of arrhythmic risk. CLINICAL TRIAL REGISTRATION:RCT#NCT03352648.

Hypertrophic cardiomyopathy (HCM) is a major health concern, with cardiac magnetic resonance (CMR) playing a crucial role in risk assessment. We investigated for the first time the utility of sequential CMR, particularly strain analysis, for tracking HCM progression. We retrospectively evaluated HCM patients undergoing two CMR scans over a 10-year period. We measured changes in left ventricular (LV) strain parameters and examined their yearly changes as predictors of a composite of sudden cardiac death, life-threatening ventricular arrhythmias, stroke, new-onset atrial fibrillation, and heart failure hospitalizations. Patients (n = 114) were predominantly male (73%), with a median age of 51 years (interquartile range 36-60), obstructive HCM in 14%, and a median HCM risk score of 2% (1-3%). Only one patient (0.9%) had LGE >= 15% on the first scan, while 8 (7.0%) had LGE >= 15% after a median of 5.1 years (3.5-6.5). Absolute changes in LV strain displayed significant relationships with changes in LGE mass (longitudinal strain: beta = 0.227, p = 0.016; circumferential strain: beta = 0.421, p < 0.001; radial long-axis: beta=-0.261, p = 0.006). During a 4.3-year median follow-up after the second CMR scan (interquartile range 2.2-6.9), 40 patients experienced an event; hard arrhythmic events were infrequent. Among patients with LGE < 15% at baseline, yearly absolute changes in radial short-axis strain predicted outcomes beyond baseline HCM score and LGE extent (hazard ratio 1.12, 95% confidence interval 1.03-1.22, p = 0.011). In patients with predominantly early-stage HCM, worsening short-axis radial strain was associated with composite adverse events after the second CMR, independent of baseline LGE and ESC SCD risk.

Substance use represents a relevant yet underrecognized determinant of cardiovascular diseases, acting through substance-specific and often multifactorial mechanisms. This document proposes the concept substance-related cardiovascular diseases (Sr-CVD) as a possible novel nosological entity, outlining its clinical implications. Available epidemiological and pathophysiological evidence is reviewed, and the cal, instrumental, and therapeutic-management features of the main cardiovascular conditions associated with substance use are described. These elements support clinical suspicion, differential diagnosis, and precision medicine approach. In cases where a definite causal relationship cannot be established, the "cardiovascular diseases in individuals with substance use" is proposed to identify a population at increased cardiovascular risk with specific clinical needs. Sr-CVD represent a heterogeneous group of conditions requiring a structured and multidisciplinary clinical approach. The introduction of this conceptual framework improve the recognition, management, and prevention of substance-related cardiovascular damage.

Cardiovascular magnetic resonance (CMR) has emerged as the reference noninvasive modality for a comprehensive assessment of myocardial injury following acute myocardial infarction (AMI). Beyond accurate quantification of ventricular volumes and ejection fraction, CMR uniquely enables in vivo characterization of the infarct size, the ischemic area at risk, microvascular obstruction, intramyocardial hemorrhage, and interstitial remodeling-pathophysiological processes that are all tightly linked to adverse left ventricular remodeling and long-term clinical outcomes. Advances in late gadolinium enhancement imaging and parametric mapping techniques, including native T1, T2, T2*, and extracellular volume quantification, have now expanded the ability of CMR to capture both irreversible myocardial necrosis and dynamic inflammatory injury within the infarcted and the remote myocardium. Importantly, these imaging biomarkers provide prognostic information incremental to conventional clinical parameters and have become central to risk stratification, etiologic diagnosis in myocardial infarction with non-obstructive coronary arteries (MINOCA), and surrogate endpoint selection in cardioprotective clinical trials. This review provides a contemporary overview of the role of CMR in AMI, with emphasis on optimal timing, pragmatic protocol design, infarct severity phenotyping, post-infarction complications, and risk stratification beyond ejection fraction. Emerging developments, including accelerated imaging, artificial intelligence-assisted analysis, low-field systems, and complementary integration with cardiac computed tomography, are discussed as key drivers shaping the future clinical implementation of CMR in ischemic heart disease.

Substance use represents a relevant yet underrecognized determinant of cardiovascular diseases, acting through substance-specific and often multifactorial mechanisms. This document proposes the concept of substance-related cardiovascular diseases (Sr-CVD) as a possible novel nosological entity, outlining its main clinical implications. Available epidemiological and pathophysiological evidence is reviewed, and the clinical, instrumental, and therapeutic-management features of the main cardiovascular conditions associated with substance use are described. These elements support clinical suspicion, differential diagnosis, and a precision medicine approach. In cases where a definite causal relationship cannot be established, the term "cardiovascular diseases in individuals with substance use" is proposed to identify a population at increased cardiovascular risk with specific clinical needs. Sr-CVD represent a heterogeneous group of conditions requiring a structured and multidisciplinary clinical approach. The introduction of this conceptual framework may improve the recognition, management, and prevention of substance-related cardiovascular damage.

BACKGROUND:The Left Atrioventricular Coupling Index (LACI), calculated as the ratio of left atrial (LA) to left ventricular (LV) end-diastolic volume (EDV) has emerged as a novel imaging biomarker of LA-LV coupling. However, reference thresholds are undefined and its predictive value beyond established clinical and imaging markers remains uncertain, limiting broader clinical implementation. METHODS:Two large datasets were leveraged to 1) investigate demographic variations of LACI in health, 2) establish population-specific reference thresholds, 3) characterise the relationship between LACI and cardiac structure/function, and 4) investigate its incremental predictive value for cardiovascular outcomes. Cardiovascular magnetic resonance (CMR) scans were performed and analysed using standardised protocols. In the Healthy Hearts Consortium (HHC), a large image bank of verified healthy individuals, demographic variations of LACI were examined, and population-specific reference thresholds were calculated using the 95% prediction interval method. Associations between LACI and markers of LA/LV structure and function were assessed using linear regression models. In UK Biobank, associations of LACI with incident outcomes [atrial fibrillation (AF), heart failure (HF), myocardial infarction, cardiovascular death, all-cause death] were examined over a median 5.5 years prospective follow-up, using Cox regression models adjusted for demographic, clinical, and established CMR variables. RESULTS:In the HHC (n=7,111, 54% female, median 61.5 years), a higher LACI was observed in older age, ethnicities other than White, and women (who also had a greater age-related increase in LACI). After adjustment for demographic factors, higher LACI was associated with poorer LA function and higher LV filling pressures. In UK Biobank (n=25,849, 52% female, median 63.0 years), higher LACI was independently predictive of incident AF [HR per 1 standard deviation increase 1.31 (1.19, 1.44)] and HF [HR 1.15 (1.07, 1.24)], in Cox models adjusted for demographic, clinical, and established CMR variables. Applying the newly derived reference thresholds in a population-specific manner to the UKB cohort revealed a significantly higher probability of AF and HF amongst those with a raised LACI. CONCLUSION:LACI is a robust predictor of AF and HF with incremental value over established clinical and imaging markers. The provided population-specific reference thresholds permit its broader clinical application.

Cardiac magnetic resonance imaging (CMRI) has become an indispensable tool in evaluating arrhythmic risk and guiding therapeutic decisions in patients with non-ischemic cardiomyopathies (NICMs), including dilated (DCM), hypertrophic (HCM), and arrhythmogenic cardiomyopathies (ACM). Both European and American guidelines have given an additive and different value of late gadolinium enhancement (LGE) in specific morpho-functional (hypertrophic, dilated, and arrhythmogenic) phenotypes. In particular, LGE plays a different weight in relation to different cardiomyopathies. In dilated cardiomyopathy, LGE is able to predict arrhythmic risk in relationship to the presence and localization (septal and/or ring like LGE). On the contrary, in HCM, LGE is related to increased risk of cardiac death according to the extent (LGE >15%), while in ACM, it has a greater role in the presence of fat infiltration associated with LGE. In this review, we aim to identify predictors of sudden cardiac death related to myocardial structural features seen in CMRI in cardiomyopathies, going beyond the sole assessment of left ventricular function and ejection fraction.

The right vagus nerve is essential for cardiac homeostasis, and its intrathoracic resection can lead to postoperative cardiac complications. Strategies to restore vagal innervation after transection at the cardiac level remain lacking. Here, we show that early reconnection of the right vagus nerve using an implantable chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit preserved cardiac mechanical function in adult male minipigs subjected to right cardiac vagotomy. Treated animals displayed improved global circumferential, longitudinal, and radial strains and reduced diastolic dyssynchrony. Histological analysis revealed partial repair with about 20% viable vagal fascicles, restoration of myocardial parasympathetic fibers, normalization of oxidative stress and aging markers, and prevention of interstitial fibrosis. These findings suggest that maintaining even limited vagal input prevents early cardiac remodeling by mitigating oxidative stress-induced premature senescence of cardiac cells. Reconnection of the right vagus nerve with chitosan/poly-ε-caprolactone cuff-like nerve guidance conduit may represent a therapeutic approach to preventing right vagotomy-induced heart failure after thoracic surgery or cardiothoracic transplantation.