Patients with cancer undergoing chemotherapy with an anthracycline-based regimen are at increased risk of cardiotoxicity, predisposing to heart failure, arrhythmias and death. Whether carvedilol may confer benefit to prevent anthracycline-induced cardiotoxicity remains to be determined.

CARDIOTOX is a double-blind, placebo controlled randomized clinical trial that plan to enroll 1,018 patients across 25 study sites in Brazil. Patients with active cancer scheduled to undergo an anthracycline-based chemotherapy regimen are eligible. Patients with prior HF or cardiomyopathy are excluded. Patients are randomized in 1:1 ratio to carvedilol (starting dose 6.25mg BID up titrated to 25mg BID or maximum tolerated dose) or placebo, stratified by site and use of renin-angiotensin blockers at baseline. Study drug is administered through the duration of chemotherapy and up to 30 days after the last dose of anthracycline. Patients are scheduled to undergo echocardiographic evaluations at baseline and at 3, 6, and 12 months. The study primary endpoint is the composite of new left ventricle ejection fraction (LVEF) reduction by at least 10% leading to an LVEF <50%, cardiovascular death, myocardial infarction, urgent care visit or hospitalization for heart failure, or clinically significant arrhythmias at 12 months. Echocardiographic images will be analyzed by a central core lab, clinical outcomes will be adjudicated, and safety endpoints include serious adverse events and adverse events of special interest (symptomatic bradycardia, hypotension, syncope and bronchospasm).

The CARDIOTOX trial is the largest trial to date analyzing the potential role of beta-blockers as prophylactic therapy to prevent cardiotoxicity induced by anthracyclines.

Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox).

gov ID NCT04939883. https://clinicaltrials.gov/study/NCT04939883.

Myocardial fibrosis of the left ventricle (LV) has been associated with atrial fibrillation and other arrhythmias in individuals with hypertrophic cardiomyopathy (HCM). However, few studies have quantitatively examined the segmental relationship between diffuse LV fibrosis and atrial arrhythmias in HCM using T1 mapping and extracellular volume fraction (ECV). The aim of this study is to explore this relationship through T1 mapping, offering imaging insights into the pathophysiology of HCM with atrial arrhythmia.

A total of 38 patients with HCM were classified into two groups-those with atrial arrhythmia and those without-based on electrocardiographic and Holter monitor recordings. A covariance analysis was conducted to compare T1 mapping parameters between the two groups, adjusting for wall thickness (WT) as a covariate. Analysis was performed collectively for all 16 myocardial segments, as well as for each segment individually.

Native T1 values were elevated in the entire LV myocardium and in segments S1-3 in patients with HCM with atrial arrhythmias compared to those without (P < 0.001; P < 0.05, 1316.0 ms ± 15.9 vs 1263.1 ms ± 13.6, 1350.5 ms ± 14.2 vs 1311.9 ms ± 11.7, 1305.7 ms ± 2.5 vs 1271.5 ms ± 10.6, respectively). Notably, the basal anterior segment (S1) and basal inferotseptal segment (S3) exhibited prolonged ECV and elevated native T1 values in patients with HCM and atrial arrhythmia (P < 0.05). Multivariable binary logistic regression analysis identified myocardial native T1 values in the basal anteroseptal segment (S2) as a predictor of atrial arrhythmia presence in HCM, with values exceeding 1350 ms correlating with an increased likelihood of arrhythmia development. No significant difference in WT was observed between the groups in hypertrophic myocardial regions (P > 0.05), while non-hypertrophic myocardium in individuals with HCM and atrial arrhythmias exhibited reduced wall thickness (7.7 mm ± 3.0 vs 9 mm ± 3.0, P < 0.001) compared to those without arrhythmias.

Fibrosis in the basal septal and anterior regions of the left ventricle plays a crucial role in myocardial tissue remodeling, contributing to the development of atrial arrhythmia in HCM. Elevated native T1 values in the basal anteroseptal segment may may serve as a significant marker for the concurrent occurrence of atrial arrhythmias in individuals with HCM.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition with potentially serious manifestations. Management has traditionally comprised therapies to palliate symptoms and implantable cardioverter-defibrillators to prevent sudden cardiac death. The need for disease-modifying therapies has been recognized for decades. More recently, an increasing number of novel and repurposed therapies hypothesized to target HCM disease pathways have been evaluated, culminating in the recent regulatory approval of mavacamten, a novel oral myosin inhibitor. HCM poses several unique challenges for clinical trials, which are important to recognize when designing trials and interpreting findings. This manuscript discusses the key considerations in the context of recent and ongoing randomized trials, including the roles of genotype, phenotype and symptom status in patient selection, the evidence base for clinical and mechanistic outcome measurements, trial duration and sample size.

Improving clinical prediction of sudden cardiac death is a crucial step in the management of patients with hypertrophic cardiomyopathy. However, finding the optimal method for risk evaluation has been challenging, given the complexity and the wide variation in clinical phenotypes. This is particularly important, as these patients are often of younger age and defibrillator implantation is associated with a low but tangible long-term risk of adverse events. A number of risk factors, including degree of hypertrophy, presence of syncope and family history of sudden cardiac death, have typically been considered to indicate a higher risk. The European risk score for prediction of sudden cardiac death is widely used; however, it may not apply well in patients with specific forms of the condition, such as those with extreme hypertrophy. Increasing evidence suggests that the presence and extent of myocardial fibrosis assessed with cardiac magnetic resonance imaging should be considered in clinical decision-making. Some research suggests that integrating electrophysiological studies into traditional risk assessment models may further optimize risk prediction and significantly improve accuracy in detecting high risk patients. Novel cardiac imaging techniques, better understanding of the genetic substrate and artificial intelligence-based algorithms may prove promising for risk refinement. The present review article provides an updated and in-depth viewpoint.

Background: Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy (HCM) remains challenging. Late gadolinium enhancement (LGE) on cardiac MRI signifies myocardial fibrosis and is linked to adverse outcomes in HCM. However, the threshold of LGE that is clinically significant remains a subject of debate. We hypothesized that even small amounts of LGE (≥ 5%) or a history of syncope are associated with worse outcomes. Methods: Between May 2018 and June 2023, HCM patients were prospectively enrolled at the Medical University of Vienna, Austria, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia, appropriate ICD therapy, and all-cause mortality. Results: In total, 230 patients were included. The median age of patients was 56 (IQR 44, 64) years, 40% (n = 94) were female, and 43% (n = 84) had significant left ventricular outflow tract obstruction (LVOTO). Over a median follow-up of 3.2 years, 29 patients (13%) met the composite endpoint. While the ESC HCM risk score was not associated with the primary endpoint, both LGE > 5% (Adj. HR 6.16) and a history of at least one syncope (Adj. HR 3.40) were independently associated with the primary endpoint. These associations were consistent across patients with and without LVOTO. Conclusions: In conclusion, our findings indicate that the combination of a history of syncope together with small amounts of LGE (≥ 5%) in cardiac MRI are associated with unfavorable clinical outcomes in HCM patients.

The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan.

This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis.

The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy.

As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.

To prevent sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM), the HCM Risk-SCD calculator and guideline recommendations are used to aid decision making for implantable cardioverter-defibrillator placement.

The aim of this study was to assess the clinical profiles and occurrence of SCD by phenotypes of HCM and validate the performance of the current guidelines from a large-scale Japanese multicenter registry.

This was a retrospective, multicenter, observational, longitudinal cohort study that enrolled 3,611 consecutive patients with HCM. The primary endpoint was a composite of SCD or an equivalent event.

The 5-year cumulative incidence of SCD events was markedly high in patients with end-stage HCM, defined by ejection fraction <50% (18.5%), followed by midventricular obstruction and nonobstructive HCM (6.9% and 4.7%). The 5-year cumulative incidence rates of SCD events for each recommendation class by the 2 guidelines were as follows: with the 2024 ACC (American College of Cardiology)/AHA (American Heart Association) guidelines, 23.8%, 7.2%, 5.7%, and 2.3% for Classes 1, 2a, 2b, and 3, respectively, and with the 2023 ESC (European Society of Cardiology) guidelines, 23.8%, 2.9%, 9.3%, and 2.6%, respectively. The 5-year risk was not well stratified between Classes 2a and 2b with the 2024 ACC/AHA guidelines (P = 0.101), and the event rate was even reversed with the 2023 ESC guidelines (P = 0.545).

Among HCM phenotypes, the prognosis of patients with end-stage HCM was markedly worse. The 2024 ACC/AHA and 2023 ESC guidelines well stratified SCD risk in patients with HCM; the 2024 ACC/AHA guidelines seemed to better stratify SCD risk between Classes 2a and 2b compared with the 2023 ESC guidelines.

Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death in young individuals. Lumican, is an indicator of fibrosis. We aimed to evaluate the relation between serum Lumican levels and presence and extent of myocardial fibrosis in HCM.

The patients diagnosed with HCM between June 2022 and March 2023 were enrolled consecutively in this prospective study. Age and gender-matched healthy individuals formed control group. Two groups were generated according to extent of late gadolinium enhancement (LGE) in HCM patients.

A total of 114 patients were enrolled. Serum Lumican, NT-proBNP levels and maximum wall thickness were revealed as independent risk factors associated with LGE. A cut-off value of 9.06 for Lumican was associated with 67.8% sensitivity and 65.5% specificity in prediction of LGE.

Myocardial fibrosis is one of the important mechanisms in HCM pathophysiology. LGE on cardiac magnetic resonance imaging allows comprehensive evaluation of myocardial fibrosis, the support of diagnosis with a biomarker would be beneficial in clinical practice. Our study revealed that serum Lumican level is an independent predictor of severe LGE in HCM patients. Further studies with larger patient numbers may clarify the importance of Lumican in HCM pathophysiology.

Sudden cardiac death (SCD), the most devastating complication of hypertrophic cardiomyopathy (HCM), is primarily triggered by ventricular tachycardia or fibrillation. Despite advances in knowledge, the mechanisms driving ventricular arrhythmia in HCM remain incompletely understood, stemming from an interplay of multiple pro-arrhythmic factors. Myocyte disarray and myocardial fibrosis form a structural substrate favorable to re-entrant arrhythmias by altering myocardial electrophysiological properties, while cellular abnormalities predominate in patients without evident structural remodeling. Traditional SCD risk prediction models rely on clinical risk factors and regression-based risk estimation, often overlooking specific arrhythmic substrates. Emerging techniques now allow for the direct assessment of these substrates, providing deeper insights into the arrhythmogenic mechanisms and paving the way for more personalized SCD risk stratification. This review explores the contribution of cellular, structural, and electrophysiological substrates to arrhythmic risk in HCM, emphasizing their distinct roles. Furthermore, it highlights the potential of substrate-based approaches to refining SCD prevention strategies and improving outcomes for patients with HCM.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in hypertrophic cardiomyopathy (HCM) typically represents myocardial fibrosis and may lead to fatal ventricular arrhythmias. However, CMR is resource-intensive and sometimes contraindicated. Thus, in patients with HCM, we aimed to detect LGE on CMR by applying machine learning (ML) algorithm to clinical parameters.

In this trans-Pacific multicenter study of HCM, a ML model was developed to distinguish the presence or absence of LGE on CMR by ridge classification method using 22 clinical parameters including 9 echocardiographic data. Among 742 patients in this cohort, the ML model was constructed in 2 institutions in the United States (training set, n = 554) and tested using data from an institution in Japan (test set, n = 188). LGE was detected in 299 patients (54%) in the training set and 76 patients (40%) in the test set. In the test set, the area under the receiver-operating-characteristic curve (AUC) of the ML model derived from the training set was 0.77 (95% confidence interval [CI] 0.70-0.84). When compared with a reference model constructed with 3 conventional risk factors for LGE on CMR (AUC 0.69 [95% CI 0.61-0.77]), the ML model outperformed the reference model (DeLong's test P = 0.01).

This trans-Pacific study demonstrates that ML analysis of clinical parameters can distinguish the presence of LGE on CMR in patients with HCM. Our ML model would help physicians identify patients with HCM in whom the pre-test probability of LGE is high, and therefore CMR will have higher utility.

The application of computer assisted techniques to the electrocardiogram (ECG) analysis is showing promising results. Our main aim was to apply a machine learning approach to the ECG analysis in patients with hypertrophic cardiomyopathy (HCM), to identify predictors of macroscopic fibrosis, a marker of ventricular arrhythmias and sudden cardiac death.

136 patients diagnosed with HCM were included. The main clinical and echocardiographic variables were collected. All patients underwent cardiac magnetic resonance (CMR) and the presence of macroscopic fibrosis was assessed on late gadolinium enhancement (LGE) sequences. From the 12‑lead digitized ECGs of each patient 468 morphological variables were quantified with a dedicated software.

The mean age of the population was 62.6 ± 14.1 years, and in 82 patients (60.3 %) LGE was observed. After preselecting significant ECG variables from the univariate analysis, a multivariate regression was performed, obtaining a predictive model composed of five parameters: the duration of the QRS in I, the duration of the QT interval in V3, the duration of the T wave in aVF, the peak-to peak amplitude of the QRS in V1, and the amplitude of the S wave in V4. A random forest algorithm confirmed that the duration of the QRS was the strongest predictor of fibrosis.

In patients with HCM the addition of a computer-assisted ECG analysis can help to identify predictors of LGE, being the duration of the QRS the strongest one. Our findings can be especially useful when access to CMR is scarce, to select patients at higher risk.

miR-199a carried by adeno-associated virus serotype 6 (AAV6) proved cardioreparative in a pig model when administered early after myocardial infarction (MI). To test whether the therapeutic efficacy of miR-199a is maintained when its administration is delayed, AAV6-miR-199a or a control AAV6 were injected 1 or 2 weeks after MI. Scar mass and cardiac contractile performance parameters were not significantly different between AAV6-miR-199a-treated and AAV6-control pigs. Nonetheless, most AAV6-miR-199a-treated pigs died from sudden death at 40 to 52 days after vector administration. For clinical translation, it appears mandatory to administer miR-199a early after MI and through modalities other than permanent expression from a viral vector.

The first European Society of Cardiology (ESC) guidelines on the management of cardiomyopathies (CMPs), published 1 year ago, remain highly relevant. These guidelines provide a comprehensive framework to manage the complexity of CMPs, consolidating previous approaches. All CMPs are now addressed systematically in one document. The ESC recommends a 'CMP-oriented' approach, emphasizing thorough clinical assessments and phenotype-first categorization into hypertrophic, dilated, arrhythmogenic, restrictive, and non-dilated left ventricular CMP. Despite the utility of this method, certain classifications, such as arrhythmogenic right ventricular CMP and the novel non-dilated left ventricular CMP, raise controversies. Key advances in the guidelines include the use of genetic testing and cardiac magnetic resonance imaging to refine diagnoses and inform treatment, especially for high-risk genotypes. These guidelines advocate for personalized, multidisciplinary care. Overall, they represent a significant step forward but highlight the evolving nature of CMP management as scientific understanding progresses.

Over the past decades, hypertrophic cardiomyopathy has become a contemporary treatable disease. However, limited data exist on the global trends of implantable cardioverter defibrillator (ICD) utilization and its impact on mortality/morbidity burden reduction.

Electronic databases were systematically searched up to March 2024 for studies reporting on ICD utilization rates in hypertrophic cardiomyopathy. A random effects model was used to pool study estimates across time-era, geographic region, and age group. Primary outcome was global trends in ICD utilization. Secondary outcomes included trends of sudden cardiac death, appropriate/inappropriate shocks, and ICD-related complications.

In total, 234 studies (N=92 500, 514 748 patient-years) met inclusion criteria. Mean age was 46.2 (12.4) years and 37.49% were women. A total of 12 139 patients (16.43%) received an ICD over 429 766 person-years of follow-up, with an ICD implantation rate of 2.79%/y ([95% CI, 2.35%-3.32%] I²=97.80%). Rates of ICD implantation steadily increased over time from 1990 (1.09%) to 2021 (4.01%; P=0.002), with noticeable geographic variation (P=0.008). The overall rate of appropriate ICD discharges and ICD-related complications was 3.44%/y ([95% CI, 3.08%-3.84%] I²=88.40%) and 1.98%/y ([95% CI, 1.52%-2.59%] I²=90.44%), respectively, with no significant trend over time. The overall rate of inappropriate discharges was 3.58%/y ([95% CI, 3.08%-4.16%] I2=88.03%), and declined significantly over time (P=0.044). There was a significant decline in the rates of sudden cardiac death from 1990 (0.84%/y) to 2020 (0.31%/y).

Dramatic increases in ICD utilization have occurred, representing a 3.7-fold increase, with appropriate therapies occurring in 3.44%/y. In parallel a significant reduction in sudden cardiac death was observed, but there are insufficient data to demonstrate that a causative relationship exists. Geographic disparities in ICD utilization were evident, highlighting the need to improve access to specialized care for patients with hypertrophic cardiomyopathy. Geographic disparities in ICD utilization were evident, highlighting the need to improve access to specialized care for patients with hypertrophic cardiomyopathy.

URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023407126.

Myocardial disarray, an early feature of hypertrophic cardiomyopathy (HCM) and a substrate for ventricular arrhythmia, is poorly characterized in pre-hypertrophic sarcomeric variant carriers (SARC+LVH-). Using diffusion tensor cardiac magnetic resonance (DT-CMR) we assessed myocardial disarray and fibrosis in both SARC+LVH- and HCM patients and evaluated the relationship between microstructural alterations and electrocardiographic (ECG) parameters associated with arrhythmic risk.

Sixty-two individuals (24 SARC+LVH-, 24 HCM, and 14 matched controls) were evaluated with multi-parametric CMR including stimulated echo acquisition mode DT-CMR, and blinded quantitative 12-lead ECG analysis. Mean diastolic fractional anisotropy (FA) was reduced in HCM compared with SARC+LVH- and controls (0.49 ± 0.05 vs. 0.52 ± 0.04 vs. 0.53 ± 0.04, P = 0.009), even after adjustment for differences in extracellular volume (ECV) (P = 0.038). Both HCM and SARC+LVH- had segments with significantly reduced diastolic FA relative to controls (54 vs. 25 vs. 0%, P = 0.002). Multiple repolarization parameters were prolonged in HCM and SARC+LVH-, with corrected JT interval (JTc) being most significant (354 ± 42 vs. 356 ± 26 vs. 314 ± 26 ms, P = 0.002). Among SARC+LVH-, JTc duration correlated negatively with mean diastolic FA (r = -0.6, P = 0.002). In HCM, the JTc interval showed a stronger association with ECV (r = 0.6 P = 0.019) than with mean diastolic FA (r = -0.1 P = 0.72). JTc discriminated SARC+LVH- from controls [area under the receiver operator curve 0.88, confidence interval 0.76-1.00, P < 0.001], and in HCM correlated with the European Society of Cardiology HCM sudden cardiac death risk score (r = 0.5, P = 0.014).

Low diastolic FA, suggestive of myocardial disarray, is present in both SARC+LVH- and HCM. Low FA and raised ECV were associated with repolarization prolongation. Myocardial disarray assessment using DT-CMR and repolarization parameters such as the JTc interval demonstrate significant potential as markers of disease activity in HCM.

Cardiovascular magnetic resonance (CMR) imaging has become a cornerstone in the diagnosis, risk stratification, and management of cardiovascular disease (CVD), particularly heart failure (HF) and cardiomyopathies. Renowned as the gold standard for non-invasive quantification of ventricular volumes and ejection fraction, CMR delivers superior spatial and temporal resolution with excellent tissue-blood contrast. Recent advancements, including T1, T2, and T2* mapping, extracellular volume quantification, and late gadolinium enhancement, enable precise tissue characterization, allowing early detection of myocardial changes such as fibrosis, edema, and infiltration. These features provide critical insights into the pathophysiological mechanisms underlying HF phenotypes and diverse cardiomyopathies, enhancing diagnostic accuracy and guiding therapeutic decisions. This review explores the expanding role of CMR in CV disease, highlighting its diagnostic value in HF and in several cardiomyopathies, as well as its contribution to improving patient outcomes through detailed tissue characterization and prognosis.

Late gadolinium enhancement (LGE) on cardiac MRI has been shown to predict adverse outcomes in a range of cardiac diseases. However, no study has systematically reviewed and analyzed the literature across all cardiac pathologies including rare diseases.

PubMed, EMBASE and Web of Science were searched for studies evaluating the relationship between LGE burden and cardiovascular outcomes. Outcomes included all-cause mortality, MACE, sudden cardiac death, sustained VT or VF, appropriate ICD shock, heart transplant, and heart failure hospitalization. Only studies reporting hazards ratios with LGE as a continuous variable were included.

Of the initial 8928 studies, 95 studies (23,313 patients) were included across 19 clinical entities. The studies included ischemic cardiomyopathy (7182 patients, 33 studies), hypertrophic cardiomyopathy (5080 patients, 17 studies), non-ischemic cardiomyopathy not otherwise specified (2627 patients, 11 studies), and dilated cardiomyopathy (2345 patients, 14 studies). Among 42 studies that quantified LGE by percent myocardium, a 1 % increase in LGE burden was associated with life-threatening ventricular arrhythmias (LTVA) with a pooled hazard ratio of 1.04 (CI 1.02-1.05), and MACE with a pooled hazard ratio of 1.06 (CI 1.04-1.07). The risk of these events was similar across disease types, with minimal heterogeneity.

Despite mechanistic differences in myocardial injury, LGE appears to have a fairly consistent, dose-dependent effect on risk of LTVA, MACE, and mortality. These data can be applied to derive a patient's absolute risk of LTVA, and therefore can be clinically useful in informing decisions on primary prevention ICD implantation irrespective of the disease etiology.

Cardiac magnetic resonance (CMR) allows for analysis of cardiac function and myocardial tissue characterization. Increased left ventricular mass (LVM) is an independent predictor of cardiovascular events; however, the diagnosis of left ventricular hypertrophy and its prognostic value strongly depend on the LVM indexation method. Evaluation of the quantity and distribution of late gadolinium enhancement assists in clinical decisions on diagnosis, cardiovascular assessment, and interventions, including the placement of cardiac implantable electronic devices and the choice of an optimal procedural approach. Novel CMR techniques, such as T1 and T2 mapping, may be used for the longitudinal follow-up of myocardial fibrosis and myocardial edema or inflammation in different groups of patients, including patients with systemic sclerosis, myocarditis, cardiac sarcoidosis, amyloidosis, and both ischemic and non-ischemic cardiomyopathy, among others. Moreover, CMR tagging and feature tracking techniques might improve cardiovascular risk stratification in patients with different etiologies of left ventricular dysfunction. This review summarizes the knowledge about the current role of CMR in diagnostics and cardiovascular risk assessment to enable more personalized approach in clinical decision making.

This work proposes a convolutional neural network (CNN) that utilizes different combinations of parametric images computed from cine cardiac magnetic resonance (CMR) images, to classify each slice for possible myocardial scar tissue presence. The CNN performance comparison in respect to expert interpretation of CMR with late gadolinium enhancement (LGE) images, used as ground truth (GT), was conducted on 206 patients (158 scar, 48 control) from Centro Cardiologico Monzino (Milan, Italy) at both slice- and patient-levels. Left ventricle dynamic features were extracted in non-enhanced cine images using parametric images based on both Fourier and monogenic signal analyses. The CNN, fed with cine images and Fourier-based parametric images, achieved an area under the ROC curve of 0.86 (accuracy 0.79, F1 0.81, sensitivity 0.9, specificity 0.65, and negative (NPV) and positive (PPV) predictive values 0.83 and 0.77, respectively), for individual slice classification. Remarkably, it exhibited 1.0 prediction accuracy (F1 0.98, sensitivity 1.0, specificity 0.9, NPV 1.0, and PPV 0.97) in patient classification as a control or pathologic. The proposed approach represents a first step towards scar detection in contrast-free CMR images. Patient-level results suggest its preliminary potential as a screening tool to guide decisions regarding LGE-CMR prescription, particularly in cases where indication is uncertain.

Altitude is a known factor in cardiovascular disease, but its impact on hypertrophic cardiomyopathy (HCM) patients remains unclear. This study aimed to determine whether living at high altitudes affects the extent of late gadolinium enhancement (LGE) and left ventricular (LV) strain in HCM patients.

This retrospective cross-sectional study was conducted across four hospitals located at different altitudes in China. A total of 256 HCM patients who underwent cardiac magnetic resonance (CMR) imaging between May 2019 and November 2021 were included. Patients were categorized into two groups: the high-altitude group (median interquartile range [IQR]: 1520.00 [1520.00, 1917.00] meters, n = 132) and the low-altitude group (86.45 [43.50, 150.75] meters, n = 124). The extent of LGE and global LV strain were assessed and compared between these groups.

The median age of the study population was 55 years (IQR: 46-63), with 59% of participants being male. The high-altitude group exhibited a significantly greater extent of LGE compared to the low-altitude group (median [IQR]: 8.10 [4.78, 19.98]% vs. 6.20 [1.89, 13.81]%; p = 0.008). Multivariable analysis identified altitude as an independent predictor of increased LGE extent (β = 4.41; 95% CI: 2.04 to 6.78; p < 0.001). Additionally, altitude was positively associated with LV strain in the longitudinal, circumferential, and radial directions (all p < 0.050).

HCM patients living at higher altitudes exhibit a significant increase in LGE extent and more favorable LV strain parameters.

Question Does altitude affect the extent of late gadolinium enhancement (LGE) and left ventricular strain in patients with hypertrophic cardiomyopathy (HCM)? Findings High altitude is associated with a significantly greater extent of LGE and less impairment in global longitudinal strain in HCM patients. Clinical relevance HCM patients living at higher altitudes exhibit a significant increase in LGE extent and the mismatch of left ventricular strains. Doctors should consider these findings to tailor treatment and follow-up plans for HCM patients living in high altitudes.

Cardiac magnetic resonance (CMR) imaging enables a one-stop assessment of heart structure and function. Artificial intelligence (AI) can simplify and automate work flows and improve image post-processing speed and diagnostic accuracy; thus, it greatly affects many aspects of CMR. This review highlights the application of AI for left heart analysis in CMR, including quality control, image segmentation, and global and regional functional assessment. Most recent research has focused on segmentation of the left ventricular myocardium and blood pool. Although many algorithms have shown a level comparable to that of human experts, some problems, such as poor performance of basal and apical segmentation and false identification of myocardial structure, remain. Segmentation of myocardial fibrosis is another research hotspot, and most patient cohorts of such studies have hypertrophic cardiomyopathy. Whether the above methods are applicable to other patient groups requires further study. The use of automated CMR interpretation for the diagnosis and prognosis assessment of cardiovascular diseases demonstrates great clinical potential. However, prospective large-scale clinical trials are needed to investigate the real-word application of AI technology in clinical practice.

The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM.

We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80-94] vs. 98 ms [88-108]; P < 0.01). Multivariable logistic regression identified for the novel diagnostic HCM (D-HCM) score: absence of antihypertensive drugs (+2); family history of unexplained sudden death (+2); QRS duration [<95 ms] = +1; maximum wall thickness (mm) [≥17] = +1. A cumulative QRS-HCM score ≥2 supports the diagnostic certainty of true HCM with a sensitivity of 79%, specificity of 99%, negative predictive value (NPV) of 55%, and positive predictive value (PPV) of 99%.

The QRS duration in patient with HCM is significantly shorter compared with patients with HHD-related LVH. QRS duration can be used as a diagnosis marker to distinguish between HCM and HHD. The D-HCM score is a novel, simple, and accurate diagnosis tool for HCM patients with mild to moderate phenotypes.

The ability to predict sudden cardiac death (SCD) in children and adolescents with hypertrophic cardiomyopathy (HCM) is currently inadequate. Late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging is associated with SCD events in adults with HCM.

To examine the prognostic significance of LGE in patients with HCM who are younger than 21 years.

This multicenter, retrospective cohort study was conducted from April 8, 2015, to September 12, 2022, in patients with HCM who were younger than 21 years and had undergone CMR imaging across multiple sites in the US, Europe, and South America. Observers of CMR studies were masked toward outcomes and demographic characteristics.

Natural history of HCM.

The primary outcome was SCD and surrogate events, including resuscitated cardiac arrest and appropriate discharges from an implantable defibrillator. Continuous and categorical data are expressed as mean (SD), median (IQR), or number (percentage), respectively. Survivor curves comparing patients with and without LGE were constructed by the Kaplan-Meier method, and likelihood of subsequent clinical events was further evaluated using univariate and multivariable Cox proportional hazards models.

Among 700 patients from 37 international centers, median (IQR) age was 14.8 (11.9-17.4) years, and 518 participants (74.0%) were male. During a median (IQR) [range] follow-up period of 1.9 (0.5-4.1) [0.1-14.8] years, 35 patients (5.0%) experienced SCD or equivalent events. LGE was present in 230 patients (32.9%), which constituted an mean (SD) burden of 5.9% (7.3%) of left ventricular myocardium. The LGE amount was higher in older patients and those with greater left ventricular mass and maximal wall thickness; patients with LGE had lower left ventricular ejection fractions and larger left atrial diameters. The presence and burden of LGE was associated with SCD, even after correcting for existing risk stratification tools. Patients with 10% or more LGE, relative to total myocardium, had a higher risk of SCD (unadjusted hazard ratio [HR], 2.19; 95% CI, 1.59-3.02; P < .001). Furthermore, the addition of LGE burden improved the performance of the HCM Risk-Kids score (before LGE addition: 0.66; 95% CI, 0.58-0.75; after LGE addition: 0.73; 95% CI, 0.66-0.81) and Precision Medicine in Cardiomyopathy score (before LGE addition: 0.68; 95% CI, 0.49-0.77; after LGE addition: 0.73; 95% CI, 0.64-0.82) SCD predictive models.

In this retrospective cohort study, quantitative LGE was a risk factor for SCD in patients younger than 21 years with HCM and improved risk stratification.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder, more often presenting with asymmetrical septal hypertrophy. Here we report the case of a patient, affected by arterial hypertension, presenting to the emergency department with chest pain, electrocardiographic changes and troponin rise. Further diagnostic work-up ruled out ischemic heart disease and lead to the diagnosis of a rare HCM phenotype affecting the lateral wall of the left ventricle. Cardiac magnetic resonance imaging proved to be a reliable diagnostic test in this case thanks to its tissue characterization ability, allowing the identification of diffuse fibrosis through native T1 mapping, edema through T2 mapping and replacement fibrosis with late gadolinium enhancement, providing us with robust diagnostic and prognostic information. The association of arterial hypertension with atypical HCM forms emerged from multicentric studies, however, further research is needed to fully clarify the complex interactions between arterial hypertension and phenotypic expression of HCM.

Hypertrophic cardiomyopathy (HCM) can cause myocardial fibrosis, which can be a substrate for fatal ventricular arrhythmias and subsequent sudden cardiac death. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) represents myocardial fibrosis and is associated with sudden cardiac death in patients with HCM, CMR is resource-intensive, can carry an economic burden, and is sometimes contraindicated. In this study for patients with HCM, we aimed to distinguish between patients with positive and negative LGE on CMR using deep learning of echocardiographic images.

In the cross-sectional study of patients with HCM, we enrolled patients who underwent both echocardiography and CMR. The outcome was positive LGE on CMR. Among the 323 samples, we randomly selected 273 samples (training set) and employed deep convolutional neural network (DCNN) of echocardiographic 5-chamber view to discriminate positive LGE on CMR. We also developed a reference model using clinical parameters with significant differences between patients with positive and negative LGE. In the remaining 50 samples (test set), we compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the DCNN-derived probability and the reference model.

Among the 323 CMR studies, positive LGE was detected in 160 (50%). The reference model was constructed using the following 7 clinical parameters: family history of HCM, maximum left ventricular (LV) wall thickness, LV end-diastolic diameter, LV end-systolic volume, LV ejection fraction < 50%, left atrial diameter, and LV outflow tract pressure gradient at rest. The discriminant model combining the reference model with DCNN-derived probability significantly outperformed the reference model in the test set (AUC 0.86 [95% confidence interval 0.76-0.96] vs. 0.72 [0.57-0.86], P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the combined model were 0.84, 0.76, 0.78, and 0.83, respectively.

Compared to the reference model solely based on clinical parameters, our new model integrating the reference model and deep learning-based analysis of echocardiographic images demonstrated superiority in distinguishing LGE on CMR in patients with HCM. The novel deep learning-based method can be used as an assistive technology to facilitate the decision-making process of performing CMR with gadolinium enhancement.

The risk stratification for fatal arrhythmias remains inadequate. Cardiac magnetic resonance (CMR) imaging provides a detailed evaluation of arrhythmogenic substrates. This study investigated the predictive capacity of multiparametric CMR for fatal ventricular arrhythmias (VAs) in a heterogeneous disease cohort.

The study included 396 consecutive patients with structural heart disease (SHD, n = 248) and non-apparent SHD (n = 148) who underwent CMR scans between 2018 and 2022. The primary endpoint was fatal composite arrhythmias.

Thirty-three patients (8.3 %) experienced fatal arrhythmias (25 with SHD, 8 with non-apparent SHD) over a median follow-up of 24 months. The independent risk factors for patients with SHD included syncope (hazard ratio [HR] = 5.347; P < 0.001), VA history (HR = 3.705; P = 0.004), right ventricular ejection fraction (RVEF) ≤ 45 % (HR = 2.587; P = 0.039), and the presence of late gadolinium enhancement (LGE) (HR = 4.767; P = 0.040). In the non-apparent SHD group, fatal arrhythmias were independently correlated with VA history (HR = 10.23; P = 0.005), RVEF ≤ 45 % (HR = 8.307; P = 0.015), and CMR myocardial abnormalities (HR = 5.203; P = 0.033). Patients at high risk of fatal arrhythmia in the SHD and non-apparent SHD groups exhibited 3-year event-free survival rates of 69.4 % and 83.5 %, respectively.

CMR provides effective prognostic information for patients with and without apparent SHD. The presence of LGE, CMR myocardial abnormalities, and right ventricular dysfunction are strong risk markers for fatal arrhythmias.

Most acquired and inherited cardiomyopathies are characterized by regional left ventricular involvement and nonischemic myocardial scars, often with a disease-specific pattern. Irrespective of the etiology and pathophysiological mechanisms, myocardial disorders are invariably associated with cardiac fibrosis, which contributes to dysfunction and electrical instability. Accordingly, cardiac magnetic resonance plays a central role in the diagnostic work-up and prognostic risk stratification of cardiomyopathies, particularly with the increasing correlation between genetic background and specific disease phenotype. Starting from pattern and distribution of myocardial fibrosis at cardiac magnetic resonance, we provide a practical regional atlas of nonischemic myocardial scar to guide the diagnostic approach to nonischemic cardiomyopathies.