Arrhythmic Mitral Valve Prolapse Phenotype: An Unsupervised Machine Learning Analysis Using a Multicenter Cardiac MRI Registry.

Purpose To use unsupervised machine learning to identify phenotypic clusters with increased risk of arrhythmic mitral valve prolapse (MVP). Materials and Methods This retrospective study included patients with MVP without hemodynamically significant mitral regurgitation or left ventricular (LV) dysfunction undergoing late gadolinium enhancement (LGE) cardiac MRI between October 2007 and June 2020 in 15 European tertiary centers. The study end point was a composite of sustained ventricular tachycardia, (aborted) sudden cardiac death, or unexplained syncope. Unsupervised data-driven hierarchical k-mean algorithm was utilized to identify phenotypic clusters. The association between clusters and the study end point was assessed by Cox proportional hazards model. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 female, 230 male) with two phenotypic clusters were identified. Patients in cluster 2 (199 of 474, 42%) had more severe mitral valve degeneration (ie, bileaflet MVP and leaflet displacement), left and right heart chamber remodeling, and myocardial fibrosis as assessed with LGE cardiac MRI than those in cluster 1. Demographic and clinical features (ie, symptoms, arrhythmias at Holter monitoring) had negligible contribution in differentiating the two clusters. Compared with cluster 1, the risk of developing the study end point over a median follow-up of 39 months was significantly higher in cluster 2 patients (hazard ratio: 3.79 [95% CI: 1.19, 12.12], P = .02) after adjustment for LGE extent. Conclusion Among patients with MVP without significant mitral regurgitation or LV dysfunction, unsupervised machine learning enabled the identification of two phenotypic clusters with distinct arrhythmic outcomes based primarily on cardiac MRI features. These results encourage the use of in-depth imaging-based phenotyping for implementing arrhythmic risk prediction in MVP. Keywords: MR Imaging, Cardiac, Cardiac MRI, Mitral Valve Prolapse, Cluster Analysis, Ventricular Arrhythmia, Sudden Cardiac Death, Unsupervised Machine Learning Supplemental material is available for this article. © RSNA, 2024.

CMR Mapping: The 4th-Era Revolution in Cardiac Imaging.

Cardiac magnetic resonance (CMR) imaging has witnessed substantial progress with the advent of parametric mapping techniques, most notably T1 and T2 mapping. These advanced techniques provide valuable insights into a wide range of cardiac conditions, including ischemic heart disease, cardiomyopathies, inflammatory cardiomyopathies, heart valve disease, and athlete's heart. Mapping could be the first sign of myocardial injury and oftentimes precedes symptoms, changes in ejection fraction, and irreversible myocardial remodeling. The ability of parametric mapping to offer a quantitative assessment of myocardial tissue properties addresses the limitations of conventional CMR methods, which often rely on qualitative or semiquantitative data. However, challenges persist, especially in terms of standardization and reference value establishment, hindering the wider clinical adoption of parametric mapping. Future developments should prioritize the standardization of techniques to enhance their clinical applicability, ultimately optimizing patient care pathways and outcomes. In this review, we endeavor to provide insights into the potential contributions of CMR mapping techniques in enhancing the diagnostic processes across a range of cardiac conditions.

[Persistent ST-elevation with elevated myocardial necrosis markers: a case of myocardial contusion]. / Sopraslivellamento persistente del tratto ST con marcatori di miocardiocitonecrosi elevati: un caso di contusione cardiaca.

Myocardial contusion is a rare and potentially fatal complication of chest trauma. There is no unique definition for this entity: some authors define myocardial contusion as a mild increase in cardiac biomarkers in the context of chest trauma, while for others the diagnosis requires evidence of pathologic findings at cardiac imaging. Consequently, the real incidence of myocardial contusion remains unknown, varying in reports between 8% and 71%. We describe a case of cardiac contusion secondary to a low-energy blunt chest trauma, manifesting as persistent ST-elevation associated with elevation of myocardial necrosis markers, with consequent myocardial stunning of the right ventricular free wall. As there is no consensus regarding the diagnostic pathway, it is essential to integrate first-level exams (ECG and laboratory findings) with cardiac magnetic resonance imaging, to define the presence of cardiac contusion and its extent, particularly if the echocardiographic data are unconclusive.

Cardiovascular Magnetic Resonance in Patients with Cardiac Electronic Devices: Evidence from a Multicenter Study.

BACKGROUND: Most recent cardiac implantable electronic devices (CIEDs) can safely undergo a cardiovascular magnetic resonance (CMR) scan under certain conditions, but metal artifacts may degrade image quality. The aim of this study was to assess the overall diagnostic yield of CMR and the extent of metal artifacts in a multicenter, multivendor study on CIED patients referred for CMR. METHODS: We analyzed 309 CMR scans from 292 patients (age 57 ± 16 years, 219 male) with an MR-conditional pacemaker (n = 122), defibrillator (n = 149), or loop recorder (n = 38); CMR scans were performed in 10 centers from 2012 to 2020; MR-unsafe implants were excluded. Clinical and device parameters were recorded before and after the CMR scan. A visual analysis of metal artifacts was performed for each sequence on a segmental basis, based on a 5-point artifact score. RESULTS: The vast majority of CMR scans (n = 255, 83%) were completely performed, while only 32 (10%) were interrupted soon after the first sequences and 22 (7%) were only partly acquired; CMR quality was non-diagnostic in 34 (11%) scans, poor (<1/3 sequences were diagnostic) in 25 (8%), or acceptable (1/3 to 2/3 sequences were diagnostic) in 40 (13%), while most scans (n = 201, 68%) were of overall good quality. No adverse event or device malfunctioning occurred, and only nonsignificant changes in device parameters were recorded. The most affected sequences were SSFP (median score 0.32 [interquartile range 0.07-0.91]), followed by GRE (0.18 [0.02-0.59]) and LGE (0.14 [0.02-0.55]). ICDs induced more artifacts (median score in SSFP images 0.87 [0.50-1.46]) than PMs (0.11 [0.03-0.28]) or ILRs (0.11 [0.00-0.56]). Moreover, most artifacts were located in the anterior, anteroseptal, anterolateral, and apical segments of the LV and in the outflow tract of the RV. CONCLUSIONS: CMR is a versatile imaging technique, with a high safety profile and overall good image quality even in patients with MR-conditional CIEDs. Several strategies are now available to optimize image quality, substantially enhancing overall diagnostic yield.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Consensus Statement on the definition and classification of metabolic hyperferritinaemia.

Hyperferritinaemia is a common laboratory finding that is often associated with metabolic dysfunction and fatty liver. Metabolic hyperferritinaemia reflects alterations in iron metabolism that facilitate iron accumulation in the body and is associated with an increased risk of cardiometabolic and liver diseases. Genetic variants that modulate iron homeostasis and tissue levels of iron are the main determinants of serum levels of ferritin in individuals with metabolic dysfunction, raising the hypothesis that iron accumulation might be implicated in the pathogenesis of insulin resistance and the related organ damage. However, validated criteria for the non-invasive diagnosis of metabolic hyperferritinaemia and the staging of iron overload are still lacking, and there is no clear evidence of a benefit for iron depletion therapy. Here, we provide an overview of the literature on the relationship between hyperferritinaemia and iron accumulation in individuals with metabolic dysfunction, and on the associated clinical outcomes. We propose an updated definition and a provisional staging system for metabolic hyperferritinaemia, which has been agreed on by a multidisciplinary global panel of expert researchers. The goal is to foster studies into the epidemiology, genetics, pathophysiology, clinical relevance and treatment of metabolic hyperferritinaemia, for which we provide suggestions on the main unmet needs, optimal design and clinically relevant outcomes.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

AIMS: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. CONCLUSION: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Myocardial Fibrosis at Cardiac MRI Helps Predict Adverse Clinical Outcome in Patients with Mitral Valve Prolapse.

Background Patients with mitral valve prolapse (MVP) may develop adverse outcomes even in the absence of mitral regurgitation or left ventricular (LV) dysfunction. Purpose To investigate the prognostic value of mitral annulus disjunction (MAD) and myocardial fibrosis at late gadolinium enhancement (LGE) cardiac MRI in patients with MVP without moderate-to-severe mitral regurgitation or LV dysfunction. Materials and Methods In this longitudinal retrospective study, 118 144 cardiac MRI studies were evaluated between October 2007 and June 2020 at 15 European tertiary medical centers. Follow-up was from the date of cardiac MRI examination to June 2020; the minimum and maximum follow-up intervals were 6 months and 156 months, respectively. Patients were excluded if at least one of the following conditions was present: cardiomyopathy, LV ejection fraction less than 40%, ischemic heart disease, congenital heart disease, inflammatory heart disease, moderate or worse mitral regurgitation, participation in competitive sport, or electrocardiogram suggestive of channelopathies. In the remainder, cardiac MRI studies were reanalyzed, and patients were included if they were aged 18 years or older, MVP was diagnosed at cardiac MRI, and clinical information and electrocardiogram monitoring were available within 3 months from cardiac MRI examination. The end point was a composite of adverse outcomes: sustained ventricular tachycardia (VT), sudden cardiac death (SCD), or unexplained syncope. Multivariable Cox regression analysis was performed. Results A total of 474 patients (mean age, 47 years ± 16 [SD]; 244 women) were included. Over a median follow-up of 3.3 years, 18 patients (4%) reached the study end point. LGE presence (hazard ratio, 4.2 [95% CI: 1.5, 11.9]; P = .006) and extent (hazard ratio, 1.2 per 1% increase [95% CI: 1.1, 1.4]; P = .006), but not MAD presence (P = .89), were associated with clinical outcome. LGE presence had incremental prognostic value over MVP severity and sustained VT and aborted SCD at baseline (area under the receiver operating characteristic curve, 0.70 vs 0.62; P = .03). Conclusion In contrast to mitral annulus disjunction, myocardial fibrosis determined according to late gadolinium enhancement at cardiac MRI was associated with adverse outcome in patients with mitral valve prolapse without moderate-to-severe mitral regurgitation or left ventricular dysfunction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gerber in this issue.

Cardiac magnetic resonance abnormalities in patients with acute myocarditis proven by septal endomyocardial biopsy.

BACKGROUND: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). METHODS: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. RESULTS: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). CONCLUSION: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.

Report from the Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Congress.

Overview of the meeting The Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Meeting mainly focused on the diagnosis, management and prevention of cardiovascular toxicity of cancer drugs, in particular, cardiac dysfunction induced by anthracyclines. Although a variety of cardiac biomarkers and imaging modalities are available, there remains no consensus regarding their appropriate use to identify early and late cardiotoxicity and to guide preventive strategies. At the same time, the multitude of pharmacological trials, aimed at preventing cardiac damage through a neurohormonal blockade, provided conflicting results. Nevertheless, the advent of novel heart failure medications can change the decision-making of the cardio-oncologist. This symposium attempted to harmonize these issues.

Acute Myocarditis Associated With Desmosomal Gene Variants.

BACKGROUND: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. OBJECTIVES: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. METHODS: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. RESULTS: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Effusive-constrictive pericarditis after the second dose of BNT162b2 vaccine (Comirnaty): a case report.

BACKGROUND: Whereas effusive-constrictive pericarditis (ECP) can rarely occur in coronavirus disease 2019 (COVID-19), to date no cases of ECP related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine have been documented. CASE SUMMARY: A 59-year-old Caucasian man presented to our emergency department with ECP. Symptoms occurred shortly after the second dose of BNT162b2 (Comirnaty) vaccine. No other aetiological causes were identified. Guidelines-directed therapy for acute pericarditis was implemented, with clinical benefit. DISCUSSION: Systemic inflammatory response to COVID-19 can rarely trigger pericarditis. In our case, a strong temporal relationship between the second dose of BNT162b2 vaccine and symptoms occurrence was documented, indicating a possible rare adverse reaction to the vaccine, similarly to natural infection. Further research is needed to confirm a causal relationship.

A method for T1 and T2 relaxation times validation and harmonization as a support to MRI mapping.

We present a proof-of-concept study focusing on a method for the intra- and inter-center validation and harmonization of data obtained from MRI T1 and T2 maps. The method is based on a set of MnCl2 samples that provide in-scan ground-truth reference values regardless of the details of the MRI protocol. The relaxation times of MnCl2 aqueous solutions were first measured by means of an NMR laboratory relaxometer, as a function of concentration and temperature. The obtained T1 and T2 values, once renormalized at the scanner temperature, were used as reference values for the MRI mapping measurements of the MnCl2 relaxation times. By using different clinical MRI scanners and sequences, we found a good agreement for standard and turbo sequences (limits of agreement: 5% for IR, SE, IR-TSE; 10% for TSE), while an under-estimation and an over-estimation were found respectively for MOLLI and T2-prep TrueFISP, as already reported in the literature. The linearity of the relaxation rates with the concentration predicted by the Solomon-Bloembergen-Morgan theory was observed for every dataset at all temperatures, except for T2-prep TrueFISP maps results. Some preliminary results of an in vivo experiment are also presented.