Multi-parametric non-contrast cardiac magnetic resonance for the differentiation between cardiac amyloidosis and hypertrophic cardiomyopathy.

AIM: To evaluate the ability of fast strain-encoded (SENC) cardiac magnetic resonance (CMR) derived myocardial strain and native T1 mapping to discriminate between hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis. METHODS: Ninety nine patients (57 with hypertrophic cardiomyopathy and 42 with cardiac amyloidosis) were systematically analysed. LV-ejection fraction, LV-mass index, septal wall thickness and native T1 mapping values were assessed. In addition, global circumferential and longitudinal strain and segmental circumferential and longitudinal strain in basal, mid-ventricular, and apical segments were calculated. A ratio was built by dividing native T1 values by basal segmental strain (T1-to-basal segmental strain ratio). RESULTS: Myocardial strain was equally distributed in apical and basal segments in HCM patients, whereas an apical sparing with less impaired apical strain was noticed in cardiac amyloidosis (apical-to-basal-ratio of 1.01 ± 0.23 versus 1.20 ± 0.28, p < 0.001). T1 values were significantly higher in amyloidosis compared to HCM patients (1170.7 ± 66.4 ms versus 1078.3 ± 57.4ms, p < 0.001). The T1-to-basal segmental strain ratio exhibited high accuracy for the differentiation between the two clinical entities (Sensitivity = 85%, Specificity = 77%, AUC = 0.90, 95% CI = 0.81-0.95, p < 0.001). Multivariable analysis showed that age and the T1-to-basal-strain-ratio were the most robust factors for the differentiation between HCM and cardiac amyloidosis. CONCLUSION: The T1-to-basal-segmental strain ratio, combining information from segmental circumferential and longitudinal strain and native T1 mapping aids the differentiation between HCM and cardiac amyloidosis with high accuracy and within a fast CMR protocol, obviating the need for contrast agent administration.

Quantification of myocardial extracellular volume without blood sampling.

Aims: Cardiac magnetic resonance (CMR) T1 relaxation time mapping is an established technique primarily used to identify diffuse interstitial fibrosis and oedema. The myocardial extracellular volume (ECV) can be calculated from pre- and post-contrast T1 relaxation times and is a reproducible parametric index of the proportion of volume occupied by non-cardiomyocyte components in myocardial tissue. The conventional calculation of the ECV requires blood sampling to measure the haematocrit (HCT). Given the high variability of the HCT, the blood collection is recommended within 24 h of the CMR scan, limiting its applicability and posing a barrier to the clinical routine use of ECV measurements. In recent years, several research groups have proposed a method to determine the ECV by CMR without blood sampling. This is based on the inverse relationship between the T1 relaxation rate (R1) of blood and the HCT. Consequently, a 'synthetic' HCT could be estimated from the native blood R1, avoiding blood sampling. Methods and results: We performed a review and meta-analysis of published studies on synthetic ECV, as well as a secondary analysis of previously published data to examine the effect of the chosen regression modell on bias. While, overall, a good correlation and little bias between synthetic and conventional ECV were found in these studies, questions regarding its accuracy remain. Conclusion: Synthetic HCT and ECV can provide a 'non-invasive' quantitative measurement of the myocardium's extracellular space when timely HCT measurements are not available and large alterations in ECV are expected, such as in cardiac amyloidosis. Due to the dependency of T1 relaxation times on the local setup, calculation of local formulas using linear regression is recommended, which can be easily performed using available data.

Myocarditis following COVID-19 vaccine: incidence, presentation, diagnosis, pathophysiology, therapy, and outcomes put into perspective. A clinical consensus document supported by the Heart Failure Association of the European Society of Cardiology (ESC) and the ESC Working Group on Myocardial and Pericardial Diseases.

Over 10 million doses of COVID-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non-invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyond guideline-directed treatment of heart failure and arrhythmias includes non-specific measures to control pain. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS-CoV-2 infection-related hospitalization and death are hugely greater than the risks from post-vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area.

Synthetic Extracellular Volume in Cardiac Magnetic Resonance Without Blood Sampling: a Reliable Tool to Replace Conventional Extracellular Volume.

BACKGROUND: The calculation of extracellular volume (ECV) in cardiac magnetic resonance requires hematocrit, limiting its applicability in clinical practice. Based on the linear relationship between hematocrit and blood T1 relaxivity, a synthetic ECV could be estimated without a blood sample. We aim to develop and test regression models for synthetic ECV without blood sampling in 1.5-T and 3.0-T scanners. METHODS: A total of 1101 subjects who underwent cardiac magnetic resonance scanning with native and postcontrast T1 mapping and venous hematocrit within 24 hours were retrospectively enrolled. Subjects were randomly split into derivation (n=550) and validation (n=551) subgroups for each scanner. Different regression models were derived controlling for sex, field strength, and left ventricle/right ventricle blood pool and validated in the validation group. We performed additional validation analyses in subgroups of patients with histological validation (n=17), amyloidosis (n=29), anemia (n=185), and reduced ejection fraction (n=322). RESULTS: In the derivation group, 8 specific models and 2 common estimate models were derived. In the validation group, using specific models, synthetic ECV had high agreement with conventional ECV (R2, 0.87; P<0.0001 and R2, 0.88, P<0.0001; -0.16% and -0.10%, left ventricle and right ventricle model, respectively). Common models also performed well (R2, 0.88; P<0.0001 and R2, 0.89, P<0.0001; -0.21% and -0.18%, left ventricle and right ventricle model, respectively). Histological validation demonstrated equal performance of synthetic and measured ECV. Synthetic ECV as calculated by the common model showed a bias in the anemia cohort significantly reduced by the specific model (-2.45 to -1.28, right ventricle common and specific model, respectively). CONCLUSIONS: Synthetic ECV provided a promising way to calculate ECV without blood sampling. Specific models could provide the most accurate value, while common models could be more suitable in routine clinical practice because of their simplicity while maintaining adequate accuracy.

CMR findings after COVID-19 and after COVID-19-vaccination-same but different?

Cardiac involvement has been described in varying proportions of patients recovered from COVID-19 and proposed as a potential cause of prolonged symptoms, often described as post-COVID or long COVID syndrome. Recently, cardiac complications have been reported from COVID-19 vaccines as well. We aimed to compare CMR-findings in patients with clinical cardiac symptoms after COVID-19 and after vaccination. From May 2020 to May 2021, we included 104 patients with suspected cardiac involvement after COVID-19 who received a clinically indicated cardiac magnetic resonance (CMR) examination at a high-volume center. The mean time from first positive PCR to CMR was 112 ± 76 days. During their COVID-19 disease, 21% of patients required hospitalization, 17% supplemental oxygen and 7% mechanical ventilation. In 34 (32.7%) of patients, CMR provided a clinically relevant diagnosis: Isolated pericarditis in 10 (9.6%), %), acute myocarditis (both LLC) in 7 (6.7%), possible myocarditis (one LLC) in 5 (4.8%), ischemia in 4 (3.8%), recent infarction in 2 (1.9%), old infarction in 4 (3.8%), dilated cardiomyopathy in 3 (2.9%), hypertrophic cardiomyopathy in 2 (1.9%), aortic stenosis, pleural tumor and mitral valve prolapse each in 1 (1.0%). Between May 2021 and August 2021, we examined an additional 27 patients with suspected cardiac disease after COVID-19 vaccination. Of these, CMR provided at least one diagnosis in 22 (81.5%): Isolated pericarditis in 4 (14.8%), acute myocarditis in 9 (33.3%), possible myocarditis (acute or subsided) in 6 (22.2%), ischemia in 3 (37.5% out of 8 patients with stress test), isolated pericardial effusion (> 10 mm) and non-compaction-cardiomyopathy each in 1 (3.7%). The number of myocarditis diagnoses after COVID-19 was highly dependent on the stringency of the myocarditis criteria applied. When including only cases of matching edema and LGE and excluding findings in the right ventricular insertion site, the number of cases dropped from 7 to 2 while the number of cases after COVID-19 vaccination remained unchanged at 9. While myocarditis is an overall rare side effect after COVID-19 vaccination, it is currently the leading cause of myocarditis in our institution due to the large number of vaccinations applied over the last months. Contrary to myocarditis after vaccination, LGE and edema in myocarditis after COVID-19 often did not match or were confined to the RV-insertion site. Whether these cases truly represent myocarditis or a different pathological entity is to be determined in further studies.

Relationship Between Quality of Life Indicators and Cardiac Status Indicators in Chemotherapy Patients.

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients. METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value. RESULTS: Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). CONCLUSIONS: Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management.

Fast-Strain Encoded Cardiac Magnetic Resonance During Vasodilator Perfusion Stress Testing.

Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD). Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease. Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain (GLS and GCS and SLS and SCS, respectively), were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as "ischemic." All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint. Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint (death in n = 2, infarction in n = 3 and urgent revascularization in n = 20). Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% (χ2 = 37.8, AUC = 0.79, 95% CI = 0.71-0.87, p < 0.001). In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes (AUCPerf = 0.81 vs. AUCSAS = 0.74, p = NS vs. each other, and χ2 = 30.8, HR = 10.3 and χ2 = 9.5, HR = 3.5, respectively, p < 0.01 for both). Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration.

Impact of Muscle Mass as a Prognostic Factor for Failed Waiting Time Prior to Heart Transplantation.

Objectives: Clinical deterioration during the waiting time impairs the prognosis of patients listed for heart transplantation. Reduced muscle mass increases the risk for mortality after cardiac surgery, but its impact on resilience against deterioration during the waiting time remains unclear. Methods: We retrospectively analyzed data from 93 patients without a VAD who were listed in Eurotransplant status "high urgent (HU)" for heart transplantation between January 2015 and October 2020. The axial muscle area of the erector spinae muscles at the level of thoracic vertebra 12 indexed to body surface area (TMESA/BSA) measured in the preoperative thoracic computed tomography scan was used to measure muscle mass. Results: Forty patients (43%) underwent emergency VAD implantation during the waiting time and four patients (4%) died during the waiting time. The risk of emergency VAD implantation/death during the waiting time decreased by 10% for every cm2/m2 increase in muscle area [OR 0.901 (95% CI: 0.808-0.996); p = 0.049]. After adjusting for gender [OR 0.318 (95% CI: 0.087-1.073); p = 0.072], mean pulmonary artery pressure [OR 1.061 (95% CI: 0.999-1.131); p = 0.060], C-reactive protein [OR 1.352 (95% CI: 0.986-2.027); p = 0.096], and hemoglobin [OR 0.862 (95% CI: 0.618-1.177); p = 0.360], TMESA/BSA [OR 0.815 (95% CI: 0.698-0.936); p = 0.006] remained an independent risk factor for emergency VAD implantation/death during the HU waiting time. Conclusion: Muscle area of the erector spinae muscle appears to be a potential, easily identifiable risk factor for emergency VAD implantation or death in patients on the HU waiting list for heart transplantation. Identifying patients at risk could help optimize the outcome and the timing of VAD support.

Cardiovascular magnetic resonance findings in non-hospitalized paediatric patients after recovery from COVID-19.

AIMS: Our study aimed to investigate the cardiac involvement with sensitive tissue characterization in non-hospitalized children with coronavirus disease 2019 (COVID-19) infection using cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: We prospectively enrolled children who recovered from mildly symptomatic COVID-19 infection between November 2020 and January 2021. Patients underwent CMR at 1.5 T (Achieva, Philips Healthcare, Best, the Netherlands) including cine images, native T1 and T2 mapping. Healthy children and paediatric patients with biopsy-proven myocarditis served as control groups. We performed CMR in 18 children with a median (25th-75th percentile) age of 12 (10-15) years, 38 (24-47) days after positive PCR test, and compared them with 7 healthy controls [15 (10-19) years] and 9 patients with myocarditis [10 (4-16) years]. The COVID-19 patients reported no cardiac symptoms. None of the COVID-19 patients showed CMR findings consistent with a myocarditis. Three patients (17%) from the COVID-19 cohort presented with minimal pericardial effusion. CMR parameters of COVID-19 patients, including volumetric and strain values as well as T1 and T2 times, were not significantly different from healthy controls, but from myocarditis patients. These had significantly reduced left ventricular (LV) ejection fraction (P = 0.035), LV global longitudinal strain, and left atrial strain values as well as elevated native T1 values compared with COVID-19 patients (P < 0.001, respectively). CONCLUSIONS: There was no evidence of myocardial inflammation, fibrosis, or functional cardiac impairment in the studied cohort of children recently. CMR findings were comparable with those of healthy controls. Pericardial effusion suggests a mild pericarditis in a small subgroup. This is pointing to a minor clinical relevance of myocardial involvement in children after mildly symptomatic COVID-19 infections.

Cardiac Magnetic Resonance Reveals Incipient Cardiomyopathy Traits in Adult Patients With Phenylketonuria.

Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age- and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m2 [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m2 [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, -29.9±4.2 % versus -32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m2 [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

Multi-parametric assessment of left ventricular hypertrophy using late gadolinium enhancement, T1 mapping and strain-encoded cardiovascular magnetic resonance.

AIM: To evaluate the ability of single heartbeat fast-strain encoded (SENC) cardiovascular magnetic resonance (CMR) derived myocardial strain to discriminate between different forms of left ventricular (LV) hypertrophy (LVH). METHODS: 314 patients (228 with hypertensive heart disease (HHD), 45 with hypertrophic cardiomyopathy (HCM), 41 with amyloidosis, 22 competitive athletes, and 33 healthy controls) were systematically analysed. LV ejection fraction (LVEF), LV mass index and interventricular septal (IVS) thickness, T1 mapping and atypical late gadolinium enhancement (LGE) were assessed. In addition, the percentage of LV myocardial segments with strain ≤ - 17% (%normal myocardium) was determined. RESULTS: Patients with amyloidosis and HCM exhibited the highest IVS thickness (17.4 ± 3.3 mm and 17.4 ± 6 mm, respectively, p < 0.05 vs. all other groups), whereas patients with amyloidosis showed the highest LV mass index (95.1 ± 20.1 g/m2, p < 0.05 vs all others) and lower LVEF compared to controls (50.5 ± 9.8% vs 59.2 ± 5.5%, p < 0.05). Analysing subjects with mild to moderate hypertrophy (IVS 11-15 mm), %normal myocardium exhibited excellent and high precision, respectively for the differentiation between athletes vs. HCM (sensitivity and specificity = 100%, Area under the curve; AUC%normalmyocardium = 1.0, 95%CI = 0.85-1.0) and athletes vs. HHD (sensitivity = 83%, specificity = 75%, AUC%normalmyocardium = 0.85, 95%CI = 0.78-0.90). Combining %normal myocardial strain with atypical LGE provided high accuracy also for the differentiation of HHD vs. HCM (sensitivity = 82%, specificity = 100%, AUCcombination = 0.92, 95%CI = 0.88-0.95) and HCM vs. amyloidosis (sensitivity = 83%, specificity = 100%, AUCcombination = 0.83, 95%CI = 0.60-0.96). CONCLUSION: Fast-SENC derived myocardial strain is a valuable tool for differentiating between athletes vs. HCM and athletes vs. HHD. Combining strain and LGE data is useful for differentiating between HHD vs. HCM and HCM vs. cardiac amyloidosis.

Multiparametric Early Detection and Prediction of Cardiotoxicity Using Myocardial Strain, T1 and T2 Mapping, and Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years of Follow-Up.

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed. METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures. RESULTS: Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping, P<0.001 for all). In addition, normal myocardium (%) at baseline accurately identified patients with subsequent CTX (P<0.001), which was not achieved by any other markers. CONCLUSIONS: Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228.

Left and right ventricular strain using fast strain-encoded cardiovascular magnetic resonance for the diagnostic classification of patients with chronic non-ischemic heart failure due to dilated, hypertrophic cardiomyopathy or cardiac amyloidosis.

AIMS: To compare the ability of left ventricular (LV) and right ventricular (RV) strain measured by fast-strain encoded cardiovascular magnetic resonance (CMR) (fast-SENC) with LV- and RV-ejection fraction for the diagnostic classification of patients with different stages of chronic heart failure (stages A-D based on American College of Cardiology/American Heart Association guidelines) due to non-ischemic cardiomyopathies. METHODS: Our study population consisted of 276 consecutive patients who underwent CMR for clinical reasons, and 19 healthy subjects. Wall motion score index and non-infarct related late gadolinium enhancement (LGE), LV ejection fraction (LVEF) and RV ejection fraction (RVEF) and global LV- and RV-longitudinal (GLS) and circumferential strain (GCS) based on fast-SENC acquisitions, were calculated in all subjects. The percentage of LV and RV myocardial segments with strain ≤ - 17% (%normal LV and RV myocardium) was determined in all subjects. RESULTS: LVEF and RVEF, LV-GLS, LV-GCS, RV-GLS, RV-GCS and %normal LV- and RV myocardium depressed with increasing heart failure stage (p < 0.001 for all by ANOVA). By multivariable analysis, %normal LV and RV myocardium exhibited closer associations to heart failure stages than LVEF and RVEF (rpartial = 0.79 versus rpartial = 0.21 for %normal LV myocardium versus LVEF and rpartial = 0.64 versus rpartial = 0.20 for %normal RV myocardium versus RVEF, respectively). Furthermore, %normal LV and RV myocardium exhibited incremental value for the identification of patients (i) with subclinical myocardial dysfunction and (ii) with symptomatic heart failure, surpassing that provided by LVEF and RVEF (ΔAUC = 0.22 for LVEF and ΔAUC = 0.19 for RVEF with subclinical dysfunction, and ΔAUC = 0.19 for LVEF and ΔAUC = 0.22 for RVEF with symptomatic heart failure, respectively, p < 0.001 for all). %normal LV myocardium reclassified 11 of 31 (35%) patients judged as having no structural heart disease by clinical and imaging data to stage B, i.e., subclinical LV-dysfunction. CONCLUSIONS: In patients with non-ischemic cardiomyopathy, %normal LV and RV myocardium, by fast-SENC, enables improved identification of asymptomatic patients with subclinical LV-dysfunction. This technique may be useful for the early identification of such presumably healthy subjects at risk for heart failure and for monitoring LV and RV deformation during pharmacologic interventions in future studies.

COVID-19 vs. Classical Myocarditis Associated Myocardial Injury Evaluated by Cardiac Magnetic Resonance and Endomyocardial Biopsy.

Background: Despite the ongoing global pandemic, the impact of COVID-19 on cardiac structure and function is still not completely understood. Myocarditis is a rare but potentially serious complication of other viral infections with variable recovery, and is, in some cases, associated with long-term cardiac remodeling and functional impairment. Aim: To assess myocardial injury in patients who recently recovered from an acute SARS-CoV-2 infection with advanced cardiac magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB). Methods: In total, 32 patients with persistent cardiac symptoms after a COVID-19 infection, 22 patients with acute classic myocarditis not related to COVID-19, and 16 healthy volunteers were included in this study and underwent a comprehensive baseline CMR scan. Of these, 10 patients post COVID-19 and 13 with non-COVID-19 myocarditis underwent a follow-up scan. In 10 of the post-COVID-19 and 15 of the non-COVID-19 patients with myocarditis endomyocardial biopsy (EMB) with histological, immunohistological, and molecular analysis was performed. Results: In total, 10 (31%) patients with COVID-19 showed evidence of myocardial injury, eight (25%) presented with myocardial oedema, eight (25%) exhibited global or regional systolic left ventricular (LV) dysfunction, and nine (28%) exhibited impaired right ventricular (RV) function. However, only three (9%) of COVID-19 patients fulfilled updated CMR-Lake Louise criteria (LLC) for acute myocarditis. Regarding EMB, none of the COVID-19 patients but 87% of the non-COVID-19 patients with myocarditis presented histological findings in keeping with acute or chronic inflammation. COVID-19 patients with severe disease on the WHO scale presented with reduced biventricular longitudinal function, increased RV mass, and longer native T1 times compared with those with only mild or moderate disease. Conclusions: In our cohort, CMR and EMB findings revealed that SARS-CoV-2 infection was associated with relatively mild but variable cardiac involvement. More symptomatic COVID-19 patients and those with higher clinical care demands were more likely to exhibit chronic inflammation and impaired cardiac function compared to patients with milder forms of the disease.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Diagnostic value of cardiovascular magnetic resonance in comparison to endomyocardial biopsy in cardiac amyloidosis: a multi-centre study.

BACKGROUND: Cardiac amyloidosis (CA) is an infiltrative disease characterised by accumulation of amyloid deposits in the extracellular space of the myocardium-comprising transthyretin (ATTR) and light chain (AL) amyloidosis as the most frequent subtypes. Histopathological proof of amyloid deposits by endomyocardial biopsy (EMB) is the gold standard for diagnosis of CA. Cardiovascular magnetic resonance (CMR) allows non-invasive workup of suspected CA. We conducted a multi-centre study to assess the diagnostic value of CMR in comparison to EMB for the diagnosis of CA. METHODS: We studied N = 160 patients characterised by symptoms of heart failure and presence of left ventricular (LV) hypertrophy of unknown origin who presented to specialised cardiomyopathy centres in Germany and underwent further diagnostic workup by both CMR and EMB. If CA was diagnosed, additional subtyping based on EMB specimens and monoclonal protein studies in serum was performed. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as native and post-contrast T1-mapping (in a subgroup)-allowing to measure extracellular volume fraction (ECV) of the myocardium. RESULTS: An EMB-based diagnosis of CA was made in N = 120 patients (CA group) whereas N = 40 patients demonstrated other diagnoses (CONTROL group). In the CA group, N = 114 (95%) patients showed a characteristic pattern of LGE indicative of CA. In the CONTROL group, only 1/40 (2%) patient showed a "false-positive" LGE pattern suggestive of CA. In the CA group, there was no patient with elevated T1-/ECV-values without a characteristic pattern of LGE indicative of CA. LGE-CMR showed a sensitivity of 95% and a specificity of 98% for the diagnosis of CA. The combination of a characteristic LGE pattern indicating CA with unremarkable monoclonal protein studies resulted in the diagnosis of ATTR-CA (confirmed by EMB) with a specificity of 98% [95%-confidence interval (CI) 92-100%] and a positive predictive value (PPV) of 99% (95%-CI 92-100%), respectively. The EMB-associated risk of complications was 3.13% in this study-without any detrimental or persistent complications. CONCLUSION: Non-invasive CMR shows an excellent diagnostic accuracy and yield regarding CA. When combined with monoclonal protein studies, CMR can differentiate ATTR from AL with high accuracy and predictive value. However, invasive EMB remains a safe invasive gold-standard and allows to differentiate CA from other cardiomyopathies that can also cause LV hypertrophy.

Prevalence and prognostic impact of hsCRP elevation are age-dependent in women but not in men undergoing percutaneous coronary intervention.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) predicts outcomes after percutaneous coronary intervention (PCI). OBJECTIVE: We studied the prevalence and prognostic impact of hsCRP elevation according to age in men and women undergoing PCI. METHODS: We included patients undergoing PCI at our center from 2010 until 2017, excluding those with myocardial infarction (MI) on presentation, neoplastic disease and hsCRP >10 mg/L at baseline. Elevated hsCRP was defined as >3 mg/L. The outcome of interest was major adverse cardiac events (MACE) consisting of all-cause death, MI and target vessel revascularization. The association between hsCRP elevation and outcomes was assessed using adjusted Cox models. RESULTS: 10,432 men and 4,345 women were included. Elevation of hsCRP was present in 25.7% of men and 37.0% of women (p < .01). In men, prevalence of hsCRP elevation was stable across age strata (ptrend  = .42). In women, hsCRP elevation was most prevalent in patients <50 years (44.6%) and decreased stepwise with increasing age (ptrend < .001). After stratifying the population into age quartiles (Q1: <59 years, Q2: 59-66 years, Q3: 67-74 years, Q4: ≥75 years), hsCRP elevation was associated with increased risk of MACE across all age groups in men (HR [95% CI] Q1: 1.49 [1.12-1.98]; Q2: 1.51 [1.21-2.06]; Q3: 1.76 [1.27-2.51]; Q4: 1.43[1.03-1.97]). In women, hsCRP elevation was associated with increased risk of MACE only among older patients (HR [95% CI] Q1: 1.08 [0.64-0.82]; Q2: 1.52 [0.93-2.46]; Q3: 1.65 [1.08-2.50]; Q4: 1.52 [1.02-1.28]). CONCLUSION: Among patients undergoing PCI, prevalence and prognostic value of hsCRP elevation were age-dependent exclusively in women.

Cardiac Myxomas Show Elevated Native T1, T2 Relaxation Time and ECV on Parametric CMR.

Introduction: While cardiac tumors are rare, their identification and differentiation has wide clinical implications. Recent cardiac magnetic resonance (CMR) parametric mapping techniques allow for quantitative tissue characterization. Our aim was to examine the range of values encountered in cardiac myxomas in correlation to histological measurements. Methods and Results: Nine patients with histologically proven cardiac myxomas were included. CMR (1.5 Tesla, Philips) including parametric mapping was performed in all patients pre-operatively. All data are reported as mean ± standard deviation. Compared to myocardium, cardiac myxomas demonstrated higher native T1 relaxation times (1,554 ± 192 ms vs. 1,017 ± 58 ms, p < 0.001), ECV (46.9 ± 13.0% vs. 27.1 ± 2.6%, p = 0.001), and T2 relaxation times (209 ± 120 ms vs. 52 ± 3 ms, p = 0.008). Areas with LGE showed higher ECV than areas without (54.3 ± 17.8% vs. 32.7 ± 18.6%, p = 0.042), with differences in native T1 relaxation times (1,644 ± 217 ms vs. 1,482 ± 351 ms, p = 0.291) and T2 relaxation times (356 ± 236 ms vs. 129 ± 68 ms, p = 0.155) not reaching statistical significance. Conclusions: Parametric CMR showed elevated native T1 and T2 relaxation times and ECV values in cardiac myxomas compared to normal myocardium, reflecting an increased interstitial space and fluid content. This might help in the differentiation of cardiac myxomas from other tumor entities.