Intense 68 Ga-OncoFAP Uptake as a New Promising Diagnostic Biomarker in Cardiac Sarcoidosis.

ABSTRACT: A 72-year-old man revealed typical findings of cardiac sarcoidosis on cardiovascular MRI. However, 18 F-FDG PET showed no hypermetabolism. Therefore, immunosuppression was not initiated. After 2 years, ventricular arrhythmias and heart failure worsened. 68 Ga-fibroblast activation protein inhibitor PET was initiated to evaluate potential adverse remodeling due to progressive myocardial fibrosis. A second 18 F-FDG PET still revealed no hypermetabolism, and the patient received an implanted cardioverter defibrillator after electrophysiological risk stratification. We present a case of intense fibroblast activation despite a missing 18 F-FDG uptake (mismatch).

Validation of the PRAETORIAN score in a large subcutaneous implantable cardioverter-defibrillator collective: Usefulness in clinical routine.

BACKGROUND: To assess the risk of unsuccessful conversion of ventricular fibrillation during defibrillation testing (DFT) with the subcutaneous implantable cardioverter-defibrillator (S-ICD), the PRAETORIAN score has been proposed. OBJECTIVE: The purpose of this study was to validate the PRAETORIAN score in a large S-ICD collective. METHODS: A retrospective single-center analysis of S-ICD patients receiving intraoperative DFT was performed. DFT was performed using a stepwise protocol with 65-J standard polarity, change of polarity, increase to 80 J, and repositioning if necessary. If all DFTs failed, we switched to a transvenous ICD. RESULTS: Overall, 398 patients were analyzed (268 male [67.3%]; mean age 42.4 ± 15.9 years; mean body mass index [BMI] 25.9 ± 4.8 kg/m2). Successful DFT with the first ICD shock was observed in 264 patients (66.3%). One hundred fourteen patients were defibrillated with the second (n = 104) or third (n = 10) DFT after changing shock polarity and/or shock energy. Overall, 20 patients needed at least 3 DFT (ie, 80 J and/or re-positioning). The majority (n = 88 [65.7%]) of DFT failures occurred before 2015 with the first-generation S-ICD. PRAETORIAN score was an independent predictor of DFT failure (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.003-1.011 P ≤.001), while whereas BMI alone was not (P = .31). Presence of hypertrophic cardiomyopathy (HCM) (OR 2.6; 95% CI 1.3-4.4; P = .004) was predictive for at least 1 unsuccessful DFT in our multivariate regression analysis. CONCLUSION: PRAETORIAN score proved to be a useful and valid predictive tool for successful DFT, whereas BMI only had a limited role. Patients with HCM were at increased risk for DFT failure or needed higher DFT energy.

Cardiac Sarcoidosis-Diagnostic and Therapeutic Challenges.

Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials.

The new European Society of Cardiology guideline for the management of cardiomyopathies: key messages for cardiac electrophysiologists.

Electrocardiographic findings and arrhythmias are common in cardiomyopathies. Both may be an early indication of a specific diagnosis or may occur due to myocardial fibrosis and/or reduced contractility. Brady- and tachyarrhythmias significantly contribute to increased morbidity and mortality in patients with cardiomyopathies. Antiarrhythmic therapy including risk stratification is often challenging and plays a major role for these patients. Thus, an "electrophysiological" perspective on guidelines on cardiomyopathies may be warranted. As the European Society of Cardiology (ESC) has recently published a new guideline for the management of cardiomyopathies, this overview aims to present key messages of these guidelines. Innovations include a new phenotype-based classification system with emphasis on a multimodal imaging approach for diagnosis and risk stratification. The guideline includes detailed chapters on dilated and hypertrophic cardiomyopathy and their phenocopies, arrhythmogenic right ventricular cardiomyopathy, and restrictive cardiomyopathy as well as syndromic and metabolic cardiomyopathies. Patient pathways guide clinicians from the initial presentation to diagnosis. The role of cardiovascular magnetic resonance imaging and genetic testing during diagnostic work-up is stressed. Concepts of rhythm and rate control for atrial fibrillation have led to new recommendations, and the role of defibrillator therapy in primary prevention is discussed in detail. Whilst providing general guidelines for management, the primary objective of the guideline is to ascertain the disease etiology and disease-specific, individualized management.

Therapeutic value of tafamidis in patients with wild-type transthyretin amyloidosis (ATTRwt) with cardiomyopathy based on cardiovascular magnetic resonance (CMR) imaging.

OBJECTIVES: The purpose of this study was to carefully analyse the therapeutic benefit of tafamidis in patients with wild-type transthyretin amyloidosis (ATTRwt) and cardiomyopathy (ATTRwt-CM) after one year of therapy based on serial multi-parametric cardiovascular magnetic resonance (CMR) imaging. BACKGROUND: Non-sponsored data based on multi-parametric CMR regarding the effect of tafamidis on the cardiac phenotype of patients with ATTRwt-CM are not available so far. METHODS: The present study comprised N = 40 patients with ATTRwt-CM who underwent two serial multi-parametric CMR studies within a follow-up period of 12 ± 3 months. Baseline (BL) clinical parameters, serum biomarkers and CMR findings were compared to follow-up (FU) values in patients treated "with" tafamidis 61 mg daily (n = 20, group A) and those "without" tafamidis therapy (n = 20, group B). CMR studies were performed on a 1.5-T system and comprised cine-imaging, pre- and post-contrast T1-mapping and additional calculation of extracellular volume fraction (ECV) values. RESULTS: While left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi), left ventricular wall thickness (LVWT), native T1- and ECV values remained unchanged in the tafamidis group A, a slight reduction in LV-EF (p = 0.003) as well as a subtle increase in LVMi (p = 0.034), in LVWT (p = 0.001), in native T1- (p = 0.038) and ECV-values (p = 0.017) were observed in the untreated group B. Serum NT-proBNP levels showed an overall increase in both groups, however, with the untreated group B showing a relatively higher increase compared to the treated group A. Assessment of NYHA class did not result in significant intra-group differences when BL were compared with FU, but a trend to improvement in the treated group A compared to a worsening trend in the untreated group B (∆p = 0.005). CONCLUSION: As expected, tafamidis does not improve cardiac phenotype in patients with ATTRwt-CM after one year of therapy. However, tafamidis seems to slow down cardiac disease progression in patients with ATTRwt-CM compared to those without tafamidis therapy based on multi-parametric CMR data already after one year of therapy.

Predictors for major in-hospital complications after catheter ablation of ventricular arrhythmias: validation and modification of the Risk in Ventricular Ablation (RIVA) Score.

OBJECTIVE AND BACKGROUND: Catheter-based treatment of patients with ventricular arrhythmias (VA) reduces VA and mortality in selected patients. With regard to potential risks of catheter ablation, a benefit-risk assessment should be carried out. This can be performed with risk scores such as the recently published "Risk in Ventricular Ablation (RIVA) Score". We sought to validate this score and to test for possible additional predictors in a large database of VT ablations. METHODS AND RESULTS: We analyzed 1964 catheter ablations for VA in patients with (1069; 54.4%) and without (893, 45.6%) structural heart disease (SHD) and observed an overall major adverse event rate of 4.0% with an in-hospital mortality of 1.3% with significantly less complications occurring in patients without structural heart disease (6.5% vs. 1.1%; p ≤ 0.01). The RIVA Score demonstrated to be a valid predictive tool for major in-hospital complications (OR 1.18; 95% CI 1.12, 1.25; p ≤ 0.001). NYHA Class ≥ III (OR 2.5; 95% CI 1.5, 4.2; p < 0.001) and age (OR 1.04; 95% CI 1.02, 1.07; p ≤ 0.001) proved to be additional predictive parameters. Hence, a modified RIVA Score (mRIVA) model was analyzed with a subset of established predictors (SHD, eGFR, epicardial puncture) as well as new predictive parameters (age, NYHA Class ≥ III), that achieved a higher predictive value for major complications compared with the model based on all RIVA variables. CONCLUSION: Adding age and functional heart failure status (NYHA class) as simple clinical parameters to the recently published RIVA Score increases the predictive value for ablation-associated complications in a large VT ablations registry.

Serial Cardiovascular Magnetic Resonance Studies Prior to and After mRNA-Based COVID-19 Booster Vaccination to Assess Booster-Associated Cardiac Effects.

Background: mRNA-based COVID-19 vaccination is associated with rare but sometimes serious cases of acute peri-/myocarditis. It is still not well known whether a 3rd booster-vaccination is also associated with functional and/or structural changes regarding cardiac status. The aim of this study was to assess the possible occurrence of peri-/myocarditis in healthy volunteers and to analyze subclinical changes in functional and/or structural cardiac parameters following a mRNA-based booster-vaccination. Methods and Results: Healthy volunteers aged 18-50 years (n = 41; m = 23, f = 18) were enrolled for a CMR-based serial screening before and after 3rd booster-vaccination at a single center in Germany. Each study visit comprised a multi-parametric CMR scan, blood analyses with cardiac markers, markers of inflammation and SARS-CoV-2-IgG antibody titers, resting ECGs and a questionnaire regarding clinical symptoms. CMR examinations were performed before (median 3 days) and after (median 6 days) 3rd booster-vaccination. There was no significant change in cardiac parameters, CRP or D-dimer after vaccination, but a significant rise in the SARS-CoV-2-IgG titer (p < 0.001), with a significantly higher increase in females compared to males (p = 0.044). No changes regarding CMR parameters including global native T1- and T2-mapping values of the myocardium were observed. A single case of a vaccination-associated mild pericardial inflammation was detected by T2-weighted CMR images. Conclusion: There were no functional or structural changes in the myocardium after booster-vaccination in our cohort of 41 healthy subjects. However, subclinical pericarditis was observed in one case and could only be depicted by multiparametric CMR.

A compartment-based myocardial density approach helps to solve the native T1 vs. ECV paradox in cardiac amyloidosis.

Cardiovascular magnetic resonance (CMR) plays an important clinical role for diagnosis and therapy monitoring of cardiac amyloidosis (CA). Previous data suggested a lower native T1 value in spite of a higher LV mass and higher extracellular volume fraction (ECV) value in wild-type transthyretin amyloidosis (ATTRwt) compared to light-chain amyloidosis (AL)-resulting in the still unsolved "native T1 vs. ECV paradox" in CA. The purpose of this study was to address this paradox. The present study comprised N = 90 patients with ATTRwt and N = 30 patients with AL who underwent multi-parametric CMR studies prior to any specific treatment. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as T2-mapping and pre-/post-contrast T1-mapping allowing to measure myocardial ECV. Left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi) and left ventricular wall thickness (LVWT) were significantly higher in ATTRwt in comparison to AL. Indexed ECV (ECVi) was also higher in ATTRwt (p = 0.041 for global and p = 0.001 for basal septal). In contrast, native T1- [1094 ms (1069-1127 ms) in ATTRwt vs. 1,122 ms (1076-1160 ms) in AL group, p = 0.040] and T2-values [57 ms (55-60 ms) vs. 60 ms (57-64 ms); p = 0.001] were higher in AL. Considering particularities in myocardial density, "total extracellular mass" (TECM) was substantially higher in ATTRwt whereas "total intracellular mass" (TICM) was rather similar between ATTRwt and AL. Consequently, the "ratio TICM/TECM" was lower in ATTRwt compared to AL (0.58 vs. 0.83; p = 0.007). Our data confirm the presence of a "native T1 vs. ECV paradox" with lower native T1 values in spite of higher myocardial mass and ECV in ATTRwt compared to AL. Importantly, this observation can be explained by particularities regarding myocardial density that result in a lower TICM/TECM "ratio" in case of ATTRwt compared to AL-since native T1 is determined by this ratio.

CMR-based T1-mapping offers superior diagnostic value compared to longitudinal strain-based assessment of relative apical sparing in cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative disease. In the present study, we compared the diagnostic accuracy of cardiovascular magnetic resonance (CMR)-based T1-mapping and subsequent extracellular volume fraction (ECV) measurement and longitudinal strain analysis in the same patients with (a) biopsy-proven cardiac amyloidosis (CA) and (b) hypertrophic cardiomyopathy (HCM). N = 30 patients with CA, N = 20 patients with HCM and N = 15 healthy control patients without relevant cardiac disease underwent dedicated CMR studies. The CMR protocol included standard sequences for cine-imaging, native and post-contrast T1-mapping and late-gadolinium-enhancement. ECV measurements were based on pre- and post-contrast T1-mapping images. Feature-tracking analysis was used to calculate 3D left ventricular longitudinal strain (LV-LS) in basal, mid and apical short-axis cine-images and to assess the presence of relative apical sparing. Receiver-operating-characteristic analysis revealed an area-under-the-curve regarding the differentiation of CA from HCM of 0.984 for native T1-mapping (p < 0.001), of 0.985 for ECV (p < 0.001) and only 0.740 for the "apical-to-(basal + midventricular)"-ratio of LV-LS (p = 0.012). A multivariable logistical regression analysis showed that ECV was the only statistically significant predictor of CA when compared to the parameter LV-LS or to the parameter "apical-to-(basal + midventricular)" LV-RLS-ratio. Native T1-mapping and ECV measurement are both superior to longitudinal strain measurement (with assessment of relative apical sparing) regarding the appropriate diagnosis of CA.

Diagnostic value of the novel CMR parameter "myocardial transit-time" (MyoTT) for the assessment of microvascular changes in cardiac amyloidosis and hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is present in various non-ischemic cardiomyopathies and in particular in those with left-ventricular hypertrophy. This study evaluated the diagnostic value of the novel cardiovascular magnetic resonance (CMR) parameter "myocardial transit-time" (MyoTT) in distinguishing cardiac amyloidosis from other hypertrophic cardiomyopathies. METHODS: N = 20 patients with biopsy-proven cardiac amyloidosis (CA), N = 20 patients with known hypertrophic cardiomyopathy (HCM), and N = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion acquisitions at rest for MyoTT measurement. MyoTT was defined as the blood circulation time from the orifice of the coronary arteries to the pooling in the coronary sinus (CS) reflecting the transit-time of gadolinium in the myocardial microvasculature. RESULTS: MyoTT was significantly prolonged in patients with CA compared to both groups: 14.8 ± 4.1 s in CA vs. 12.2 ± 2.5 s in HCM (p = 0.043) vs. 7.2 ± 2.6 s in controls (p < 0.001). Native T1 and extracellular volume (ECV) were significantly higher in CA compared to HCM and controls (p < 0.001). Both parameters were associated with a higher diagnostic accuracy in predicting the presence of CA compared to MyoTT: area under the curve (AUC) for native T1 = 0.93 (95% confidence interval (CI) = 0.83-1.00; p < 0.001) and AUC for ECV = 0.95 (95% CI = 0.88-1.00; p < 0.001)-compared to the AUC for MyoTT = 0.76 (95% CI = 0.60-0.92; p = 0.008). In contrast, MyoTT performed better than all other CMR parameters in differentiating HCM from controls (AUC for MyoTT = 0.93; 95% CI = 0.81-1.00; p = 0.003 vs. AUC for native T1 = 0.69; 95% CI = 0.44-0.93; p = 0.20 vs. AUC for ECV = 0.85; 95% CI = 0.66-1.00; p = 0.017). CONCLUSION: The relative severity of CMD (measured by MyoTT) in relationship to extracellular changes (measured by native T1 and/or ECV) is more pronounced in HCM compared to CA-in spite of a higher absolute MyoTT value in CA patients. Hence, MyoTT may improve our understanding of the interplay between extracellular/intracellular and intravasal changes that occur in the myocardium during the disease course of different cardiomyopathies.

"Myocardial transit-time" (MyoTT): a novel and easy-to-perform CMR parameter to assess microvascular disease.

BACKGROUND: Myocardial microvascular disease may occur during the disease course of different cardiac as well as systemic disorders. With the present study, we introduce a novel and easy-to-perform cardiovascular magnetic resonance (CMR) parameter named "myocardial transit-time" (MyoTT). METHODS: N = 20 patients with known hypertrophic cardiomyopathy (HCM) and N = 20 control patients without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as first-pass perfusion acquisitions at rest for MyoTT measurement. MyoTT was defined as the blood circulation time from the orifice of the coronary arteries to the pooling in the coronary sinus (CS), and accordingly measured as the temporal difference between the appearances of CMR contrast agent in the aortic root and the CS reflecting the transit-time of gadolinium in the myocardial microvasculature. RESULTS: Patients with HCM had a significantly prolonged MyoTT compared to controls (11.0 (9.1-14.5) s vs. 6.5 (4.8-8.4) s, p < 0.001). This significant difference did not change when the individual heart rate was taken into consideration (MyoTT indexed, p < 0.001). Significant correlations were found between MyoTT and maximal left ventricular (LV) wall thickness (r = 0.771, p < 0.001), MyoTT and presence of LGE (r = 0.760, p < 0.001) as well as MyoTT and LV global longitudinal strain (r = 0.672, p < 0.001). ROC analysis resulted in an area-under-curve (AUC) of 0.90 for MyoTT and showed an optimal sensitivity/specificity cut-off of 7.85 s to differentiate HCM from controls. CONCLUSION: "Myocardial transit-time" is a novel and easy-to-perform CMR parameter that allows a quick assessment of the extent of myocardial microvascular disease. This novel CMR parameter may open new vistas in the assessment of microvascular disease-not only in HCM patients. Future studies will show the usefulness and clinical relevance of this novel CMR parameter.

Introduction of a CMR-conditional cardiac phantom simulating cardiac anatomy and function and enabling training of interventional CMR procedures.

Interventional magnetic resonance imaging (MRI) procedures promise to open-up new vistas regarding clinically relevant diagnostic and/or therapeutic procedures in the field of cardiology. However, a number of major limitations and challenges regarding interventional cardiovascular magnetic resonance (CMR) procedures still delay their translation from pre-clinical studies to human application. A CMR-conditional cardiac phantom was constructed using MR-safe or -conditional materials only that is based on a unique modular composition allowing quick replacement of individual components. A maximal flow of 76 ml/sec in the aorta and 111 ml/sec in the pulmonary artery were measured, whereas the maximal flow velocity was 56 cm/sec and 89 cm/sec, respectively. A conventional wedge-pressure catheter was advanced over a MRI-conditional guidewire into the right ventricle and thereafter positioned in the pulmonary artery. Pulmonary artery pressure was measured, obtaining the following values for our cardiac phantom: max/min/mean = 16/10/12 mmHg. The presented CMR-conditional cardiac phantom is the first of its kind that does not only mimic cardiac mechanics with adjustable fluid pressure in a four chamber setup that is closely adapted to that of the human heart, but also enables introduction and testing of interventional tools such as guidewires and catheters.