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.

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.

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.

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.

Objectives and background: The aim of the study was to evaluate the long-term effects of tafamidis on cardiac disease progression beyond 12 months of treatment by performing (among others) serial multi-parametric cardiovascular magnetic resonance (CMR) studies in patients with transthyretin (ATTR) cardiac amyloidosis (CA) cardiomyopathy (ATTR-CM). Methods: Patients with confirmed ATTR-CM ( N = 56) were divided into two groups: in the larger group A ( N = 39; 95% male), treatment with tafamidis 61 mg once daily was initiated after the first CMR study, whereas group B ( N = 17; 76% male) comprised ATTR-CM patients who did not receive tafamidis. The observational follow-up period lasted 27 ± 6 months. During this period, patients underwent two multi-parametric CMR studies at our institution as part of a routine clinical observation pipeline. Results: Clinical symptoms assessed by the NYHA class showed a slight, however, significant increase in both groups. NT-proBNP levels substantially increased in both groups at follow-up, however, with a significantly higher increase in the tafamidis-naïve group B ( p = 0.014). LV systolic function, defined by LV-EF and 3D global longitudinal peak strain, significantly worsened in both groups at follow-up (54% to 48% p < 0.001 vs 56% to 46%, p < 0.001; −7.4 to −5.3, p < 0.001 vs −8.8 to −4.8, p < 0.001). However, the tafamidis-naïve group B experienced a substantially higher impairment of both parameters when compared to group A (∆p = 0.008 and ∆p = 0.003, respectively). LV wall thickness considerably increased in both groups at follow-up, however, with a significantly higher increase in the tafamidis-naïve group B (from 18.2 mm to 21.1 mm at follow-up, p < 0.001) compared to the tafamidis-treated group A (from 18.5 mm to 19.2 mm, p = 0.012; ∆ p < 0.001). Both global native T1 and global ECV values were significantly elevated in both groups—at baseline and at follow-up—with a significant increase in both groups during follow-up. However, a substantially higher increase in global ECV was observed in the tafamidis-naïve group B compared to the tafamidis-treated group A (group A: 51% to 57%, p < 0.001; group B: 50% to 67%, p < 0.001; ∆p < 0.001). Conclusion: Substantial worsening of clinical symptoms, serum biomarkers, and imaging parameters occurred in both tafamidis-treated and tafamidis-naïve ATTR-CM patients within a follow-up period of approximately 2 years. However, the “extent of worsening” is significantly lower in the tafamidis-treated compared to the tafamidis-naïve patients. Graphical