Fabian aus dem Siepen

Green tea extract as a treatment for patients with wild-type transthyretin amyloidosis: an observational study

Background Causative treatment of patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is lacking. Recent reports indicate the potential use of epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, to inhibit amyloid fibril formation. We sought to investigate changes of cardiac function and morphology in patients with wtATTR-CM after consumption of green tea extract (GTE). Methods Twenty-five male patients (71 [64; 80] years) with wtATTR-CM were submitted to clinical examination, echocardiography, cardiac magnetic resonance imaging (cMRI) (n=14), and laboratory testing before and after daily consumption of GTE capsules containing 600 mg epigallocatechin-3-gallate for at least 12 months. Results A significant decrease of left ventricular (LV) myocardial mass by 6% (196 [100; 247] vs 180 [85; 237] g; P=0.03) by cMRI and total cholesterol by 8.4% (191 [118; 267] vs 173 [106; 287] mg/dL; P=0.006) was observed after a 1-year period of GTE consumption. LV ejection fraction by cMRI (53% [33%; 69%] vs 54% [28%; 71%]; P=0.75), LV wall thickness (17 [13; 21] vs 18 [14; 25] mm; P=0.1), and mitral annular plane systolic excursion (10 [5; 23] vs 8 [4; 13] mm; P=0.3) by echocardiography remained unchanged. Conclusion This study supports LV mass stabilization in patients with wtATTR-CM consuming GTE potentially indicating amyloid fibril reduction.

Standardized assessment of global longitudinal and circumferential strain - a modality independent software approach

Mean GLS values were -16.2±5.3% and -17.3±5.3% for echocardiography and CMR, respectively. GLS did not differ significantly between the two imaging modalities, which showed strong correlation (r=0.86), a small bias (-1.1%) and narrow 95% limits of agreement (LOA, ±5.4%). Mean GCS values were -17.9±6.3% and -24.4 ±7.8% for echocardiography and CMR, respectively. GCS was significantly underestimated by echocardiography (p<0.001). A weaker correlation (r=0.73), a higher bias (-6.5%) and wider LOA (±10.5%) were observed for GCS. GLS showed a strong correlation (r=0.92) when image quality was good, while correlation dropped to r=0.82 with poor acoustic windows in echocardiography. GCS assessment revealed only a strong correlation (r=0.87) when echocardiographic image quality was good. No significant differences for GLS between two different echocardiographic vendors could be detected. Conclusions Quantitative assessment of GLS using a standardized software algorithm allows the direct comparison of values acquired irrespective of the imaging modality. GLS may therefore serve as a reliable parameter for the assessment of global left ventricular function in clinical routine besides standard evaluation of the ejection fraction.

Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies

Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental information beyond LV EF and the presence of myocardial fibrosis.

The prognostic value of right ventricular long axis strain in non-ischaemic dilated cardiomyopathies using standard cardiac magnetic resonance imaging

ObjectiveTo investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM).MethodsIn 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences.ResultsThe primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below −10% (log-rank, p < 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (>45%, n = 213) reduced RV-LAS was still associated with poor outcome.ConclusionAssessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters.Key points• Impaired right ventricular longitudinal function (RV-LAS) is associated with poorer cardiac outcomes.• Poor outcome is associated with decreased RV-LAS even in patients with RVEF >45%.• Addition of RV-LAS to known risk factors enhances the power prognostic information.

Myocardial contraction fraction derived from cardiovascular magnetic resonance cine images—reference values and performance in patients with heart failure and left ventricular hypertrophy

Aims Left ventricular hypertrophy (LVH) has strong prognostic implications and is associated with heart failure. Recently, myocardial contraction fraction (MCF) was identified as a useful marker for specifically identifying cardiac amyloidosis (CA). The purpose of this study was to evaluate the diagnostic accuracy of MCF for the discrimination of different forms of LVH. Methods and results We analysed cardiovascular magnetic resonance (CMR) scans of patients with CA (n = 132), hypertrophic cardiomyopathy (HCM, n = 60), hypertensive heart disease (HHD, n = 38) and in 100 age- and gender-matched healthy controls. MCF was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume. The diagnostic accuracy of MCF was compared to that of LV ejection fraction (EF) and the mass index (MI). Compared with controls (136.3 ± 24.4%, P < 0.05), mean values for MCF were significantly reduced in LVH (HHD:92.6 ± 20%, HCM:80 ± 20.3%, transthyretin CA:74.9 ± 32.2% and light-chain (AL) CA:50.5 ± 21.4%). MCF performed better than LVEF (AUC = 0.96 vs. AUC = 0.6, P < 0.001) and was comparable to LVMI (AUC = 0.95, P = 0.4) in discriminating LVH from controls. There was a significant yet weak correlation between MCF and LVEF (r = 0.43, P < 0.0001). MCF outperformed LVEF and LVMI in discriminating between different etiologies of LVH and between AL and other forms of LVH (AUC = 0.84, P < 0.0001). Moreover, cut-off values for MCF <50% and LVEF <60% allowed to identify patients with high probability for CA. Conclusion In patients with heart failure MCF discriminates CA from other forms of LVH. As it can easily be derived from standard, non-contrast cine images, it may be a very useful marker in the diagnostic workup of patients with LVH.

Assessment of myocardial strain in patients with myocarditis by cardiac magnetic resonance imaging

Background Myocarditis is associated with a considerable morbidity and mortality in the acute phase as well as in the long term. It is found in up to 12% of young adults with sudden cardiac death and is regarded as a cause of dilated cardiomyopathy which is currently the most frequent reason for heart transplantation. Therefore, techniques for the diagnosis and the assessment of prognosis are of great interest. In this study we evaluate the novel post-procession feature tracking imaging (FTI) algorithm for strain analysis on patients with myocarditis. Methods We retrospectively included 36 patients (31 male, 5 female) who were admitted with acute myocarditis. A control group (31 male, 5 female) was drawn from a reference population of proven healthy volunteers and was matched with regard to age and gender. CMR imaging was performed on a 1.5 T whole-body MRI (Achieva, Philips Healthcare). Short axis views covering both ventricles as well as 2-, 3- and 4-chamber views were obtained using a SSFP sequence. Enddiastolic and endsystolic volumes as well as ejection fraction (EF) were derived from short axis segmentation. In addition we measured the circumferential und longitudinal strain applying a post-procession FTI algorithm (TomTec Imaging Systems). Results The study population and the control group showed similar characteristics regarding age and gender (40.3 ± 13.7 yrs. vs. 40.3 ± 15.7 yrs., p > 0.99). In patients with myocarditis the EF was significantly reduced compared to healthy controls (54.3 ± 8.4% vs. 67.8 ± 5.3%, p < 0.001). Furthermore the patients showed significantly lower values for the global circumferential strain (-24.4 ± 4.2% vs. -28.8 ± 3.8%, p < 0.001) as well as for the global longitudinal strain (-17.7 ± 4.5% vs. -23.6 ± 3.0%, p < 0.001). Global circumferential strain (r = -0.77, p < 0.001) and global longitudinal strain (r = -0.65, p < 0.001) correlated well with EF. In the subgroup of myocarditis patients with preserved ejection fraction (EF≥55%, 16 pts.) the global longitudinal strain (-20.4 ± 4.5% vs. -23.7 ± 2.6%, p < 0.05) was significantly reduced compared to the age- and gender matched control subgroup whereas the global circumferential strain did not show a significant difference (-27.3 ± 2.7% vs. -28.9 ± 3.8%, p = n.s.). Conclusions FTI strain analysis offers a fast quantitative assessment of myocardial strain patterns without the need for additional dedicated strain imaging sequences. Myocarditis patients with preserved EF show reduced longitudinal strain whereas the circumferential strain is not significantly

Extracellular volume assessed by CMR T1-mapping correlates with histologically determined amount of diffuse fibrosis in DCM

Background Diffuse myocardial fibrosis (MF) in dilated cardiomyopathy (DCM) is closely related to systolic and diastolic cardiac failure and could be identified as a major independent value prediciting clinical outcome. It results from elevated levels of collagen and is therefore associated with an expansion of the extracellular volume (ECV). Up to now, the detection of MF requires myocardial biopsy. Recent reports indicate that CMR T1-Mapping has the potential to detect MF non-invasively. We compared the ECV values derived from T1-mapping with the collagen volume fraction (CVF) as meausured in histological samples. Methods All CMR examinations were performed in a 1.5 T CMR scanner (Achieva, Philips Healthcare). Short axis slices covering the left ventricle were acquired using SSFPsequences to measure volumes and ejection fraction. T1- relaxation times were measured from 24 patients (54 ± 13 years,16 males) with DCM before and 15 minutes after injection of gadolinium-DTPA contrast agent (Magnevist, 0.2 mmol/kg body weight). T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times (TI; 100-4400 msec.) using a single breathhold modified Look-Locker inversion-recovery sequence (MOLLI, TR/TE = 3.5/1.8 msec, flip angle = 35°) in late diastole. The formula for calculating the extracellular volume fractions is given in Figure 1. Myocardial biopsies were taken and stained with Acid Fuchsin Orange-G (AFOG). Tissue collagen content was quantified histologically by using an automated image analysis system and correlated with ECV measurements. Results The DCM patients had a mean left ventricular ejection fraction (LVEF) of 39 ± 16%. Average ECV fraction was 27 ± 4% and CVF was 19 ± 4% in our study population. There was a strong correlation between ECV and CVF (r = 0.85; p = 0.01, Figure 2). Patients with severe

Non-invasive risk stratification of patients with TTR amyloidosis

Methods 30 patients (21 male, 9 female; median age 69.5 years) with diagnosis of TTR amyloidosis (wild-type n=13, hereditary n=17) were evaluated by cardiac MRI (CMR; Achieva Intera Philips Medical Systems, Best, The Netherlands), and Technetium-DPD scintigraphy. EDV, ESV, EF and myocardial mass were analyzed on a standard workstation (Philips Viewforum). Longitudinal function was assessed by mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursion. Atrial septum thickness was measured on SSFP-4 chamber views. Gadolinium contrast-enhanced CMR (CE-CMR) was assessed semi-quantitatively (absent=0, weak=1, moderate=2, severe=3) in an AHA modified 16 segment model of the left ventricle as well as for the right/left atrium and right ventricle. Nuclear DPDretention was assessed semi-quantitatively using a region of interest technique by comparison of counts in the heart at 3 hours after injection with whole body counts at 5 min after injection.

Wild-type transthyretin amyloidosis in female patients

Results Comparison of clinical findings between males and females affected by wt-ATTR amyloidosis are shown in table 1. Female patients with wt-ATTR did not differ from male patients regarding demographic or clinical parameters except for modified body mass index (1140±184 vs. 1029±154, p<0.05), glomerular filtration rate (66±23 vs. 85±31 ml/min*m*1.73; p<0.05), NYHA class (2.4±0.7 vs. 2.9±0.3; p<0.01) and PQ interval (211±50 ms vs. 170±26; p<0.01). Interestingly, both groups especially did not differ in age at onset of symptoms, but longer delay between start of symptoms and diagnosis of wt-ATTR in females was observed when compared to male patients with wt-ATTR. In total, 6 deaths (35%) occurred in females and 45 deaths (24%) in males. No gender differences were observed regarding mean survival (females 54±35 month, males 56±107 months). By multivariate analysis independent predictors of mortality in the whole cohort were use of diuretics (HR 8.657, 95%CI 1.160-64.17; p=0.035) and hs-TnT (HR 1.009, 95%CI 1.004-1.015; p=0.001). In total, 6 deaths (35%) occurred in females and 45 deaths (24%) in males. No gender differences were observed regarding mean survival (females 54±35 month, males 56±107 months). By multivariate analysis independent predictors of mortality in the whole cohort were use of diuretics (HR 8.657, 95%CI 1.160-64.17; p=0.035) and hs-TnT (HR 1.009, 95%CI 1.004-1.015; p=0.001).

T1 mapping: useful for treatment monitoring in patients with senile systemic amyloidosis?

Background Recent reports indicate that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is potent to inhibit fibril formation of several amyloidogenic proteins in vitro. In vivo studies revealed reduction of left ventricular myocardial mass (LVM) after 12 months of daily consumption of 450 mg EGCG. However, the underlying process of LVM reduction, either due to reduction of amyloid or due to atrophy of cardiomyocytes, remained unknown. T1-mapping has the potential to monitor the extent of the extracellular volume (ECV). We sought to investigate the use of T1 mapping for monitoring of treatment effects in a cohort of patients with senile systemic amyloidosis (SSA) treated with EGCG for 12 months. Methods CMR examinations were performed in 8 patients (70 ± 8 years, 7 males) with histologically proven SSA before and 12 months after daily consumption of 450 mg EGCG using a 1.5 T CMR scanner (Achieva, Philips Healthcare). Short axis slices were acquired using SSFPsequences to measure left ventricular volumes, ejection fraction (EF) and LVM. T1-maps were created out of 11 mid-ventricular short axis views with increasing inversion times (TI; 100-4400 msec) using a single breathhold modified Look-Locker inversion-recovery sequence (MOLLI, TR/TE = 3,5/1,8 msec, flip angle = 35°) in late diastole before and 15 minutes after injection of gadolinium-DTPA contrast agent (0.2 mmol/kg body weight). ECV was calculated using the formula given in Figure 1. Results After 12 months of EGCG consumption a significant decrease of LVM (-14.5 ± 12.9 g, p < 0.05, Figure 2) was observed. Moreover, a significant decrease of native T1 (-63.3 ± 64.1 ms, p < 0.05, Figure 2) was noticed. There was no significant change in ECV and EF. Conclusions