Extracellular remodeling in patients with wild-type amyloidosis consuming epigallocatechin-3-gallate: preliminary results of T1 mapping by cardiac magnetic resonance imaging in a small single center study.

OBJECTIVES: T1 mapping by cardiac magnetic resonance imaging (CMR) is able to determine the extracellular volume fraction. Wild-type transthyretin amyloidosis (WT-ATTR) is characterized by extracellular amyloid deposition in the heart. Recent reports indicated a reduction of left ventricular (LV) myocardial mass in WT-ATTR after consumption of epigallocatechin-3-gallate, the main catechin in green tea. It remained unclear, whether reduction of LV myocardial mass reflects decrease of amyloid load or progressive atrophy of cardiomyocytes. METHODS: This study included 7 male patients with CMR repetitively performed before and 12 months after daily consumption of green tea extract (600 mg epigallocatechin-3-gallate). Short axis slices as well as 2-, 3-, and 4-chamber views were acquired using SSFP sequences. T1 mapping was created out of 11 mid-ventricular short axis views with increasing inversion times using a single breath-hold modified look-locker inversion recovery sequence before and 15 min after Gadolinium contrast administration. RESULTS: After 12 months, a significant decrease of LV myocardial mass [198 (160; 212) vs. 180 (142; 204) g; p < 0.05] was observed. Moreover, a significant decrease of native [T1 1110 (1072; 1150) ms vs. 1080 (970; 1101), p < 0.05 or p = 0.03] was noticed. The calculated extracellular volume decreased in 5 patients (62.5%) by 7% and increased in 2 patients (37.5%) by 9.5%, in trend resulting in a (not significant) decrease of median ECV by 2.4%. Left ventricular ejection fraction (LVEF) [57 (48; 65) vs. 55 (47; 64) %; p = 0.3] remained unchanged. CONCLUSIONS: This study provided further evidence of LV myocardial mass reduction in patients with WT-ATTR daily consuming green tea extract. Additionally, this study gave first insights into the histomorphological correlate of LV mass reduction using T1 mapping. LV mass reduction appeared to be rather due to a decrease of amyloid load than atrophy of cardiomyocytes.

Green tea halts progression of cardiac transthyretin amyloidosis: an observational report.

BACKGROUND: Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy. METHODS: 19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months. RESULTS: Five patients were not followed up for reasons of death (n = 2), discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (-12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p < 0.01) and LDL cholesterol (105.8 ± 7.6 vs. 89.5 ± 8.0 mg/dL; p < 0.01) decreased significantly during the observational period. No serious adverse effects were reported by any of the participants. CONCLUSIONS: Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation.

Multicentre evaluation of a new point-of-care test for the determination of CK-MB in whole blood.

BACKGROUND: The point-of-care (POC) test Roche CARDIAC CK-MB is a new assay which has been developed for the existing Roche Cardiac reader system. METHODS: We performed a multicentre evaluation at six sites to assess the analytical performance of the POC CK-MB assay and to compare it with a quantitative laboratory CK-MB assay. RESULTS: Within-series coefficients of variation (CV) resulting from 34 ten-fold measurements with patient samples ranged from 4.3% to 16.4%. Using quality control material, the mean CV values for day-to-day imprecision were 6.5% for the low level control and 8.4% for the high level control. Based upon 847 pairs of values, the mean relative bias of three independently calibrated lots of the POC CK-MB assay ranged from -6% to -11% in method comparisons with the lab CK-MB assay. The mean relative lot-to-lot differences of POC CK-MB were between -2% and +1%. No interference was observed with lipaemic blood (triglyceride concentrations up to 8.1 mmol/L), icteric blood (bilirubin concentrations up to 513 micromol/L), haemolytic blood (haemoglobin concentrations up to 0.12 mmol/L), biotin (up to 30 mg/L) and rheumatoid factor (up to 119 IU/mL), or with 53 standard or cardiological drugs even in toxic concentrations. There was no influence on the results by varying haematocrit values in the range from 21% to 54%. A slight interference with human anti-mouse antibodies type 2 was found. No significant influence on the results with POC CK-MB was found by using sample volumes between 135 and 165 microL. High CK-MB concentrations above the measuring range of POC CK-MB (1-40 microg/L) did not lead to false low results due to potential high-dose hook effect. No significant effect of sample age on recovery occurred up to a sample age of 24 h. No cross-reactivity was found between the POC CK-MB assay and either CK-MM or CK-BB. A substudy with healthy individuals confirmed the reference limits of 3.8 microg/L for females and 6.7 microg/L for males. CONCLUSIONS: The POC CK-MB assay showed a very good analytical performance with an excellent concordance with the calibration and reference laboratory method. It should be therefore suitable for its intended use in POC settings. Clin Chem Lab Med 2008;46:630-8.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS: We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS: 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION: Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Very early cardiac magnetic resonance imaging for quantification of myocardial tissue perfusion in patients receiving tirofiban before percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND: Assessment of myocardial blood flow is important for identification and monitoring of microvascular effects of glycoprotein IIb/IIIa inhibitors. Magnetic resonance imaging is a novel noninvasive method providing complementary information on myocardial blood flow and cardiac function. METHODS AND RESULTS: Patients (n = 53) admitted within 12 (mean, 5.8) hours after onset of symptoms were randomized to tirofiban or standard therapy before primary percutaneous coronary intervention (PCI) with stenting. Myocardial blood flow was graded by measurement of corrected Thrombolysis in Myocardial Infarction frame counts and by semiquantitative analysis of signal intensity curves from first-pass contrast-enhanced magnetic resonance perfusion. Pretreatment with tirofiban proved safe and resulted in a significantly lower corrected Thrombolysis in Myocardial Infarction frame counts (21 vs 34, P = .008) indicating improved myocardial blood flow. Magnetic resonance imaging revealed higher normalized peak signal intensities (2.19 vs 1.63, P = .046) and a trend to steeper upslopes (0.79 vs 0.48, P = .1). Cardiac left ventricular wall motion analysis resulted in a significantly lower number of myocardial segments with abnormal wall thickening (6.4 vs 8.5, P = .025). CONCLUSIONS: Pretreatment with tirofiban appears safe and improves myocardial flow after primary PCI with stenting. Magnetic resonance imaging proved useful as a complementary method for noninvasive assessment of myocardial blood flow and cardiac function in patients with ST-segment elevation myocardial infarction undergoing primary PCI.