Quantitative 99mTc-DPD-SPECT/CT assessment of cardiac amyloidosis.

INTRODUCTION: Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring. METHODS AND MATERIALS: 136 patients received 99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest. RESULTS: Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%. CONCLUSION: We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.

Epicardial fat and incident heart failure with preserved ejection fraction in patients with coronary artery disease.

BACKGROUND: We aimed to determine, whether epicardial adipose tissue (EAT) as local source of inflammation, as well as its change over time, associates with the development of heart failure with preserved ejection fraction (HFpEF) in patients with coronary artery disease. METHODS AND RESULTS: We retrospectively included 379patients (aged 65.2 ± 11.7 years, 70.2%male) with coronary artery disease but without heart failure at baseline, undergoing clinical and echocardiographic assessment in 2010-2013 and receiving a second assessment in 2014-2018. EAT thickness was defined as space between the myocardium and the pericardium and indexed (EATi) by body surface area. Change in EATi was calculated as the difference of follow-up and baseline EATi. HFpEF was defined according to presence of dyspnea, elevated natriuretic peptides, and structural and/or functional alterations on echocardiography in accordance with current European Society of Cardiology guidelines. During a median follow-up of 4.3 years, 142patients (37.5%) developed HFpEF. Patients with onset of HFpEF had higher EATi at baseline (2.4 ± 1.3 vs. 1.9 ± 0.9 mm/m2, p = 0.001). In multivariable regression analysis, EATi associated with onset of HFpEF (1.25 [1.01-1.54], p = 0.04). Likewise, an increase in EATi over time was linked HFpEF development, independent of other risk factors and baseline EATi (1.39 [1.04-1.87], p = 0.03). EATi was significantly associated with follow-up b-type natriuretic peptide (BNP) levels (4.31[0.58-8.05], p = 0.024), but not with baseline BNP (2.24[-0.27-4.76], p = 0.08). CONCLUSION: EATi is associated with the development of HFpEF. The finding of changes in EATi altering the risk of HFpEF manifestation support the rationale for further research on epicardial fat modulation as a treatment target for HFpEF.

Impact of dietary nitrate on age-related diastolic dysfunction.

AIMS: Diastolic dysfunction is highly prevalent, and ageing is the main contributor due to impairments in active cardiac relaxation, ventriculo-vascular stiffening, and endothelial dysfunction. Nitric oxide (NO) affects cardiovascular functions, and NO bioavailability is critically reduced with ageing. Whether replenishment of NO deficiency with dietary inorganic nitrate would offer a novel approach to reverse age-related cardiovascular alterations was not known. METHODS AND RESULTS: A dietary nitrate supplementation was applied to young (6 month) and old (20 month) wild-type mice for 8 weeks and compared with controls. High-resolution ultrasound, pressure-volume catheter techniques, and isolated heart measurements were applied to assess cardiac diastolic and vascular functions. Cardiac manganese-enhanced magnetic resonance imaging was performed to study the effects of dietary nitrate on myocyte calcium handling. In aged mice with preserved systolic function, dietary nitrate supplementation improved LV diastolic function, arterial compliance, and coronary flow reserve. Mechanistically, improved cardiovascular functions were associated with an accelerated cardiomyocyte calcium handling and augmented NO/cyclic guanosine monophosphate/protein kinase G signalling, while enhanced nitrate reduction was related to age-related differences in the oral microbiome. CONCLUSION: Dietary inorganic nitrate reverses age-related LV diastolic dysfunction and improves vascular functions. Our results highlight the potential of a dietary approach in the therapy of age-related cardiovascular alterations.