Nuclear cardiology at the door of a new era: better to save mSv or to reduce imaging time?

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Myocardial blood flow regulation in infarcted patients with stress-induced normalization of negative T waves

The correlation of stress-induced normalization of negative T waves (NTW) with regional myocardial blood flow (MBF) regulation and tissue viability remains still dented

Wild-type transthyretin cardiac amyloidosis is not rare in elderly subjects: the CATCH screening study

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. Objective: We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. Methods: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity-troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Results: Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP <300 ng/L. The prevalence of ATTR-CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). Conclusions: ATTRwt-CA is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease

Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning

Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.We thank FPLD2 patients for donating biological samples. We thank the Italian Network for Laminopathies and the European Consortium of Lipodystrophies (ECLip) for support and helpful discussion. We thank Aurelio Valmori for the technical support. The studies were supported by Rizzoli Orthopedic Institute “5 per mille” 2014 project to MC, AIProSaB project 2016 and Fondazione Del Monte di Bologna e Ravenna grant 2015–2016 “New pharmacological approaches in bone laminopathies based on the use of antibodies neutralizing TGF beta 2” to GL. GL is also supported by PRIN MIUR project 2015FBNB5Y.S

Nuclear medicine techniques for the diagnosis of cardiac amyloidosis: the state of the art

Amyloidosis is a disease characterized by the deposition of amorphous protein material in the extracellular space which leads to progressive dysfunction of the affected organ. The forms of amyloidosis that most frequently involve the heart are transthyretin amyloidosis (ATTR) and immunoglobulin light chain amyloidosis (AL). Nuclear medicine offers numerous imaging techniques for the evaluation of patients with cardiac amyloidosis, and in the last decade osteophilic tracer scintigraphy has assumed a fundamental role in the diagnostic process of this disease. New PET radiopharmaceuticals for the detection of amyloid deposits are proving very effective in diagnosing the presence of AL amyloidosis and could soon allow a differential diagnosis without the need for invasive and potentially risky techniques such as endomyocardial biopsy

Comparison Between Ultrafast and Standard Single-Photon Emission CT in Patients With Coronary Artery Disease

Background— A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results— A total of 34 patients underwent single-day 99m Tc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT ( P =0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease ( P =0.003) versus S-SPECT. Conclusions— This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease

Stress-induced alteration of left ventricular eccentricity: An additional marker of multivessel CAD

BackgroundAbnormal left ventricular (LV) eccentricity index (EI) is a marker of adverse cardiac remodeling. However, the interaction between stress-induced alterations of EI and major cardiac parameters has not been explored. We sought to evaluate the relationship between LV EI and coronary artery disease (CAD) burden in patients submitted to myocardial perfusion imaging (MPI).Methods and resultsThree-hundred and forty-three patients underwent MPI and coronary angiography. LV ejection fraction (EF) and EI were computed from gated stress images as measures of stress-induced functional impairment.One-hundred and thirty-six (40%), 122 (35%), and 85 (25%) patients had normal coronary arteries, single-vessel CAD, and multivessel CAD, respectively. Post-stress EI was lower in patients with multivessel CAD than in those with normal coronary arteries and single-vessel CAD (P=0.001). This relationship was confirmed only in patients undergoing exercise stress test, where a lower post-stress EI predicted the presence of multivessel CAD (P=0.039).ConclusionsPost-stress alterations of LV EI on MPI may unmask the presence of multivessel CAD