Cardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac ...amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients.
The authors sought to develop and validate a deep learning–based model that automatically detects significant cardiac uptake (Perugini grade ≥2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis.
The model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set.
The training data set consisted of 3,048 images: 281 positives (Perugini grade ≥2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age <90 years, body mass index, injection-acquisition delay, radionuclides, and the indication of WBS only slightly affected performances.
The authors’ detection model is effective at identifying patients with cardiac uptake Perugini grade ≥2 on WBS and may help in the diagnosis of patients with cardiac amyloidosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Reply: Deep Learning on Bone Scintigraphy Delbarre, Marc-Antoine; Girardon, François; Damy, Thibaud
JACC. Cardiovascular imaging,
August 2023, 2023-08-00, 20230801, Volume:
16, Issue:
8
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: We assesse the evolution and prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (cTnT-HS) in transthyretin amyloid cardiomyopathy ...(ATTR-CA) before and after tafamidis treatment. Methods and Results: 454 ATTR-CA patients without tafamidis (Cohort A) and 248 ATTR-CA with tafamidis (Cohort B) were enrolled. Event-free survival (EFS) events were death, heart transplant, or acute heart failure. In Cohort A, 27% of patients maintained NT-proBNP < 3000 ng/L and 14% cTnT-HS < 50 ng/L at 12 months relative to baseline levels. In Cohort B, the proportions were 49% and 29%, respectively. In Cohort A, among the 333 patients without an increased NT-proBNP > 50% relative to baseline EFS was extended compared to the 121 patients with an increased NT-proBNP > 50% (HR: 0.75 0.57; 0.98; p = 0.032). In Cohort A, baseline NT-proBNP > 3000 ng/L and cTnT-HS > 50 ng/L and a relative increase of NT-proBNP > 50% during follow-up were independent prognostic factors of EFS. The slopes of logs NT-proBNP and cTnT-HS increased with time before and stabilized after tafamidis. Conclusion: ATTR-CA patients with increasing NT-proBNP had an increased risk of EFS. Tafamidis stabilize NT-proBNP and cTnT-HS increasing, even if initial NT-proBNP levels were >3000 ng/L. Thus suggesting that all patients, irrespective of baseline NT-proBNP levels, may benefit from tafamidis.
Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific ...rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors. 2-2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110β with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure–activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.
Aims
Iron deficiency (ID) is common in patient with chronic heart failure (HF) and has been widely studied. In contrast, data concerning ID in cardiac amyloidosis (CA) are limited. Amyloidosis is a ...severe and fatal systemic disease, characterized by an accumulation of amyloid fibrils in various tissues/organs, including nerves, kidneys, gastrointestinal tract, and heart. Amyloid deposits in the heart eventually cause HF. The main subtypes of CA are light chain (AL), hereditary transthyretin (ATTRv), and wild‐type transthyretin (ATTRwt). We performed this study to determine the prevalence, clinical outcome (all‐cause mortality), and determinants of ID among the three main subtypes of CA.
Methods and results
Iron deficiency status were analysed in 816 CA patients enrolled at the French Referral Centre for Cardiac Amyloidosis: 271 (33%) had AL, 164 (20%) ATTRv, and 381 (47%) ATTRwt. ID affected 49% of CA patients, 45% with AL, 58% with ATTRv, and 48% with ATTRwt. We identified ATTR status (ATTRv P = 0.003, ATTRwt P = 0.037), diabetes (P = 0.003), aspirin treatment (P = 0.009), haemoglobin levels (P = 0.006), and altered global longitudinal strain (P = 0.02) as independent ID determinants. There is no difference in all‐cause mortality considering ID status.
Conclusions
Iron deficiency is common in patients with CA, irrespective of the subtype. Patients seem more likely to have ID if diagnosed with ATTR, if diabetic, and/or treated with aspirin. In CA, the benefit of intravenous iron therapy, for ID, on morbidity and mortality needs further study.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Dyspnoea is a common persistent symptom after COVID-19. Whether it is associated with functional respiratory disorders remains unclear.
We assessed the proportion and characteristics of patients with ..."functional respiratory complaints" (FRCs) (as defined by Nijmegen Questionnaire >22) among 177 post-COVID-19 individuals who benefited from outclinic evaluation in the COMEBAC study (
, symptomatic and/or intensive care unit (ICU) survivors at 4 months). In a distinct explanatory cohort of 21 consecutive individuals with unexplained post-COVID-19 dyspnoea after routine tests, we also analysed the physiological responses to incremental cardiopulmonary exercise testing (CPET).
In the COMEBAC cohort, 37 patients had significant FRCs (20.9%, IC95: 14.9-26.9). The prevalence of FRCs ranged from 7.2% (ICU patients) to 37.5% (non-ICU patients). The presence of FRCs was significantly associated with more severe dyspnoea, lower 6-min walk distance, more frequent psychological and neurological symptoms (cognitive complaint, anxiety, depression, insomnia and post-traumatic stress disorders) and poorer quality of life (all p<0.01). In the explanatory cohort, seven out of 21 patients had significant FRCs. Based on CPET, dysfunctional breathing was identified in 12 out of 21 patients, five out of 21 had normal CPET, three out of 21 had deconditioning and one out of 21 had evidence of uncontrolled cardiovascular disease.
FRCs are common during post-COVID-19 follow-up, especially among patients with unexplained dyspnoea. Diagnosis of dysfunctional breathing should be considered in those cases.
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