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1.
Lancet Digit Health ; 6(4): e251-e260, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519153

RESUMO

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.


Assuntos
Amiloidose , Cardiomiopatias , Humanos , Amiloidose/diagnóstico por imagem , Amiloidose/metabolismo , Inteligência Artificial , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/metabolismo , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos , Estudos Retrospectivos
2.
Life (Basel) ; 14(1)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276275

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system. METHODS: We aimed to investigate the effect of ICI on arterial 2-[18F]FDG uptake by using 2-[18F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[18F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[18F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy. RESULTS: ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[18F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[18F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[18F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers. CONCLUSIONS: ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation.

3.
Amyloid ; 31(1): 42-51, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37599395

RESUMO

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.


Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Humanos , Qualidade de Vida , Compostos de Organotecnécio , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/genética , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/genética , Miocárdio
4.
Cancers (Basel) ; 15(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067379

RESUMO

In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients' sensitivity to antibody drugs. Several PET tracers, diverse from 2-[18F]FDG (or 2-Deoxy-2-[18F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells.

5.
Cancers (Basel) ; 15(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38136430

RESUMO

Receptor tyrosine kinases, or RTKs, are one large family of cell surface receptors involved in signal transduction, which represent an integral part of the signaling pathways. They play a crucial role in most important cellular processes, starting with the cell cycle, proliferation and differentiation, as well as cell migration, metabolism and survival. The introduction of ImmunoPET evaluating the expression of RTKs by specific monoclonal antibodies (mAbs) or antibody fragments is regarded as a promising tool for imaging treatment efficacy and developing anticancer therapeutics. Our review focuses mainly on the current clinical research regarding ImmunoPET targeting RTKs, with particular interest in the epidermal growth factor family, or HER family, and vascular endothelial-derived growth factor/receptor.

6.
Front Cardiovasc Med ; 10: 1168360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37608818

RESUMO

Primary pulmonary artery hypertension (PAH) is a clinical diagnosis that requires the exclusion of other underlying causes of pulmonary hypertension (PH). Increased pulmonary artery (PA) pressure and subsequent right ventricular (RV) pressure overload often result in a flattening of the curved interventricular septum, leading to a D-shaped left ventricle (LV), as observed in echocardiographic short-axis views. A similar finding may be also observed on myocardial perfusion SPECT images, the so-called Movahed's sign. We present a clinical case of a female patient with PAH and progression of exertional dyspnea that underwent myocardial perfusion SPECT to investigate LV myocardial ischemia. The SPECT images revealed enhanced tracer uptake in the dilated right ventricle. Additionally, we observed a D-shaped LV or Movahed's sign, which may serve as a potential marker of RV pressure overload, along with a small stress-induced perfusion defect on the LV septal wall. Our findings highlight the importance of considering the presence of a D-shaped LV and signs of RV pressure overload, as they can alter the interpretation of LV perfusion deficits on SPECT images. This case report aims to emphasize the complex nature of right heart abnormalities in pathologies such as PAH and the consideration of the RV implications in myocardial SPECT images-which typically focus solely on the LV.

9.
Biology (Basel) ; 11(10)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36290299

RESUMO

Cardiac amyloidosis (CA) is a heterogeneous group of diseases in which extracellular insoluble amyloid proteins are deposited in specific organs and tissues locally or systemically, thereby interfering with physiological function. Transthyretin protein (TTR) and light chain (AL) amyloidosis are the most common types of cardiac amyloidosis. Radionuclide bone scintigraphy has recently become the most common non-invasive test for the diagnosis of TTR-CA but is of limited value for the diagnosis of AL-CA. PET has proved promising for the diagnosis of CA and its applications are expected to expand in the future. This review summarizes the current bone scintigraphy and amyloid-targeting Positron emission tomography (PET) imaging, the binding imaging properties of radiotracers, and the values of diagnosis, prognosis, and monitoring therapy response in CA.

10.
Life (Basel) ; 12(8)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36013396

RESUMO

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) imaging with 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG) is a sensitive diagnostic imaging modality in oncology and could be a useful diagnostic tool in patients with fever of unknown origin (FUO) or with inflammation of unknown origin (IUO). CASE PRESENTATION: We report a case of a patient originally presenting with a clinical history of FUO and later with persistent high-sensitivity C-reactive protein (hsCRP) levels, even after antibiotic therapy. The patient underwent 2-[18F]FDG PET/CT to investigate and to localize a possible focus of infection or inflammation. 2-[18F]FDG hotspots were detected in both thyroid lobes. Thyroid diagnostic examinations and follow up were performed. Subacute thyroiditis (SAT) was then diagnosed by thyroid examinations, and other possible causes of FUO or IUO were not found. CONCLUSION: This case illustrates the potential diagnostic value of 2-[18F]FDG PET/CT in patients with atypical SAT, who originally present with only a clinical history of FUO.

11.
JACC Cardiovasc Interv ; 15(17): 1748-1758, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36008266

RESUMO

BACKGROUND: Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking. OBJECTIVES: This study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR. METHODS: Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints. RESULTS: A total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1). CONCLUSIONS: Dual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.


Assuntos
Amiloidose , Insuficiência da Valva Mitral , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico por imagem , Amiloidose/terapia , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Masculino , Insuficiência da Valva Mitral/diagnóstico , Resultado do Tratamento
12.
Life (Basel) ; 12(7)2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35888127

RESUMO

(1) This study compared [68Ga]PentixaFor uptake in active arterial segments with corresponding [18F]FDG arterial uptake as well as the relationship with cardiac [68Ga]PentixaFor uptake. (2) Method: Tracer uptake on atherosclerotic lesions in the large arteries was measured and target-to-background ratios (TBR) were calculated to adjust background signals with two investigators blinded to the other PET scan. On a patient-based and lesion-to-lesion analysis, TBR values of two tracers were compared and the relationship with cardiac inflammation was further explored. Furthermore, two cardiovascular risk-related groups were divided to explore the value of risk stratification of the two tracers in atherosclerosis. (3) Results: [68Ga]PentixaFor PET/MRI identified more lesions (88% vs. 48%; p < 0.001) and showed higher uptake than [18F]FDG PET/MRI (TBR, 1.90 ± 0.36 vs. 1.63 ± 0.29; p < 0.001). In the patient-based analysis, the TBR of [68Ga]PentixaFor uptake was also significantly higher than [18F]FDG uptake (1.85 ± 0.20 vs. 1.42 ± 0.19; p < 0.001). The TBR of active lesions for [68Ga]PentixaFor was significantly increased in the high-risk group (n = 9), as compared to the low-risk group (n = 10) (2.02 ± 0.15 vs. 1.86 ± 0.10, p = 0.015), but not for [18F]FDG (1.85 ± 0.10 vs. 1.80 ± 0.07, p = 0.149). (4) Conclusion: [68Ga]PentixaFor PET/MRI identified many more lesions than [18F]FDG PET/MRI. Patients with high-risk cardiovascular factors illustrated an increased uptake of [68Ga]PentixaFor. There was a correlation between the elevated uptake of [68Ga]PentixaFor in the active arterial segments and heart.

13.
Circ Cardiovasc Imaging ; 15(7): e014115, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35861981

RESUMO

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.


Assuntos
Neuropatias Amiloides Familiares , Estenose da Valva Aórtica , Cardiomiopatias , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico por imagem , Neuropatias Amiloides Familiares/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Cardiomiopatias/complicações , Feminino , Humanos , Masculino , Pré-Albumina , Resultado do Tratamento
14.
J Nucl Med ; 63(12): 1906-1911, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35710734

RESUMO

The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Consecutive all-comers undergoing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic-acid (99mTc-DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade 1 was defined as low-grade uptake and grade 2 or 3 as confirmed CA. All-cause mortality, cardiovascular death, and heart failure hospitalization (HHF) served as endpoints. Results: In total, 17,387 scans from 11,527 subjects (age, 61 ± 16 y; 63.0% women, 73.6% cancer) were analyzed. Prevalence of 99mTc-DPD positivity was 3.3% (n = 376/11,527; grade 1: 1.8%, grade 2 or 3: 1.5%), and was higher among cardiac than noncardiac referrals (18.2% vs. 1.7%). In individuals with more than 1 scan, progression from grade 1 to grade 2 or 3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade 1 than grade 2 or 3 (73.3% vs. 15.4%). After a median of 6 y, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive 99mTc-DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade 0, mortality: adjusted hazard ratio [AHR] 1.46 [95% CI 1.12-1.90]; cardiovascular death: AHR 2.34 [95% CI 1.49-3.68]; HHF: AHR 2.25 [95% CI 1.51-3.37]). One-year mortality was substantially higher in cancer than noncancer patients. Among noncancer patients, also grade 1 had worse outcomes than grade 0 (HHF/death: AHR 1.45 [95% CI 1.01-2.09]), presumably because of longer observation and higher prognostic impact of early infiltration. Conclusion: Positive 99mTc-DPD was identified in a substantial number of consecutive 99mTc-DPD referrals and associated with adverse outcomes.


Assuntos
Amiloidose , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Prevalência , Amiloidose/diagnóstico por imagem , Cintilografia , Encaminhamento e Consulta
15.
J Nucl Cardiol ; 29(4): 1946-1951, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35112308

RESUMO

BACKGROUND: Among the other variants, the apical pattern of hypertrophic cardiomyopathy (AHCM) is probably the most important, with possible aneurysmatic evolution. METHODS AND RESULTS: We analyzed 12 patients with AHCM who underwent [13N]NH3-PET/CT. Regional perfusion, stress global myocardial blood flow (MBF), and transmural perfusion patterns were assessed. To evaluate the LV-MBF distribution, we compared the apex with septum and infero-lateral wall. Furthermore, global stress MBF distribution in AHCM patients was compared with a reference septal HCM cohort. Visual regional perfusion analysis demonstrated an apical hypoperfusion in 10 of 12 patients, without correlation with the stress MBF of the whole LV. Significant differences among stress MBF in apical, in septal, and in the infero-lateral walls were recorded (P < .02). The transmural analysis showed a significant difference among the three segment groups for epicardial (P < .003) as well for endocardial MBF (P < .005). In the post hoc analysis, the apical MBF was significantly lower than in septal and infero-lateral walls in epicardium (P < .005) and significantly lower than the infero-lateral MBF in endocardium (P < .001). CONCLUSION: In patients with AHCM, more severe apical microvascular impairment was found as compared to patients with classical septal HCM, supporting the suspicion that ischemia could play a role in the future aneurysmatic evolution of AHCM.


Assuntos
Cardiomiopatia Hipertrófica , Imagem de Perfusão do Miocárdio , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Circulação Coronária/fisiologia , Humanos , Pericárdio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons
17.
Biology (Basel) ; 10(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34827199

RESUMO

Background: Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. Methods: We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUVmax) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. Results: ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, p < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, p < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. Conclusions: Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.

19.
J Nucl Cardiol ; 27(5): 1665-1674, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-30238298

RESUMO

BACKGROUND: This study examined whether measuring myocardial blood flow (MBF) in the sub-endocardial (SEN) and sub-epicardial (SEP) layers of the left ventricular myocardium using 13NH3 positron emission tomography (PET) and an automated procedure gives reasonable results in patients with known or suspected coronary artery disease (CAD). METHODS: Resting and stress 13NH3 dynamic PET were performed in 70 patients. Using ≥ 70% diameter stenosis in invasive coronary angiography (ICA) to identify significant CAD, we examined the diagnostic value of SEN- and SEP-MBF, and coronary flow reserve (CFR) vs. the corresponding conventional data averaged on the whole wall thickness. RESULTS: ICA demonstrated 36 patients with significant CAD. Their global stress average [1.61 (1.26, 1.87) mL·min-1·g-1], SEN [1.39 (1.2, 1.59) mL·min-1·g-1] and SEP [1.22 (0.96, 1.44) mL·min-1·g-1] MBF were significantly lower than in the 34 no-CAD patients: 2.05 (1.76, 2.52), 1.72 (1.53, 1.89) and 1.46 (1.23, 1.89) mL·min-1·g-1, respectively, all P < .005. In the 60 CAD vs. the 150 non-CAD territories, stress average MBF was 1.52 (1.10, 1.83) vs. 2.06 (1.69, 2.48) mL·min-1·g-1, SEN-MBF 1.33 (1.02, 1.58) vs. 1.66 (1.35, 1.93) mL·min-1·g-1, and SEP-MBF 1.07 (0.80, 1.29) vs. 1.40 (1.12, 1.69) mL·min-1·g-1, respectively, all P < .05. Using receiver operating characteristics analysis for the presence of significant CAD, the areas under the curve (AUC) were all significant (P < .0001 vs. AUC = 0.5) and similar: stress average MBF = 0.79, SEN-MBF = 0.75, and SEP-MBF = 0.73. AUC was 0.77 for the average CFR, 0.75 for SEN, and 0.70 for SEP CFR. The stress transmural perfusion gradient (TPG) AUC (0.51) was not significant. However, stress TPG was significantly lower in segments subtended by totally occluded arteries vs. those subtended by sub-total stenoses: 1.10 (0.86, 1.33) vs. 1.24 (0.98, 1.56), respectively, P < .005. CONCLUSION: Automatic assessment of SEN- and SEP-MBF (and CFR) using 13NH3 PET gives reasonable results that are in good agreement with the conventional average whole wall thickness data. Further studies are needed to examine the utility of layer measurements such as in patients with hibernating myocardium or microvascular disease.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária/fisiologia , Tomografia por Emissão de Pósitrons , Idoso , Doença da Artéria Coronariana/fisiopatologia , Feminino , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Radioisótopos de Nitrogênio , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
20.
Eur J Nucl Med Mol Imaging ; 45(4): 530-537, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29196789

RESUMO

PURPOSE: Primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) aims to achieve myocardial salvage (MS). Because the reference method for measuring MS requires myocardial perfusion imaging (MPI) after tracer injection before PCI, alternative approaches have been proposed, but none has gained wide acceptance. Gated SPECT MPI can assess infarct size (IS), but can also show myocardial stunning. Thus, we compared functional and perfusion abnormalities early after AMI to estimate MS, and to predict left ventricular ejection fraction (LVEF) recovery at follow-up. METHODS: We studied 120 patients with AMI. Gated SPECT MPI was performed early (before hospital discharge) and at 6 months after AMI to measure IS, MS and functional outcome. MS was defined as the difference between the number of segments with abnormal thickening (i.e. the stunned area or area at risk) and the number of segments with abnormal perfusion (i.e. the final IS), expressed as a percentage of the total number of segments in the AHA model. LVEF was calculated using quantitative gated SPECT. RESULTS: The area at risk was 40 ± 25%, IS was 17.3 ± 16% and MS was 22 ± 19%. Early LVEF was 46.6 ± 11.6% and late LVEF was 51.4 ± 11.6%, with 54 patients showing at least an increase in LVEF of more than 5 units. ROC analysis showed that MS was able to predict LVEF recovery with an area under the curve (AUC) of 0.79 (p < 0.0001), and using a cut off >23% detected LVEF recovery with 74% sensitivity and 71% specificity. Conversely, IS was associated with an AUC 0.53 (not significant). CONCLUSION: MS assessed by a single early gated SPECT MPI study can accurately predict LVEF evolution after primary PCI for AMI.


Assuntos
Infarto do Miocárdio/diagnóstico por imagem , Intervenção Coronária Percutânea , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Miocárdio , Volume Sistólico , Função Ventricular Esquerda
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