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INTRODUCTION: The Phase 3 APOLLO-B study evaluates patisiran in patients (pts) with transthyretin (ATTR) cardiac amyloidosis over a 12-month (M) double-blind (DB) period, followed by an open-label extension (OLE) period when all pts receive patisiran (NCT03997383). Hypothesis: Patisiran provides long-term benefit in pts with ATTR cardiac amyloidosis. Aims: Describe safety and efficacy of patisiran during the APOLLO-B OLE (18M+). METHODS: Pts (18-85 yrs) with ATTR cardiac amyloidosis and heart failure history were randomized 1:1 to patisiran or placebo (pbo). Pts completing DB period were eligible to receive patisiran in the OLE for ≤36M. Results summarized based on DB treatment arm. Exploratory assessments include change from study baseline (CFB) in 6-minute walk test (6MWT), KCCQ-OS, NT-proBNP, and troponin I. RESULTS: In the DB period, 359 pts (pbo n=178; patisiran n=181) received study drug (median [range] age, 76.0 [41, 85] yrs; male, 89%; wtATTR, 80%; tafamidis at baseline, 25%); 334 (93%) entered the OLE. In patisiran arm, M12 and M18 results, respectively, were similar for each endpoint: 6MWT and KCCQ-OS (mean [SEM] CFB) −8.09 [5.73] vs −9.21 [6.04] meters (m) and 0.60 [1.36] vs 0.22 [1.48]; NT-proBNP and troponin I (geometric mean fold-CFB [95%CI]) 1.10 [1.03, 1.17] vs 1.17 [1.07, 1.27] and 1.11 [1.05, 1.18] vs 1.09 [1.01, 1.17]). In pbo arm, patisiran initiation in OLE was associated with a slower rate of worsening or relative stability across endpoints; CFB at M12 vs M18, respectively: 6MWT, −25.43 [5.61] vs −31.08 [5.45] m; KCCQ-OS, −3.41 [1.33] vs −4.02 [1.49]; NT-proBNP, 1.39 [1.28, 1.51] vs 1.53 [1.38, 1.71]; and troponin I, 1.29 [1.21, 1.38] vs 1.21 [1.13, 1.30]. Patisiran had an acceptable safety profile; no new concerns. OLE analyses are ongoing; updated data to be presented. CONCLUSIONS: The M18 results provide evidence that beneficial effects observed in DB period on functional capacity, health status, and quality of life were maintained by continued treatment with patisiran during the OLE. Pbo-treated pts initiating patisiran at M12 showed slowed worsening or stabilization in most endpoints at M18. Early treatment initiation is important: pbo-treated pts did not recover functional capacity or health lost prior to initiating OLE patisiran.
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PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Terapia de Ressincronização Cardíaca/métodos , Estudos Prospectivos , Teorema de Bayes , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Eletrocardiografia , Aprendizado de Máquina , Resultado do TratamentoRESUMO
BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.
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Disfunção Ventricular Esquerda , Estudos de Coortes , Humanos , Perfusão , Estudos Prospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
PURPOSE: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response. METHODS: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR). RESULTS: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01). CONCLUSION: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Hipertensão , Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Humanos , Hipertensão/complicações , Razão de Chances , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period. MATERIAL & METHODS: Left ventricular diastolic dyssynchrony was assessed by GMP-SPECT at baseline and after CRT procedure in 160 subjects from 10 different cardiological centers. CRT procedure was performed as per current guidelines. Outcomes were defined as improvement in ≥1 New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) by 5%, and reduction in end-systolic volume (ESV) by 15% and 5% points in Minnesota Living with Heart Failure Questionnaire. LVDD was defined as diastolic phase standard deviation ≥40 ± 14°. RESULTS: Improvement in NYHA functional class occurred in 105 (65.6%), LVEF in 74 (46.3%), decrease in ESV in 86 (53.8%), and Minnesota score in 85 (53.1%) cases. Baseline LV diastolic standard deviation was 53.53° ± 20.85 and at follow-up 40.44° ± 26.1283; (P < 0.001). LVDD was not associated with improvement in clinical outcomes at follow-up. CONCLUSION: CRT improves both systolic and diastolic dyssynchrony values at 6-month follow-up. LVDD at baseline is correlated with cardiac functionality at follow-up, but not with overall favorable clinical outcomes.
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Terapia de Ressincronização Cardíaca , Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca , Imagem de Perfusão do Miocárdio , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Diástole , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/terapiaRESUMO
BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.
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Terapia de Ressincronização Cardíaca , Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Imagem de Perfusão do Miocárdio , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
BACKGROUND: Glomerular filtration rate (GFR) is usually estimated from equations using serum creatinine (sCr), with adjustment for gender, age, and race (black or nonblack). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is the preferred equation for adults, but it was validated for the United States population. We intended to evaluate if the race-ethnicity adjustment proposed for the sCr-based CKD-EPI equations is appropriate for the Brazilian population. METHODS: CKD outpatients had blood samples collected for determination of sCr and serum cystatin C (sCys) levels. GFR was measured (mGFR) by plasma clearance of 51Cr-EDTA and used as the reference. We compared values of mGFR and estimated GFR (eGFR) by CKD-EPI equations based on sCr (eGFRCr) and on the combination of sCr and sCys (eGFRCr-Cys). For African Brazilian patients, eGFR was calculated either without or with race adjustment. Accuracy was considered acceptable if the difference between the values of eGFR and mGFR was ≤30% (P30). RESULTS: 100 patients were enrolled (58 ± 14 years, 46% male, 39% white and 61% African Brazilian). Mean mGFR was 46.7 ± 29.2 ml/min/1.73 m2. Mean eGFRCr and eGFRCr-Cys without race adjustment were 47.8 ± 30.1 ml/min/1.73 m2 and 46.4 ± 30.3 ml/min/1.73 m2, respectively. The corresponding P30 accuracy values were 79.0% and 83.0%. In the African Brazilian subgroup, values for mean mGFR and eGFRCr either without or with race adjustment were 49.8 ± 32.2 ml/min/1.73 m2, 50.4 ± 32.7 ml/min/1.73 m2, and 58.4 ± 37.9 ml/min/1.73 m2 (P < 0.001 vs. mGFR), respectively. P30 accuracy values for eGFRCr either without or with race adjustment were 75.4% and 67.2%, respectively. CONCLUSIONS: The use of CKD-EPI equations without race-ethnicity adjustment seems more appropriate for the Brazilian population.
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Cardiac sympathetic overdrive provides inotropic support to the failing heart. However, as myocardial insult evolves, this compensatory response impairs contractile function and constitutes an independent mortality predictor and a primary target in the treatment of heart failure (HF). In this prospective, randomized, double-blind, controlled crossover trial, we proposed cervicothoracic transcutaneous electrical nerve stimulation (CTENS) as a nonpharmacological therapy on cardiac sympathetic activity in patients with HF. Seventeen patients with HF were randomly assigned to an in-home CTENS (30 min twice daily, 80-Hz frequency, and 150-µs pulse duration) or a control intervention (Sham) for 14 consecutive days. Following a 60-day washout phase, patients were crossed over to the opposite intervention. The heart-to-mediastinum ratio (HMR) and washout rate (WR) (indexes of sympathetic innervation density and activity from planar 123iodo-metaiodobenzylguanidine myocardial scintigraphy images, respectively), as well as blood pressure (BP) and heart rate (HR), were quantified before and after each intervention. HMR, BP, and HR did not change throughout the study. Nonetheless, CTENS reduced WR (CTENS -4 ± 10 vs. Sham +5 ± 15%, P = 0.03) when compared with Sham. When allocated in two independent groups, preserved (PCSI, HMR > 1.6, n = 10) and impaired cardiac sympathetic innervation (ICSI, HRM ≤1.6, n = 7), PCSI patients showed an important attenuation of WR (-11 ± 9 vs. Sham +8 ± 19%, P = 0.007) after CTENS. Nonetheless, neither Sham nor CTENS evoked changes in WR of the ICSI patients (P > 0.05). These findings indicate that CTENS attenuates the cardiac sympathetic overdrive in patients with HF and a preserved innervation constitutes an essential factor for this beneficial neuromodulatory impact. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT03354689. NEW & NOTEWORTHY We found that short-term cervicothoracic transcutaneous electrical nerve stimulation (CTENS) attenuates cardiac sympathetic overdrive in patients with heart failure and a preserved autonomic innervation may constitute an essential factor to maximize this beneficial neuromodulatory effect. CTENS then emerges as an alternative noninvasive and nonpharmacological strategy to attenuate exaggerated cardiac sympathetic drive in patients with heart failure.
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3-Iodobenzilguanidina/administração & dosagem , Insuficiência Cardíaca/terapia , Coração/inervação , Radioisótopos do Iodo/administração & dosagem , Contração Miocárdica , Compostos Radiofarmacêuticos/administração & dosagem , Sistema Nervoso Simpático/fisiopatologia , Estimulação Elétrica Nervosa Transcutânea , Idoso , Pressão Sanguínea , Brasil , Estudos Cross-Over , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema Nervoso Simpático/diagnóstico por imagem , Fatores de Tempo , Estimulação Elétrica Nervosa Transcutânea/efeitos adversos , Resultado do TratamentoAssuntos
3-Iodobenzilguanidina , Carbazóis/uso terapêutico , Insuficiência Cardíaca/genética , Polimorfismo Genético , Propanolaminas/uso terapêutico , Receptores Adrenérgicos beta 1/genética , Antagonistas Adrenérgicos beta/uso terapêutico , Carvedilol , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Receptores Adrenérgicos beta 1/efeitos dos fármacos , Receptores Adrenérgicos beta 1/metabolismoRESUMO
Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG) has been studied in Parkinson's disease (PD), especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.
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3-Iodobenzilguanidina , Coração/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Doença de Parkinson/diagnóstico por imagem , Compostos Radiofarmacêuticos , Transmissão Sináptica/fisiologia , Idoso , Brasil , Distribuição de Qui-Quadrado , Feminino , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG) has been studied in Parkinson's disease (PD), especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.
A cintilografia miocárdica com meta-iodo-benzil-guanidina (123I cMIBG) foi estudada na doença de Parkinson (DP), especialmente nos países asiáticos, mas não na América Latina. A quase totalidade desses estudos inclui indivíduos com DP com disautonomia definida. Nosso objetivo é relatar a neurotransmissão simpática cardíaca em doentes brasileiros com DP de novo esporádica, sem disautonomia clinicamente definida. Foi avaliada retrospectivamente uma série de 21 casos consecutivos com DP sem sintomas ou sinais de disautonomia observáveis pelos testes de beira-de-leito. Com a aplicação dos critérios de exclusão, este número foi reduzido para 14. A captação do 123I MIBG pelo SPECT foi baixa ou ausente em todos os pacientese; a relação coração / mediastino foi baixa em 12 dos 14. Concluímos que a 123c MIBG é capaz de identificar alteração da neurotransmissão simpática cardíaca em doentes com DP de novo sem disautonomia clinicamente definida.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coração , Imagem de Perfusão do Miocárdio/métodos , Doença de Parkinson , Compostos Radiofarmacêuticos , Transmissão Sináptica/fisiologia , Brasil , Distribuição de Qui-Quadrado , Coração/fisiopatologia , Doença de Parkinson/fisiopatologia , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único/métodosAssuntos
Humanos , Feminino , Idoso , Esvaziamento Gástrico , Gastroparesia , Gastroparesia/diagnóstico , Cintilografia/métodos , Cisaprida/administração & dosagem , Transtornos da Motilidade Esofágica , Fármacos Gastrointestinais/uso terapêutico , Comportamento Alimentar , Metoclopramida/administração & dosagem , Motilidade GastrointestinalRESUMO
The objective of this study was to investigate safety and feasibility of autologous bone marrow mononuclear cells (BMMNC) transplantation in ST elevation myocardial infarction (STEMI), comparing anterograde intracoronary artery (ICA) delivery with retrograde intracoronary vein (ICV) approach. An open labeled, randomized controlled trial of 30 patients admitted with STEMI was used. Patients were enrolled if they 1) were successfully reperfused within 24 h from symptoms onset and 2) had infarct size larger than 10% of the left ventricle (LV). One hundred million BMMNC were injected in the infarct-related artery (intra-arterial group) or vein (intravenous group), 1% of which was labeled with Tc(99m)-hexamethylpropylenamineoxime. Cell distribution was evaluated 4 and 24 h after injection. Baseline MRI was performed in order to evaluate microbstruction pattern. Baseline radionuclide ventriculography was performed before cell transfer and after 3 and 6 months. All the treated patients were submitted to repeat coronary angiography after 3 months. Thirty patients (57 +/- 11 years, 70% males) were randomly assigned to ICA (n = 14), ICV (n = 10), or control (n = 6) groups. No serious adverse events related to the procedure were observed. Early and late retention of radiolabeled cells was higher in the ICA than in the ICV group, independently of microcirculation obstruction. An increase of EF was observed in the ICA group (p = 0.02) compared to baseline. Injection procedures through anterograde and retrograde approaches seem to be feasible and safe. BMMNC retention by damaged heart tissue was apparently higher when the anterograde approach was used. Further studies are required to confirm these initial data.
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Transplante de Medula Óssea/métodos , Leucócitos Mononucleares/transplante , Infarto do Miocárdio/terapia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Nitratos , Ventriculografia com Radionuclídeos , Tecnécio Tc 99m Exametazima , Tecnécio Tc 99m Sestamibi , Transplante AutólogoAssuntos
Dor no Peito , Isquemia Miocárdica/patologia , Dor , Síndrome Coronariana Aguda/diagnóstico , Idoso , Angiografia Coronária/métodos , Diagnóstico por Imagem/métodos , Humanos , Masculino , Imagem de Perfusão do Miocárdio/métodos , Compostos Radiofarmacêuticos/farmacologia , Descanso , Tecnécio Tc 99m Sestamibi/farmacologiaRESUMO
Dementia with Lewy bodies (DLB) is the second most common cause of dementia. The diagnosis of DLB is particularly important because these patients show good response to cholinesterase inhibitors. Clinical and neuroimaging criteria for DLB have not been acceptable for predictive accuracy. We report a case of progressive dementia in which the differentiation of DLB and Alzheimer disease (AD) on the basis of clinical criteria alone was not possible. The patient was admitted to the hospital because he became worse after he had started treatment for severe AD. Both MRI and brain magnetic resonance spectroscopy were normal. The patient underwent myocardial scintigraphy with I-123 MIBG showing marked reduction in cardiac MIBG accumulation. The heart to mediastinum ratio of MIBG uptake was impaired in both early and delayed images. FDG-PET scan before and after activation with a visual attention task showed occipital cortex hypometabolism as compared with AD and a normal control. This case illustrates the value of combining activated brain FDG PET and cardiac MIBG. The association of these 2 techniques could be used as a potential diagnostic tool in a patient with dementia misdiagnosed as AD.
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3-Iodobenzilguanidina , Doença de Alzheimer/diagnóstico por imagem , Fluordesoxiglucose F18 , Coração/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Humanos , Aumento da Imagem/métodos , Masculino , Cintilografia , Compostos RadiofarmacêuticosRESUMO
OBJECTIVE: To evaluate the feasibility of monitoring the autologous mononuclear bone marrow (ABMMN) cells implanted into the brain after acute ischemic stroke by the technique of labeling with Tc-99m-HMPAO. CASE REPORT: A 37-year-old man presented with aphasia, right-side hypoesthesia, and right homonymous hemianopsia after an acute ischemic stroke of the left middle cerebral artery. He was included in an autologous bone marrow mononuclear cell-based therapy research protocol about the safety of intra-arterial autologous bone marrow mononuclear cell transplantation for acute ischemic stroke. Nine days after the stroke he received 3.0 x 10(7) ABMMN cells delivered into the left cerebral middle artery via a balloon catheter. Approximately 1% of these cells were labeled with 150 MBq (4 mCi) Tc-99m by incubation with hexamethylpropylene amine oxime (HMPAO). RESULTS: Brain perfusion images with Tc-99m ECD demonstrated hypoperfusion in the left temporal and parietal regions. The perfusion brain images were compared with tomographic views of the brain obtained 8 hours after ABMMN-labeled cell delivery, revealing intense accumulation of the ABMMN-labeled cells in the ipsilateral hemisphere. A whole-body scan was done and showed left brain, liver, and spleen uptake. CONCLUSIONS: Our results showed that Tc-99m HMPAO can be used to label ABMMN cells for in vivo cell visualization, and that brain SPECT imaging with labeled ABMMN cells is a feasible noninvasive method for studying the fate of transplanted cells in vivo. Additionally, our findings demonstrate the localization of these intra-arterially injected cells.
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Células da Medula Óssea/diagnóstico por imagem , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Leucócitos Mononucleares/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Imagem de Difusão por Ressonância Magnética , Humanos , Injeções Intra-Arteriais , Masculino , Cintilografia , Transplante AutólogoAssuntos
Células da Medula Óssea/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/cirurgia , Tecnécio Tc 99m Exametazima , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Resultado do TratamentoRESUMO
BACKGROUND: Cell-based therapies for treatment of ischemic heart disease are currently under investigation. We previously reported the results of a phase I trial of transendocardial injection of autologous bone marrow mononuclear (ABMM) cells in patients with end-stage ischemic heart disease. The current report focuses on postmortem cardiac findings from one of the treated patients, who died 11 months after cell therapy. METHODS AND RESULTS: Anatomicopathologic, morphometric, and immunocytochemical findings from the anterolateral ventricular wall (with cell therapy) were compared with findings from the interventricular septum (normal perfusion and no cell therapy) and from the inferoposterior ventricular wall (extensive scar tissue and no cell therapy). No signs of adverse events were found in the cell-injected areas. Capillary density was significantly higher (P<0.001) in the anterolateral wall than in the previously infarcted tissue in the posterior wall. The prominent vasculature of the anterolateral wall was associated with hyperplasia of pericytes, mural cells, and adventitia. Some of these cells had acquired cytoskeletal elements and contractile proteins (troponin, sarcomeric alpha-actinin, actinin), as well as the morphology of cardiomyocytes, and appeared to have migrated toward adjacent bundles of cardiomyocytes. CONCLUSIONS: Eleven months after treatment, morphological and immunocytochemical analysis of the sites of ABMM cell injection showed no abnormal cell growth or tissue lesions and suggested that an active process of angiogenesis was present in both the fibrotic cicatricial tissue and the adjacent cardiac muscle. Some of the pericytes had acquired the morphology of cardiomyocytes, suggesting long-term sequential regeneration of the cardiac vascular tree and muscle.
Assuntos
Células da Medula Óssea/citologia , Transplante de Medula Óssea , Insuficiência Cardíaca/terapia , Isquemia Miocárdica/terapia , Miocárdio/patologia , Transplante de Células-Tronco , Desmina/análise , Insuficiência Cardíaca/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Neovascularização Fisiológica , Tomografia Computadorizada de Emissão de Fóton Único , Transplante AutólogoRESUMO
OBJECTIVE: This study aimed at assessing the effects of autologous transendocardial transplantation of bone marrow mononuclear cells (ATTBMMC) on symptoms, exercise capacity, myocardial perfusion and contractility in patients with severe ischemic heart disease during a 6-month follow-up period. METHODS: This prospective study comprised 21 patients as follows: the first 14 patients forming the treated group, and the last 7 patients forming the control group. Initially, all patients underwent clinical and laboratory assessment, treadmill testing, echocardiography, myocardial scintigraphy, and 24-hour Holter. The bone marrow mononuclear cells (BMMC) were isolated, washed, and diluted in 0.9% saline solution for transendocardial injection in areas of viable myocardium in the treated group, (15 0.2-mL injections). All patients were reassessed in the end of 2 and 6 months of follow-up. RESULTS: The demographic data and other characteristics did not significantly differ between the groups in the initial evaluation. No major adverse events related to the ATTBMMC were observed. In the end of 6 months, a reduction in the ischemic area was observed on nuclear perfusion imaging (P=0.05), as was a significant improvement in symptoms, functional capacity, and left ventricular overall function. CONCLUSION: This study showed that transendocardial injections of BMMC are safe in human beings with ischemic heart disease associated with severe ventricular dysfunction. The effects observed in the short run were maintained up to the sixth month of follow-up.
Assuntos
Transplante de Medula Óssea , Tolerância ao Exercício/fisiologia , Isquemia Miocárdica/cirurgia , Estudos Epidemiológicos , Teste de Esforço , Feminino , Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Isquemia Miocárdica/diagnóstico por imagem , Neovascularização Fisiológica , Cintilografia , Transplante AutólogoRESUMO
OBJETIVO: Este estudo tem por objetivo avaliar os efeitos, no seguimento de 6 meses, do transplante autólogo, transendocárdico, de células mononucleares da medula óssea (TACMMO), sobre os sintomas, capacidade de exercício, perfusão e contratilidade miocárdica nos portadores de cardiopatia isquêmica grave. MÉTODOS: Vinte e um pacientes foram incluídos neste estudo prospectivo (os 14 primeiros pacientes, grupo tratado; os 7 últimos pacientes, grupo controle). Inicialmente todos os indivíduos foram submetidos à avaliação clínica e laboratorial, teste ergométrico, ecocardiograma, cintilografia miocárdica e Holter de 24 horas. As CMMO foram isoladas, lavadas e diluídas em salina 0,9 por cento para injeção transendocárdica em áreas de miocárdio viável no grupo tratado, (15 injeções de 0,2 ml). Todos os pacientes foram reavaliados ao final de 2 e 6 meses de acompanhamento. RESULTADOS: Os dados demográficos e demais características não diferiram significativamente entre os grupos na avaliação inicial. Não foram observados eventos adversos maiores relacionados ao TACMMO. Ao final de 6 meses, houve redução da área isquêmica na imagem de perfusão nuclear (p=0,05) e melhora significativa dos sintomas, da capacidade funcional e da função global do ventrículo esquerdo. CONCLUSAO: Este estudo demonstra a segurança da realização de injeções transendocárdicas de CMMO em humanos com cardiopatia isquêmica associada a grave disfunção ventricular. Os efeitos observados em curto prazo foram mantidos até 6 meses de acompanhamento.