RESUMO
BACKGROUND: There are novel medications approved for the treatment of hereditary transthyretin amyloidosis (ATTRv), classified as transthyretin (TTR) stabilizers or gene silencers. While many patients may be on both classes of medications, there is no data available on the safety and efficacy of combination therapy. OBJECTIVES: To describe ATTRv patient and TTR-targeted therapy characteristics in a US cohort, and compare outcomes with combination therapy versus monotherapy. METHODS: We performed a retrospective cohort study with electronic health record data of patients with ATTRv seen at a single institution between January 2018 and December 2022. We collected data on symptomatology, gene mutation, disease severity, ATTRv treatment, hospitalizations, and mortality. RESULTS: One hundred sixty-two patients with ATTRv were identified. The average age at diagnosis was 65 years. 86 patients (53%) had the V122I variant. 119 patients were symptomatic, of whom 103 were started on ATTRv-specific treatment. 41 patients (40%) had cardiomyopathy only, and 53 (51%) had a mixed phenotype of cardiomyopathy and neuropathy. 38 patients (37%) received therapy with both a gene silencer and protein stabilizer. 9 patients (15%) in the monotherapy group had two or more cardiac hospitalizations after starting treatment, compared to 3 patients (9%) on combination therapy (p=0.26). The adjusted hazard ratio of all-cause mortality for the patients on combination therapy compared to monotherapy was 0.37 (0.08-1.8, p=0.21). CONCLUSIONS: While the efficacy is unproven, over one-third of patients with ATTRv are on both a stabilizer and a silencer. There were no safety issues for combination therapy. There was a trend towards improved hospitalizations and survival in patients in the combination group but this was not statistically significant. Larger studies with longer follow-up are necessary to determine benefit of combination therapy.
Assuntos
Neuropatias Amiloides Familiares , Humanos , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Amiloides Familiares/genética , Masculino , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Pré-Albumina/genética , Pré-Albumina/metabolismo , Idoso de 80 Anos ou mais , AdultoRESUMO
BACKGROUND: We employed deep learning to automatically detect myocardial bone-seeking uptake as a marker of transthyretin cardiac amyloid cardiomyopathy (ATTR-CM) in patients undergoing 99mTc-pyrophosphate (PYP) or hydroxydiphosphonate (HDP) single-photon emission computed tomography (SPECT)/computed tomography (CT). METHODS: We identified a primary cohort of 77 subjects at Brigham and Women's Hospital and a validation cohort of 93 consecutive patients imaged at the University of Pennsylvania who underwent SPECT/CT with PYP and HDP, respectively, for evaluation of ATTR-CM. Global heart regions of interest (ROIs) were traced on CT axial slices from the apex of the ventricle to the carina. Myocardial images were visually scored as grade 0 (no uptake), 1 (uptake
Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Aprendizado Profundo , Humanos , Feminino , Neuropatias Amiloides Familiares/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Cintilografia , Pirofosfato de Tecnécio Tc 99m , Miocárdio , Cardiomiopatias/diagnóstico por imagem , Pré-AlbuminaAssuntos
Cardiomiopatias/cirurgia , Vasoespasmo Coronário/complicações , Parada Cardíaca/etiologia , Transplante de Coração , Índice de Gravidade de Doença , Adulto , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Nitroglicerina/uso terapêutico , Reoperação , Resultado do TratamentoRESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis and vascular stiffening. Whether SLE alters left ventricular (LV) structure and function in the absence of valvular and clinical coronary artery disease is unknown. METHODS AND RESULTS: SLE patients without clinical or echocardiographic evidence of valvular or coronary disease were age and gender matched to a reference group (n=173 in both groups). Subjects underwent echocardiography to quantify LV structure and function and carotid ultrasonography to detect atherosclerosis. Disease characteristics and radial applanation tonometry to measure arterial stiffness were evaluated in SLE patients. The 2 groups were similar in subjects' body size, hypertension and diabetes status, smoking status, and cholesterol levels. LV mass (38.3 versus 32.8 g/m(2.7)), ejection fraction (71% versus 67%), and prevalence of LV hypertrophy (17.9% versus 6.4%) were higher in SLE patients than in referent subjects (all P<0.001). The combination of SLE and hypertension further increased LV mass. In multivariable analysis, LV mass was associated with SLE (P<0.001) in addition to body mass index, diabetes mellitus, and hypertension. Among SLE patients, LV mass was associated with arterial stiffness (P<0.001). Carotid atherosclerosis, SLE duration, damage index, serum creatinine, and homocysteine were significantly related to LV mass in univariate but not multivariable analyses. CONCLUSIONS: SLE predicts increased LV mass, possibly because of inflammation-related arterial stiffening. Excess LV hypertrophy may contribute to the increased cardiac morbidity and mortality observed in SLE patients.