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1.
bioRxiv ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38558967

RESUMO

Background: Cardiac dysfunction in AL amyloidosis is thought to be partly related to the direct impact of AL LCs on cardiomyocyte function, with the degree of dysfunction at diagnosis as a major determinant of clinical outcomes. Nonetheless, mechanisms underlying LC-induced myocardial toxicity are not well understood. Methods: We identified gene expression changes correlating with human cardiac cells exposed to a cardiomyopathy-associated κAL LC. We then sought to confirm these findings in a clinical dataset by focusing on clinical parameters associated with the pathways dysregulated at the gene expression level. Results: Upon exposure to a cardiomyopathy-associated κAL LC, cardiac cells exhibited gene expression changes related to myocardial contractile function and inflammation, leading us to hypothesize that there could be clinically detectable changes in GLS on echocardiogram and serum inflammatory markers in patients. Thus, we identified 29 patients with normal IVSd but abnormal cardiac biomarkers suggestive of LC-induced cardiac dysfunction. These patients display early cardiac biomarker staging, abnormal GLS, and significantly reduced serum inflammatory markers compared to patients with clinically evident amyloid fibril deposition. Conclusion: Collectively, our findings highlight early molecular and functional signatures of cardiac AL amyloidosis, with potential impact for developing improved patient biomarkers and novel therapeutics.

2.
J Heart Lung Transplant ; 41(4): 538-549, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35153130

RESUMO

BACKGROUND: Heart transplantation (HTx) from hepatitis C virus (HCV)-viremic donors to nonviremic recipients decreases mortality and costs. Consequently, many transplant centers have reported their results using this strategy. Hence, there is a need for an outcome analysis. METHODS: We performed a systematic review with meta-analysis. In August 2020, we searched PubMed and EMBASE for publications containing data of nonviremic recipients who underwent HTx from HCV-viremic donors once direct-acting antiviral (DAA) therapy had become available (≥2014). RESULTS: We identified 398 publications, 13 of which met inclusion criteria, and analyzed the outcomes of 195 recipients. The HCV-transmission rate was >97% but, the cure rate was 100% with DAA therapy. The 6 and 12-month survival were 95.6% and 92.9%, respectively. Of 10 deaths reported, none were associated with HCV infection. The acute cellular rejection (ACR) rate was 31.1%. The overall DAA failure rate was 1.1%, defined as the need to alter the initial DAA therapy due to failure to cure HCV. However, the DAA failure rate was 0% when the DAA therapy was started within the first 2 weeks post-HTx. No statistically significant differences in HCV cure rates, survivals, ACR rates, and DAA failure rates were observed when outcomes were stratified by therapeutic approach type (i.e., a prophylactic approach in which DAA was given to the recipient before confirming HCV-transmission vs a reactive approach, in which DAA was given to the recipient only after an HCV-transmission was confirmed). CONCLUSIONS: Excellent clinical outcomes have been observed in nonviremic recipients of HTx from HCV-viremic donors since DAA had become available.


Assuntos
Transplante de Coração , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Doadores de Tecidos
3.
Future Cardiol ; 17(4): 631-635, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33078963

RESUMO

Introduction: Takotsubo is often described as stress-induced cardiomyopathy and is a known cause of heart failure. Objective: Review the clinical course of a young coronavirus disease 2019 (COVID-19) patient who developed Takotsubo following cardiac tamponade. Case presentation: A 42-year-old woman presented to the emergency department with fever, altered mental status and hypoxia. She was ultimately found to be in cardiac tamponade and within 2 hours of a pericardiocentesis she developed Takotsubo and was in cardiogenic shock. Her family decided to place her on comfort measures and she died the same day. Discussion: This case illustrates the increasing number of cardiovascular complications being reported in COVID-19 and highlights the importance of clinicians to be aware of these challenges. Conclusion: Here, we report a distinct presentation of cardiogenic shock in a young COVID-19 patient. The rapid onset of her suspected Takotsubo and the severity of her disease were striking features in this case.


Assuntos
COVID-19/complicações , Tamponamento Cardíaco/virologia , Choque Cardiogênico/virologia , Cardiomiopatia de Takotsubo/virologia , Adulto , Evolução Fatal , Feminino , Humanos , SARS-CoV-2
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