Survival in a Real-World Cohort of Patients With Transthyretin Amyloid Cardiomyopathy Treated With Tafamidis: An Analysis From the Transthyretin Amyloidosis Outcomes Survey (THAOS).

BACKGROUND: In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality rates, leading to its approval in many countries for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Real-world evidence on survival in patients with ATTR-CM following tafamidis treatment has not been extensively reported. METHODS AND RESULTS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) was a longitudinal, observational, phase 4 study of patients with transthyretin amyloidosis and asymptomatic participants carrying pathogenic transthyretin variants. Patients from THAOS with a predominantly cardiac phenotype at enrollment were included, and survival was analyzed according to tafamidis treatment status (treated or untreated). Results are based on the completed THAOS dataset. In tafamidis-treated (n = 587) and tafamidis-untreated (n = 854) patients, respectively, median age at enrollment was 77.7 and 76.4 years, 91.8% and 90.0% were male, and 91.8% and 83.8% had wild-type disease. Survival rates (95% CI) at 30 and 42 months, respectively, were 84.4% (80.5-87.7) and 76.8% (70.9-81.7) in tafamidis-treated patients, and 70.0% (66.4-73.2) and 59.3% (55.2-63.0) in tafamidis-untreated patients. Survival rates in genotype subgroups (wild-type and variant) were similar to those of the overall cohort. Survival rates were better in a contemporary cohort, as reflected by a sensitivity analysis performed in patients enrolled after vs before 2019. No new safety signals were identified. CONCLUSIONS: In this real-world cohort of patients with ATTR-CM, survival rates were higher than in ATTR-ACT and consistent with more recent reports, suggesting early diagnosis and treatment with tafamidis has improved life expectancy in ATTR-CM. These results provide further evidence supporting tafamidis' safety and effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00628745.

The effect of long-term tafamidis treatment on quality of life in people with transthyretin amyloid cardiomyopathy (ATTR-CM): A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary explains some results of a study called ATTR-ACT and its ongoing long-term extension study that were published in the European Journal of Heart Failure. The purpose of ATTR-ACT was to find out if a drug called tafamidis is an effective treatment for people with a heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM). People took tafamidis or placebo for up to 2.5 years in ATTR-ACT (the initial study). A placebo looks like the study medicine but does not contain any active ingredients. After people completed the initial study, they could take part in the extension study. An extension study allows people to continue receiving treatment after the original clinical study ends and helps researchers understand how well a treatment works over a longer time period. This extension study allows people to receive tafamidis for up to an additional 5 years. People who took placebo in the initial study now receive tafamidis. People who took tafamidis in the initial study continue tafamidis treatment. Researchers looked at changes in peoples' ability to enjoy life ('quality of life') and heart failure symptoms since they started ATTR-ACT. Results are available for the first 2.5 years of the extension study. WHAT ARE THE KEY TAKEAWAYS?: During the initial study, there was less worsening of quality of life and heart failure symptoms in people who took tafamidis compared to people who took placebo. In the extension study, quality of life and heart failure symptoms were maintained or nearly maintained in people who took tafamidis in the initial study. In people who started tafamidis in the extension study, quality of life and heart failure symptoms continued to worsen, but the worsening slowed down. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Tafamidis slows the worsening of quality of life and heart failure symptoms in people with ATTR-CM. People with ATTR-CM should start treatment early to receive the most benefit.Clinical Trial Registration: NCT01994889 (ATTR-ACT) (ClinicalTrials.gov).

Long-Term Efficacy and Safety of ARRY-371797 (PF-07265803) in Patients With Lamin A/C-Related Dilated Cardiomyopathy.

Dilated cardiomyopathy associated with lamin A/C (LMNA) gene variants (LMNA-related dilated cardiomyopathy [DCM]) is a life-threatening condition with a high unmet need, accounting for approximately 6% of idiopathic DCM cases. Currently, no disease-specific treatments target the underlying disease mechanism. ARRY-371797 (PF-07265803), a potent, selective, oral, small-molecule inhibitor of the p38α mitogen-activated protein kinase pathway, improved 6-minute walk test (6MWT) distance in 12 patients with symptomatic LMNA-related DCM in a 48-week, open-label, phase 2 study. This long-term extension study examined the safety and efficacy of ARRY-371797 in patients from the phase 2 study. 6MWT, N-terminal pro-B-type natriuretic peptide concentration, and 12-item Kansas City Cardiomyopathy Questionnaire score were assessed at weeks 48, 72, 96, 120, and 144 from phase 2 study baseline. Eight patients enrolled (mean [SD] age, 51 [10] years, 4 male). Mean 6MWT increased by >30 m (>10%) from phase 2 study baseline up to week 120. The decrease in N-terminal pro-B-type natriuretic peptide observed in the phase 2 study was maintained throughout the present study. Twelve-item Kansas City Cardiomyopathy Questionnaire Physical Limitation increased from baseline at all visits except week 96 (range: -0.8 [week 96] to 13.8 [week 120]); results for other domains were variable. Treatment was generally well tolerated; 2 patients discontinued because of causes not considered treatment-related. There were no deaths. ARRY-371797 was generally well tolerated over median (range) 155.7 (61 to 327)-week exposure; evidence suggested preserved exercise capacity over the study period. The ongoing, pivotal, phase 3, randomized, placebo-controlled study REALM-DCM investigates the efficacy and safety of ARRY-371797 (PF-07265803) in LMNA-related DCM. (ClinicalTrials.gov Identifier: NCT02351856).

Terapia celular no tratamento do infarto agudo do miocárdio / Cell therapy in the treatment of acute myocardial infarction

Neste artigo, os autores abordam os conceitos e evidências atualmente disponíveis sobre a terapia celular no tratamento de pacientes pós-infarto agudo do miocárdio. Os tipos celulares potencialmente candidatos ao uso clínico são enfatizados, considerando-se as vias de administração e as perspectivas futuras.

In this article, the authors discuss the concepts and available current evidence about cell therapy in the treatment of patients with acute myocardial infarction. The cell types that are potential candidates for clinical use are detailed as are the administration routes and future perspectives.

Cirurgia transesfenoidal no tratamento primário da acromegalia: relato de caso / Transsphenoidal surgery in initial treatment of acromegaly: case report

A acromegalia é um distúrbio geralmente causado pela hipersecreçäo do hormônio do crescimento (GH) por um adenoma pituitário. As conseqüências tardias associadas säo desfigurantes, incapacitantes e levam a uma reduçäo da expectativa de vida do paciente. Dessa forma, o diagnóstico precoce e a instauraçäo do tratamento adequado säo cruciais, sendo fundamental a identificaçäo da origem do excesso de GH para que a mesma possa ser removida ou suprimida. Dentro desse contexto, a cirurgia transesfenoidal é aceita como terapia de escolha no tratamento primário da acromegalia. Neste relato, säo revisadas e discutidas as características clínicas, os diagnósticos de laboratório e por imagem, o manejo cirúrgico e o segmento clínico de um paciente com tumor pituitário secretor de GH.

Avaliação cardiológica pré-operatória em cirurgia não cardíaca / Evaluation cardiovascular preoperative in non-cardiac surgery

Revisão bibliográfica sobre avaliação e manejo de pacientes com risco de eventos cardiovasculares perioperatórios, com base nas diretrizes da American College of Cardiology/American Heart Association e na rotina de avaliação do serviço de Cardiologia do Hospital São Lucas da PUCRS

A tomografia computadorizada do diagnóstico diferencial do edema de membros inferiores / Computer tomography scan of the diferencial diagnosis of lower limbs edema

O presente estudo tem por objetivo observar, com base em relatos existentes na literatura e em casos clínicos selecionados, a utilidade e auxílio da tomografia computadorizada no diagnóstico diferencial dos pacientes com edema de membros inferiores.

Mixoma de átrio esquerdo / Left atrial myxoma

Os autores apresentam um caso de paciente portadora de mixoma de átrio esquerdo. Embora seja este o tumor benigno cardíaco mais freqüente, pouca atençao tem sido dada à correlaçao clinicopatológica deste tumor, permanecendo, por vezes, como um achado ecocardiográfico casual. Este artigo objetiva a fazer uma breve revisao sobre o quadro clínico, o diagnóstico e o tratamento deste tipo de patologia.

Prevalência dislipidemia em pacientes com doença arterial coronariana / Prevalence of hyperlipedemia in patients with coronarian arterial disease

Este trabalho objetivou verificar a prevalencia de dislipidemias em pacientes com Doenca Arterial Coronariana (DAC) estabelecida, selecionados aleatoriamente em consultorios cardioløgicos. Foi determinada a frequencia de desvios dos valores considerados ideais para a faixa etaria da colesterolemia total-CT, suas fracoes (HDL-C e LDL-C), e trigliceridemia-TG. No conjunto estudado, nenhum dos pacientes apresentou HDL-C em n­veis sericos indicativos de risco negativo para DAC, sendo que 100 por cento dos pacientes apresentaram pelo menos um dos quatro valores lip­dicos alterados. Os resultados confirmam a preponderancia de n­veis lip­dicos alterados como FR no desenvolvimento de DAC.