World heart federation consensus on Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM)

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms). It is a systemic disease, and while the genetic forms may exhibit a variety of symptoms, a predominant cardiac phenotype is often present. This document aims to provide an overview of ATTR-CM amyloidosis focusing on cardiac involvement, which is the most critical factor for prognosis. It will discuss the available tools for early diagnosis and patient management, given that specific treatments are more effective in the early stages of the disease, and will highlight the importance of a multidisciplinary approach and of specialized amyloidosis centres. To accomplish these goals, the World Heart Federation assembled a panel of 18 expert clinicians specialized in TTR amyloidosis from 13 countries, along with a representative from the Amyloidosis Alliance, a patient advocacy group. This document is based on a review of published literature, expert opinions, registries data, patients' perspectives, treatment options, and ongoing developments, as well as the progress made possible via the existence of centres of excellence. From the patients' perspective, increasing disease awareness is crucial to achieving an early and accurate diagnosis. Patients also seek to receive care at specialized amyloidosis centres and be fully informed about their treatment and prognosis.

Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).

BACKGROUND: Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood. METHODS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020). RESULTS: Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]). CONCLUSIONS: Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT00628745.

Impact of Non-Cardiac Clinicopathologic Characteristics on Survival in Transthyretin Amyloid Polyneuropathy.

INTRODUCTION: Hereditary (variant) transthyretin amyloidosis (ATTRv) with polyneuropathy (ATTR-PN) is a rare genetic disorder that causes progressive autonomic and sensorimotor neuropathy, severe disability, and death within 10 years of onset. Previous studies have primarily focused on how baseline cardiac characteristics affect mortality, but the impact of non-cardiac baseline characteristics is less defined. METHODS: We systematically searched PubMed/Medline (1990-2019) to identify studies that assessed the impact of baseline ATTR-PN characteristics on survival. Outcomes were first summarized descriptively. Extracted survival data were then disaggregated, and parametric mixture models were used to assess survival differences among patient groups defined by factors known to affect survival. RESULTS: The search yielded 1193 records, of which 35 were retained for analysis. Median survival ranged from 0.5 to > 25 years. The largest survival differences were between cohorts who underwent liver transplantation (LTx) versus those who did not. Among LTx cohorts, pre-LTx ATTR-PN disease duration ≥ 7 years, poor nutritional status, and late disease onset reduced median survival by 13, 12, and 10 years, respectively. Other prognostic survival factors included non-Val30Met genotype and baseline presence of urinary incontinence, erectile dysfunction, or muscle weakness. CONCLUSION: Survival in patients with ATTR-PN is highly variable and affected by non-cardiac baseline characteristics, such as autonomic dysfunction, large fiber involvement, late-onset disease, and non-Val30Met mutation. Careful interpretation of these findings is warranted given that this synthesis did not control for differences between studies. Survival in patients with ATTR-PN remains poor among those who are untreated or with delayed diagnosis.

Correction to: Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

The original version of this article unfortunately contained a mistake.

Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

"A dor e o incômodo são passageiros, mas o orgulho é eterno": dores e moralidades entre ultramaratonistas do Rio de Janeiro / "Pain and nuisance are passengers, but pride is eternal": pains and morals among ultramarathoners in Rio de Janeiro

O objetivo desta dissertação é compreender as práticas e representações que atravessam o universo da ultramaratona no Rio de Janeiro, com foco especial nos sentidos atribuídos à dor por estes atletas. Para tanto, foi realizada uma etnografia a partir de observação-participante em uma prova de ultramaratona de 235Km e seis entrevistas com ultramaratonistas de ambos os sexos, maiores de idade e que completaram ao menos uma vez o percurso da prova etnografada. A partir de um questionamento inicial sobre os sentidos da dor para ultramaratonistas, foi analisada como se desenvolve uma ultramaratona, sendo lida a partir de teorias da ação ritual. Os pares mente-corpo e prazer-dor assumem um papel central na forma como estes atletas significam o doer. Tornar-se ultramaratonista requer vencer a dor, sensação incitada pela atividade, mas evitada a todo tempo através da gestão de técnicas físicas e morais, configurando um dispositivo da dor

Respostas afetivas e cardiovasculares de mulheres jovens a uma sessão de treinamento com Nintendo Wii: uma nova perspectiva de exercício físico / Affective and cardiovascular responses of healthy young women to a training session with nintendo wii: a new perspective of exercise

O objetivo deste estudo foi verificar as respostas afetivas e cardiovasculares de mulheres jovens em uma sessão de treinamento com Nintendo Wii. Participaram 15 mulheres saudáveis (25±6 anos; 24±4 kg/m2) que jogaram o game Free Run durante 10 min. As respostas afetivas foram avaliadas pelas escalas de sensação e ativação, caracterizadas no modelo circumplexo. O humor foi avaliado pela escala de Perfil de Estados de Humor. A frequência cardíaca (FC), a pressão arterial (PA) e o duplo produto (DP) foram medidos. Avaliou-se a percepção subjetiva de esforço com a Escala de Borg C-10. As variáveis foram mensuradas pré, durante e aos 5 e 10 min pós-intervenção. A valência afetiva manteve-se positiva em todos os momentos, apresentando-se mais elevada pós 5 e 10 min (p<0,01). O modelo circumplexo mostrou respostas de calma e relaxamento pré-atividade, euforia durante e imediatamente pós-atividade; retornando ao relaxamento nos momentos pós 5 e 10 min. A FC apresentou aumento significante durante a sessão em relação ao repouso (173±7 vs. 76±9 bpm, p<0,05), e manteve elevada pós 5 (104±10 bpm) e 10 min (100±9 bpm). Houve aumento significante da PA sistólica imediatamente pós-exercício (149±14 mmHg), pós 5 (118±14 mmHg) e 10 min (110±11 mmHg) em relação ao repouso (113±8 mmHg). O DP manteve-se nos parâmetros de segurança para a atividade aeróbia (26.447±3.400 mmHg.bpm). Em conclusão, uma sessão com Wii provoca em mulheres jovens sensação de euforia e aumento da sobrecarga cardiovascular durante sua realização. Estes parâmetros tendem a retornar ao basal 10 minutos após a sessão.

The purpose of this study was check affective and cardiovascular responses of young women to a training session with Nintendo Wii. Fifteen healthy women (25±6 years; 24±4 kg/m2) played Free Run video game during 10 min. Affective responses were evaluated by Feeling and Felt Arousal scales, characterizing the circumplex model. Mood was evaluated by Profile of Mood State. Heart rate (HR), blood pressure (BP) and rate pressure product (RPP) were measured. Rate perceptive effort (RPE) was assessed by Borg Scale C-10. Variables were measured pré, during and at 5 and 10 min post-intervention. Affective valency remained positive at all moments, showing elevated values at post 5 and 10 min (p<0.01). Circumplex model revealed calm and relaxation pre-activity, euphory during and post-activity; and returned to relaxation at post 5 and 10 min. HR showed significant increase during the session in relation to rest (173±7 vs.76±9 bpm, p<0.05); and at post 5 (104±10 bpm) and 10 min (100±9 bpm). There was a significant increase in systolic BP immediately post-exercise (149±14 mmHg), and at post 5 (118±14 mmHg) and 10 min (110±11 mmHg) in comparison with pre-value (113±8 mmHg); (p<0.05). RPP remained in accord with safety parameters for aerobic activity (26.447±3.400 mmHg.bpm). In conclusion one session of Wii promotes a feeling of euphoria and cardiovascular overload in young women during exercise. These parameters tended to return to basal values at 10 minutes post session.

Hemodynamic responses of unfit healthy women at a training session with nintendo wii: a possible impact on the general well-being.

AIMS: The purpose of this study was assess the effect of a training session with Nintendo Wii® on the hemodynamic responses of healthy women not involved in regular physical exercise. METHOD: Twenty-five healthy unfit women aged 28 ± 6 years played for 10 minutes the game Free Run (Wii Fit Plus). The resting heart rate (RHR), systolic and diastolic blood pressures (SBP and DBP), and double (rate-pressure) product (DP) were measured before and after activity. The HR during the activity (exercise heart rate, EHR) was measured every minute. RESULTS: A statistically significant difference was observed between the RHR (75 ± 9 bpm) and the mean EHR (176 ± 15 bpm) (P < 0.001). The EHR remained in the target zone for aerobic exercise until the fifth minute of activity, which coincided with the upper limit of the aerobic zone (80% heart rate reserve (HRR) + RHR) from the sixth to tenth minute. The initial (110 ± 8 mmHg) and final (145 ± 17 mmHg) SBP (P < 0.01) were significantly different, as were the initial (71 ± 8 mmHg) and final (79 ± 9 mmHg) DBP (P < 0.01). A statistically significant difference was observed between the pre- (8.233 ± 1.141 bpm-mmHg) and post-activity (25.590 ± 4.117 bpm-mmHg) DP (P < 0.01). CONCLUSION: Physical exercise while playing Free Run sufficed to trigger acute hemodynamic changes in healthy women who were not engaged in regular physical exercise.

Favelas sob o controle das milícias no Rio de Janeiro: que paz? / Favelas under the control of militias in Rio de Janeiro: what peace?

O presente artigo analisa o surgimento e expansão das milícias no Rio de Janeiro que controlam territórios de favelas, comparando este poder militar com o domínio exercido por facções de traficantes em outras favelas. Os dados são da Pesquisa de Vitimização em Favelas 2007, de reportagens de jornais de grande circulação do país e da pesquisa etnográfica realizada na favelas Rio das Pedras em 2007 e 2008.