Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report.

Introduction: Cardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case report: A 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. Discussion: CA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. Conclusions: Various diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.

Takotsubo Multicenter Registry (REMUTA) - Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality. / Registro Multicêntrico de Takotsubo (REMUTA) ­ Aspectos Clínicos, Desfechos Intra-Hospitalares e Mortalidade a Longo Prazo.

BACKGROUND: Takotsubo syndrome (TTS) is an acquired form of cardiomyopathy. National Brazilian data on this condition are scarce. The Takotsubo Multicenter Registry (REMUTA) is the first to include multicenter data on this condition in Brazil. OBJECTIVE: To describe the clinical characteristics, prognosis, in-hospital treatment, in-hospital mortality, and mortality during 1 year of follow-up. METHODS: This is an observational, retrospective registry study including patients admitted to the hospital with diagnosis of TTS and patients admitted for other reasons who developed this condition. Evaluated outcomes included triggering factor, analysis of exams, use of medications, complications, in-hospital mortality, and mortality during 1 year of follow-up. A significance level of 5% was adopted. RESULTS: The registry included 169 patients from 12 centers in the state of Rio de Janeiro, Brazil. Mean age was 70.9 ± 14.1 years, and 90.5% of patients were female; 63% of cases were primary TTS, and 37% were secondary. Troponin I was positive in 92.5% of patients, and median BNP was 395 (176.5; 1725). ST-segment elevation was present in 28% of patients. Median left ventricular ejection fraction was 40 (35; 48)%. We observed invasive mechanical ventilation in 25.7% of cases and shock in 17.4%. Mechanical circulatory support was used in 7.7%. In-hospital mortality was 10.6%, and mortality at 1 year of follow-up was 16.5%. Secondary TTS and cardiogenic shock were independent predictors of mortality. CONCLUSION: The results of the REMUTA show that TTS is not a benign pathology, as was once thought, especially regarding the secondary TTS group, which has a high rate of complications and mortality. (Arq Bras Cardiol. 2020; 115(2):207-216).

FUNDAMENTO: A síndrome de takotsubo (takotsubo) é uma forma de cardiomiopatia adquirida. Dados nacionais sobre essa condição são escassos. O Registro REMUTA é o primeiro a incluir dados multicêntricos dessa condição no nosso país. OBJETIVO: Descrever as características clínicas, prognóstico, tratamento intra-hospitalar e mortalidade hospitalar e em 1 ano de seguimento. MÉTODOS: Estudo observacional, retrospectivo, tipo registro. Incluídos pacientes internados com diagnóstico de takotsubo ou que desenvolveram esta condição durante internação por outra causa. Os desfechos avaliados incluíram fator desencadeador, análise dos exames, uso de medicações, complicações e óbito intra-hospitalar e em 1 ano de seguimento. O nível de significância adotado foi de 5%. RESULTADOS: Foram incluídos 169 pacientes, em 12 centros no Estado do Rio de Janeiro. A idade média foi de 70,9 ± 14,1 anos e 90,5% eram do sexo feminino; 63% dos casos foram de takotsubo primário e 37% secundário. Troponina I foi positiva em 92,5% dos pacientes e a mediana de BNP foi de 395 (176,5; 1725). Supradesnivelamento do segmento ST esteve presente em 28% dos pacientes. A fração de ejeção do ventrículo esquerdo teve mediana de 40 (35; 48)%. Observamos taxa de 25,7% de ventilação mecânica invasiva e 17,4% de choque. Suporte circulatório mecânico foi utilizado em 7,7%. A mortalidade intra-hospitalar foi de 10,6% e a mortalidade ao final de 1 ano foi de 16,5%. Takotsubo secundário e choque cardiogênico foram preditores independentes de mortalidade. CONCLUSÃO: Os resultados do REMUTA mostram que takotsubo não se trata de patologia benigna como se pensava, especialmente no grupo de takotsubo secundário que acarreta elevada taxa de complicações e de mortalidade. (Arq Bras Cardiol. 2020; 115(2):207-216).

Registro Multicêntrico de Takotsubo (REMUTA) - Aspectos Clínicos, Desfechos Intra-Hospitalares e Mortalidade a Longo Prazo / Takotsubo Multicenter Registry (REMUTA) - Clinical Aspects, In-Hospital Outcomes, and Long-Term Mortality

Resumo Fundamento A síndrome de takotsubo (takotsubo) é uma forma de cardiomiopatia adquirida. Dados nacionais sobre essa condição são escassos. O Registro REMUTA é o primeiro a incluir dados multicêntricos dessa condição no nosso país. Objetivo Descrever as características clínicas, prognóstico, tratamento intra-hospitalar e mortalidade hospitalar e em 1 ano de seguimento. Métodos Estudo observacional, retrospectivo, tipo registro. Incluídos pacientes internados com diagnóstico de takotsubo ou que desenvolveram esta condição durante internação por outra causa. Os desfechos avaliados incluíram fator desencadeador, análise dos exames, uso de medicações, complicações e óbito intra-hospitalar e em 1 ano de seguimento. O nível de significância adotado foi de 5%. Resultados Foram incluídos 169 pacientes, em 12 centros no Estado do Rio de Janeiro. A idade média foi de 70,9 ± 14,1 anos e 90,5% eram do sexo feminino; 63% dos casos foram de takotsubo primário e 37% secundário. Troponina I foi positiva em 92,5% dos pacientes e a mediana de BNP foi de 395 (176,5; 1725). Supradesnivelamento do segmento ST esteve presente em 28% dos pacientes. A fração de ejeção do ventrículo esquerdo teve mediana de 40 (35; 48)%. Observamos taxa de 25,7% de ventilação mecânica invasiva e 17,4% de choque. Suporte circulatório mecânico foi utilizado em 7,7%. A mortalidade intra-hospitalar foi de 10,6% e a mortalidade ao final de 1 ano foi de 16,5%. Takotsubo secundário e choque cardiogênico foram preditores independentes de mortalidade. Conclusão Os resultados do REMUTA mostram que takotsubo não se trata de patologia benigna como se pensava, especialmente no grupo de takotsubo secundário que acarreta elevada taxa de complicações e de mortalidade. (Arq Bras Cardiol. 2020; 115(2):207-216)

Abstract Background Takotsubo syndrome (TTS) is an acquired form of cardiomyopathy. National Brazilian data on this condition are scarce. The Takotsubo Multicenter Registry (REMUTA) is the first to include multicenter data on this condition in Brazil. Objective To describe the clinical characteristics, prognosis, in-hospital treatment, in-hospital mortality, and mortality during 1 year of follow-up. Methods This is an observational, retrospective registry study including patients admitted to the hospital with diagnosis of TTS and patients admitted for other reasons who developed this condition. Evaluated outcomes included triggering factor, analysis of exams, use of medications, complications, in-hospital mortality, and mortality during 1 year of follow-up. A significance level of 5% was adopted. Results The registry included 169 patients from 12 centers in the state of Rio de Janeiro, Brazil. Mean age was 70.9 ± 14.1 years, and 90.5% of patients were female; 63% of cases were primary TTS, and 37% were secondary. Troponin I was positive in 92.5% of patients, and median BNP was 395 (176.5; 1725). ST-segment elevation was present in 28% of patients. Median left ventricular ejection fraction was 40 (35; 48)%. We observed invasive mechanical ventilation in 25.7% of cases and shock in 17.4%. Mechanical circulatory support was used in 7.7%. In-hospital mortality was 10.6%, and mortality at 1 year of follow-up was 16.5%. Secondary TTS and cardiogenic shock were independent predictors of mortality. Conclusion The results of the REMUTA show that TTS is not a benign pathology, as was once thought, especially regarding the secondary TTS group, which has a high rate of complications and mortality. (Arq Bras Cardiol. 2020; 115(2):207-216)