Guía de tratamiento farmacológico específico de la cardiomiopatía amiloidótica por transtiretina, 2021 / Specific pharmacological treatment guide for transthyretin amyloid cardiomyopathy, 2021

Resumen Con el propósito de confeccionar una guía con la mejor evidencia disponible en el tratamiento de la amiloidosis por depósito de transtiretina (ATTR), se generó un listado de preguntas en formato PICO centradas en la efectividad y seguridad y se realizó una búsqueda en PubMed, Cochrane y Epistemokus de los artículos publicados entre 2000-2020 y se incluyeron dos estudios de extensión en relación al tafamidis. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE, emitiéndose 11 recomendaciones para ATTRv y ATTwt. Se consideraron los siguientes fármacos: tafamidis, diflunisal, inotersen, patisiran y doxiciclina más ácido ursodesoxicolico. El grupo de expertos consensuó que el único tratamiento que demostró reducir de la mortalidad global, mortalidad cardiovascular, internaciones cardiovasculares y la progresión de la cardiopatía con un nivel moderado de evidencia fue el tafamidis 80 mg, mientras que para la formulación tafamidis 20 mg la calidad de evidencia es baja. Para inotersen y diflunisal, se formuló una recomendación en contra del tratamiento dada la falta de evidencia de calidad respecto a su efectividad, el perfil de toxicidad y la falta de disponibilidad en el ámbito local. Con respecto al patisirán, la recomendación se focalizó en la población ATTRv. El panel de expertos consensuó que el tratamiento con doxiciclina más ácido ursodeoxicólico podría ser utilizado ante la imposibilidad de iniciar tratamiento con tafamidis, recomendación débil y calidad de evidencia muy baja.

Abstract This clinical practice guideline for treating transthyretin amyloid (ATTR) cardiomyopathy is based on the best available evidence of clinical effectiveness. The PICO format was used to generate a list of ques tions focused on the effectiveness and safety of the specific treatment of patients with ATTR cardiomyopathy. The search was conducted in PubMed, Cochrane and Epistemokus, between July-August 2020, and selected articles between 2000-2020, in English and Spanish. The level of evidence and recommendations were analyzed and classified by the GRADE system. The following drugs were included in the analysis: tafamidis, diflunisal, inotersen, patisiran y doxycycline and ursodeoxycholic acid. The expert panel had an agreement that tafamidis 80mg/daily is the only available drug with moderate evidence and weak recommendation for the reduction of total mortality, cardiovascular morbidity, heart failure hospitalization and progression of the disease in patients with ATTR cardiomyopathy and NYHA class ≤ 3. In contrast, tafamidis 20 mg/daily had low-quality evidence in this group of patients. The expert panel did not recommend inotersen, patisiran and diflunisal in patients with ATTR cardiomyopathy due to the lack of supporting evidence, local drug availability, and the potential risk of toxicity. When patients did not have access to tafamidis, the expert panel stated a weak recommendation to use doxycycline and ursodeoxycholic acid in patients with ATTR cardiomyopathy.

[Specific pharmacological treatment guide for transthyretin amyloid cardiomyopathy, 2021]. / Guía de tratamiento farmacológico específico de la cardiomiopatía amiloidótica por transtiretina, 2021.

This clinical practice guideline for treating transthyretin amyloid (ATTR) cardiomyopathy is based on the best available evidence of clinical effectiveness. The PICO format was used to generate a list of questions focused on the effectiveness and safety of the specific treatment of patients with ATTR cardiomyopathy. The search was conducted in PubMed, Cochrane and Epistemokus, between July-August 2020, and selected articles between 2000-2020, in English and Spanish. The level of evidence and recommendations were analyzed and classified by the GRADE system. The following drugs were included in the analysis: tafamidis, diflunisal, inotersen, patisiran y doxycycline and ursodeoxycholic acid. The expert panel had an agreement that tafamidis 80mg/daily is the only available drug with moderate evidence and weak recommendation for the reduction of total mortality, cardiovascular morbidity, heart failure hospitalization and progression of the disease in patients with ATTR cardiomyopathy and NYHA class = 3. In contrast, tafamidis 20 mg/daily had low-quality evidence in this group of patients. The expert panel did not recommend inotersen, patisiran and diflunisal in patients with ATTR cardiomyopathy due to the lack of supporting evidence, local drug availability, and the potential risk of toxicity. When patients did not have access to tafamidis, the expert panel stated a weak recommendation to use doxycycline and ursodeoxycholic acid in patients with ATTR cardiomyopathy.

Con el propósito de confeccionar una guía con la mejor evidencia disponible en el tratamiento de la amiloidosis por depósito de transtiretina (ATTR), se generó un listado de preguntas en formato PICO centradas en la efectividad y seguridad y se realizó una búsqueda en PubMed, Cochrane y Epistemokus de los artículos publicados entre 2000-2020 y se incluyeron dos estudios de extensión en relación al tafamidis. Los niveles de evidencia y los grados de recomendación se basaron en el sistema GRADE, emitiéndose 11 recomendaciones para ATTRv y ATTwt. Se consideraron los siguientes fármacos: tafamidis, diflunisal, inotersen, patisiran y doxiciclina más ácido ursodesoxicolico. El grupo de expertos consensuó que el único tratamiento que demostró reducir de la mortalidad global, mortalidad cardiovascular, internaciones cardiovasculares y la progresión de la cardiopatía con un nivel moderado de evidencia fue el tafamidis 80 mg, mientras que para la formulación tafamidis 20 mg la calidad de evidencia es baja. Para inotersen y diflunisal, se formuló una recomendación en contra del tratamiento dada la falta de evidencia de calidad respecto a su efectividad, el perfil de toxicidad y la falta de disponibilidad en el ámbito local. Con respecto al patisirán, la recomendación se focalizó en la población ATTRv. El panel de expertos consensuó que el tratamiento con doxiciclina más ácido ursodeoxicólico podría ser utilizado ante la imposibilidad de iniciar tratamiento con tafamidis, recomendación débil y calidad de evidencia muy baja.

Relation of ventricular-vascular coupling to exercise capacity in ischemic cardiomyopathy: a cardiac multi-modality imaging study.

The purpose of this study was to examine the relationship between noninvasive measurements of ventricular-vascular coupling (VVC) with exercise tolerance, and compared the value of VVC versus other traditional determinants of exercise capacity in this population. 43 patients with ischemic CMP (age 59 +/- 9 years, mean EF 24 +/- 8%) underwent cardiopulmonary exercise testing, echocardiography and cardiac magnetic resonance (CMR). VVC was defined non-invasively by the ratio of ventricular systolic elastance (Ees) to the arterial elastance (Ea), where Ees = end-systolic pressure/end-systolic volume index and Ea = end-systolic pressure/stroke volume index. VVC significantly correlated with baseline heart rate (HR), peak exercise systolic blood pressure, maximum oxygen consumption (MVO(2)) and peak O(2) pulse (MVO(2)/HR). A higher VVC was associated with higher LVEF and RVEF but showed inverse relation to mitral E wave velocity. Univariate predictors of MVO(2) are baseline HR, chronotropic reserve, VVC and aortic distensibility; whilst mitral E wave velocity, LVEF, VVC, Ees significantly correlated with peak O(2) pulse. By stepwise multivariate analysis, VVC remained the only independent predictor of peak O(2) pulse. Ventricular-vascular coupling at rest may be a clinically important parameter in predicting exercise capacity in patients with advanced heart failure, and may become an additional target for therapeutic interventions.

Sudden death in a patient with lamin A/C gene mutation and near normal left ventricular systolic function.

Mutations in the lamin A/C gene seem to be important aetiological factors in familial DCM. Heart disease caused by lamin A/C gene mutations is characterised by conduction system disorders with the need for permanent pacemaker implantations, atrial fibrillation, severe heart failure, and increased risk for sudden cardiac death. We described an asymptomatic 28-year-old man with a R190W lamin A/C gene mutation and mild left ventricular enlargement and near normal left ventricular ejection fraction who suffered from sudden cardiac death during sleeping. His electrocardiogram did not show conduction system disease and the most remarkable finding was a progressive decrease in voltage, which may be a marker of disease progression. The case study's mother had a similar phenotype to this and also had died suddenly. Sudden cardiac death in some lamin A/C gene mutations may occur even before the development of severe left ventricular dysfunction and implantable cardioverter-defibrillator should be early considered.

[Clinical significance of late gadolinium enhancement on cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy]. / Significado clínico del realce tardío de gadolinio con resonancia magnética en pacientes con miocardiopatía hipertrófica.

INTRODUCTION AND OBJECTIVES: In patients with hypertrophic cardiomyopathy, myocardial fibrosis can be detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. We investigated the relationships between the extent of LGE, left ventricular morphology and function, and clinical characteristics. METHODS: Both cine and gadolinium-enhanced magnetic resonance imaging were performed in 104 patients with hypertrophic cardiomyopathy. RESULTS: Fifty patients (48%) showed LGE (range: 1-11 segments). The extent of LGE was positively correlated with maximum left ventricular wall thickness (r=0.53, P< .001), left ventricular mass (r=0.41, P< .001), and the number of hypokinetic segments (r=0.51, P< .001), and inversely correlated with ejection fraction (r=-0.32, P=.001), the magnitude of the subaortic gradient increase during exercise echocardiography (r=-0.26, P=.023), and age at diagnosis (r=-0.20, P=.04). Four of the five patients with an ischemic response on exercise echocardiography had > or =3 segments showing LGE (P=.003). Severe hypertrophy (i.e., > or =30 mm) and nonsustained ventricular tachycardia occurred more frequently as the number of LGE segments increased (P< .001 and P=.04, respectively). CONCLUSIONS: Extensive LGE reflects greater disease expression. It is associated with more severe myocardial damage (i.e., a lower ejection fraction and a larger number of hypokinetic segments) and with adverse clinical characteristics (e.g., young age at diagnosis, severe hypertrophy, nonsustained ventricular tachycardia, and an ischemic response on exercise), suggesting that it may be closely linked to prognosis.

Significado clínico del realce tardío de gadolinio con resonancia magnética en pacientes con miocardiopatía hipertrófica / Clinical significance of late gadolinium enhancement on cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy

Introducción y objetivos. La fibrosis miocárdica puede ser detectada en la miocardiopatía hipertrófica (MCH) mediante resonancia magnética cardiaca (RM) con realce tardío de gadolinio (RT). Analizamos la relación entre la extensión del RT y la morfología y función del ventrículo izquierdo (VI) y los datos clínicos. Métodos. Estudiamos con RM a 104 pacientes diagnosticados de MCH. Se obtuvieron secuencias de cine-RM y secuencias de realce tardío. Resultados. Cincuenta pacientes presentaron RT (48%; rango: 1-11 segmentos). La extensión del RT se correlacionó positivamente con el grosor máximo (r = 0,53; p < 0,001), la masa (r = 0,41; p < 0,001) y el número de segmentos hipocinéticos (r = 0,51; p < 0,001) del ventrículo izquierdo, e inversamente con la fracción de eyección (r = -­0,32; p = 0,001), la capacidad de incrementar el gradiente subaórtico durante la ecocardiografía de ejercicio (r = ­-0,26; p = 0,023) y la edad en el momento del diagnóstico (r = ­-0,20; p = 0,04). Cuatro de los 5 pacientes con una respuesta isquémica en la ecocardiografía de ejercicio presentaron ≥ 3 segmentos con RT (p = 0,003). La hipertrofia severa (≥ 30 mm) y la taquicardia ventricular no sostenida (TVNS) se asociaron con la extensión del RT (p < 0,001 y p = 0,04, respectivamente). Conclusiones. La extensión del RT refleja una mayor expresión de esta enfermedad. Se asocia con un daño miocárdico más severo (menor fracción de eyección y mayor número de segmentos hipocinéticos) y con parámetros clínicos adversos (edad más joven en el momento del diagnóstico, hipertrofia severa, TVNS y respuesta isquémica al ejercicio), lo que indica que podría vincularse al pronóstico

Introduction and objectives. In patients with hypertrophic cardiomyopathy, myocardial fibrosis can be detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. We investigated the relationships between the extent of LGE, left ventricular morphology and function, and clinical characteristics. Methods. Both cine and gadolinium-enhanced magnetic resonance imaging were performed in 104 patients with hypertrophic cardiomyopathy. Results. Fifty patients (48%) showed LGE (range: 1­11 segments). The extent of LGE was positively correlated with maximum left ventricular wall thickness (r=0.53, P<.001), left ventricular mass (r=0.41, P<.001), and the number of hypokinetic segments (r=0.51, P<.001), and inversely correlated with ejection fraction (r=-­0.32, P=.001), the magnitude of the subaortic gradient increase during exercise echocardiography (r=­-0.26, P=.023), and age at diagnosis (r=-­0.20, P=.04). Four of the five patients with an ischemic response on exercise echocardiography had ≥3 segments showing LGE (P=.003). Severe hypertrophy (i.e., ≥30 mm) and nonsustained ventricular tachycardia occurred more frequently as the number of LGE segments increased (P<.001 and P=.04, respectively). Conclusions. Extensive LGE reflects greater disease expression. It is associated with more severe myocardial damage (i.e., a lower ejection fraction and a larger number of hypokinetic segments) and with adverse clinical characteristics (e.g., young age at diagnosis, severe hypertrophy, nonsustained ventricular tachycardia, and an ischemic response on exercise), suggesting that it may be closely linked to prognosis

Interpretation of electrocardiographic abnormalities in hypertrophic cardiomyopathy with cardiac magnetic resonance.

AIMS: To clarify the mechanisms of electrocardiographic abnormalities in hypertrophic cardiomyopathy, 102 patients were examined with cardiac magnetic resonance. Distribution and magnitude of hypertrophy and late-enhancement were correlated with electrocardiographic abnormalities. METHODS AND RESULTS: Abnormal Q waves were associated with greater upper anterior septal thickness (22+/-7 mm vs. 18+/-5 mm, P=0.001) and increased ratios of upper anterior septum to mean inferolateral (P=0.01), anterolateral (P=0.002), apical (P=0.001), and right ventricular (P=0.001) wall thickness. There was no relation between abnormal Q waves and late-enhancement, except for Q waves >/=40 ms (P=0.02). Conduction disturbances and absent septal Q waves were associated with late-enhancement (89 vs. 45%, P=0.01 and 75 vs. 39%, P=0.002, respectively). The depth of negative T waves was related to an increased ratio of the mean thickness between apical and basal level (P=0.01), and to the presence of apical late-enhancement (P=0.03). CONCLUSION: Abnormal Q waves reflect the interrelation between upper anterior septal thickness and other regions of the left and right ventricles, and wider Q waves are associated with late-enhancement. Conduction disturbances and absent septal Q waves are associated with late-enhancement. The depth of negative T waves is related to craniocaudal asymmetry and apical late-enhancement.