Serum Biomarkers and Their Association with Myocardial Function and Exercise Capacity in Cardiac Transthyretin Amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR amyloidosis) is a frequent etiology of heart failure. Inflammation and mineral metabolism are associated with myocardial dysfunction and clinical performance. Cardiac global longitudinal strain (GLS) allows function assessment and is associated with prognosis. Our aim was to describe possible correlations between GLS, biomarker levels and clinical performance in ATTR amyloidosis. METHODS: Thirteen patients with ATTR amyloidosis were included. Clinical characteristics; echocardiographic features, including strain assessment and 6 min walk test (6MWT); and baseline inflammatory, mineral metabolism and cardiovascular biomarker levels were assessed. RESULTS: Of the 13 patients, 46.2% were women, and the mean age was 79 years. TAPSE correlated with NT-ProBNP (r -0.65, p < 0.05) and galectin-3 (r 0.76, p < 0.05); E/E' ratio correlated with hsCRP (r 0.58, p < 0.05). Left ventricular GLS was associated with NT-ProBNP (r 0.61, p < 0.05) (patients have a better prognosis if the strain value is more negative) and left atrial GLS with NT-ProBNP (r -0.73, p < 0.05) and MCP1 (r 0.55, p < 0.05). Right ventricular GLS was correlated with hsTnI (r 0.62, p < 0.05) and IL6 (r 0.881, p < 0.05). Klotho levels were correlated with 6MWT (r 0.57, p < 0.05). CONCLUSIONS: While inflammatory biomarkers were correlated with cardiac function, klotho levels were associated with clinical performance in the population with TTR-CA.

Prevalence and prognostic value of monoclonal gammopathy in heart failure patients with preserved ejection fraction: A prospective study.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) and monoclonal gammopathy of uncertain significance (MGUS) are two entities that share pathophysiological mechanisms. The aim herein, was to assess the prevalence of MGUS in patients with HFpEF and no left ventricular (LV) hypertrophy, as well as its association with a pre-specified clinical endpoint at 12 months. METHODS: The present study prospectively enrolled 69 patients admitted with HF, with ejection fraction ≥ 50%, and LV wall thickness < 12 mm. All patients were screened for MGUS. Clinical events were determined over a 12 month follow-up. The pre-specified composite clinical endpoint was readmission for HF or death. RESULTS: The prevalence of MGUS in this population was 13%. There were no differences in the incidence of the composite clinical endpoint between patients with and without MGUS. Multivariate analysis showed that treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) was associated with fewer clinical events (HR: 0.153, 95% CI: 0.037-0.622, p = 0.009) and indicated a trend to lower risk of readmission for HF and death. Beta-blockers were associated with lower rates of the composite clinical endpoint (HR: 0.192, 95% CI: 0.05-0.736, p = 0.016), readmission for HF (HR: 0.272, 95% CI: 0.087-0.851, p = 0.025) and indicated a trend to lower mortality. Moreover, potassium serum levels > 5 mEq/L were associated with higher rates of the composite endpoint (HR: 6.074, 95% CI: 1.6-22.65, p = 0.007). CONCLUSIONS: The prevalence of MGUS in patients with HFpEF without hypertrophy was 3-fold that of the general population. There was no significant correlation between clinical outcomes and the presence of MGUS. Beta-blockers and ACEIs/ARBs reduced the composite of mortality and readmissions for HF in HFpEF patients. Hyperpotassemia was related to worse prognosis.

Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy.

AIMS: As evidenced by scintigraphy imaging, the prevalence of transthyretin (TTR) cardiac amyloidosis in heart failure patients with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH) ranges between 13% and 19%. The natural evolution of cardiac amyloidosis begins with the deposition of amyloid material in the myocardium, with LVH ensuing at later stages. With current imaging modalities, it is possible to detect TTR cardiac amyloidosis before the hypertrophic stage. The aim of this study was to determine the prevalence of TTR cardiac amyloidosis in HFpEF patients without LVH. METHODS AND RESULTS: The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. Transthyretin gene sequencing was performed in positive patients. From July 2017 to January 2020, 329 patients with HFpEF and LV thickness <12 mm were identified. After exclusions, 58 patients completed the study with cardiac scintigraphy (79 years, 54% men; median LVEF 60% and LV wall thickness 10.5 mm). Three patients (5.2%) were positive for TTR cardiac amyloidosis; genetic analysis excluded the presence of hereditary TTR amyloidosis. Positive patients baseline characteristics (84 years, 67% men, LVEF 60%, and LV wall thickness 11 mm) were similar to patients without TTR, except for troponin levels (0.05 vs. 0.02 ng/mL, P = 0.03) and glomerular filtration rate (82 vs. 60 mL/min, P = 0.032), which were higher in TTR patients. CONCLUSIONS: In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Early diagnosis of cardiac involvement in TTR amyloidosis (before manifest LVH) would seem recommendable because newly approved specific treatments can prevent additional deposition of amyloid material.

Tratamiento con radioyodo en el hipertiroidismo: resultados a largo plazo / Radioiodine in hyperthyroidism: long-term outcomes

Introducción: El 131I es una opción terapéutica eficaz para el tratamiento del hipertiroidismo, aunque en un alto porcentaje de pacientes se desarrolla hipotiroidismo definitivo. Objetivo: Evaluar la función tiroidea a largo plazo de pacientes con hipertiroidismo tras el tratamiento con 131I. Pacientes y método: Se estudió retrospectivamente a 128 pacientes hipertiroideos que recibieron 131I entre 1994 y 1999. Se excluyó a 32 por pérdida en el seguimiento y se clasificó a los 96 sujetos incluidos, según la afección tiroidea, en GB (Graves-Basedow, n = 46), BMN (bocio multinodular, n = 35) y AT (adenoma tóxico, n = 15). El tiempo de seguimiento fue 7,3 ± 0,2 años y la dosis media de 131I, 12,2 ± 0,3 mCi. Resultados: De los 96 pacientes, en el 58,3% se desarrolló hipotiroidismo, el 34,4% mantenía normofunción tiroidea y el 7,3% restante permanecía con hiperfunción clínica o subclínica. El 19,8% (n = 19) precisó más de una dosis de 131I. En el grupo GB, el 87% evolucionó a hipotiroidismo, el 10,9% persistía eutiroideo y el 2,1%, con hiperfunción; recibieron 2 dosis de 131I 10 (21,7%) pacientes. Del grupo BMN, el 28,6% quedó hipotiroideo; el 54,3%, eutiroideo y el 17,1%, con hiperfunción; 7 (20%) pacientes necesitaron 2 dosis y 2 (5,7%) pacientes, 3 dosis. En el grupo AT, el 40% desarrolló hipotiroidismo y el 60% mantenía normofunción tiroidea; 2 (13,3%) pacientes recibieron 2 dosis. Conclusiones: La tasa de hipotiroidismo definitivo en el grupo GB es superior a la de los otros 2 grupos. El alto porcentaje de pacientes con BMN que persisten hipertiroideos tras 131I indica que son necesarias dosis superiores en este grupo

Background: Radioiodine treatment is a safe and effective therapeutic option for hyperthyroidism, although the incidence of subsequent definitive hypothyroidism is high. Objective: To evaluate long-term thyroid function after radioiodine treatment in hyperthyroid patients. Patients and method: We performed a retrospective study of 128 hyperthyroid patients administered 131I between 1994 and 1999. We excluded 32 patients who were lost to follow-up. The 96 patients included were categorized into Graves' disease (GD), n = 46, toxic multinodular goiter (TMG), n = 35, and toxic adenoma (TA), n = 15. The mean time of follow-up was 7.3 ± 0.2 years and the mean 131I dose was 12.2 ± 0.3 mCi. Results: Among the 96 patients, hypothyroidism developed in 58.3%, normal thyroid function was achieved in 34.4% and some degree of hyperthyroidism persisted in 7.3%. More than one radioiodine dose was required in 19.8% (n = 19). In GD patients, hypothyroidism appeared in 87%, euthyroidism was achieved in 10.9%, and hyperthyroidism persisted in 2.1%. Ten patients required second 131I doses. In the TMG group, hypothyroidism developed in 28.6%, euthyroidism was achieved in 54.3% and hyperthyroidism was present in 17.1%. Seven patients (20%) were administered a second radioiodine dose and two patients (5.7%) received a third dose. In the TA group, hypothyroidism developed in 40% and euthyroidism was achieved in 60%. Two patients (13.3%) received a second 131I dose. Conclusions: The incidence of definitive hypothyroidism was higher in the GD group than in the TMG and TA groups. The high percentage of TMG patients with persistent hyperthyroidism suggests the need for higher radioiodine doses in this group

La concentración de ácido hialurónico citosólico define ciertas propiedades clinicobiológicas del carcinoma ductal infiltrante de mama CD44v5 positivo / The cytosolic hyaluronic acid level defines some clinical-biological properties of CD44v5-positive infiltrating ductal carcinomas of the breasst

Fundamento: El ácido hialurónico es uno de los ligandos de la molécula de adhesión CD44. En este estudio hemos querido analizar si su concentración citosólica podía modular ciertos parámetros clinicobiológicos en el carcinoma ductal infiltrante (CDI) de mama CD44v5+. Pacientes y métodos: Hemos determinado, mediante un método de radioligando, las concentraciones citosólicas de ácido hialurónico en 127 casos. Así mismo, dosificamos los valores citosólicos de receptor de estrógenos, progesterona, pS2, catepsina D y activador del plasminógeno tipo tisular (t-AP), así como las del receptor del factor de crecimiento epidérmico (EGFR) en las membranas celulares. Se tuvieron presentes también el estado menopáusico, tamaño, invasión ganglionar axilar, grado histológico, ploidía y fase de síntesis celular. Resultados: Los CDI con ácido hialurónico positivo (> 4.800 ng/mg de proteína) que representa la mediana obtenida en 252 CDI, cursaron con mayores concentraciones de receptores de progesterona (p = 0,035) y t-AP (p = 0,000), mientras que los CDI con ácido hialurónico negativo mostraron con mayor frecuencia un tamaño superior a 2 cm (p = 0,015), aneuploidía (p = 0,002) y una fase S mayor del 14 por ciento (p = 0,019), así como un grado histológico 3 que rozó la significación estadística (p = 0,062), indicadores todos ellos de un peor comportamiento y evolución. Conclusiones: Los resultados anteriores indican que, como ocurre con el de membrana, la concentración del ácido hialurónico citosólico parece modular ciertas propiedades clínicobiológicas del CDI/CD44v5+, lo que realza el papel de ambos parámetros y podría ayudar a explicar algunas discordancias descritas en la bibliografía acerca de su interés práctico cuando se consideran aisladamente cada uno de ellos (AU)