Phenotypic Expression and Outcomes in Patients with the p.Arg301Gln GLA Variant in Anderson-Fabry Disease.

The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.

Endocarditis infecciosa de válvula nativa: factores asociados a resultados adversos / Mortality predictors in patients with native valve infec tive endocarditis

Resumen Introducción : La mortalidad de la endocarditis infec ciosa (EI) en Argentina continúa siendo elevada. El obje tivo del trabajo fue describir las características clínicas e identificar factores asociados a mortalidad en pacientes con EI de válvula nativa. Métodos : Estudio de cohorte retrospectiva que inclu yó pacientes adultos con diagnóstico de EI de válvula nativa internados durante 2011-2021. Resultados : Se incluyeron 129 pacientes con una edad promedio de 66±17 años. El organismo responsa ble más frecuente (38.8%, n = 50) fue el Staphylococcus aureus (SA). El 63.6% presentó criterios de indicación quirúrgica. La mortalidad durante la internación fue del 22.5%. En el análisis multivariado que incluyó índice de comorbilidad Charlson, infección por SA y la presencia de criterios de indicación quirúrgica, se observó un OR ajustado de mortalidad de 1.32 (IC95% 1.10-1.57; p = 0.003), 2.75 (IC95% 1.11-6.8; p = 0.028) y 4.14 (IC95% 1.34-12; p = 0.013), respectivamente. En el análisis mul tivariado para mortalidad alejada que agregó el criterio quirúrgico y la realización de cirugía durante la inter nación, se observó un OR ajustado de 1.62 (IC95% 1.31- 2.00; p < 001), 0.77 (IC95% 0.31-1.93; p = 0.58), 7.49 (IC95% 2.07-27.07; p = 0.002) y 0.21 (IC95% 0.06-0.70; p = 0.01), respectivamente. Conclusiones : La mortalidad de la EI se asoció al grado de comorbilidad previa, a la forma de presenta ción y, en relación inversa, a la realización oportuna del tratamiento quirúrgico.

Abstract Introduction : Mortality of infective endocarditis (IE) in Argentina continues to be high. The aim objective was to describe the clinical characteristics and identify factors associated with in-hospital and long-term mortality in patients with native valve IE. Methods : Retrospective cohort study including adult patients with diagnosis of native valve IE, hospitalized during 2011-2021. Results : A total of 129 patients with a mean age of 66±17 years were included. The most frequent respon sible organism was Staphylococcus aureus (SA) (38.8%). Surgical indication criteria were present in 63.6% of the patients. Mortality during hospitalization was 22.5% .In the multivariate analysis that included Charlson comorbidity index, SA infection and the presence of surgical indication criteria, an adjusted OR of mor tality of 1.32 (95%CI 1.10-1.57; p = 0.003), 2.75 (95%CI 1.11-6.8; p = 0.028) and 4.14 (95%CI 1.34-12; p = 0.013), respectively, was observed. In the multivariate analysis for long term mortality, that added surgical indication criteria and the performance of surgery during hospitalization, an adjusted OR of 1.62 (CI95% 1.31-2.00; p<001), 0.77 (95%CI 0.31-1.93; p = 0.58), 7.49 (95%CI 2.07-27.07; p = 0.002) and 0.21 (95%CI 0.06-0.70; p = 0.01), respec tively, was observed. Conclusions : Mortality in IE was associated with the degree of previous comorbidity, with the presence of surgical indication criteria and, inversely, with the timely completion of surgical treatment.

[Mortality predictors in patients with native valve infective endocarditis]. / Endocarditis infecciosa de válvula nativa: factores asociados a resultados adversos.

INTRODUCTION: Mortality of infective endocarditis (IE) in Argentina continues to be high. The aim objective was to describe the clinical characteristics and identify factors associated with in-hospital and long-term mortality in patients with native valve IE. METHODS: Retrospective cohort study including adult patients with diagnosis of native valve IE, hospitalized during 2011-2021. RESULTS: A total of 129 patients with a mean age of 66±17 years were included. The most frequent responsible organism was Staphylococcus aureus (SA) (38.8%). Surgical indication criteria were present in 63.6% of the patients. Mortality during hospitalization was 22.5% .In the multivariate analysis that included Charlson comorbidity index, SA infection and the presence of surgical indication criteria, an adjusted OR of mortality of 1.32 (95%CI 1.10-1.57; p = 0.003), 2.75 (95%CI 1.11-6.8; p = 0.028) and 4.14 (95%CI 1.34-12; p = 0.013), respectively, was observed. In the multivariate analysis for long term mortality, that added surgical indication criteria and the performance of surgery during hospitalization, an adjusted OR of 1.62 (CI95% 1.31-2.00; p<001), 0.77 (95%CI 0.31-1.93; p = 0.58), 7.49 (95%CI 2.07-27.07; p = 0.002) and 0.21 (95%CI 0.06-0.70; p = 0.01), respectively, was observed. CONCLUSIONS: Mortality in IE was associated with the degree of previous comorbidity, with the presence of surgical indication criteria and, inversely, with the timely completion of surgical treatment.

Introducción: La mortalidad de la endocarditis infecciosa (EI) en Argentina continúa siendo elevada. El objetivo del trabajo fue describir las características clínicas e identificar factores asociados a mortalidad en pacientes con EI de válvula nativa. Métodos: Estudio de cohorte retrospectiva que incluyó pacientes adultos con diagnóstico de EI de válvula nativa internados durante 2011-2021. Resultados: Se incluyeron 129 pacientes con una edad promedio de 66±17 años. El organismo responsable más frecuente (38.8%, n = 50) fue el Staphylococcus aureus (SA). El 63.6% presentó criterios de indicación quirúrgica. La mortalidad durante la internación fue del 22.5%. En el análisis multivariado que incluyó índice de comorbilidad Charlson, infección por SA y la presencia de criterios de indicación quirúrgica, se observó un OR ajustado de mortalidad de 1.32 (IC95% 1.10-1.57; p = 0.003), 2.75 (IC95% 1.11-6.8; p = 0.028) y 4.14 (IC95% 1.34-12; p = 0.013), respectivamente. En el análisis multivariado para mortalidad alejada que agregó el criterio quirúrgico y la realización de cirugía durante la internación, se observó un OR ajustado de 1.62 (IC95% 1.31- 2.00; p < 001), 0.77 (IC95% 0.31-1.93; p = 0.58), 7.49 (IC95% 2.07-27.07; p = 0.002) y 0.21 (IC95% 0.06-0.70; p = 0.01), respectivamente. Conclusiones: La mortalidad de la EI se asoció al grado de comorbilidad previa, a la forma de presentación y, en relación inversa, a la realización oportuna del tratamiento quirúrgico.

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy.

INTRODUCTION: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype-phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM. METHODS: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM. RESULTS: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity. CONCLUSIONS: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.

Prevalencia de dilatación aórtica en pacientes con válvula aórtica bicúspide según los valores de referencia de la población argentina / Prevalence of Aortic Dilation in Patients with Bicuspid Aortic Valve According to Reference Values for the Argentine Population

RESUMEN Introducción: Una proporción significativa de los pacientes con válvula aórtica bicúspide (VAB) desarrollan una dilatación de la aorta que los predispone a serias complicaciones. Objetivos: Estimar la prevalencia de dilatación aórtica aplicando los valores de referencia de la población argentina en pacientes con VAB y la influencia de los distintos métodos de indexación (talla, T, y superficie corporal, SC). Materiales y métodos: Se incluyeron consecutivamente 581 pacientes adultos con VAB. Se definió la dilatación según el criterio propuesto por las guías (fórmulas de Devereux) y sobre la base de los valores propuestos por el registro MATEAR (Medición de Aorta Torácica por Ecocardiografía en Argentina). Resultados: La edad media fue de 44,9 años (±16), 68,7% sexo masculino. Sobre la base del registro MATEAR se observó alta prevalencia de dilatación de la raíz aórtica o aorta ascendente (72,3% según T y 61,5% según SC) que resultó, en la raíz, mayor que la obtenida según las fórmulas de Devereux (T 47% vs. 31,5%; SC 35,2% vs. 26,5% p < 0,001). Se observó una subestimación sistemática al indexar por SC en pacientes con índice de masa corporal >25 kg/m² (57,8% de la población). Conclusiones: La prevalencia de dilatación aórtica, cuando aplicamos los valores de referencia para la población argentina, fue alta y en la raiz significativamente mayor que la determinada por puntos de corte originados en otras poblaciones. Se observó una subestimación sistemática al corregir por superficie corporal en pacientes con índice de masa corporal >25 kg/m², por lo que indexar por talla sería la opción más recomendable.

ABSTRACT Background: A significant proportion of patients with bicuspid aortic valve (BAV) develop aortic dilation predisposing to serious complications. Objective: The aim of this study was to estimate the prevalence of aortic dilation applying reference values for the Argentine population in patients with BAV, and the influence of different indexing methods [height, (H) and body surface area (BSA)] Methods: A total of 581 adult patients with BAV were consecutively included in the study. Aortic dilation was defined according to guideline criteria (Devereux formula) and the reference values suggested by the Echocardiography Thoracic Aortic Assessment in Argentina (MATEAR) registry. Results: Mean age was 44.9±16 years and 68.7% were men. A high prevalence of aortic root or ascending aorta dilation was observed based on MATEAR criteria (72.3% according to H and 61.5 % according to BSA). This was significantly higher for the aortic root than the one obtained with the Devereux formula (H: 47% vs. 31.5%; BSA: 35.2% vs. 26.5% P <0.001). A systematic underestimation was found when indexing for BSA in patients with body mass index (BMI) >25 kg/m² (57.8% of population). Conclusions: When applying the reference values for the Argentine population the prevalence of aortic dilation was high and significantly greater than at the root that determined by cutoff points originating in other populations. Systematic underestimation was observed when correcting for BSA in patients with BMI >25 kg/m², so indexing by H would be the most recommended option.

Prognostic value of NT-proBNP, and echocardiographic indices of diastolic function, in hospitalized patients with acute heart failure and preserved left ventricular ejection fraction.

BACKGROUND: Several parameters have proven useful in assessing prognosis in outpatients with heart failure with preserved ejection fraction (HFpEF). In contrast, prognostic determinants in HFpEF hospitalized for an acute event are poorly investìgated. AIM: To determine the predictive value of NT-proBNP, and diastolic function (assessed by E/e'), in patients with HFpEF hospitalized for acute heart failure. METHODS AND RESULTS: We evaluated 205 consecutive HFpEF patients admitted for acute heart failure (median age: 76[53,81], 36% male, median EF: 61 [54,77]). We assessed clinical, echocardiographic, and NT-proBNP values, on admission and at discharge. Primary end-point was the composite of all-cause death and/or HF rehospitalization. After a mean follow up of 28±10 months, 82 patients met the primary end-point; there were 30 deaths (14.6%), and 72 patients (35%) were rehospitalized for HF. By multivariable analysis, predictors of the composite end-point were: discharge E/e´ ≥14 (HR: 4.63 CI 95%: 2.71-18.2, p<0.0001), discharge NT-proBNP ≥1500 pg/ml (HR: 5.23, CI 95%: 2.87-17.8, p < 0.0001), ≥50% NT-proBNP decrease between admission and discharge (HR: 0.62, CI 95%: 0.25-0.79, p = 0.019). Combining E/e´ and NT-proBNP values at discharge further and significantly improved discrimination power compared to each variable analyzed separately (AUC, NT-proBNP at discharge: 0.80; E/e´ at discharge: 0.77; E/e´ + NT-proBNP: 0.88; p < 0.01). CONCLUSIONS: In HFpEF patients hospitalized with acute heart failure, assessment of E/e´ ratio and NT-proBNP at discharge provides prognostic information on top of other variables, and allows to easily identify a population at higher risk of subsequent death or rehospitalization for heart failure, during a medium-term follow up.

Estudio descriptivo de validez y aplicabilidad de la regla nemotécnica POUNDing en pacientes con migraña / Validity and applicability of the mnemonic POUNDing rule in patients with migraine. A descriptive study

INTRODUCCIÓN: En la valoración inicial de un paciente con cefalea, el médico se plantea con frecuencia si el dolor se corresponde con una migraña y si el paciente precisa pruebas de neuroimagen. El objetivo del trabajo fue valorar la validez y aplicabilidad de la regla nemotécnica POUNDing en pacientes diagnosticados de migraña. PACIENTES Y MÉTODOS: Estudio descriptivo, de aplicación de la regla POUNDing en pacientes con diagnóstico de migraña y con realización de alguna prueba de imagen cerebral (tomografía computarizada o resonancia magnética), en un centro de salud urbano y en una consulta de Neurología del Hospital Universitario de Badajoz. RESULTADOS: Se incluyó a 116 pacientes (edad media 45,6 años; 79,3% mujeres; 70 procedentes de consultas de Neurología y 46 del centro de salud). Destacaron en las comparaciones los elevados valores predictivos positivos: 90,9% (IC 95%: 57,1-99,5%); 100% (IC 95%: 73,2-99,3%) y 96,0% (IC 95%: 77,7-99,8%), en los pacientes de la consulta de Neurología, del centro de salud y en la población total, respectivamente, y sus bajos valores predictivos negativos: 6,8% (IC 95%: 2,2-17,3%); 3,1% (IC 95%: 0,2-18,0%) y 5,5% (IC 95%: 2,0-12,9%), también respectivamente en los pacientes de la consulta de Neurología, del centro de salud y en la población total. CONCLUSIONES: La regla POUNDing presenta un alto valor predictivo positivo y podría ser de gran ayuda en la aceptación o rechazo de un diagnóstico de migraña, al facilitar un uso más eficiente de las pruebas de neuroimagen

INTRODUCTION: In assessing the patient with headache, clinicians are often faced with 2 important questions: Is this headache a migraine? Does this patient require neuroimaging? The aim of this study was to assess the validity and applicability of the mnemonic POUNDing rule in patients diagnosed with migraine. PATIENTS AND METHODS: A descriptive, validation study of the POUNDing rule in patients with a diagnosis of migraines and with a brain imaging test (computed tomography or magnetic resonance imaging), in an urban health centre and a neurology clinic of the University Hospital of Badajoz. RESULTS: A total of 116 patients were included (mean age 45.6 years; 79.3% women, 70 from the neurology clinics, and 46 from the health centre). The best validity parameters of the POUNDing rule were its positive predictive values: 90.9% (95% CI: 57.1-99.5%), 100% (95% CI: 73.2-99.3%), and 96.0% (95% CI: 77.7-99.8%) in the patients of the neurology clinic, the health centre and in the total population, respectively, and its low negative predictive values: 6.8% (95% CI: 2.2-17.3%), 3.1% (95% CI: 0.2-18.0%), and 5.5% (95% CI: 2.0-12.9%), also respectively in the patients of the neurology clinic, the health centre and in the total population. CONCLUSIONS: The POUNDing mnemonic rule has a high positive predictive values and can be a great help in accepting or rejecting a diagnosis of migraine, facilitating a more efficient use of neuroimaging tests

[Validity and applicability of the mnemonic POUNDing rule in patients with migraine. A descriptive study]. / Estudio descriptivo de validez y aplicabilidad de la regla nemotécnica POUNDing en pacientes con migraña.

INTRODUCTION: In assessing the patient with headache, clinicians are often faced with 2 important questions: Is this headache a migraine? Does this patient require neuroimaging? The aim of this study was to assess the validity and applicability of the mnemonic POUNDing rule in patients diagnosed with migraine. PATIENTS AND METHODS: A descriptive, validation study of the POUNDing rule in patients with a diagnosis of migraines and with a brain imaging test (computed tomography or magnetic resonance imaging), in an urban health centre and a neurology clinic of the University Hospital of Badajoz. RESULTS: A total of 116 patients were included (mean age 45.6 years; 79.3% women, 70 from the neurology clinics, and 46 from the health centre). The best validity parameters of the POUNDing rule were its positive predictive values: 90.9% (95% CI: 57.1-99.5%), 100% (95% CI: 73.2-99.3%), and 96.0% (95% CI: 77.7-99.8%) in the patients of the neurology clinic, the health centre and in the total population, respectively, and its low negative predictive values: 6.8% (95% CI: 2.2-17.3%), 3.1% (95% CI: 0.2-18.0%), and 5.5% (95% CI: 2.0-12.9%), also respectively in the patients of the neurology clinic, the health centre and in the total population. CONCLUSIONS: The POUNDing mnemonic rule has a high positive predictive values and can be a great help in accepting or rejecting a diagnosis of migraine, facilitating a more efficient use of neuroimaging tests.

DIFFUSE LARGE B-CELL LYMPHOMA-ASSOCIATED-RETINOPATHY CHARACTERIZED BY MINIMAL MORPHOLOGIC CHANGES AND SEVERE FUNCTIONAL IMPAIRMENT.

PURPOSE: To report the case of a patient whose retinal disease was found to be associated with a diffuse large B-cell lymphoma found 30 years after the apparent successful treatment of a classical Hodgkin lymphoma. METHODS: Observational case report. RESULTS: The authors describe the case of a 69-year-old man referred to their Department because of progressive, bilateral vision loss over the last few months. Deterioration in color vision and intense photophobia were also present. His best-corrected visual acuity was 20/400 in the right eye (RE) and 20/800 in the left eye (LE). Slit lamp and fundus examination failed to show any abnormalities. Spectral domain optical coherence tomography (SD-OCT) detected diffuse attenuation of the ellipsoid layers in addition to a focal subfoveal defect in both eyes. Both fluorescein and indocyanine angiographies (FA and ICGA) were normal. Full flash electroretinogram (ERG) revealed bilateral cone rod dysfunction with decreased amplitudes of both a and b waves. CONCLUSION: Because of the late onset of the disease, poor visual acuity compared with a small macular anatomical lesion and a history of Hodgkin lymphoma 30 years ago, a neoplastic etiology was investigated. Poor performance status and chest pain led to a thoracic CT scan, which identified a massive mediastinal tumor. Serum analysis found an abnormal amount of antibody activity within the 40 kD region of Western blot of retina. The diagnosis of diffuse large B-cell lymphoma was established. Systemic examinations found a Stage IV non-Hodgkin lymphoma.

Precursors of type 3 neovascularization: a multimodal imaging analysis.

PURPOSE: To study the advent of exudative age-related macular degeneration in uninvolved fellow eyes of patients with unilateral Type 3 neovascularization and to investigate the precursors at the site of lesion development. METHODS: We studied 37 consecutive patients with the diagnosis of unilateral Type 3 neovascularization, for the advent of exudative age-related macular degeneration in uninvolved fellow eyes (study eyes). Looking for the precursors of Type 3 neovascularization, we reviewed the multimodal imaging (fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography) in the study eyes and interpreted the changes over time at the site of lesion development. RESULTS: Of the 37 patients, 12 (32%) developed exudative age-related macular degeneration in the study eye, after a mean of 19.6 ± 9.5 months (range, 9-36 months) from the diagnosis of Type 3 neovascularization in the first involved eye (baseline). All these patients (12 of 12 eyes; 100%) developed Type 3 neovascularization in the study eye. Retrospective analysis of the precursors of these lesions revealed, at baseline, a focal hyperautofluorescence (fundus autofluorescence) that turned to focal hypoautofluorescence over time. In all eyes, a focal hyperfluorescence (fluorescein angiography and indocyanine green angiography) appeared over time at the site of Type 3 neovascularization development. The corresponding spectral-domain optical coherence tomography showed a localized retinal pigment epithelial (RPE) elevation characterized by a focal disruption of the RPE and photoreceptors and by the overlying outer plexiform layer that progressively took contact with the RPE. Based on these findings, it seems that a small, localized RPE elevation might be the lesion before the development of Type 3 neovascularization. This precursor lesion progresses over time to focal atrophy of RPE and photoreceptor. CONCLUSION: Type 3 neovascularization presents a predictable symmetry and bilaterality. Identification of the precursors of Type 3 neovascularization looks particularly useful for clinicians to detect the earliest changes in the vasogenic process in the fellow eye.