Cardiac amyloidosis and red flags: natural history and its impact in morbimortality. / Amiloidosis cardiaca y red flags: historia natural e impacto en la morbimortalidad.

INTRODUCTION AND OBJECTIVES: Red flags (RF) are typical cardiac and extracardiac manifestations that may precede the definitive diagnosis of cardiac amiloidosis (CA) by several years, playing a pivotal role in the early diagnosis of the disease. The principal aim of the research was to determine the chronology of onset of RF throughout the natural history of CA as well as its prognostic influence. PATIENTS AND METHODS: Observational, retrospective inquiry of consecutive patients with a definitive diagnosis of CA in a terciary hospital centre in Ciudad Real (Spain) between February 2016 and December 2023. We defined 21 RF and 3 adverse clinical events, establishing the date of occurrence of each of them. RESULTS: 102 patients (81.6±7.7 years; 84,3% males) with a diagnosis of CA (89.2% TTR; 10,8% AL) were included. The prevalence of RF was very high (8.4±2.3). In the natural history, the first to appear were integumentary, with the most specific cardiological ones being the closest to diagnosis. The 2-year mortality was 49%, with biomarker RFs and the presence of ≥10 RFs being associated with higher mortality. CONCLUSIONS: RFs proved highly prevalent among patients with CA and substantially preceded disease diagnosis. RF burden was associated with prognosis in the follow-up of ATTR patients.

Usefulness of risk scores and predictors of atrial fibrillation recurrence after elective electrical cardioversion.

INTRODUCTION: Electrical cardioversion (ECV) is a frequently used procedure for restoring sinus rhythm in atrial fibrillation (AF); however, the rate of recurrence is high. The identification of patients at high risk of recurrence could influence the decision-making process. The present study evaluates the predictive value of risk scores in atrial fibrillation recurrence after elective electrical cardioversion. METHODS: Unicentric, observational, and prospective study of adult patients who have undergone an elective ECV as rhythm control strategy between July 2017 and September 2022. RESULTS: From the 283 analyzed patients (mean age 63.95 ± 10.76212, 74.9% male); 99 had paroxysmal AF (35%) and 159 (59%) presented AF recurrence during a follow-up of 6 months. In patients with post-ECV AF recurrence, the period of time from diagnosis until the performance of the procedure was longer (393 ± 891 vs. 195 ± 527, p = .02). No paroxysmal AF (71.3% vs. 57.8%, p = .02) and LA dilatation with >40 mL/m2 (35.9% vs. 23.3%, p = .02) volumes were more frequent within these patients. AF recurrence was more frequent in patients who had previous ECV (HR = 1.32; 95% CI: 1.12-2.35; p = .01) and more than 1 shock to recover sinus rhythm (HR = 1.62; 95% CI: 1.07-1.63; p = .01). The SLAC, ALARMEc, ATLAS, and CAAP-AF scores were statistically significant, although with a moderate predictive capacity for post-ECV recurrence. CONCLUSIONS: Risk scores analyzed showed a modest value predicting AF recurrence after ECV. Previous ECV, and greater difficulty in restoring SR were independent predictors of recurrence.

Intermediate-effect size p.Arg637Gln in FHOD3 increases risk of HCM and is associated with an aggressive phenotype in homozygous carriers.

Formin homology 2 domain-containing 3 (FHOD3) gene has emerged as one of the main non-sarcomeric genes associated with hypertrophic cardiomyopathy (HCM), but no cases of biallelic variants associated with disease have been described to date. From 2014 until 2021, FHOD3 was evaluated in our center by next-generation sequencing in 22 806 consecutive unrelated probands. The p.Arg637Gln variant in FHOD3 was enriched in our HCM cohort (284 of 9668 probands; 2.94%) compared with internal controls (64 of 11 480; 0.59%) and gnomAD controls (373 of 64 409; 0.58%), with ORs of 5.40 (95% CI: 4.11 to 7.09) and 5.19 (95% CI: 4.44 to 6.07). The variant affects a highly conserved residue localised in a supercoiled alpha helix considered a clustering site for HCM variants, and in heterozygosis can act as a predisposing factor (intermediate-effect variant) for HCM, with an estimated penetrance of around 1%. Additionally, seven homozygous carriers of p.Arg637Gln in FHOD3 were identified. All but one (unaffected) showed an early presentation and a severe HCM phenotype. All this information suggest that p.Arg637Gln variant in FHOD3 is a low-penetrant variant, with an intermediate effect, that contributes to the development of HCM in simple heterozygosis, being associated with a more severe phenotype in homozygous carriers.

Cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy.

BACKGROUND: Spinal stenosis (SS) is a manifestation associated with cardiac amyloidosis (CA). However, there is a lack of studies assessing the prevalence of CA among patients with SS. We aimed to address the prevalence of CA among patients with SS and YLH. METHODS: We performed a cross-sectional study of consecutive patients older than 65 years with SS and yellow ligament hypertrophy (YLH). All the patients were assessed with an electrocardiogram, echocardiogram and biohumoral evaluation. Patients with CA red flags was further studied with cardiac magnetic resonance and 99mTc-DPD scintigraphy. A cohort of patients with confirmed CA and SS was used to assess clinical features associated with CA. RESULTS: 105 patients (75.0 ± 6.6 years old; 45.7% males) with SS and YLH [5.5 [5-7] mm] were screened. Prevalence of red flags of CA was high and 58 patients presented clinical suspicion of CA. One patient (0.95%) was finally diagnosed of CA. Patients with confirmed CA presented a more expressive phenotype than the screened population. Patients with suspected CA had greater YLH than patients without suspicion of CA (6.4 ± 1.3 vs. 5.0 ± 0.8 mm; p < 0.001) and patients with confirmed CA presented greater YLH than the screening population (6.7 ± 1.8 vs. 5.7 ± 1.2 mm; p = 0.018). CONCLUSION: Despite red flags of CA are common among patients with SS, the prevalence of confirmed CA was low in our sample of screened patients.

Development and Validation of a Prediction Model and Score for Transthyretin Cardiac Amyloidosis Diagnosis: T-Amylo.

BACKGROUND: Although transthyretin cardiac amyloidosis (ATTR-CA) is often underdiagnosed, clinical suspicion is essential for early diagnosis. OBJECTIVES: The aim of this study was to develop and validate a feasible prediction model and score to facilitate the diagnosis of ATTR-CA. METHODS: This retrospective multicenter study enrolled consecutive patients who underwent 99mTc-DPD scintigraphy for suspected ATTR-CA. ATTR-CA was diagnosed if Grade 2 or 3 cardiac uptake was evidenced on 99mTc-DPD scintigraphy in the absence of a detectable monoclonal component or by demonstration of amyloid by biopsy. A prediction model for ATTR-CA diagnosis was developed in a derivation sample of 227 patients from 2 centers using multivariable logistic regression with clinical, electrocardiography, analytical, and transthoracic echocardiography variables. A simplified score was also created. Both of them were validated in an external cohort (n = 895) from 11 centers. RESULTS: The obtained prediction model combined age, gender, carpal tunnel syndrome, interventricular septum in diastole thickness, and low QRS interval voltages, with an area under the curve (AUC) of 0.92. The score had an AUC of 0.86. Both the T-Amylo prediction model and the score showed a good performance in the validation sample (ie, AUC: 0.84 and 0.82, respectively). They were tested in 3 clinical scenarios of the validation cohort: 1) hypertensive cardiomyopathy (n = 327); 2) severe aortic stenosis (n = 105); and 3) heart failure with preserved ejection fraction (n = 604), all with good diagnostic accuracy. CONCLUSIONS: The T-Amylo is a simple prediction model that improves the prediction of ATTR-CA diagnosis in patients with suspected ATTR-CA.

[Differences among renin-angiotensin system inhibitor drugs in prognosis of hypertense patients with COVID-19]. / Diferencias entre fármacos inhibidores del sistema renina-angiotensina en pacientes hipertensos ingresados por COVID-19.

Introduction: Concerns have been raised about Renin-angiotensin system inhibitors (RASi) in patients with COVID-19. Although recent trials have proved its security, evidence regarding intrinsic differences between RASi is lacking, especially in patients with arterial hypertension. Our objective was to analyse the prognosis of hypertense patients who received angiotensin converting enzyme inhibitors (ACEi) or angiotensin-2 receptor blockers (ARBs) and were hospitalized due to COVID-19. Materials and methods: 392 consecutive patients with hypertension and COVID-19 were analyse. Incidence of the combined event (death or mechanical ventilation need) was the primary endpoint. Secondary, incidence of each event and time to event were analysed. Results: 155 received ACEi and 237 ARBs. During the hospitalization, the combined event was observed in the 31,6 % of patients. No differences were observed between those previously treated with ACEi and ARBs (33.5 vs. 30.9%; p = 0.51). In the survival analysis, no differences were observed regarding time to combined event (p = 0.91). In-hospital mortality was similar in both groups (32.3 vs. 29.1%; p = 0.51), as well as the need of mechanical ventilation (3.2 vs. 5.9%; p = 0.23). Conclusions: The type of RASi was not associated with in-hospital major events in patients with arterial hypertension hospitalized due to COVID-19.

Introducción: Han surgido dudas sobre la seguridad de los fármacos inhibidores del sistema renina-angiotensina (SRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19). Aunque estudios recientes han demostrado la seguridad de este grupo de fármacos, la evidencia sobre la comparativa de los diferentes fármacos inhibidores del SRA es escasa, sobre todo en pacientes hipertensos. Nuestro objetivo fue analizar el pronóstico de los pacientes hipertensos tratados con inhibidores de la enzima convertidora de angiotensina (IECA) o antagonistas del receptor de angiotensina II (ARA II) que presentaron COVID-19. Materiales y métodos: Se analizaron 582 pacientes hipertensos con COVID-19. Se registró la incidencia del evento combinado de muerte o necesidad de ventilación mecánica invasiva (VMI) durante la hospitalización. De forma secundaria, se analizó la incidencia de eventos de manera independiente y se realizó un análisis de supervivencia para analizar el tiempo hasta los eventos. Resultados: 155 pacientes recibían tratamiento previo con IECA y 237 con ARA II. Durante la hospitalización por COVID-19, se observó una incidencia del evento combinado del 31.6%. No se detectaron diferencias entre los pacientes que recibían tratamiento con IECA y los tratados con ARA II (33.5 vs. 30.9%; p = 0.51). En el análisis de supervivencia, no se hallaron diferencias en el tiempo hasta el evento combinado (p = 0.91). La mortalidad intrahospitalaria fue similar en ambos grupos (32.3 vs. 29.1%; p = 0.51), así como la necesidad de VMI (3.2 vs. 5.9%; p = 0.23). Conclusiones: El tipo de inhibidor del SRA no se asoció a diferencias pronósticas significativas entre los pacientes hipertensos ingresados con COVID-19.

[Cardiovascular disease after COVID-19 infection in elderly patients. Results of annual follow-up of a cohort of survivors]. / Enfermedad cardiovascular tras infección por SARS-CoV-2 en pacientes ancianos. Resultados del seguimiento anual de una cohorte de supervivientes.

INTRODUCTION: Although the effects of SARS-CoV-2 infection on the cardiovascular system is well known in the acute phase, the cardiovascular impact of the elderly population surviving COVID-19 respiratory infection after 1 year of follow-up has not been sufficiently studied. METHODS: Observational registry of 240 elderly patients (75 years or older), consecutively admitted for COVID-19 respiratory infection and survivors of the same, between March 1 and April 30, 2020, at the Hospital General Universitario de Ciudad Real. The incidence of major cardiovascular events [MACE] (cardiovascular death [CD], acute coronary syndrome [ACS], cerebrovascular disease [CVD], venous thromboembolic disease [VTE] and heart failure [HF]) was prospectively analysed. RESULTS: The mean age was 83.75±5.75 years. After a mean follow-up of 352.2±70.4 days, 13.8% of patients died and 9.6% had MACE, the most frequent being heart failure, with no differences in severity or overall course of acute illness. In the multivariate Cox regression model, the risk of developing MACE was higher in patients with chronic obstructive pulmonary disease and (HR 4.29; 95%CI 1.62-11.39; P=.003) and loop diuretic (HR 2.99; 95%CI 1.27-7.07; P=.01). CONCLUSIONS: In elderly COVID-19 survivors, the incidence of MACE after one year of follow-up is high, the main manifestation being heart failure.

[Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19]. / Mortalidad y factores pronósticos asociados en pacientes ancianos y muy ancianos hospitalizados con infección respiratoria COVID-19.

INTRODUCTION: Elderly patients with COVID-19 has a worse clinical evolution, being more susceptible to develop serious manifestations. The differences between the elderly and very elderly population, mortality and associated prognostic factors of SARS-CoV-2 infection have not been enough studied yet. METHODS: An observational study of 416 elderly patients admitted consecutively to Hospital General Universitario de Ciudad Real for COVID-19 respiratory infection from March 1st to April 30th, 2020. Data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions and clinical outcomes during the hospitalization and after discharge, until June 15, 2020 with the aim of analyzing mortality, and associated prognostic factors. RESULTS: The mean age was 84.43±5.74 years old; elderly patients (75-84 years) were 50.2% of the sample and very elderly (≥85 years) the remaining 49.8%. In Cox regression model, mortality rate was higher in very elderly group (HR = 2.58; 95% CI: 1.23-5.38; P = .01), hypertensive (HR = 3, 45; 95% CI: 1.13-10.5; P = .03) and chronic kidney disease patients (HR = 3.86; 95% CI: 1.3-11.43; P = .02). In contrast, calcium antagonists (HR = 0.27; 95% CI: 0.12-0.62; P = .002) and anticoagulant therapy during hospitalization (HR = 0.26; 95% CI: 0.08 0, 83; P = .02) were associated with a longer time free of mortality. CONCLUSIONS: Mortality rate was higher in very eldery patients compared with eldery; and in hypertensive and chronic kidney disease patients. Anticoagulation therapy and calcium chanel bloquers treatment during hospitalization were associated with a higher survival in the short-term follow-up in patients hospitalized with COVID-19.

Biomarcadores inflamatorios y extensión de aterosclerosis coronaria en pacientes con síndrome coronario agudo: Estudio observacional prospectivo en un hospital general universitario / Circulating markers of inflammation and severity of coronary atherosclerosis in acute coronary syndrome: Prospective observational study in a general university hospital

Resumen Objetivo: Encontrar una relación entre los niveles de proteína C reactiva (PCR) y fibrinógeno, y la extensión de la aterosclerosis en el síndrome coronario agudo. Métodos: Estudio observacional prospectivo, en el que se incluyeron 873 pacientes con síndrome coronario atendidos en un hospital entre 2016 y 2018. Se analizaron niveles de PCR y fibrinógeno, marcadores metabólicos y extensión de la aterosclerosis coronaria. Resultados: No se halló correlación positiva entre los niveles de PCR y fibrinógeno y los marcadores metabólicos, así como tampoco con enfermedad de uno, dos y tres vasos (p 0,829; p 0,810). Conclusiones: Los niveles sanguíneos de PCR y fibrinógeno se relacionan con la tasa de eventos cardiovasculares, pero no se ha podido demostrar que exista relación entre estos y la severidad de la aterosclerosis coronaria.

Abstract Objective: To determine whether there is a relationship between C - reactive protein and fibrinogen levels and the extent of atherosclerosis in acute coronary syndrome. Methods: A prospective observational study was conducted that include 873 patients with coronary syndrome treated in a hospital between the years 2016 and 2018. An analysis was made that included C - reactive protein and fibrinogen levels, metabolic markers, extent of coronary atherosclerosis. Results: No positive correlation was found between the C - reactive protein and fibrinogen levels and the metabolic markers, nor with one, two, or three vessel disease (P=.829; P=.810). Conclusions: Although blood C-Reactive Protein and fibrinogen levels are associated with the rate of cardiovascular events, this study was unable to demonstrate whether there is a relationship between these and the severity of the coronary atherosclerosis.

Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection.

INTRODUCTION: Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients. METHODS: This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes. RESULTS: The mean age was 78 years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups. CONCLUSIONS: RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization.

INTRODUCCIÓN: La presencia de hipertensión arterial se asocia con peor pronóstico en pacientes con COVID-19, y se ha sugerido que el uso de inhibidores del eje renina-angiotensina puede influir en el pronóstico de los pacientes. MÉTODOS: Registro observacional de 921 pacientes consecutivos ingresados por infección respiratoria COVID-19 entre el 1 de marzo y el 30 abril de 2020 en el Hospital General Universitario de Ciudad Real. Se registraron datos clínicos y analíticos, intervenciones terapéuticas y desarrollo de eventos durante el ingreso hospitalario. RESULTADOS: La mediana de edad fue de 78 años y el 59,2% tenían hipertensión arterial. Aunque el perfil clínico fue más desfavorable en el grupo de pacientes con prescripción previa de IECA o ARA2 respecto al resto, los primeros presentaron menor riesgo de desarrollo del evento primario combinado (mortalidad total o necesidad de soporte ventilatorio invasivo). Asimismo, el empleo previo al ingreso o durante el mismo de estos fármacos mostró un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva. En el análisis de supervivencia no se observó mayor riesgo de presentar más precozmente ninguno de los eventos registrados. CONCLUSIONES: La prescripción previa al ingreso por infección respiratoria COVID-19 de inhibidores del eje renina-angiotensina se asoció a un menor riesgo de desarrollo del evento primario combinado y a un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva.

Infarto de miocardio tras la administración de adrenalina intragingival ¿Una nueva causa de infarto agudo de miocardio sin enfermedad coronaria aterosclerótica obstructiva? / Myocardial infarction after intra-gingival administration of adrenaline. A new cause of myocardial infarction without obstructive coronary atherosclerosis?

Resumen Es frecuente la relación entre la adrenalina administrada por vía intramuscular y el desarrollo de cardiopatía isquémica. La adrenalina potencia las hemostasias primaria y secundaria -puede producir trombosis intracoronaria- y causa vasoconstricción transitoria arteriolar. Se presenta un caso clínico de una paciente que acudió a urgencias por dolor torácico pocas horas después de una intervención dentaria. En el estudio posterior se descubrió un infarto de miocardio por trombosis intracoronaria de la descendente anterior distal.

Abstract There is a relationship between adrenaline administered intramuscularly and the development of ischaemic heart disease. Adrenaline promotes primary and secondary haemostasis, which can produce a coronary thrombosis and cause a transient arteriolar vasoconstriction. A case is presented of a patient who was seen in the Emergency Department with chest pain a few hours after dental treatment. In the subsequent work-up, it was discovered that she had a myocardial infarction due to a coronary thrombosis of the left anterior distal artery.

[Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection]. / Análisis de la relación entre los inhibidores del sistema renina-angiotensina y la evolución de pacientes hospitalizados por infección respiratoria COVID-19.

INTRODUCTION: Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients. METHODS: This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes. RESULTS: The mean age was 78years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups. CONCLUSIONS: RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization.