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Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3–87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.

Introduction and objectives: There is great interest in the development of devices for the percutaneous management of mitral regurgitation (MR). For this reason, having an experimental model that reproduces the conditions of the disease is of great importance. Our objective was to validate an experimental model of MR in a porcine model. Methods: For the model creation phase 3, 2-month-old 25 ± 3 kg large white pigs were used. An acute myocardial infarction was caused in the circumflex artery territory that hampered the perfusion of the posteromedial papillary muscle. Then, volume overload was induced in the animal by creating an arteriovenous shunt and connecting the aorta and the pulmonary artery using a Dacron tube. Echocardiography and magnetic resonance imaging were performed before the intervention and on week 8. Afterwards, the animal was euthanized to conduct the pathological study. Results: One out of the 3 pigs died during the intervention due to ventricular fibrillation. The remaining 2 pigs survived the procedure and were euthanized as scheduled on week 8. In both cases a transmural infarction occurred, 1 at lateral level and the other one at posteroinferior level with moderate secondary mitral regurgitation. Ventricular dimensions and volumes increased and the overall contractility was maintained...

Background: Administration of Hydroxychloroquine and Azithromycin in patients with coronavirus disease 2019 (COVID-19) prolongs QTc corrected interval (QTc). The effect and safety of Lopinavir/Ritonavir in combination with these therapies have seldom been studied. Objectives: Our aim was to evaluate changes in QTc in patients receiving double (Hydroxychloroquine + Azithromycin) and triple therapy (Hydroxychloroquine + Azithromycin + Lopinavir/Ritonavir) to treat COVID-19. Secondary outcome was the incidence of in-hospital all-cause mortality. Methods: Patients under treatment with double (DT) and triple therapy (TT) for COVID-19 were consecutively included in this prospective observational study. Serial in-hospital electrocardiograms were performed to measure QTc at baseline and during therapy. Results: 168 patients (±66.2 years old) were included: 32.1% received DT and 67.9% received TT. The mean baseline QTc was 410.33 ms. Patients under DT and TT prolonged QTc interval respect baseline values (p, Highlights • What is known? • Hydroxychloroquine and Azithromycin prolong QTc in patients with COVID-19, prompting ECG monitoring due to increased risk of ventricular arrythmias. • What is the new? • The impact of Lopinavir/Ritonavir in addition to Hydroxychloroquine and Azithromycin on QTc has not been studied previously. In our series, triple therapy did not further prolong QTc interval compared to double therapy.

A 78-year-old woman with a history of transient ischemic attack was admitted for sudden aphasia. In order to assess the potential cardioembolic source an echocardiogram was performed, which revealed a large mass consistent with a thrombus in transit through a patent foramen ovale. Because of the high risk of systemic embolism, emergent surgical thrombectomy was performed with the intention to discharge the patient safely without any new embolic events. This case report highlights the importance of echocardiography in the evaluation of cardioembolic stroke and the requirement of an emergent approach in case of impending paradoxical embolism.

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is the most common arrhythmia in the elderly. Age increases both thromboembolic risk and bleeding complications. However, these patients are not anticoagulated on many occasions. AF in the context of acute coronary syndrome (ACS) increases the complexity of the management of these patients and they are underrepresented in clinical trials. Purpose The objective of the study was to analyze the impact of AF in nonagenarian patients at 12 months. Other objectives were to evaluate the therapeutic strategy for ACS and AF and to compare clinical events according to AF subtype and treatment at discharge. Methods A retrospective, multicenter and observational study was carried out, in which all nonagenarian patients admitted for ACS and AF (prevalent or incident) between 2005 and 2018 were consecutively included. Patients with type 2 myocardial infarction were excluded. Baseline characteristics were analyzed and mortality at 12 months was analyzed in all patients and according to AF subtype (incident AF was considered when occurred during admission and prevalent AF was considered in patients with previous history of AF) Results 680 patients with a mean age of 92.6 ± 2.4 years were analyzed. Patients with AF more frequently presented chronic kidney disease (CKD) and non-ST-segment elevation acute coronary syndrome (Non-STEMI) and arterial hypertension (HBP) (Table 1). Mortality rate was similar in patients with previous AF and those without history of AF (Figure 1 A). 21.6% (147) of the patients had AF at admission, of which only 47.7% of the patients were previously anticoagulated. Treatment at discharge is shown in Figure 1 B. Mortality at 1 year according to discharge treatment and AF subtype are represented in figures 1C and 1D. Conclusions This is the largest registry of ACS and AF in this population. Patients with prevalent AF had more frequent Non-STEMI and comorbidities, with a similar mortality to AF subgroup at 1 year. Previous AF was no related to higher mortality in this cohort. Half of the patients were not anticoagulated at discharge. OAC was not associated with prognostic benefit in our series.

Background: Cytoplasmatic expression of Aldehyde dehydrogenase 1 A1 (ALDH1A1) has been identified as a cancer stem cell marker and related to an unfavorable prognosis. However, nuclear expression of ALDH1A1 has not been described in breast cancer (BC) patients yet. Methods: A retrospective, historical cohort study of patients diagnosed with early or locally advanced triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) BC treated with neoadjuvant chemotherapy was conducted. Patients who had an available tumor sample from the diagnosis and who underwent surgery after the neoadjuvant treatment were included. Metastatic patients and non-evaluative biopsy sample cases were excluded. Immunostaining against ALDH1A1 was performed. The aim of this study was to assess the expression of nuclear ALDH1A1 in BC and its relation with clinicopathological features and outcomes.Results: 75 patients were analyzed (100% women, mean age 53.6±11.7 years, 42.7% TN, 57.3% HER2+ tumors). 28% had obesity, 32 (42.7%) had a tumor size ≤5 cm and 52 (69.3%) positive lymph nodes. 40 (53.3%) patients had cytoplasmatic ALDH1A1 expression. From them, 18 (24%) also expressed nuclear ALDH1A1 staining and 22 (29.3%) only had cytoplasmatic expression. 57 (76%) patients had negative nuclear ALDH1A1. At the end of the follow-up (54.4 [38.3-87.6] months), 47 patients (62.7%) remained disease free and 20 (26.7%) died. Patients with nuclear ALDH1A1 had higher prevalence of obesity when comparing to exclusively positive cytoplasmatic ALDH1A1 (p = 0.003) and versus those with negative ALDH1A1 expression (p = 0.017); and also, smaller size compared to those without nuclear ALDH1A1 staining (p = 0.044). Furthermore, in patients with positive nuclear ALDH1A1 a tendency to superior disease-free survival (DFS) and overall survival (OS) was observed when compared to positive cytoplasmatic and negative ALDH1A1 tumors, albeit not statistically significant. Conclusions: In this cohort, nuclear positive expression of ALDH1A1 was higher in patients with obesity and smaller tumors. Patients with positive nuclear ALDH1A1 carcinomas appear to have better DFS and OS, although this was not statistically significant. Further research studies are needed to understand the functions of this enzyme and its possible role as a predictive and prognostic marker in BC.

Tricuspid valve regurgitation is one of the most common valvular disorders and moderate to severe tricuspid regurgitation is consistently associated to an increased morbidity and mortality. From an etiopathological perspective, tricuspid regurgitation can be classified in primary, due to the organic disease of any of the valve components, or secondary, as a result of tricuspid valve annulus dilatation, adverse right ventricular remodeling and tricuspid valve leaflet tethering. Despite its poor prognosis, most patients with tricuspid insufficiency are managed conservatively and only those with concomitant left heart valvular disease do finally go surgery in the real-world setting. In fact, outcomes of conventional surgery in patients with isolated tricuspid regurgitation are poor and this approach has not proven yet any survival benefit over stand-alone medical therapy. Given this unmet need, new transcatheter techniques have been developed in the last years, including leaflet plication, percutaneous annuloplasty and valve implantation in either the tricuspid position (orthotopic implantation) or in a different position such as the vena cava (heterotopic implantation). These techniques, with promising outcomes, are seen as an interesting alternative to open-heart surgery given the much lower periprocedural risk.

To the Editor, Spontaneous coronary artery dissection (SCAD) is a misdiagnosed condition that has emerged as an important cause of acute coronary syndrome and sudden death, especially in women under 50. In these patients it is responsible for 30% of all the cases of such syndrome.1 However, only between 10% and 15% of all SCADs are diagnosed in male patients.

Objectives: To evaluate the feasibility of QTc monitoring with a smart device in COVID-19 patients receiving QTc-interfering therapies.Background: QTc prolongation is an adverse effect of COVID-19 therapies. The use of a handheld device in this scenario has not been addressed.Methods: Prospective study of consecutive COVID-19 patients treated with hydroxychloroquine ± azithromycin ± lopinavir-ritonavir. ECG monitoring was performed with 12-lead ECG or with KardiaMobile-6L. Both registries were also sequentially obtained in a cohort of healthy patients. We evaluated differences in QTc in COVID-19 patients between 3 different monitoring strategies: 12-lead ECG at baseline and follow-up (A), 12-lead ECG at baseline and follow-up with the smart device (B), and fully monitored with handheld 6-lead ECG (group C). Time needed to obtain an ECG registry was also documented.Results: 182 COVID-19 patients were included (A: 119(65.4%); B: 50(27.5%); C: 13(7.1%). QTc peak during hospitalization did significantly increase in all groups. No differences were observed between the 3 monitoring strategies in QTc prolongation (p=0.864). In the control group, all but one ECG registry with the smart device allowed QTc measurement and mean QTc did not differ between both techniques (p=0.612), displaying a moderate reliability (ICC 0.56 [0.19-0.76]). Time of ECG registry was significantly longer for the 12-lead ECG than for handheld device in both cohorts (pConclusion: QTc monitoring with KardiaMobile-6L in COVID-19 patients was feasible. Time of ECG registration was significantly lower with the smart device, which may offer an important advantage for prevention of virus dissemination among healthcare providers.

Supplemental Digital Content is available in the text., Background: Coronavirus disease 2019 (COVID-19) has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias. The incidence and pathophysiology of these manifestations remain elusive. In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic. Methods: We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias. Patients with documented atrial fibrillation, atrial flutter, supraventricular tachycardia, nonsustained or sustained ventricular tachycardia, ventricular fibrillation, atrioventricular block, or marked sinus bradycardia (heart rate

Background Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since the outbreak originated in Wuhan, China in December 2019. Cardiovascular complications in patients with severe COVID-19 have been reported and are associated with a worse outcome. Coagulopathy is one of the most common life-threatening complication increasing mortality; however, little evidence is available regarding prevention strategies or its treatment in COVID-19 patients. Case summary We report a case of a 70-year-old woman admitted to hospital with severe COVID-19 bilateral pneumonia who developed severe coagulopathy with multiple both, venous and arterial, embolisms in major vessels such as bilateral pulmonary embolism, acute thrombus in abdominal aorta, and acute thrombotic occlusion of the right iliac common artery. The patient underwent emergent surgical thrombectomy of the right lower limb; in spite of anticoagulant treatment at therapeutic doses, patient presented poor clinical evolution and an infracondylar amputation of right lower limb was made finally. Subsequently, the patient received low molecular weight heparin (LMWH), antibiotics and antiviral therapy improving her renal function and her pneumonia, so she could be discharged safely. Discussion Prothrombotic coagulopathy due to enhanced acute inflammatory response and diffuse intravascular coagulation has been described in severe critical COVID-19 patients. This state of hypercoagulability is associated with organ dysfunction and mortality and may predispose to both, venous and arterial, thromboembolism. Little data are available regarding the best therapeutic and prevention strategies in this scenario, although thrombosis prophylaxis with LMWH has been associated with a better outcome.

Resumen El paciente con fibrilacion auricular y enfermedad coronaria combina a menudo altos riesgos isquemico y hemorragico. En el contexto de la anticoagulacion oral, el clopidogrel es el inhibidor del P2Y12 con mejor perfil de seguridad y, aunque recomendado para los pacientes con sindrome coronario agudo, el pretratamiento antes de un procedimiento invasivo continua siendo objeto de debate. Para los pacientes electivos que van a someterse a una intervencion coronaria, no se recomienda la terapia puente con heparina periprocedimiento, dado que esta estrategia se ha relacionado con una mayor incidencia de eventos adversos. El acceso radial deberia ser de eleccion en la mayoria de los casos, siempre que la situacion hemodinamica y la anatomia coronaria lo permitan. Aunque la evidencia es aun escasa, se recomienda administrar dosis bajas de heparina no fraccionada durante el procedimiento. Informacion sobre el suplemento: este articulo forma parte del suplemento titulado «Actualizacion en el tratamiento de los pacientes con fibrilacion auricular sometidos a intervencion coronaria», que ha sido patrocinado por Boehringer Ingelheim.

Objectives: MitraClip is an established therapy for patients with mitral regurgitation (MR) that are considered of high-risk or inoperable. However, late bleeding events (BE) after hospital discharge and their impact on prognosis in this cohort of patients have been poorly investigated. Our purpose is to address the incidence, related factors and clinical implications of BE after hospital discharge in patients treated with MitraClip. Methods: Prospective registry of all consecutive patients (n = 80) who underwent MitraClip implantation in our Institution between June 2014 and December 2017. BE were defined according to MVARC definitions. A combined clinical end-point including admission for heart failure (HF) and all-cause mortality was established to analyze prognostic implications of BE. Results: During a median follow up of 523.5 days, 41 BE were reported in 21 patients. Atrial fibrillation (AF, HR 4.54, CI95% 1.20–17.10) and combined antithrombotic therapy at discharge (HR 3.52, CI95% 1.03–11.34) were independently associated with BE. In the study period, 15 (18.8%) patients died, 20 (25%) were admitted for HF and 29 (36.3%) presented the combined end-point. After multivariable adjustment BE remained independently associated with an adverse outcome (HR 3.80, CI 95% 1.66–8.72). In the subgroup of patients with AF, HAS-BLED score was higher among subjects with BE (3.1 ± 1.3 vs 2.1 ± 0.9, p = 0.003). HAS-BLED score had a significant discrimination power for the occurrence BE (AUC: 0.677 [0.507–0.848]) in this subgroup. Conclusions: BE are common after MitraClip and are associated with an impaired outcome. Strategies to reduce bleeding events are paramount in this cohort of patients. Keywords: MitraClip, Atrial fibrillation, Bleeding events