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We present an asymptomatic pregnant patient with congenitally corrected transposition of the great arteries and severe atrioventricular bioprosthesis regurgitation - with increased maternal and fetal risk due to volume overload. She was considered high risk for reintervention and was submitted to an off-label post-partum transcatheter valve-in-valve implantation with a Sapiens 3 valve. The procedure was successful, and she remains asymptomatic 30 months after - and even went through another successful pregnancy.

For decades, only two nitroheterocyclic drugs have been used as therapeutic agents for Chagas disease. However, these drugs present limited effectiveness during the chronic phase, possess unfavorable pharmacokinetic properties, and induce severe adverse effects, resulting in low treatment adherence. A previous study reported that N -(cyclohexylcarbamothioyl) benzamide ( BTU-1 ), N -( tert -butylcarbamothioyl) benzamide ( BTU-2 ), and (4-bromo- N -(3-nitrophenyl) carbamothioyl benzamide ( BTU-3 ) present selective antiprotozoal activity against all developmental forms of Trypanosoma cruzi Y strain. In this study, we investigated the mechanism of action of these compounds through microscopy and biochemical analyses. Transmission electron microscopy analysis showed nuclear disorganization, changes in the plasma membrane with the appearance of blebs and extracellular arrangements, intense vacuolization, mitochondrial swelling, and formation of myelin-like structures. Biochemical results showed changes in the mitochondrial membrane potential, reactive oxygen species content, lipid peroxidation, and plasma membrane fluidity. In addition, the formation of autophagic vacuoles was observed. These findings indicate that BTU-1 , BTU-2, and BTU-3 induced profound morphological, ultrastructural, and biochemical alterations in epimastigote forms, triggering an autophagic-dependent cell death pathway.

Ureases are enzymes produced by fungi, plants, and bacteria associated with agricultural and clinical problems. The urea hydrolysis in NH 3 and CO 2 leads to the loss of N-urea fertilizers in soils and changes the human stomach microenvironment, favoring the colonization of H. pylori. In this sense, it is necessary to evaluate potential enzyme inhibitors to mitigate the effects of their activities and respond to scientific and market demands to produce fertilizers with enhanced efficiency. Thus, biophysical and theoretical studies were carried out to evaluate the influence of the N-alkyl chain in benzoyl-thiourea derivatives on urease enzyme inhibition. A screening based on IC 50 , binding constants, and theoretical studies demonstrated that BTU1 without the N-alkyl chain (R = H) was more active than other compounds, so the magnitude of the interaction was determined as BTU1 > BTU2 > BTU3 > BTU4 > BTU5, corresponding to progressively increased chain length. Thus, BTU1 was selected for interaction and soil application essays. The binding constants (K b ) for the supramolecular urease-BTU1 complex ranged from 7.95 to 5.71 × 10 3  M -1 at different temperatures (22, 30, and 38 °C), indicating that the preferential forces responsible for the stabilization of the complex are hydrogen bonds and van der Waals forces (ΔH = -15.84 kJ mol -1 and ΔS = -36.61 J mol -1  K -1 ). Theoretical and experimental results (thermodynamics, synchronous fluorescence, and competition assay) agree and indicate that BTU1 is a mixed inhibitor. Finally, urease inhibition was evaluated in the four soil samples, where BTU1 was as efficient as NBPT (based on ANOVA two-way and Tukey test with 95% confidence), with an average inhibition of 20% of urease activity. Thus, the biophysics and theoretical studies are strategies for evaluating potential inhibitors and showed that increasing the N-alkyl chain in benzoyl-thiourea derivatives did not favor urease inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction and Objectives: Acute total occlusion of the unprotected left main coronary artery (LMCA) is a dramatic event. There are limited data regarding this population. We aimed to describe the clinical presentation and outcomes of patients and to determine predictors of in-hospital mortality., Methods: This retrospective study included patients presenting with acute (<12 h) myocardial infarction due to total occlusion of the LMCA (TIMI flow 0) between January 2008 and December 2020 in three tertiary hospitals., Results: During this period, 11036 emergent coronary angiographies were performed, 59 (0.5%) of which revealed acute total occlusion of the LMCA. Patients' mean age was 61.2 (SD±12.2) years and 73% were male. No patients had left dominance. At presentation, 73% were in cardiogenic shock, aborted cardiac arrest occurred in 27% and 97% underwent myocardial revascularization. Primary percutaneous coronary intervention was performed in 90% of cases and angiographic success was achieved in 56% of procedures, while 7% of patients underwent surgical revascularization. In-hospital mortality was 58%. Among survivors, 92% and 67% were alive after one and five years, respectively. After multivariate analysis, only cardiogenic shock and angiographic success were independent predictors of in-hospital mortality. Use of mechanical circulatory support and presence of well-developed collateral circulation were not predictive of short-term prognosis., Conclusion: Acute total occlusion of the LMCA is associated with a dismal prognosis. Cardiogenic shock and angiographic success play a major role in predicting the prognosis of these patients. The effect of mechanical circulatory support on patient prognosis remains to be determined., (Copyright © 2023. Publicado por Elsevier España, S.L.U.)

Cytomegalovirus (CMV) infection is a frequent complication after a solid organ transplant, and in 86% of the cases, CMV disease occurred during the first 6 months after transplantation. Invasive CMV infections may be present as ulcerative infections of the upper gastrointestinal tract with esophagitis, gastritis, and ulcerations of the duodenum and the small bowel; however, CMV infections of the pancreatobiliary system, especially papillitis, are rarely observed. We present a case report of a man who underwent a heart transplant 6 years before, with a clinical picture of duodenitis and a simultaneous pseudotumor of major duodenal papilla who developed signs of acute abdomen caused by gastrointestinal CMV infection, successfully treated with medical therapy with valganciclovir. There is an urgent need for developments in CMV and solid organ transplantation to stratify the risk of late-onset CMV disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tuberculosis is a disease with a significant global burden in terms of morbidity and mortality. It usually presents as a pulmonary disease but can occasionally have extrapulmonary presentations. Immunosuppressed people are at an increased risk of tuberculosis and more frequently have atypical manifestations of the disease. Cutaneous involvement is estimated to occur in only 2% of extrapulmonary presentations. We report a case of a heart transplant recipient with disseminated tuberculosis who initially presented with cutaneous manifestations in the form of multiple abscesses that were mistaken for a community-acquired bacterial infection. The diagnosis was made after positive nucleic acid amplification testing and cultures for Mycobacterium tuberculosis from the drainage of the abscesses. After initiating antituberculous treatment, the patient had 2 instances of immune reconstitution inflammatory syndrome. A combination of diminished immunosuppression due to discontinuation of mycophenolate mofetil in the setting of acute infection, rifampin drug interactions with cyclosporine, and the beginning of treatment of tuberculosis all contributed to this paradoxical worsening. The patient responded favorably to increased glucocorticoid therapy and showed no signs of treatment failure after 6 months of antituberculous therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Stage IV colorectal cancer treatment includes targeted therapy depending on RAS status. During disease progression, loss or gain of RAS mutations could happen, supporting the hypothesis of the evolutionary pressure of therapy. Circulating tumor DNA (ctDNA) are nucleic acids released to the bloodstream by the tumor during its development and may be detected by liquid biopsy. The Idylla© Biocartis, a fully automated real-time-PCR-based molecular diagnostic system, was used in a patient with metastatic colorectal cancer with a NRAS mutation in progression after several therapeutic lines. The ctDNA mutational analysis was performed and revealed the absence of mutations in the KRAS, NRAS, and BRAF genes. The patient started the third line of palliative chemotherapy with irinotecan + cetuximab and achieved a partial response for the first time. The authors describe a case in which liquid biopsy determined the higher progression-free survival achieved. [ABSTRACT FROM AUTHOR]

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Dextro-transposition of the great arteries (D-TGA) is a congenital heart disease (CHD) classically palliated with atrial switch (ATR-S) and nowadays corrected with arterial switch (ART-S). Our aim was to observe a group of D-TGA patients followed in an adult CHD outpatient clinic. We analyzed a group of D-TGA patients born between 1974 and 2001. Adverse events were defined as a composite of death, stroke, myocardial infarction or coronary revascularization, arrhythmia, and ventricular, baffle, or significative valvular dysfunction. A total of 79 patients were enrolled, 46% of whom were female, with a mean follow-up of 27±6 years after surgery. ATR-S was performed in 54% and ART-S in 46%; the median age at procedure was 13 months and 10 days, respectively. During follow-up, almost all ART-S remained in sinus rhythm versus 64% of ATR-S (p=0.002). The latter group had a higher incidence of arrhythmias (41% versus 3%, p<0.001), mostly atrial flutter or fibrillation; the median time to first arrhythmia was 23 years. Systemic ventricle systolic dysfunction (SVSD) was more frequent in ATR-S (41% versus 0%, p<0.001); the mean time to SVSD was 25 years. In ART-S, the most frequent complication was significant valvular regurgitation (14%). Regarding time-to-event analysis, 80% and 40% of ATR-S maintained adverse events-free after 20 and 30 years, respectively; the time-to-first adverse event was 23 years, and there was no difference compared to ART-S (Log-rank=0.596). ART-S tended to maintain more preserved biventricular function than ATR-S (Log-rank=0.055). After a long term free of adverse events, ATR-S patients experienced more arrhythmias and SVSD. ART-S complications were predominantly anastomosis-related; SVSD or arrhythmias were rare.

Breast cancer (BC) patients treated with anthracyclines and/or anti-HER2-targeted therapies (AHT) are highly associated with cardiovascular toxicity (CVT). Our objective was to evaluate the risk of CVT secondary to cancer treatment and the role of cardioprotective-drugs (CPD) in BC patients. We collected a retrospective cohort of females with BC treated with chemotherapy and/or AHT from 2017 to 2019. CVT was defined as LVEF<50% or decline ≥10% during follow-up. As CPD, we considered renin-angiotensin-aldosterone-system inhibitors and beta-blockers. A subgroup analysis of the AHT patients was also performed. A total of 203 women were enrolled. The majority had high or very-high CVT risk score and normal cardiac function at presentation. As for CPD, 35.5% were medicated pre-chemotherapy. All patients were submitted to chemotherapy; AHT were applied to 41.7%. During a 16 months follow-up, 8.5% developed CVT. There was a significant decrease of GLS and LVEF at 12-months (decrease of 1.1% and 2.2%, p<0.001). AHT and combined therapy were significantly associated with CVT. In the AHT sub-group analysis (n=85), 15.7% developed CVT. Patients previously medicated with CPD had a significative lower incidence of CVT (2.9% vs 25.0%, p=0.006). Patients already on CPD presented a higher LVEF at 6-months follow-up (62.5% vs 59.2%, p=0.017). Patients submitted to AHT and anthracycline therapy had higher risk of developing CVT. In the AHT sub-group, pre-treatment with CPD was significantly associated with a lower prevalence of CVT. These results highlight the importance of cardio-oncology evaluation and strengthen the value of primary prevention.

Introduction: Cryptococcus neoformans is one of the leading causes of invasive fungal infections worldwide. Cryptococcal meningoencephalitis is the main challenge of antifungal therapy due to high morbidity and mortality rates, especially in low- and middle-income countries. This can be partly attributed to the lack of specific diagnosis difficulty accessing treatment, antifungal resistance and antifungal toxicity., Methods: In the present study, the effect of the synthetic thiourea derivative N -(butylcarbamothioyl) benzamide (BTU-01), alone and combined with amphotericin B (AmB), was evaluated in planktonic and sessile (biofilm) cells of C. neoformans ., Results: BTU-01 alone exhibited a fungistatic activity with minimal inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL for planktonic cells; and sessile MICs ranging from 125.0 to 1000.0 μg/mL. BTU-01 caused a concentration-dependent inhibitory activity on cryptococcal urease and did not interfere with plasma membrane fluidity. Molecular docking was performed on Canavalia ensiformis urease, and BTU-01 showed relevant interactions with the enzyme. The combination of BTU-01 and AmB exhibited synergistic fungicidal activity against planktonic and sessile cells of C. neoformans. Microscopic analysis of C. neoformans treated with BTU-01, alone or combined with AmB, revealed a reduction in cell and capsule sizes, changes in the morphology of planktonic cells; a significant decrease in the number of cells within the biofilm; and absence of exopolymeric matrix surrounding the sessile cells. Neither hemolytic activity nor cytotoxicity to mammalian cells was detected for BTU-01, alone or combined with AmB, at concentrations that exhibited antifungal activity. BTU-01 also displayed drug-likeness properties., Conclusion: These results indicate the potential of BTU-01, for the development of new strategies for controlling C. neoformans infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Andriani, Spoladori, Fabris, Camargo, Pereira, Santos, Bartolomeu-Gonçalves, Alonso, Lancheros, Alonso, Nakamura, Macedo, Pinge-Filho, Yamauchi, Bispo, Tavares and Yamada-Ogatta.)

Objective: Hydroxychloroquine (HCQ) is used in the treatment of inflammatory rheumatic diseases and is considered a safe drug. The role of HCQ in the COVID-19 pandemic highlighted some deleterious cardiac effects of HCQ. We aim to evaluate the prevalence and development of cardiac-adverse events in HCQ-treated patients with inflammatory rheumatic diseases., Methods: We performed a cross-sectional study where patients aged ≥18 years with a diagnosis of inflammatory rheumatic disease currently exposed or not to hydroxychloroquine underwent electrocardiogram (ECG) and echocardiogram. Comparisons between groups were evaluated using chi-square, t test, and Mann-Whitney U test. Logistic regression was performed to determine predictors of changes in ECG and echocardiography., Results: Eighty patients were included, 75 (93.8%) female, aged 52 ± 13 years. ECG changes were seen in higher proportion in patients with hypertension (40.6% vs 12.5%, p = .004) and higher median potassium levels-4.5 (4.1-4.8) versus 4.2 (4.0-4.4), p = .023. Echocardiography changes were seen in older patients (59 ± 11 vs 50 ± 13 years, p = .003) and in patients with higher cumulative dose-1752 (785-2190) versus 438 (328-1022) g, p = 0.008 - and time of exposure to HCQ - 12 (6-15) versus 4 (2-9) years, p = 0.028. HCQ cumulative dose (OR 1.001, CI95% 1.000-1.002, p = .033) and exposure time (OR 1.136, CI95% 1.000-1.289, p = .049) were predictors of echocardiography changes, but when adjusted for age, neither HCQ cumulative dose nor exposure time were predictors of echocardiography changes., Conclusion: No association was found between changes in ECG and echocardiogram in patients under HCQ, which remains a safe drug in patients with inflammatory rheumatic diseases.

We present a case of a 41-year-old patient with an unknown complex cardiac anatomy, who was previously submitted to two cardiac surgeries. Using multimodality imaging, a retrospective diagnosis was established, revealing a heterotaxy syndrome (left isomerism).

Introduction: Spontaneous coronary artery dissection (SCAD) represents 1-4% of all acute coronary syndromes (ACS), and is a particularly important cause among young women and individuals with few cardiovascular risk factors., Objectives: To characterize clinical background, therapeutic management and clinical outcomes in a SCAD population., Methods: We retrospectively analyzed all consecutive patients diagnosed with SCAD at a tertiary center between August 2009 and May 2020, with a median follow-up of 40 months (IQR 14-95 months). SCAD was classified according to the Saw angiographic SCAD classification., Results: A total of 36 patients were included, 94% female, mean age 51 years (±11 years). A trigger was only detected in 8% and associated conditions in 31% of patients, mainly inflammatory or autoimmune systemic diseases and migraine. Most patients had non-ST-elevation ACS and 33% presented with ST-elevation ACS. The most frequent culprit lesion was the left anterior descending (LAD) artery (67%); mid to distal segments were the most affected (94%) and type 2 dissection the most prevalent (60%). Almost all patients were successfully medically managed, with only four undergoing percutaneous intervention. During follow-up, ischemic events recurred in 15% of patients and no patient died. Patients with type 2 dissection exhibited lower risk of recurrence compared to type 1 (p=0.049, OR=0.13)., Conclusion: SCAD patients were mainly young or middle-aged women; the LAD artery was the most affected vessel and type 2 dissection the most prevalent. This report showed for the first time a correlation between type 2 SCAD and lower risk of recurrence., (Copyright © 2023 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Elderly people represent a vulnerable and increasing population presenting with acute coronary syndrome (ACS). Our goal was to evaluate a group of very old patients who underwent emergency coronary angiography (CA). We retrospectively analyzed a group of very old patients (≥90 years old) who underwent emergency CA from 2008 to 2020. Survival and major adverse cardiovascular events (MACE) (a composite of all-cause death, ischemic stroke, ACS, or hospitalization for acute heart failure) were compared with an aged-matched control population with ACS not submitted to emergency CA. A total of 34 patients were enrolled, 56% of whom were female, with a median age of 92 years old. Almost all patients had ST elevation-ACS. In CA, 65% had multivessel disease, and coronary intervention was performed in 71%. More than one-third evolved in Killip class III/IV, and 70% had left ventricular dysfunction. Regarding mortality, 38% of patients died in the index event versus 25% in the aged-matched control group (p=0.319). During 5 years of follow-up, there was no significant difference in mortality between the 2 groups (Log-rank=0.403) and more than 50% of patients died in 2 years. Comparing MACE occurrence, both groups were similar (Log-rank=0.662), with more than 80% having at least one event in 5 years. Very old patients submitted to emergency CA had a high rate of multivessel disease and left ventricular dysfunction, in-hospital and follow-up mortality, and MACE. Compared to an aged-matched control group not submitted to emergency CA, they showed no survival or MACE benefit during a 5-year follow-up.

Thiamine deficiency is commonly associated with malnutrition, alcoholism and bariatric surgery. Thiamine deficiency can manifest in different ways, especially in developing countries: as peripheric neuropathy, as Wernicke encephalopathy or as beriberi disease. The authors present the case of a 72-year-old male, with a hiatal hernia that led to thiamine deficiency due to malnutrition. The initial clinical manifestation was an ST-elevation myocardial infarct equivalent, an ECG with a shark-fin pattern that evolved to a Wellens type B pattern. The patient evolved with severe altered mental status. A Wernicke encephalopathy diagnosis was confirmed by MRI; the patient was medicated with high-dose thiamine, with quick recovery, both neurologic and cardiac. The clinical history and response to treatment confirm the diagnosis of Wernicke encephalopathy and beriberi disease.

Life-threatening ventricular arrhythmias (VA) may occur in patients with unknown cardiac disease. A sizable part of them remains labeled as Idiopathic VA and limited data is available regarding their natural history. Our aim was to evaluate the long-term clinical outcomes of survivors of an idiopathic life-threatening VA. Patients who survived an idiopathic life-threatening VA referred to an ICD were included and followed for a median follow-up of 7 years. Clinical and device data were collected and a comparison between genders was made. A total of 29 patients, 41% female, mean age of 50 (19) years were studied; all were implanted with an ICD at index hospitalization. At follow-up, an etiological diagnosis was established in 38% of patients. Genetic testing improved the diagnosis and allowed the identification of a distinct clinical entity in 60% of patients (p=0.04, OR=7.0), especially in women. Regarding ICD data, 31% received appropriate therapies with a median time to first appropriate shock of 39 months (IQR 12-46 months). Men had a significantly higher prevalence of appropriated shocks (50% vs 8%, p=0.04), with a similar time to the first arrhythmic event between genders. Two of the patients died, both from non-arrhythmic causes. Etiologic diagnosis and recurrence prediction in patients with idiopathic VA is challenging, even with long-term follow-up and sophisticated diagnostic evaluation.  Genetic testing significantly improved the diagnostic yield, especially in women. Arrhythmia recurrence occurred in about one-third of patients and is significantly higher in men, underscoring the importance of ICD implantation.