Pharmacological Triggers of Takotsubo Cardiomyopathy: An Updated Review of Evidence and Recommendations.

BACKGROUND: Previous publications in 2011, 2016, and 2022 have presented lists of drugs associated with takotsubo cardiomyopathy (TCM). This review aims to provide updated drug lists that have been reported as potential causes of TCM. METHODS: Following the same methodology employed in previous reviews, a detailed investigation was carried out in the PubMed/Medline database from June 2022 to July 2023 to identify drug-induced TCM (DITC) case reports. Various search terms related to the drug-induced transient left ventricular ballooning syndrome, ampulla cardiomyopathy, apical ballooning syndrome, drug-induced broken heart syndrome, drug triggered takotsubo cardiomyopathy, takotsubo cardiomyopathy, and iatrogenic takotsubo cardiomyopathy were utilized. Filters for fulltext availability, case reports, human studies, and English language were applied. Articles reporting drugs associated with TCM development were included in the analysis. RESULTS: Foremost 192 case reports were initially identified, with 75 drugs meeting the inclusion criteria after a thorough review. The latest revision identified seven drugs that might lead to TCM, with four drugs (57.14%) already reported in previous reviews and three drugs (42.86%) newly identified. Consequently, the updated drug list potentially triggering TCM in 2023 comprises a sum of 75 drugs. CONCLUSION: The recent 75 drugs provided additional evidence linking to TCM development. The updated list predominantly includes drugs that induce sympathetic overstimulation, although some drugs on the list have unclear associations with sympathetic nervous system activation.

Síndrome de barlow: causa olvidada de miocardiopatía dilatada y muerte súbita / Barlow syndrome: A rare etiology of sudden death

Resumen Se presenta el caso de una mujer de 60 años, con an tecedente de prolapso de la válvula mitral, que consultó por disnea y palpitaciones de 2 semanas de evolución hasta clase funcional IV. En el electrocardiograma de ingreso se evidenció ritmo de fibrilación auricular de moderada respuesta con extrasístoles ventriculares fre cuentes. Se realizó ecocardiograma transtorácico donde se observó prolapso de la válvula mitral con deterioro grave de la función ventricular. Se diagnosticó síndrome de Barlow. La paciente intercurrió durante la internación con tres episodios de paro cardiorrespiratorio que revir tieron con maniobras de reanimación cardiopulmonar avanzada. Durante la internación se realizó balance negativo, se revirtió a ritmo sinusal y se colocó cardio desfibrilador implantable en prevención secundaria. En el seguimiento persiste con deterioro grave de la función ventricular. Destacamos el síndrome de Barlow como una causa poco frecuente de muerte súbita y su asociación con miocardiopatía dilatada.

Abstract We present the case of a 60-year-old woman, with a history of mitral valve prolapse, who consulted for dyspnea and palpitations of 2 weeks of evolution up to functional class IV. The admission electrocardio gram showed a moderately responsive atrial fibrilla tion rhythm with frequent ventricular extra systoles. A transthoracic echocardiogram was performed which showed mitral valve prolapse with severe impairment of ventricular function. Barlow syndrome was diagnosed. During hospitalization, the patient presented three epi sodes of cardiorespiratory arrest that were reversed with advanced cardiopulmonary resuscitation maneuvers. During admission, a negative balance was performed, sinus rhythm was reverted and an implantable auto matic defibrillator was placed in secondary prevention. During follow-up, severe deterioration of ventricular function persisted. We highlight Barlow syndrome as a rare cause of sudden death and its association with dilated cardiomyopathy.

Being exposed to the same trigger increases the risk of recurrence of takotsubo cardiomyopathy in children and can have fatal results: a case report.

Takotsubo cardiomyopathy has an incidence of 1% of acute coronary syndrome in the adult population, and the risk of recurrence is approximately 1.5% per year. However, only a few cases have been reported in children. Having a neurologic disorder and being exposed to the same trigger repeatedly have been associated with an increased risk.

[Barlow syndrome: A rare etiology of sudden death]. / Síndrome de Barlow: causa olvidada de miocardiopatía dilatada y muerte súbita.

We present the case of a 60-year-old woman, with a history of mitral valve prolapse, who consulted for dyspnea and palpitations of 2 weeks of evolution up to functional class IV. The admission electrocardiogram showed a moderately responsive atrial fibrillation rhythm with frequent ventricular extra systoles. A transthoracic echocardiogram was performed which showed mitral valve prolapse with severe impairment of ventricular function. Barlow syndrome was diagnosed. During hospitalization, the patient presented three episodes of cardiorespiratory arrest that were reversed with advanced cardiopulmonary resuscitation maneuvers. During admission, a negative balance was performed, sinus rhythm was reverted and an implantable automatic defibrillator was placed in secondary prevention. During follow-up, severe deterioration of ventricular function persisted. We highlight Barlow syndrome as a rare cause of sudden death and its association with dilated cardiomyopathy.

Se presenta el caso de una mujer de 60 años, con antecedente de prolapso de la válvula mitral, que consultó por disnea y palpitaciones de 2 semanas de evolución hasta clase funcional IV. En el electrocardiograma de ingreso se evidenció ritmo de fibrilación auricular de moderada respuesta con extrasístoles ventriculares frecuentes. Se realizó ecocardiograma transtorácico donde se observó prolapso de la válvula mitral con deterioro grave de la función ventricular. Se diagnosticó síndrome de Barlow. La paciente intercurrió durante la internación con tres episodios de paro cardiorrespiratorio que revirtieron con maniobras de reanimación cardiopulmonar avanzada. Durante la internación se realizó balance negativo, se revirtió a ritmo sinusal y se colocó cardiodesfibrilador implantable en prevención secundaria. En el seguimiento persiste con deterioro grave de la función ventricular. Destacamos el síndrome de Barlow como una causa poco frecuente de muerte súbita y su asociación con miocardiopatía dilatada.

Arrhythmic syncope: From diagnosis to management.

Syncope is a concerning symptom that affects a large proportion of patients. It can be related to a heterogeneous group of pathologies ranging from trivial causes to diseases with a high risk of sudden death. However, benign causes are the most frequent, and identifying high-risk patients with potentially severe etiologies is crucial to establish an accurate diagnosis, initiate effective therapy, and alter the prognosis. The term cardiac syncope refers to those episodes where the cause of the cerebral hypoperfusion is directly related to a cardiac disorder, while arrhythmic syncope is cardiac syncope specifically due to rhythm disorders. Indeed, arrhythmias are the most common cause of cardiac syncope. Both bradyarrhythmia and tachyarrhythmia can cause a sudden decrease in cardiac output and produce syncope. In this review, we summarized the main guidelines in the management of patients with syncope of presumed arrhythmic origin. Therefore, we presented a thorough approach to syncope work-up through different tests depending on the clinical characteristics of the patients, risk stratification, and the management of syncope in different scenarios such as structural heart disease and channelopathies.

Advances in symptomatic therapy for left ventricular non-compaction in children.

Left ventricular non-compaction is a complex cardiomyopathy and the third largest childhood cardiomyopathy, for which limited knowledge is available. Both pathogenesis and prognosis are still under investigation. Currently, no effective treatment strategy exists to reduce its incidence or severity, and symptomatic treatment is the only clinical treatment strategy. Treatment strategies are constantly explored in clinical practice, and some progress has been made in coping with the corresponding symptoms because the prognosis of children with left ventricular non-compaction is usually poor if there are complications. In this review, we summarized and discussed the coping methods for different left ventricular non-compaction symptoms.

Advancements in pharmacological therapy for transthyretin cardiac amyloidosis and its comorbidities / 中国药房

Transthyretin cardiac amyloidosis myocardiopathy （ATTR-CM） is an infiltrative cardiomyopathy characterized by the deposition of amyloidogenic material in the myocardial interstitium due to the misfolding of monomers following the dissociation of unstable transthyretin （TTR） tetramers. Previous treatments for ATTR-CM lacked specificity，primarily targeting symptomatic management of heart failure and arrhythmias. In recent years，researchers have developed two major classes of drugs addressing the pathogenesis of ATTR-CM. The first class stabilizes TTR tetramer structure （such as tafamidis and acoramidis）， while the second class interferes with TTR synthesis （such as patisiran）. Among these，tafamidis has been confirmed as the only currently effective treatment for ATTR-CM，while other drugs are still in clinical trial stages with limited clinical evidence. Concerning the management of comorbidities in ATTR-CM，treatment mainly focuses on common cardiac comorbidities （such as heart failure and arrhythmias）. Traditional drugs used to improve heart failure prognosis （such as β-blockers and renin-angiotensin- receptor blocker），have not demonstrated prognosis improvement in ATTR-CM patients and may even lead to adverse reactions. For ATTR-CM patients with concurrent atrial fibrillation，anticoagulation therapy is recommended to prevent thrombus formation，and amiodarone can be used for rhythm control. Despite significant advancements in pharmaceutical treatments for ATTR-CM，the overall prognosis remains poor，necessitating further research into the pathogenesis and target development to enhance the prognosis of ATTR-CM patients.

Paciente adulto con alteraciones cardiacas secundarias a enfermedad de Fabry / An adult patient with heart abnormalities secondary to Fabry disease

Resumen Introducción: La enfermedad de Fabry es una entidad crónica, progresiva, poco frecuente, de origen genético y patrón de herencia recesivo ligado al cromosoma X. Se caracteriza por déficit enzimático de alfa-galactosidasa causado por mutaciones en el gen GLA, lo que produce almacenamiento anormal de esfingolípidos celulares y tisulares Caso clínico: Se describe el caso de un paciente de 53 años, con antecedente familiar y compromiso cardíaco predominante, dado por hipertrofia ventricular izquierda, arritmias auriculares e insuficiencia cardiaca congestiva secundaria, quien, adicionalmente, tiene manifestaciones multisistémicas que han evolucionado desde la infancia. Entre los pilares de tratamiento requirió implantación definitiva de marcapasos y terapia de reemplazo enzimático. Conclusiones: La enfermedad de Fabry es una entidad de compromiso sistémico y progresivo, de baja prevalencia, cuya importancia se debe reflejar en el entrenamiento del personal de salud para el adecuado diagnóstico, con miras a mejorar la calidad de vida de los pacientes.

Abstract Introduction: Fabry’s disease is a chronic, progressive and a multisystemic disease of genetic origin, with a recessive pattern of inheritance tied to the X chromosome, characterized by the lisosomal deposit of globotriaosylceramide as a consequence of a deficiency in the activity of the alpha-galactosidase A enzyme. Clinical case: We present a clinical case of a 53-year old male patient carrying this disease with family history of Fabry’s disease, who suffers cardiac compromise as the main clinical manifestation. He is a patient who required the implantation of a permanent pacemaker and enzyme replacement therapy. Conclusions: Fabry´s disease is a systemic and progressive disease, low fre-quency, and not well known by the health personnel, which implies a late diagnosis, being the cardiac compromise the second in frequency after renal compromise, which can lead to the patient to a hypertrophic cardiomyopathy and a rhythm and cardiac conduction disorder.

Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation.

Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-α, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA-a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function.

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease.

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?" and "Could Se be recommended as a therapeutic strategy for CCC?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-ß as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-ß pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.

Translational research in Chagas disease: perspectives in nutritional therapy emerging from selenium supplementation studies as a complementary treatment

Translational research (TR) is an interdisciplinary branch of the biomedical field that seeks to connect its three supporting pillars: basic research on the bench, the hospital beds and other health system services, and the delivery of products for the well-being and health of the community. Here, we review the five transition stages of the TR spectrum, registering the lessons learned during > 20 years leading to the first clinical trial designed and performed in Brazil for testing a complementary treatment for Chagas disease (CD): the selenium trial (STCC). Lessons learned were: (1) to consider all the TR spectrum since the beginning of the project; (2) to start simultaneously animal studies and translation to humans; (3) to ensure a harmonious interaction between clinical and basic research teams; (4) to include MSc and PhD students only in pre-clinical and basic studies (TR0) or vertical clinical studies using retrospective samples and data (TR1); (5) to identify potential suppliers in the national commercial market for a future final treatment since the pre-clinical stage; (6) to keep an international network of experts as permanent advisers on the project. In the whole process, some perspectives were created: a complementary clinical trial for the opened questions and the construction of a Brazilian clinical CD platform.

Heart Failure in Type 1 Diabetes: A Complication of Concern? A Narrative Review.

Heart failure (HF) has been a hot topic in diabetology in the last few years, mainly due to the central role of sodium-glucose cotransporter 2 inhibitors (iSGLT2) in the prevention and treatment of cardiovascular disease and heart failure. It is well known that HF is a common complication in diabetes. However, most of the knowledge about it and the evidence of cardiovascular safety trials with antidiabetic drugs refer to type 2 diabetes (T2D). The epidemiology, etiology, and pathophysiology of HF in type 1 diabetes (T1D) is still not well studied, though there are emerging data about it since life expectancy for T1D has increased in the last decades and there are more elderly patients with T1D. The association of T1D and HF confers a worse prognosis than in T2D, thus it is important to investigate the characteristics, risk factors, and pathophysiology of this disease in order to effectively design prevention strategies and therapeutic tools.

Acute and Delayed Doxorubicin-Induced Myocardiotoxicity Associated with Elevation of Cardiac Biomarkers, Depletion of Cellular Antioxidant Enzymes, and Several Histopathological and Ultrastructural Changes.

Doxorubicin (DOX; Adricin) is an anthracycline antibiotic, which is an efficient anticancer chemotherapeutic agent that targets many types of adult and pediatric tumors, such as breast cancer, leukemia, and lymphomas. However, use of DOX is limited due to its cardiotoxic effects. This study sequentially investigated the mechanistic pathways of the cardiotoxic process of DOX in rats at different post-treatment periods using cumulative dose, which is used in therapeutic regimes. In this regard, 56 male albino rats were used for the experiment. The experimental animals were divided into seven groups (n = 8/group) based on dose and sacrifice schedule as follows: G1 (2 mg/kg body weight [BW] and sacrificed at day 4), G2 (4 mg/kg BW and sacrificed at day 8), G3 (6 mg/kg BW and sacrificed at day 15), G4 (8 mg/kg BW and sacrificed at day 30), G5 (10 mg/kg BW and sacrificed at day 60), G6 (10 mg/kg BW and sacrificed at day 90), and G7 (10 mg/kg BW and sacrificed at day 120). As expected, G1, G2, and G3-treated groups revealed features of acute toxic myocarditis associated with degenerative and necrotic changes in myocytes, mitochondrial damage, elevation of cardiac biomarkers, and depletion of cellular antioxidant enzymes. However, these changes increased in severity with subsequent treatment with the same dose until reaching a cumulative dose of 10 mg/kg BW for 30 d. Furthermore, after a cumulative dose of 10 mg/kg BW with a withdrawal period of 2-3 months, various predominant changes in chronicity were reported, such as disorganization and atrophy of myocytes, condensation and atrophy of mitochondria, degranulation of mast cells, and fibrosis with occasional focal necrosis, indicating incomplete elimination of DOX and/or its metabolites. Altogether, these data provide interesting observations associated with the cardiotoxic process of DOX in rats that would help understand the accompanying changes underlying the major toxic effects of the drug. Future research is suggested to explore more about the dose-dependent mechanisms of such induced toxicity of DOX that would help determine the proper doses and understand the resulting cardiomyopathy.

A systematic review of historical and current trends in Chagas disease.

INTRODUCTION: Chagas disease (CD) is caused by Trypanosoma cruzi. When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient's health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide. MATERIALS AND METHODS: We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms 'American trypanosomiasis' or 'Chagas disease'. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures. RESULTS: From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%. DISCUSSION: CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD's diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines.

Programming by Methyl Donor Deficiency during Pregnancy and Lactation Produces Cardiomyopathy in Adult Rats Subjected to High Fat Diet.

SCOPE: Vitamin B12 and folate (methyl donors) deficiency is frequent during pregnancy. Experimental rat models with methyl donor deficit during pregnancy and lactation (Initial methyl donor deficit (iMDD)) produce impaired myocardium fatty acid oxidation and mitochondrial energy metabolism at weaning. METHODS AND RESULTS: The consequences of iMDD on heart of rat pups under normal diet after weaning and high fat diet (HF) between day (D) 50 and D185 are investigated. iMDD/HF induces increased histological fibrosis and increased B-type natriuretic peptide blood level. Inflammation is evidenced by increased protein expression of NFkB, Caspase1, and IL1ß and fibrosis by increased expression of αSMA, col1a1, and col1a2 in females, but not in males. Fibrosis is related to increased angiotensin at D50 and D185 and increased protein expression of TGFB1 and AT1 angiotensin receptors at D185. The limited fibrosis in males is consistent with increased expression of AT2, the antagonist receptor of AT1. The increased expression of GLUT4 and decreased expression of PGC1α and PPARα reflect a shift from fatty acid oxidation to glycolysis. CONCLUSION: Developmental programming by iMDD produces cardiomyopathy in female offspring exposed to HF. The cardiomyopathy is linked to inflammation and fibrosis through angiotensin-AT2 and TGFB1 pathways and alteration of energy metabolism.

Deletion of Smad3 protects against diabetic myocardiopathy in db/db mice.

Diabetic cardiomyopathy (DCM) is a common diabetic complication characterized by diastolic relaxation abnormalities, myocardial fibrosis and chronic heart failure. Although TGF-ß/Smad3 signalling has been shown to play a critical role in chronic heart disease, the role and mechanisms of Smad3 in DCM remain unclear. We reported here the potential role of Smad3 in the development of DCM by genetically deleting the Smad3 gene from db/db mice. At the age of 32 weeks, Smad3WT-db/db mice developed moderate to severe DCM as demonstrated by a marked increase in the left ventricular (LV) mass, a significant fall in the LV ejection fraction (EF) and LV fractional shortening (FS), and progressive myocardial fibrosis and inflammation. In contrast, db/db mice lacking Smad3 (Smad3KO-db/db) were protected against the development of DCM with normal cardiac function and undetectable myocardial inflammation and fibrosis. Interestingly, db/db mice with deleting one copy of Smad3 (Smad3 ± db/db) did not show any cardioprotective effects. Mechanistically, we found that deletion of Smad3 from db/db mice largely protected cardiac Smad7 from Smurf2-mediated ubiquitin proteasome degradation, thereby inducing IBα to suppress NF-kB-driven cardiac inflammation. In addition, deletion of Smad3 also altered Smad3-dependent miRNAs by up-regulating cardiac miR-29b while suppressing miR-21 to exhibit the cardioprotective effect on Smad3KO-db/db mice. In conclusion, results from this study reveal that Smad3 is a key mediator in the pathogenesis of DCM. Targeting Smad3 may be a novel therapy for DCM.

["Staghorn" heart. The pathology of the explanted heart of a patient with clinical diagnosis and genetic variants of non-compacted myocardiopathy]. / Corazón en «asta de ciervo¼. Estudio anatomopatológico del corazón explantado de una paciente con diagnóstico clínico y variantes genéticas de miocardiopatía no compactada.

Non-compacted myocardiopathy is rare, the prevalence ranging between 0.01-0.26%. in adults. We present the macroscopic, microscopic and electron microscopy findings of cardiac transplant samples from a 36-year-old patient diagnosed with non-compacted myocardiopathy. This condition shows a high genetic and phenotypic heterogeneity, with superposition of different phenotypes and variability in the hereditary patterns. Clinical diagnosis is established by coupling imaging results to clinical characteristics. The clinical manifestations of non-compacted myocardiopathy are variable, including arrhythmic events and variable degrees of cardiac failure, although some patients may be asymptomatic. In certain cases a heart transplant may be necessary. The differential diagnosis should be made with hypertrophic and dilated myocardiopathy. However, only a few reports can be found in the literature that discuss the pathology of this condition.

Patologías del niño inmigrante en la Unidad de Cuidados Intensivos: actualización / Pathologies of the immigrant child in the Intensive Care Unit: update

Resumen: Cada vez es más frecuente la atención médica en la Unidad de Cuidados Intensivos (UCI) de niños o adolescentes inmigrantes como también de aquellos nacidos en nuestro país con padres en tal condición. Esto ha ocasionado, en la actualidad, que el equipo de salud se deba enfrentar con problemas diagnósticos derivados del escaso conocimiento de condiciones genéticas propias de esta población y/o el desarrollo de diversas patologías infrecuentes en nuestro país, algunas resultantes de su condi ción sanitaria. En esta revisión se abordan diversos aspectos de la patología hematológica, infecciosa, parasitaria, respiratoria y cardiovascular, todos tópicos relevantes de conocer durante su estadía en la UCI. Es un deber del equipo de salud actualizarse sobre patologías de baja prevalencia en nuestro país, algunas de ellas muy poco conocidas hasta hace una década, pero que, actualmente, están cada vez más presentes en las UCI del sistema de salud público chileno.

Abstract: It is increasingly common to provide medical care in the Intensive Care Unit (ICU) for immigrant children and adolescents as well as those born in Chile with parents in such condition. Currently, this has caused that the health team has to face diverse infrequent pathologies in our country and/ or diagnostic problems derive from the poor knowledge of genetic conditions of this population, some resulting from their health conditions. This review addresses several aspects of hematological, infectious, parasitic, respiratory, and cardiovascular pathologies, all relevant topics to know during their stay in the ICU. It is a duty of the health team to be updated on pathologies of low prevalence in our country, some of them very little known until a decade ago, but which are currently increasingly present in the ICUs of the Chilean public health system.

Mutations of histone demethylase genes encoded by X and Y chromosomes, Kdm5c and Kdm5d, lead to noncompaction cardiomyopathy in mice.

Mammalian X and Y chromosomes evolved from a pair of autosomes. Although most ancestral genes have been lost from the Y chromosome, a small number of ancestral X-Y gene pairs are still present on the sex chromosomes. The KDM5C and KDM5D genes, which encode H3K4 histone demethylases, are a surviving ancestral gene pair located on the X and Y chromosomes, respectively. Mutations in KDM5C cause X-linked intellectual disability in human males, suggesting functional divergence between KDM5C and KDM5D in the nervous system. In this study, to explore the functional conservation and divergence between these two genes in other organs, we generated female mice lacking Kdm5c (homozygous X5c- X5c- females) and male mice lacking both Kdm5c and Kdm5d (compound hemizygous X5c- Y5d- males). Both X5c- X5c- females and X5c- Y5d- males showed lower body weights and postnatal lethality. Histological examination of the hearts showed prominent trabecular extension and a thin layer of compacted myocardium in the left and right ventricles, indicating noncompaction cardiomyopathy. However, hemizygous males lacking either Kdm5c or Kdm5d showed no signs of noncompaction cardiomyopathy. These results clearly demonstrate that the function of Kdm5c and Kdm5d in heart development is conserved.

Miocardiopatía de y movimiento sistólico anterior de válvula mitral / Myocardiopaty and sistolic anterior movement of mitral valve

Tako tsubo cardiomyopathy associated with left ventricular outflow tract obstruction (LVOT) is a rare cause of persistent perioperative hypotension. One of the causes of this association is the systolic anterior motion (SAM) of the mitral valve. We report a case of a 67-year-old woman who, after undergoing liver segmentectomy because of metastasis, presents post-operative hypotension that is difficult to manage. Upon evaluation with a transthoracic echocardiogram, the diagnostic suspicion of Tako tsubo syndrome associated with LVOT obstruction secondary to SAM was raised. As initial therapy, a volume expander, in association with propanolol and phenylephrine were administred, achieving partial hemodynamic response. Later, she evolved with signs of heart failure and was transferred to the intensive care unit for management. In this unit, non-invasive ventilatory support, diuretic and vasopressor therapy were required, achieving favorable results on the second post-operative day. Echocardiography was essential to make the differential diagnosis against a persistent post-operative hypotension

La cardiomiopatía de Tako tsubo asociada a obstrucción del tracto de salida del ventrículo izquierdo (TSVI) es una causa poco frecuente de hipotensión persistente en el perioperatorio. Uno de los motivos de esta asociación es el movimiento anormal sistólico (SAM) de la válvula mitral. A continuación, presentamos el caso de una mujer de 67 años que, tras ser sometida a segmentectomía hepática por metástasis, presenta cuadro de hipotensión postoperatoria de difícil manejo. Al ser evaluada con ecocardiograma transtorácico se plantea la sospecha diagnóstica de síndrome de Tako tsubo asociado a obstrucción del TSVI secundario a SAM. Como terapia inicial se realizó aporte de volumen, en asociación con propanolol y fenilefrina, logrando parcial respuesta hemodinámica. Posteriormente, evolucionó con signos de insuficiencia cardiaca y fue trasladada a unidad de cuidados intensivos para su manejo. En esta unidad requirió apoyo ventilatorio no invasivo, terapia diurética y vasopresora, logrando resultados favorables al segundo día postoperatorio. La ecocardiografía fue fundamental para realizar el diagnóstico diferencial frente a un cuadro de hipotensión postoperatoria persistente.