RESUMO
Treatments for structural heart diseases (SHD) have been considerably evolved by the widespread of transcatheter approach in the last decades. The progression of transcatheter treatments for SHD was feasible due to the improvement of devices and the advances in imaging techniques. In this setting, the cardiovascular imaging is pivotal not only for the diagnosis but even for the treatment of SHD. With the aim of fulfilling these tasks, a multimodality imaging approach with new imaging tools for pre-procedural planning, intra-procedural guidance, and follow-up of SHD was developed. This review will describe the current state-of-the-art imaging techniques for the most common percutaneous interventions as well as the new imaging tools. The imaging approaches will be addressed describing the use in pre-procedural planning, intra-procedural guidance, and follow-up.
RESUMO
A great deal of evidence has revealed an important link between gut microbiota and the heart. In particular, the gut microbiota plays a key role in the onset of cardiovascular (CV) disease, including heart failure (HF). In HF, splanchnic hypoperfusion causes intestinal ischemia resulting in the translocation of bacteria and their metabolites into the blood circulation. Among these metabolites, the most important is Trimethylamine N-Oxide (TMAO), which is responsible, through various mechanisms, for pathological processes in different organs and tissues. In this review, we summarise the complex interaction between gut microbiota and CV disease, particularly with respect to HF, and the possible strategies for influencing its composition and function. Finally, we highlight the potential role of TMAO as a novel prognostic marker and a new therapeutic target for HF.
Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Insuficiência Cardíaca , Humanos , Metilaminas/metabolismo , Insuficiência Cardíaca/metabolismoRESUMO
Gitelman syndrome (GS), or congenital hypokalemic hypomagnesemia hypocalciuria with metabolic alkalosis, is a congenital inherited tubulopathy. This tubulopathy is associated with disorders of water-electrolyte homeostasis, such as metabolic alkalosis, hypokalemia, hyponatremia, hypomagnesemia and hypocalciuria. GS has an autosomal recessive inheritance. The loss-of-function mutation involves the gene that codifies for thiazide-sensitive sodium-chloride co-transporter located in the distal convoluted tubule. The physiopathology of the syndrome is characterized by activation of the renin-angiotensin-aldosterone system (RAAS) with a low plasmatic concentration of angiotensin-II. Despite hyper-activation of RAAS, average or low blood pressure is detected in association with low peripheral resistance and reduced response to vasopressors. Clinical findings are brief episodes of fatigue, syncope, vertigo, ataxia and blurred vision; sudden cardiac death might occur. This review aims to give insight into cardiovascular implications and management of GS.
RESUMO
Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Volume Sistólico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologiaRESUMO
BACKGROUND: Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood. We previously studied the role of FOXL2C134W, its partner SMAD3 and its antagonist FOXO1 in cellular models of aGCT. METHODS: In this work, seeking more comprehensive profiling of FOXL2C134W transcriptomic effects, we performed an RNA-seq analysis comparing the effect of FOXL2WT/SMAD3 and FOXL2C134W/SMAD3 overexpression in an established human GC line (HGrC1), which is not luteinized, and bears normal alleles of FOXL2. RESULTS: Our data shows that FOXL2C134W/SMAD3 overexpression alters the expression of 717 genes. These genes include known and novel FOXL2 targets (TGFB2, SMARCA4, HSPG2, MKI67, NFKBIA) and are enriched for neoplastic pathways (Proteoglycans in Cancer, Chromatin remodeling, Apoptosis, Tissue Morphogenesis, Tyrosine Kinase Receptors). We additionally expressed the FOXL2 antagonistic Forkhead protein, FOXO1. Surprisingly, overexpression of FOXO1 mitigated 40% of the altered genome-wide effects specifically related to FOXL2C134W, suggesting it can be a new target for aGCT treatment. CONCLUSIONS: Our transcriptomic data provide novel insights into potential genes (FOXO1 regulated) that could be used as biomarkers of efficacy in aGCT patients.
Assuntos
Tumor de Células da Granulosa , Neoplasias Ovarianas , Adulto , Linhagem Celular Tumoral , DNA Helicases , Feminino , Proteína Forkhead Box L2 , Proteína Forkhead Box O1/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Tumor de Células da Granulosa/genética , Humanos , Mutação , Proteínas Nucleares , Neoplasias Ovarianas/genética , Proteína Smad3/genética , Fatores de Transcrição , Transcriptoma/genéticaRESUMO
BACKGROUND: In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown. METHODS: In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system. RESULTS: Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis). CONCLUSIONS: Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.
Assuntos
Síndrome do Ovário Policístico , Células Tecais , Androgênios/farmacologia , Animais , Família 17 do Citocromo P450 , Feminino , Humanos , Masculino , Camundongos , Fenótipo , Esteroide 17-alfa-Hidroxilase/genéticaRESUMO
BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.
Assuntos
COVID-19 , Coração/fisiopatologia , COVID-19/patologia , Estudos Transversais , Ecocardiografia , Humanos , Miocárdio , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Full-grown mouse antral oocytes are classified as surrounding nucleolus (SN) or not-surrounding nucleolus (NSN), depending on the respective presence or absence of a ring of Hoechst-positive chromatin surrounding the nucleolus. In culture, both types of oocytes resume meiosis and reach the metaphase II (MII) stage, but following insemination, NSN oocytes arrest at the two-cell stage whereas SN oocytes may develop to term. By coupling time-lapse bright-field microscopy with image analysis based on particle image velocimetry, we provide the first systematic measure of the changes to the cytoplasmic movement velocity (CMV) occurring during the germinal vesicle-to-MII (GV-to-MII) transition of these two types of oocytes. Compared to SN oocytes, NSN oocytes display a delayed GV-to-MII transition, which can be mostly explained by retarded germinal vesicle break down and first polar body extrusion. SN and NSN oocytes also exhibit significantly different CMV profiles at four main time-lapse intervals, although this difference was not predictive of SN or NSN oocyte origin because of the high variability in CMV. When CMV profile was analyzed through a trained artificial neural network, however, each single SN or NSN oocyte was blindly identified with a probability of 92.2% and 88.7%, respectively. Thus, the CMV profile recorded during meiotic resumption may be exploited as a cytological signature for the non-invasive assessment of the oocyte developmental potential, and could be informative for the analysis of the GV-to-MII transition of oocytes of other species.
Assuntos
Nucléolo Celular/metabolismo , Citoplasma/metabolismo , Meiose/fisiologia , Oócitos/metabolismo , Animais , Feminino , CamundongosRESUMO
Background: Residual interatrial shunt following percutaneous patent foramen ovale (PFO) closure is a rare complication that can be associated with persistent migraine. Case summary: A 32-year-old woman with a history of percutaneous PFO closure due to a previous coronary paradoxical embolism and a condition of drug-refractory migraine underwent transoesophageal echocardiography (TOE) to investigate further recurrent migraine attacks. A partial displacement of a PFO occluder device was found, and it was successfully treated through the fluoroscopic and TOE-guided positioning of a second occluder in overlap with the previous one. The patient reported no more migraine attacks at the 6-month follow-up visit. Discussion: Residual interatrial shunt should be suspected in patients with persistent migraine and a history of percutaneous PFO closure. Fluoroscopic and TOE-guided closure of residual interatrial shunt with a second PFO occlude device seems to be a safe and clinically effective strategy to manage persistent migraine.
RESUMO
BACKGROUND: Echocardiographic grading of mitral regurgitation (MR) in mitral valve prolapse (MVP) is challenging. Three-dimensional (3D) vena contracta area (VCA) has been proposed as a valuable method. However, data defining the cutoff values of severity and validation in the subset of patients with MVP are scarce. The aim of this study was to validate the 3D VCA by 3D color-Doppler transesophageal echocardiography (TEE) in patients with MVP and to define the cutoff values of severity grading. The secondary aim was to compare 3D VCA to the effective regurgitant orifice area estimation by proximal isovelocity surface area (EROA-PISA) method. METHODS: A total of 1,138 patients with at least moderate MR who underwent TEE were included. Three-dimensional VCA was measured, and the cutoff value and area under the curve (AUC) for the prediction of severe MR were estimated by receiver operating characteristic curve using a guideline-suggested multiparametric approach as the reference standard. In a subgroup of patients, 3D regurgitant volume (RV) and 3D fraction were calculated from mitral and left ventricular outflow tract stroke volumes to further validate 3D VCA against a 3D volumetric reference standard. RESULTS: The optimal 3D VCA cutoff value for predicting severe MR was 0.45 cm2 (specificity, 0.87; sensitivity, 0.90) with an AUC of 0.95 using a multiparametric approach as reference. Three-dimensional VCA had a good linear correlation with EROA-PISA (r = 0.62, P < .05) with larger values compared to EROA-PISA (0.63 cm2 vs 0.44 cm2, P < .05). A cutoff of 0.50 cm2 (AUC of 0.84; sensitivity, 0.78; specificity, 0.78) predicts an EROA-PISA of 0.40 cm2. Three-dimensional VCA had a good linear correlation with 3D RV (r = 0.56, P < .01), with an AUC of 0.86 to predict a 3D fraction >50%. CONCLUSIONS: The present study suggests 0.45 cm2 as the best cutoff value of 3D VCA to define severe MR in patients with MVP, showing an optimal agreement with the reference standard multiparametric approach and 3D RV.
Assuntos
Ecocardiografia Tridimensional , Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Índice de Gravidade de Doença , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Ecocardiografia Tridimensional/métodos , Feminino , Masculino , Prolapso da Valva Mitral/complicações , Prolapso da Valva Mitral/diagnóstico por imagem , Prolapso da Valva Mitral/fisiopatologia , Pessoa de Meia-Idade , Idoso , Ecocardiografia Transesofagiana/métodos , Ecocardiografia Doppler em Cores/métodos , Reprodutibilidade dos Testes , Valva Mitral/diagnóstico por imagem , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUNDS: Mitral annular disjunction (MAD) is commonly evaluated at end-systole. However, a systolic-only disjunction is merely apparent and two distinct phenotypes have been identified: True-MAD (atrial displacement of the posterior leaflet in diastole and systole) and Pseudo-MAD (apparent displacement in systole only). The prevalence of True-MAD and Pseudo-MAD in mitral valve prolapse (MVP) is not known. Aim of this study was to assess the prevalence of True-MAD and Pseudo-MAD in myxomatous MVP patients by transthoracic echocardiography (TTE) and to validate TTE compared to cardiac magnetic resonance (CMR) (reference standards). METHODS: Consecutive patients who underwent TTE for MVP were included. Mitral annular phenotype was evaluated in TTE parasternal long-axis view. Accuracy (against CMR) and intra/inter rater reliability of TTE were also assessed. RESULTS: Six-hundred-three consecutive patients were included. The prevalence of True-MAD and Pseudo-MAD was 7% (42) and 37% (221) (p<0.05), respectively. Accordingly, 221 of 263 (84%) patients classically classified as "MAD" would have been reclassified as Pseudo-MAD. Pseudo-MAD prevalence and systolic length increased with higher mitral regurgitation (MR) severity (23% for mild MR, 36% for moderate MR, 44% for severe MR (p<0.05); 6 ± 2 mm for mild MR; 8 ± 2 mm for moderate MR; 10 ± 2mm for severe MR (p<0.05), while True-MAD prevalence was consistent across MR grades. Pseudo-MAD was linked to systolic curling and Pickelhaube. TTE showed an overall accuracy of 0.89 (Cohen k 0.80), a substantial inter-rater agreement of 0.87 (k 0.76) and an almost perfect intra-rater agreement of 0.93 (k 0.85). CONCLUSION: True-MAD, unlike Pseudo-MAD, is rare in patients with MVP. Pseudo-MAD is associated with the grade of MR and other echocardiographic features of advanced myxomatous degeneration. TTE is an accurate and reliable first line method to assess mitral annulus morphology in MVP.
RESUMO
Background: We aimed to assess the characteristics, management and long-term prognosis of a cohort of patients with multiple valvular disease, focusing on the context of severe mitral or aortic disease with concomitant significant tricuspid regurgitation (TR). Methods: After using a propensity score matching for age, 975 patients with ≥ moderate TR, diagnosed at our centers from 2012 to 2020, were included and divided in four groups, including isolated TR patients as reference group. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization + any valvular intervention. Results: Patients with isolated TR (356, 37 %) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). Patients with severe mitral regurgitation (MR) + TR (466, 48 %) showed higher rates of concomitant coronary artery disease, advanced functional class symptoms and larger left atrial volumes. Severe aortic stenosis (AS) patients (131, 13 %) were older, with more comorbidities and lower LVEF. Patients with severe aortic regurgitation and TR (22, 2 %) were younger, with larger LV dimensions and higher pulmonary arterial pressures.After a median follow-up of 2.8 years, both endpoints were univariably more frequent in patients with severe AS + TR (all p < 0.001), but after comprehensive adjustment difference in the primary endpoint became insignificant, underscoring the serious outcomes of all significant TR groups significantly. Overall, in 44 (5 %) patients tricuspid intervention was performed, with no differences between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment. Conclusions: In the context of severe left-sided VD, concomitant significant TR is common, and each subtype presents with different clinical and echocardiographic features: patients with severe AS and TR have considerable worse prognosis, although comprehensive adjustment reflected the poor outcomes affecting all types of patients with significant TR. In this scenario, TR was profoundly undertreated.
RESUMO
AIMS: The prevalence, the etiologies and the clinical features of tricuspid regurgitation (TR) in the context of concomitant degenerative mitral valve (MV) disease are poorly defined. This paper aims to assess the prevalence, determinants and clinical consequences of TR in severe degenerative mitral regurgitation (DMR). METHODS AND RESULTS: Clinical and echocardiographic characteristics were collected among patients with severe DMR. 884 patients were included in our study, 31% with > moderate TR. Tricuspid valve prolapse (TVP) was the most common etiology (487 patients, 55%), followed by atrial functional TR (AFTR, 172 patients, 19%) and ventricular functional TR (VFTR, 42 patients, 5%), while TR etiology was mixed in 183 (21%) patients. Patients with TVP were younger, had better clinical presentation, had few comorbidities, and had less hemodynamically relevant TR. VFTR patients were characterized by older age, worst clinical presentation and both highest comorbidity rate and prevalence of >mild TR. AFTR group showed an intermediate profile of clinical presentation and comorbidities and the largest tricuspid annulus (TA) diameter.MV surgery was performed in 785 (88%) patients; 132 (15%) underwent simultaneous TV intervention, more often AFTR patients (32%). TA dilatation (OR 3.68, CI 2.05-6.62, p <0.001) and >mild TR (OR 9.30, CI 5.10-16.95, p<0.001) were independently associated with TV intervention. CONCLUSIONS: In patients with severe DMR, TR presents with different etiologies, clinical features and echocardiographic phenotypes that require a comprehensive assessment at the time of DMR surgery to ensure the best management for these patients.
RESUMO
AIMS AND DATA SYNTHESIS: Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. CONCLUSIONS: We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Angiopatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Glicemia , Glucose , Hemoglobinas Glicadas , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Fatores de Risco , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/complicaçõesRESUMO
AIMS: Conduction abnormalities, requiring a permanent pacemaker (PPM), are the most common electrical complications after transcatheter aortic valve implantation (TAVI). The exact mechanism for conduction system defects is not yet clear. The local inflammatory process and edema are thought to play a role in the development of electrical disorders. Corticosteroids are effective anti-inflammatory and antiedematous agents. We aim to investigate the potential protective effect of corticosteroids on conduction defects after TAVI. METHODS: This is a retrospective study of a single center. We analyzed 96 patients treated with TAVI. Thirty-two patients received oral prednisone 50âmg for 5 days after the procedure. This population was compared with the control group. All patients were followed up after 2 years. RESULTS: Of the 96 patients included, 32 (34%) were exposed to glucocorticoids after TAVI. No differences in age, preexisting right bundle branch block or left bundle branch block, or valve type were seen among patients exposed to glucocorticoids versus those who were unexposed. We observed no significant differences between the two groups in the overall frequency of new PPM implantations during hospitalization (12% vs. 17%, P â=â0.76). The incidence of atrioventricular block (AVB) (STx 9% vs. non-STx 9%, P â=â0.89), right bundle branch block (STx 6% vs. non-STx 11%, P â=â0.71), and left bundle branch block (STx 34% vs. non-STx 31%, P â=â0.9) was not significantly different between the STx and non-STx groups. At 2 years after TAVI, none of the patients had implanted PPM or had severe arrhythmias documented by 24-h Holter ECG or cardiac examination. CONCLUSION: Oral prednisone treatment does not appear to significantly reduce the incidence of AVB requiring acute PPM implantation after TAVI.
Assuntos
Estenose da Valva Aórtica , Bloqueio Atrioventricular , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Bloqueio de Ramo/diagnóstico , Estudos Retrospectivos , Prednisona/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Doença do Sistema de Condução Cardíaco/diagnóstico , Doença do Sistema de Condução Cardíaco/complicações , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Bloqueio Atrioventricular/terapia , Marca-Passo Artificial/efeitos adversos , Corticosteroides , Valva Aórtica/cirurgia , Resultado do TratamentoRESUMO
The mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) syndrome is a mitochondrial disorder, commonly caused by m.3243A>G mutation in the MT-TL1 gene. It encodes for the mitochondrial leucine transfer RNA (tRNA Leu [UUR]), implicated in the translation of proteins involved in the assembly and function of mitochondrial complexes in the electron transport chain. The m.3243A>G mutation determines complex I (CI) deficiency, ultimately leading to NADH accumulation, higher rates of glycolysis in order to compensate for the reduced ATP production and increase in lactates, the end-product of glycolysis. Disruption of the oxidative phosphorylation function with an inability to produce sufficient energy results in multi-organ dysfunction, with high energy demanding cells, such as myocytes and neurons, being the most affected ones. Therefore, MELAS syndrome is characterized by a heterogeneous clinical spectrum. Here we report on a case of a 55-year-old man affected by MELA syndrome with no cardiovascular risk factors. He was admitted to our department because of a non ST-segment elevation myocardial infarction (NSTEMI). A coronary angioplasty of the posterior descending artery and of the left anterior descending artery was realized. Transthoracic echocardiography showed inferior and anterior left ventricular wall hypokinesis together with a moderate left ventricle hypertrophy. Cardiac involvement is reported in about a third of the patients and left ventricular hypertrophy (LVH) is the most common phenotype, with possible dilated cardiomyopathy in end-stage disease; brady- arrhythmias and tachy-arrhythmias are also frequently reported as well as Wolff- Parkinson-White (WPW) syndrome. Organ impairment and clinical manifestations depend on the heteroplasmy level of mutant DNA in cells that can differ among individuals, explaining why some patients present a more severe disease. A clear relationship between MELAS syndrome and atherosclerosis has never been established, however recently advocated. In vitro studies in MELAS patients have shown that higher mitochondrial ROS levels and increased expression of oxidative stress-related genes, as a consequence of complex I deficiency and disrupted electron transport, allow circulating LDL to be promptly oxidized into ox-LDL, contributing to endothelial dysfunction and atherosclerosis plaque formation. In light of the recent evidence suggesting a possible link between mitochondrial disorders and atherosclerosis, we speculate that MELAS syndrome may have played a role in the pathogenesis of coronary artery disease in our patient. Further investigations are needed to confirm a pathogenetic link.
Assuntos
Acidose Láctica , Aterosclerose , Síndrome MELAS , Infarto do Miocárdio , Acidente Vascular Cerebral , Masculino , Humanos , Síndrome MELAS/complicações , Síndrome MELAS/genética , Síndrome MELAS/patologiaRESUMO
Atherosclerosis is a chronic inflammatory disease characterized by lipid and inflammatory cell deposits in the inner layer of large- and medium-sized elastic and muscular arteries. Diabetes mellitus (DM) significantly increases the risk of cardiovascular diseases and the overall and cardiovascular mortality, and it is a pro-atherogenic factor that induces atherosclerosis development and/or accelerates its progression through a multifactorial process. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of drugs, belonging to the armamentarium to fight type 2 DM, that have shown robust reductions in atherosclerotic events and all-cause mortality in all studies. Preclinical studies have shown that GLP-1RAs play a role in the immunomodulation of atherosclerosis, affecting multiple pathways involved in plaque development and progression. In this review, we wanted to explore the translational power of such preclinical studies by analyzing the most recent clinical trials investigating the atheroprotective effect of GLP-1RAs.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Hipoglicemiantes/uso terapêutico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismoRESUMO
Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is emerging as an effective treatment for patients with symptomatically failing bioprosthetic valves and a high prohibitive surgical risk; a longer life expectancy has led to a higher demand for these valve reinterventions due to the increased possibilities of outliving the bioprosthetic valve's durability. Coronary obstruction is the most feared complication of valve-in-valve (ViV) TAVR; it is a rare but life-threatening complication and occurs most frequently at the left coronary artery ostium. Accurate pre-procedural planning, mainly based on cardiac computed tomography, is crucial to determining the feasibility of a ViV TAVR and to assessing the anticipated risk of a coronary obstruction and the eventual need for coronary protection measures. Intraprocedurally, the aortic root and a selective coronary angiography are useful for evaluating the anatomic relationship between the aortic valve and coronary ostia; transesophageal echocardiographic real-time monitoring of the coronary flow with a color Doppler and pulsed-wave Doppler is a valuable tool that allows for a determination of real-time coronary patency and the detection of asymptomatic coronary obstructions. Because of the risk of developing a delayed coronary obstruction, the close postprocedural monitoring of patients at a high risk of developing coronary obstructions is advisable. CT simulations of ViV TAVR, 3D printing models, and fusion imaging represent the future directions that may help provide a personalized lifetime strategy and tailored approach for each patient, potentially minimizing complications and improving outcomes.
RESUMO
Severe tricuspid valve (TV) regurgitation (TR) has been associated with adverse long-term outcomes in several natural history studies, but isolated TV surgery presents high mortality and morbidity rates. Transcatheter tricuspid valve interventions (TTVI) therefore represent a promising field and may currently be considered in patients with severe secondary TR that have a prohibitive surgical risk. Tricuspid transcatheter edge-to-edge repair (T-TEER) represents one of the most frequently used TTVI options. Accurate imaging of the tricuspid valve (TV) apparatus is crucial for T-TEER preprocedural planning, in order to select the right candidates, and is also fundamental for intraprocedural guidance and post-procedural follow-up. Although transesophageal echocardiography represents the main imaging modality, we describe the utility and additional value of other imaging modalities such as cardiac CT and MRI, intracardiac echocardiography, fluoroscopy, and fusion imaging to assist T-TEER. Developments in the field of 3D printing, computational models, and artificial intelligence hold great promise in improving the assessment and management of patients with valvular heart disease.
RESUMO
Background: Percutaneous left atrial appendage occlusion (LAAO) presents many technical complex features, and it is often performed under the intraprocedural surveillance of a product specialist (PS). Our aim is to assess whether LAAO is equally safe and effective when performed in high-volume centers without PS support. Methods: Intraprocedural results and long-term outcome were retrospectively assessed in 247 patients who underwent LAAO without intraprocedural PS monitoring between January 2013 and January 2022 at three different hospitals. This cohort was then matched to a population who underwent LAAO with PS surveillance. The primary end point was all-cause mortality at 1â year. The secondary end point was a composite of cardiovascular mortality plus nonfatal ischemic stroke occurrence at 1â year. Results: Of the 247 study patients, procedural success was achieved in 243 patients (98.4%), with only 1 (0.4%) intraprocedural death. After matching, we did not identify any significant difference between the two groups in terms of procedural time (70 ± 19â min vs. 81 ± 30â min, p = 0.106), procedural success (98.4% vs. 96.7%, p = 0.242), and procedure-related ischemic stroke (0.8% vs. 1.2%, p = 0.653). Compared to the matched cohort, a significant higher dosage of contrast was used during procedures without specialist supervision (98 ± 19 vs. 43 ± 21, p < 0.001), but this was not associated with a higher postprocedural acute kidney injury occurrence (0.8% vs. 0.4%, p = 0.56). At 1â year, the primary and the secondary endpoints occurred in 21 (9%) and 11 (4%) of our cohort, respectively. Kaplan-Meier curves showed no significant difference in both primary (p = 0.85) and secondary (p = 0.74) endpoint occurrence according to intraprocedural PS monitoring. Conclusions: Our results show that LAAO, despite the absence of intraprocedural PS monitoring, remains a long-term safe and effective procedure, when performed in high-volume centers.