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1.
Nature ; 594(7861): 88-93, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33827113

RESUMO

COVID-19 is a disease with unique characteristics that include lung thrombosis1, frequent diarrhoea2, abnormal activation of the inflammatory response3 and rapid deterioration of lung function consistent with alveolar oedema4. The pathological substrate for these findings remains unknown. Here we show that the lungs of patients with COVID-19 contain infected pneumocytes with abnormal morphology and frequent multinucleation. The generation of these syncytia results from activation of the SARS-CoV-2 spike protein at the cell plasma membrane level. On the basis of these observations, we performed two high-content microscopy-based screenings with more than 3,000 approved drugs to search for inhibitors of spike-driven syncytia. We converged on the identification of 83 drugs that inhibited spike-mediated cell fusion, several of which belonged to defined pharmacological classes. We focused our attention on effective drugs that also protected against virus replication and associated cytopathicity. One of the most effective molecules was the antihelminthic drug niclosamide, which markedly blunted calcium oscillations and membrane conductance in spike-expressing cells by suppressing the activity of TMEM16F (also known as anoctamin 6), a calcium-activated ion channel and scramblase that is responsible for exposure of phosphatidylserine on the cell surface. These findings suggest a potential mechanism for COVID-19 disease pathogenesis and support the repurposing of niclosamide for therapy.


Assuntos
Anoctaminas/antagonistas & inibidores , COVID-19/patologia , Fusão Celular , Avaliação Pré-Clínica de Medicamentos , Células Gigantes/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , Animais , Anoctaminas/metabolismo , COVID-19/metabolismo , COVID-19/virologia , Sinalização do Cálcio/efeitos dos fármacos , Linhagem Celular , Canais de Cloreto/metabolismo , Chlorocebus aethiops , Feminino , Células Gigantes/metabolismo , Células Gigantes/virologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/efeitos dos fármacos
2.
J Cardiovasc Pharmacol ; 83(5): 364-376, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38335530

RESUMO

ABSTRACT: Myocarditis is an inflammatory disease of the myocardium characterized by a great heterogeneity of presentation and evolution. Treatment of myocarditis is often supportive, and the evidence for immunosuppression is scarce and debated. Conventional treatment is based on clinical presentation, ranging from conservative to advanced mechanical assist devices. In this setting, immunosuppression and immunomodulation therapies are mostly reserved for patients presenting with major clinical syndromes. In this review, we will summarize the current evidence and strategies for conventional and immunosuppressive treatments for patients presenting with acute myocarditis.


Assuntos
Imunossupressores , Miocardite , Miocardite/imunologia , Miocardite/terapia , Miocardite/tratamento farmacológico , Humanos , Doença Aguda , Resultado do Tratamento , Imunossupressores/uso terapêutico , Animais , Agentes de Imunomodulação/uso terapêutico , Imunomodulação
3.
Circulation ; 145(15): 1123-1139, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35404682

RESUMO

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.


Assuntos
COVID-19 , Miocardite , Adulto , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , Feminino , Humanos , Masculino , Miocardite/diagnóstico , Miocardite/epidemiologia , Miocardite/terapia , Prevalência , Estudos Retrospectivos , SARS-CoV-2 , Volume Sistólico , Função Ventricular Esquerda
4.
J Pharmacol Exp Ther ; 386(2): 205-211, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37164369

RESUMO

Due to the ageing population, patients often present to the hospital with a high burden of comorbidities and polypharmacy. For patients admitted with decompensated heart failure (HF), the evidence on the effects of contraindicated drugs on long-term mortality is scarce. Therefore, we aimed to investigate the effect of contraindicated medications on outcomes of patients admitted with decompensated HF. We analyzed all consecutive patients from the National Heart Failure Audit admitted to two tertiary centers with acutely decompensated HF between April 2020 and October 2021. We included medication classes listed as contraindicated (class III) in the most recent European and American guidelines on the management of HF. The primary outcome measure was in-hospital mortality. The secondary outcome measure was overall mortality. Overall, 716 patients admitted with acute HF were included. One-fifth (n = 156, 21.8%) were on at least one contraindicated medication at admission. The prevalence of comorbidities was comparable between medication groups. During hospitalization, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased in-hospital mortality (29% versus 9%, P = 0.013). On multivariable analyses, NSAID use was independently associated with worse in-hospital mortality (hazard ratio, 6.86; 95% confidence interval, 1.61-25.5; P = 0.005). However, other contraindicated medications were not associated with adverse outcomes. Postdischarge, the use of erythropoietin during admission was associated with increased mortality (54% versus 31%, P = 0.031). NSAID use is associated with increased in-hospital mortality for patients admitted with acute HF. However, inpatient use of other contraindicated medications was not associated with adverse in-hospital outcomes. Further studies are needed to confirm these results in larger and prospective cohorts. SIGNIFICANCE STATEMENT: Use of nonsteroidal anti-inflammatory drugs is associated with a worse in-hospital mortality in patients with decompensated heart failure. The prognostic role of other contraindicated medications remains still uncertain.


Assuntos
Assistência ao Convalescente , Insuficiência Cardíaca , Humanos , Estados Unidos , Prognóstico , Estudos Prospectivos , Alta do Paciente , Insuficiência Cardíaca/tratamento farmacológico , Anti-Inflamatórios
5.
Heart Fail Rev ; 28(2): 379-386, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36781809

RESUMO

Cardiac conduction system pacing provides physiological ventricular activation by directly stimulating the conduction system. This review describes the two types of conduction system pacing: His bundle pacing (HBP) and left bundle area pacing (LBAP). The most significant advantage of HB pacing is that it can provide a regular, narrow QRS; however, the disadvantages are challenging implantation and a high risk of re-intervention due to lead dislodgement and the development of high pacing threshold. LBAP provides optimum physiological activation of the left ventricle by engaging the left bundle/fascicular fibers. LBAP is more physiological than traditional RV apical pacing and could be an attractive alternative to conventional cardiac resynchronization therapy (CRT). The advantages of LBAP are a relatively more straightforward implantation technique than HBP, better lead stability and pacing thresholds. HBP and LBAP are more physiological than right ventricular pacing and may be used instead of conventional pacemakers. Both HBP and LBBP are being investigated as alternatives to conventional CRT.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Fascículo Atrioventricular , Eletrocardiografia/métodos , Resultado do Tratamento , Sistema de Condução Cardíaco , Terapia de Ressincronização Cardíaca/métodos , Estimulação Cardíaca Artificial/métodos
6.
Catheter Cardiovasc Interv ; 102(1): 80-90, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37191312

RESUMO

BACKGROUND: We aimed to develop a machine learning algorithm to predict the presence of a culprit lesion in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We used the King's Out-of-Hospital Cardiac Arrest Registry, a retrospective cohort of 398 patients admitted to King's College Hospital between May 2012 and December 2017. The primary outcome was the presence of a culprit coronary artery lesion, for which a gradient boosting model was optimized to predict. The algorithm was then validated in two independent European cohorts comprising 568 patients. RESULTS: A culprit lesion was observed in 209/309 (67.4%) patients receiving early coronary angiography in the development, and 199/293 (67.9%) in the Ljubljana and 102/132 (61.1%) in the Bristol validation cohorts, respectively. The algorithm, which is presented as a web application, incorporates nine variables including age, a localizing feature on electrocardiogram (ECG) (≥2 mm of ST change in contiguous leads), regional wall motion abnormality, history of vascular disease and initial shockable rhythm. This model had an area under the curve (AUC) of 0.89 in the development and 0.83/0.81 in the validation cohorts with good calibration and outperforms the current gold standard-ECG alone (AUC: 0.69/0.67/0/67). CONCLUSIONS: A novel simple machine learning-derived algorithm can be applied to patients with OHCA, to predict a culprit coronary artery disease lesion with high accuracy.


Assuntos
Reanimação Cardiopulmonar , Doença da Artéria Coronariana , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Retrospectivos , Resultado do Tratamento , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Angiografia Coronária , Algoritmos
7.
Europace ; 25(3): 940-947, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36638366

RESUMO

AIMS: There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. METHODS AND RESULTS: Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). CONCLUSION: Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.


Assuntos
Desfibriladores Implantáveis , Humanos , Estudos Retrospectivos , Desfibriladores Implantáveis/efeitos adversos , Prognóstico , Fatores de Risco , Síncope/diagnóstico , Síncope/epidemiologia , Síncope/etiologia
8.
Curr Cardiol Rep ; 25(7): 649-661, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37329419

RESUMO

PURPOSE OF REVIEW: Heart failure (HF) is commonly associated with iron deficiency (ID), defined as insufficient levels of iron to meet physiological demands. ID's association with anaemia is well understood but it is increasingly recognised as an important comorbidity in HF, even in the absence of anaemia. This review summarises contemporary evidence for the measurement and treatment of ID, in both HFrEF and HFpEF, and specific HF aetiologies, and highlights important gaps in the evidence-base. RECENT FINDINGS: ID is common among patients with HF and associated with increased morbidity and mortality. Correcting ID in patients with HF can impact upon functional status, exercise tolerance, symptoms, and overall quality of life, irrespective of anaemia status. ID is a modifiable comorbidity in HF. Therefore, recognising and treating ID has emerging therapeutic potential and is important for all clinicians who care for patients with HF to understand the rationale and approach to treatment.


Assuntos
Anemia Ferropriva , Anemia , Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Qualidade de Vida , Volume Sistólico/fisiologia , Anemia/complicações
9.
Am J Physiol Heart Circ Physiol ; 322(6): H975-H993, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35394857

RESUMO

Voltage-gated sodium channels (VGSCs) are macromolecular assemblies composed of a number of proteins regulating channel conductance and properties. VGSCs generate Na+ current (INa) in myocytes and play fundamental roles in excitability and impulse conduction in the heart. Moreover, VGSCs condition mechanical properties of the myocardium, a process that appears to involve the late component of INa. Variants in the gene SCN1B, encoding the VGSC ß1- and ß1B-subunits, result in inherited neurological disorders and cardiac arrhythmias. But the precise contributions of ß1/ß1B-subunits and VGSC integrity to the overall function of the adult heart remain to be clarified. For this purpose, adult mice with cardiac-restricted, inducible deletion of Scn1b (conditional knockout, cKO) were studied. Myocytes from cKO mice had increased densities of fast (+20%)- and slow (+140%)-inactivating components of INa, with respect to control cells. By echocardiography and invasive hemodynamics, systolic function was preserved in cKO mice, but diastolic properties and ventricular compliance were compromised, with respect to control animals. Importantly, inhibition of late INa with GS967 normalized left ventricular filling pattern and isovolumic relaxation time in cKO mice. At the cellular level, cKO myocytes presented delayed kinetics of Ca2+ transients and cell mechanics, defects that were corrected by inhibition of INa. Collectively, these results document that VGSC ß1/ß1B-subunits modulate electrical and mechanical function of the heart by regulating, at least in part, Na+ influx in cardiomyocytes.NEW & NOTEWORTHY We have investigated the consequences of deletion of Scn1b, the gene encoding voltage-gated sodium channel ß1-subunits, on myocyte and cardiac function. Our findings support the notion that Scn1b expression controls properties of Na+ influx and Ca2+ cycling in cardiomyocytes affecting the modality of cell contraction and relaxation. These effects at the cellular level condition electrical recovery and diastolic function in vivo, substantiating the multifunctional role of ß1-subunits in the physiology of the heart.


Assuntos
Sódio , Canais de Sódio Disparados por Voltagem , Potenciais de Ação , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Diástole , Camundongos , Miócitos Cardíacos/metabolismo , Sódio/metabolismo , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/genética , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo
10.
Heart Fail Rev ; 27(5): 1795-1805, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35315505

RESUMO

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by left or biventricular systolic impairment. Historically, most of the clinical attention has been devoted to the evaluation of left ventricular function and morphology, while right ventricle (RV) has been for many years the forgotten chamber. Recently, progresses in cardiac imaging gave clinicians precious tools for the evaluation of RV, raising the awareness of the importance of biventricular assessment in DCM. Indeed, RV involvement is far from being uncommon in DCM, and the presence of right ventricular dysfunction (RVD) is one of the major negative prognostic determinants in DCM patients. However, some aspects such as the possible role of specific genetic mutations in determining the biventricular phenotype in DCM, or the lack of specific treatments able to primarily counteract RVD, still need research. In this review, we summarized the current knowledge on RV involvement in DCM, giving an overview on the epidemiology and pathogenetic mechanisms implicated in determining RVD. Furthermore, we discussed the imaging techniques to evaluate RV function and the role of RV failure in advanced heart failure.


Assuntos
Cardiomiopatia Dilatada , Insuficiência Cardíaca , Disfunção Ventricular Direita , Cardiomiopatia Dilatada/epidemiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Prevalência , Prognóstico , Disfunção Ventricular Direita/epidemiologia , Função Ventricular Direita/fisiologia
11.
Heart Fail Rev ; 27(2): 587-594, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33907929

RESUMO

Heart failure with preserved ejection fraction (HFpEF) remains an elusive entity, due to its heterogeneous clinical profile and an arbitrarily defined nosology. Several pathophysiological mechanisms recognized as central for the development of HFpEF appear to be in common with the process of physiological aging of the heart. Both conditions are characterized by progressive impairment in cardiac function, accompanied by left ventricular hypertrophy, diastolic dysfunction, sarcomeric, and metabolic abnormalities. The neurological paradigm of dementia-intended as a progressive, multifactorial organ damage with decline of functional reserve, eventually leading to irreversible dysfunction-is well suited to represent HFpEF. In such perspective, certain phenotypes of HFpEF may be viewed as a maladaptive response to environmental modifiers, causing premature and pathological aging of the heart. We here propose that the 'HFpEF syndrome' may reflect the interplay of adverse structural remodelling and erosion of functional reserve, mirroring the processes leading to dementia in the brain. The resulting conceptual framework may help advance our understanding of HFpEF and unravel potential therapeutical targets.


Assuntos
Demência , Insuficiência Cardíaca , Coração , Humanos , Volume Sistólico/fisiologia , Função Ventricular Esquerda
12.
Eur J Clin Invest ; 52(10): e13815, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35598175

RESUMO

BACKGROUND: Prognostic stratification of acute myocarditis (AM) presenting with normal left ventricular ejection fraction (LVEF) relies mostly on late gadolinium enhancement (LGE) characterization. Left ventricular peak global longitudinal strain (LV-GLS) measured by feature tracking analysis might improve prognostication of AM presenting with normal LVEF. METHODS: Data of patients undergoing cardiac magnetic resonance (CMR) for clinically suspected AM in seven European Centres (2013-2020) were retrospectively analysed. Patients with AM confirmed by CMR and LVEF ≥50% were included. LGE was visually characterized: localized versus. non-localized, subepicardial versus midwall. LV-GLS was measured by dedicated software. The primary outcome was the first occurrence of an adverse cardiovascular event (ACE) including cardiac death, life-threatening arrhythmias, development of heart failure or of LVEF <50%. RESULTS: Of 389 screened patients, 256 (66%) fulfilled inclusion criteria: median age 36 years, 71% males, median LVEF 60%, median LV-GLS -17.3%. CMR was performed at 4 days from hospitalization. At 27 months, 24 (9%) patients experienced ≥1 ACE (71% developed LVEF <50%). Compared to the others, they had lower median LV-GLS values (-13.9% vs. -17.5%, p = .001). At Kaplan-Meier analysis, impaired LV-GLS (both considered as > -20% or quartiles), non-localized and midwall LGE were associated with ACEs. Patients with LV-GLS ≤-20% did not experience ACEs. LV-GLS remained associated with ACEs after adjustment for non-localized and midwall LGE. CONCLUSION: In AM presenting with LVEF ≥50%, LV-GLS provides independent prognostic value over LGE characterization, improving risk stratification and representing a rationale for further studies of therapy in this cohort.


Assuntos
Miocardite , Função Ventricular Esquerda , Adulto , Meios de Contraste , Feminino , Gadolínio , Humanos , Imagem Cinética por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Miocardite/diagnóstico por imagem , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Volume Sistólico
13.
Circ Res ; 126(10): 1394-1414, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32379579

RESUMO

While clinical gene therapy celebrates its first successes, with several products already approved for clinical use and several hundreds in the final stages of the clinical approval pipeline, there is not a single gene therapy approach that has worked for the heart. Here, we review the past experience gained in the several cardiac gene therapy clinical trials that had the goal of inducing therapeutic angiogenesis in the ischemic heart and in the attempts at modulating cardiac function in heart failure. Critical assessment of the results so far achieved indicates that the efficiency of cardiac gene delivery remains a major hurdle preventing success but also that improvements need to be sought in establishing more reliable large animal models, choosing more effective therapeutic genes, better designing clinical trials, and more deeply understanding cardiac biology. We also emphasize a few areas of cardiac gene therapy development that hold great promise for the future. In particular, the transition from gene addition studies using protein-coding cDNAs to the modulation of gene expression using small RNA therapeutics and the improvement of precise gene editing now pave the way to applications such as cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies that were unapproachable until a decade ago.


Assuntos
Terapia Genética , Cardiopatias/terapia , Miocárdio/patologia , Neovascularização Fisiológica , Regeneração , Ensaios Clínicos como Assunto , Técnicas de Transferência de Genes , Terapia Genética/efeitos adversos , Cardiopatias/genética , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Recuperação de Função Fisiológica , Resultado do Tratamento
14.
J Cardiovasc Pharmacol ; 80(4): 502-514, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35067533

RESUMO

ABSTRACT: Rapid advancements in oncological treatments over the past few decades have led to a significant improvement in cancer outcomes. Chemotherapeutic agents play a pivotal role in cancer treatment, with almost one-third of patients receiving them during their cancer treatment in the United Kingdom. The success of chemotherapeutic drugs has, however, resulted in an increasing incidence of cardiovascular side effects and complications. The most common cardiac manifestation is the development of cardiotoxicity, defined as the development of left ventricular systolic dysfunction, after treatment. This article provides an up-to-date review of the commonly used chemotherapeutic agents that cause cardiotoxicity and discusses current treatment options and evidence gaps.


Assuntos
Antineoplásicos , Neoplasias , Disfunção Ventricular Esquerda , Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Humanos , Neoplasias/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/tratamento farmacológico
15.
Infection ; 50(1): 243-249, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34490592

RESUMO

INTRODUCTION: Culture-negative infective endocarditis (IE) accounts for 7-31% of all cases. Metagenomics has contributed to improving the aetiological diagnosis of IE patients undergoing valve surgery. We assessed the impact of 16S ribosomal DNA gene polymerase chain reaction (16S rDNA PCR) in the aetiological diagnosis of culture-negative IE. METHODS: Between January 2016 and January 2020, clinical data from culture-negative IE patients were reviewed retrospectively. Identification of bacteria was performed using 16S rDNA PCR in heart valve specimens. RESULTS: 36 out of 313 patients (12%) with culture-negative IE had their valve tissue specimens submitted for 16S rDNA PCR. 16S rDNA PCR detected and identified bacterial nucleic acid in heart valve tissue significantly more frequently compared to valve culture alone 25(70%) vs 5(12%); p < 0.05. Mean age was 57 years (SD 18) and 80% were male. Native and aortic valve were involved in 76% and 52% of cases, respectively. Streptococcus spp. (n 15) were the most commonly detected organisms, followed by bacteria of the HACEK group (Haemophilus parainfluenzae 2, Aggregatibacter actinomycetemcomitans 1), nutritionally variant streptococci (Abiotrophia defectiva 2), and one each of Staphylococcus aureus, Corynebacterium pseudodiphtheriticum, Helcococcus kunzii, Neisseria gonorrhoeae, Tropheryma whipplei. CONCLUSION: 16S rDNA PCR may be a useful diagnostic tool for the identification of the causative organism in culture-negative IE. Efforts towards a shorter turnaround time for results should be consider and further studies assessing the clinical impact of this technique in culture-negative IE are needed.


Assuntos
Endocardite Bacteriana , Endocardite , DNA Ribossômico/genética , Endocardite/diagnóstico , Endocardite Bacteriana/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Estudos Retrospectivos
16.
Eur Heart J Suppl ; 24(Suppl I): I160-I164, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36380793

RESUMO

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model.

17.
Curr Cardiol Rep ; 24(9): 1085-1091, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35751835

RESUMO

PURPOSE OF THE REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. RECENT FINDINGS: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.


Assuntos
COVID-19 , Cardiopatias , COVID-19/complicações , Coração , Cardiopatias/terapia , Humanos , Pandemias , SARS-CoV-2
18.
Inflamm Res ; 70(1): 7-10, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33079210

RESUMO

OBJECTIVE: The orf8b protein of the coronavirus SARS-CoV, analogous to SARS-CoV-2, triggers the NLRP3 inflammasome in macrophages in vitro. Deregulated inflammasome-mediated release of interleukin-1 family cytokines is important in hyper-inflammatory syndromes, like happens in SARS-CoV-2-mediated cytokine release syndrome. We propose that an intense inflammasome formation characterizes the lungs of patients with fatal COVID-19 disease due to pneumonia and acute respiratory distress syndrome (ARDS). METHODS: Samples from four patients with confirmed COVID-19 pneumonia who had been hospitalized at the Hospital of the University of Trieste (Italy) and died of ARDS and four lung samples from a historical repository from subjects who had died of cardiopulmonary arrest and had not been placed on mechanical ventilation and without evidence of pulmonary infection at postmortem examination were collected. Pathology samples had been fixed in formalin 10% at time of collection and subsequently embedded in paraffin. We conducted staining for ASC (Apoptosis-associated Speck-like protein containing a Caspase recruitment domain), NLRP3 (NACHT, LRR, and PYD domains-containing protein 3), and cleaved caspase-1. RESULTS: Intense expression of the inflammasome was detected, mainly in leukocytes, within the lungs of all patients with fatal COVID-19 in the areas of lung injury. The number of ASC inflammasome specks per high power fields was significantly higher in the lungs of patients with fatal COVID-19 as compared with the lungs of control subjects (52 ± 22 vs 6 ± 3, P = 0.0064). CONCLUSIONS: These findings identify the presence of NLRP3 inflammasome aggregates in the lungs of fatal COVID-19 pneumonia thus providing the potential molecular link between viral infection and cytokine release syndrome.


Assuntos
COVID-19/patologia , Inflamassomos , Pulmão/patologia , Adulto , Idoso , Autopsia , Proteínas Adaptadoras de Sinalização CARD/análise , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspase 1/análise , Caspase 1/metabolismo , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/patologia , Feminino , Parada Cardíaca/etiologia , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/análise , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia Viral/etiologia , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/patologia
19.
Pacing Clin Electrophysiol ; 44(12): 1995-2004, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34672370

RESUMO

INTRODUCTION: Generic ICD programming, where shock-reduction programming is extrapolated from trials of one manufacturer to another, may reduce non-essential ICD therapies beyond that seen in randomized trials. However, the benefits and risks are unknown. The purpose of this retrospective cohort study was to evaluate the impact of a standardized programming protocol, based on generic programming, across manufacturers. METHODS: We included all new ICDs in a single center (2009-2019). In 2013 a standardized programming protocol based on generic programming was introduced, incorporating high detection rates (200 bpm for primary prevention) and long detection (30/40 or equivalent in VF zone) for all patients. Patients were classified into three groups based on implant programming: pre-guideline (PS), post-guideline and guideline compliant (GC) and post-guideline but not guideline compliant (NGC). The end-points were the first occurrence of any device therapy (ATP or shock), ICD shock, syncope and all-cause mortality. Survival analysis was used to evaluate outcomes. RESULTS: 1003 patients were included (mean follow-up 1519 ± 1005 days). In primary prevention patients (n = 583) freedom from ICD therapy (91.5% vs. 73.6%, p < .001) or shock (94.7% vs 84.8%, p = .02) were significantly higher in GC compared to PS patients, without significant increase in syncope or mortality. In secondary prevention patients (n = 420) freedom from any ICD therapy or any shock were non-significantly higher in GC compared to PS patients, without an increase in syncope or mortality. CONCLUSIONS: In primary prevention patients a standardized programming protocol, incorporating generic programming, reduced the burden of ICD therapy without an increase in adverse outcomes.


Assuntos
Algoritmos , Desfibriladores Implantáveis/normas , Desenho de Prótese , Idoso , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos Retrospectivos , Prevenção Secundária
20.
Heart Fail Rev ; 25(2): 245-255, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31267323

RESUMO

Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestation, from sex-determined differential gene expression to sex hormones interaction with their specific receptors in different tissues. More recently, differential non-coding RNAs regulation also turned out to be an involved mechanism. This review focuses on sex impact on the various heart failure syndromes, including coronary artery disease, heart failure with preserved ejection fraction and with reduced ejection fraction, with particular attention to dilated cardiomyopathy. Despite similar genetic predisposition in terms of identified causative mutations, other causes, such as cardiotoxic drugs exposure or stress-induced cardiomyopathy, are more prevalent in women. Beyond this, differences in disease presentation and natural history reveal a more severe clinical onset with otherwise better long-term outcomes in women compared to men. Understanding the varying characteristics of disease manifestation and outcomes is warranted for a prompt and tailored treatment for both men and women. This is a mandatory step in the road to the personalized medicine. Moreover, despite a higher enrollment in the last years, the under-representation of females in clinical trials is the first obstacle to overcome in the long way to develop appropriate sex-based therapy approach.


Assuntos
Insuficiência Cardíaca/epidemiologia , Medição de Risco/métodos , Volume Sistólico/fisiologia , Feminino , Saúde Global , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Morbidade/tendências , Prognóstico , Fatores de Risco , Fatores Sexuais , Função Ventricular Esquerda/fisiologia
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