RESUMO
Chronic total occlusions (CTOs) are frequent in patients with previous coronary artery bypass graft (CABG) surgery. Percutaneous coronary intervention (PCI) is the usual revascularization strategy. Whether or not the presence of a graft on a CTO vessel and post-PCI graft patency impacts outcomes after CTO-PCI is unknown. We sought to evaluate the impact of post-PCI graft patency on the durability of CTO-PCI. In total, 259 patients with previous CABG who underwent CTO-PCI in 12 international centers in 2019 to 2023 were categorized into "grafted" and "ungrafted" groups based on the presence of graft on a CTO vessel. The grafted group was subdivided into "graft-occluded" and "graft-patent" groups, depending on graft patency. The primary end points were (1) technical success rate, (2) target vessel failure, and (3) CTO failure rates at 1 year. CTO failure was defined as target vessel revascularization and/or significant in-stent restenosis. A total of 199 patients (77%) were in the grafted group. Grafted CTOs showed higher complexity and lower technical success rates (70% vs 80%, p = 0.004) than nongrafted CTOs. Of the grafted CTOs, 140 (70%) were in the grafted-occluded group and 59 (30%) were in the grafted-patent group. The technical success was lower in the former group (65% vs 81%, p = 0.022). An occluded graft was an independent predictor of technical failure (odds ratio 2.04, 95% confidence interval 1.03 to 4.76, p = 0.049) and persistent post-PCI graft patency was a strong independent predictor of CTO failure at 1 year (hazard ratio 5.6, 95% confidence interval 1.2 to 27.5, log-rank p = 0.033). In conclusion, in patients with previous CABG who underwent CTO-PCI, post-PCI graft patency was a significant predictor of CTO failure.
Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Oclusão Coronária , Oclusão de Enxerto Vascular , Intervenção Coronária Percutânea , Grau de Desobstrução Vascular , Humanos , Masculino , Feminino , Ponte de Artéria Coronária/métodos , Oclusão Coronária/cirurgia , Oclusão Coronária/fisiopatologia , Idoso , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Doença Crônica , Oclusão de Enxerto Vascular/diagnóstico por imagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The "Minimalistic Hybrid Approach" (MHA) has been proposed to reduce the invasiveness of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). AIMS: This study aims to assess whether MHA may also reduce the utilization of PCI resources (devices, radiations, and contrast) by comparing it with other conventional algorithms. METHODS: We aimed to assess the impact of MHA on device, radiation, and contrast usage during CTO-PCI analyzing data from the Belgian Working Group on CTO (BWG-CTO) registry. Patients were divided, depending on the algorithm used, into two groups: Conventional versus Minimalistic. Primary objectives were procedure performance measures such as device usage (microcatheters and guidewires), radiological parameters, and contrast use. At 1-year follow-up, patients were evaluated for target vessel failure (TVF), defined as a composite of cardiac death, new myocardial infarction, and target vessel revascularization. RESULTS: Overall, we analyzed 821 CTO-PCIs (Conventional n = 650, Minimalistic n = 171). The Minimalistic group demonstrated higher complexity of CTO lesions. After adjusting for propensity score, the Minimalistic group had a significantly lower number of microcatheters used (1.49 ± 0.85 vs. 1.24 ± 0.64, p = 0.026), while the number of guidewires was comparable (4.80 ± 3.29 vs. 4.35 ± 2.94, p = 0.30). Both groups had similar rates of success and procedural complications, as well as comparable procedural and fluoroscopic times and contrast volume used. At the 1-year follow-up, both groups showed comparable rates of TVF (hazard ratio: 0.57; 95% confidence interval: 0.24-1.34, p = 0.195). CONCLUSION: The MHA may slightly reduce the number of dedicated devices used during CTO-PCI, without adversely affecting the procedural success or long-term outcome.
Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Oclusão Coronária/etiologia , Fatores de Risco , Doença Crônica , Algoritmos , Sistema de Registros , Angiografia CoronáriaRESUMO
BACKGROUND: The percutaneous treatment of calcified coronary lesions remains challenging and is associated with worse clinical outcomes. In addition, coronary artery calcification is associated with more frequent peri-procedural myocardial infarction. STUDY DESIGN AND OBJECTIVES: The ShOckwave ballooN or Atherectomy with Rotablation in calcified coronary artery lesions (SONAR) study is an investigator-initiated, prospective, randomized, international, multicenter, open label trial (NCT05208749) comparing a lesion preparation strategy with either shockwave intravascular lithotripsy (IVL) or rotational atherectomy (RA) before drug-eluting stent implantation in 170 patients with moderate to severe calcified coronary lesions. The primary endpoint is difference in the rate of peri-procedural myocardial infarction. Key secondary endpoints include rate of peri-procedural microvascular dysfunction, peri-procedural myocardial injury, descriptive study of IMR measurements in calcified lesions, technical and procedural success, interaction between OCT calcium score and primary endpoint, 30-day and 1-year major adverse clinical events. CONCLUSIONS: The SONAR trial is the first randomized controlled trial comparing the incidence of peri-procedural myocardial infarction between 2 contemporary calcium modification strategies (Shockwave IVL and RA) in patients with calcified coronary artery lesions. Furthermore, for the first time, the incidence of peri-procedural microvascular dysfunction after Shockwave IVL and RA will be evaluated and compared.
Assuntos
Aterectomia Coronária , Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Calcificação Vascular , Humanos , Aterectomia Coronária/efeitos adversos , Estudos Prospectivos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Cálcio , Angiografia Coronária , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/terapia , Calcificação Vascular/etiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/etiologia , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , AterectomiaRESUMO
Background: The presence of a chronic total occlusion (CTO) and severe left ventricular (LV) systolic dysfunction are known negative prognostic factors in patients with coronary artery disease. Several studies have examined the effect of CTO revascularization on mortality, symptoms, occurrence of myocardial infarction (MI), and cardiac function in patients with normal or reduced LV function. However, the effect of CTO revascularization on heart failure-related events in patients with LV dysfunction, such as heart failure hospitalization (HFH), the occurrence of atrial fibrillation (AF), and a worsening renal function (WRF), has not yet been evaluated. To assess the success rate and safety of CTO percutaneous coronary interventions (PCIs) in coronary patients with LV ejection fractions of ≤ 40% and evaluate the impact of successful CTO revascularization on HFH, occurrence of AF, and WRF. Methods: Prospectively, data were collected from CTO PCIs performed at three referral centers and analyzed. From a total of 1435 CTO PCIs, 132 (9.2%) patients with a left ventricular ejection fraction (LVEF) of ≤ 40% were included in this analysis. The median follow-up duration was 23.18 months (interquartile range (IQR): 11.02-46.66 months). Results: A successful CTO PCI was achieved in 109 of these patients, while the procedure was unsuccessful in 23 patients (82.5% procedural success rate). Overall, the intervention had an acceptable number of peri-procedural (or in-hospital) complications (9.1%). During the follow-up period, the rates of all-cause death, cardiovascular death, and non-fatal MI were not significantly different between the two groups. The rates of HFH were significantly lower in the successful PCI group, while WRF and AF did not differ between successful and unsuccessful PCI groups. Successful PCI and higher estimated glomerular filtration rate (eGFR) were independent predictors of a lower risk of HFH, while prior stroke and diabetes were independent predictors of a higher risk of HFH. Conclusions: In patients with reduced LV systolic function (ejection fraction, EF ≤ 40%), CTO PCI is a safe and effective procedure and successful CTO PCI is independently associated with a lower risk of HFH during follow-up. Further expansion of this cohort is necessary to confirm these results.
RESUMO
BACKGROUND: The postdischarge prognostic implication of periprocedural myocardial injury in patients undergoing percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) remains scarcely studied. AIMS: The aim of this study is to assess the prognostic value of periprocedural myocardial injury, defined by increased high-sensitive troponin T (hs-TnT) levels according to updated guidelines, after CTO PCI. METHODS: Between September 2011 and April 2020, 726 patients undergoing CTO PCI at 2 Belgian referral centres were prospectively included and divided into 4 groups based on postprocedural hs-TnT levels (unelevated; ≥5 times the upper limit of normal (ULN); ≥35 times the ULN; ≥70 times the ULN). Postprocedural hs-TnT levels were subsequently related to patient and procedural characteristics, 1-year major adverse cardiac and cerebrovascular events (MACCE; excluding in-hospital MACCE) as well as 1-year mortality. RESULTS: At 1 year follow-up (FU), elevated hs-TnT≥5 times and ≥35 times the ULN were associated with higher MACCE rates (p=0.001; p=0.007, respectively). In addition, they also resulted in a higher 1-year mortality rate (p=0.009;p=0.021, respectively). Patients with increased hs-TnT≥5 times the ULN (35% of patients) more frequently had signs of more advanced atherosclerotic disease (previous CABG p<0.001; stroke p≤0.001 and peripheral vascular disease p<0.001) and had higher procedural complexity (Japanese CTO Score p=<0.001, stent length>48 mm p<0.001, procedure time p<0.001). Antegrade wire escalation did not result in lower event rate of postdischarge MACCE compared with the other CTO crossing techniques combined (p=0.158). CONCLUSION: Periprocedural myocardial injury was associated with a significantly higher rate of MACCE and all-cause mortality after 12 months of FU.
Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Prognóstico , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Resultado do Tratamento , Assistência ao Convalescente , Fatores de Risco , Biomarcadores , Fatores de Tempo , Alta do Paciente , Troponina TRESUMO
BACKGROUND: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown. AIM: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019. METHODS: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction. RESULTS: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock. CONCLUSIONS: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms.
Assuntos
COVID-19/epidemiologia , Pandemias , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , França/epidemiologia , Pesquisas sobre Atenção à Saúde , Ruptura Cardíaca Pós-Infarto/epidemiologia , Mortalidade Hospitalar , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Admissão do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , Utilização de Procedimentos e Técnicas , Prognóstico , Fatores de Risco , SARS-CoV-2 , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Fumar/epidemiologia , Stents , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Echocardiography is a reliable and reproducible method to assess non-invasively cardiac function in clinical and experimental research. Significant progress in the development of echocardiographic equipment and transducers has led to the successful translation of this methodology from humans to rodents, allowing for the scoring of disease severity and progression, testing of new drugs, and monitoring cardiac function in genetically modified or pharmacologically treated animals. However, as yet, there is no standardization in the procedure to acquire echocardiographic measurements in small animals. This position paper focuses on the appropriate acquisition and analysis of echocardiographic parameters in adult mice and rats, and provides reference values, representative images, and videos for the accurate and reproducible quantification of left ventricular function in healthy and pathological conditions.
Assuntos
Pesquisa Biomédica/normas , Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia/normas , Função Ventricular Esquerda , Animais , Doenças Cardiovasculares/fisiopatologia , Consenso , Diástole , Modelos Animais de Doenças , Camundongos , Ratos , SístoleRESUMO
AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high risk of sudden cardiac death. Three different prediction models for the indication of implanted cardioverter defibrillator (ICD) are now available: the 5 year ARVC risk score, the International Task Force Consensus (ITFC) criteria, and the Heart Rhythm Society (HRS) criteria. We compared these three prediction models in a validation cohort of patients with definite ARVC. METHODS AND RESULTS: In a cohort of 140 patients with definite ARVC, the 5 year ARVC risk score and the ITFC and HRS criteria were compared for the prediction of a major combined endpoint of sudden cardiac death, appropriate ICD intervention, resuscitated cardiac arrest, and sustained ventricular tachycardia. During the follow-up, 65 major events occurred. The 5 year ARVC risk score with a threshold >10%, derived from the maximally selected rank statistic, predicted 62 (95%) events [odds ratio (OR) 9.1, 95% confidence interval (CI) 2.6-32, P = 0.0006], the ITFC criteria 53 (81%, OR 4.8, 95% CI 2.2-10.3, P = 0.0001), and the HRS criteria 29 (45%, OR 4.2, 95% CI 1.9-9.3, P = 0.0003). At the analysis of decision curve for ICD implantation, a 5 year ARVC risk score >10% showed a greater net benefit than the ITFC and HRS criteria over a wide range of threshold probability of events. Finally, at multivariate analysis, the 5 year ARVC risk score >10% was the only independent predictor of major events. CONCLUSIONS: The 5 year score with a threshold of >10% was more effective for predicting events than the ITFC and HRS criteria.
RESUMO
BACKGROUND: Cardiac magnetic resonance (CMR) is widely used to assess tissue and functional abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC). Recently, a ARVC risk score was proposed to predict the 5-year risk of malignant ventricular arrhythmias in patients with ARVC. However, CMR features such as fibrosis, fat infiltration, and left ventricular (LV) involvement were not considered. OBJECTIVES: The authors sought to evaluate the prognostic role of CMR phenotype in patients with definite ARVC and to evaluate the effectiveness of the novel 5-year ARVC risk score to predict cardiac events in different CMR presentations. METHODS: A total of 140 patients with definite ARVC were enrolled (mean age 42 ± 17 years, 97 males) in this multicenter prospective registry. As per study design, CMR was performed in all the patients at enrollment. The novel 5-year ARVC risk score was retrospectively calculated using the patient's characteristics at the time of enrollment. During a median follow-up of 5 years (2 to 8 years), the combined endpoint of sudden cardiac death, appropriate implantable cardioverter-defibrillator intervention, and aborted cardiac arrest was considered. RESULTS: CMR was completely negative in 14 patients (10%), isolated right ventricular (RV) involvement was found in 58 (41%), biventricular in 52 (37%), and LV dominant in 16 (12%). During the follow-up, 48 patients (34%) had major events, but none occurred in patients with negative CMR. At Kaplan-Meier analysis, patients with LV involvement (LV dominant and biventricular) had a worse prognosis than those with lone RV (p < 0.0001). At multivariate analysis, the LV involvement, a LV-dominant phenotype, and the 5-year ARVC risk score were independent predictors of major events. The estimated 5-year risk was able to predict the observed risk in patients with lone RV but underestimated the risk in those with LV involvement. CONCLUSIONS: Different CMR presentations of ARVC are associated with different prognoses. The 5-year ARVC risk score is valid for the estimation of risk in patients with lone-RV presentation but underestimated the risk when LV is involved.
Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Fenótipo , Sistema de Registros , Adulto , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
Defining short-term prognosis in nonischemic cardiomyopathy (NICM) is challenging in clinical practice. Although left ventricular reverse remodeling (LVRR) is a key prognostic marker in NICM there are few parameters able to predict it. We investigated whether a complete structural and functional cardiac magnetic resonance imaging (cMRI) evaluation was incremental to the classic clinical-echocardiographic approach in predicting LVRR in a large cohort of NICM patients receiving evidence-based treatment. Patients with a recent diagnosis of NICM (<3 months) who underwent complete clinical, echocardiographic and cMRI assessment were consecutively enrolled from 2008 to 2016. LVRR was defined as an increase in ≥10 points or normalization of left ventricular ejection fraction, associated with a ≥10% reduction or normalization of left ventricular end-diastolic diameter at midterm (median time 20 months) echocardiographic follow-up. Among 80 NICM patients included in the study, LVRR was observed in 43 (54%). At multivariate analysis, the clinical-echocardiographic evaluation failed to identify independent predictors of LVRR. However, absence of late gadolinium enhancement (odds ratio [OR] 9.07; confidence interval [CI] 2.7 to 13.1; p value 0.0003), left ventricular mass (OR 1.018; CI 1.001 to 1.036; p value 0.045) and peak circumferential strain (OR 1.213; CI 1.011 to 1.470; p value 0.049) assessed by cMRI were independently associated with LVRR. A model for LVRR prediction based on cMRI and clinical-echocardiographic parameters performed significantly better than the clinical-echocardiographic model alone (area under curve 0.84 vs 0.72; p value 0.023). In conclusion, an integrated imaging approach with the addition of a structural and functional cMRI study to the standard-of-care evaluation improves the prediction of LVRR in a large cohort of patients with recently diagnosed NICM receiving evidence-based treatment.
Assuntos
Cardiomiopatias/diagnóstico , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Adulto , Idoso , Cardiomiopatias/fisiopatologia , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.
Assuntos
Ecocardiografia/métodos , Cardiopatias/diagnóstico por imagem , Coração/fisiologia , Função Ventricular Esquerda/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Volume Cardíaco/fisiologia , Coração/diagnóstico por imagem , Coração/fisiopatologia , Cardiopatias/fisiopatologia , Hemodinâmica , Humanos , Hidrodinâmica , Imageamento por Ressonância Magnética , Fluxo Sanguíneo Regional/fisiologiaRESUMO
BACKGROUND: Transplantation of cells into the infarcted heart has significant potential to improve myocardial recovery; however, low efficacy of cell engraftment still limits therapeutic benefit. Here, we describe a method for the unbiased, in vivo selection of cytokines that improve mesenchymal stromal cell engraftment into the heart both in normal conditions and after myocardial infarction. METHODS: An arrayed library of 80 secreted factors, including most of the currently known interleukins and chemokines, were individually cloned into adeno-associated viral vectors. Pools from this library were then used for the batch transduction of bone marrow-derived mesenchymal stromal cells ex vivo, followed by intramyocardial cell administration in normal and infarcted mice. Three weeks after injection, vector genomes were recovered from the few persisting cells and identified by sequencing DNA barcodes uniquely labeling each of the tested cytokines. RESULTS: The most effective molecule identified by this competitive engraftment screening was cardiotrophin-1, a member of the interleukin-6 family. Intracardiac injection of mesenchymal stromal cells transiently preconditioned with cardiotrophin-1 preserved cardiac function and reduced infarct size, parallel to the persistence of the transplanted cells in the healing hearts for at least 2 months after injection. Engraftment of cardiotrophin-1-treated mesenchymal stromal cells was consequent to signal transducer and activator of transcription 3-mediated activation of the focal adhesion kinase and its associated focal adhesion complex and the consequent acquisition of adhesive properties by the cells. CONCLUSIONS: These results support the feasibility of selecting molecules in vivo for their functional properties with adeno-associated viral vector libraries and identify cardiotrophin-1 as a powerful cytokine promoting cell engraftment and thus improving cell therapy of the infarcted myocardium.
Assuntos
Citocinas/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Infarto do Miocárdio/cirurgia , Miocárdio/metabolismo , Regeneração , Animais , Apoptose , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Citocinas/genética , Dependovirus/genética , Modelos Animais de Doenças , Quinase 1 de Adesão Focal/metabolismo , Biblioteca Gênica , Vetores Genéticos , Sobrevivência de Enxerto , Masculino , Camundongos Endogâmicos C57BL , Contração Miocárdica , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Recuperação de Função Fisiológica , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fatores de Tempo , Transdução Genética , Transfecção/métodosAssuntos
Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Restritiva/genética , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Restritiva/diagnóstico por imagem , Cardiomiopatia Restritiva/patologia , Conectina/genética , Feminino , Genótipo , Coração/diagnóstico por imagem , Humanos , MAP Quinase Quinase Quinases/genética , Miocárdio/patologia , Fenótipo , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto JovemRESUMO
AIMS: The prognostic stratification of patients with Idiopathic Dilated Cardiomyopathy (iDCM) is a difficult task. Here, we assessed the additive value of the evaluation of biomarkers of inflammasome activation and systemic inflammation for the long-term risk stratification of iDCM patients. METHODS AND RESULTS: We studied 156 ambulatory iDCM patients (mean age 58 years, 77% men, 79% in NYHA class 1-2, median Left Ventricular Ejection Fraction (LVEF) 35%, mean sodium 139 mEq/L, median BNP 189 pg/mL, median IL-1 beta (IL-1ß) 1.08 pg/mL, median IL-6 1.7 pg/mL and median IL-10 2.7 pg/mL).During the follow-up period of 89.6 months, 35 patients (22%) died/underwent heart transplantation. Patients who died/underwent heart transplantation were more likely to be male, to be in NYHA class III, to have atrial fibrillation, to have lower LVEF and higher BNP levels. IL-1ß, IL-6 and IL-10 levels did not differ significantly between the groups of patients with good or bad prognosis. IL-1ß levels did not vary significantly among either the different NYHA classes or the quartiles of LVEF. In a multivariable model, however, IL-1ß was a strong and independent predictor of all-cause mortality (HR 1.193, 95% CI 1.056 - 1.349, p=0.005 for log squared transformed values). Other factors associated with the outcome were: male gender, presence of atrial fibrillation and sodium concentration. The estimated time-dependent ROC curve of the multivariable model showed an AUC 0.74 (95% CI 0.65-0.86). CONCLUSIONS: Serum levels of IL-1ß could be useful to predict the long-term outcome of patients with iDCM.
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Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/mortalidade , Interleucina-1beta/sangue , Assistência Ambulatorial , Biomarcadores , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/terapia , Comorbidade , Feminino , Testes de Função Cardíaca , Transplante de Coração , Humanos , Masculino , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Curva ROC , Fatores de TempoRESUMO
RATIONALE: Recent evidence indicates that a few human microRNAs (miRNAs), in particular hsa-miR-199a-3p and hsa-miR-590-3p, stimulate proliferation of cardiomyocytes and, once expressed in the mouse heart using viral vectors, induce cardiac regeneration after myocardial infarction. Viral vectors, however, are not devoid of safety issues and, more notably, drive expression of the encoded miRNAs for indefinite periods of time, which might not be desirable in light of human therapeutic application. OBJECTIVE: As an alternative to the use of viral vectors, we wanted to assess the efficacy of synthetic miRNA mimics in inducing myocardial repair after single intracardiac injection using synthetic lipid formulations. METHODS AND RESULTS: We comparatively analyzed the efficacy of different lipid formulations in delivering hsa-miR-199a-3p and hsa-miR-590-3p both in primary neonatal mouse cardiomyocytes and in vivo. We established a transfection protocol allowing persistence of these 2 mimics for at least 12 days after a single intracardiac injection, with minimal dispersion to other organs and long-term preservation of miRNA functional activity, as assessed by monitoring the expression of 2 mRNA targets. Administration of this synthetic formulation immediately after myocardial infarction in mice resulted in marked reduction of infarct size and persistent recovery of cardiac function. CONCLUSIONS: A single administration of synthetic miRNA-lipid formulations is sufficient to stimulate cardiac repair and restoration of cardiac function.