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Congenital heart disease (CHD) is a structural abnormality of the heart and/or great vessels and patients with CHD are at an increased risks of various morbidities throughout their lives and reduced long-term survival. Eventually, CHD may result in various complications including heart failure, arrhythmias, stroke, pneumonia, and sudden death. Unfortunately, the exact etiology and pathophysiology of some CHD remain unclear. Although the quality of life and prognosis of patients with CHD have significantly improved following technological advancement, the influence of CHD is lifelong, especially in patients with complicated CHD. Thus, the management of CHD remains a challenge due to its high prevalence. Finally, there are some disagreements on CHD among international guidelines. In this review, we provide an update of the pathophysiology, diagnosis, and treatment in most common type of CHD, including patent foramen ovale, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, coarctation of the aorta, transposition of the great arteries, congenitally corrected transposition of the great arteries, coronary anomalies, left and right ventricular outflow tract obstruction, tetralogy of Fallot and Ebstein anomaly. In particular, we focus on what is known and what is unknown in these areas, aiming to improve the current understanding of various types of CHD.
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AIMS: Novel echocardiographic parameters of right ventricular (RV) function, including speckle-tracking-derived, three-dimensional, and RV-pulmonary artery coupling parameters, have emerged for the evaluation of pulmonary arterial hypertension (PAH). The relative role of these parameters in the risk stratification of PAH patients is unclear. We compared the performance of multiple RV parameters and sought to establish an optimal model for identifying the risk profile of patients with PAH. METHODS AND RESULTS: Comprehensive risk assessments were performed for 70 patients with PAH. The risk profile of every patient was determined based on the guideline recommendations. Conventional parameters, including fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), novel speckle-tracking-derived RV longitudinal strain (RVLS), and three-dimensional RV ejection fraction (3D-RVEF), were used to evaluate RV function. Pressure-strain loops were measured for the assessment of RV myocardial work, including RV global wasted work (RVGWW). RV-pulmonary artery coupling was assessed by indexing RV parameters to the estimated pulmonary artery systolic pressure (PASP). The median age was 34 (30-43) years, and 62 (88.6%) patients were female. Forty-five patients were classified into the low-risk group, while 25 patients were classified into the intermediate-high-risk group. Most RV parameters could be used to determine the risk profile and exhibited significantly improved diagnostic performance after indexing to PASP (including FAC/PASP, TAPSE/PASP, and 3D-RVEF/PASP). RVLS/PASP showed the best performance, with an area under the curve of 0.895. In multivariate analysis (Model 1), only RVGWW (>90.5 mmHg%), RVLS (> -16.7%), and TAPSE (<17.5 mm) remained significant (all P < 0.05). Model 1 outperformed every single RV parameter, with a significantly larger area under the curve (all P < 0.05). With PASP indexing in Model 2, RVLS/PASP > -0.275 [odds ratio (OR) 20.63, 95% confidence interval (CI) 4.62-92.11, P < 0.001] and RVGWW > 90.5 mmHg% (OR 6.17, 95% CI 1.37-27.76, P = 0.018) independently identified a higher risk profile. The addition of RVGWW to two models determined incremental value in identification (continuous net reclassification improvement 1.058, 95% CI 0.639-1.477, P < 0.001). CONCLUSIONS: The combination models for RV function outperformed any single parameter in identifying the risk profile of patients with PAH. Comprehensive assessment of RV-pulmonary artery coupling using multiparametric methods is clinically meaningful in patients with PAH.
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Ventrículos do Coração , Função Ventricular Direita , Humanos , Feminino , Masculino , Adulto , Função Ventricular Direita/fisiologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/diagnóstico , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Volume Sistólico/fisiologia , Ecocardiografia/métodos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/diagnóstico por imagem , Ecocardiografia Tridimensional/métodos , Estudos Retrospectivos , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico , Medição de Risco/métodos , Pessoa de Meia-IdadeRESUMO
Introduction: Hepatic hereditary haemorrhagic telangiectasia (HHHT) is a rare autosomal dominant genetic disease. Some patients may develop cardiac failure, portal hypertension, and biliary ischaemia. To date, there is no standard surgical treatment for HHHT. The present authors propose a move from open to laparoscopic surgery; however, laparoscopic surgery has not been reported previously as a surgical treatment for HHHT. Report: Two women were admitted with histories of exertional dyspnoea and upper abdominal pain, respectively. Combined with recurrent epistaxis and their positive family history, a diagnosis of clinical HHHT was made based on Curacao criteria after comprehensive evaluation of imaging features. Next generation sequencing (NGS) results also confirmed typical gene mutations responsible for HHT. Both patients underwent laparoscopic double hepatic artery banding and or ligation successfully and were discharged four to six days after operation without severe complications. The symptoms of cardiac insufficiency including exertional dyspnoea and shortness of breath of the first patient improved six months after the operation. The second patient, with epigastric pain, remained pain free without medication three months after the operation. Discussion: Laparoscopic surgery for HHHT is technically challenging. Clinical data and follow up information showed that laparoscopic double hepatic artery banding and or ligation was a technically feasible surgical approach for HHHT patients with simple hepatic artery dilation.
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Patients with device detected atrial high-rate episodes (AHRE) have an increased risk of MACE. The R2CHA2DS2-VASc, CHADS2, R2CHADS2 and CHA2DS2-VASc score have been investigated for predicting major adverse cardiovascular events (MACE) in different groups of patients. We aimed to evaluate the R2CHA2DS2-VASc score in combination with AHRE ≥ 6 min for predicting MACE in patients with dual-chamber PPM but no prior atrial fibrillation (AF). We retrospectively enrolled 376 consecutive patients undergoing dual-chamber PPM implantation and no prior AF. The primary endpoint was subsequent MACE. For all patients in the cohort, CHADS2, R2CHADS2, CHA2DS2-VASc, R2CHA2DS2-VASc scores and AHRE ≥ or < 6 min were determined. AHRE was recorded as a heart rate > 175 bpm (Medtronic) or > 200 bpm (Biotronik) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine the independent predictors of MACE. ROC-AUC analysis was performed for CHADS2, R2CHADS2, CHA2DS2-VASc, and R2CHA2DS2-VASc scores and then adding AHRE ≥ 6 min to the four scores. The median age was 77 years, and 107 patients (28.5%) developed AHRE ≥ 6 min. After a median follow-up of 32 months, 46 (12.2%) MACE occurred. Multivariate Cox regression analysis showed that R2CHA2DS2-VASc score (HR, 1.485; 95% CI, 1.212-1.818; p < 0.001) and AHRE ≥ 6 min (HR, 2.125; 95% CI, 1.162-3.887; p = 0.014) were independent predictors for MACE. The optimal R2CHA2DS2-VASc score cutoff value was 4.5 (set at ≥ 5), with the highest Youden index (AUC, 0.770; 95% CI, 0.709-0.831; p < 0.001). ROC-AUC analysis of the four risk scores separately combined with AHRE ≥ 6 min all showed better discriminatory power than the four scores alone (All Z-statistic p < 0.05). In patients with PPM who develop AHRE ≥ 6 min, it is crucial to perform risk assessment with either four scores to further stratify risk for MACE.
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Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Idoso , Prognóstico , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Medição de RiscoRESUMO
Aim: Selexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients. Methods and results: A single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis. Conclusion: Triple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.
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Discotomia Percutânea , Deslocamento do Disco Intervertebral , Estenose Espinal , Idoso , Endoscopia , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Resultado do TratamentoRESUMO
AIMS: Several predicting models have been evaluated for new-onset atrial fibrillation (AF) in several clinical conditions, but never in patients with cardiac implantable electronic devices (CIED). We aimed to evaluate the five predicting models compared with atrial high rate episodes (AHRE) to predict new AF in patients with CIED. METHODS AND RESULTS: We retrospective enrolled 470 consecutive patients with CIED and without a history of AF. The five predicting models, including CHA2 DS2 -VASc score, C2 HEST score, mCHEST score, HAT2 CH2 score, and HAVOC score were used. The primary endpoint was new AF documented by 12-lead electrocardiography (ECG) or 30-s ECG strip. Multivariable Cox regression analysis was used to determine variables associated with independent factors of new AF. Patients' median age was 76 years and 58.7% were male. During follow-up (median 29 months), 34 new AF occurred (incidence rate 2.99/100 patient-years, 95% CI 1.67-6.20). Multivariable Cox regression analysis showed AHRE ≥6 min and 24 h, and HAT2 CH2 score were independent predictors for new AF. Optimal AHRE cutoff value was 9.3 min with highest Youden index (AUC, 0.806; 95% CI, 0.722-0.889; p < .001). The AF occurrence rate of AHRE ≥9.3 min was 7 times AHRE <9.3 min (p < .001). CONCLUSIONS: We compared 5 predicting models for new AF in patients with CIED and without a history of AF. AHRE ≥6 min and 24 h, and HAT2 CH2 score were independent predictors for AF.
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Fibrilação Atrial , Acidente Vascular Cerebral , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Eletrocardiografia/efeitos adversos , Eletrônica , Feminino , Átrios do Coração , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Objectives: The HAT2CH2 score has been evaluated for predicting new-onset atrial fibrillation in several clinical conditions, but never for adverse neurologic events. We aimed to evaluate the effectiveness of HAT2CH2 score in predicting neurologic events in patients with cardiac implantable electronic device (CIED), comparing with atrial high-rate episodes (AHRE). Methods: This case-control study enrolled 314 consecutive patients aged 18 years or older with CIED implantation between January 2015 and April 2021. Patient data were analyzed retrospectively. The primary endpoint was subsequent neurologic events (NE) after implantation. AHRE was defined as > 175 bpm (Medtronic®) lasting ≥ 30 seconds. Variables associated with independent risk of NE were identified using multivariate Cox regression analysis with time-dependent covariates. Results: Patients' median age was 73 years and 61.8% of them were male. During follow-up (median 32 months), 18 NE occurred (incidence rate 2.15/100 patient-years, 95% CI 1.32-4.30). Multiple Cox regression analysis showed that the HAT2CH2 score (HR 2.424, 95% CI 1.683 - 3.492, p < 0.001) was an independent predictor for NE. Optimal HAT2CH2 score cutoff value was 3 with highest Youden index (AUC, 0.923; 95% CI, 0.881-0.966; p < 0.001). Both AHRE ≥ 1 minute and HAT2CH2 score ≥ 3 had the highest AUC of the receiver-operating characteristic (0.898, 95% CI, 0.831-0.965, p < 0.001). Significant increase was observed in NE occurrence rates using the HAT2CH2 score (p < 0.001). Conclusion: The HAT2CH2 score and episodes of AHRE lasting ≥ 1 minute are independent risk factors for NE in patients with CIED.
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Fibrilação Atrial , Desfibriladores Implantáveis , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos de Casos e Controles , Desfibriladores Implantáveis/efeitos adversos , Eletrônica , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The HAT2CH2 score has been evaluated for predicting new-onset atrial fibrillation (AF) in several clinical conditions but never for adverse neurologic events. We aimed to evaluate the HAT2CH2 score for predicting neurologic events in patients with cardiac implantable electronic devices (CIED). METHODS AND RESULTS: We retrospectively reviewed 470 consecutive patients who had CIED without a history of AF. The primary endpoint was a neurologic event, i.e. ischemic stroke or transient ischemic attack. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent factors of neurologic events. Patients' median age was 76 years, and 58.7% were male. During follow-up (median 29 months), 21 neurologic events occurred (incidence rate 1.85/100 patient-years, 95% CI 1.03-3.83). Multivariable Cox regression analysis revealed that the HAT2CH2 score (HR 3.397, 95% CI 2.357-4.895, p < 0.001) was an independent predictor for neurologic events. Optimal HAT2CH2 score cut-off value was 3, with highest Youden index (AUC, 0.923; 95% CI, 0.886-0.959; p < 0.001). The rate of neurologic events increased significantly with increasing HAT2CH2 score (p < 0.001). CONCLUSIONS: The HAT2CH2 score can predict the occurrence of neurologic events in patients with CIED with no history of AF. Further study of the utility of the HAT2CH2 score for the assessment of neurologic event risk and the selection of anti-thrombotic therapy in patients with CIED without prior AF is warranted.
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Desfibriladores Implantáveis , Doenças do Sistema Nervoso , Idoso , Fibrilação Atrial/epidemiologia , Desfibriladores Implantáveis/efeitos adversos , Feminino , Humanos , Masculino , Doenças do Sistema Nervoso/epidemiologia , Estudos RetrospectivosAssuntos
Cardiomiopatias , Marca-Passo Artificial , Acidente Vascular Cerebral , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Átrios do Coração/fisiopatologia , Humanos , Marca-Passo Artificial/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
Background: Patients with sustained atrial high-rate episodes (AHRE) have a high risk of major adverse cardio/cerebrovascular events (MACCE). However, the prediction model and factors for the occurrence of AHRE are unknown. We aimed to identify independent factors and various risk models for predicting MACCE and AHRE. Methods: We retrospectively enrolled 314 consecutive patients who had cardiac implantable electronic devices (CIEDs). The primary endpoint was MACCE after AHRE ≥3, 6 min, and 6 h. Atrial high-rate episodes was defined as >175 bpm (Medtronic®) lasting ≥30 s. Multivariate Cox and logistic regression analysis with time-dependent covariates were used to determine variables associated with independent risk of MACCE and occurrence of AHRE ≥3 min, respectively. Results: One hundred twenty-five patients (39.8%) developed AHRE ≥3 min, 103 (32.8%) ≥6 min, and 55 (17.5%) ≥6 h. During follow-up (median 32 months), 77 MACCE occurred (incidence 9.20/100 patient years, 95% CI 5.66-18.39). The optimal AHRE cutoff value was 3 min for MACCE, with highest Youden index 1.350 (AUC, 0.716; 95% CI, 0.638-0.793; p < 0.001). Atrial high-rate episodes ≥3 min-6 h were independently associated with MACCE. HATCH score and left atrial diameter were independently associated with AHRE ≥3 min. The optimal cutoff for HATCH score was 3 and for left atrial diameter was 4 cm for AHRE ≥3 min. Conclusion: Patients with CIEDs who develop AHRE ≥3 min have an independently increased risk of MACCE. Comprehensive assessment using HATCH score and echocardiography of patients with CIEDs is warranted.
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Patients with atrial high-rate episodes (AHRE) have a high risk of neurologic events, although the causal role and optimal cutoff threshold of AHRE for major adverse cardio/cerebrovascular events (MACCE) are unknown. This study aimed to identify independent factors for AHRE and subsequent atrial fibrillation (AF) after documented AHRE. We enrolled 470 consecutive patients undergoing cardiac implantable electrical device (CIED) implantations. The primary endpoint was subsequent MACCE after AHRE ≥ 6 min, 6 h, and 24 h. AHRE was defined as > 175 beats per minute (bpm) (Medtronic®) or > 200 bpm (Biotronik®) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of MACCE. The patients' median age was 76 year, and 126 patients (26.8%) developed AHRE ≥ 6 min, 63 (13.4%) ≥ 6 h, and 39 (8.3%) ≥ 24 h. During follow-up (median: 29 months), 142 MACCE occurred in 123 patients. Optimal AHRE cutoff value was 6 min, with highest Youden index for MACCE. AHRE ≥ 6 min ~ 24 h was independently associated with MACCE and predicted subsequent AF. Male gender, lower body mass index, or BMI, and left atrial diameter were independently associated with AHRE ≥ 6 min ~ 24 h. Patients with CIEDs who develop AHRE ≥ 6 min have an independently increased risk of MACCE. Comprehensive assessment of patients with CIEDs is warranted.
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Fibrilação Atrial/epidemiologia , Desfibriladores Implantáveis/efeitos adversos , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Taquicardia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/etiologia , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Taquicardia/complicações , Taquicardia/fisiopatologia , Taiwan/epidemiologiaRESUMO
BACKGROUND: Patients with atrial high-rate episode (AHRE) are at higher risk of neurological events. This study aimed to identify the optimal cutoff threshold for AHRE duration in patients with dual chamber permanent pacemakers (PPM) without prior atrial fibrillation. METHODS: We included 355 consecutive patients receiving dual chamber pacemaker implantation. Primary outcome was composite endpoint of subsequent neurological events after various AHRE durations. AHRE was defined as >175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) for longer than 30 s. Cox regression analysis with time-dependent covariates was conducted. RESULTS: The mean age of included patients was 75.6 ± 11.3 years. Among 355 included patients, some had multiple AHREs; 125 patients (35.2%) developed AHRE ≥2 min, 107 (30.1%) had ≥5 min, 55 (15.5%) had ≥6 h, and 37 (10.4%) had ≥24 h. The mean follow-up was 42.1 ± 31.2 months. During follow-up, 19 neurological events occurred. After adjustment for CHA2 DS2 -VASc score and device type, multivariate Cox regression analysis indicated AHRE ≥2 min (HR 13.605, 95% CI 3.010-61.498), and AHRE ≥5 min (HR 5.819, 95% CI 2.056-16.470) were significantly associated with neurological events. Hence, the optimal AHRE cutoff value was 2 min with the highest Youden index (sensitivity, 89.5%; specificity, 67.8%; AUC, 0.823, 95% CI, 0.763-0.884; p < 0.001). CONCLUSIONS: Patients with dual chamber PPM who develop AHRE have increased risk of neurological events. Comprehensive assessment of the risks and benefits of prescribing anticoagulants should be considered in PPM patients with AHRE ≥2 min.
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Fibrilação Atrial , Marca-Passo Artificial , Anticoagulantes , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Átrios do Coração , Humanos , Análise Multivariada , Fatores de RiscoRESUMO
Patients with atrial high-rate episodes (AHRE) are at higher risk of major adverse cardiovascular events (MACE). The cutoff threshold for AHRE duration for MACE, with/without history of atrial fibrillation (AF) or myocardial infarction (MI), is unknown. A total of 481 consecutive patients with/without history of AF or MI receiving dual-chamber pacemaker implantation were included. The primary outcome was a composite endpoint of MACE after AHRE ≥ 5 min, ≥ 6 h, and ≥ 24 h. AHRE was defined as > 175 bpm (MEDTRONIC) or > 200 bpm (BIOTRONIK) lasting ≥ 5 min. Cox regression analysis with time-dependent covariates was conducted. Patients' mean age was 75.3 ± 10.7 years and 188 (39.1%) developed AHRE ≥ 5 min, 115 (23.9%) ≥ 6 h, and 83 (17.3%) ≥ 24 h. During follow-up (median 39.9 ± 29.8 months), 92 MACE occurred (IR 5.749%/year, 95% CI 3.88-5.85). AHRE ≥ 5 min (HR 5.252, 95% CI 2.575-10.715, P < 0.001) and ≥ 6 h (HR 2.548, 95% CI 1.284-5.058, P = 0.007) was independently associated with MACE, but not AHRE ≥ 24 h. Patients with history of MI (IR 17.80%/year) had higher MACE incidence than those without (IR 3.77%/year, p = 0.001). Significant differences were found between MACE patients with/without history of AF in AHRE ≥ 5 min but not AHRE ≥ 6 h or ≥ 24 h. Patients with dual-chamber pacemakers who develop AHRE have increased risk of MACE, particularly after history of AF or MI.
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Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Átrios do Coração/patologia , Marca-Passo Artificial/efeitos adversos , Idoso , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Análise Multivariada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Curva ROC , Análise de Regressão , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: CX-5461 is a novel selective RNA polymerase I (Pol I) inhibitor. Previously, we found that CX-5461 could inhibit pathological arterial remodelling caused by angioplasty and transplantation. In the present study, we explored the pharmacological effects of CX-5461 on experimental pulmonary arterial hypertension (PAH) and PAH-associated vascular remodelling. EXPERIMENTAL APPROACH: PAH was induced in Sprague-Dawley rats by monocrotaline or Sugen/hypoxia. KEY RESULTS: We demonstrated that CX-5461 was well tolerated for in vivo treatments. CX-5461 prevented the development of pulmonary arterial remodelling, perivascular inflammation, pulmonary hypertension, and improved survival. More importantly, CX-5461 partly reversed established pulmonary hypertension. In vitro, CX-5461 induced cell cycle arrest in human pulmonary arterial smooth muscle cells. The beneficial effects of CX-5461 in vivo and in vitro were associated with increased activation (phosphorylation) of p53. CONCLUSION AND IMPLICATIONS: Our results suggest that pharmacological inhibition of Pol I may be a novel therapeutic strategy to treat otherwise drug-resistant PAH.
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Hipertensão Arterial Pulmonar , Remodelação Vascular , Animais , Benzotiazóis , Proliferação de Células , Modelos Animais de Doenças , Monocrotalina , Músculo Liso Vascular , Miócitos de Músculo Liso , Naftiridinas , Artéria Pulmonar , RNA Polimerase I , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Patients with atrial high-rate episodes (AHRE) have a high risk of cardiovascular and cerebrovascular events (CCE); however, the optimal cut-off threshold for AHRE duration and the prediction power of AHRE with CHA2DS2-VASc score is unknown. METHODS: We enrolled 355 consecutive patients undergoing dual chamber pacemaker implantations. The primary endpoint was subsequent CCE after AHRE ≥ 30 seconds, 1 minute, 2 minutes, 5 minutes, 6 hours, and 24 hours. AHRE was defined as >175 bpm (Medtronic, Dublin, Ireland) or >200 bpm (Biotronik, Berlin, Germany) lasting ≥30 seconds. Multivariate Cox regression analysis with time-dependent covariates was used to determine the variables associated with higher risks of CCE. RESULTS: The average age of the patients was 75.6 ± 11.3 years, and 162 patients (45.6%) developed AHRE ≥ 30 seconds, 145 (40.8%) ≥1 minute, 125 (35.2%) ≥2 minutes, 107 (30.1%) ≥5 minutes, 55 (15.5%) ≥6 hours, and 37 (10.4%) ≥24 hours. During follow-up (mean 42.1 ± 31.2 months), 145 CCE occurred in 107 patients (incidence rate 11.64/100 patient-years, 95% CI 9.99-13.70). The optimal AHRE cut-off value was 1 minute (sensitivity, 57.9%; specificity, 66.0%; area-under-the-curve, 0.631; 95% CI, 0.563-0.698; p < 0.001). Multivariate Cox regression analysis demonstrated that all categories of AHRE duration were independently associated with CCE. The occurrence of CCE increased with AHRE ≥30 seconds and CHA2DS2-VASc score ≥2 (males) or ≥3 (females). CONCLUSION: Patients with dual chamber pacemakers who develop AHRE ≥ 30 seconds have an increased risk of CCE. The combination of AHRE duration ≥30 seconds and CHA2DS2-VASc score ≥2 (males) or ≥3 (females) is a useful risk-stratification predictor for subsequent CCE.
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Arritmias Cardíacas/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Indicadores Básicos de Saúde , Marca-Passo Artificial/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/etiologia , Doenças Cardiovasculares/etiologia , Desenho de Equipamento , Feminino , Alemanha , Átrios do Coração/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Valores de Referência , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de TempoRESUMO
Background: The HAT2CH2 score has been evaluated for predicting new onset atrial fibrillation, but never for adverse systemic thromboembolic events (STE) in elderly. We aimed to evaluate the HAT2CH2 score and comparing to atrial high rate episodes (AHRE) ≥24 h for predicting STE in older patients with cardiac implantable electronic devices (CIED) implantation. Methods: We retrospective enrolled 219 consecutive patients ≥ 65 years of age undergoing CIED implantation. The primary endpoint was subsequent STE. For all patients in the cohort, the CHA2DS2-VASc, C2HEST, mC2HEST, HAVOC, HAT2CH2 scores and AHRE ≥ 24 h were determined. AHRE was defined as > 175 bpm lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of STE. Results: The median patient age was 77 years, and 61.2% of the cohort was male. During follow-up (median, 35 months), 16 STE occurred (incidence rate, 2.51/100 patient-years; 95% CI, 1.65-5.48). Multiple Cox regression analysis showed that the HAT2CH2 score (HR, 3.405; 95% CI, 2.272-5.104; p < 0.001) was an independent predictor for STE. The optimal HAT2CH2 score cutoff value was 3, with the highest Youden index (AUC, 0.907; 95% CI, 0.853-0.962; p < 0.001). The STE rate increased with increasing HAT2CH2 score (p < 0.001). Conclusions: This study is the first to show the prognostic value of the HAT2CH2 score for STE occurrence in older patients with CIEDs.
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BACKGROUND: Thrombi are an important challenge when establishing hemodialysis access for hemodialysis. We developed a minimally invasive thrombectomy (MIT) salvage treatment to solve this problem when traditional percutaneous transluminal angioplasty (PTA) fails. OBJECTIVES: The study aimed to investigate the safety and patency rate following MIT as a rescue procedure for traditional PTA with organized thrombi obstructing hemodialysis access. METHODS: This was a prospective study of MIT as a rescue procedure for traditional PTA to remove organized thrombi and establish hemodialysis access. We included patients with (1) stenotic lesions, (2) vascular access thrombi, (3) high venous pressure, (4) vascular collapse and suction. Nephrologists evaluated hemodialysis access immediately post-thrombi removal and patency at 7, 30, 60, 120, and 180 days post-removal, in addition to complications. Kaplan-Meier survival analysis was performed to analyze the primary and secondary patency rates after clinical procedural success. RESULTS: From June 2014 to May 2015, 746 patients underwent PTA in our hospital, and 425 patients consented to participate in this study. Of these patients, we enrolled 46 who underwent simultaneous PTA and MIT. Immediate clinical success was achieved in 100% of the patients in the MIT group. No complications were observed in any of the 46 patients, including major bleeding, shock, or hospitalization. The primary and secondary patency rates did not differ between MIT and PTA alone (p = 0.93 and p = 0.28, respectively). CONCLUSIONS: MIT can be considered a safe rescue procedure for removing organized thrombi to establish vascular access for hemodialysis when initial and traditional PTA fails.
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Hepatic damage has been recognized as one of the major complications in diabetes mellitus. Our previous studies have verified that grape seed procyanidin B2 (GSPB2) played a protective effect on hepatic damage of diabetes. We used isobaric tag for relative and absolute quantitation proteomics here to identify the alterant mitochondrial protein profile in diabetic liver and to seek the protective targets of GSPB2. Proteomics found that 171 proteins were upregulated or downregulated in the liver mitochondria of diabetic group compared to the control group. Of these proteins, 61 were normalized after GSPB2 treatment. These back-regulated proteins are involved in the process of fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and apoptosis. Some differentially expressed proteins were confirmed by western blotting. Our study might help to better understand the mechanism of mitochondrial dysfunction in diabetic liver damage, and provide novel targets for estimating the protective effects of GSPB2. PRACTICAL APPLICATIONS: Grape seed procyanidin B2 (GSPB2), a polyphenolic component found in red wine and grapes, has beneficial effects such as antioxidative stress, antiapoptosis, and cardiovascular protection. We used proteomics here to identify the differentially expressed mitochondrial proteins in diabetic liver after GSPB2 treatment and to seek the protective targets of GSPB2. We found that the differentially expressed proteins were involved in carbon metabolism, oxidative phosphorylation, fatty acid metabolism, citrate cycle, oxidative stress, and apoptosis. These proteins may play a key role in diabetic hepatic damage as functional proteins. Targeting these proteins including apply of GSPB2 could potentially lead to an effective treatment in the diabetic hepatic disease.
Assuntos
Extrato de Sementes de Uva , Mitocôndrias Hepáticas , Proteômica , Vitis , Animais , Biflavonoides , Catequina , Extrato de Sementes de Uva/farmacologia , Camundongos , Proantocianidinas , SementesRESUMO
BACKGROUND: Subclavian vein obstruction may occur in patients with pacemaker leads, which may make the implantation of new pacemaker leads difficult. CASE SUMMARY: We report two cases in which upgrading to cardiac resynchronization therapy pacemaker was challenging due to total central vein occlusion. In the first case, a 78-year-old woman with permanent pacemaker implantation, 5 years ago, was successfully treated by balloon venoplasty. In the second case, balloon venoplasty was unsuccessful in a 46-year-old woman who has received twice single-chamber implantable cardioverter-defibrillator, 12 years and 5 years ago, due to vessel crowding, so a contralateral side puncture, along with a tunnel technique, was performed to solve this problem. DISCUSSION: Cardiac implantable electronic device-related subclavian vein stenosis can present a challenge to common cardiac resynchronization therapy device upgrades in the absence of appropriate techniques.