Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

Factors Associated with the Prognosis of Patients with Acute Myocardial Infarction and Cardiogenic Shock.

BACKGROUND Patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) usually have high mortality. This study aimed to identify factors related to the short-term survival of patients with AMI and CS treated by percutaneous coronary intervention (PCI) under intra-aortic balloon pump (IABP) support. MATERIAL AND METHODS This retrospective study included consecutive patients with AMI and CS treated with PCI under IABP support. Clinical characteristics, including the infarct-related artery, lesion number, aspiration catheter usage, conventional or delayed stenting, and thrombolysis in myocardial infarction (TIMI) flow grade before and after PCI, were collected. Patients were followed up postoperatively for 30 days. Multivariate logistic regression was used to identify factors associated with the 30-day mortality. RESULTS There were marked differences between the nonsurvival group (n=49) and the survival group (n=92) in the no-reflow after surgery (49.0% vs 14.1%, P<0.001), postoperative TIMI grade 3 flow (65.3% vs 91.3%, P<0.001), and delayed stent implantation (18.4% vs 37.0%, P=0.022). Factors associated with 30-day mortality were postoperative TIMI grade 3 flow (odds ratio [OR]: 0.227; 95% confidence interval [CI]: 0.076-0.678; P=0.008), delayed stent implantation (OR: 0.371; 95% CI: 0.139-0.988; P=0.047), and intraoperative no-reflow (OR: 2.737; 95% CI: 1.084-6.911; P=0.033). CONCLUSIONS For patients with AMI complicated by CS treated with emergent PCI under IABP support, prevention of no-reflow during surgery by delayed stent implantation can reduce postoperative 30-day mortality in selected cases.

Imatinib atenua a fibrose miocárdica em associação com a inibição da atividade do PDGFRα / Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity

FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ). OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA)/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON): grupo deoxicorticosterona (grupo DOCA); grupo deoxicorticosterona e Imatinib (grupo DOCA IMA). A Pressão Arterial Sistólica (PAS) foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.

BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were signiflcantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.

Imatinib attenuates myocardial fibrosis in association with inhibition of the PDGFRα activity.

BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRß) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were significantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.

[The safety and outcome of patients with acute myocardial infarction transferred for primary angioplasty].

OBJECTIVE: To evaluate the safety and outcome of patients with acute myocardial infarction (AMI) transferred for primary percutaneous coronary intervention (PCI). METHODS: Data from patients with ST elevation AMI urgently transferred from first admitted hospitals to our cath-lab to receive primary PCI were analyzed. According to time intervals from symptom onset to transfer, the patients were divided into early transfer (< 6 h, n = 26), delayed transfer (6 - 24 h, n = 39) and late transfer (24 h to 1 week, n = 18) group. The major cardiac events during transfer periods and one month after PCI were obtained and echocardiogram and left ventricular systolic functions were compared among groups. RESULTS: There was no serious cardiac event during transfer period and all 83 patients received primary PCI with a mean transfer-to-balloon time about 180 minutes. Success rate of PCI was 92.3% in early transfer group, 89.7% in delayed transfer group, and 94.4% in late transfer group (P > 0.05). At one month follow-up after PCI, 0, 10.3% and 16.7% of patients developed heart failure in early, delayed transfer and late transfer group respectively (P > 0.05 vs. early), the LVEF of early transfer group (53.2% +/- 9.7%) was also significantly higher than delayed transfer group (48.6% +/- 8.2%, P < 0.05) and late transfer group (43.1% +/- 10.3%, P < 0.01). CONCLUSIONS: Transfer patients with AMI for primary PCI is safe in the observed time intervals during acute phase. Early transferred patients are associated with better outcome at 1 month post PCI compared to delayed and late transferred AMI patients.

[Effects of delayed opening of infarct-related artery on late left ventricular remodeling in patients with acute anterior myocardial infarction].

OBJECTIVE: To assess the effect of delayed opening of the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) on the late left ventricular remodeling after acute anterior myocardial infarction (AAMI). METHODS: Sixty four patients with initial Q-wave AAMI and with the total occluded IRA conformed by angiogram at 9.1 +/- 2.3 (2 - 14) days after the onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re-opened). Two-D echocardiogram was performed at acute phase (about 3 weeks), 2 and 6 months after onset of AAMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up. RESULTS: VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were similar in 2 groups at acute phase and 2 months after the onset of AAMI. There were no differences between the parameters above at acute phase and 2 months in each group too. VWMA scores and LVEF did not changed significantly at 6 months in each group compared with those at acute phase and 2 months (P > 0.05). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than those in the control group (P < 0.01, P < 0.05). The rate of congestive heart failure events was 19% in control group and 2.0% in successful PCI group (P > 0.05) respectively. CONCLUSIONS: Delayed opening of IRA in AAMI could prevent the late phase but not the early phase of left ventricular remodeling after AMI.