Determinants of device success after transcatheter aortic valve replacement in patients with type-0 bicuspid aortic stenosis.

Background: Clinical evidence of transcatheter aortic valve replacement in patients with type-0 bicuspid aortic valve was relatively scarce. Aims: Our goal was to explore determinants of device success after transcatheter aortic valve replacement in patients with type-0 bicuspid aortic valve morphology. Methods: In this retrospective multicenter analysis, we included 59 patients with symptomatic severe aortic stenosis with type-0 bicuspid aortic valve morphology who underwent transcatheter aortic valve replacement. Type-0 bicuspid aortic valve was identified with multidetector computed tomography scans. The technical success rate was 89.8%, and the device success rate was 81.4%. Patients were divided into a device success group and a device failure group according to Valve Academic Research Consortium- 3 criteria. Results: When we compared the two groups, we found that the ellipticity index of the aortic root and the presence of bulky calcifications at the commissure were statistically different (ellipticity index 35.7 ± 1.7 vs. 29.7 ± 1.1, p = 0.018; bulky calcification at the commissure, 54.5% vs. 4.5%, p < 0.001). Further multivariate logistic analysis showed that bulky calcification at the commissure had a negative correlation with device success (odds ratio 0.030, 95% confidence interval 0.003-0.285, p = 0.002). Yet there was no statistical correlation between the ellipticity index and device success (odds ratio 0.818, 95% confidence interval 0.667-1.003, p = 0.053). Conclusions: The presence of bulky calcifications at the commissure is negatively correlated with device success after transcatheter aortic valve replacement in patients with type-0 bicuspid aortic valve.

Effectiveness and safety of transcatheter aortic valve replacement in elderly people with severe aortic stenosis with different types of heart failure.

BACKGROUND: Impaired left ventricular function is an independent predictor of adverse clinical outcomes in patients with aortic stenosis. The aim of this study is to evaluate the short-term changes of echocardiographic parameters, New York Heart Association (NYHA) class and B-type natriuretic peptide (BNP) level and adverse events amongst patients with heart failure (HF) after transcatheter aortic valve replacement (TAVR) procedure. METHODS: This was a retrospective cohort study conducted at affiliated Yantai Yuhuangding Hospital of Qingdao University between September 2017 and September 2022. TAVR cases were stratified into three groups [heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), heart failure with preserved ejection fraction (HFpEF)] by left ventricular ejection fraction (LVEF). Baseline characteristics, changes in echocardiographic parameters (1 week and 1 month), BNP (1 month), and NYHA class (6 months) post-TAVR were compared across the three groups. Meanwhile, we observed the adverse events of the patients after TAVR. RESULTS: A total of 96 patients were included, of whom 15 (15.6%) had HFrEF, 15 (15.6%) had HFmrEF, and 66 (68.8%) had HFpEF. Compared to the HFpEF subgroup, patients in the HFrEF subgroup were younger (p < 0.05), and with a higher BNP (p < 0.05). The left ventricular end-diastolic dimension (LVEDD) in HFrEF group decreased significantly after TAVR. HFmrEF and HFrEF patients showed significant improvements in LVEF after TAVR. The pulmonary artery systolic pressure (PASP), aortic valve peak gradient (AVPG) and aortic valve peak gradient (Vmax) decreased significantly 1 month after TAVR in all three groups compared to the baseline (all p < 0.05). BNP significantly reduced in HFrEF group compared to HFpEF patients after TAVR (p < 0.05). The majority of patients experienced an improvement at least one NYHA class in all three groups 6 months post-TAVR. There is no significant increase in the risk of adverse events in the HFrEF group. CONCLUSIONS: Patients who underwent TAVR achieved significant improvements in BNP, NYHA class, LVEDD, LVEF, and PASP across the three HF classes, with a more rapid and pronounced improvement in the HFrEF and HFmrEF groups. Complication rates were low in the different HF groups. There is no significant increase in the risk of periprocedural complications in the HFrEF and HFmrEF groups.

Role of JNK signalling pathway and platelet­lymphocyte aggregates in myocardial ischemia­reperfusion injury and the cardioprotective effect of ischemic postconditioning in rats.

In myocardial ischemia­reperfusion injury (MIRI), increased activity of the c­Jun N­terminal kinase (JNK) pathway and the activation of platelets that leads to the formation of platelet­leukocyte aggregates (PLAs) have been observed. It was hypothesized that ischemic postconditioning in MIRI exerts cardioprotective effects by altering JNK activity, which in turn leads to reduced PLA levels. A total of 60 rats were randomly divided into 6 groups (n=10 for each group): i) Control; ii) ischemia­reperfusion injury alone; iii) ischemia­reperfusion with postconditioning (PostC group), iv) treatment with the JNK inhibitor­SP600125; v) postC and treatment with anisomycin; and vi) treatment with the JNK activator­anisomycin. Subsequently, the levels of PLA, infarct size, myocardial injury markers (creatinine kinase­muscle/brain and troponin I) and were measured. Western blotting was used to determine the protein expression of phosphorylated­JNK. MIRI led to increased myocardial infarct size that was associated with raised troponin I and creatine kinase­muscle/brain. At different time points of MIRI, the level of PLA gradually increased. Compared with the injury­reperfusion group, the level of PLA in the PostC and Inhibitor­JNK groups was significantly reduced at 60 min and 3 h following reperfusion. MIRI was able to increase the expression of phosphorylated JNK. These effects were significantly reduced by ischemic postC or by treatment with SP600125. By contrast, the addition of anisomycin attenuated these protective effects. JNK is a critical mediator of MIRI. Ischemic postC can reduce the level of PLA during reperfusion by inhibiting the phosphorylation of JNK MAPK, thereby reducing MIRI. Pharmacological inhibition and activation of JNK can improve and reduce cardioprotective effects, respectively. These results explained the mechanism of the cardioprotection of postC and provided novel insight and target for the therapeutic strategy of MIRI.

Role of miR-128 in hypertension-induced myocardial injury.

The present study aimed to investigate the role and mechanism of micro RNA (miR)-128 in hypertension-induced myocardial injury. The peripheral blood of patients with hypertension was collected and the expression of miR-128 was detected using fluorescence reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary myocardial cells isolated from rat in vitro were cultured under conditions of hypoxia and glucose deprivation, and miR-128 expression was measured by RT-qPCR. The expression of c-Met protein was measured using western blot analysis and the apoptosis of transfected cells was measured by flow cytometry in rat myocardial cells following transfection with miR-128 mimics or c-Met siRNA. A luciferase assay was applied to assess the binding of miR-128 to c-Met mRNA. miR-128 expression was significantly higher in hypertension patients compared with controls (P<0.05). miR-128 expression was higher in patients with stage III/IV hypertension compared with patients with stage II hypertension. Similarly, miR-128 expression in primary cardiomyocytes cultured under deprivation of oxygen and glucose increased with the culture time and reached a peak at 12 h. c-Met expression decreased significantly (P<0.05) and the ratio of apoptotic cells increased significantly (P<0.05), following transfection of miR-128 mimics. The number of apoptotic cells also increased when c-Met expression was knocked down by siRNA. The dual luciferase assay indicated that fluorescence intensity decreased significantly in miR-128 mimics and wild type c-Met group (P<0.05), indicating that miR-128 can directly target c-Met. Therefore, the results of the current study suggest that miR-128 may promote myocardial cell injury by regulating c-Met expression.

Increased Platelet-leukocyte Aggregates Are Associated With Myocardial No-reflow in Patients With ST Elevation Myocardial Infarction.

OBJECTIVE: We aimed to investigate the association between platelet-leukocyte aggregates (PLA) levels on admission and the risk of myocardial no-reflow in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 83 patients with STEMI undergoing primary PCI were included in the current study. Platelet-leukocyte conjugates (PLA), including platelet-monocyte aggregates (PMA), platelet-neutrophil aggregates (PNA) and platelet-lymphocyte aggregates were studied by flow cytometry in peripheral venous blood. No-reflow was defined as coronary blood flow grade thrombolysis in myocardial infarction ≤2 or thrombolysis in myocardial infarction 3 and myocardial blush grade ≤2. RESULTS: No-reflow was observed in 19 patients (22.9%). Compared with the reflow group, the level of PNA (76.5 ± 13.3) and PMA (90.3 ± 5.2) before PCI no-reflow group was significantly higher than that in normal reflow (P < 0.001). Using multiple logistic regression analysis, PNA (odds ratio [OR] = 1.179; 95% CI: 1.035-1.342; P = 0.013) and PMA (OR = 1.248; 95% CI: 1.040-1.498; P = 0.017) were found to be a significant predictor of no-reflow together with pain to balloon time (OR = 1.022; 95% CI: 1.002-1.041; P = 0.028), estimated glomerular filtration rate (OR = 1.311; 95% CI: 1.009-1.856; P = 0.047) and higher thrombus burden (OR = 0.061; 95% CI: 0.006-0.658; P = 0.021). Receiver operating characteristic curve analysis revealed that PNA (area under the curve = 0.881; 95% CI: 0.809-0.952; P < 0.001), PMA (area under the curve = 0.794; 95% CI: 0.699-0.889; P < 0.001) have important predictive value for the myocardial no-reflow. CONCLUSIONS: Our study indicated that preprocedural increased PLA levels display a significantly independent association with no-reflow phenomenon after PCI. Increased PLA levels may predict the development of no-reflow phenomenon in patients with STEMI who underwent PCI.

Matrix Metalloproteinase-9 in the Culprit Coronary Artery and Myocardial No-Reflow.

BACKGROUND: Matrix Metalloproteinases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 in the culprit coronary artery as a predictor of no-reflow in patients with ST-elevation AMI. METHODS: Ninety patients with ST-elevation AMI who underwent emergency percutaneous coronary intervention were consecutively recruited in this study. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of percutaneous coronary intervention. No-reflow was defined as a coronary thrombolysis in myocardial infarction flow grade ≤2 after vessel reopening or thrombolysis in myocardial infarction flow 3 with a final myocardial blush grade ≤2. RESULTS: No-reflow was observed in 25 patients (27.8%). Using multiple logistic regression analysis, local MMP-9 levels (odds ratio [OR] = 3.356; confidence interval [CI]: 1.441-5.881; P = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR = 6.985; CI: 2.574-11.533; P = 0.009) and time to balloon (OR = 2.143; CI: 1.216-5.901; P = 0.042). CONCLUSIONS: Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI.

Activation of SHH signaling pathway promotes vasculogenesis in post-myocardial ischemic-reperfusion injury.

This study aimed to investigate the potential roles of sonic Hedgehog (SHH) expression in vasculogenesis in post-myocardial ischemic-reperfusion injury (MIRI) and its underlying mechanism. Cardiac microvascular endothelial cells (CMECs) isolated from the SD rat hearts tissues were used to construct the MIRI model. mRNA level of SHH in control cells and MIRI cells was detected using RT-PCR analysis. Furthermore, effects of SHH expression on CMECs viability and apoptosis were analyzed using MTT assay and Annexin-V-FITC kit respectively. Moreover, effects of SHH expression on the pathway signal proteins expression was analyzed using ELISA and western blotting. mRNA level of SHH was significantly decreased compared to the controls (P<0.05). Besides, CMECs viability was significantly increased while cell apoptosis was decreased by SHH application compared with the controls (P<0.05). Vasculogenesis-related factors including VEGF, FGF and Ang were significantly increased by SHH application, as well as the SHH signal proteins including Patch-1, Gli1, Gli2 and SMO (P<0.05). However, these effects of SHH application on biological factors levels were reversed by the SHH inhibitor application. This study suggested that SHH over expression may play a pivotal contribute role in vasculogenesis through activating the SHH signals in post-MIRI.

Prospective study of effects of endogenous estrogens on myocardial no-reflow risk in postmenopausal women with acute myocardial infarction.

The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no-reflow in postmenopausal women with ST-elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal-reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C-reaction protein (Hs-CRP) were significantly higher in the no-reflow group (P < 0.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus score ≥ 4, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no-reflow (P < 0.05). After adjusting for these factors, thrombus score ≥ 4 (OR = 4.994, CI 1.987-10.518; P = 0.035), SHBG (OR = 0.800, CI 0.341-0.983; P = 0.047), and estradiol levels (OR 4.091, CI 1.105-8.582; P = 0.046) continued to demonstrate strong positive associations with the risk of no-reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no-reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no-reflow. However, our results need to be confirmed in a larger population.

The beneficial effects of postconditioning on no-reflow phenomenon after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

No-reflow phenomenon is a serious complication of percutaneous coronary intervention (PCI) which is closely related to the incidence of major adverse cardiovascular events. It has been demonstrated that Postconditioning (PostC) during primary PCI confers protection against ischemia-reperfusion injury and thus might reduce infarct size. However, whether PostC may exert its beneficial effects on acute myocardial infarction (AMI) patients by reducing no-reflow phenomenon is still unknown. Sixty two patients diagnosed with ST-elevation AMI were randomly assigned to study group (n = 32) or control group (n = 30). Blood samples were obtained and assayed for creatine kinase MB (CK-MB) and high-sensitive C-reactive protein (hs-CRP). Determinants of reflow, including final thrombolysis in myocardial infarction (TIMI) grade-3 flow, ST-segment resolution (STR), myocardial blush grades-3 (MBG-3) and corrected thrombolysis in myocardial infarction frame count (cTFC), were comparative between the two groups. Compared with control group, more patients in study group were identified as the final TIMI grade-3 flow (81.3 vs. 56.7%, P = 0.036), MBG-3 (23 vs. 14%, P = 0.043) and STR ≥50% (93.8 vs. 73.3%, P = 0.029), while patients in study group had less cTFC (28.5 ± 9.1 vs. 37.4 ± 12.4, P = 0.002) After PCI, study group was associated with lower levels of CK-MB (2,397.6 ± 470.2 vs. 2,159.9 ± 485.5, P = 0.028), Troponin-I (197.5 ± 32.5 vs. 154 ± 43.1, P = 0.041) and hs-CRP (5.5 ± 4.5 vs. 9.5 ± 5.2 mg/L, P = 0.019) in comparison with control group. Left ventricle ejection fraction was better in the study group than in the control group (55.1 ± 9.8 vs. 42.9 ± 10.7, P = 0.042). PostC could improve myocardial reperfusion in patients with ST-elevation AMI undergoing PCI by reducing no-reflow. However, due to the limited sample size, the results of our study should not be considered conclusive.

Association between local interleukin-6 levels and slow flow/microvascular dysfunction.

We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5 ± 10.3 years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5%). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135-2.268; P = 0.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (OR = 8.065, CI 1.244-52.632; P = 0.029) and thrombus score (OR = 12.500, CI 1.100-142.857; P = 0.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274-2.281, P < 0.001; optimal threshold ≥11.3 pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73% and specificity of 71%. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI.

Mutation analysis of KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 genes in Chinese patients with long QT syndrome.

Long QT syndrome (LQTS) is the prototype of the cardiac ion channelopathies, which cause syncope and sudden death. Inherited LQTS is represented by the autosomal dominant Romano-ward syndrome (RWS), which is not accompanied by congenital deafness, and the autosomal recessive Jervell and Lange-Nielsen syndrome (JLNS), which is accompanied by congenital deafness. The LQTS-causing mutations have been reported in patients and families from Europe, North America and Japan. Few genetic studies have been carried out in families with JLNS from China. This study investigates the molecular pathology in four families with LQTS (including a family with JLNS) in the Chinese population. Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, KCNE2 and SCN5A mutation. A missense mutation G314S in an RWS family was identified, and a single nucleotide polymorphism (SNP) G643S was indentified in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients. Our data provide useful information for the identification of polymorphisms and mutations related to LQTS and the Brugada Syndrome (BS) in Chinese populations.

Inhibitory effect of rhynchophylline on human ether-a-go-go related gene channel.

We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.

[Relationship between congenital long QT syndrome and Brugada syndrome gene mutation].

OBJECTIVE: To investigate the molecular pathology in families with long QT syndrome (LQTS) including Jervell-Longe-Nielsen syndrome (JLNS) and Romano-ward syndrome (RWS) and Brugada syndrome (BS) in Chinese population. METHODS: Polymerase chain reaction and DNA sequencing were used to screen for KCNQ1, KCNH2, KCNE1, and SCN5A mutation. RESULTS: We identified a novel mutation N1774S in the SCN5A gene of the BS family, a novel mutation G314S in a RWS family which had also been found in Europe, North America, and Japan, and a single nucleotide polymorphisms (SNPs) G643S in the KCNQ1 of the JLNS family. In this JLNS family, another heterozygous novel mutation in exon 2a was found in KCNQ1 of the patients. CONCLUSION: New mutations were found in our experiment, which expand the spectrum of KCNQ1 and SCN5A mutations that cause LQTS and BS.

[Mutation analysis of a Chinese family with inherited long QT syndrome].

OBJECTIVE: To identify the mutation of a Chinese family with inherited long QT syndrome(LQTS). METHODS: The disease-causing gene was tentatively determined in light of the clinical manifestations and electrophysiological properties, and then polymerase chain reaction and DNA sequencing were used for screening and identifying mutation. RESULTS: A missense mutation G940A(G314S) in the KCNQ1 gene was identified, which was the 'hot spot' of long QT syndrome mutation. CONCLUSION: The mutation that is involved with long QT syndrome in Chinese patients is the same as that in the European, American and Japanese patients.

[PCR site-directed mutagenesis of long QT syndrome KCNQ1 gene in vitro].

To study PCR site-directed mutagenesis of long QT syndrome KCNQ1 gene in vitro. The site-directed mutagenesis of LQTS gene KCNQ1 was made by PCR. Two sets of primers were designed according to the sequence of KCNQ1 cDNA, and mismatch was introduced into primers. Mutagenesis was performed in a three-step PCR. The amplified fragments from the third PCR which contained the mutation site were subcloned into the T-vecor PCR2.1. Then the fragments containing the mutation site was obtained from PCR2.1 with restriction enzyme digestion and was inserted into the same restriction site of pIRES2-EGFP-KCNQ1. With Effectene Transfection Reagent, pIRES(2)-EGFP-KCNQ1 was transfected into HEK293 cell. The sequencing analysis showed that the mutation site was correct. Mutation from T to C in 934 site of KCNQ1 cDNA was found. Under the fluorescence microscope, the green fluorescence was spread in the transfected HEK293 cell, meaning the pIRES(2)-EGFP-KCNQ1 containing the mutation site was expressed correctly.