Ruiyan Zhang

Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions Results From a Multicenter, Randomized, Prospective DKCRUSH-III Study

OBJECTIVES The study aimed to investigate the difference in major adverse cardiac event (MACE) at 1-year after double kissing (DK) crush versus Culotte stenting for unprotected left main coronary artery (UPLMCA) distal bifurcation lesions. BACKGROUND DK crush and Culotte stenting were reported to be effective for treatment of coronary bifurcation lesions. However, their comparative performance in UPLMCA bifurcation lesions is not known. METHODS A total of 419 patients with UPLMCA bifurcation lesions were randomly assigned to DK (n = 210) or Culotte (n = 209) treatment. The primary endpoint was the occurrence of a MACE at 1 year, including cardiac death, myocardial infarction, and target vessel revascularization (TVR). In-stent restenosis (ISR) at 8 months was secondary endpoint, and stent thrombosis (ST) served as a safety endpoint. Patients were stratified by SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) and NERS (New Risk Stratification) scores. RESULTS Patients in the Culotte group had significant higher 1-year MACE rate (16.3%), mainly driven by increased TVR (11.0%), compared with the DK group (6.2% and 4.3%, respectively; all p < 0.05). ISR rate in side branch was 12.6% in the Culotte group and 6.8% in the DK group (p = 0.037). Definite ST rate was 1.0% in the Culotte group and 0% in the DK group (p = 0.248). Among patients with bifurcation angle ≥70°, NERS score ≥20, and SYNTAX score ≥23, the 1-year MACE rate in the DK group (3.8%, 9.2%, and 7.1%, respectively) was significantly different to those in the Culotte group(16.5%, 20.4%, and 18.9%, respectively; all p < 0.05). CONCLUSIONS Culotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151).

A randomised comparison of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent with a durable polymer everolimus-eluting stent: clinical and angiographic follow-up of the TARGET I trial

AIMS The study sought to evaluate the safety and efficacy of FIREHAWK, a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (SES) for treating patients with single de novo coronary lesions compared with the durable polymer everolimus-eluting stent (EES) XIENCE V. METHODS AND RESULTS A total of 458 patients with single de novo native coronary lesions ≤24 mm in length and a coronary artery ≥2.25 to ≤4.0 mm in diameter were enrolled in the TARGET I study, a prospective, randomised, non-inferiority trial. The primary endpoint was in-stent late lumen loss (LLL) at nine-month follow-up. The secondary endpoint, target lesion failure (TLF), was defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or ischaemia-driven target lesion revascularisation (iTLR). Patients were centrally randomised to treatment with either biodegradable polymer SES (n=227) or durable polymer EES (n=231). The nine-month in-stent LLL of the biodegradable polymer SES was comparable to the EES group (0.13 ± 0.24 mm vs. 0.13 ± 0.18 mm, p=0.94; difference and 95% confidence interval 0.00 [-0.04, 0.04] mm; p for non-inferiority <0.0001). Cardiac death (0.4% vs. 0.0%), TVMI (1.3% vs. 1.7%), iTLR (0.4% vs. 0.4%) and TLF (2.2% vs. 2.2%) were similar between the biodegradable polymer SES and durable polymer EES groups at 12-month follow-up (all p>0.05). No definite/probable stent thrombosis was observed in both of these groups. CONCLUSIONS In the multicentre TARGET I trial, the novel abluminal groove-filled biodegradable polymer SES FIREHAWK was non-inferior to the durable polymer EES XIENCE V with respect to the primary endpoint of in-stent LLL at nine months for treating patients with single de novo coronary lesions. The incidences of clinical endpoints were low in both of the stents at 12-month follow-up. (ClinicalTrials.gov identifier: NCT01196819).

Clinical Outcome After DK Crush Versus Culotte Stenting of Distal Left Main Bifurcation Lesions: The 3-Year Follow-Up Results of the DKCRUSH-III Study.

OBJECTIVES The present study aimed to investigate the difference in major adverse cardiac events (MACE) at 3 years after double-kissing (DK) crush versus culotte stenting for unprotected left main distal bifurcation lesions (LMDBLs). BACKGROUND The multicenter and randomized DKCRUSH-III (Comparison of double kissing crush versus culotte stenting for unprotected distal left main bifurcation lesions: results from a multicenter, randomized, prospective study) showed that DK crush stenting was associated with fewer MACE at 1-year follow-up in patients with LMDBLs compared with culotte stenting. Here, we report the 3-year clinical outcome of the DKCRUSH-III study. METHODS A total of 419 patients with LMDBLs who were randomly assigned to either the DK crush or culotte group in the DKCRUSH-III study were followed for 3 year. The primary endpoint was the occurrence of a MACE at 3 years. Stent thrombosis (ST) was the safety endpoint. Patients were classified by simple and complex LMDBLs according to the DEFINITION (Definition and Impact of Complex Bifurcation Lesions on Clinical Outcomes After Percutaneous Coronary Intervention Using Drug-Eluting Stents) study criteria. RESULTS At 3 years, MACE occurred in 49 patients the culotte group and in 17 patients in the DK crush group (cumulative event rates of 23.7% and 8.2%, respectively; p < 0.001), mainly driven by increased myocardial infarction (8.2% vs. 3.4%, respectively; p = 0.037) and target-vessel revascularization (18.8% vs. 5.8%, respectively; p < 0.001) between groups. Definite ST rate was 3.4% in the culotte group and 0% in the DK crush group (p = 0.007). Complex LMDBLs were associated with a higher rate of MACE (35.3%) at 3 years compared with a rate of 8.1% in patients with simple LMDBLs (p < 0.001), with an extremely higher rate in the culotte group (51.5% vs. 15.1%, p < 0.001). CONCLUSIONS Culotte stenting for LMDBLs was associated with significantly increased rates of MACE and ST. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-11001877).

Bone marrow‑derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model

The transplantation of mesenchymal stem cells (MSCs) is considered to be a promising treatment for ischemic heart disease; however, the therapeutic effects and underlying mechanisms of action require further evaluation. Mitochondrial dysfunction is a key event in simulated ischemia/reperfusion (SI/R) injury. The purpose of the present study was to investigate the mechanism of mitochondrial transfer, which may be involved the antiapoptotic action of co-culture with MSCs. An in vitro model of simulated ischemia/reperfusion (SI/R) was used in the present study. The apoptotic indexes were significantly increased when H9c2 cardiomyocytes were induced in the SI/R group. Following co-culture with bone marrow-derived (BM)-MSCs, H9c2 cells exhibited marked resistance against the SI/R-induced apoptotic process. Besides, mitochondrial transfer via a tunneling nanotube (TNT) like structure was detected by confocal fluorescent microscopy. In addition, following pretreated with latrunculin-A (LatA), an inhibitor of TNT formation, the BM-MSCs were not able to rescue injured H9c2 cells from apoptosis, as previously observed. In conclusion, the anti-apoptotic ability of BM-MSCs may be partially attributed to the recovery of mitochondrial dysfunction in SI/R, and the formation of TNTs appears to be involved in this action of mitochondrial transfer between adjacent cells.

Morphological characteristics of severe aortic stenosis in China: imaging corelab observations from the first Chinese transcatheter aortic valve trial.

We sought to describe the morphological characteristics of aortic valve disease in a Chinese population presenting for transcatheter aortic valve replacement (TAVR).

All-Trans Retinoic Acid Ameliorates Myocardial Ischemia/Reperfusion Injury by Reducing Cardiomyocyte Apoptosis

Myocardial ischemia/reperfusion (I/R) injury interferes with the restoration of blood flow to ischemic myocardium. Oxidative stress-elicited apoptosis has been reported to contribute to I/R injury. All-trans retinoic acid (ATRA) has anti-apoptotic activity as previously reported. Here, we investigated the effects and the mechanism of action of ATRA on myocardial I/R injury both in vivo and in vitro. In vivo, ATRA reduced the size of the infarcted area (17.81±1.05% vs. 24.41±1.03%, P<0.05) and rescued cardiac function loss (ejection fraction 46.42±6.76% vs. 37.18±4.63%, P<0.05) after I/R injury. Flow-cytometric analysis and TUNEL assay demonstrated that the protective role of ATRA on myocardial I/R injury was related to its anti-apoptotic effects. The anti-apoptotic effects of ATRA were associated with partial inhibition of reactive oxygen species (ROS) production and significantly less phosphorylation of mitogen-activated protein kinases (MAPKs) including p38, JNK, and ERK. Western blot analysis also revealed that ATRA pre-treatment increased a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression (0.65 ± 0.20 vs. 0.41±0.02 in vivo) and reduced the level of receptor for advanced glycation end-products (RAGE) (0.38 ± 0.17 vs. 0.52 ± 0.11 in vivo). Concomitantly, the protective role of ATRA on I/R injury was not observed in RAGE-KO mice. The current results indicated that ATRA could prevent myocardial injury and reduced cardiomyocyte apoptosis after I/R effectively. One possible mechanism underlying these effects is that ATRA could increase ADAM10 expression and thus cleave RAGE, which is the main receptor up-stream of MAPKs in myocardial I/R injury, resulting in the down-regulation of MAPK signaling and protective role on myocardial I/R injury.

Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction

Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B‐cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B‐cell‐deficient μMT mice or CD20 antibody‐mediated B‐cell‐depleted mice. Obstructed kidneys of μMT and anti‐CD20‐treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild‐type mice. Mechanistically, anti‐CD20 attenuated UUO‐induced alterations of renal tumour necrosis factor‐α (TNF‐α), vascular cell adhesion molecule 1 (VCAM‐1) pro‐inflammatory genes, and CC chemokine ligand‐2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post‐UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early‐stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy.

IL-34 is associated with the presence and severity of renal dysfunction and coronary artery disease in patients with heart failure.

Pro-inflammatory mediators are identified in patients with heart failure (HF), some of which may be used as biomarkers with diagnostic or prognostic value. As an additional ligand of Colony Stimulating Factor-1 Receptor (CSF-1R), interleukin-34 (IL-34) has been identified as a pro-inflammatory cytokine participating in chronic heart failure (CHF). However, the potential impact of IL-34 in CHF complications remains unknown. In order to determine the clinical significance of serum IL-34 in CHF patients, especially those with kidney dysfunction and coronary artery disease (CAD) comorbid conditions, serum IL-34 was measured in 510 consecutive patients with CHF in a cross-sectional study. The present study demonstrated that higher serum IL-34 levels were associated with poorer renal function and more severe anemia in patients with CHF. After adjusting for age, gender, conventional risk factors, and other significant covariates, IL-34 positively correlated with the presence and severity of renal dysfunction (as measured by eGFR and cystatin C) on multivariable linear and logistic regression analysis. IL-34 was also demonstrated to be an independent risk factor for CAD among HF patients. In conclusion, elevated serum IL-34 levels were demonstrated to be independently associated with renal insufficiency and CAD in patients with CHF, regardless of the systolic function.

The Effect of Renin-Angiotensin-Aldosterone System Blockade Medications on Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography: A Meta-Analysis

Background Contrast-induced nephropathy (CIN) is the main complication of contrast media administration (CM) in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). There are inconsistent results in the literature regarding the effect of renin-angiotensin-aldosterone system (RAAS) blockers (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) on CIN. We evaluated the association between the administration of ACEI/ARBs and CIN, as well as the effect of ACEI/ARBs on post-procedural changes in renal function index, in patients undergoing CAG. Methods We searched Pubmed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for relevant studies. The primary search generated 893 potentially relevant articles. A total of 879 studies were excluded because they did not meet the selection criteria. Finally, 14 studies were eligible for inclusion. There were 7,288 patients that received ACEI/ARBs and 8,159 patients that received placebo or naive to ACEI/ARBs in the study. A random or a fixed effect model was used to calculate the pooled odd ratios (ORs). Results The risk of CIN was significantly increased in the ACEI/ARBs group compared to the control group (OR= 1.50, 95%CI: 1.03-2.18, P =0.03). The magnitude of association was significantly reinforced in the observational studies (OR=1.84, 95%CI 1.19-2.85, P=0.006) but not in the randomized controlled trials (OR=0.88, 95%CI 0.41-1.90 P=0.74). The summary adjusted OR of 4 observational studies was 1.56 (95%CI 1.25-1.94, P<0.0001) and was weaker than the unadjusted OR. Conclusions Although there is some evidence to suggest that the administration of RAAS blockers was associated with the increased risk of CIN in patients undergoing CAG, the robustness of our study remains weak. The results are based on small observational studies and need further validation.

Prognostic Significance of Interleukin‐34 (IL‐34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency

Background Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long‐term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin‐34 (IL‐34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL‐34 in HF remains unclear, so that the present study aimed to determine it. Methods and Results This prospective, observational study included 510 consecutive HF patients with their serum IL‐34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all‐cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL‐34 increased, determined by log‐rank tests with Kaplan–Meier curves. Serum IL‐34 was also a significant prognostic predictor of the primary end point (1.301 [1.115–1.518]; P=0.001), cardiovascular death (1.347 [1.096–1.655]; P=0.005), HF hospitalization (1.234 [1.018–1.494]; P=0.032), and all‐cause mortality (1.343 [1.115–1.618]; P=0.002) in HF as per SD increase in the log IL‐34 level after adjusting for age, sex, traditional risk factors, and N‐terminal pro‐brain natriuretic peptide. Especially, IL‐34 had a more‐significant prognostic value in HF patients with kidney impairment than those without. Conclusions IL‐34 is a significant predictor of cardiovascular death, HF hospitalization, and all‐cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL‐34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers.