Dedicated two-stent technique in complex bifurcation percutaneous coronary intervention with use of everolimus-eluting stents: The EES-bifurcation study

Objectives

To compare the outcomes of initial one-stent (1S) versus dedicated two-stent (2S) strategies in complex bifurcation percutaneous coronary intervention (PCI) using everolimus-eluting stents (EES).

Background

PCI of true bifurcation lesions is technically challenging and historically associated with reduced procedural success and increased restenosis. Prior studies comparing initial one-stent (1S) versus dedicated two-stent (2S) strategies using first-generation drug-eluting stents have shown no reduction in ischemic events and more complications with a 2S strategy.

Methods

We performed a retrospective study of 319 consecutive patients undergoing PCI at a single referral center with EES for true bifurcation lesions, defined by involvement of both the main vessel (MV) and side branch (SB). Baseline, procedural characteristics, quantitative coronary angiography and clinical outcomes in-hospital and at one year were compared for patients undergoing 1S (n = 175) and 2S (n = 144) strategies.

Results

Baseline characteristics were well-matched. 2S strategy was associated with greater SB acute gain (0.65 ± 0.41 mm vs. 1.11 ± 0.47 mm, p < 0.0001). In-hospital serious adverse events were similar (9% with 2S vs. 8% with 1S, p = 0.58). At one year, patients treated by 2S strategy had non-significantly lower rates of target vessel revascularization (5.8% vs. 7.4%, p = 0.31), myocardial infarction (7.8% vs. 12.2%, p = 0.31) and major adverse cardiovascular events (16.6% vs. 21.8%, p = 0.21).

Conclusion

In this study of patients undergoing PCI for true coronary bifurcation lesions using EES, 2S strategy was associated with superior SB angiographic outcomes without excess complications or ischemic events at one year.     

Growth differentiation factor-15 in Takotsubo cardiomyopathy: Diagnostic and prognostic value

Background

Growth differentiation factor-15 (GDF-15), a stress responsive cytokine, has emerged as a marker of adverse outcome in various cardiovascular diseases. Since GDF-15 has not been evaluated in patients with Takotsubo cardiomyopathy (TTC), the present study sought to investigate the diagnostic and prognostic value in this patient cohort.

Methods

A total of 22 patients presenting with TTC were matched for age and gender with 22 ST-segment elevation myocardial infarction (STEMI) patients. GDF-15 concentrations were measured at admission and 1 day thereafter. The primary clinical endpoint of the TTC cohort was the composite of death, cardiogenic shock, or new congestive heart failure within 6 months.

Results

TTC patients showed significantly higher GDF-15 values on admission compared to patients presenting with STEMI (median 3047 ng/l [interquartile range 2256–7572] versus median 1527 ng/l [interquartile range 1152–2677]; p = 0.002). TTC patients with a biventricular ballooning pattern and patients experiencing major adverse cardiac events during the first 6 months after acute presentation showed significantly higher GDF-15 concentrations on admission (p = 0.008 and p = 0.005, respectively). Biventricular ballooning was identified as a predictor for elevated GDF-15 values on admission (p = 0.03). High GDF-15 levels on admission were the only significant predictor for the combined clinical endpoint in multivariable regression analysis (p = 0.02).

Conclusion

TTC patients showed markedly high, but transient elevation of GDF-15 levels. Biventricular ballooning was associated with particularly high GDF-15 concentrations. Elevated GDF-15 values on admission were a strong predictor of adverse clinical outcome.     

Three-year Follow-up of Patients With Bifurcation Lesions Treated With Sirolimus- or Everolimus-eluting Stents: SEAside and CORpal Cooperative Study

Introduction and objectives

To compare the 3-year incidence of major events in patients with bifurcation lesions treated with provisional sirolimus-eluting stents vs everolimus-eluting stents.

Methods

A pooled analysis of 2 prospective randomized trials with similar methodology (SEAside and CORpal) was performed. In these trials, 443 patients with bifurcation lesions were randomly assigned to treatment with either sirolimus-eluting stents or everolimus-eluting stents. The clinical follow-up was extended up to 3 years to assess major adverse cardiovascular events (death or acute myocardial infarction or target vessel revascularization).

Results

At 3 years, survival free of major adverse cardiovascular events was 93.2% vs 91.3% in the everolimus-eluting stent group vs the sirolimus-eluting stent group (P = .16). Exploratory land-mark analysis for late events (occurring after 12 months) showed significantly fewer major adverse cardiovascular events in the everolimus-eluting stent group: 1.4% vs 5.4% in the sirolimus-eluting stent group (P = .02).

Conclusions

Provisional stenting with either sirolimus-eluting stents or everolimus-eluting stents in bifurcation lesions is associated with low rates of major adverse events at 3-years’ follow-up. The results of a subanalysis of events beyond 1 year, showing a lower event rate with everolimus-eluting stents than with sirolimus-eluting stents, suggest that studies exploring the long-term clinical benefit of the latest generation of drug-eluting stents are warranted.     

Metabolomics signature improves the prediction of cardiovascular events in elderly subjects

Aims

Age is one of the most important determinants of cardiovascular health, therefore the management of cardiovascular diseases (CVD) in elderly people entails great challenge. A possible explanation of vascular senescence process is the mitochondrial damage and dysfunction. We hypothesized that metabolomic profiling would identify biomarkers predicting major cardiovascular events (MACEs) in elderly people, improving the clinical standard cardiovascular risk factors.

Methods and results

Targeted-mass-spectrometry-based profiling of 49 metabolites was performed in a group of very old participants (n = 67, mean age = 85 ± 3 years) with a high rate of previous CVD (68%). Principal Component Analysis, Random Survival Forest analysis and Cox proportional hazards regression modeling were used to evaluate the relation between the metabolite factors and recurring MACEs. We tested discrimination ability and reclassification of clinical and metabolomic models.At follow-up (median = 3.5 years), 17 MACEs occurred (5 cardiovascular deaths, 1 nonfatal myocardial infarction, 7 nonfatal strokes and 4 peripheral artery surgeries) (incidence = 7.3% person-years). Metabolite factor 1, composed by medium- and long-chain acylcarnitines, and factor 7 (alanine) were independently associated with MACEs, after adjustment for clinical CV covariates [HR = 1.77 (95%CI = 1.11–2.81, p = 0.016) and HR = 2.18 (95%CI = 1.17–4.07, p = 0.014), respectively]. However, only factor 1 significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 7%, p = 0.01) and correctly reclassifying 41% of events and 37% of non-events resulting in a cNRI = 0.79 (p = 0.005).

Conclusions

Aging mitochondrial dysfunction evaluated by metabolomic profiling is associated with MACEs, independently of standard predictors.     

Polymorphism in miRNA-1 target site and circulating miRNA-1 phenotype are associated with the decreased risk and prognosis of coronary artery disease

MiRNA molecules have been identified to play key roles in a broad range of physiologic and pathologic processes. Polymorphisms in microRNA target sites (PolymiRTSs) can disturb or obstruct miRNA binding and consequentially influence regulation of the target genes. A two-step study design was used in this study. A case-control study was designed to assess the relationship between miRNA-1 target site rs9548934C→T polymorphism in target gene (Component of Oligomeric Golgi Complex 6, COG6) and risk of coronary artery disease (CAD) in 1013 patients and 610 normal controls. This genetic variant was also evaluated for the association with major adverse cardiovascular events (MACE) of CAD in a follow-up study, including 785 (785/1013) patients followed up for 42 months. The phenotypes of circulating miRNA-1 levels in 34 cases were slightly lower than that of 40 controls but not significantly different (P = 0.090). The CT and CT/TT genotypes were associated with a 34% and 26% decreased risk of CAD, and the TT and CT/TT genotypes were associated with a 76% and 49% decreased risk of MACE of CAD. Cox regression analysis showed that rs9548937 C/T variant was associated with a decreased risk of MACE, while age, diabetes mellitus, higher levels of CRP (≥ 3.80 mg/L) and three pathological changes in the coronary artery were associated with an increased risk of MACE. Our findings implicate miRNA-1 target site rs9548934C→T genotypes, circulating miRNA-1 phenotype and CRP levels may modulate the occurrence and MACE of CAD.