Erika Yamamoto

Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study)

Aims Plaque erosion, compared with plaque rupture, has distinctly different underlying pathology and therefore may merit tailored therapy. In this study, we aimed to assess whether patients with acute coronary syndrome (ACS) caused by plaque erosion might be stabilized by anti-thrombotic therapy without stent implantation. Methods and results This was a single-centre, uncontrolled, prospective, proof-of concept study. Patients with ACS including ST-segment elevation myocardial infarction were prospectively enrolled. If needed, aspiration thrombectomy was performed. Patients diagnosed with plaque erosion by optical coherence tomography (OCT) and residual diameter stenosis <70% on coronary angiogram were treated with anti-thrombotic therapy without stenting. OCT was repeated at 1 month and thrombus volume was measured. The primary endpoint was >50% reduction of thrombus volume at 1 month compared with baseline. The secondary endpoint was a composite of cardiac death, recurrent ischaemia requiring revascularization, stroke, and major bleeding. Among 405 ACS patients with analysable OCT images, plaque erosion was identified in 103 (25.4%) patients. Sixty patients enrolled and 55 patients completed the 1-month follow-up. Forty-seven patients (47/60, 78.3%; 95% confidence interval: 65.8-87.9%) met the primary endpoint, and 22 patients had no visible thrombus at 1 month. Thrombus volume decreased from 3.7 (1.3, 10.9) mm3 to 0.2 (0.0, 2.0) mm3. Minimal flow area increased from 1.7 (1.4, 2.4) mm2 to 2.1 (1.5, 3.8) mm2. One patient died of gastrointestinal bleeding, and another patient required repeat percutaneous coronary intervention. The rest of the patients remained asymptomatic. Conclusion For patients with ACS caused by plaque erosion, conservative treatment with anti-thrombotic therapy without stenting may be an option.

Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2).

Despite improving success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, the clinical benefit of recanalization of CTO is still a matter of debate. Of 13,087 patients who underwent PCI in the CREDO-Kyoto registry cohort-2, 1,524 patients received PCI for CTO (CTO-PCI). Clinical outcomes were compared between 1,192 patients with successful CTO-PCI and 332 patients with failed CTO-PCI. In-hospital death tended to occur less frequently in the successful CTO-PCI group than in the failed CTO-PCI group (1.4% vs 3.0%, p = 0.053). Through 3-year follow-up, the cumulative incidence of all-cause death was not significantly different between the successful and failed CTO-PCI groups (9.0% vs 13.1%, p = 0.18), whereas the cumulative incidence of cardiac death was significantly less in the successful CTO-PCI group than in the failed CTO-PCI group (4.5% vs 8.4%, p = 0.03). However, after adjusting confounders, successful CTO-PCI was associated with lesser risk for neither all-cause death (hazard ratio 0.93, 95% confidence interval 0.64 to 1.37, p = 0.69) nor cardiac death (hazard ratio 0.71, 95% confidence interval 0.44 to 1.16, p = 0.16). The cumulative incidence of coronary artery bypass grafting (CABG) was remarkably less in patients with successful PCI compared with those with failed PCI (1.8% vs 19.6%, p <0.0001). In conclusion, successful CTO-PCI compared with failed PCI was not associated with lesser risk for 3-year mortality. However, successful CTO-PCI was associated with significantly less subsequent CABG.

High-sensitivity cardiac troponin T in essential hypertension

BACKGROUND Myocyte injury might be involved in the progression of essential hypertension (EHT) toward heart failure (HF). However, in the absence of high-sensitivity (hs) assay, cardiac troponin T (TnT) in EHT has not been measurable. METHODS AND RESULTS We studied 236 consecutive ambulatory patients (mean age=65.5 years; 110 men) with treated EHT (mean systolic blood pressure=134.3 mmHg, mean serum N-terminal pro-B-type natriuretic peptide=86.6 pg/ml) for mean 65.6 months. Patients with a history of HF were excluded. Single and multiple variable analyses were performed in search of clinical correlates of elevated hs-TnT (≥0.003 ng/ml). Serum concentration of hs-TnT was ≥0.003 ng/ml (mean=0.008 ng/ml) in 184 patients. By single variable analysis, age, uric acid, log-transformed N-terminal pro-B-type natriuretic peptide, brachial-ankle pulse wave velocity, Cornell electrocardiographic (ECG) voltage, and number of antihypertensive medications were associated with log-transformed hs-TnT, while hemoglobin and estimated glomerular filtration rate (eGFR) were inversely correlated with log-transformed hs-TnT. By multivariate analysis, age, eGFR and Cornell voltage were independent correlates of log-transformed hs-TnT, even after adjustment for clinical backgrounds including known prognostic biomarkers of EHT. CONCLUSIONS hs-TnT was ≥0.003 ng/ml in 78% of patients presenting with treated EHT and independently correlated with age, renal function, and ECG voltage of hypertrophy.

In patients with heart failure and non-ischemic heart disease, cardiac troponin T is a reliable predictor of long-term echocardiographic changes and adverse cardiac events

BACKGROUND The relationships between (1) serum concentration of cardiac troponin T (cTnT) and clinical hemodynamic profiles, (2) cTnT versus B-type natriuretic peptide (BNP) and long-term echocardiographic changes, and (3) cTnT versus BNP and echocardiographic changes, and rates of adverse cardiac events, have not been well elucidated. METHODS Retrospective analysis of 100 consecutive patients with heart failure, left ventricular ejection fraction < 50%, and non-ischemic heart disease was performed. RESULTS Baseline cTnT was > or = 0.01 ng/ml in 30 patients. By multiple variable logistic regression analysis, diabetes mellitus [DM; odds ratio (OR) 7.5; p=0.014], serum creatinine (OR 25.9; p=0.0157), and pulmonary capillary wedge pressure (PCWP; OR 1.12; p=0.0214) were independent predictors of baseline elevation of cTnT. At a follow-up of 40.6+/-20.6 months, echocardiograms and cTnT and BNP measurements were available in 93 patients, of whom 23 experienced an adverse cardiac event. By multiple variable analyses, elevated cTnT at follow-up was negatively correlated with echocardiographic improvements in cardiac function (OR 0.10; p=0.019), and was a significant predictor of adverse cardiac events after adjustment for covariables, including follow-up BNP and echocardiographic changes (hazard ratio 5.6; p=0.0046). CONCLUSIONS DM, serum creatinine, and PCWP were correlated with elevated baseline serum cTnT concentrations. cTnT concentration during follow-up might be a surrogate marker of heart failure.

Microcatheter-facilitated reverse wire technique for side branch wiring in bifurcated vessels: an in vitro evaluation.

AIMS To assess when and how the microcatheter-facilitated reverse wire technique should be applied to cross the guidewire into side branches in coronary bifurcations. METHODS AND RESULTS Three interventional cardiologists with different levels of experience performed in vitro bench testing using an originally developed coronary bifurcation simulator which had six coronary bifurcations. The bifurcation angles were 90, 105, 120, 135, 150 and 165 degrees (°). Experiment 1 was conducted to assess in what coronary bifurcation the reverse wire technique is required. Antegrade guidewire advancement was conducted with two different guidewires: the spring coil guidewire SION blue and the polymer-jacket hydrophilic guidewire Fielder FC. Experiment 2 was conducted to determine what the optimal guidewire selection and the optimal guidewire shape for the reverse wire technique would be. Assessment of the guidewire crossability into the highly angulated side branch was performed, and then the balloon crossability was assessed. A total of four guidewire types were compared in experiment 2. In experiment 1, guidewire crossing was impossible by conventional antegrade wiring when the bifurcation angle became 150° or more. In experiment 2, guidewire crossing of more than 150° of bifurcation angle was achievable independent of the guidewire types and shape. Balloon deliverability was best when using a polymer-jacket hydrophilic guidewire with a round shape 3 cm from the guidewire tip. CONCLUSIONS Although the guidewire crossing into the side branch was impossible by conventional antegrade methods when the bifurcation angle became 150° or more, the guidewire crossing into such a highly angulated side branch was easily possible using the reverse wire technique. The optimal guidewire selection for the reverse wire technique is the polymer-jacket hydrophilic guidewire with a round shape 3 cm from the guidewire tip.

Clinical, Angiographic, IVUS, and OCT predictors for Irregular Protrusion after coronary stenting.

AIMS Irregular protrusion identified by optical coherence tomography (OCT) immediately following stent implantation has been reported as an independent predictor for adverse cardiac events at one year. However, baseline characteristics for the development of irregular protrusion are unknown. The aim of the study was to identify predictors for irregular protrusion following stent implantation. METHODS AND RESULTS A total of 900 lesions in 786 patients who had post-stent OCT imaging were analysed. The patients were divided into two groups: those with (484 lesions, 456 patients) and those without (416 lesions, 330 patients) irregular protrusion. Baseline characteristics (n=786) as well as pre-stent angiogram (n=786), intravascular ultrasound (IVUS; n=31) and OCT (n=159) findings were compared between the two groups. Multivariate analysis showed that patients with irregular protrusion had higher low-density lipoprotein (LDL) cholesterol levels and lesions with greater stent length, greater percent atheroma volume on IVUS, greater lipid content and a higher prevalence of thrombus on OCT before stent implantation. CONCLUSIONS Irregular protrusion was found more frequently in patients with higher LDL cholesterol levels. In addition, lesions treated with longer stents, with greater plaque burden, larger lipid content and a higher prevalence of thrombus were identified as predictors for irregular protrusion following stent implantation.

Prediction of the true fractional flow reserve of left main coronary artery stenosis with concomitant downstream stenoses: in vitro and in vivo experiments.

AIMS The functional impact of downstream coronary stenoses on left main coronary artery (LMCA) stenosis has not been fully elucidated. This study therefore aimed to use in vitro and in vivo experiments to assess two novel equations that predict the true fractional flow reserve (FFR) of a left main coronary artery (LMCA) stenosis with concomitant downstream stenoses. METHODS AND RESULTS Two novel equations were derived. One equation predicts the true fractional flow reserve (FFR) of an LMCA stenosis with a downstream stenosis (Equation A), and the other predicts the true FFR of an LMCA stenosis with downstream stenoses in both the left anterior descending and left circumflex arteries (Equation B). The equations were validated in both in vitro and in vivo models of the coronary circulation. The agreements between the apparent FFR (FFRapp), the predicted FFR (FFRpred) and the true FFR (FFRtrue) were assessed by Passing-Bablok regression analysis. Passing-Bablok regression analysis revealed that there were fixed proportional errors between FFRapp-m and FFRtrue-m, though a very small fixed error and no proportional errors between FFRpred-m and FFRtrue-m. The absolute differences between FFRpred and FFRtrue were significantly lower as compared to those between FFRapp and FFRtrue in all experiments. CONCLUSIONS Two novel equations which predict the true FFR of LMCA stenosis were demonstrated to be correct. The study also revealed that the functional impact of downstream stenoses on the LMCA stenosis became stronger when the downstream stenoses became more severe.

Prevention of neointimal formation using miRNA-126-containing nanoparticle-conjugated stents in a rabbit model

Background Despite recent progress with drug-eluting stents, restenosis and thrombosis after endovascular intervention are still major limitations in the treatment of cardiovascular diseases. These problems are possibly caused by inappropriate inhibition of neointimal formation and retardation of re-endothelialization on the surface of the stents. miR-126 has been shown to have the potential to enhance vascular endothelial cell proliferation. Methods and results We designed and constructed a 27-nt double strand RNA (dsRNA) conjugated to cholesterol, which has high membrane permeability, and formed mature miR-126 after transfection. For site-specific induction of miR-126, we utilized poly (DL-lactide-co-glycolide) nanoparticles (NPs). miR-126-dsRNA-containing NPs (miR-126 NPs) significantly reduced the protein expression of a previously identified miR-126 target, SPRED1, in human umbilical vascular endothelial cells (HUVECs), and miR-126 NPs enhanced the proliferation and migration of HUVECs. On the other hand, miR-126 NPs reduced the proliferation and migration of vascular smooth muscle cells, via the suppression of IRS-1. Finally, we developed a stent system that eluted miR-126. This delivery system exhibited significant inhibition of neointimal formation in a rabbit model of restenosis. Conclusions miR-126 NP-conjugated stents significantly inhibited the development of neointimal hyperplasia in rabbits. The present study may indicate the possibility of a novel therapeutic option to prevent restenosis after angioplasty.

Serial measurements of high sensitive cardiac troponin I in patients with acutely decompensated heart failure treated with carperitide or nitrates.

BACKGROUND In patients with acutely decompensated heart failure (ADHF), elevated serum concentration of cardiac troponin is an independent predictor of adverse cardiac events. In ADHF with a preserved systolic blood pressure, treatment with intravenous vasodilator is recommended. However, the effect of vasodilators on troponin concentrations has not been elucidated well. METHODS AND RESULTS Serial high sensitive cardiac troponin I (hs-TnI) was measured in 36 patients presenting with ADHF and preserved systolic blood pressure, of whom 20 were treated with atrial natriuretic peptide (ANP) and 16 with nitrates. The concentrations of hs-TnI ranged from 0.069+/-0.114ng/ml at baseline to 0.076+/-0.121ng/ml at 5h, 0.062+/-0.106ng/ml at 1 day, and 0.056+/-0.089ng/ml at day 7 (n=36,ns). The relative change in hs-TnI between baseline and at 5h, day 1 and day 7 were 1.13+/-0.43, 0.95+/-0.44 and 0.93+/-0.64 in patients treated with ANP, and 1.02+/-0.19, 0.95+/-0.31 and 1.19+/-1.38 in patients treated with nitrates (ns; ANP versus nitrates). On day 7, a hs-TnI change, >20% decrease from baseline, was observed in 55% patients with ANP versus 56% patients with nitrates (ns). The cardiac event rates were similar in both groups. CONCLUSIONS In ADHF patients with preserved systolic blood pressure, the administration of intravenous vasodilators did not decrease hs-TnI over the first 7 days. Treatments with ANP and nitrates were associated with similar short-term decreases in hs-TnI and long-term adverse cardiac events.

EROSION Study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography–Based Management in Plaque Erosion): A 1-Year Follow-Up Report

Background— The initial EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography–Based Management in Plaque Erosion) demonstrated that patients with acute coronary syndrome caused by plaque erosion might be stabilized with aspirin and ticagrelor without stenting for ⩽1 month. However, a long-term evaluation of outcomes is lacking. The aim of this study was to assess whether the initial benefit of noninterventional therapy for patients with acute coronary syndrome caused by plaque erosion is maintained for ⩽1 year. Methods and Results— Among 53 patients who completed clinical follow-up, 49 underwent repeat optical coherence tomography imaging at 1 year. Median residual thrombus volume decreased significantly from 1 month to 1 year (0.3 mm3 (0.0–2.0 mm3] versus 0.1 mm3 [0.0–2.0 mm3]; P=0.001). Almost half of the patients (46.9%) had no residual thrombus at 1 year. Minimal effective flow area remained unchanged (2.1 mm2 [1.5–3.8 mm2] versus 2.1 mm2 [1.6–4.0 mm2]; P=0.152). Among 53 patients, 49 (92.5%) remained free from major adverse cardiovascular event for ⩽1 year: 3 (5.7%) patients required revascularization because of exertional angina and 1 (1.9%) patient had gastrointestinal bleeding. Conclusions— One-year follow-up optical coherence tomography demonstrated a further decrease in thrombus volume between 1-month and 1-year follow-up. A majority (92.5%) of patients with acute coronary syndrome caused by plaque erosion managed with aspirin and ticagrelor without stenting remained free of major adverse cardiovascular event for ⩽1 year. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02041650.