Multiparametric exercise stress cardiovascular magnetic resonance in the diagnosis of coronary artery disease: the EMPIRE trial.

BACKGROUND: Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard. METHODS: In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study. RESULTS: In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ2 for the diagnosis of FFR-positive increased from 7.6 to 55.9; P < 0.001) and excellent performance [c-statistic area under the curve 0.97 (95% CI: 0.94-1.00)] in discriminating between FFR-normal and FFR-positive patients. CONCLUSION: The study demonstrates the clinical potential of using in-scanner multiparametric ExCMR to accurately diagnose CAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03217227, Registered 11 July 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03217227?id=NCT03217227&draw=2&rank=1&load=cart.

Angiographic, optical coherence tomography and histology findings from combination of a drug-coated balloon with an everolimus-eluting stent in a porcine model.

BACKGROUND: We designed a porcine model to compare the angiographic, optical coherence tomography (OCT) and histological findings of implanting an everolimus-eluting stent (EES) in the same segment of the coronary artery pre-treated with a drug-coating balloon (DCB; paccocath as carrier) with EES alone and DCB plus a bare metal stent (BMS). METHODS: Seven female swine averaging 46.0±2.4kg were treated by random assignment as follows: DCB followed by EES; DCB followed by BMS; and EES alone. Quantitative coronary angiography (QCA) and OCT were carried out post-implantation and repeated after 28±1days. RESULTS: All arteries remained patent and demonstrated no sign of thrombus formation. There was no significant difference at 1month between the treatment groups in lumen loss (0.64±0.43, 0.44±0.43 and 0.33±0.28mm for EES, DCB/EES and DCB/BMS respectively, p=0.37) and binary restenosis (6.86 (2.91-9.12), 4.93 (-1.53-10.7) and 4.18 (3.27-10.2)% respectively, p=0.87). OCT found mean neointimal thickness of 0.15±0.09, 0.07±0.03 and 0.08±0.03mm (p=0.05) for EES, DCB/EES and DCB/BMS respectively. Endothelial strut coverage was 92.3±5.5, 85.4±8.6 and 89.1±8.9% (p=0.05) and mean neointimal area was 1.06±0.42, 0.95±0.24 and 1.20±0.28mm2 (p=0.09) respectively. Inflammation score was similar between the three groups: 0.20 (0.20-0.28), 0.30 (0.22-0.48), 0.30 (0.20-0.38) for EES, DCB/EES and DCB/BMS respectively (p=0.14) and there were no differences in fibrin deposition. CONCLUSIONS: The combination of DCB with EES appeared to be safe and effective. Using EES to bail out suboptimal DCB therapy appeared to be safe and effective in this porcine model.

Comparison of novel 6.5 Fr sheathless guiding catheters versus 5 Fr guiding catheters for transradial coronary intervention.

AIMS: To assess the safety and efficacy of a novel sheathless (SH) 6.5 Fr (French) hydrophilic-coated guiding catheter (GC) compared to the standard 5 Fr GCs in transradial coronary interventions (TRI). METHODS AND RESULTS: Patients undergoing TRI with 6.5 Fr SH or 5 Fr GCs were included. Baseline characteristics and in-hospital outcomes were recorded. Primary endpoints were procedural success and presence of radial pulse at discharge. Secondary endpoints were successful GC support, in-hospital adverse events, access-site complications, procedural duration and contrast load. There were 269 patients with 146 procedures in each group. The SH GC group had more non-ST elevation MI, in-stent restenosis, high-risk and bifurcation lesions. Procedural success in both arms was 95.2%. One patient in each group (0.7%) experienced radial artery occlusion (RAO) after TRI, without clinical sequelae. One access-site haematoma and one minor stroke occurred in the 5 Fr group (none in the SH group, both p=ns). Mean procedure time (52±21 vs. 45±21 minutes, p=0.004) and contrast load (160±45 ml vs. 140±45 ml, p=0.003) were greater in the SH group. CONCLUSIONS: Both 6.5 Fr SH GCs and 5 Fr GCs achieved high procedural TRI success with low RAO rates. The SH GC eliminated the disadvantages of the 5 Fr GC whilst maintaining the advantage of low RAO rates, and may become the GC of choice in TRI.

Different expression of large-conductance calcium-activated K+ channels in human internal mammary and radial arteries.

AIMS: In this study, we investigated and compared the electrophysiological and molecular properties of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels between human internal mammary arteries (IMA) and radial arteries (RA). METHODS AND RESULTS: IMA and RA sections were obtained from 79 patients (including 9 females) undergoing coronary artery bypass graft surgery. We examined the effects of K(+) channel blockers tetraethylammonium (TEA), iberiotoxin (IBTX), and 4-aminopyridine (4-AP) on isolated smooth muscle cells (SMCs) using patch clamping. Both TEA (1 mM) and IBTX (0.1 µM) significantly decreased K(+) currents in IMA SMCs and RA SMCs, while 4-AP (1 mM) only had a weak effect. IBTX had a greater K(+)-blocking effect on IMA SMCs than on RA SMCs. Consistently, TEA and IBTX evoked significant constriction of both intact vascular rings. IBTX had a greater constrictor effect on IMA rings (18.5 ± 6.7%, n= 8) than on RA rings (10.6 ± 3.1%, n= 8), P< 0.05. RT-PCR and western blot analysis demonstrated that gene and protein expression of the α-subunit of BK(Ca) channels from IMA was greater than that from RA. CONCLUSION: The density of BK(Ca) channels is greater in human IMA than in RA resulting in greater BK(Ca) currents in SMCs from IMA. This may partly explain the finding of less spasm in IMA grafts than in RA grafts. Our results may be of value in determining the best anti-spasm agent to use peri-operatively.

Angiopoietin: a TIE(d) balance in tumor angiogenesis.

Angiopoietins (ANG-1 and ANG-2) and their TIE-2 receptor tyrosine kinase have wide-ranging effects on tumor malignancy that includes angiogenesis, inflammation, and vascular extravasation. These multifaceted pathways present a valuable opportunity in developing novel inhibition strategies for cancer treatment. However, the regulatory role of ANG-1 and ANG-2 in tumor angiogenesis remains controversial. There is a complex interplay between complementary yet conflicting roles of both the ANGs in shaping the outcome of angiogenesis. Embryonic vascular development suggests that ANG-1 is crucial in engaging interaction between endothelial and perivascular cells. However, recruitment of perivascular cells by ANG-1 has recently been implicated in its antiangiogenic effect on tumor growth. It is becoming clear that TIE-2 signaling may function in a paracrine and autocrine manner directly on tumor cells because the receptor has been increasingly found in tumor cells. In addition, alpha(5)beta(1) and alpha(v)beta(5) integrins were recently recognized as functional receptors for ANG-1 and ANG-2. Therefore, both the ligands may have wide-ranging functions in cellular activities that affect overall tumor development. Collectively, these TIE-2-dependent and TIE-2-independent activities may account for the conflicting findings of ANG-1 and ANG-2 in tumor angiogenesis. These uncertainties have impeded development of a clear strategy to target this important angiogenic pathway. A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway.