Trends in the Detection, Management and 30-Day Outcomes of Spontaneous Coronary Artery Dissection: A Six-Year, New Zealand Centre Experience.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an important but under-recognised cause of acute coronary syndrome (ACS), particularly in younger women. We assessed trends in the detection, management and outcomes of all patients with SCAD over 6 consecutive years. METHODS: All patients with first diagnosis of SCAD at Christchurch Public Hospital, New Zealand, between January 2014 and January 2020 were included. Patient management and outcomes were determined by retrospective review of medical records. SCAD presentations were compared to total ACS presentations, obtained from a national ACS (ANZACS-QI) database. RESULTS: We identified 113 patients with angiographic diagnosis of SCAD. Median age was 54 years (88% female). The detection of SCAD increased over the period, both as a total number (Kendall's τ 0.87, p=0.015) and as a proportion of all ACS (p value for trend <0.0001). In 2019, SCAD represented 2.4% of all ACS and 18% of ACS in females aged less than 60 years. The most common presentation was non-ST elevation myocardial infarction (NSTEMI) in 72%; and, there was an increase in NSTEMI compared with STEMI over the period (p=0.023). Initial strategy of percutaneous coronary intervention (PCI) was undertaken in 12% of patients, with a significant trend towards a more conservative approach over the study period (p=0.019). The rate of 30-day major adverse cardiovascular events (MACE) was 8.8% overall, and significantly reduced over the study period to 3% in 2019 (p value for trend, 0.006). CONCLUSIONS: The detection of SCAD has increased and is a particularly important cause of ACS in younger women. This increase has been largely driven by an increasing number of NSTEMI patients diagnosed with SCAD, associated with a significant improvement in 30-day MACE.

A myeloperoxidase precursor, pro-myeloperoxidase, is present in human plasma and elevated in cardiovascular disease patients.

Myeloperoxidase (MPO)-derived oxidants have emerged as a key contributor to tissue damage in inflammatory conditions such as cardiovascular disease. Pro-myeloperoxidase (pro-MPO), an enzymatically active precursor of myeloperoxidase (MPO), is known to be secreted from cultured bone marrow and promyelocytic leukemia cells, but evidence for the presence of pro-MPO in circulation is lacking. In the present study, we used a LC-MS/MS in addition to immunoblot analyses to show that pro-MPO is present in human blood plasma. Furthermore, we found that pro-MPO was more frequently detected in plasma from patients with myocardial infarction compared to plasma from control donors. Our study suggests that in addition to mature MPO, circulating pro-MPO may cause oxidative modifications of proteins thereby contributing to cardiovascular disease.

Serial Assessment of Tissue Precursors and Progression of Coronary Calcification Analyzed by Fusion of IVUS and OCT: 5-Year Follow-Up of Scaffolded and Nonscaffolded Arteries.

OBJECTIVES: The aim of this study was to assess calcium growth with fused grayscale intravascular ultrasound (IVUS), IVUS-virtual histology, and optical coherence tomography (OCT) from baseline to 5-year follow-up in patients treated with bioresorbable vascular scaffolds. BACKGROUND: IVUS and OCT have individual strengths in assessing plaque composition and volume. Fusion of images obtained using these methods could potentially aid in coronary plaque assessment. METHODS: Anatomic landmarks and endoluminal radiopaque markers were used to fuse OCT and IVUS images and match baseline and follow-up. RESULTS: Seventy-two IVUS-virtual histology and OCT paired matched cross-sectional in- and out-scaffold segments were fused at baseline and follow-up. In total, 46 calcified plaques at follow-up were detected using the fusion method (33 in-scaffold, 13 out-scaffold), showing either calcium progression (52.2%) or de novo calcifications (47.8%). On OCT, calcification volume increased from baseline to follow-up by 2.3 ± 2.4 mm3 (p = 0.001). The baseline virtual histologic tissue precursors of dense calcium at follow-up were necrotic core in 73.9% and fibrous or fibrofatty plaque in 10.9%. In 15.2%, calcium was already present at baseline. Precursors on OCT were lipid pool in 71.2%, fibrous plaque in 4.3%, and fibrocalcific plaque in 23.9%. CONCLUSIONS: The use of OCT and IVUS fusion imaging shows similar calcium growth in- and out-scaffold segments. Necrotic core is the most frequent precursor of calcification. The scaffold resorption process creates a tissue layer that re-caps the calcified plaques. (Absorb Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Differences in neointimal thickness between the adluminal and the abluminal sides of malapposed and side-branch struts in a polylactide bioresorbable scaffold: evidence in vivo about the abluminal healing process.

OBJECTIVES: The goal of this study was to describe the neointimal healing on the abluminal side (ABL) of malapposed (ISA) struts and nonapposed side-branch (NASB) struts in terms of coverage by optical coherence tomography (OCT) and in comparison with the adluminal side (ADL). BACKGROUND: The neointimal healing on the ABL of ISA and NASB struts has never to our knowledge been explored in vivo and could be involved in the correction of acute malapposition. The bioresorbable vascular scaffold (BVS) is made of a translucent polymer that enables imaging of the ABL with OCT. METHODS: Patients enrolled in the ABSORB B (ABSORB Clinical Investigation Cohort B) study were treated with implantation of a BVS and imaged with OCT at 6 months. Thickness of coverage on the ADL and ABL of ISA and NASB struts was measured by OCT. RESULTS: Twenty-eight patients were analyzed; 114 (2.4%) struts were malapposed or at side branches. In 76 ISA struts (89.4%) and 29 NASB struts (100%), the thickness of ABL coverage was >30 µm. Coverage was thicker on the ABL than on the ADL side (101 vs. 71 µm; 95% confidence interval [CI] of the difference: 20 to 40 µm). In 70 struts (60.7%, 95% CI: 50.6% to 70.0%), the neointimal coverage was thicker on the ABL, versus only 20 struts (18.5%, 95% CI: 11.6% to 28.1%) with thicker neointimal coverage on the ADL side (odds ratio: 3.35, 95% CI: 2.22 to 5.07). CONCLUSIONS: Most of the malapposed and side-branch struts are covered on the ABL side 6 months after BVS implantation, with thicker neointimal coverage than on the ADL side. The physiological correction of acute malapposition involves neointimal growth from the strut to the vessel wall or bidirectional. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification.

OBJECTIVES: The purpose of this study is to assess jailing of side branches (SB) by the everolimus-eluting, bioresorbable vascular scaffold (BVS) with 3-dimensional (3D) optical coherence tomography (OCT) reconstruction. BACKGROUND: Because BVS struts at the SB orifice are suspected of being bioresorbed and/or forming a neointimal bridge, OCT has been used to evaluate the struts in detail at that particular site. Our understanding of the 3D relationship of the strut and the SB orifice is limited by the use of 2-dimensional OCT images. Fourier-domain OCT enables reliable 3D reconstruction of coronary vessels. METHODS: The ABSORB Cohort B (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trial is a multicenter single-arm trial to assess the safety and performance of the BVS. Fourier-domain OCT pullbacks (C7-XR system, LightLab Imaging Inc., Westford, Massachusetts) are obtained at pullback speed of 20 mm/s and 3D renderings are performed. The orifices of the SB are assessed visually. The area of SB orifice and the number of strut-free compartments delineated by the BVS struts are evaluated. RESULTS: Fifty-one OCT pullbacks were acquired: 33 pullbacks were imaged with Fourier-domain OCT and 27 treated segments had 46 side branches. Three-dimensional assessment was feasible in 87% (40 of 46) of pullbacks. The mean area of the SB orifice was 1.16 +/- 1.02 mm(2). The mean number of strut-free compartments was 2.0 +/- 1.1. The classification of the overhanging struts is proposed. CONCLUSIONS: This study demonstrates that 3D OCT reconstruction is feasible to evaluate the orifices of SB jailed with BVS. (ABSORB Clinical Investigation, Cohort B; NCT00856856).

Factors influencing local and systemic levels of plasma myeloperoxidase in ST-segment elevation acute myocardial infarction.

Myeloperoxidase (MPO) is associated with risk in acute coronary syndromes. However, the precise role it plays in ST-elevation myocardial infarction (STEMI) remains unclear. In this study we tested the hypothesis that levels of MPO in plasma after a myocardial infarction are affected by its ability to bind to the endothelium and there is local release of the enzyme at the culprit lesion. We measured plasma MPO in systemic circulation and throughout the coronary circulation in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). MPO levels at the femoral artery were higher (p <0.001) in patients with STEMI (n = 67, median 45 ng/ml, interquartile range 34 to 83) compared to control patients (n = 12, 25 ng/ml, 19 to 30) with chronic stable angina undergoing elective PCI. After administration of the anticoagulant bivalirudin in 13 patients with STEMI, plasma MPO was increased only at the culprit coronary artery lesion before PCI (178 ng/ml, 91 to 245) versus all other sites (femoral artery 86 ng/ml, 54 to 139, p = 0.019). Administration of heparin caused a marked increase of plasma MPO. Even so, it was still possible to detect an increase of plasma MPO at culprit lesion in patients with STEMI (n = 54, 171 ng/ml, 122 to 230) versus controls (n = 12, 136 ng/ml, 109 to 151, p <0.05) after heparin and before PCI. MPO levels were higher at the culprit lesion in patients with STEMI who presented early and in those with restricted flow (p <0.05). In conclusion, our results demonstrate that, in addition to a systemic increase of MPO in patients presenting early with STEMI, levels of this leukocyte enzyme are increased at the culprit coronary lesion before PCI.

One-year clinical outcome of various doses and pharmacokinetic release formulations of paclitaxel eluted from an erodable polymer - Insight in the Paclitaxel In-Stent Controlled Elution Study (PISCES).

AIMS: The one year clinical benefit of various doses and release durations of paclitaxel eluted from an erodable polymer has not been evaluated so far. METHODS AND RESULTS: Conor paclitaxel-eluting stents have intra-stent wells in which drug and polymer are deposited. Stents with six different release formulations (dose: 10 microg or 30 microg, duration: 5, 10 or 30 days, direction: mural or bidirectional) were implanted in 6 patient cohorts. Clinical follow-up was conducted at 4 and 12 months. Quantitative angiography and IVUS were performed at 4 months, and additional angiographic and IVUS follow-up were performed for groups D5 (10microg/30days/mural) and D6 (30microg/30days/mural), as they had shown the most favorable results at 4 months. At one year, the lowest major adverse cardiac event rates were observed in the slow release (30 day) group (5.1% in D5 and 6.9% in D6). One-year in-stent late loss was 0.52+/-0.34 mm in D5 and 0.36+/-0.50mm in D6 (p=0.20) while neointimal area was 0.99+/-0.54 mm2 in D5 and 0.77+/-0.92 mm2 in D6 (p=0.42). Corresponding in-stent binary restenosis at one year was 0% and 5.6% respectively (p=0.36). CONCLUSIONS: Patients who received the slow release formulation stent had better clinical outcome at one year than those who received the fast release formulation. However, the effect on neointimal suppression requires investigation in a larger population to determine whether the high dose formulation confers an additional clinical benefit.

One-year clinical outcome of various doses and pharmacokinetic release formulations of paclitaxel elutedfrom an erodable polymer - Insight in the PaclitaxelIn-Stent Controlled Elution Study (PISCES)

The one year clinical benefit of various doses and release durations of paclitaxel eluted from an erodablepolymer has not been evaluated so far.Methods and results: Conor paclitaxel-eluting stents have intra-stent wells in which drug and polymer aredeposited. Stents with six different release formulations (dose: 10 μg or 30 μg, duration: 5, 10 or 30 days,direction: mural or bidirectional) were implanted in 6 patient cohorts. Clinical follow-up was conducted at4 and 12 months. Quantitative angiography and IVUS were performed at 4 months, and additional angiographicand IVUS follow-up were performed for groups D5 (10μg/30days/mural) and D6(30μg/30days/mural), as they had shown the most favorable results at 4 months. At one year, the lowestmajor adverse cardiac event rates were observed in the slow release (30 day) group (5.1% in D5 and 6.9%in D6). One-year in-stent late loss was 0.52±0.34 mm in D5 and 0.36±0.50mm in D6 (p=0.20) whileneointimal area was 0.99±0.54 mm2 in D5 and 0.77±0.92 mm2 in D6 (p=0.42). Corresponding in-stentbinary restenosis at one year was 0% and 5.6% respectively (p=0.36).Conclusions: Patients who received the slow release formulation stent had better clinical outcome at oneyear than those who received the fast release formulation. However, the effect on neointimal suppressionrequires investigation in a larger population to determine whether the high dose formulation confers anadditional clinical benefit.

Detection of enterovirus capsid protein VP1 in myocardium from cases of myocarditis or dilated cardiomyopathy by immunohistochemistry: further evidence of enterovirus persistence in myocytes.

The association of enteroviruses with myocardial disease has been investigated extensively by molecular biological techniques to detect viral RNA, but remains controversial. This retrospective study investigated the involvement of enterovirus in myocarditis or dilated cardiomyopathy (DCM) by detection of viral antigens in myocardial samples from a new patient series using an optimized immunohistochemical technique. Formalin-fixed, paraffin-embedded biopsy, autopsy or explanted myocardial tissue samples were obtained from 136 subjects. These comprised histologically proven cases of acute fatal myocarditis (n=10), DCM (n=89, including 10 patients with healing/borderline myocarditis) and a comparison group of samples from 37 unused donor hearts and cases with other conditions. A monoclonal antibody 5-D8/1 directed against a conserved, non-conformational epitope in capsid protein VP1 was employed for broad detection of different enterovirus serotypes. Investigations were performed blindly. Histological sections from 7 of 10 fatal myocarditis cases, 47 of 89 patients (52.8%) with DCM were positive for the viral capsid protein VP1 by immunohistochemical staining. Consecutive sections of positive samples were negative when the antibody was omitted or replaced with subclass- and concentration-matched normal mouse IgG. In contrast, only 3 of 37 samples (8.1%) in the comparison group were positive (Yates corrected chi(2)=19.99, P<0.001: odds ratio =12.68). VP1 staining was distributed in individual or grouped myofibers and localized in the cytoplasm of myocytes. In some cases, VP1 was detected in only a few myofibers within an entire section. These results provide further evidence of enterovirus involvement in a high proportion of DCM cases and demonstrate that VP1 is present in disease stages from acute myocarditis, healing myocarditis to end-stage DCM requiring cardiac transplantation, indicating translation of viral protein during persistent enterovirus infection.

Vasopeptidase inhibition with omapatrilat in chronic heart failure: acute and long-term hemodynamic and neurohumoral effects.

OBJECTIVES: We investigated the acute and long-term hemodynamic and neurohumoral effects of the vasopeptidase inhibitor omapatrilat in human heart failure. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition constitutes a major advance in the treatment of chronic heart failure (CHF). Simultaneous inhibition of both neutral endopeptidase and ACE with omapatrilat may represent a new treatment strategy in CHF. METHODS: Three hundred and sixty-nine patients with symptomatic heart failure were randomized to double-blind treatment with omapatrilat (first 190 patients: 2.5 mg, 5 mg or 10 mg; last 179 patients: 2.5 mg, 20 mg or 40 mg once daily) for 12 weeks. RESULTS: Acutely, the 10 mg, 20 mg and 40 mg doses of omapatrilat produced greater reductions in pulmonary capillary wedge pressure (PCWP), systolic blood pressure (SBP) and systemic vascular resistance compared with 2.5 mg. Higher doses were associated with greater increases in vasodilator and natriuretic peptides, in addition to ACE inhibition. After 12 weeks, omapatrilat 20 mg and 40 mg showed greater falls from baseline in PCWP (40 mg: 0 h to 12 h average change -7.3 +/- 0.8 mm Hg) and SBP (40 mg: -11.7 +/- 1.7 mm Hg) than 2.5 mg (both p < 0.01 vs. 2.5 mg). The incidence of adverse experiences and patient withdrawal were similar in all groups. CONCLUSIONS: In CHF, the acute hemodynamic benefit seen with higher doses of omapatrilat was associated with increases in plasma vasodilator and natriuretic peptide levels in addition to ACE inhibition. After 12 weeks, the hemodynamic benefit was maintained. Omapatrilat may be a promising new agent in CHF.