Delayed recovery of coronary resistive vessel function after coronary angioplasty

AbstractObjectives. The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty.Background. The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis.Methods. Twelve men (mean age 52 ± 10 years) with singlevessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg·kg−1over 4 min) was determined from intracoronary Doppler measurement of coronary How velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients with positron emission tomography with H215O at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty.Results. The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 ± 0.41 and 1.62 ± 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2and PET3was 0.98 ± 0.16, 0.94 ± 0.09 and 0.99 ± 0.13 ml·min−1·g−1, respectively, in the remote region and 1.19 ± 0.23 (p < 0.01 vs. remote region), 1.17 ± 0.19 (p < 0.01 vs. remote region) and 1.10 ± 0.08 ml·min-1·g−1(p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2and PET3was 3.04 ± 0.68, 3.00 ± 0.71 and 3.00 ± 0.60 ml·ml·min−1g−1, respectively, in the remote region and 2.11 ± 0.80 (p < 0.01 vs. remote region), 2.28 ± 0.73 (p = NS vs. remote region) and 3.06 ± 0.86 ml · min−1· g−1(p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2and PET3was 3.15 ± 0.85, 3.18 ± 0.68 and 3.08 ± 0.75, respectively, in the remote region and 1.80 ± 0.68 (p < 0.01 vs. remote region), 1.94 ± 0.49 (p < 0.01 vs. remote region) and 2.77 ± 0.74 (p = NS vs. remote region), respectively, in the angioplasty region.Conclusions. After successful angioplasty, basal myocardial blood flow is increased for ≥7 days in the angioplasty region, with a reduction in the dipyridamole · induced increase in maximal myocardial blood flow for ≥24 h after the procedure. Thus, the coronary vasodilator response is impaired for ≥7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months

Five-year follow-up of intracoronary autologous cell therapy in acute myocardial infarction: the REGENERATE-AMI trial

Aims: The long-term outcomes of the intracoronary delivery of autologous bone marrow-derived cells (BMCs) after acute myocardial infarction are not well established. Following the promising 1 year results of the REGENERATE-AMI trial (despite it not achieving its primary endpoint), this paper presents the analysis of the 5 year clinical outcomes of these acute myocardial infarction patients who were treated with an early intracoronary autologous BMC infusion or placebo. Methods and results: A 5 year follow-up of major adverse cardiac events (defined as the composite of all-cause death, recurrent myocardial infarction, and all coronary revascularization) and of rehospitalization for heart failure was completed in 85 patients (BMC n = 46 and placebo n = 39). The incidence of major adverse cardiac events was similar between the BMC-treated patients and the placebo group (26.1% vs. 18.0%, P = 0.41). There were no cases of cardiac death in either group, but an increase in non-cardiac death was seen in the BMC group (6.5% vs. 0%, P = 0.11). The rates of recurrent myocardial infarction and repeat revascularization were similar between the two groups. There were no cases of rehospitalization for heart failure in either group. Conclusion: This 5 year follow-up analysis of the REGENERATE-AMI trial did not show an improvement in clinical outcomes for patients treated with cell therapy. This contrasts with the 1 year results which showed improvements in the surrogate outcome measures of ejection fraction and myocardial salvage index

Invasive or non-invasive imaging for detecting high-risk coronary lesions?

INTRODUCTION: Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an arsenal of invasive and non-invasive imaging modalities have been developed that are capable of identifying these features allowing in vivo assessment of plaque vulnerability. Areas covered: This review article presents the available and emerging imaging modalities introduced to assess plaque morphology and biology, describes the evidence from the first large scale studies that evaluated the efficacy of invasive and non-invasive imaging in detecting lesions that are likely to progress and cause cardiovascular events and discusses the potential implications of the in vivo assessment of coronary artery pathology in the clinical setting. Expert commentary: Invasive imaging, with its high resolution, and in particular hybrid intravascular imaging appears as the ideal approach to study the mechanisms regulating atherosclerotic disease progression; whereas non-invasive imaging is expected to enable complete assessment of coronary tree pathology, detection of high-risk lesions, more accurate risk stratification and thus to allow a personalized treatment of vulnerable patients

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 μm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization

Methylglyoxal: a novel upstream regulator of DNA methylation.

peer reviewed[en] BACKGROUND: Aerobic glycolysis, also known as the Warburg effect, is predominantly upregulated in a variety of solid tumors, including breast cancer. We have previously reported that methylglyoxal (MG), a very reactive by-product of glycolysis, unexpectedly enhanced the metastatic potential in triple negative breast cancer (TNBC) cells. MG and MG-derived glycation products have been associated with various diseases, such as diabetes, neurodegenerative disorders, and cancer. Glyoxalase 1 (GLO1) exerts an anti-glycation defense by detoxifying MG to D-lactate. METHODS: Here, we used our validated model consisting of stable GLO1 depletion to induce MG stress in TNBC cells. Using genome-scale DNA methylation analysis, we report that this condition resulted in DNA hypermethylation in TNBC cells and xenografts. RESULTS: GLO1-depleted breast cancer cells showed elevated expression of DNMT3B methyltransferase and significant loss of metastasis-related tumor suppressor genes, as assessed using integrated analysis of methylome and transcriptome data. Interestingly, MG scavengers revealed to be as potent as typical DNA demethylating agents at triggering the re-expression of representative silenced genes. Importantly, we delineated an epigenomic MG signature that effectively stratified TNBC patients based on survival. CONCLUSION: This study emphasizes the importance of MG oncometabolite, occurring downstream of the Warburg effect, as a novel epigenetic regulator and proposes MG scavengers to reverse altered patterns of gene expression in TNBC

Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis.</p> <p>Methods</p> <p>We searched the MEDLINE, EMBASE and ISI Web of Science databases (2001 to 15 July 2011). Random effects models were used to calculate summary risk ratios (RR) for restenosis. The primary endpoint was angiographic restenosis > 50%.</p> <p>Results</p> <p>A total of 7 studies enrolling 1,425 subjects were integrated in this analysis. On average across studies, the presence of a good collateralization was predictive for restenosis (risk ratio (RR) 1.40 (95% CI 1.09 to 1.80); <it>P </it>= 0.009). This risk ratio was consistent in the subgroup analyses where collateralization was assessed with intracoronary pressure measurements (RR 1.37 (95% CI 1.03 to 1.83); <it>P </it>= 0.038) versus visual assessment (RR 1.41 (95% CI 1.00 to 1.99); <it>P </it>= 0.049). For the subgroup of patients with stable coronary artery disease (CAD), the RR for restenosis with 'good collaterals' was 1.64 (95% CI 1.14 to 2.35) compared to 'poor collaterals' (<it>P </it>= 0.008). For patients with acute myocardial infarction, however, the RR for restenosis with 'good collateralization' was only 1.23 (95% CI 0.89 to 1.69); <it>P </it>= 0.212.</p> <p>Conclusions</p> <p>The risk of restenosis after percutaneous coronary intervention (PCI) is increased in patients with good coronary collateralization. Assessment of the coronary collateral circulation before PCI may be useful for risk stratification and for the choice of antiproliferative measures (drug-eluting stent instead bare-metal stent, cilostazol).</p

Mechanisms of angina pectoris in syndrome X

Syndrome X defines a group of patients who present with typical, usually exertional angina pectoris and a normal coronary arteriogram. They often have a positive exercise test, but direct signs of ischemia are detectable in only a minority of patients. A reduced coronary vasodilative response to dipyridamole or pacing is observed in such patients with or without a positive electrocardiographic exercise test. It is proposed that patients with syndrome X have a patchily distributed abnormal constriction of coronary prearteriolar vessels not involved in metabolic autoregulation of flow. An increased resistance of prearteriolar vessels can explain the reduced coronary vasodilative response observed in these patients, even when arterioles dilate maximally. Distal to the most constricted arterioles a localized compensatory increase of adenosine concentration can cause angina even in the absence of ischemia because adenosine is an algogenic substance. Ischemia can develop when myocardial metabolic demand exceeds blood supply or when metabolic or pharmacologic arteriolar vasodilation causes excessive reduction of pressure at the origin of the arterioles and possibly prearteriolar collapse.The more severe and confluent is the patchy prearteriolar constriction, the more detectable become the signs of myocardial ischemia. The proposed abnormal prearteriolar constriction could be caused by lack of endothelium-derived relaxing factor flow-mediated vasodilation, by abnormal nervous stimuli or by a combination of these two mechanisms. However, the causes of abnormal coronary prearteriolar constriction are not necessarily the same in all patients

Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension

AbstractEndothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring.Acetylcholine, calcitonin gene related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 ± 34 to 113 ± 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 ± 12 to 13 ± 8 U, with a concomitant increase in cardiac output from 3.1 ± 1 to 4.7 +- 2 liters · min−1and decrease in systemic vascular resistance from 30 ± 9 to 13 ± 4 U.Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease ia response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired ia these patients