Predictors of endothelial function improvement in patients with mild hypertriglyceridemia without evidence of coronary artery disease treated with purified eicosapentaenoic acid.

BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. METHODS: Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables. RESULTS: EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p < 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p < 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (ß = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (ß = 0.301, p = 0.048). CONCLUSIONS: EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

An Unexpected Complication of Subcutaneous ICD Implantation and its Successful Management.

Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious complications. We present a case where an inappropriate lead placement resulted in puncturing the lung parenchyma, and successful management of the lead-related pneumothorax through thoracoscopic lead removal and partial lung resection. (Level of Difficulty: Intermediate.).

Multiple coronary artery spasms triggering life-threatening ventricular arrhythmia associated with the radiofrequency ablation of ganglionated plexuses of the left atrium.

We report a case of multiple coronary spasms leading to life-threatening ventricular arrhythmia, during left atrium (LA) ablation. Coronary artery spasm is a rare complication during radiofrequency catheter ablation of atrial fibrillation (AF). Previous reports mention that autonomic imbalance leads to coronary artery spasm and ST-segment elevation in the inferior leads, during trans-septal LA catheterization and AF ablation procedures. However, there are few reports detailing the association between ablation sites and changes in the electrocardiogram. We encountered transient ST-segment elevation and refractory ventricular arrhythmia, associated with coronary artery spasm, during radiofrequency ablation of ganglionated plexuses (superior surface of left and right atrium). .

New insights into spotty calcification and plaque rupture in acute coronary syndrome: an optical coherence tomography study.

Although recent optical coherence tomography (OCT) studies have focused on spotty calcification, whether there were any characteristics in the concomitant existence of calcification and plaque rupture remains unknown. The aim of the present study was to investigate the characteristics of spotty calcification in acute coronary syndrome (ACS) patients with or without plaque rupture, using OCT. This study enrolled 98 consecutive patients with ACS. OCT image acquisitions were performed in the culprit lesions, and patients were divided into the plaque rupture group (n = 38) and the non-rupture group (n = 60). The frequency of spotty calcification (p = 0.006), thin-capped fibroatheroma (p = 0.012), macrophage infiltration (p = 0.022), and the number of spotty calcification per patient (p < 0.001) were significantly higher and the largest arc and the minimum depth of spotty calcification from the luminal surface were significantly smaller in the rupture group. Moreover, in the rupture group, most of the spotty calcifications in the site nearest to the minimum lumen area were observed in the proximal portion of that site, and tended to be located near the plaque rupture. Multivariate analysis revealed that the presence of spotty calcification (OR 3.19, 95 % CI 1.12-9.76, p = 0.030) and age (OR 1.08, 95 % CI 1.02-1.14, p = 0.008) were independent predictive factors for plaque rupture. This study demonstrates the characteristics of spotty calcification in ACS patients with plaque rupture and the positional relationship between spotty calcification and plaque rupture. These detailed observations could impact on treatment strategies for the prevention of ACS.

Vascular Functional and Morphological Alterations in Smokers during Varenicline Therapy.

BACKGROUND: Varenicline has been reported to achieve high rates of smoking cessation. It remains undetermined whether varenicline therapy improves vascular function in smokers. METHODS: Consecutive Seventy-two smokers (age 57 ± 12 years) who succeeded in complete smoking cessation and 46 normal healthy volunteers (age 24 ± 3 years) with no cardiovascular risk factors were enrolled into this study. Vascular function and structure were assessed by flow-mediated dilation (FMD), nitroglycerin-induced vasodilation, and brachial artery intima-media thickness (baIMT) at baseline and 20 weeks after the initiation of varenicline therapy in smokers. FMD and baIMT were measured simultaneously using a semi-automatic vessel wall-tracking software program. 75 µg dose of a nitroglycerin tablet were sublingually administered for the nitroglycerin-induced vasodilation measurement. RESULTS: Exhaled-carbon monoxide concentration decreased significantly (20.0 ± 11.1 ppm at baseline vs 1.9 ± 1.5 ppm after 20 weeks, p < 0.001). FMD was significantly improved after 20 weeks (4.09% ± 1.83% at baseline vs 4.77% ± 2.33% after 20 weeks, p = 0.010), whereas nitroglycerin-induced vasodilation and baIMT were not significantly changed. CONCLUSIONS: Smoking cessation with varenicline therapy significantly increased FMD without significant changes of nitroglycerin-induced vasodilation or baIMT from baseline to 20 weeks. It appears to improve vascular function in smokers, which depends on endothelial function rather than on vascular smooth muscle function or changes in vascular structure.

Insulin resistance is associated with coronary plaque vulnerability: insight from optical coherence tomography analysis.

AIMS: Previous studies have reported that insulin resistance plays an important role in the progression of atherosclerosis. However, the relationship between insulin resistance and coronary plaque instability is not well established. The purpose of this study was to assess the relationship between insulin resistance and coronary plaque characteristics identified by optical coherence tomography (OCT). METHODS AND RESULTS: This study enrolled 155 consecutive patients undergoing percutaneous coronary intervention. OCT image acquisitions were performed in the culprit lesions. Insulin resistance was identified using the homeostasis model assessment of insulin resistance (HOMA-IR). Subjects were divided into three tertiles according to the HOMA-IR values. Patients in the higher HOMA tertile had more frequent prevalence of lipid-rich plaques than those in the middle and lower tertiles (83 vs. 62 vs. 57%; P = 0.01). The thin-cap fibroatheroma (TCFA) prevalence rates among the higher (>2.5), middle (1.4-2.5), and lower HOMA-IR (<1.4) tertiles were 50, 29, and 26% (P = 0.02). The microvessel prevalence rates of the three tertiles were 54, 39, and 28% (P = 0.02). Furthermore, in the higher HOMA-IR group, the fibrous cap was significantly thinner compared with the other two tertiles (vs. lower HOMA-IR, P = 0.009; vs. middle HOMA-IR, P = 0.008). On multivariate analysis, acute coronary syndrome [odds ratio (OR): 17.98; 95% confidence interval (CI): 7.12-52.02; P < 0.0001] and HOMA-IR >2.50 (OR: 3.57; 95% CI: 1.42-9.55; P = 0.007) were independent predictors for the presence of TCFA. CONCLUSION: This study suggests that insulin resistance might be associated with coronary plaque vulnerability.

The strain pattern, and not Sokolow-Lyon electrocardiographic voltage criteria, is independently associated with anatomic left ventricular hypertrophy.

Although obesity and chest-wall thickness influence the Sokolow-Lyon electrocardiographic (ECG) voltage criteria and strain pattern, these factors have not been taken into account in previous studies that evaluate the relationship between the ECG criteria and anatomic left ventricular hypertrophy (LVH). The introduction of multislice computed tomography (MSCT) has enabled assessment of not only coronary artery stenoses but also left ventricular volume and mass, left atrial volume, and chest-wall thickness. We hypothesized that evaluating the relation between the ECG voltage criteria or strain pattern and the aforementioned factors using MSCT would be highly valuable. The study population consisted of 93 patients who required MSCT angiography. The Sokolow-Lyon voltage and strain patterns were determined to detect anatomic LVH, which was defined as increased left ventricular mass. The Sokolow-Lyon voltage criteria, as an indicator of anatomic LVH, had a sensitivity of 57 %, specificity of 67 %, positive predictive value of 36 %, and negative predictive value of 82 %. By contrast, the strain pattern had a sensitivity of 65 %, specificity of 87 %, positive predictive value of 63 %, and negative predictive value of 88 %. Multivariate analysis revealed that the strain pattern was associated with the presence of anatomic LVH, whereas the Sokolow-Lyon voltage was not. This MSCT study demonstrated that even after removing the effects of various factors, the strain pattern remained associated with the presence of anatomic LVH, in contrast to the Sokolow-Lyon voltage.

Serum n-3 to n-6 polyunsaturated fatty acids ratio correlates with coronary plaque vulnerability: an optical coherence tomography study.

A low ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) has been demonstrated to be associated with a higher risk of cardiovascular events. Optical coherence tomography (OCT) is useful for the assessment of coronary plaque vulnerability. The purpose of this study was to evaluate the association between EPA/AA ratio and coronary plaque vulnerability. This study involved 58 patients with stable angina pectoris undergoing percutaneous coronary intervention. OCT image acquisition was performed before the procedure in the culprit lesions. We assessed lipid-rich plaque length and arc, fibrous cap thickness, frequency of thin-cap fibroatheroma (TCFA), thrombus, ruptured plaque, macrophage infiltration, and microvessels using OCT. Patients were divided into two groups according to the median value of serum EPA/AA ratio: a low-EPA/AA group (n = 29, EPA/AA ratio <0.36) and a high-EPA/AA group (n = 29, EPA/AA ratio ≥0.36). In qualitative analyses, TCFA (35.4 vs 6.9 %, P = 0.0095), macrophage infiltration (48.3 vs 13.8 %, P = 0.0045), and microvessels (44.8 vs 10.3 %, P = 0.0033) were more frequently observed in the low-EPA/AA group. In quantitative analyses, the low-EPA/AA group had wider maximum lipid arc (114.0 ± 94.8° vs 56.4 ± 66.0°, P = 0.0097), longer lipid length (4.8 ± 4.5 vs 1.6 ± 2.6 mm, P = 0.0037), and thinner fibrous cap (69.3 ± 28.3 vs 113.3 ± 46.6 µm, P = 0.005) compared with the high-EPA/AA group. EPA/AA ratio was positively correlated with fibrous cap thickness (r = 0.46, P = 0.007). In a multivariate model, an EPA/AA ratio <0.36 was associated with the presence of TCFA (odds ratio 6.41, 95 % confidence interval 1.11-61.91, P = 0.0371). In our detailed OCT analysis, lower EPA/AA ratio was associated with higher vulnerability of coronary plaques to rupture.

A case of a lesion containing an intracoronary thrombus detected as hyperintense plaque on T1-weighted cardiovascular magnetic resonance in a patient with silent myocardial ischemia.

Many investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on noncontrast T1-weighted imaging (T1WI) in cardiovascular magnetic resonance indicate the presence of mural or intraplaque hemorrhage containing methemoglobin. However, coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIPs on T1WI remains unknown. Incidentally, it is very rare to find an intracoronary thrombus at the culprit lesion site in patients in stable condition. This article reports the case of a lesion containing an intracoronary thrombus, detected as HIP on T1WI associated with the filter no-reflow phenomenon in a patient with silent myocardial ischemia.

Simultaneous assessment of endothelial function and morphology in the brachial artery using a new semiautomatic ultrasound system.

The accuracy of measurements of the intima-media thickness (IMT) and flow-mediated dilatation (FMD) of the brachial artery made using a new semiautomated ultrasound system and the relationships among those parameters and the Framingham Risk Score (FRS) as a predictor of coronary heart disease (CHD) are unknown. We enrolled 70 subjects, including 47 patients with cardiovascular risk factors and 23 normal healthy volunteers. IMT and FMD were simultaneously measured using a new semiautomated ultrasound system, and the measurements were compared with those obtained manually as a reference standard (study 1). In addition, we enrolled 200 consecutive patients with risk factors but no CHD to examine the relationships among IMT, FMD and the FRS. The optimal cutoff values of FMD and IMT were determined in 200 patients without CHD, and the subjects were classified into four groups. The 10-year Framingham risks for each group were compared (study 2). FMD and IMT measurements made using the new semiautomated ultrasound system showed a good correlation with the measurements determined manually (study 1). Furthermore, FMD and IMT showed a significant correlation with the FRS. The 10-year Framingham risk was markedly higher in group D (FMD <5.5% and IMT >0.3 mm; 19.0±11.3%; study 2). In conclusion, the measurements made using a new semiautomated ultrasound system provided reliable and simultaneous evaluations of IMT and FMD. The combination of IMT and FMD measurements of the brachial artery may be beneficial for risk stratification of patients with cardiovascular risk factors but no CHD.

Typical coronary appearance of dilated cardiomyopathy versus left ventricular concentric hypertrophy: coronary volumes measured by multislice computed tomography.

Several coronary angiographic studies have reported that enlarged and tortuous epicardial coronary arteries are characteristic of patients with left ventricular concentric hypertrophy (LVCH). Recently, we showed that small volumes opacified by contrast medium can be accurately measured by 64-multislice computed tomography (MSCT) and that there is a direct relationship between the coronary artery volume and left ventricular (LV) mass. However, the relationship of coronary artery volume with LV mass in patients with dilated cardiomyopathy (DCM) is unknown. The present study was designed to investigate this issue. Thirteen patients with DCM and 18 patients with LVCH who underwent MSCT angiography were included in this analysis. The coronary arteries were segmented on a workstation, and the appropriate window settings obtained from the results of the phantom experiments were applied to the volume-rendered images to calculate the total coronary artery volume (right and left coronary arteries). The absolute coronary lengths and volumes in patients with LVCH and DCM were greater than those in controls. The coronary artery volumes adjusted for LV mass in patients with DCM were found to be smaller than those in patients with LVCH or in controls, and these values did not differ between patients with LVCH and controls (DCM 4.1 ± 0.9, LVCH 5.4 ± 1.4, controls 5.5 ± 2.3 ml/100 g of LV mass, P < 0.005; DCM vs LVCH, P < 0.01; and DCM vs control, P < 0.0005). This study showed that the increase in the coronary artery volume in patients with LVCH matched the increase in LV mass, but a decreased coronary volume with regard to LV mass was characteristic of patients with DCM.

Impact of lesion length on functional significance in intermediate coronary lesions.

BACKGROUND: Myocardial fractional flow reserve (FFR) is useful in the evaluation of coronary lesion ischemia. However, the impact of lesion length on FFR has not been adequately assessed. HYPOTHESIS: We hypothesized that lesion length would influence functional significance in intermediate coronary lesions. METHODS: FFR measurements were assessed in 136 patients (163 lesions) with stable angina who had >40% stenotic coronary lesion by quantitative coronary angiography (QCA). One hundred sixty-three lesions were classified as intermediate (40%-70% stenosis; n=107; group I) or significant (≥70%; n=56; group S) by QCA. We assessed the relationships between lesion length, coronary stenosis, and FFR in these 163 lesions. RESULTS: Regression analysis revealed an inverse correlation between the percentage of diameter stenosis (%DS) and FFR in group S (r = -0.83, P < 0.0001). In group I, no significant correlation was found between %DS and FFR (r = -0.06, P = 0.55), whereas lesion length was significantly inversely correlated with FFR (r = -0.79, P < 0.0001). Receiver operating characteristic curve analysis demonstrated that the best cutoff value for predicting an FFR value <0.80 was a lesion length >16.1 mm in group I (sensitivity, 86%; specificity, 94%). CONCLUSIONS: These study findings suggest that lesion length has a physiologically significant impact on intermediate-grade coronary lesions.

Hyperintense plaque identified by magnetic resonance imaging relates to intracoronary thrombus as detected by optical coherence tomography in patients with angina pectoris.

AIMS: Many investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on non-contrast T1-weighted imaging (T1WI) in magnetic resonance indicate the presence of mural or intraplaque haemorrhage containing methemoglobin. Coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIP on T1WI remains unknown. The aim of this study was to compare HIPs on T1WI with coronary plaque morphology assessed by optical coherence tomography (OCT), which allows us to identify not only plaque rupture, but also fibrous cap thickness and intracoronary thrombus in vivo, in patients with angina pectoris. METHODS AND RESULTS: Twenty-six lesions from 26 patients with either stable or unstable angina pectoris were examined in this study. All patients underwent T1WI within 24 h before the day on which invasive coronary angiography was performed, and pre-interventional OCT was performed on a native atherosclerotic lesion, considered to be the culprit lesion. Of the 26 lesions studied, 16 (62%) were HIPs and 10 (38%) were non-HIPs. The signal intensity of the coronary plaque to cardiac muscle ratio in HIPs was significantly higher than that in non-HIPs. There were no significant differences in the frequency of lipid-rich plaque, thin-cap fibroatheroma, plaque rupture, and calcification between HIPs and non-HIPs. In contrast, the frequency of thrombus was significantly higher in HIPs than in non-HIPs (P = 0.004). CONCLUSION: This study shows that the HIPs on T1WI in angina patients relate to the presence of intracoronary thrombus as detected by OCT imaging.

Optical coherence tomography images of bell-shaped appearance in late sirolimus-eluting stent restenosis with extension of previous incomplete stent apposition.

Late adverse events including late stent thrombosis and late catch-up phenomenon after percutaneous coronary intervention have been a serious clinical problem in the drug-eluting stent era. Recently, peri-stent contrast staining, namely extension of incomplete stent apposition was reported following drug-eluting stent implantation. Here, we report a case of late incomplete stent apposition with late stent restenosis 3 years after sirolimus-eluting stent implantation. We evaluated this restenotic site by intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Though IVUS demonstrated irregular structure within stent at the stenotic site, OCT detected unusual bell-shaped image of late stent restenosis with extension of incomplete stent apposition.