Impact of Malondialdehyde-Modified Low-Density Lipoprotein on Tissue Characteristics in Patients With Stable Coronary Artery Disease　- Integrated Backscatter-Intravascular Ultrasound Study.

BACKGROUND: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is considered to play an essential role in plaque destabilization. We aimed to investigate the association between the tissue characteristics of culprit plaque assessed by integrated backscatter (IB)-intravascular ultrasound (IVUS) and the serum MDA-LDL levels in patients with stable coronary artery disease. METHODS AND RESULTS: The study group consisted of 179 patients undergoing IB-IVUS during elective percutaneous coronary intervention. Patients were classified into 2 groups based on serum MDA-LDL level: low MDA-LDL group (<102 U/L, n=88) and high MDA-LDL group (≥102 U/L, n=91). Plaques in the high MDA-LDL group had higher %lipid (45.2±12.5% vs. 54.9±14.5%, P<0.001) and lower %fibrosis (43.0±9.1% vs. 36.4±11.4%, P<0.001) than did plaques in the low MDA-LDL group. Lipid-rich plaque (%lipid >60% or %fibrosis <30%) was significantly more frequently found in the high MDA-LDL group than in the low MDA-LDL group (14.3% vs. 39.8%, P<0.001). The incidence of MACE (cardiac death, myocardial infarction and/or hospitalization for heart failure) during 3 years was significantly higher in the high MDA-LDL group than in the low MDA-LDL group (6.6% vs. 15.9%, P=0.02). CONCLUSIONS: Higher MDA-LDL might be associated with greater lipid and lower fibrous content, contributing to coronary plaque vulnerability. (Circ J 2016; 80: 2173-2182).

Influence of dual antiplatelet therapy on mean platelet volume in patients with coronary artery disease undergoing percutaneous coronary intervention.

Mean platelet volume (MPV) is a well-established marker of platelet activation, and recent studies have shown that platelet activation is central to the processes in the pathophysiology of coronary artery disease (CAD). The study population consisted of 45 patients with stable CAD who underwent successful percutaneous coronary intervention (PCI) with drug-eluting stents. We selected 45 age- and sex-matched control subjects without cardiovascular diseases who did not require antiplatelet therapy. Hematological test was performed 3 times within 1 month before DAPT (baseline), at 2 weeks after PCI (post PCI) and at 9 months after PCI (follow-up). Compared to control subjects, MPV was significantly larger in patients with CAD (10.0 ± 0.6 vs 10.7 ± 0.8 fl, p < 0.01) although there was no significant difference in white blood cell count, hemoglobin, and platelet count between the 2 groups. In patients with CAD, DAPT did not affect platelet count (19.3 ± 4.8 × 10(4)-18.9 ± 4.6 × 10(4)/µl) or MPV (10.7 ± 0.8-10.5 ± 0.9 fl) during the follow-up period. MPV remained to be higher at follow-up in patients with CAD despite DAPT compared to control subjects (10.1 ± 0.7 vs 10.5 ± 0.9 fl, p < 0.05). Our data suggested that MPV might not be suitable for monitoring the effects of DAPT on platelet activity in patients with CAD undergoing PCI.

Effects of the topographical extent of coronary artery ectasia on coronary blood flow in patients with aortic aneurysms.

Aortic aneurysms are associated with coronary artery ectasia (CAE). However, the relation between the extent of CAE and coronary blood flow in patients with aortic aneurysms is not fully understood. This study was undertaken to assess the angiographic characteristics and effects of the topographical extent of CAE on coronary blood flow in patients with aortic aneurysms. This study consisted of 93 consecutive patients with aortic aneurysms (AA group) and 79 patients without aortic aneurysms who had angiographically normal coronary arteries as the control group (Control group). Coronary flow velocity was determined using the thrombolysis in myocardial infarction frame count (TFC) and the topographical extent of CAE was assessed. In the AA group, 43 patients (46.2 %) had significant coronary artery stenosis and 37 patients (40.2 %) had diffuse CAE. TFC was significantly higher in the AA group than in the control group in all 3 coronary arteries. Furthermore, mean corrected TFC (CTFC) was significantly higher in the AA group than in the control group (40.1 ± 10.7 vs. 25.8 ± 6.5, p < 0.001). In the AA group, mean CTFC in patients with diffuse CAE was significantly higher than that in patients with segmental CAE (50.2 ± 8.7 vs. 33.6 ± 5.2, p < 0.001). The mean CTFC correlated positively with the topographical extent of CAE. Many patients with aortic aneurysms were accompanied with angiographic coronary artery stenosis and CAE. Furthermore, patients with aortic aneurysms had higher CTFC than those without aortic aneurysms and it was primarily driven by more frequent prevalence of diffuse CAE.

Value of resting echocardiographic findings and dobutamine stress echocardiography for diagnosing myocardial ischemia in patients with suspected angina pectoris.

BACKGROUND: We evaluated the diagnostic value of resting echocardiographic findings including total heart calcification (THC) score in combination with dobutamine stress echocardiography (DSE) for detection of myocardial ischemia. METHODS: Altogether, 110 patients with suspected angina pectoris underwent resting echocardiography and DSE. On the basis of resting echocardiography, we determined the THC score, left anterior descending artery diastole-to-systole velocity ratio (LAD-DSVR), and positive myocardial velocity during isovolumic relaxation phase (VIVR ) detected by color-coded tissue Doppler imaging. Myocardial ischemia was diagnosed by a 25% or greater reduction in the internal diameter of major coronary vessels with impaired fractional flow reserve (FFR ≤0.80). RESULTS: DSE had excellent specificity (89%) but modest sensitivity (52%) for wall-motion abnormality (WMA) analysis. Multivariate analysis showed that THC score ≥2 (odds ratio and 95% confidence interval: 4.49 [2.29-10.6]; P = 0.018), LAD-DSVR ≤1.5 (6.43 [1.39-20.3], P = 0.019), and duration of positive VIVR ≥71 msec (7.93 [3.72-12.1]; P < 0.001) were independent predictors of ischemia. The combination of inducible WMA and THC score yielded significantly higher sensitivity for ischemia detection than the inducible WMA alone (80% vs. 52%, P = 0.0008). Using receiver operating characteristics analyses, adding all three resting echocardiographic findings to clinical variables plus inducible WMA further improved prediction of ischemia (P = 0.028). CONCLUSIONS: Integration of DSE and resting echocardiographic findings describing degree of heart calcification, impaired LAD flow, and extent of delayed ejection motion of the myocardium improves detection of coronary angiogram-based FFR-guided ischemia.

Validation of automated quantification of myocardial perfusion single-photon emission computed tomography using Heart Score View in patients with known or suspected coronary artery disease.

Heart Score View (HSV) is a free software package for automated quantification of myocardial single photon emission computed tomography (SPECT) imaging using a standard Windows computer. We compared scoring results of myocardial perfusion among visual analysis, Quantitative Perfusion SPECT (QPS), and HSV in patients with known or suspected coronary artery disease.This study included 75 consecutive patients with known or suspected coronary artery disease who underwent adenosive stress-rest Tl-201 SPECT. Analysis of myocardial perfusion SPECT was performed on a standard 17-segment model visually and using QPS and HSV.There were 54 male and 21 female patients with a mean age of 70.5 ± 10.7 years. Thirteen patients (17%) had prior myocardial infarction. Summed stress score (SSS) and summed rest score (SRS) in the mid and basal areas were significantly higher on HSV than visual analysis or QPS. There was no significant difference in SDS in the whole area among the 3 methods. Similar results were found even in patients without prior myocardial infarction. Manual setting of the left ventricular cavity improved the correlations of SSS, SRS and SDS between HSV and the other methods.Our data suggested that HSV was comparable with visual analysis or QPS in scoring myocardial perfusion when manual setting of the left ventricular cavity is applied.

Effects of aliskiren on the fibrinolytic system in patients with coronary artery disease receiving angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker.

Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. We evaluated the effects of aliskiren on the fibrinolytic system in patients with coronary artery disease who were receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). We studied 17 patients with coronary artery disease whose systolic blood pressure was more than 130 mmHg despite treatment with ACEIs or ARBs. Aliskiren (150 mg) was added to ACEIs or ARBs, and was continued for 6 weeks. Aliskiren significantly decreased systolic blood pressure (140 ± 6-128 ± 8 mmHg, P < 0.001) and plasma renin activity (1.8 ± 2.3-0.6 ± 0.9 ng/ml/h, P < 0.01) after 6 weeks. However, it did not affect plasminogen activator inhibitor-1 (28.8 ± 14.5-30.6 ± 13.6 ng/ml, P = 0.84), fibrinogen (305 ± 72 vs 301 ± 71 mg/dl, P = 0.33), or D-dimer (0.49 ± 0.24-0.51 ± 0.28 µg/ml, P = 0.70) levels. Our data suggested that patients receiving ACEIs or ARBs would not be expected to have any changes in biomarkers of the fibrinolytic system with additional pharmacologic inhibition of the renin-angiotensin-aldosterone system.

Effects of lipid-lowering therapy with strong statin on serum polyunsaturated fatty acid levels in patients with coronary artery disease.

Residual risk of cardiovascular events after treatment with stain might be explained in part because patients have low levels of n-3 polyunsaturated fatty acids (PUFA). We examined how lipid-lowering therapy with strong statin affected serum PUFA levels in patients with coronary artery disease. The study population consisted of 46 patients with coronary artery disease whose low-density lipoprotein (LDL) cholesterol was more than 100 mg/dl. Lipid-lowering therapy was performed with a strong statin including atorvastatin (n = 22), rosuvastatin (n = 9) or pitavastatin (n = 15). Serum PUFA levels were determined by gas chromatography. The treatment with strong statin decreased the sum of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) levels (195 ± 41 to 184 ± 44 µg/ml, P < 0.05) as well as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels (233 ± 71 to 200 ± 72 µg/ml, P < 0.001). These effects of strong statin resulted in a significant decrease in ratio of the sum of EPA and DHA levels to the sum of DGLA and AA levels (1.20 ± 0.27 to 1.10 ± 0.35, P < 0.05). The percent decrease in the LDL cholesterol level correlated significantly with that in the sum of EPA and DHA levels (r = 0.38, P < 0.01). In conclusion, our results showed that lipid-lowering therapy with strong statin mainly reduced n-3 PUFAs in proportion to the decrease in the LDL cholesterol level in patients with coronary artery disease.

Effects of ezetimibe on serum polyunsaturated fatty acids in patients with coronary artery disease.

Residual risk of cardiovascular disease might stem, at least partially, from low serum concentrations of n-3 polyunsaturated fatty acid (PUFA). The purpose of this study was to evaluate the effects of ezetimibe on serum lipids and PU-FAs in patients with coronary artery disease who were intolerant of new or high-dose statin therapy. The study population consisted of 13 patients who were intolerant of new statin therapy and 10 patients who were intolerant of high-dose statin therapy for the treatment of low-density lipoprotein (LDL) cholesterol. Patients who were intolerant of high-dose statin therapy continued taking a statin, but at a lower dose during the study period. Blood samples were collected before and 12 weeks after ezetimibe (10 mg). We measured serum lipids and PUFAs including dihomo-γ-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid. Ezetimibe significantly decreased LDL cholesterol (138 ± 19 mg/dL to 97 ± 34 mg/dL, P < 0.01), but did not significantly affect high-density lipoprotein cholesterol, triglyceride, or any of the PUFAs measured during the follow-up period. Consequently, it did not affect the ratio of EPA to AA (0.40 ± 0.17 to 0.43 ± 0.18, P = ns) or the ratio of n-3 PUFA to n-6 PUFA (1.10 ± 0.39 to 1.09 ± 0.36, P = ns) during the follow-up period. Ezetimibe in combination with a low-dose statin, or as monotherapy in statin-intolerant patients, decreased LDL cholesterol, but did not significantly affect serum PUFA concentrations in patients with coronary artery disease.

Usefulness of post-systolic index in facilitating stratification of risk in patients with intermediate- or low-risk non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Although there is reportedly a usefulness of left ventricular global longitudinal strain (LV GLS) on 2D speckle-tracking echocardiography in excluding significant coronary artery disease (CAD) in suspected intermediate- or low-risk non-ST-segment elevation-acute coronary syndrome (NSTE-ACS), the efficacy of post-systolic index (PSI) in this context is yet unknown. Therefore, we explored the usefulness of PSI in facilitating stratification of risk in patients with intermediate- or low-risk NSTE-ACS. METHODS AND RESULTS: We assessed 50 consecutive patients suspected of intermediate- or low-risk NSTE-ACS, and finally analyzed 43 patients whose echocardiographic images were suitable for strain analysis. All patients underwent CAG. Among the 43 analyzed patients, 26 had CAD, and 21 underwent percutaneous coronary intervention (PCI). Patients with CAD had higher PSI (25% [20.8-40.3%] vs 15% [8.0-27.5%], P = 0.007). Receiver-operator characteristic curve analysis identified that a PSI of > 20% detected performance of PCI (sensitivity 80.7%, specificity 70.6%, area under curve [AUC] 0.72, 95% confidence interval [CI] 0.57-0.88). Moreover, the AUC obtained using the GRACE risk score was 0.57 (95% CI 0.39-0.75), and increased to 0.75 (95% CI 0.60-0.90) when PSI and LV GLS were added. Thus, the addition of PSI and LV GLS improved the classification of performance of PCI (net reclassification improvement [95%CI] 0.09 [0.0024-0.18], P = 0.04). CONCLUSIONS: Post-systolic index is a useful parameter that can facilitate stratification of risk in patients with intermediate- or low-risk NSTE-ACS. We recommend measuring PSI in routine clinical practice.

External side-compression of radial artery: a simple technique for successful advancement of guidewires through the radial approach.

BACKGROUND: The transradial approach has several pitfalls that include problems regarding the radial puncture and difficulties with the catheter technique. We evaluated whether external side-compression of radial artery was helpful to yield the success rate for advancement of guidewires under the presence of side branches or arterial tortuosity. METHODS AND RESULTS: The study population consisted of 11 patients with unsuccessful advancement of guidewires into the brachial artery. In 7 patients, the J-tip hydrophilic guidewire was not advanced into the brachial artery because it always directed into the side branch. During external side-compression of radial artery at the culprit site with a finger of the second operator, the guidewire was successfully advanced into the brachial artery in all patients. In 4 patients, the guidewire was not advanced into the brachial artery because the radial artery was tortuous. During external side-compression of radial artery at the culprit site, the guidewire was successfully advanced into the brachial artery in 2 patients. In the remaining 2 patients in whom this attempt was unsuccessful, coronary angiography was performed through the right brachial artery. Overall success rate of this technique was 82%. CONCLUSION: External side-compression of radial artery is an easy and feasible technique for difficulties in the advancement of guidewires due to the presence of side branches or arterial tortuosity.

Six recurrences of myocarditis in 3 years: A case report.

A recent study revealed that recurrence of myocarditis occurs in a significant proportion of patients, but multiple recurrences of myocarditis have rarely been reported. The pathophysiology and best treatments for multiple recurrences of myocarditis remain unclear. A 60-year-old man presented to our emergency department with fever and chest pain. Physical examination, imaging, and laboratory findings were consistent with fulminant myocarditis. Paired titers confirmed adenovirus infection. The patient was treated with intra-aortic balloon pump and percutaneous cardiopulmonary support for 7 days and was discharged with near-normal electrocardiographic and echocardiographic findings on day 26. Over the subsequent 3 years, the patient experienced six episodes of recurrence of myocarditis with a progressive decrease in his ability to perform activities of daily living. At the time of his sixth recurrence, he died of ventricular fibrillation. Autopsy revealed mild enlargement of the left ventricle, extensive inflammatory cell infiltration, and mild interstitial fibrosis, suggesting left ventricle remodeling because of repetitive myocarditis. We have presented a case of multiple recurrences of myocarditis. This is the largest number of recurrences in a single patient reported to date. Further studies are needed to elucidate the underlying pathogenesis and best treatment of this condition. .

Predictive value of plaque morphology assessed by frequency-domain optical coherence tomography for impaired microvascular perfusion after elective stent implantation: the intracoronary electrocardiogram study.

Aims: This study was undertaken to assess the association between plaque features at culprit lesions assessed by frequency-domain optical coherence tomography (FD-OCT) and impaired microvascular perfusion estimated by intracoronary electrocardiogram (IcECG) after elective percutaneous coronary intervention (PCI). Furthermore, we investigated whether IcECG could predict future cardiac events. Methods and results: This study consisted of 84 patients who underwent both FD-OCT and IcECG during PCI. Patients were classified into two groups based on ST-segment elevation (ST-E) on IcECG after the procedure; ST-E (-) group (n = 53) and ST-E (+) group (n = 31). Minimum fibrous cap thickness was significantly thinner in the ST-E (+) group than in the ST-E (-) group (240 µm [IQR 180 to 310] vs. 100 µm [IQR 60 to 120], P < 0.001). Plaque rupture (7.5% vs. 35.5%, P = 0.001), lipid-rich plaque (75.5% vs. 100%, P < 0.001), the thin cap fibroatheroma (0% vs. 25.8%, P < 0.001) on pre-FD-OCT, protrusion (18.9% vs. 56.7%, P < 0.001), and intra-stent dissection (15.1% vs. 50.0%, P < 0.001) on post-FD-OCT were significantly more frequently found in the ST-E (+) group than in the ST-E (-) group. The incidence of MACE (cardiac death, myocardial infarction, revascularization, hospitalization for heart failure) during 1-year was significantly higher in the ST-E (+) group than in the ST-E (-) group (5.7% vs. 19.4%, P < 0.05). Conclusion: Plaque features assessed by FD-OCT might be associated with impaired microvascular perfusion and ST-segment elevation on IcECG after the procedure could predict 1-year cardiac events after elective PCI.

A case of acute and late coronary events after blunt chest trauma: Attention to the late onset angina.

Mechanisms of acute myocardial infarction caused by traumatic coronary artery injury have been reported. However, late-onset coronary artery stenosis associated with trauma is less well known. We experienced a case in which acute myocardial infarction of the right coronary artery occurred at the time of blunt chest trauma (BCT) caused by a traffic accident and an increase in coronary artery stenosis in the left anterior descending artery (LAD) branch about 1 year later. A comparison of a volume-rendering image created from enhanced-contrast computed tomography at the time of trauma and coronary angiography revealed that the trauma site and the stenotic lesion in the LAD were in very close proximity, suggesting to us that traumatic coronary artery injury without flow limitation may have developed into high-grade stenosis in the LAD 1 year later. In this case we were able to demonstrate a causal relationship between BCT and delayed coronary artery stenosis. After BCT, it is necessary to be aware of the possibility of delayed coronary artery stenosis even if coronary injury is absent in the acute phase. .

Idiopathic left ventricular tachycardia following atrioventricular conduction block by rapid atrial tachycardia.

The present case demonstrated a rare situation alternating between a repetitive atrial tachycardia (AT) and ventricular tachycardia (VT). A unique induction mechanism was noted in which the VT was induced after Wenckebach AV node conduction block following the repetitive rapid AT.

Comparison of the cardioprotective effect of prodromal angina pectoris and collateral circulation in patients with a first anterior wall acute myocardial infarction.

To compare the cardioprotective effect of prodromal angina pectoris and collateral circulation, 245 patients with first anterior acute myocardial infarction who underwent coronary angioplasty within 12 hours of symptoms were studied. Prodromal angina pectoris and collateral circulation were independently associated with higher predischarge left ventricular ejection fraction (LVEF), and a combination of prodromal angina pectoris and collateral circulation afforded cumulative improvement in LVEF in patients without diabetes mellitus. In patients with diabetes mellitus, collateral circulation, but not prodromal angina pectoris, was associated with higher predischarge LVEF.

Impact of prodromal angina pectoris and white blood cell count on outcome of patients with acute myocardial infarction.

BACKGROUND: Elevation of white blood cell (WBC) count at admission is associated with adverse outcome after acute myocardial infarction (AMI). Prodromal angina, by the mechanism of ischemic preconditioning, improves left ventricular (LV) function and survival after reperfusion therapy in patients with AMI. Recent experimental studies have reported that preconditioning has anti-inflammatory effect. METHODS: This study consisted of 598 patients with first anterior wall AMI who underwent coronary angiography within 12 h after symptom onset. WBC count was measured at the time of hospital admission. Prodromal angina was defined as angina occurring within 24 h before the onset of AMI. Serial measurements of LV ejection fraction (EF) were obtained before reperfusion therapy and before discharge in 421 patients (71%). RESULTS: High WBC count (>10.2 x 103/mm3, n=297) was associated with higher 30-day mortality (8% vs. 4%, p=0.02) and lower predischarge LVEF (51+/-15% vs. 57+/-14%, p<0.001), although there was no significant difference in acute LVEF (47+/-10% vs. 49+/-11%, p=0.07). High WBC count was an independent predictor of 30-day mortality (p=0.009) and predischarge LVEF (p=0.002). Prodromal angina was associated with lower 30-day mortality (3% vs. 7%, p=0.02) and preserved predischarge LVEF (57+/-15% vs. 53+/-14%, p=0.006). Patients with prodromal angina had lower WBC count (10.0+/-3.3 x 10(3)/mm3 vs. 11.0+/-3.9 x 10(3)/mm3, p=0.001) and prodromal angina was an independent predictor of WBC count (p<0.001). CONCLUSIONS: Elevation of WBC count and lack of prodromal angina were associated with impaired LV function and mortality after reperfusion in patients with AMI. Prodromal angina might have contributed to favorable outcome after AMI through its anti-inflammatory effect.

Takotsubo-like transient biventricular dysfunction with pressure gradients.

A 78-year-old woman was admitted to our hospital due to chest oppressive sensation. Admission electrocardiography revealed ST-segment elevation in I, II, III, aV(F) and V(2-6) leads. Left ventriculography showed apical akinesis and basal hyperkinesis with a pressure gradient of 60 mmHg between the left ventricular apex and the base. Right ventriculography also showed similar abnormal wall motion with a pressure gradient of 28 mmHg. Follow-up cardiac catheterization after 16 days showed normal wall motion with no pressure gradients. However, dobutamine stress (10 microg/kg/min) caused a pressure gradient of 60 mmHg between the left ventricular apex and the aorta.

Impact of electrocardiographic findings for diagnosis of left ventricular hypertrophy in patients with primary aldosteronism.

BACKGROUND: Compared to patients with similar levels of hypertension, patients with primary aldosteronism have a greater left ventricular hypertrophy (LVH). The presence of LVH should be detected as early as possible to prevent cardiovascular complications associated with the condition. We evaluated comparative diagnostic value of electrocardiographic (ECG) indexes for LVH in patients with primary aldosteronism. METHODS: ECG and echocardiographic data were obtained in 88 patients with primary aldosteronism. We analyzed the four most commonly used ECG indexes, including Sokolow-Lyon index, Cornell voltage index, Cornell product index, and Gubner index. RESULTS: Echocardiographic LVH was found in 35 patients (40%). Sensitivity ranged from 0% for Gubner index to 49% for Cornell product index. Specificity ranged from 81% for Sokolow-Lyon index to 100% for Gubner index. Sokolow-Lyon index (r=0.43, p<0.001), Cornell voltage index (r=0.55, p<0.001) and Cornell product index (r=0.52, p<0.001) correlated significantly with left ventricular mass (LVM) index. No significant correlation was found between Gubner index and LVM index. CONCLUSIONS: ECG indexes had a reasonably high specificity, but a low sensitivity for LVH in patients with primary aldosteronism. Cornell voltage index and Cornell product index had a better diagnostic value of LVH, and had a better correlation with LVM index in these patients.

Acute myocardial infarction associated with myocardial bridging in a young adult.

A 28-year-old man was admitted because of chest pain. Emergency coronary angiography showed a massive thrombus in the proximal segment and another occlusive thrombus in the distal segment of the left anterior descending artery. He was treated with thrombolytic therapy. Repeat coronary angiography showed disappearance of the thrombi in the proximal and distal segments and obvious myocardial bridging in the mid segment. Intravascular ultrasound revealed an atherosclerotic plaque in the segment immediately proximal to the myocardial bridging, but did not reveal any plaque within or distal to the site. He was discharged 12 days later.