Diagnostic significance of paradoxical left ventricular hypertrophy in detecting cardiac amyloidosis.

Background: Cardiac amyloidosis (CA) progresses rapidly with a poor prognosis. Therefore, methods for early diagnosis that are easily accessible in any hospital, are required. We hypothesized that based on the pathology of CA, morphological left ventricular hypertrophy (LVH) without electrical augmentation, namely paradoxical LVH, could be used to diagnose CA. This study aimed to investigate whether paradoxical LVH has diagnostic significance in identifying CA in patients with LVH. Methods: Patients who presented with left ventricular (LV) wall thickness ≥ 12 mm on cardiac magnetic resonance (CMR) were enrolled from a multicentre CMR registry. Paradoxical LVH was defined as a LV wall thickness ≥ 12 mm on CMR, SV1 + RV5 < 3.5 mV, and a lack of secondary ST-T abnormalities. The diagnostic significance of paradoxical LVH in identifying CA was assessed. Results: Of the 110 patients enrolled, 30 (27 %) were diagnosed with CA and 80 (73 %) with a non-CA aetiology. The CA group demonstrated paradoxical LVH more frequently than the non-CA group (80 % vs. 16 %, P < 0.001). It was an independent predictor for detecting CA in patients with LVH (odds ratio: 33.44, 95 % confidence interval: 8.325-134.3, P < 0.001). The sensitivity, specificity, positive predict value, negative predict value and accuracy of paradoxical LVH for CA detection were 80 %, 84 %, 65 %, 92 % and 83 %, respectively. Conclusions: Paradoxical LVH can be used for identifying CA in patients with LVH. Our findings could contribute to the early diagnosis of CA, even in non-specialized hospitals.

Impact of pulmonary vein anatomy and left atrial size on postoperative atrial fibrillation after esophagectomy for esophageal cancer.

BACKGROUND: This study aimed to investigate the relationship between postoperative atrial fibrillation (POAF) after esophagectomy and pre-existing cardiac substrate. METHODS: We retrospectively analyzed 212 consecutive patients from between July 2010 and December 2022 who were scheduled to undergo esophagectomy for esophageal cancer without previous history of atrial fibrillation. All the patients underwent both echocardiography and contrast-enhanced multi-detector computed tomography (MDCT). RESULTS: POAF occurred in 49 patients (23.1%). Multivariable logistic analysis demonstrated that independent predictors for POAF were age [OR; 1.06 (1.01-1.10), P < 0.01), three-field lymph node dissection [OR; 2.55 (1.25-5.23), P < 0.01), left atrial dilatation (> 35 mm) assessment by echocardiography [OR; 3.05 (1.49-6.25), P < 0.01) and common left pulmonary vein [OR; 3.03 (1.44-6.39), P < 0.01). The correlation coefficient was high for left atrial dimensions assessed by echocardiography and MDCT (r = 0.91, P < 0.01). Combination of left atrial dilatation by echocardiography and common left pulmonary vein had high odds ratio [OR; 8.10 (2.62-25.96), P < 0.01). Instead of echocardiographic assessment, combination of left atrial enlargement (> 35 mm) assessed by MDCT and common left pulmonary vein also showed high odds ratio for POAF [OR; 11.23 [2.19-57.63], P < 0.01). CONCLUSION: Incidence of POAF after esophagectomy was related to both left atrial enlargement and common left pulmonary vein assessed by preoperative MDCT. Additional analysis of atrial size and pulmonary vein variation would facilitate preoperative assessment of the risk of POAF, but future studies must ascertain therapeutic strategy.

Relationship between postoperative atrial fibrillation and its recurrence after lung resection.

PURPOSE: Atrial fibrillation (AF) frequently occurs after pulmonary resection and is commonly referred to as postoperative atrial fibrillation (POAF). This study explored whether or not POAF is related to the recurrence of AF in the chronic phase. METHODS: A total of 1311 consecutive patients without a history of AF who underwent lung resection based on a diagnosis of lung tumor were retrospectively analyzed. RESULTS: POAF occurred in 46 patients (3.5%), and a logistic regression analysis revealed that the age (p < 0.05), history of hyperthyroidism (p < 0.05), and major lung resection (p < 0.05) were independent predictors of POAF. AF events in the chronic phase were observed in 15 (32.6%) and 45 (3.6%) patients with and without POAF, respectively. A Cox regression analysis revealed that POAF was the only independent predictor of AF development in the chronic phase (p < 0.01). The Kaplan-Meier curve and log-rank test revealed that the cumulative incidence of AF in the chronic phase was significantly higher in patients with POAF than in those without POAF (p < 0.01). CONCLUSION: POAF was an independent predictor for AF in the chronic phase after lung resection. Further investigations including cases of catheter ablation and optimal medical therapy for patients with POAF after lung resection are needed.

Risk Factors for Chronic Atrial Fibrillation Development After Esophagectomy for Esophageal Cancer.

BACKGROUND: This study investigates the prognosis of patients with postoperative atrial fibrillation (POAF), aiming to elucidate predictors of occurrence of atrial fibrillation (AF) in the chronic phase after esophagectomy. METHODS: We retrospectively analyzed 415 consecutive patients between July 2010 and December 2021 who were scheduled to undergo esophagectomy for esophageal cancer and had no previous history of AF. RESULTS: POAF occurred in 73 patients (18%). Their ages were higher than those without POAF (72 [66-77] vs 68 [62-75], P < 0.01). Three-field lymph node dissection was more frequent in patients with POAF (63% vs 50%, P = 0.04). Overall survival rates were not significantly different between those with and without POAF in patients with stage III/IV cancer (P = 0.37), but overall survival rate of patients with POAF was lower than in those without POAF in stage I/II cancer (P = 0.03). Seventeen patients (4.1%) had recurrence of AF or new onset 31 days after esophagectomy. POAF was the only independent predictor of AF development in the chronic phase (HR: 4.09, 95%CI: [1.42-11.74], P = 0.01). AF development in the chronic phase was observed in 8 patients (11.0%) with and 9 patients (2.6%) without POAF (P < 0.01). AF development rates were not significantly different in patients with stage III/IV cancer (P = 0.05), but there was significant difference in patients with stage I/II cancer (P < 0.01). CONCLUSION: The occurrence of POAF after esophagectomy is related with future development of AF and overall survival prognosis. Future studies must ascertain optimal therapeutic strategy.

Significance of in vitro photodynamic cytodiagnosis with 5-aminolevulinic acid in biliary brush cytology for malignant biliary stricture.

BACKGROUND: For the early diagnosis of malignant biliary stricture due to biliary-pancreatic carcinoma, conventional biliary brush cytology with endoscopic retrograde cholangiopancreatography (ERCP; the conventional method) is not sensitive enough. METHODS: Two hundred nine patients with biliary stricture who were admitted between September 2015 and June 2020 were enrolled in this study. Biliary brush cytology was performed on all patients. Samples were diagnosed independently by an expert pathologist and medical doctor with conventional cytology and photodynamic diagnosis (PDD) with 5-aminolevulinic acid. RESULTS: The definitive diagnoses were 49 benign and 160 malignant diseases. The conventional method had a sensitivity of 77.5% (124/160) and specificity of 100% (49/49). The PDD method had a sensitivity of 77.5% (124/160) and specificity of 67.3% (33/49). The conventional method identified 36 malignant diseases as false negatives, while the PDD method enabled successful diagnoses of malignant diseases in 19 of these 36 patients. When PDD was combined with the conventional method, the sensitivity significantly increased to 89.4% (143/160, P = 0.006), and for biliary tract diseases only, the sensitivity increased to 95.6% (88/92, P = 0.001). CONCLUSIONS: Malignant biliary stricture can be diagnosed effectively and safely with the in vitro PDD method. The sensitivity could be further increased by combining PDD with the conventional method.

Real-time venography-guided extrathoracic puncture technique for cardiovascular implantable electronic device implantation.

Central venous access is an essential technique for cardiovascular implantable electronic device (CIED) implantation, and the use of axillary vein approach has recently been increasing. This study sought to examine whether real-time venography-guided extrathoracic puncture facilitates the procedure. We retrospectively analyzed 179 consecutive patients who underwent CIED implantation using the axillary vein puncture method. Patients were divided into two groups: the conventional method group (CG, n = 107) and the real-time venography-guided group (RG, n = 82). The application of real-time venography was at the discretion of individual operators. Operators with experience of less than 50 CIED implantations were defined as inexperienced operators in this study. Puncture duration and number of attempts were significantly less in the RG group than in the CG group (283 ± 198 vs. 421 ± 361 s, p < 0.01, and 3.19 ± 2.00 vs. 4.18 ± 2.85, p < 0.01). These benefits of real-time venography were observed in inexperienced operators, but not in experienced operators. In addition, the success rate without extra attempts at puncture was higher in the RG group (54% vs. 32%, p < 0.01). Although the total amount of contrast medium was higher in the RG group (16.3 ± 4.1 mL vs. 11.9 ± 6.6 mL, p < 0.01), serum levels of creatinine pre- and post-operation were not different in the two groups (p = NS). We concluded that real-time venography is a safe and effective method for axillary vein puncture, especially in inexperienced operators.

Oral Zinc Supplementation Decreases the Risk of HCC Development in Patients With HCV Eradicated by DAA.

We have reported that the plasma zinc concentration gradually decreases with the progression of fibrosis and is related to hepatocellular carcinoma (HCC) development. The aim of this study was to examine the impact of the zinc concentration on HCC development (study 1) and the relationship between zinc intake and HCC development (study 2) in patients with hepatitis C virus (HCV) eradicated by direct-acting antivirals (DAAs). A total of 599 sustained virological response (SVR) patients treated with DAAs without a history of HCC were retrospectively analyzed in this study. Eighty patients received supplemental zinc (Zn treatment group), and 519 patients did not receive zinc (no Zn treatment group). In study 1, the cumulative incidence rate of HCC was compared between the Zn treatment group and the no Zn treatment group. In study 2, the risk factors for HCC development were examined in the no Zn treatment group. In study 1, in the Zn treatment group, HCC did not develop during follow-up, and the cumulative risk of HCC was significantly lower in the Zn treatment group than in the no Zn treatment group (P = 0.048). In study 2, the 1-year and 3-year cumulative incidence rates of HCC were 1.8% and 5.6%, respectively. The risk factors for HCC identified by multivariate analysis were male sex, cirrhosis, low platelet count before treatment, and low serum zinc concentration 12 weeks after the end of DAA therapy. Conclusion: The Zn concentration is related to HCC development in patients with HCV eradicated by DAA therapy. Oral zinc supplementation is recommended as a means of suppressing HCC development in patients who have achieved SVR.

Cancer-related vulnerable lesions in patients with stable coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) has become a major cause of morbidity and mortality in cancer survivors. It is still unclear whether cancer history influences lesion characteristics. The purpose of this study was to investigate cancer-related lesion morphology in patients with CAD. METHODS: This study enrolled 400 patients with stable CAD. The patients were classified into a cancer survivor group (n = 69) and a noncancer group (n = 331). We investigated coronary lesion morphology by optical coherence tomography, and we assessed the prognosis in terms of both all-cause mortality and major adverse cardiovascular events (MACE). RESULTS: Adenocarcinoma was the most common histopathological diagnosis. Serum C-reactive protein levels were significantly higher in the cancer survivor group than in the noncancer group (cancer survivors 0.12 [0.05-0.42] mg/dL vs. noncancer 0.08 [0.04-0.17] mg/dL, p = 0.019). The cancer survivor group was more likely than the noncancer group to have thrombi (cancer survivors 30.4% vs. noncancer 15.4%, p = 0.004), and layered fibrotic plaques (LFPs; cancer survivors 18.8% vs. noncancer 3.6%, p < 0.0001). Cancer survivors had poorer outcomes than noncancer controls in terms of both all-cause mortality (p = 0.020) and MACE (p = 0.036). CONCLUSIONS: Because of underlying inflammation, CAD patients with cancer had more high-risk lesions than those without cancer, which could result in poorer prognosis for the former. This result might inform the management of CAD in cancer patients in terms of secondary prevention.

Impact of left ventricular ejection fraction and preoperative hemoglobin level on perioperative adverse cardiovascular events in noncardiac surgery.

The prediction of a perioperative adverse cardiovascular event (PACE) is an important clinical issue in the medical management of patients undergoing noncardiac surgery. Although several predictors have been reported, simpler and more practical predictors of PACE have been needed. The aim of this study was to investigate the predictors of PACE in noncardiac surgery. We retrospectively analyzed 723 patients who were scheduled for elective noncardiac surgery and underwent preoperative examinations including 12-lead electrocardiography, transthoracic echocardiography, and blood test. PACE was defined as cardiac death, non-fatal myocardial infarction, unstable angina, congestive heart failure, arrhythmia attack that needs emergency treatment (rapid atrial fibrillation, ventricular tachycardia, and bradycardia), acute pulmonary embolism, asystole, pulseless electrical activity, or stroke during 30 days after surgery. PACE occurred in 54 (7.5%) of 723 patients. High-risk operation (11% vs. 3%, p = 0.003) was more often seen, left ventricular ejection fraction (LVEF) (55 ± 8% vs. 60 ± 7%, p = 0.001) and preoperative hemoglobin level (11.8 ± 2.2 g/dl vs. 12.7 ± 2.0 g/dl, p = 0.001) were lower in patients with PACE compared to those without PACE. By multivariate logistic regression analysis, high-risk operation (odds ratio (OR): 7.05, 95% confidence interval (CI) 2.16-23.00, p = 0.001), LVEF (OR 1.06, every 1% decrement, 95% CI 1.03-1.09, p = 0.001), and preoperative hemoglobin level (OR 1.22, every 1 g/dl decrement, 95% CI 1.07-1.39, p = 0.003) were identified as independent predictors of PACE. Receiver operating characteristic analysis demonstrated that LVEF of 58% (sensitivity = 80%, specificity = 61%, area under the curve (AUC) = 0.723) and preoperative hemoglobin level of 12.2 g/dl (sensitivity = 63%, specificity = 64%, AUC = 0.644) were optimal cut-off values for predicting PACE. High-risk operation, reduced LVEF, and reduced preoperative hemoglobin level were independently associated with PACE in patients undergoing noncardiac surgery.

Impact of instantaneous wave-free ratio on graft failure after coronary artery bypass graft surgery.

BACKGROUND: We aimed to assess an impact of instantaneous wave-free ratio (iFR) on a graft failure after coronary artery bypass grafting (CABG). METHODS AND RESULTS: A total of 131 coronary arteries from 88 patients who underwent invasive coronary angiography, intracoronary pressure measurements, CABG, and scheduled follow-up coronary computed tomography angiography within one year were investigated. All studied arteries had FFR <0.80. The rate of graft failure was significantly higher in vessels with negative iFR (>0.89) than in those with positive iFR (<0.89) (25.7% vs. 7.3%, p = 0.012). The graft failure rates increased as the preoperative iFR values rose (iFR <0.80, 3.3%; iFR: 0.80-0.84, 5.6%; iFR: 0.85-0.89, 16.0%; iFR: 0.90-0.94, 28.0%; and iFR: 0.95-1.00, 50.0%; p = 0.002). A cut-off value of iFR to predict graft failures was determined as 0.84 by receiver-operating characteristic curve analysis with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88%, 62%, 25%, 97%, and 66%, respectively. CONCLUSIONS: The risk of graft failure becomes higher, as the preoperative iFR increases. The graft failure is significantly more frequent when a bypass graft is anastomosed on vessels with negative iFR than those with positive iFR.

Molecular Imaging of Apoptosis in Atherosclerosis by Targeting Cell Membrane Phospholipid Asymmetry.

BACKGROUND: Apoptosis in atherosclerotic lesions contributes to plaque vulnerability by lipid core enlargement and fibrous cap attenuation. Apoptosis is associated with exteriorization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the cell membrane. Although PS-avid radiolabeled annexin-V has been employed for molecular imaging of high-risk plaques, PE-targeted imaging in atherosclerosis has not been studied. OBJECTIVES: This study sought to evaluate the feasibility of molecular imaging with PE-avid radiolabeled duramycin in experimental atherosclerotic lesions in a rabbit model and compare duramycin targeting with radiolabeled annexin-V. METHODS: Of the 27 rabbits, 21 were fed high-cholesterol, high-fat diet for 16 weeks. Nine of the 21 rabbits received 99mTc-duramycin (test group), 6 received 99mTc-linear duramycin (duramycin without PE-binding capability, negative radiotracer control group), and 6 received 99mTc-annexin-V for radionuclide imaging. The remaining normal chow-fed 6 animals (disease control group) received 99mTc-duramycin. In vivo microSPECT/microCT imaging was performed, and the aortas were explanted for ex vivo imaging and for histological characterization of atherosclerosis. RESULTS: A significantly higher duramycin uptake was observed in the test group compared with that of disease control and negative radiotracer control animals; duramycin uptake was also significantly higher than the annexin-V uptake. Quantitative duramycin uptake, represented as the square root of percent injected dose per cm (√ID/cm) of abdominal aorta was >2-fold higher in atherosclerotic lesions in test group (0.08 ± 0.01%) than in comparable regions of disease control animals (0.039 ± 0.0061%, p = 3.70·10-8). Mean annexin uptake (0.060 ± 0.010%) was significantly lower than duramycin (p = 0.001). Duramycin uptake corresponded to the lesion severity and macrophage burden. The radiation burden to the kidneys was substantially lower with duramycin (0.49% ID/g) than annexin (5.48% ID/g; p = 4.00·10-4). CONCLUSIONS: Radiolabeled duramycin localizes in lipid-rich areas with high concentration of apoptotic macrophages in the experimental atherosclerosis model. Duramycin uptake in atherosclerotic lesions was significantly greater than annexin-V uptake and produced significantly lower radiation burden to nontarget organs.

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.

Rat Model of Cardiotoxic Drug-Induced Cardiomyopathy.

Cardiotoxicity from cancer drugs remains a clinical problem. To find reliable markers of cardiotoxicity, animal models were proposed and potential new diagnostic markers have been actively investigated using these models. Here we describe our protocols, using male Sprague-Dawley rats, for inducing cardiomyopathy by single injection of high-dose doxorubicin (5-10 mg/kg) or multiple injections (2-4 times) of low-dose doxorubicin (2.5 mg/kg) with combined single injection of trastuzumab (10 mg/kg). The cardiotoxicity is evaluated by imaging modalities (echocardiography and nuclear imaging), serum troponin levels, and histopathological analyses.

Noninvasive assessment of left ventricular end-diastolic pressure by deceleration time of early diastolic mitral annular velocity in patients with heart failure.

OBJECTIVE: To examine the diagnostic ability of the deceleration time of early mitral annular velocity (e'DT) as determined by tissue Doppler velocity image, a method for assessing LV filling pressure. BACKGROUNDS: Estimation of LV filling pressure by Doppler echocardiography requires a combination of various parameters. Therefore, there remains a need for a simple index in LV filling pressure estimation. The e' is known to be reduced and delayed with increased LV filling pressure during development of heart failure. Thus, we hypothesized that e'DT would be shortened as LV filling pressure is increased. METHODS: Simultaneous LV end-diastolic pressure (LVEDP) measurement and Doppler echocardiography were performed in 94 patients who were admitted to our hospital for heart failure. Exclusion criteria were atrial fibrillation, mitral valve surgery, and acute coronary syndrome. RESULTS: The e'DT in 31 patients with LVEDP >16 mm Hg (68±13 ms) was significantly shorter than that in 63 patients with LVEDP ≤16 mm Hg (103±27 ms). Both e'DT and early transmitral flow velocity (E)/e' were significantly correlated with LVEDP. In 30 patients with 10-14 E/e', significance of correlation in e'DT was remained, while E/e' was not. The area under the ROC curve for prediction of LVEDP >16 mm Hg for e'DT was greater than that for E/e' (0.91 vs 0.74, P=.046). CONCLUSION: The e'DT is useful to assess LV filling pressure, especially in 10-14 E/e'. This simple tissue Doppler index may be a potential parameter for easily distinguishing between mild and severe heart failures.

Myocardial Damage Detected by Two-Dimensional Speckle-Tracking Echocardiography in Patients with Extracardiac Sarcoidosis: Comparison with Magnetic Resonance Imaging.

BACKGROUND: The aim of this study was to determine whether two-dimensional speckle-tracking echocardiography can identify the myocardial damage detected by delayed enhancement (DE) magnetic resonance imaging via the differences in myocardial deformation in patients with extracardiac sarcoidosis who showed no structural and functional abnormalities in the heart. METHODS: Forty-five patients with biopsy-proven extracardiac sarcoidosis were analyzed retrospectively. Patients with abnormal electrocardiographic and echocardiographic findings, including ventricular arrhythmias, heart block, regional wall motion abnormalities, valvular heart disease, and cardiomyopathy, were excluded. Ten age-matched healthy control subjects were recruited as a control group. Comprehensive echocardiography and DE magnetic resonance imaging were performed, and circumferential, longitudinal, and radial strain were consecutively assessed using two-dimensional speckle-tracking echocardiographic software in a 16-segment model of the left ventricle in accordance to the presence (DE+) or absence (DE-) of DE. RESULTS: Among the 45 patients, 36 segments in 13 patients showed DE. DE+ segments had lower peak circumferential strain than DE- and control segments (-14 ± 5% vs -28 ± 7% vs -30 ± 7%, P < .0001). Peak longitudinal strain in DE+ segments was significantly decreased compared with control segments (-19 ± 4% vs -23 ± 5%, P = .005). However, peak radial strain was similar among the three groups: 41 ± 17% in DE+ segments, 45 ± 23% in DE- segments, and 46 ± 18% in control segments (P = .50). CONCLUSIONS: Circumferential and longitudinal strain via two-dimensional speckle-tracking echocardiography can identify the myocardial damage detected by DE magnetic resonance imaging in patients with extracardiac sarcoidosis.

Long-term outcome after deferral of revascularization in patients with intermediate coronary stenosis and gray-zone fractional flow reserve.

BACKGROUND: A strategy of deferred percutaneous coronary intervention for coronary stenosis with fractional flow reserve (FFR) 0.75-0.80, termed the gray zone, remains a matter of debate. The aim of this study was to assess the safety of deferring revascularization for patients with FFR 0.75-0.80 compared with those with FFR >0.80. METHODS AND RESULTS: We assessed 3-year clinical outcome in 150 patients with angiographically intermediate stenosis who had revascularization deferred on the basis of FFR ≥ 0.75 (FFR 0.75-0.80, n=56; FFR >0.80, n=94). Target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction (MI), and ischemia-driven target vessel revascularization (TVR) was evaluated during follow-up. Cardiac death was observed in 1 patient with FFR 0.75-0.80. There was no target vessel-related MI in either group. The incidence of ischemia-driven TVR was higher in patients with FFR 0.75-0.80 than in those with FFR >0.80 (14% vs. 3%, P=0.020). TVF-free survival was significantly worse for the patients with FFR 0.75-0.80 than those with FFR >0.80 (hazard ratio, 5.2; 95% confidence intervals: 1.4-19.5; P=0.015). CONCLUSIONS: Patients with FFR 0.75-0.80 were at higher risk of TVF mainly due to TVR than those with FFR >0.80.

Effect of atorvastatin therapy on fibrous cap thickness in coronary atherosclerotic plaque as assessed by optical coherence tomography: the EASY-FIT study.

BACKGROUND: The detailed mechanism of plaque stabilization by statin therapy is not fully understood. OBJECTIVES: The aim of this study was to assess the effect of lipid-lowering therapy with 20 mg/day of atorvastatin versus 5 mg/day of atorvastatin on fibrous cap thickness in coronary atherosclerotic plaques by using optical coherence tomography (OCT). METHODS: Seventy patients with unstable angina pectoris and untreated dyslipidemia were randomized to either 20 mg/day or 5 mg/day of atorvastatin therapy. OCT was performed to assess intermediate nonculprit lesions at baseline and 12-month follow-up. RESULTS: Serum low-density lipoprotein cholesterol level was significantly lower during therapy with 20 mg/day compared with 5 mg/day of atorvastatin (69 mg/dl vs. 78 mg/dl; p = 0.039). The increase in fibrous cap thickness was significantly greater with 20 mg/day compared with 5 mg/day of atorvastatin (69% vs. 17%; p < 0.001). The increase in fibrous cap thickness correlated with the decrease in serum levels of low-density lipoprotein cholesterol (R = -0.450; p < 0.001), malondialdehyde-modified low-density lipoprotein (R = -0.283; p = 0.029), high-sensitivity C-reactive protein (R = -0.276; p = 0.033), and matrix metalloproteinase-9 (R = -0.502; p < 0.001), and the decrease in grade of OCT-derived macrophages (R = -0.415; p = 0.003). CONCLUSIONS: Atorvastatin therapy at 20 mg/day provided a greater increase in fibrous cap thickness in coronary plaques compared with 5 mg/day of atorvastatin. The increase of fibrous cap was associated with the decrease in serum atherogenic lipoproteins and inflammatory biomarkers during atorvastatin therapy. (Effect of Atorvastatin Therapy on Fibrous Cap Thickness in Coronary Atherosclerotic Plaque as Assessed by Optical Coherence Tomography: The EASY-FIT Study; NCT00700037).

Acceleration time of systolic coronary flow velocity to diagnose coronary stenosis in patients with microvascular dysfunction.

BACKGROUND: The aim of this study was to test whether acceleration time of systolic coronary flow velocity could contribute to the diagnosis of coronary stenosis in patients with microvascular dysfunction, on the basis of the hypothesis that systolic coronary flow is less influenced by microvascular function because of compressed myocardium. METHODS: Coronary flow velocity was assessed in the left anterior descending coronary artery during hyperemia with intravenous adenosine by echocardiography in 502 patients who were scheduled for coronary angiography because of coronary artery disease and significant valvular disease. Coronary flow velocity reserve (CFVR) and the percentage acceleration time (%AT), as the percentage of the time from the beginning to the peak of systolic coronary flow over systolic time during hyperemia, were calculated. The diagnostic ability of CFVR and %AT for angiographic coronary artery stenosis was then analyzed. As invasive substudies, fractional flow reserve and %AT by a dual-sensor (pressure and Doppler velocity) guidewire were measured simultaneously with %AT on transthoracic echocardiography (n = 14). RESULTS: Patients with coronary stenosis had significantly lower CFVR (1.7 ± 0.4) and greater %AT (65 ± 9%) compared with those without stenosis (2.6 ± 0.6 and 50 ± 13%, respectively). Percentage acceleration time by Doppler echocardiography was in good agreement with %AT (r = 0.98) and fractional flow reserve (r = 0.74) invasively measured by dual-sensor guidewire. Cutoff values of CFVR and %AT were determined as 2.0 and 60% in receiver operating characteristic curve analysis. The sensitivity, specificity, and accuracy of CFVR to detect coronary stenosis were 71.1%, 77.3%, and 75.4%, while those of %AT were 83.4%, 71.8%, and 75.4%, respectively. In addition, %AT provided high accuracy to detect coronary stenosis, especially in patients with previous myocardial infarctions, valvular disease, and left ventricular hypertrophy (81.1%, 84.1%, and 73.4%, respectively). CONCLUSIONS: The %AT of systolic coronary flow velocity is a promising marker to diagnose coronary stenosis in patients with microvascular dysfunction.

High-density lipoprotein cholesterol level is associated with fibrous cap thickness in acute coronary syndrome.

BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) level has been reported as an independent risk factor for coronary artery disease, few studies addressed the direct relationship between the presence of thin-cap fibroatheroma (TCFA) that is considered as vulnerable plaque in pathology and HDL-C level. The aim of this study was to investigate whether lesion vulnerability is related to HDL-C level in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A total of 261 patients with ACS who underwent optical coherence tomography prior to percutaneous coronary intervention, were enrolled. Patients were divided into a TCFA group (n=124) and a non-TCFA group (n=137). TCFA was defined as a lipid plaque (lipid content in ≥1 quadrant) covered with <70 µm-thickness fibrous caps. There were no differences in patient characteristics and clinical results between the 2 groups except for HDL-C level, low-density lipoprotein cholesterol (LDL-C) level, and high-sensitive C-reactive protein (hs-CRP) level. On multivariate regression analysis, low HDL-C level (ß coefficient: 0.302, P<0.001), high LDL-C level (ß coefficient: -0.172, P=0.008), hs-CRP level (ß coefficient: -0.145, P=0.017), and current smoking (ß coefficient: -0.124, P=0.028) were identified as independent contributors to fibrous cap thickness. CONCLUSIONS: HDL-C is correlated with fibrous cap thickness of the culprit lesion in patients with ACS. HDL-C may be considered as a therapeutic target for plaque stabilization.