A Continuous Murmur as the Only Clinical Sign for Complex Coronary Artery Fistulas Diagnosis.

An asymptomatic patient presented at our hospital exhibiting a Brugada electrocardiography pattern with coronary artery fistulas. Coronary artery fistula is a congenital or acquired rare abnormal condition with increased symptoms and complications over time. In the absence of the therapeutic consensus, we discuss the association and management for this condition. (Level of Difficulty: Advanced.).

Differences in lesion characteristics and patient background associated with the medium-term clinical outcomes of bare-metal and first-, second- and third-generation drug-eluting stents.

We investigated the lesion characteristics and patient background factors associated with the medium-term incidence of major adverse cardiac events (MACEs) for bare-metal stents (BMS) and 1st-, 2nd- and 3rd-generation drug-eluting stents (DES) using the PCI-Registry (FU-Registry). Between January 2003 and March 2016, 2967 cases/3508 lesions for which percutaneous coronary intervention was performed at Fukuoka University Hospital and related facilities were enrolled. Patients were divided into BMS and 1st-, 2nd- and 3rd-generation drug-eluting stent (DES) groups. The incidence of MACEs in the BMS group (26.2%) was significantly higher than those in the 1st, 2nd and 3rd DES groups (18.0%, 12.5%, and 11.0%, respectively). The incidence of MACEs in the BMS group was strongly associated with insulin use, hemodialysis, low high-density lipoprotein cholesterol, stent minimum lesion diameter, stent length, severe calcification and a small vessel diameter of less than 2.5 mm. Some of these factors showed no association with MACEs among the drug-elution groups, and only hemodialysis, arteriosclerosis obliterans and severe calcification showed a strong correlation in the 2nd DES group. In the 3rd DES group, none of the factors considered were associated with MACEs. In conclusion, in stent implantation, the number of factors associated with MACEs has gradually decreased as the stent generation increased.

A Strict Target for Low-Density Lipoprotein Cholesterol May not Be Necessary for Secondary Prevention of Cardiovascular Disease in All Elderly Patients With Dyslipidemia.

According to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2017, standard statin therapy for hyper-low-density lipoprotein cholesterol cholesterolemia in elderly patients may be effective for the secondary prevention of coronary artery disease, as in non-elderly adults. On the other hand, high-intensity statin therapy may not be recommended in all elderly cardiovascular disease patients with dyslipidemia, and particularly in elderly patients aged ≥ 85 years. In any case, tailor-made medical care with use of statin is required that matches the background of each patient.

Atherosclerotic Coronary Artery Disease in Patients With Cardiometabolic Syndrome.

Major risk factors for cardiovascular disease (CVD) include aging, gender, smoking, family history and cardiometabolic syndrome. The relative residual risks for CVD after statin treatment for primary and secondary prevention have been reported by several large-scale randomized clinical trials. Statin treatment appears to prevent one-third of the onset and progression of CVD, but not the remaining two-thirds. There are three major problems regarding the residual risk of CVD: 1) Insufficient reduction of low-density lipoprotein cholesterol levels; 2) Low levels of high-density lipoprotein cholesterol and elevated triglyceride; and 3) Insufficient control of other risk factors (high blood pressure, obesity, metabolic syndrome, type 2 diabetes, etc.). Thus, a multifaceted preventive approach should be needed to prevent CVD after statin treatment.

Influence of chronic kidney disease on coronary plaque components in coronary artery disease patients with both diabetes mellitus and hypertension.

Chronic kidney disease (CKD) is well known to be associated with an increased incidence of coronary artery disease (CAD). Diabetes mellitus (DM) and hypertension (HTN), both of which are traditional risk factors for CAD, are the two most common causes of CKD. However, the influence of CKD on coronary atherosclerosis in CAD patients who have both DM and HTN remains uncertain. In these patients, we examined the relationship between CKD and coronary plaque using integrated backscatter intravascular ultrasound (IB IVUS). Two hundred two CAD patients with both DM and HTN who underwent percutaneous coronary intervention using IB IVUS were included. The patients were divided into two groups: CKD group (n = 106) and non-CKD group (n = 96). Gray-scale and IB IVUS examinations were conducted for the non-culprit segment of a coronary artery. As a result, although there was no significant difference in the percentage of plaque volume, the percentage of lipid volume was significantly higher in the CKD group than in the non-CKD group [median (IQR): 56.7% (45.4-67.0%) vs. 52.0% (38.3-60.2%), p = 0.03]. In all of the patients, estimated glomerular filtration rate levels were negatively correlated with the percentage of lipid volume (r = - 0.15, p = 0.03) and positively correlated with the percentage of fibrosis volume (r = 0.15, p = 0.04). A multivariate regression analysis showed that CKD was an independent predictor associated with the increased lipid volume (ß = 0.15, p = 0.047) and decreased fibrosis volume (ß = - 0.16, p = 0.03) in coronary plaques. In conclusion, among CAD patients who had both DM and HTN, CKD was associated with lipid-rich coronary plaques. CKD may contribute to the vulnerability of coronary plaque in these very high-risk patients.

Correction to: Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

Unfortunately, the Fig. 1 was published incorrectly in the original publication of the article. The correct figure is as below.

Impact of the triglyceride level on coronary plaque components in female patients with coronary artery disease treated with statins.

Several studies have reported that elevated triglyceride (TG) levels may be more strongly associated with an increased risk of coronary artery disease (CAD) in females than in males. We examined gender differences in the relationship between TG levels and coronary atherosclerosis using integrated backscatter intravascular ultrasound (IB IVUS) in CAD patients treated with statins. Three hundred seventy-eight CAD patients (105 females and 273 males) who underwent percutaneous coronary intervention using IB IVUS, and who were already receiving statin treatment, were included. Gray-scale and IB IVUS examinations were performed for the non-culprit segment of a coronary artery and fasting serum TG concentrations were measured. We found that TG levels were significantly correlated with increased lipid (r = 0.40, p < 0.001) and decreased fibrous (r = - 0.37, p < 0.001) plaque components in females, but not in males. Low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were not related to either the gray-scale or IB IVUS parameters in both genders. After adjustment for conventional coronary risk factors by a multivariate stepwise regression analysis, higher TG levels in females were independently associated with increased lipid (ß = 0.31, p< 0.001) contents in coronary plaques. In conclusion, among CAD patients treated with statins, TG levels were associated with lipid-rich coronary plaques in females, but not in males. TG levels may be more important indicators of residual risk after statin treatment in females than in males.

Impact of von Willebrand factor on coronary plaque burden in coronary artery disease patients treated with statins.

High von Willebrand factor (VWF) levels have been reported to be associated with an increased risk of cardiovascular events. However, the relationship between VWF levels and coronary atherosclerosis in patients with coronary artery disease (CAD) who have already received stain treatment is still unclear. We examined the association between VWF levels and coronary plaque as assessed by intravascular ultrasound (IVUS) in CAD patients treated with statins. Ninety-one CAD patients who underwent percutaneous coronary intervention under IVUS guidance, and who were already receiving statin treatment based on Japanese guidelines, were included. An IVUS examination was performed for the culprit lesion, and plasma VWF antigen levels were measured using enzyme-linked immuno sorbent assay. In all of the patients, the low-density lipoprotein cholesterol levels just before the IVUS examination were low (86 ± 26 mg/dL). The VWF levels were positively correlated with the plaque burden expressed as percent atheroma volume (PAV) (r = 0.39, P = .001), while there was no significant association between VWF and plaque composition. Multivariate stepwise regression analysis showed that higher VWF levels were independently associated with increased PAV (ß=0.26, P = .01). In CAD patients who had already been treated with statins, higher VWF levels were associated with a higher coronary plaque burden, suggesting that a high VWF level may be a marker of the residual cardiovascular risk after statin treatment.

Associations between microalbuminuria and parameters of flow-mediated vasodilatation obtained by continuous measurement approaches.

The associations between microalbuminuria and various parameters of flow-mediated vasodilatation (FMD) are not completely understood. We retrospectively analyzed 265 consecutive patients who underwent coronary angiography and in whom we could measure FMD and the urine albumin-creatinine ratio (UACR). Using 15 continuous measurement approaches, we measured FMD as the magnitude of the percentage change in the brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120-s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups according to UACR: normoalbuminuria (NOR, n = 211) and microalbuminuria (MIC, n = 54). The MIC group showed a significantly higher percentage of coronary artery disease than the NOR group. FMD-AUC60 and FMD-AUC120, but not FMD-MDR, in the MIC group were significantly lower than those in the NOR group. On the other hand, bFMD in the MIC group tended to be lower than that in the NOR group, but this difference was not significant. A multiple regression analysis indicated that FMD-AUC120 and diabetes mellitus were predictors of MIC. Finally, we defined the cut-off value of FMD-AUC120 for the presence of MIC in all patients as 8.4 mm x second (sensitivity 0.640, specificity 0.588) by a receiver-operating characteristic curve analysis. In conclusion, this study provides more definitive evidence for the association of microalbuminuria with endothelial dysfunction. FMD-AUC120 may be a superior marker for MIC.

Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

It is not yet clear whether the discordance of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) predicts the follow-up clinical outcome (major adverse cardiovascular events: MACEs) in patients with coronary stent implantation. Among 2015 patients with coronary stent implantation (Fukuoka University [FU]-Registry), excluding those with acute coronary syndrome or hemodialysis, we selected 801 patients who had undergone successful stent implantation with a follow-up until 18 months, and classified them into 3 groups according to baseline LDL-C and non-HDL-C levels [percentile(P)non-HDL-C more than (P)LDL-C, (P)non-HDL-C equal to (P)LDL-C, and (P)non-HDL-C less than (P) LDL-C]. We found that the discordance of (P)LDL-C and (P)non-HDL-C was not a significant predictor of MACEs. Higher LDL-C level was consistently and independently associated with higher incidences of MACEs after controlling for conventional risk factors and the type of stent used by multivariate Cox regression analyses. In conclusion, LDL-C levels are more important than non-HDL-C levels and the discordance of LDL-C and non-HDL-C levels as predictors of MACEs in patients with stable angina after stent implantation.

Sex difference between target levels of cholesterol-related parameters and post-PCI long-term clinical outcomes: From the FU-Registry.

BACKGROUND: Since single lipid parameters are too weak to predict the risk of coronary artery disease, we examined whether the allocation of patients into four groups based on achievement of the target levels set by the Japan Atherosclerosis Guidelines at the time of percutaneous coronary intervention (PCI) would reveal different long-term (5 years) clinical outcomes in males and females. METHODS: The results of a 5-year follow-up study are summarized as FU-Registry, Long-Term Clinical Outcome Results. The subjects consisted of 1158 patients who underwent elective PCI. The male and female patients were separately allocated into four groups: (1) high-density lipoprotein cholesterol (HDL-C≥40mg/dl as well as low-density lipoprotein-cholesterol (LDL-C)≥100mg/dl); (2) HDL-C≥40mg/dl as well as LDL-C<100mg/dl; (3) HDL-C<40mg/dl as well as LDL-C≥100mg/dl; (4) HDL-C<40mg/dl as well as LDL-C<100mg/dl, for a comparison of both patient as well as lesion characteristics and the endpoint of major adverse cardiac events (MACEs). RESULTS: Regarding lesion characteristics, significant differences (p<0.05) were detected in the usage rate of a drug-eluting stent (DES) as well as the bend, stent reference diameter, and stent minimum lumen diameter in females by ANOVA, and in severe calcification, the bend, and usage rate of DES (p<0.001) in males. In females, significant differences (p<0.05) were observed in MACEs and target lesion revascularization-PCI. In contrast, among males, the four groups had nearly equivalent outcomes. Uni- and multivariate analyses revealed that HDL-C as well as LDL-C in females were associated with MACEs [OR 3.29 (95% CI 1.05-8.57, p=0.04)], while no association was observed in male multivariate analysis. CONCLUSION: In female patients, HDL-C<40mg/dl and LDL-C≥100mg/dl were even more strongly related to MACEs, whereas the combination of LDL-C and HDL-C was not related to MACEs in male patients.

A rare case of acute myocardial infarction with a non-specific symptom in a young female with systemic lupus erythematosus.

A 31-year-old female with an 18-year history of systemic lupus erythematosus (SLE) complained of epigastralgia and consulted the emergency outpatient department at our hospital. Her physical examination revealed tenderness at the scrobiculus cordis, which was a non-specific symptom of coronary heart disease (CHD). We ultimately gave a diagnosis of acute myocardial infarction based on coronary angiography and performed percutaneous coronary intervention. Although pre-interventional intravascular ultrasound demonstrated distinct atherosclerotic lesions in the coronary arteries, there were no atherosclerotic lesions in other systemic arteries. Although CHD in young SLE patients is a significant cause of morbidity and premature death, it tends to be misdiagnosed because their symptoms may be non-specific. In addition, this case highlights the fact that even SLE patients with no systemic atherosclerosis are at risk for the development of CHD. .

Is a bare-metal stent still useful for improving the outcome of percutaneous coronary intervention? From the FU-Registry.

BACKGROUND: Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is increasingly being used for the treatment of coronary artery diseases. However, the role and effectiveness of PCI with a bare metal stent (BMS) have not yet been established. METHODS: Among the 2197 patients (2653 lesions) treated with PCI from 2003 to 2012 at three institutions in Fukuoka, 859 patients (1032 lesions) without acute coronary syndrome and in whom we were able to perform follow-up coronary angiography after stent placement and collect detailed data were selected for this study. Among the patients treated by BMS, the cut-off lesion reference for the development of in-stent restenosis (ISR) was calculated by comparing patients with and without ISR. In all patients with a lesion reference above/below the cut-off point of BMS-ISR, medium-term clinical and angiographic outcomes were compared between the BMS and DES groups. RESULTS: In patients treated with a BMS, the lesion reference [odds ratio 0.68, 95% confidence interval (CI) 0.43-0.97, p=0.03] was strongly correlated with ISR, and the area under the receiver operating characteristic curve was 0.704, with moderate accuracy. Calculation of the cut-off lesion reference for BMS-ISR, using a relative cumulative frequency distribution and a sensitivity/specificity curve, showed that the cut-off lesion reference for BMS-ISR was 3.08mm, and the sensitivity/specificity was 60.4%. For the DES and BMS groups in cases with a lesion reference over 3.08mm, BMS placement did not correlate with ISR (odds ratio 0.98, 95% CI 0.85-1.12), and there was also no correlation between BMS and major adverse cardiac events. CONCLUSION: In patients with a lesion reference≧3.08mm, medium-term clinical and angiographic outcomes were equivalent between the use of a DES and BMS. Thus, BMS placement is well worth considering, especially in patients with a lesion reference≧3.08mm, in whom double-antiplatelet therapy needs to be stopped at an early stage.

Depressor and Anti-Inflammatory Effects of Angiotensin II Receptor Blockers in Metabolic and/or Hypertensive Patients With Coronary Artery Disease: A Randomized, Prospective Study (DIAMOND Study).

BACKGROUND: We compared the efficacy and safety of azilsartan to those of olmesartan in a prospective, randomized clinical trial. METHODS: Forty-four hypertensive patients who had coronary artery disease (CAD) were enrolled. We randomly assigned patients to changeover from their prior angiotensin II receptor blockers (ARBs) to either azilsartan or olmesartan, and followed the patients for 12 weeks. RESULTS: Office systolic blood pressure (SBP) in the azilsartan group was significantly decreased after 12 weeks. SBP and diastolic blood pressure (DBP) after 12 weeks in the azilsartan group were significantly lower than those in the olmesartan group. The percentage of patients who reached the target BP at 12 weeks (78%) in the azilsartan group was significantly higher than that at 12 weeks (45%) in the olmesartan group. There were no significant changes in pentraxin-3, high-sensitively C-reactive protein or adiponectin in blood after 12 weeks in either group. Although serum levels of creatinine (Cr) in the azilsartan group significantly increased, these changes were within the respective normal range. CONCLUSION: In conclusion, the ability of azilsartan to reduce BP may be superior to that of prior ARBs with equivalent safety in hypertensive patients with CAD.

Association of Arterial Pressure Volume Index With the Presence of Significantly Stenosed Coronary Vessels.

BACKGROUND: A blood pressure (BP) monitoring system (PASESA(®)) can be used to easily analyze the characteristics of central and peripheral arteries during the measurement of brachial BP. METHODS: We enrolled 108 consecutive patients (M/F = 86/22, age 70 ± 10 years) who underwent coronary angiography (CAG) due to suspected coronary artery disease (CAD) in whom we could measure various parameters using PASESA(®) in addition to brachial-ankle pulse wave velocity (baPWV). The patients were divided into two groups: patients who did not have significantly stenosed coronary vessel disease (n = 33, non-SVD group) and those who had at least one significantly stenosed coronary vessel (n = 75, SVD group). The characteristics of central and peripheral arteries (arterial velocity pulse index (AVI) and arterial pressure volume index (API), respectively) and baPWV were measured. Estimated central BP (eCBP) was calculated from the data obtained from PASESA(®), and CBP was also measured simultaneously by invasive catheterization. RESULTS: API, but not AVI and baPWV, in the SVD group was significantly higher than that in the non-SVD group. Although eCBP was significantly associated with CBP, there was no difference in eCBP between the groups. There were significant associations among API, AVI and baPWV, albeit these associations were relatively weak. A multivariate logistic regression revealed that API and ß-blocker were significant independent variables that were associated with the presence of significant coronary stenosis. The cut-off level of API that gave the greatest sensitivity and specificity for the presence of SVD was 24 units (sensitivity 0.636 and specificity 0.667). CONCLUSION: In conclusion, API, but not AVI or baPWV, is associated with the presence of significant coronary stenosis.

Association between cholesterol efflux capacity and coronary restenosis after successful stent implantation.

The measurement of high-density lipoprotein (HDL) functionality could be useful for identifying patients who have an increased risk of coronary restenosis after stent implantation. In the present study, we elucidates whether HDL functionality can predict restenosis. The participants included 48 consecutive patients who had stable angina and were successfully implanted with a drug-eluting stent (DES) or bare-metal stent. Follow-up coronary angiography was performed after 6-8 months of stenting. Cholesterol efflux and the anti-inflammatory capacity of HDL were measured before stenting (at baseline) and at follow-up. The mean age was 64 ± 11 years and the body mass index was 24 ± 3 kg/m(2). While HDL cholesterol (HDL-C) significantly increased from baseline to follow-up, there was no significant association between HDL-C level at baseline and in-stent late loss. Cholesterol efflux capacity was significantly increased from baseline to follow-up. The efflux capacity at baseline was negatively correlated with in-stent late loss, whereas the anti-oxidative activity of HDL at baseline was not associated with in-stent late loss. We analyzed the predictors of in-stent late loss using independent variables (efflux capacity and anti-oxidative capacity at baseline in addition to age, gender, HDL-C and low-density lipoprotein cholesterol at baseline, hypertension, diabetes mellitus, smoking, lesion length and DES implantation, history of myocardial infarction and prior percutaneous coronary intervention) by a multiple regression analysis. The efflux capacity at baseline was only independently associated with in-stent late loss. In conclusion, cholesterol efflux capacity at baseline could predict coronary restenosis in patients with successful stent implantation.

A relative difference in systolic blood pressure between arms by synchronal measurement and conventional cardiovascular risk factors are associated with the severity of coronary atherosclerosis.

It is not known the relationships between a difference in systolic blood pressure (SBP) or diastolic BP (DBP) between arms by synchronal measurement and the presence of coronary artery disease (CAD), and between a difference in BP between arms and the severity of coronary atherosclerosis. We enrolled 425 consecutive patients (M/F = 286/139, 67 ± 13 year) who were admitted to our University Hospital and in whom we could measure the absolute (|rt. BP - lt. BP|) and relative (rt. BP - lt. BP) differences in SBP and DBP using a nico PS-501(®) (Parama-Tech). We divided all patients into those who did and did not have CAD. The relative differences in SBP between arms in patients with CAD were significantly lower than those in patients without CAD. However, the relative difference in SBP between arms was not a predictor of the presence of CAD. We also divided 267 patients who underwent coronary angiography into tertiles according to the Gensini score (low, middle, and high score groups). Interestingly, the middle + high score groups showed significantly lower relative differences in SBP between arms than the low score group. The mean Korotkoff sound graph in the middle + high Gensini score group was significantly higher than that in the low Gensini score group. Among conventional cardiovascular risk factors and nico parameters, the relative difference in SBP between arms in addition to the risk factors (age, gender, body mass index, hypertension, dyslipidemia, and diabetes mellitus) was associated with the score by a logistic regression analysis. In conclusion, the relative difference in SBP between arms as well as conventional risk factors may be associated with the severity of coronary arteriosclerosis.

Impact of the Absolute Difference in Diastolic Blood Pressure Between Arms in Patients With Coronary Artery Disease.

BACKGROUND: We investigated the relationship between the severity and presence of coronary artery disease (CAD) and a difference in systolic and diastolic blood pressure (SBP and DBP) between arms or between lower limbs. METHODS: We enrolled 277 patients who underwent coronary angiography. We calculated the absolute (|right BP (rt. BP) - left BP (lt. BP)|) and relative (rt. BP - lt. BP) differences in SBP or DBP between arms or between lower limbs, and assessed the severity of CAD in terms of the Gensini score. RESULTS: The absolute difference in DBP between arms in the CAD group was significantly lower than that in the non-CAD group, whereas the absolute difference in DBP between lower limbs in the CAD group was significantly higher. There were no differences in the absolute or relative difference in SBP between arms or lower limbs between the groups. The absolute difference in DBP between arms decreased as the Gensini score increased. In a logistic regression analysis, the presence of CAD was independently associated with the absolute difference in DBP between arms, in addition to male, family history, dyslipidemia, diabetes mellitus and hypertension. CONCLUSION: The absolute difference in DBP between arms in addition to traditional factors may be a critical risk factor for the presence of CAD.

Association Between Visit-to-Visit Variability in Blood Pressure and Cardiovascular Events in Hypertensive Patients After Successful Percutaneous Coronary Intervention.

BACKGROUND: Visit-to-visit variability (VVV) in blood pressure (BP) in addition to high BP has been shown to be a strong predictor of coronary events and stroke. Therefore, we investigated the associations between VVV in BP or BP levels and cardiovascular events after successful percutaneous coronary intervention (PCI). METHODS: We enrolled 176 hypertensive patients who had undergone successful PCI and who had four clinic visits to measure BP until follow-up coronary angiography (CAG) at 6 - 9 months after PCI. The patients were divided into those with acute coronary syndrome (ACS group; n = 50) and those with stable angina pectoris (SAP group; n = 126). We determined VVV in BP expressed as the standard deviation (SD) of average BP, average, and the maximum and minimum BP during the follow-up period. Major adverse cardiovascular events (MACEs) (myocardial infarction (MI), target lesion revascularization (TLR) and all-cause death) were also analyzed. RESULTS: There were no significant differences in VVV in BP, average BP or maximum or minimum BP between the patients with and without MACE in all patients, the ACS and SAP groups. Interestingly, in the ACS group, VVV in SBP and maximum SBP in patients with MI were significantly higher than those in patients without MI. The cut-off levels for VVV in BP and maximum SBP that gave the greatest sensitivity and specificity for MI in the ACS group were 15.1 and 138 mm Hg, respectively. CONCLUSION: Higher VVV in SBP and maximum SBP in patients with ACS after successful PCI were associated with the onset of MI.