Prognostic values of coronary artery calcium score and 123I-BMIPP SPECT in patients with non-ischemic heart failure with preserved ejection fraction.

This study aimed to determine whether coronary artery calcium score (CACS) can be a prognostic indicator for the development of major adverse cardiac events (MACEs) and compare the value of CACS with that of the 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) defect score (BDS) in patients with non-ischemic heart failure with preserved ejection fraction (NIHFpEF). Among 643 consecutive patients hospitalized due to acute heart failure, 108 (74 ± 13y) were identified to have NIHFpEF on non-contrast regular chest computed tomography and 123I-BMIPP single-photon emission computed tomography (SPECT). We evaluated whether CACS and BDS were associated with MACEs using multivariate Cox models. Thirty-two MACEs developed at a mean follow-up period of 2.4 years. CACS > 0 (hazard ratio [HR] 2.38, 95% confidence interval [CI] 1.02-5.54) and higher BDS (HR 16.00, 95% CI 5.88-43.49) were significantly associated with the development of MACEs. The proportion of patients who experienced MACEs was significantly higher in the CACS > 0 and high BDS group than in the CACS = 0 and low BDS group (3% vs. 75%, p < 0.001). CACS, as well as BDS, could serve as potential prognostic indicators in patients with NIHFpEF.

Prognostic values of 123I-MIBG myocardial scintigraphy and heart rate variability in patients with heart failure with preserved ejection fraction.

BACKGROUND: The aim of this study was to evaluate the prognostic values of sympathetic nerve system using 123I-MIBG myocardial scintigraphy and using Holter electrocardiogram (ECG) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Among 403 consecutive patients with stable HF who underwent 123I-MIBG myocardial scintigraphy and Holter ECG, we identified 133 patients (64 ± 16 years) who had preserved ejection fraction (≥ 50%) by echocardiography. Multivariate Cox model was used to assess if washout rate (WR) by 123I-MIBG scintigraphy and very low frequency power (VLFP) by Holter ECG was associated with major adverse cardiovascular events (MACE). During a mean follow-up of 5.4 ± 4.1 years, 39 MACE occurred. The lower nighttime VLFP (HR 3.29, 95% CI 1.56 to 6.92) and higher WR (HR 4.01, 95% CI 1.63 to 9.88) were the significant prognostic factors for MACE. As compared to high nighttime VLFP and low WR group, MACE risk was significantly the highest in the low nighttime VLFP and high WR group (HR 40.832; 95% CI 5.378 to 310.012, P < 0.001). CONCLUSION: This study demonstrated that the nighttime VLFP adding to WR could be a potential prognostic value among patients with HFpEF.

Prognostic Value of 123I-BMIPP SPECT in Patients with Nonischemic Heart Failure with Preserved Ejection Fraction.

Imaging of myocardial fatty acid metabolism using 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) SPECT is useful for identifying high-risk patients with known ischemic heart disease. However, its utility for patients who have nonischemic heart failure with preserved ejection fraction is not well known. This study aimed to evaluate the prognostic value of the 123I-BMIPP defect score in such patients. Methods: Of 804 consecutive patients who were admitted to the hospital because of acute heart failure and underwent 123I-BMIPP SPECT, we identified 133 (mean age ± SD, 73 ± 13 y) who had normal coronary arteries by invasive coronary angiography and preserved left ventricular ejection fraction (≥50%) by echocardiography. 123I-BMIPP defects were quantitatively scored to obtain summed defect scores in 17 segments of 123I-BMIPP SPECT images. The patients were divided into 2 groups based on their score. The multivariate Cox model was used to assess a possible correlation between a higher score (≥4, n = 46) and major adverse cardiac events, including cardiac death, cardiovascular events, and hospitalization for heart failure, compared with a lower score (<4, n = 87). Results: During a mean follow-up of 2.5 y, 35 major adverse cardiac events occurred. The median scores in the high-score and low-score groups were 7.13 ± 4.21 and 1.29 ± 0.80, respectively. By multivariate Cox analysis, a higher score was associated with increased major adverse cardiac events, compared with a lower score (hazard ratio, 11.04; 95% confidence interval, 4.93-24.74; P < 0.001). Conclusion: This study demonstrated that the defect score by 123I-BMIPP SPECT may have potential prognostic value in patients who have nonischemic heart failure with preserved ejection fraction.

Prognostic value of lower limb perfusion single-photon emission computed tomography-computed tomography in patients with lower limb atherosclerotic peripheral artery disease.

PURPOSE: The purpose of this study was to estimate the severity of the participants' lower limb ischemia by calculating the lower limb muscle-to-background ratio (LMBR) using lower limb perfusion single-photon emission computed tomography-computed tomography (SPECT/CT) and to evaluate the prognostic value of LMBR in peripheral artery disease (PAD) patients. MATERIALS AND METHODS: This retrospective study consists of 38 patients with PAD (70 ± 12 years) and observed over 1 year who were included in the analysis. All participants underwent lower limb perfusion SPECT/CT. LMBR was calculated by dividing counts/volume in lower limb muscle by mean counts/volume of background. All patients were divided into two groups based on their LMBR value and observed for the occurrence of a major adverse event (MAE). RESULTS: The high and low LMBR groups consisted of 26 and 12 patients, respectively. The median LMBR in the high group was 9.59 (6.11-11.87) while that in the low group was 4.35 (3.85-4.99). A significantly higher number of patients in the low LMBR group experienced MAE than in the high LMBR group (7 of 12 vs. 1 of 26, p < 0.001). CONCLUSION: This study demonstrated that the LMBR derived from lower limb perfusion SPECT/CT may have a high prognostic value in patients with PAD.

Molecular Hydrogen Alleviates Cellular Senescence in Endothelial Cells.

BACKGROUND: Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2on endothelial senescence and clarified the mechanisms involved. METHODS AND RESULTS: Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55±0.07 mmol/L. This concentration gradually decreased, and H2was almost undetectable in medium after 12 h. At 24 h after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated ß-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2on HUVECs. CONCLUSIONS: H2has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. (Circ J 2016; 80: 2037-2046).

Addition of a renin-angiotensin-aldosterone system inhibitor to a calcium channel blocker ameliorates arterial stiffness.

BACKGROUND: The aim of controlling hypertension is to protect against arteriosclerosis. Calcium channel blockers (CCBs) and renin-angiotensin-aldosterone system (RAAS) inhibitors have been reported to have antihypertensive effects, but their effect on the progression of arteriosclerosis is not fully understood. The cardio-ankle vascular index (CAVI) was developed to estimate arterial stiffness, which reflects arteriosclerosis. In this study, we investigated the longer term effects of CCBs and RAAS inhibitors on the progression of arteriosclerosis by monitoring the CAVI. METHODS: Our subjects were 115 consecutive, non-smoking hypertensive patients on oral treatment with a CCB and/or RAAS inhibitor for at least 3 years in whom the CAVI was measured on two occasions approximately 1 year apart during the period from January 2009 to December 2011. Changes in CAVI were evaluated in patients administered a CCB alone (group C), an RAAS inhibitor (group R) alone, or both drugs together (group B). Changes in laboratory findings, blood pressure, and ankle-brachial index were similarly evaluated. RESULTS: No significant change in laboratory findings, blood pressure, or ankle-brachial index was noted in any of the groups. The CAVI decreased slightly in group R (first recording 8.80±1.03, second recording 8.57±0.97, P=0.517) and increased significantly in group C (first 8.45±0.92, second 8.95±1.04, P=0.038), but showed no significant change in group B (first 9.01±1.26, second 9.05±1.35, P=0.851). CONCLUSION: Long-term administration of a CCB alone increased the CAVI, but this effect was offset by the concomitant use of a RAAS inhibitor, indicating that a RAAS inhibitor might protect against arteriosclerosis.

Efficacy of Dabigatran for Dissolving Deep Vein Thromboses in Outpatients With a Deteriorated General Condition.

Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for the prevention of ischemic strokes in patients with nonvalvular atrial fibrillation (AF). At present, NOACs have been evaluated for the treatment of deep vein thrombosis (DVT). We examined the efficacy of dabigatran, the first NOAC for anticoagulation of AF in Japan, in outpatients who suffered from DVTs under a deteriorated general condition.Thirty-six consecutive outpatients diagnosed with DVT at our institute were enrolled. Not all patients could be hospitalized due to other clinical problems; 15 (42%) had malignant tumors, 9 (25%) psychological disorders, and 6 (17%) postoperative orthopedic disease. Dabigatran was administered at a dose of 110-150 mg once or twice daily, depending on the renal function and age. The mean dosage of dabigatran was 211.7 ± 36.6 mg per day. In 18 (50%) patients, the DVTs were completely dissolved and disappeared over a treatment term of 4.3 ± 4.3 months. In 9 patients (25%), the DVTs partly dissolved, but in the remaining 9 (25%) patients, dabigatran was totally ineffective. During a follow-up of 30.5 ± 5.3 months, DVTs did not recur with dabigatran in 18 patients with an effective efficacy. In a multivariate analysis, patients with small sized thromboses and those without malignant tumors were significantly associated with the DVTs dissolving (P = 0.003 and P = 0.006, respectively).Dabigatran was effective for dissolving DVTs in outpatients with a poor condition, particularly when the size of the DVT was small and malignant tumors were absent.

Assessment of angiographic coronary calcification and plaque composition in virtual histology intravascular ultrasound.

OBJECTIVES: We assessed the relation between coronary plaque composition and angiographic calcification by using virtual histology intravascular ultrasound (VH-IVUS). BACKGROUND: The plaque vulnerability according to angiographic calcification is unclear. METHODS: Subjects were 140 consecutive patients (145 lesions) undergoing VH-IVUS before percutaneous coronary intervention. Subjects were divided into 4 groups: no calcification group (n = 27), spotty group (n = 65) that had calcium deposits under 90° in grayscale IVUS, intermediate group (n = 37) had calcium deposits with 90° or more and under 180°, and extensive group (n = 16) had calcium deposits with 180° or more. RESULTS: The number of VH thin-cap fibroatheromas in spotty group was significantly larger than no calcification group, intermediate group, and extensive group (0.66 ± 0.71 vs 0.22 ± 0.42 [P < 0.01], 0.32 ± 0.48 [P < 0.05], 0.13 ± 0.34 [P < 0.01], respectively). Spotty group without angiographic calcification had significantly larger %necrotic core than with angiographic calcification (24.5 ± 6.7% vs 19.9 ± 7.2%, P < 0.05). Intermediate group without angiographic calcification had significantly larger necrotic core area than with angiographic calcification (2.5 ± 0.9 mm(2) vs 1.7 ± 0.9 mm(2) , P < 0.05). Extensive group with angiographic calcification had significantly larger %dense calcium than without angiographic calcification (18.3 ± 4.0% vs 13.4 ± 4.4%, P < 0.05). CONCLUSIONS: Lesions with spotty calcification was highly vulnerable in VH-IVUS. Spotty or intermediate plaque calcification without angiographic calcification was more vulnerable than those with angiographic calcification. Extensive plaque calcification with angiographic calcification had more dense calcium than those without angiographic calcification.

Fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.

Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While its combined use with QT-prolonging drugs has been contraindicated because of the increase in plasma concentrations of such drugs, information is still limited whether fluvoxamine by itself may directly prolong the QT interval. We examined electropharmacological effects of fluvoxamine together with its pharmacokinetic profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. The low dose provided therapeutic plasma drug concentration, whereas the middle and high doses attained approximately 10 and 100 times of the therapeutic ones, respectively. Supra-therapeutic concentration of fluvoxamine exerted the negative chronotropic, inotropic and hypotensive effects; and suppressed the atrioventricular nodal and intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+ channels, whereas it delayed the repolarization in a reverse use-dependent manner, reflecting characteristics of rapidly activating delayed rectifier K+ current channel-blocking property. Fluvoxamine prolonged the terminal repolarization phase at 100 times higher concentration than the therapeutic, indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.

Azithromycin Can Prolong QT Interval and Suppress Ventricular Contraction, but Will Not Induce Torsade de Pointes.

Azithromycin has been reported to increase the risk of death from cardiovascular causes among patients with high baseline risk. Since the information is still limited to bridge the gap between electrophysiological properties of azithromycin in vitro and cardiac death in patients, we initially assessed its electropharmacological effects in doses of 3 and 30 mg/kg, i.v., with the halothane-anesthetized dogs (n = 4). The low dose provided 5.2 times higher than the therapeutic concentration, whereas the high dose attained 17.0 times higher. The high dose delayed the ventricular repolarization in a reverse use-dependent manner, reflecting blockade of the rapid component of delayed rectifier K(+) current, and the potency was relatively weak; namely, maximum change in QTc was +20 ms (+5.6%). The high dose also induced the negative inotropic effect possibly through Ca(2+) channel-independent pathway. In order to clarify proarrhythmic risk, 30 mg/kg, i.v., of azithromycin was examined with the chronic atrioventricular block dogs (n = 4). Azithromycin neither induced torsade de pointes nor affected beat-to-beat variability of repolarization. Thus, azithromycin can be considered to lack proarrhythmic potential, but caution has to be paid on its use for patients with left ventricular dysfunction.

Transradial versus transfemoral coronary intervention for acute myocardial infarction complicated by cardiogenic shock: is transradial coronary intervention suitable for emergency PCI in high-risk acute myocardial infarction?

BACKGROUND: Data are limited regarding the clinical results of transradial coronary intervention (TRI) in acute myocardial infarction (AMI) complicated by cardiogenic shock. OBJECTIVE: The aim of this study was to compare the clinical results of TRI and transfemoral coronary intervention (TFI) in AMI patients who had cardiogenic shock and underwent emergency percutaneous coronary intervention (PCI). METHODS: Between January 1, 2006, and August 31, 2012, a total of 507 consecutive patients with AMI underwent emergency PCI within 12 hours of onset. Eighty-five patients presented with cardiogenic shock and were enrolled. Among these patients, 60 underwent TRI and 25 underwent TFI. Outcome measures included the following: major bleeding and vascular complications; major adverse cardiac or cerebrovascular events (MACCE); all-cause death; door-to-balloon time; and PCI procedural success. RESULTS: TRI had a significantly lower rate of major bleeding and vascular complications within 30 days (6.7% vs. 28.0%; P<.05) and 1 year (log-rank P<.05) than TFI. No significant differences were observed between the two groups in the MACCE rate within 30 days (28.3% vs. 44.0%; P=.21) and 1 year (log-rank P=.06), and the all-cause death rate within 30 days (26.7% vs. 40.0%; P=.30) and 1 year (log-rank P=.09). In addition, TRI was not inferior to TFI in terms of door-to-balloon time (99.8 min vs. 110.4 min; P=.30) and PCI procedural success (95.0% vs. 96.0%; P>.99). CONCLUSION: TRI is associated with fewer major bleeding and vascular complications than TFI, and it appears suitable for both low- and high-risk AMI patients, especially when AMI is complicated by cardiogenic shock.

Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells.

AIM: Vascular senescence, which is accelerated in individuals with chronic kidney disease (CKD), contributes to the development of cardio-renal syndrome, and various uremic toxins may play important roles in the mechanisms underlying this phenomenon. We recently reported that indoxyl sulfate (IS), a uremic toxin, directly activates aryl hydrocarbon receptor (AhR) and generates oxidative stress through NADPH oxidase-4 in human umbilical vein endothelial cells (HUVECs). In the current study, we sought to examine whether IS regulates sirtuin 1 (Sirt1) and affects endothelial senescence via AhR activation. METHODS: HUVECs were incubated with 500 µmol/L of IS for the indicated time periods. In order to evaluate changes in the senescence of the HUVECs, the number of senescence-associated ß-galactosidase (SA ß-gal)-positive cells was determined using an image analysis software program. The intracellular nicotinamide phosphoribosyltransferase (iNampt) activity, cellular NAD(＋)/NADPH ratio and Sirt1 activity were analyzed according to a colorimetric assay to determine the mechanism of cellular senescence. Furthermore, we evaluated the involvement of AhR in the senescence-related changes induced by IS using AhR antagonists. RESULTS: IS decreased the iNampt activity, NAD(＋)/NADPH ratio and Sirt1 activity, resulting in an increase in the percentage of SA ß-gal-positive cells. On the other hand, the AhR antagonists restored the IS-induced decrease in the NAD(＋) content in association with an improvement in the iNampt activity and ameliorated the senescence-related changes. Taken together, these results indicate that IS impairs the iNampt-NAD(＋)-Sirt1 system via AhR activation, which in turn promotes endothelial senescence. CONCLUSIONS: The IS-AhR pathway induces endothelial senescence. Therefore, blocking the effects of AhR in the endothelium may provide a new therapeutic tool for treating cardio-renal syndrome.

Antifibrotic response of cardiac fibroblasts in hypertensive hearts through enhanced TIMP-1 expression by basic fibroblast growth factor.

BACKGROUND: Cardiac fibroblasts (CFs) play a pivotal role in the development of myocardial fibrosis. We previously demonstrated that direct injection of basic fibroblast growth factor (bFGF) into the hypertensive Dahl salt-sensitive (DS) rat heart prevented systolic dysfunction and left ventricular dilation effectively. However, the precise role played by bFGF in fibrotic response of CFs remains unclear. We suggested potential effects of bFGF on the fibrotic response of CFs in vitro. METHODS AND RESULTS: Histopathologic assessment of cardiac fibrosis demonstrated a marked decline in the extent of perivascular and interstitial fibrosis in bFGF-injected hypertensive DS rat hearts. CFs harvested from the hearts of noninjected DS rats demonstrated a significantly increased messenger RNA (mRNA) expression of matrix metalloproteinase (MMP)-2, MMP-9, and both collagen I and III. In contrast, bFGF treatment in the CFs induced a marked increase in tissue inhibitor of MMP (TIMP)-1 expression and a marked decline in MMP-9 activation. bFGF also induced a decline in α-smooth muscle actin and collagen I and III mRNA expression in the CFs accompanied by inhibited differentiation of CFs into myofibroblasts. Small interfering RNA targeting FGF receptor 1 confirmed a specific interference of the mRNA expression changes elicited by bFGF. In vivo examination confirmed many TIMP-1-positive CFs in perivascular spaces of bFGF-injected hearts. CONCLUSIONS: Up-regulated TIMP-1 expression and down-regulated MMP-9 activation by bFGF in CFs could prevent excessive ECM degradation and collagen deposition in perivascular spaces effectively, leading to prevention of cardiac fibrosis during hypertensive heart failure. SUMMARY: Cardiac fibroblasts (CFs) play a pivotal role in myocardial fibrosis. The precise role of CFs in fibrotic response played by growth factors remains unclear. Our results indicates that basic fibroblast growth factor could up-regulate TIMP-1 expression and down-regulate MMP-9 activation in CFs in perivascular spaces, leading to inhibited progression of cardiac fibrosis during hypertensive heart failure.

[Fibrates].

Although fibrates was a medicine with a long history, at the clinical spot, the profitability had not permeated as compared with statin. However, many-sided effects, such as a fall of a cardiovascular event and control of arteriosclerosis prevention and a diabetic microangiopathy, were reported as a result of the large-scale clinical test in recent years. Accumulation of the further clinical evidence of a fibrates is expected.

Cardiohemodynamic and electrophysiological effects of anti-influenza drug oseltamivir in vivo and in vitro.

Electropharmacological effects of oseltamivir were studied in comparison with pilsicainide using halothane-anesthetized dogs (n = 4) and isolated left atrium of guinea pigs (n = 5). Oseltamivir (0.3, 3 and 30 mg/kg, i.v.) or pilsicainide (1 and 3 mg/kg, i.v.) was additionally administered to the dogs. The low dose of oseltamivir provided clinically relevant plasma concentrations with C max of 4 µM. The low and middle doses of oseltamivir increased cardiac output, whereas the middle dose increased blood pressure and delayed intra-atrial conduction and ventricular repolarization. The high dose of oseltamivir exerted negative chronotropic, inotropic and hypotensive effects, while it delayed intra-atrial, atrioventricular nodal and intra-ventricular conduction and ventricular repolarization. Use-dependent delay of ventricular repolarization was observed after oseltamivir, whereas reverse use-dependent prolongation was induced by pilsicainide. Moreover, oseltamivir more selectively suppressed intra-atrial conduction than intra-ventricular conduction, which was less selective for pilsicainide. Action potential assay using isolated atrium indicated that oseltamivir (10 µM) decreased V max more than pilsicainide (10 µM) and that oseltamivir (10-100 µM) prolonged action potential duration, which was not induced by pilsicainide (1-10 µM). Thus, oseltamivir in clinically relevant to its 10 times higher doses is relatively safe, whereas 10-100 times higher doses possess unique electrophysiological profile.

Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells.

BACKGROUND: Indoxyl sulfate (IS) is a uremic toxin that causes renal injury, but little is known about its adverse effects on the cardiovascular system. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor that mediates adaptive and toxic responses in cells. Recent studies identified IS as an endogenous agonist for AhR, as well as other tryptophan metabolites. The aim of the study was to investigate whether IS activates AhR, with subsequent inflammatory responses contributing to the development of atherogenesis, in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: We demonstrated that IS stimulates the expression of AhR target genes, including cytochromes P450 1A1 and 1B1 mRNA, in a time-dependent manner, as well as translocation of AhR into the nucleus from the cytoplasm, indicating AhR activation. IS-stimulated AhR activation was accompanied by an increase in oxidative stress, proven by enhanced NADPH oxidase 4 expression and dihydroethidium staining. Additionally, AhR inhibitors abolished the IS-induced increase in monocyte chemoattractant protein-1 (MCP-1) expression in a dose-dependent manner. Taken together, these results suggest that IS activates AhR as an endogenous agonist and induces MCP-1 expression through reactive oxygen species production in HUVECs. CONCLUSIONS: Our findings give a novel understanding of the physiological effect of IS on the cardiovascular system and indicate possibilities for preventing cardiorenal syndrome by regulating serum IS levels.

Coronary computed tomography angiography-based coronary risk stratification in subjects presenting with no or atypical symptoms.

BACKGROUND: Coronary computed tomography angiography (CTA) findings of positive vessel remodeling and low-attenuation plaque, referred to as computed tomography-verified high-risk plaque (CT-HRP), have been reported to be associated with the development of subsequent acute coronary syndromes. The aim of this study was to examine the usefulness of coronary CTA for coronary risk re-stratification of patients with asymptomatic and atypical chest symptoms. METHODS AND RESULTS: A total of 1,139 subjects (M/F 602/537; mean age, 61.5±9.3 years) who were either asymptomatic or presented with atypical chest symptoms underwent coronary 64- or 320-slice multidetector computed tomography angiography and Agatston score. Age, sex, coronary risk factors, including hypertension, diabetes mellitus (DM), dyslipidemia, and smoking were investigated as predictors for CT-HRP on multivariate analysis using logistic regression analysis. CT-HRP was observed in 72 patients (6.3%). Based on Framingham risk scores (FRS), CT-HRP was observed in 0/94 subjects (0.0%) in the low-risk group, 35/806 (4.3%) in the intermediate-risk group, and 37/239 (15.5%) in the high-risk group. On logistic regression analysis significant predictors for CT-HRP in intermediate- and high-risk subjects were male sex (odds ratio [OR] 2.829; 95% confidence interval [CI] 1.460-5.479, P=0.0021), DM (OR 2.418; 95% CI 1.420-4.116, P=0.0011), and current smoking (OR 1.922; 95% CI 1.096-3.371, P=0.0160). CT-HRP prevalence for Agatston scores >500 and >250 was lower in the intermediate- and high-risk groups, respectively. CONCLUSIONS: In asymptomatic subjects and those presenting with atypical chest pain who have a more than an intermediate risk, coronary CTA is contributory to FRS. Male sex, DM and smoking were independent predictors of vulnerable plaque in the more than intermediate-risk group.

Comparison of late potentials for 24 hours between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy using a novel signal-averaging system based on Holter ECG.

BACKGROUND: Late potentials (LP) detected with signal-averaged ECGs are known to be useful in identifying patients at risk of Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Because the pathophysiology is clearly different between these disorders, we clarified the LP characteristics of these disorders. METHODS AND RESULTS: This study included 15 BS and 12 ARVC patients and 20 healthy controls. All BS patients had characteristic ECG changes and symptomatic episodes. All ARVC patients had findings that were consistent with recent criteria. Three LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) were continuously measured for 24 hours using a novel Holter-based signal-averaged ECG system. The incidences of LP determination in BS (80%) and ARVC (91%) patients were higher than in healthy controls (5%; P<0.0001 in both) but did not differ between BS and ARVC patients. In BS patients, the dynamic changes of all LP parameters were observed, and they were pronounced at nighttime. On the contrary, these findings were not observed in ARVC patients. When the SD values of the 3 LP parameters (filtered QRS duration, root mean square voltage of the terminal 40 ms of the filtered QRS complex, and duration of low-amplitude signals [<40 µV] in the terminal, filtered QRS complex) over 24 hours were compared for the 2 patient groups, those values in BS patients were significantly greater than those in ARVC patients (P<0.0001 in all). CONCLUSIONS: LP characteristics detected by the Holter-based signal-averaged ECG system over 24 hours differ between BS and ARVC patients. Dynamic daily variations of LPs were seen only in BS patients. This may imply that mechanisms of lethal ventricular arrhythmia in BS may be more correlated with autonomic abnormality than that of ARVC.

Overshoot phenomena of respiratory gas variables during exercise recovery in cardiac patients.

BACKGROUND: Transient increases (overshoot) in respiratory gas variables have been observed during exercise recovery, but their clinical significance is not clearly understood. Our group evaluated the relationship between the presence of overshoot of respiratory gas variables and the parameters obtained from cardiopulmonary exercise testing (CPX). METHODS AND RESULTS: In total, 227 patients with various cardiac diseases underwent CPX. The overshoot phenomena of O2 uptake (·VO2), ·VO2/heart rate (O2-pulse), and CO2 output (·VCO2) were analyzed by respiratory gas analysis during recovery after maximal exercise. The overshoot of ·VO2, O2-pulse, and ·VCO2 were recognized in 11 (5%), 43 (19%), and 12 (5%) patients, respectively. Compared with the patients without a ·VO2 overshoot, those with a ·VO2 overshoot had a significantly lower peak ·VO2 (12.3±3.7 vs. 17.9±6.2ml·min⁻¹·kg⁻¹, P=0.003), lower anaerobic threshold (9.4±1.7 vs. 12.4±3.3 ml·min⁻¹·kg⁻¹, P=0.001), higher ·VE-·VCO2 slope (38.0±5.2 vs. 33.2±9.6, P=0.013), and lower left ventricular ejection fraction (LVEF) (39.9±22.8 vs. 55.8±16.8%, P=0.003). Similar findings were obtained for the patients with an O2-pulse overshoot and those with a ·VCO2 overshoot. CONCLUSIONS: The overshoot phenomena of respiratory gas variables during recovery after maximal exercise are correlated with impaired cardiopulmonary function during exercise in cardiac patients.