Cardiopulmonary exercise responses in patients with non-ischemic heart failure and a mildly reduced ejection fraction.

Background: The cardiopulmonary response to exercise in patients with heart failure exhibiting a mildly reduced ejection fraction (41% ≤ EF ≤ 49%) remains unclear. Materials & methods: A total of 193 consecutive patients with heart failure (excluding those with coronary artery disease) who underwent cardiopulmonary exercise (CPX) tests were examined. CPX variables were compared among patients with reduced, mildly reduced, and preserved EF. Results: The CPX test responses of patients with mildly reduced EF were similar to those of patients with reduced or preserved EF; however, increases in systolic blood pressure during exercise differed significantly (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake in patients with mildly reduced EF (ß = 0.41, 0.35, respectively; p < 0.05). Conclusion: Measurements of grip strength and blood pressure during exercise are useful predictors of prognoses in patients with non-ischemic and mildly reduced EF.

Cardiopulmonary exercise (CPX) test is widely used to evaluate the function related to heart in heart failure patients. The heart failure patients are divided into three groups: with reduced wall motion (HFrEF), with mildly reduced wall motion (HFmrEF) and with preserved wall motion (HFpEF). We compared the cardiopulmonary reaction to exercise among the three groups. The CPX test responses of patients with HFmrEF were similar to those of patients with HFrEF or HFpEF. However, increases in systolic blood pressure during exercise differed (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake, which is an important predictor of rate of death in patients with HFmrEF. Measurements of grip strength and blood pressure during exercise are useful predictors of progress in patients with enough blood supply to the heart and HFmrEF.

Relationship between epicardial adipose tissue volume and coronary artery spasm.

BACKGROUND: Epicardial adipose tissue (EAT) is considered to play a critical role in vascular endothelial function. Coronary artery spasm has been postulated to be a causal factor in vascular endothelial abnormalities and atherosclerosis. This study aimed to investigate the relationship between coronary artery spasm and EAT volume, total abdominal adipose tissue (AAT) area, and abdominal visceral adipose tissue (AVAT) area. METHOD: Among patients undergoing coronary computed tomography (CT) to evaluate coronary artery disease, we identified 110 patients who did not have significant coronary artery stenosis and underwent a coronary spasm provocation test with cardiac catheterization. They were divided into two groups according to the results of the spasm provocation test: spasm-positive and spasm-negative. EAT volume, total AAT area, and AVAT area were evaluated using CT images. RESULTS: Seventy-seven patients were included in the spasm-positive group and 33 patients in the spasm-negative group. There were no significant differences in baseline clinical characteristics between the two groups, except for the prevalence of current smoking (48% vs. 27%, p = 0.04). EAT volume was significantly higher in the spasm-positive group (108 ±â€¯38 mL vs. 87 ±â€¯34 mL, p = 0.007), while no significant difference was seen in total AAT area (280 ±â€¯113 cm2 vs. 254 ±â€¯128 cm2, p = 0.32) or AVAT area (112 ±â€¯54 cm2 vs. 98 ±â€¯55 cm2, p = 0.27). Multivariate logistic analysis indicated that EAT volume (per 10 cm3) (odds ratio, 1.198; 95% confidence interval, 1.035-1.388; p = 0.016) was a significant predictor of coronary artery spasm. CONCLUSION: Our results suggest that EAT has a strong association with coronary artery spasm, while AAT may not.

Prospective comparison of periprocedural coagulation markers among uninterrupted anticoagulants for atrial fibrillation ablation.

BACKGROUND: The difference in coagulation state during the periprocedural period of atrial fibrillation (AF) ablation among patients with uninterrupted anticoagulation has not been fully elucidated. OBJECTIVE: The purpose of this study was to compare periprocedural trends in coagulation markers among patients on uninterrupted anticoagulation for AF ablation. METHODS: In total, 275 consecutive patients who underwent AF ablation were evaluated. These patients were divided according to the anticoagulant they received into the dabigatran group (DG) (n = 64); rivaroxaban group (RG) (n = 62); apixaban group (AG) (n = 60); edoxaban group (EG) (n = 59); and warfarin group (WG) (n = 30). The trends in coagulation markers and the rate of silent stroke (SS) confirmed by postoperative magnetic resonance imaging were evaluated. RESULTS: The fibrin monomer complex (FMC) level on postoperative day 1 and the prothrombin fragment 1+2 (PF1+2) levels on the operative day and postoperative day 1 were higher in DG than in the other groups (P <.05, <.001, and <.001, respectively). The incidence of SS in DG (17%) was significantly higher than in RG (6%), AG (3%, EG (7%), or WG (4%) (P <.05). Dabigatran use independently predicted the occurrence of SS (odds ratio 4.12; 95% confidence interval 1.37-12.7; P <.05). CONCLUSION: FMC and PF1+2 levels during the periprocedural period of AF ablation were higher in DG than in the other groups. Dabigatran use independently predicted the occurrence of SS.

Impact of periprocedural anticoagulation therapy on the incidence of silent stroke after atrial fibrillation ablation in patients receiving direct oral anticoagulants: uninterrupted vs. interrupted by one dose strategy.

AIMS: Data on the comparison between uninterrupted and interrupted by one dose strategies for direct oral anticoagulant (DOAC) use during the periprocedural period of atrial fibrillation (AF) ablation are scarce. The purpose of this study is to investigate the feasibility of uninterrupted DOAC strategy by evaluating the incidence of silent stroke (SS) and perioperative trends in coagulation markers compared with the interrupted strategy. METHODS AND RESULTS: We randomly divided 200 consecutive patients receiving DOACs, who underwent AF ablation into uninterrupted group (UG = 100) and interrupted by one dose group (IG = 100). The rate of SS confirmed by post-operative magnetic resonance imaging and periprocedural trends in coagulation markers was investigated. A significant difference in SS incidence was found between the UG and IG (UG 4%, IG 17%, P < 0.005), although there were no differences in the rate of complications including bleeding and symptomatic thrombo-embolic events between the two groups. Intraoperative cardioversion [odds ratio (OR) 7.27, 95% confidence interval (CI) 1.76-30.0; P < 0.01] and the length of procedure time (OR 1.03, 95% CI 1.01-1.05; P < 0.05) independently predicted the occurrence of SS in the IG. A significant increase in prothrombin fragment 1 + 2 (PF1 + 2) values was observed in the IG compared with the UG on the operative and first post-operative days. CONCLUSION: Silent stroke incidence in the IG was significantly higher than that in the UG; this seems to be supported by the difference in PF1 + 2 values between the UG and IG. Intraoperative cardioversion and procedure time predicted the occurrence of SS in the IG.

Clinical Characteristics of Nonobese Patients with Acute Coronary Syndrome and Increased Epicardial Fat Volume.

AIM: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV. METHODS: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal. RESULTS: EFV was increased in ACS patients compared with control subjects (120±47 versus 95±45 mL, P＜0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m2. For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r=0.23, P=0.031). These individuals were significantly older (74±10 years) and tended to have a higher homeostasis model assessment-insulin resistance value (5.5±3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio=2.01, P=0.021) and correlated with abdominal circumference (r=0.26, P=0.017). CONCLUSION: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.

Trends in physiological coagulation factors in Japanese patients receiving novel oral anticoagulants.

BACKGROUND: Little is known about physiological anticoagulation effects via antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral anticoagulants (NOACs). METHODS: We evaluated 120 consecutive patients with non-valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40) or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with NOAC groups for age, sex and type of AF during the same time period. Blood samples were obtained in pretreatment, trough and peak phases to measure the activity of physiological coagulation inhibitors, including AT III and PC/PS or thrombus formation markers such as D-dimer and thrombin-antithrombin complex (TAT). RESULTS: D-dimer, TAT and AT III values for the NOAC groups were equivalent in the peak and trough phases. PC/PS activity in both phases was equally maintained in the pretreatment phase in the NOAC groups, while the activity in the WG was significantly suppressed in steady state. Moreover, no differences in trends for PC/PS activity were observed among NOAC groups. CONCLUSIONS: PC/PS activity was constant in both peak and trough phases in the patients on NOACs compared with activity of those on warfarin. In addition, there was no difference in the findings among NOACs.

Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients.

BACKGROUND AND AIMS: Omentin, an adipocytokine secreted by visceral adipose tissue, protects against obesity-linked cardiovascular complications. However, little is known about its role in epicardial adipose tissue (EAT) and coronary artery disease (CAD). We investigated the expression of omentin in EAT from CAD subjects. METHODS: EAT, subcutaneous adipose tissue (SCAT), and plasma samples were collected from CAD (n = 15; 23.3 ± 3.1 kg/m(2)) and non-CAD patients (n = 10; 20.8 ± 3.9 kg/m(2)). Omentin mRNA expression was measured using real-time PCR, while plasma concentrations were measured using an ELISA. EAT volume was determined with 64-slice computed tomography. RESULTS: Omentin expression in EAT and EAT volume were higher in CAD patients compared with controls (2.49 ± 2.6 vs. 0.85 ± 0.3, p = 0.002 and 113 ± 58 ml vs. 92.4 ± 30 ml, p = 0.045, respectively). Omentin expression in SCAT was similar between CAD and control patients (1.37 ± 0.84 vs. 1.07 ± 0.55, p = 0.267). Plasma omentin levels were lower in CAD patients compared with controls (343 ± 158 ng/ml vs. 751 ± 579 ng/ml, p = 0.025), and were negatively associated with the expression of omentin in EAT, in patients with CAD (ß = -0.78, p = 0.049). On the other hand, there was no association between omentin in EAT and clinical variables in patients with non-CAD. CONCLUSIONS: Omentin expression increases in the EAT of non-obese CAD patients, despite a decrease in plasma levels, suggesting that omentin may play a role in the pathogenesis of CAD.

Prognostic Value of Albuminuria on Cardiovascular Outcomes After Elective Percutaneous Coronary Intervention.

Albuminuria is the most widely evaluated marker of kidney damage. Many previous studies have demonstrated an association between the presence of albuminuria and increased cardiovascular events. However, there are limited data regarding the impact of albuminuria in patients requiring coronary revascularization. This study investigated whether the urinary albumin excretion rate could predict cardiovascular events in such a population. We enrolled 698 consecutive patients who underwent elective percutaneous coronary intervention. The baseline urinary albumin-to-creatinine ratio (ACR; mg/gCr) was measured and patients were divided into those with normoalbuminuria (ACR <30 mg/gCr), microalbuminuria (ACR 30 to 300 mg/gCr), or macroalbuminuria (ACR >300 mg/gCr). We collected data on the incidences of cardiac death and/or nonfatal myocardial infarction. We identified 389, 230, and 79 patients with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. During follow-up (median: 1,564 days), 41 events occurred. The event-free survival rate was 89% in patients with macroalbuminuria, 92% in those with microalbuminuria, and 97% in those with normoalbuminuria, respectively (log-rank test p = 0.002). After adjustment for conventional risk factors, Cox analysis revealed hazard ratios for cardiac death and/or nonfatal myocardial infarction were 2.56 (95% CI 1.23 to 5.32, p = 0.01) in those with microalbuminuria and 4.02 (95% CI 1.59 to 10.12, p = 0.003) in those with macroalbuminuria compared with those with normoalbuminuria. In conclusion, an elevated urinary albumin excretion rate independently predicted adverse cardiovascular outcomes, with a gradual risk increase that progressed from microalbuminuria to macroalbuminuria in patients undergoing elective percutaneous coronary intervention.

Noninvasive mathematical analysis of spectral electrocardiographic components for coronary lesions of intermediate to obstructive stenosis severity-relationship with classic and functional SYNTAX score.

OBJECTIVES: The aim of this study was to evaluate the relationship between the multifunction cardiogram (MCG), and SYNTAX score (SS) and functional SYNTAX score (FSS) in detecting the presence of intermediate to obstructive coronary lesions. BACKGROUND: Performing coronary angiography (CAG) and measuring fractional flow reserve (FFR) to calculate the SS and FSS is inherently invasive and adds complexity. METHODS: The MCG was obtained and analyzed before performing CAG in 87 consecutive subjects with suspected coronary artery disease who were scheduled for elective CAG. The patients were divided into three groups according to risk based on high, borderline, and low MCG scores. The SS was determined, as well as FSS but only by counting lesions prone to functional ischemia (FFR ≤ 0.8). The relationship between the MCG and the SS and FSS was evaluated. RESULTS: The MCG was the only test significantly associated with the SS (odds ratio, 2.92 [1.60 - 5.31], P < 0.001) and FSS (odds ratio, 3.66 [1.95 - 6.87], P < 0.001). A high MCG score had a specificity of 92.6% (89.0-96.2%) and 92.3% (89.0-95.6%), and a predictive accuracy of 72.4% (67.6-77.2%) and 82.8% (78.7-86.8%) for the prediction of SS and FSS, respectively. CONCLUSIONS: The MCG showed high specificity and predictive accuracy especially for the FSS, suggesting that it is useful not only in identifying functionally significant ischemia but also in reducing unnecessary CAGs.

Non-invasive assessment of functionally significant coronary stenoses through mathematical analysis of spectral ECG components.

OBJECTIVES: The aim of this study was to evaluate the accuracy of the Multifunction CardioGram (MCG) in detecting the presence of functionally significant coronary ischaemia. METHODS AND RESULTS: This prospective study evaluated the accuracy of the MCG, a new ECG analysis device used to diagnose ischaemic coronary artery disease (CAD). A consecutive 112 participants suspected to have CAD who were scheduled for elective coronary angiography (CAG) from October 2012 to December 2013 were examined. Their predictive values of relevant ischaemia were measured by MCG, standard ECG and Framingham Risk Score (FRS) and compared. Five levels of ischaemia based on CAG findings adjusted by fractional flow reserve (FFR) values and three levels of MCG score of high, borderline or low were used. The MCG (OR=2.67 (1.60 to 4.44), p<0.001) was the only test significantly associated with ischaemia level. The FFR values for individual MCG scores with low, borderline and high were 0.77 (0.70 to 0.86), 0.78 (0.71 to 0.82) and 0.69 (0.65 to 0.77), respectively, p=0.042. A high MCG score had a specificity of 90.4% (87.0% to 93.9%) in model 1 adjusted by FFR≤0.8 threshold and of 87.0% (83.2% to 90.8%) in model 2 adjusted by FFR≤0.75 threshold, and a negative predictive value of 82.5% (78.3% to 86.7%) in model 1 and of 83.8% (79.6% to 87.9%) in model 2 for the prediction of severe ischaemia. CONCLUSIONS: The MCG showed high specificity with a high negative predictive value, suggesting that the MCG could be used not only to identify functionally significant ischaemia but to reduce unnecessary CAGs. TRIAL REGISTRATION NUMBER: UMIN ID: 000009992.

Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients.

OBJECTIVE: Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. METHODS: We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m(2)). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. RESULTS: EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = -0.49 and 0.20). CONCLUSIONS: In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

The different association of epicardial fat with coronary plaque in patients with acute coronary syndrome and patients with stable angina pectoris: analysis using integrated backscatter intravascular ultrasound.

OBJECTIVES: We assessed the hypothesis that the epicardial fat is associated with coronary lipid plaque. BACKGROUND: Epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS), and lipid-rich plaques have been associated with acute coronary events. METHODS: We enrolled 112 individuals who underwent percutaneous coronary intervention (PCI) (66 with ACS; 46 with stable angina pectoris [SAP]) and classified plaque components using integrated backscatter intravascular ultrasound as calcified, fibrous, or lipid. Possible effects of PCI on plaque data were minimized by assessing 10-mm vessel lengths proximal to the culprit lesions. Total plaque volume and percentage volumes of individual plaque components were calculated. EFV and abdominal visceral fat area were measured using 64-slice computed tomography. RESULTS: ACS patients had significantly higher EFV than did SAP patients (118 ± 44 vs.101 ± 41 mL, p = 0.019). In ACS patients, EFV was correlated with total plaque volume and percentage of lipid plaque (r = 0.27 and 0.31, respectively; p < 0.05). Moreover, an independent interaction between EFV and lipid-rich plaque (odds ratio, 1.04; 95% confidence interval, 1.00-1.07) were revealed. In contrast, in SAP patients, EFV was positively correlated with body mass index and abdominal visceral fat area but not with plaque characteristics. CONCLUSIONS: EFV was associated with lipid-rich plaque in patients with ACS, whereas no correlation between EFV and coronary plaque profile was apparent in SAP patients. Epicardial fat may have a role in the development of lipid plaque, which contributes to the pathogenesis of ACS.

Usefulness of serum cardiac troponins T and I to predict cardiac molecular changes and cardiac damage in patients with hypertrophic cardiomyopathy.

Cardiac troponins provide diagnostic and prognostic information on ischemic heart disease, but their roles in hypertrophic cardiomyopathy (HCM) are unclear. We sought to investigate the associations between elevated serum cardiac troponins T (cTnT) and I (cTnI) levels and cardiac injury in patients with HCM. We measured serum cTnT and cTnI in a peripheral vein of 73 consecutive HCM patients in stable condition. In addition, to examine the transcardiac release of cTnT and that of cTnI, we measured them in the aortic root and coronary sinus. Mitochondrial- and Ca(2+)-handling-related gene expression assays were analyzed by endomyocardial biopsy specimens. Based on the median value of serum cTnT, we divided the patients into two groups [group A: cTnT < 0.008 ng/mL, (n = 35), group B: cTnT group ≥ 0.008 ng/mL, (n = 38)]. Left ventricular (LV) mass index was significantly higher, while LV ejection fraction was significantly lower, in group B than in group A. Meanwhile, there was a significantly positive correlation between the transcardiac gradient of serum cTnT or cTnI, and the mRNA level of troponin I3 (r = 0.473, r = 0.516, respectively). The mRNA level of troponin T2 significantly correlated with mRNA levels of sarco-endoplasmic reticulum Ca(2+)-ATPase 2, cytochrome c oxidase subunit 5B, and troponin I3 (r = 0.486, r = 0.957, r = 0.633, respectively). These findings indicate that both elevated serum cTnT and cTnI might be associated with cardiac dysfunction in patients with HCM, resulting from the impairment of mitochondrial function and Ca(2+)-handling protein.

Relationship of myocardial fibrosis to left ventricular and mitochondrial function in nonischemic dilated cardiomyopathy--a comparison of focal and interstitial fibrosis.

BACKGROUND: Mitochondrial damage is associated with histologic myocardial fibrosis. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) can be used to identify focal fibrosis. We examined whether myocardial fibrosis on CMR and collagen volume fraction (CVF) from biopsies correlated with left ventricular (LV) and mitochondrial function in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Fifty-nine DCM patients underwent CMR, cardiac catheterization, and endomyocardial biopsy. Minimum first derivative of LV pressure (LVdP/dt(min)) was measured as an index of LV relaxation. Mitochondrial RNA expression was also analyzed. For quantitative analysis of myocardial fibrosis, percentage LGE (%LGE) and CVF were calculated. Patients were divided into 2 groups on the basis of the presence (LGE group; n = 27) or absence (non-LGE group; n = 32) of LGE. Mean CVF and absolute value of LVdP/dt(min) were significantly higher and lower, respectively, in the LGE group than in the non-LGE group. Multivariate analysis revealed that %LGE was an independent determinant of LVdP/dt(min). The abundance of mitochondrial enzyme mRNA was significantly lower in the LGE group. CONCLUSIONS: Noninvasive CMR imaging is more useful in predicting diastolic dysfunction than invasive histologic assessments. In addition, it might indicate mitochondrial dysfunction in DCM.

Increased (99m)Tc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients.

OBJECTIVES: This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM). BACKGROUND: Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial (99m)Tc-MIBI washout is reportedly caused by mitochondrial dysfunction. METHODS: Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial (99m)Tc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) (an index of myocardial contractility) and LV pressure half-time (T1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 µg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤ 24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%. RESULTS: WR was significantly correlated with the percentage changes in LV dP/dtmax (%LV dP/dtmax) (r: -0.59; p = 0.01) and T1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dtmax was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044). CONCLUSIONS: Increased (99m)Tc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients.

Association between indoxyl sulfate and cardiac dysfunction and prognosis in patients with dilated cardiomyopathy.

BACKGROUND: Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (± standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5 ± 10.7% and 204 ± 219 pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9 µg/ml) and high IS (≥ 0.9 µg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e' was significantly greater in the high IS group than in the low IS group. Furthermore, E/e' was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP. CONCLUSIONS: Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.

Cerebral embolism due to atrial myopathy in a cardiac amyloidosis patient diagnosed by cardiac magnetic resonance imaging.

A 55-year-old woman was admitted with heart failure. On the third hospital day, she suddenly developed cerebral infarction. The resting 12-lead electrocardiography showed normal sinus rhythm, and atrial fibrillation or flutter were never detected on electrocardiographic monitoring throughout the whole hospital days. She had no other conventional risk factor for cerebral infarction. Transthoracic echocardiography showed left ventricular hypertrophy. Transesophageal echocardiogram revealed strong spontaneous echo contrast in the left atrium (LA), and the blood flow in the left atrial appendage was extremely decreased (22.3 cm/s). Late gadolinium enhancement in cardiac magnetic resonance (CMR) imaging showed global subendocardial hyperenhancement of the left ventricle and both atria. Endomyocardial biopsy specimen was positive for amyloid by Congo red staining. Marked amyloid infiltration to both atria might cause atrial dysfunction leading to thrombus formation in the LA. CMR is thought to be a useful noninvasive tool to detect atrial myopathy in cardiac amyloidosis patients. .

Predictive value of heart rate recovery after exercise testing in addition to brain natriuretic peptide levels in ambulatory patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Heart rate recovery (HRR) is related to autonomic function and is a prognostic marker in cardiovascular disease. We sought to investigate the clinical utility of HRR in addition to BNP levels in ambulatory outpatients with nonischemic dilated cardiomyopathy (NICM). METHODS: Seventy-nine NICM outpatients were followed for a mean of 19 months. HRR was defined as the difference in heart rate between peak exercise and 1 minute later. On the basis of the lower tertile value, we allocated the patients to two groups: with HRR >12 bpm (n = 48; normal) and with HRR ≤12 bpm (n = 31, abnormal). RESULTS: The probability of cardiac event-free survival was significantly lower in the abnormal HRR group than in the normal HRR group (P = 0.002). Stepwise multivariate analysis revealed that plasma BNP and HRR were independent predictors of cardiac events. Patients with both HRR ≤12 bpm and BNP ≥200 pg/mL had significantly higher rates of cardiac events than those in whom only one, or neither, of these variables was abnormal. CONCLUSIONS: HRR after exercise testing, in addition to plasma BNP level, might be a useful indicator as a predictor for admission due to worsening heart failure and its combination is able to provide additive prognostic information in ambulatory outpatients with NICM.

Predictive value of functional limitation for disease severity in patients with mild chronic heart failure.

BACKGROUND: We aimed to verify a measure for functional limitation using the Performance Measure for Activity of Daily Living-8 (PMADL-8) clinical assessment tool. This tool was utilized to determine disease severity by comparing disease severity with physiological and demographic variables, which have been well documented as predictors for mortality and rehospitalization in chronic heart failure (CHF) patients. METHODS: We consecutively enrolled 125 CHF patients with impaired left ventricular systolic function who underwent cardiopulmonary exercise testing in Nagoya University Hospital. We measured PMADL-8, which had a total score that ranged from 8 to 32 points, in which higher scores indicated severe functional limitations to evaluate the patient's functional limitations and evaluate clinical physiologic variables, which were established as prognostic factors of CHF. First, the association between PMADL-8 and other clinical variables was analyzed by correlation coefficients, and then, multivariate regression analysis was performed to select independent correlate factors. Lastly, we identified the optimal PMADL-8 threshold for detecting disease severity by comparing with the threshold for disease severity in selected variables. RESULTS: The PMADL-8 indicated excellent correlation with peak oxygen uptake (peakVO(2)) (r=-0.743, p<0.001), and the multivariate regression analysis revealed that peakVO(2) was independently correlated with the PMADL-8 (p<0.001). The optimal PMADL-8 threshold for detecting a peakVO(2) value of 18 ml/min/kg was 18 points. Similarly, a peakVO(2) value of 14 ml/min/kg was 22 points, and a peakVO(2) value of 16 ml/min/kg was 20 points. CONCLUSIONS: Our data indicate that functional limitation as evaluated by the PMADL-8 is well correlated with peakVO(2). PMADL-8 may have potential as a clinical assessment tool to manage disease status in CHF patients.