Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer.

AIM: The incidence of Helicobacter pylori-negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD. METHODS: This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision-tree algorithm and random forest analysis. RESULTS: Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451-16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32). CONCLUSIONS: Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Impact of non-obese metabolic dysfunction-associated fatty liver disease on risk factors for the recurrence of esophageal squamous cell carcinoma treated with endoscopic submucosal dissection: A multicenter study.

AIM: Metabolic dysfunction is a risk factor for esophageal squamous cell carcinoma (ESCC). We investigated the impact of the recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) and its subtypes on ESCC recurrence after endoscopic treatment. METHODS: This multicenter observational cohort study enrolled consecutive patients newly diagnosed with ESCC after endoscopic treatment. Patients were classified into MAFLD or non-MAFLD groups. The MAFLD group was further classified into non-obese and obese MAFLD groups with a body mass index cutoff value of 25 kg/m2 . The impact of MAFLD on the recurrence of ESCC was evaluated using a decision tree algorithm and random forest analysis. RESULTS: A total of 147 patients (average age 69 years; male : female, 127:20; observational period, 2.4 years) were enrolled. The 1-, 3-, and 5-year recurrence rates were 2.0%, 21.1%, and 33.7%, respectively. Independent risk factors for the recurrence of ESCC were MAFLD (HR 2.2812; 95% confidence interval 1.0497-4.9571; p = 0.0373), drinking status, and smoking status. Metabolic dysfunction-associated fatty liver disease was identified as the second most important classifier for recurrence, followed by drinking status. The cumulative incidence of ESCC recurrence was higher in the MAFLD group than in the non-MAFLD group. In a subanalysis, the cumulative incidence of recurrence was significantly higher in the non-obese than in the obese MAFLD group among abstainers/non-drinkers. Directed acyclic graphs revealed that MAFLD directly contributes to ESCC recurrence. CONCLUSIONS: MAFLD was independently and directly associated with ESCC recurrence after endoscopic treatment; a high recurrence rate was observed in patients with non-obese MAFLD. Metabolic dysfunction-associated fatty liver disease may identify patients at high risk for ESCC recurrence.

Novel Non-Invasive Index for Prediction of Responders in Cardiac Resynchronization Therapy Using High-Resolution Magnetocardiography.

BACKGROUND: Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction pattern on magnetocardiography (MCG) can predict CRT responders.Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean [±SD] LV ejection fraction [LVEF] 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or <35°, respectively, in the direction of the maximal current arrow after the QRS peak. Baseline New York Heart Association functional class and LVEF were comparable between the 2 groups, but QRS duration was longer and the presence of complete left bundle branch block and LV dyssynchrony was higher in the UDC than MDC group. Six months after CRT, 30 patients were defined as responders, with significantly more in the UDC than MDC group (89% vs. 14%, respectively; P<0.001). Over a 5-year follow-up, Kaplan-Meyer analysis showed that adverse cardiac events (death or implantation of an LV assist device) were less frequently observed in the UDC than MDC group (6/28 vs. 15/28, respectively; P=0.027). Multivariate analysis revealed that UDC on MCG was the most significant predictor of CRT response (odds ratio 69.8; 95% confidence interval 13.14-669.32; P<0.001). CONCLUSIONS: Preoperative non-invasive MCG may predict the CRT response and long-term outcome after CRT.

Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography.

BACKGROUND: The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64-channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs. METHODS: Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP-VF(+)) and 103 with no history of VF (ERP-VF(-)). We measured the following MCG parameters in a time-domain waveform of relative current magnitude: (a) QRS duration (MCG-QRSD), (b) root-mean-square of the last 40 ms (MCG-RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG-LAS). RESULTS: Compared to ERP-VF(-), ERP-VF(+) subjects presented a significantly longer MCG-QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG-RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG-LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG-QRSD and MCG-RMS40 showed significantly larger area under the ROC curve compared to J-peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG-QRSD ≥ 100 ms and MCG-RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80-22.3), and 92%, 48%, and 10.9 (95% CI, 1.37-86.8), respectively. CONCLUSION: Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.

Clinical and Electrocardiographic Differences in Brugada Syndrome With Spontaneous or Drug-Induced Type 1 Electrocardiogram.

BACKGROUND: Spontaneous type 1 electrocardiogram (ECG) in the right precordial lead is a dominant predictor of ventricular fibrillation (VF) in Brugada syndrome (BrS). In some BrS patients with VF, however, spontaneous type 1 ECG is undetectable, even in repeated ECG and immediately after VF. This study investigated differences between BrS patients with spontaneous or drug-induced type 1 ECG. Methods and Results: We evaluated 15 BrS patients with drug-induced (D-BrS) and 29 with spontaneous type 1 ECG (SP-BrS). All patients had had a previous VF episode. In each D-BrS patient, ECG was recorded more than 15 times (mean, 46±34) during 7.2±5.1 years of follow-up. Age and family history were comparable between groups. Inferolateral early repolarization (ER) was observed in 13 D-BrS (87%) at least once but in only 3 SP-BrS (10%, P<0.01). Immediately after VF, inferolateral ER was accentuated in 9 of 10 D-BrS, while type 1 ECG was accentuated in 12 of 16 SP-BrS. Fragmented QRS in the right precordial lead and aVR sign were absent in D-BrS but present in 20 (69%, P<0.01) and 11 (38%, P<0.01) SP-BrS, respectively. There was no prognostic difference between groups. CONCLUSIONS: Although having similar clinical profiles, there are obvious ECG differences between VF-positive BrS patients with spontaneous or drug-induced type 1 ECG. The inferolateral lead rather than the right precordial lead on ECG may be particularly crucial in some BrS patients.

Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia.

Aims: Andersen-Tawil Syndrome (ATS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are both inherited arrhythmic disorders characterized by bidirectional ventricular tachycardia (VT). The aim of this study was to evaluate the diagnostic value of exercise stress tests for differentiating between ATS and CPVT. Methods and results: We included 26 ATS patients with KCNJ2 mutations from 22 families and 25 CPVT patients with RyR2 mutations from 22 families. We compared the clinical and electrocardiographic (ECG) characteristics, responses of ventricular arrhythmias (VAs) to exercise testing, and the morphology of VAs between ATS and CPVT patients. Ventricular arrhythmias were more frequently observed at baseline in ATS patients compared with CPVT patients [the ratio of ventricular premature beats (VPBs)/sinus: 0.83 ± 1.87 vs. 0.06 ± 0.30, P = 0.01]. At peak exercise, VAs were suppressed in ATS patients, whereas they were increased in CPVT patients (0.14 ± 0.40 vs. 1.94 ± 2.71, P < 0.001). Twelve-lead ECG showed that all 25 VPBs and 15 (94%) of 16 bidirectional VTs were right bundle branch block (RBBB) morphology in ATS patients, whereas 19 (86%) of 22 VPBs had left bundle branch block (LBBB), and 12 (71%) of 17 bidirectional VT had LBBB and RBBB morphologies in CPVT patients. Conclusion: In patients with ATS, VAs with RBBB morphology were frequently observed at baseline and suppressed at peak exercise. In contrast, exercise provoked VAs with mainly LBBB morphology in patients with CPVT. In adjunct to clinical and baseline ECG assessments, exercise testing might be useful for making the diagnosis of ATS vs. CPVT, both characterized by bidirectional VT.

Isolated Late Activation Detected by Magnetocardiography Predicts Future Lethal Ventricular Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. CONCLUSIONS: MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.

Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome.

AIMS: Published reports regarding inferolateral early repolarization (ER) syndrome (ERS) before 2013 possibly included patients with Brugada-pattern electrocardiogram (BrP-ECG) recorded only in the high intercostal spaces (HICS). We investigated the significance of HICS ECG recording in ERS patients. METHODS AND RESULTS: Fifty-six patients showing inferolateral ER in the standard ECG and spontaneous ventricular fibrillation (VF) not linked to structural heart disease underwent drug provocation tests by sodium channel blockade with right precordial ECG (V1-V3) recording in the 2nd-4th intercostal spaces. The prevalence and long-term outcome of ERS patients with and without BrP-ECG in HICS were investigated. After 18 patients showing type 1 BrP-ECG in the standard ECG were excluded, 38 patients (34 males, mean age; 40.4 ± 13.6 years) were classified into four groups [group A (n = 6;16%):patients with ER and type 1 BrP-ECG only in HICS, group B (n = 5;13%):ERS with non-type 1 BrP-ECG only in HICS, group C (n = 8;21%):ERS with non-type 1 BrP-ECG in the standard ECG, and group D (n = 19;50%):ERS only, spontaneously or after drug provocation test]. During follow-up of 110.0 ± 55.4 months, the rate of VF recurrence including electrical storm was significantly higher in groups A (4/6:67%), B (4/5:80%), and C (4/8:50%) compared with D (2/19:11%) (A, B, and C vs. D, P < 0.05). CONCLUSIONS: Approximately 30% of the patients with ERS who had been diagnosed with the previous criteria showed BrP-ECG only in HICS. Ventricular fibrillation mostly recurred in patients showing BrP-ECG in any precordial lead including HICS; these comprised 50% of the ERS cohort.

Utility of High-Resolution Magnetocardiography to Predict Later Cardiac Events in Nonischemic Cardiomyopathy Patients With Normal QRS Duration.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) patients, even those with a narrow QRS, are at increased risk for major adverse cardiac events (MACE). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect prognostic left intraventricular disorganized conduction (LiDC) by overcoming the limitations of fragmented QRS (fQRS, qualitative definitions, low specificity) and late potential (abnormality undetectable in earlier QRS).Methods and Results:We evaluated LiDC on MCG, defined as significant deviation from a global clockwise left ventricular (LV) activation pattern, and conventional noninvasive predictors of MACE, including fQRS and late potential, in 51 NIDCM patients with narrow QRS (LV ejection fraction, 22±7%; QRS duration, 99±11 ms). MACE was defined as cardiac death, lethal ventricular arrhythmias, or LV assist device (LVAD) implantation. LiDC was present in 22 patients. Baseline characteristics were comparable between patients with and without LiDC, except for the ratio of positive late potential. During a mean follow-up of 2.9 years, MACE developed in 16 NIDCM patients (3 cardiac deaths, 9 lethal ventricular arrhythmias, and 4 LVAD). MACE was more incident in patients with LiDC (13/22) than in those without (3/29, P<0.001). Multivariate analysis revealed LiDC, but not fQRS or late potential, as the strongest independent predictor of MACE (hazard ratio 4.28, 95% confidence interval 1.30-19.39, P=0.015). CONCLUSIONS: MCG accurately depicts LiDC, a promising noninvasive predictor of MACE in patients with NIDCM and normal QRS.

Targeting of high peak respiratory exchange ratio is safe and enhances the prognostic power of peak oxygen uptake for heart failure patients.

BACKGROUND: Peak oxygen uptake (V̇O2) and ventilatory efficiency (V̇E/V̇CO2slope) measured on cardiopulmonary exercise testing (CPX) are prognostic indicators in heart failure (HF) patients, but peak V̇O2is influenced by patient effort. In CPX targeting a peak respiratory exchange ratio (pRER; an objective index of effort adequacy) higher than the commonly recommended level, we assessed the safety and prognostic value of CPX parameters compared with non-CPX parameters. METHODS AND RESULTS: We studied 283 consecutive HF patients with left ventricular ejection fraction (LVEF) ≤45% (mean, 26.3%) who underwent CPX targeting pRER >1.20. The attained pRER (mean, 1.26) was consistently high irrespective of LVEF, and there was no major exercise-related adverse event. The composite of all-cause death or HF hospitalization occurred in 111 patients (39%) during a median follow-up of 47 months. Among well-known prognostic markers, peak V̇O2was the most powerful predictor of outcome as both a continuous and an optimal dichotomous variable, followed by V̇E/V̇CO2slope. On multivariate analysis, peak V̇O2was a significant independent predictor, whereas V̇E/V̇CO2slope, B-type natriuretic peptide, and LVEF were not. CONCLUSIONS: In CPX targeting pRER >1.20 for HF patients, peak V̇O2is the most powerful among well-known predictors, without an increased risk of exercise-related events. These findings advocate a high target pRER in CPX even in advanced HF.

Impact of cardiac rehabilitation on renal function in patients with and without chronic kidney disease after acute myocardial infarction.

BACKGROUND: Although there is a general fear that exercise training might deteriorate renal function in chronic kidney disease (CKD) patients, the effect of cardiac rehabilitation (CR) on renal function in acute myocardial infarction (AMI) patients with CKD remains unknown. We sought to determine whether CR is associated with amelioration or deterioration of renal function in such patients. METHODS AND RESULTS: We enrolled 528 AMI patients who participated in a 3-month CR program. Clinical data before and after CR were compared according to participation in CR and comorbidities. In patients without CKD (estimated glomerular filtration rate [eGFR] ≥60ml·min(-1)·1.73m(-2), n=348), peak oxygen uptake (VO2) and B-type natriuretic peptide (BNP) improved without a change in eGFR. In contrast, in patients with CKD (eGFR <60ml·min(-1)·1.73m(-2), n=180), eGFR improved (48±12 to 53±15ml·min(-1)·1.73m(-2), P<0.001), together with improvements in peak VO2 and BNP. When patients with CKD were divided into non-active (≤1time/week, n=70) and active participants (≥1.1time/week, n=110) according to attendance in CR, active participants showed an improvement in eGFR (50±10 to 53±13ml·min(-1)·1.73m(-2), P<0.001), whereas eGFR did not change in non-active participants. Similar results were obtained in each subgroup of patients with hypertension, dyslipidemia, or diabetes mellitus. CONCLUSIONS: In AMI patients with CKD, active participation in CR was associated with improved peak VO2, BNP, and eGFR.

Exercise-induced ST elevation in patients with non-ischemic dilated cardiomyopathy and narrow QRS complexes: novel predictor of long-term prognosis from exercise testing.

BACKGROUND: The clinical significance and prevalence of exercise-induced ST elevation (ESTE) in non-ischemic dilated cardiomyopathy (NIDCM) patients are unknown. METHODS AND RESULTS: We retrospectively examined 12-lead ECGs during cardiopulmonary exercise testing in 360 consecutive NIDCM patients (left ventricular ejection fraction (LVEF) <45%) with narrow QRS. ESTE was defined as ≥1.0mm ST (J-point) elevation compared with baseline. During long-term follow-up for major cardiac events (death, transplantation, or LV assist device implantation), ESTE was recognized in 50 patients (14%). They had much lower LVEF than patients without ESTE (20±7% vs. 27±7%, respectively, P<0.001), whereas the differences in peak VO2 (P=0.01) and VE/VCO2 slope (P=0.04) were relatively small. Major cardiac events occurred more frequently in patients with ESTE than in those without ESTE (39% vs. 12% at 48 months). Increased event rates were associated with low peak VO2 (<14ml·min(-1)·kg(-1)) in patients without ESTE (39% vs. 23%, P<0.05), but not in those with ESTE (50% vs. 62%, NS). Cox multivariate analysis revealed ESTE as the strongest independent prognosticator among exercise parameters (hazard ratio: 2.41 [95% confidence interval 1.03-5.63], P<0.05). CONCLUSIONS: A substantial number of NIDCM patients exhibit ESTE, which indicates a poor prognosis. Low peak VO2 and ESTE may reflect different aspects of the pathophysiological processes that deteriorate heart failure.

Adaptation of the respiratory controller contributes to the attenuation of exercise hyperpnea in endurance-trained athletes.

We have reported that minute ventilation [[Formula: see text]] and end-tidal CO(2) tension [[Formula: see text]] are determined by the interaction between central controller and peripheral plant properties. During exercise, the controller curve shifts upward with unchanged central chemoreflex threshold to compensate for the plant curve shift accompanying increased metabolism. This effectively stabilizes [Formula: see text] within the normal range at the expense of exercise hyperpnea. In the present study, we investigated how endurance-trained athletes reduce this exercise hyperpnea. Nine exercise-trained and seven untrained healthy males were studied. To characterize the controller, we induced hypercapnia by changing the inspiratory CO(2) fraction with a background of hyperoxia and measured the linear [Formula: see text] relation [[Formula: see text]]. To characterize the plant, we instructed the subjects to alter [Formula: see text] voluntarily and measured the hyperbolic [Formula: see text] relation ([Formula: see text]). We characterized these relations both at rest and during light exercise. Regular exercise training did not affect the characteristics of either controller or plant at rest. Exercise stimulus increased the controller gain (S) both in untrained and trained subjects. On the other hand, the [Formula: see text]-intercept (B) during exercise was greater in trained than in untrained subjects, indicating that exercise-induced upward shift of the controller property was less in trained than in untrained subjects. The results suggest that the additive exercise drive to breathe was less in trained subjects, without necessarily a change in central chemoreflex threshold. The hyperbolic plant property shifted rightward and upward during exercise as predicted by increased metabolism, with little difference between two groups. The [Formula: see text] during exercise in trained subjects was 21% lower than that in untrained subjects (P < 0.01). These results indicate that an adaptation of the controller, but not that of plant, contributes to the attenuation of exercise hyperpnea at an iso-metabolic rate in trained subjects. However, whether training induces changes in neural drive originating from the central nervous system, afferents from the working limbs, or afferents from the heart, which is additive to the chemoreflex drive to breathe, cannot be determined from these results.

Hepatitis C Virus Elimination Using Direct Acting Antivirals after the Radical Cure of Hepatocellular Carcinoma Suppresses the Recurrence of the Cancer.

It remains unclear whether hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients can be suppressed by the elimination of the virus using direct-acting antivirals (DAAs) after radical HCC treatment. We evaluated the sustained inhibitory effect of DAAs on HCC recurrence after curative treatment. This multicenter retrospective study included 190 HCV-positive patients after radical treatment for early-stage HCC. Patients were classified into the DAA treatment group (n = 70) and the non-DAA treatment group (n = 120) after HCC treatment. After propensity score matching (PSM), 112 patients were assessed for first and second recurrences using the Kaplan-Meier method and analyzed using a log-rank test. The first recurrence rates at 1 and 3 years were 3.6% and 42.1% in the DAA treatment group and 21.7% and 61.9% in the non-DAA treatment group, respectively (p = 0.0026). Among 85 patients who received radical treatment, the second recurrence rate at 3 years was 2.2% in the DAA treatment group and 33.9% in the non-DAA treatment group (p = 0.0128). In HCV-positive patients with early-stage HCC, the first and second recurrences were suppressed by DAA therapy after radical treatment, suggesting that the inhibitory effect of DAA therapy on HCC recurrence was sustained.

Effects of exercise training in patients with chronic heart failure and advanced left ventricular systolic dysfunction receiving ß-blockers.

BACKGROUND: It remains unclear whether patients with chronic heart failure (CHF) and advanced left ventricular (LV) dysfunction on ß-blocker therapy benefit from exercise training (ET). METHODS AND RESULTS: We studied 45 CHF patients with advanced LV dysfunction [ejection fraction (LVEF) < 25%] and impaired exercise tolerance [normalized peak oxygen uptake (PVO2) < 70%] receiving a ß-blocker: 33 patients participated in a cardiac rehabilitation program with ET (ET group) and 12 did not (inactive control group). Exercise capacity, LV dimension and plasma B-type natriuretic peptide (BNP) were assessed before and after a 3-month study period. At baseline, both groups had markedly reduced LVEF (ET group 18 ± 4% vs. Control group 18 ± 5%, NS) and impaired exercise capacity (normalized PVO2 51 ± 10% vs. 55 ± 9%, NS). Although one patient in the ET group withdrew from the program due to worsening CHF, no serious cardiac events occurred during the ET sessions. After 3 months, the ET group (n = 24) had significantly improved PVO2 by 16 ± 15% (1,005 ± 295 to 1,167 ± 397ml/min, P < 0.001), while the PVO2 of the control group was unchanged. LV end-diastolic dimension decreased in both groups to a similar extent, but plasma BNP was significantly decreased only in the ET group (432 to 214 pg/ml, P < 0.05). CONCLUSIONS: The data indicate that in CHF patients with advanced LV dysfunction on ß-blocker therapy, ET successfully improves exercise capacity and BNP without adversely affecting LV remodeling or causing serious cardiac complications.

Subtraction magnetocardiogram for detecting coronary heart disease.

BACKGROUND: A large-scale magnetocardiogram (MCG) database was produced, and standard MCG waveforms of healthy patients were calculated by using this database. It was clarified that the standard MCG waveforms are formed with the same shape and current distribution in healthy patients. A new subtraction method for detecting abnormal ST-T waveforms in coronary heart disease (CHD) patients by using the standard MCG waveform was developed. METHODS: We used MCGs of 56 CHD patients (63 ± 3 years old) and 101 age-matched normal control patients (65 ± 5 years old). To construct a subtracted ST-T waveform, we used standard MCG waveforms produced from 464 normal MCGs (male: 268, female: 196). The standard MCG waveforms were subtracted from each subject's measured MCGs, which were shortened or lengthened and normalized to adjust to the data length and magnitude of the standard waveform. We evaluated the maximum amplitude and maximum current-arrow magnitude of the subtracted ST-T waveform. RESULTS: The maximum magnetic field, maximum magnitude of current arrows, and maximum magnitude of total current vector increased according to the number of coronary artery lesions. The sensitivity and specificity of detecting CHD and normal control patients were 74.6% and 84.1%, respectively. CONCLUSIONS: The subtraction MCG method can be used to detect CHD with high accuracy, namely, sensitivity of 74.6% and specificity of 84.1% (in the case of maximum amplitude of total current vector). Furthermore, the subtraction MCG magnitude and its current distribution can reflect the expanse of the ischemic lesion area and the progress from ischemia to myocardial infarction.

Repolarization spatial-time current abnormalities in patients with coronary heart disease.

BACKGROUND: Magnetocardiography (MCG) is a new technique for visualizing a current distribution in the myocardium. In recent years, current distribution parameters (CDPs) have been developed based on the distribution. The CDPs reflect spatial-time current abnormalities in patients with coronary heart disease (CHD). However, the criteria and scoring method of the abnormalities using CDPs are still controversial. METHOD: We measured MCG signals for 101 normal controls and 56 CHD patients (single-, double-, and triple-vessel diseases) using a MCG system. The CDPs (maximum current vector [MCV], total current vector [TCV], current integral map, and current rotation) during ventricular repolarization were analyzed. To evaluate the CDPs that are effective in distinguishing between normal controls and CHD patients, the areas under the receiver operating characteristic curve (A(z)) are calculated. Furthermore, the total scores ("0" to "4") of four CDPs with high A(z) values are also calculated. RESULTS: MCV and TCV angles at the T-wave peak had the highest A(z) value. Furthermore, TCV angular differences between the ST-T segment also had high A(z) values. Using the four CDPs, the averaged total score for patients with triple-vessel disease was the highest ("2.67") compared to the other groups (normal controls: 0.53). Furthermore, based on the assumption that subjects with a total score over "1" were suspected of having CHD, sensitivity and specificity were 85.7% and 74.3%, respectively. CONCLUSION: We concluded that the score and criteria using MCV and TCV during repolarization in CHD patients can reflect lesion areas and time changes of electrical activation dispersion due to ischemia.

Standard template of adult magnetocardiogram.

BACKGROUND: We need to know the magnetocardiogram (MCG) features regarding waveform and two-dimensional current distribution in normal subjects in order to classify the abnormal waveform in patients with heart disease. However, a standard MCG waveform has not been produced yet, therefore, we have first made the standard template MCG waveform. METHODS AND RESULTS: We used data from 464 normal control subjects' 64-channel MCGs (268 males, 196 females) to produce a template MCG waveform. The measured data were averaged after shortening or lengthening and normalization. The time interval and amplitude of the averaged data were adjusted to mean values obtained from a database. Furthermore, the current distributions (current arrow maps [CAMs]) were calculated from the produced templates to determine the current distribution pattern. The produced template of the QRS complex had a typical shape in six regions that we defined (M1, M2, M3, M4, M5, and M6). In the P wave, the main current arrow in CAMs pointing in a lower-left direction appeared in M1. In the QRS complex, the typical wave appeared in each region, and there were two main current arrows in M2 and M5. There were negative T waves in M1, M4, and M5, and positive T waves in M3 and M6, and the main current arrow pointing in a lower-left direction appeared in M2. CONCLUSION: Template MCG waveforms were produced. These morphologic features were classified into six regions, and the current distribution was characterized in each region. Consequently, the templates and classifications enable understanding MCG features and writing clinical reports.

Postexercise VO2 "Hump" phenomenon as an indicator for inducible myocardial ischemia in patients with acute anterior myocardial infarction.

OBJECTIVES: At exercise testing with respiratory gas analysis in patients with inducible myocardial ischemia, we have occasionally observed abnormal transient oxygen uptake (VO2) components with a characteristic "Hump"-shaped morphology early after exercise, which may serve as an index for inducible ischemia. We examined this hypothesis in patients with anterior q-wave myocardial infarction in whom the accuracy to identify ischemia by exercise ECG is limited. DESIGN: From patients with acute anterior q-wave infarction but without clinically overt heart failure who underwent pre-discharge exercise testing, we examined patients with (Group-I, n = 30) and without (Group-N, n = 29) inducible ischemia. To identify "Hump", postexercise VO2 (up to 4 min) standardized for peak VO2 was exponentially fitted with use of peak VO2 and VO2 of 90-240 s, yielding "expected VO2". "D-curve" was obtained by subtracting "expected VO2" from measured VO2. RESULTS: Although exercise-induced ST depressions more frequently appeared in Group-I (27%) than in Group-N (3%, p < 0.05), the prevalence was low. D-curve peaked later (p < 0.01) and its value was greater (p < 0.05) in Group-I than in Group-N. When "Hump" was defined to be present if D-curve peaked > or =40 s and its peak value > or =15%, it was far more frequently found in Group-I (n = 17/30) than in Group-N (n = 1/29, p < 0.01). Thus, "Hump" could diagnose inducible ischemia with a sensitivity of 57% and a specificity of 97%. CONCLUSIONS: Although not highly sensitive, postexercise VO2 "Hump" with its peak occurring around 60 s after exercise is a specific marker for inducible ischemia. The identification may be useful, particularly in patients with limited accuracy of exercise ECG such as those with q-wave anterior infarction.

Efficacy of cardiac rehabilitation after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2-8 sessions/patient. METHODS: Forty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR. RESULTS: No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p<0.01), peak workload, and oxygen pulse significantly improved in the CR group compared with the non-CR group, with a tendency towards improvement in mental health-related QOL. Quadriceps strength and heart failure (HF) symptoms (WHO functional class, 2.2-1.8, p=0.01) significantly improved within the CR group. During the CR, no patient experienced adverse events or deterioration of right-sided HF or haemodynamics as confirmed via catheterisation. CONCLUSIONS: The combination of BPA and subsequent CR is a new treatment strategy for inoperable CTEPH to improve exercise capacity to near-normal levels and HF symptoms, with a good safety profile.