Differences in iron kinetics during cardiac load between patients with atrial fibrillation and those with sinus rhythm.

INTRODUCTION: The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples. METHODS: This case-control study included 178atients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups. RESULTS: The AF group had higher Log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation. CONCLUSION: Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. METHODS: Gene expression data was analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p-value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used RefEx to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. RESULTS: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, Reference expression (RefEx) was used to analyze the gene expression levels in various tissues. Four genes; FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. CONCLUSION: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.

[Generational differences in lifestyle changes among outpatients with cardiovascular disease during the coronavirus disease pandemic].

AIM: The coronavirus disease (COVID-19) pandemic has caused significant disruptions in various aspects of daily life. The Japanese Government declared a state of emergency in April 2020, which resulted in reduced physical activity. This study investigated the impact of these lifestyle changes by generation among outpatients with cardiovascular disease (CVD). METHODS: In autumn 2020, we conducted a questionnaire survey of 1,156 CVD outpatients who visited the Department of Cardiology at our institution. The survey collected data on physical activities and changes in daily behaviors over the course of the COVID-19 pandemic. Participants were classified into 3 age groups: middle-aged (n=114, ≤64 years old), semi-old (n=330, aged 65-74 years old), and old (n=712, ≥75 years old). The number of steps per day and sedentary time per day were compared between autumn 2019 and 2020, over the course of the pandemic. RESULTS: In autumn 2020, the number of steps per day was significantly decreased and sedentary time significantly increased in all age groups compared to the pre-pandemic levels. However, there were no significant differences in the extent of changes in steps per day or sedentary time over the study period across all age groups. Regarding changes in daily behaviors, only the old-age group reported a decline in volunteering and reduced utilization of daycare services. CONCLUSIONS: The COVID-19 pandemic has resulted in changes in daily activities and lifestyles across all age groups. Because lifestyle patterns differ across generations, it may be necessary to implement age-specific interventions and procedures.

Exercise Capacity and Frailty Are Associated with Cerebral White Matter Hyperintensity in Older Adults with Cardiovascular Disease.

Cerebral white matter hyperintensity (WMH) is highly prevalent among older adults. There is little information about the relationship among WMH extent, frailty status, and exercise capacity in older adults with cardiovascular disease (CVD). We assessed the association of WMH with frailty and exercise capacity in CVD patients.Seventy-eight stable older adults with CVD were evaluated for WMH, the Kihon Checklist (KCL), short physical performance battery score (SPPB), and cardiopulmonary exercise testing. WMH volume was quantified on brain magnetic resonance imaging. Patients were classified into 3 groups (using tertiles of 0.52% and 1.05%) according to WMH as a percentage of intracranial volume (ICV), and their KCL scores and exercise capacities were compared. The 3 WMH/ICV groups were mild (n = 26, 0.26% ± 0.14% of intracranial volume), moderate (n = 26, 0.70% ± 0.15%), and severe (n = 26, 1.75% ± 0.67%). Peak VO2 was 15.2 ± 3.7 mL kg-1 minute-1 (mild group), 12.9 ± 3.5 mL kg-1 min-1 (moderate), and 11.4 ± 2.3 mL kg-1 minute-1 (severe) (mild versus moderate, P = 0.049; mild versus severe, P = 0.001). Multivariate regression analysis showed significant associations of severe WMH/ICV with peak VO2 and SPPB. Cerebral WMH was strongly negatively associated with SPPB and peak VO2. WMH volume may be related to exercise capacity and frailty in stable older adult patients with CVD.

Medium-term health-related quality of life in patients with pulmonary arterial hypertension treated with goal-oriented sequential combination therapy based on exercise capacity.

BACKGROUND: Pulmonary arterial hypertension (PAH) remains a life-threatening condition, despite modern therapies. We prospectively investigated the therapeutic health-related quality of life (HRQOL) effects of goal-oriented sequential combination therapy based on exercise capacity in patients newly diagnosed with PAH. METHODS: To examine the changes in HRQOL in PAH patients, we treated 30 patients newly diagnosed with PAH with goal-oriented sequential combination therapy based on exercise capacity. We monitored exercise capacity by cardiopulmonary exercise testing and observed the benefit of using a peak VO2 cut-off of 15 mL/kg/min to guide combination therapy. First-line treatment was an endothelin receptor antagonist (ERA); second-line treatment was the addition of a phosphodiesterase-5 inhibitor (PDE-5I). At baseline and at 3, 6, and 12 months, HRQOL was evaluated by using the eight-item Medical Outcomes Survey Short Form Health Survey. RESULTS: At 12 months, 100% of PAH patients were receiving an ERA, and 82% an ERA + PDE-5I. The mean physical component summary (PCS) score was 33.5 at baseline, 41.2 at 3 months, 40.8 at 6 months, and 42.0 at 12 months, and the mean mental component summary (MCS) scores were 45.6, 47.0, 50.0, and 50.1, respectively. PCS score was significantly greater at 3 months than at baseline (P = 0.035). MCS score was comparable at 3 months and at baseline, but was significantly greater at 6 and 12 months than at baseline (P = 0.033, P = 0.028, respectively). Thus, PCS score improved soon after initiation of therapy, and MCS score improved later. CONCLUSIONS: Together, these results suggest that goal-oriented sequential combination therapy based on exercise capacity improves HRQOL in patients with PAH.

Peak Work Rate during Exercise Could Detect Frailty Status in Elderly Patients with Stable Heart Failure.

The Kihon Checklist (KCL) is a reliable tool for determining frailty status in the elderly. However, there is no information in the literature about the relationship between frailty status and exercise capacity. Here, we examined the associations between cardiopulmonary exercise testing parameters and frailty status in elderly patients with stable heart failure (HF).Ninety-two elderly patients with stable HF were evaluated using cardiopulmonary exercise testing and the KCL. A KCL score of 0-3 was classified as robust, 4-7 as pre-frail, and ≥ 8 as frail.Mean age, peak VO2, and KCL score were 81.7 years, 13.2 mL/kg/minute, and 10.7, respectively. KCL score was significantly correlated with peak VO2 (r = -0.527, P < 0.001) and peak work rate (r = -0.632, P < 0.001). In patients with frailty (n = 63), the peak work rate (WR) was significantly lower than it was in patients without frailty (n = 29; 39.9 versus 69.5 W, respectively; P < 0.001). Multivariate analysis revealed that peak WR and peak systolic blood pressure were significant, independent predictors of frailty (ß = -0.108 and -0.045, respectively). In a diagnostic performance plot analysis, a cutoff value for peak WR of 51.9 W was the best predictor of frailty.Frailty status was significantly associated with peak WR and peak systolic blood pressure in elderly patients with stable HF. Therefore, cardiopulmonary exercise testing may be useful for assessing frailty status in this patient population.

Usefulness of scoring right ventricular function for assessment of prognostic factors in patients with chronic thromboembolic pulmonary hypertension.

Right ventricular (RV) function is associated with prognosis in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to establish an RV dysfunction score using RV echocardiographic parameters to clarify the clinical characteristics in patients with CTEPH and to compare RV dysfunction score with parameters such as World Health Organization (WHO) functional class, hemodynamics, exercise capacity, and plasma BNP level. We enrolled 35 inpatients with CTEPH (mean age, 62 ± 15 years, 15 males). We constructed 'an RV dysfunction score' calculated as the summation of each point awarded for the presence of four parameters: tricuspid annular plane systolic excursion (TAPSE) < 16 mm, 1 point; tissue Doppler-derived tricuspid lateral annular systolic velocity (S') < 10 cm/s, 1 point; right ventricular fractional area change (RVFAC) < 35%, 1 point; and right ventricular myocardial performance index (RV-MPI) > 0.4, 1 point. TAPSE, S', RVFAC, and RV-MPI was 18.7 ± 4.8 mm, 11.9 ± 3.1 cm/s, 33.5 ± 13.9%, and 0.39 ± 0.2, respectively. The RV dysfunction score was associated with symptom [WHO functional class (p = 0.026)], hemodynamics [mean PAP (p = 0.01), cardiac index (p = 0.009), pulmonary vascular resistance (p = 0.001), and SvO2 (p = 0.039)], exercise capacity [6-min walk distance (p = 0.046), peakVO2 (p = 0.016), and VE/VCO2 slope (p = 0.031)], and plasma BNP level (p = 0.005). This RV dysfunction score using the four RV echocardiographic parameters could be a simple and useful scoring system to evaluate prognostic factors in patients with CTEPH.

Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dtmax) and elevation of heart rate. FFR is a marker of myocardial contractile reserve and follows an upward slope in healthy myocardium [monophasic FFR (MoF)], a pattern that becomes biphasic (BiF) under pathological conditions. However, it remains uncertain whether the FFR determines a patient's prognosis. We investigated the promising role of the FFR as a predictor of cardiac events in the setting of hypertrophic cardiomyopathy (HCM).Methods and Results:A total of 113 consecutive patients with HCM (New York Heart Association (NYHA) class I-II) were retrospectively evaluated; 27 (23.9%) had a BiF pattern and they experienced a higher incidence of cardiac events compared with those showing an MoF pattern (median follow-up, 4.7 years; P<0.001). Furthermore, Cox proportional hazard regression analysis revealed that the LV end-diastolic volume index (hazard ratio: 1.051, P=0.014) and BiF pattern (hazard ratio: 15.260, P=0.001) were independent predictors of primary cardiac events. Interestingly, abnormal reductions in myocardial regulatory molecules related to contractility (SERCA2α) were observed exclusively in the patients exhibiting a BiF pattern. CONCLUSIONS: The FFR reflects latent myocardial abnormalities and predicts cardiac events in the setting of HCM, even during the asymptomatic stages of the disease.

Abnormal Circadian Blood Pressure Profile as a Prognostic Marker in Patients with Nonischemic Dilated Cardiomyopathy.

OBJECTIVES: An abnormal circadian blood pressure (BP) profile is considered a risk factor for cardiovascular disease. However, its significance in heart failure patients with nonischemic etiology is unknown. Herein, we investigated the prognostic value of a circadian BP profile in patients with nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 114 NIDCM patients (76 males, mean age 53.1 years). The percent nighttime BP fall (%NBPF) was defined using ambulatory BP monitoring as a percent decrease in mean systolic BP in nighttime from daytime. All patients were divided into three groups: dipper (%NBPF ≥10), non-dipper (0 ≤ %NBPF < 10), and riser (%NBPF <0). RESULTS: Riser patients had the highest serum creatinine levels (dipper, 0.78 ± 0.20 mg/dl; non-dipper, 0.85 ± 0.21 mg/dl; riser, 0.99 ± 0.23 mg/dl; p = 0.006). In survival analysis, riser patients had the highest cumulative cardiac-related deaths (log-rank, p = 0.001), which was an independent predictor of cardiac-related deaths (hazard ratio, 12.6; 95% confidence interval, 1.76-253; p = 0.01). Multivariate analysis revealed that the norepinephrine level at 24-hour collected urine (24 h U-NE) and the serum creatinine level were independent determinants of %NBPF (adjusted R2 = 0.20; 24 h U-NE, p = 0.0001; serum creatinine, p = 0.04). CONCLUSIONS: The riser profile was associated with poor prognosis of NIDCM, which may reflect impaired sympathetic nervous system activity. Evaluating the circadian BP profile may be useful for risk stratification in NIDCM patients.

Impact of preoperative regular physical activity on postoperative course after open abdominal aortic aneurysm surgery.

Early ambulation after open abdominal aortic aneurysm (AAA) surgery is assumed to play a key role in preventing postoperative complications and reducing hospital length of stay. However, the factors predicting early ambulation after open AAA surgery have not yet been sufficiently investigated. Here, we investigated which preoperative and intraoperative variables are associated with start time for ambulation in patients after open AAA surgery. A total of 67 consecutive patients undergoing open AAA surgery were included in the study [male, 62 (92 %); mean age, 68 years (range, 47-82 years), mean AAA diameter, 53 mm (range, 28-80 mm)]. Preoperative physical activity was examined by means of 6-min walk distance (6MWD) and a medical interview. Patients were divided into two groups, according to when independence in walking was attained: early group <3 days (n = 36) and late group ≥3 days (n = 31), and the pre-, intra-, and postoperative recovery data were compared. There were no significant differences in patient baseline characteristics or intraoperative data between the two groups. The number of patients engaging in preoperative regular physical activity and 6MWD were significantly greater (p = 0.042 and p = 0.034, respectively) in the early group than in the late group. In addition, time to hospital discharge was significantly shorter in the early group than in the late group (p = 0.031). Binary logistic regression analysis showed that preoperative regular physical activity was the only independent factor for identifying patients in the early group (odds ratio 2.769, 95 % confidence interval 1.024-7.487, p = 0.045). These results suggest that engaging in regular physical activity is an effective predictor of early ambulation after open AAA surgery.

Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy.

BACKGROUND: Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left-sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM. METHODS: Ninety subjects with DCM underwent cardiac catheterization and CPX at our hospital. Receiver operator characteristic (ROC) analysis was performed to assess the ability of CPX variables to distinguish between the presence and absence of PH. RESULTS: Overall mean values were: mean PAP (mPAP), 18.0 ± 9.6 mmHg; plasma brain natriuretic peptide, 233 ± 295 pg/mL; and left ventricular ejection fraction, 30.2 ± 11.0%. Patients were allocated to one of two groups on the basis of mean PAP, namely DCM without PH [mean PAP (mPAP) <25 mmHg; n = 75] and DCM with PH (mPAP ≥25 mmHg; n = 15). A cutoff achieved percentage of predicted peak VO2 (%PPeak VO2 ) of 52.5% was the best predictor of an mPAP ≥25 mmHg in the ROC analysis (area under curve: 0.911). In the multivariate analysis, %PPeak VO2 was the only significant independent predictor of PH (Wald 6.52, odds ratio 0.892, 95% CI 0.818-0.974; P = 0.011). CONCLUSIONS: %PPeak VO2 was strongly associated with the presence of PH in patients with DCM. Taken together, these findings indicate that CPX variables could be important for diagnosing PH in patients with DCM.

Magnetic resonance imaging of cardiac sarcoidosis: an evaluation of the cardiac segments and layers that exhibit late gadolinium enhancement.

Cardiac sarcoidosis (CS) can cause sudden death, which is the leading cause of mortality in patients with sarcoidosis in Japan. However, it is difficult to diagnose CS because of the lack of a sensitive diagnostic method for the condition. Late gadolinium-enhanced cardiac magnetic resonance (MR) imaging demonstrates improved sensitivity for diagnosing CS. Therefore, it is important to know the late gadolinium-enhancement (LGE) characteristics of CS on cardiac MR images in order to diagnose CS accurately. In this study, we investigated the most common sites of LGE on cardiac MR images in CS. Late gadolinium-enhanced MR images of 9 consecutive patients with CS (obtained between August 2009 and July 2015) were reviewed by two radiologists. The distribution of LGE was evaluated using the American Heart Association 17-segment model of the left ventricle. The LGE in each segment was also classified into 4 patterns according to the myocardial layer in which it occurred (the subepicardial, subendocardial, intramural, and transmural layer patterns). All 9 patients exhibited LGE in their left ventricle, and 70 of 153 (46%) myocardial segments were enhanced. All of the patients displayed LGE in the basal septal wall. The patients' LGE layer patterns were as follows: subepicardial: 40% (28/70), intramural: 30% (21/70), subendocardial: 16% (11/70), and transmural: 14% (10/70). The basal septum wall and subepicardial layer often exhibit LGE on cardiac MR images in CS patients. LGE can be observed in other segments and layers in some cases.

Endomyocardial radial strain rate imaging during dobutamine stress echocardiography for the evaluation of contractile reserve in patients with dilated cardiomyopathy.

PURPOSE: Myocardial contractile reserve is associated with clinical prognosis in patients with dilated cardiomyopathy (DCM). We assessed myocardial contractile reserve using tissue Doppler strain rate imaging with dobutamine stress echocardiography in DCM patients. METHODS: Simultaneous echocardiography and left ventricular (LV) catheterization during dobutamine stress were performed in 20 patients with DCM, and echocardiography was performed in 31 control subjects. Dobutamine was infused at a starting dose of 5 µg/kg/min for 5 minutes and then at 10 µg/kg/min. Peak endomyocardial radial strain (ɛ) and systolic strain rate (SRsys ) measured with echocardiography and the maximum first derivative of LV pressure (LV dP/dtmax ) derived from catheterization were used as indices of contractility. Their percentage change from baseline to the dose of 10 µg/kg/min was calculated. RESULTS: The ɛ and SRsys were significantly smaller in DCM patients than in controls. The LV dP/dtmax , ɛ, and SRsys were significantly higher at the dose of 10 µg/kg/min than at baseline. The percentage change in SRsys was significantly correlated with the percentage change in LV dP/dtmax . CONCLUSIONS: Strain rate imaging during dobutamine stress in DCM might prove noninvasively informative for the evaluation of myocardial contractile reserve and provide insight into LV systolic dysfunction. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:555-560, 2016.

Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites.

AIMS/HYPOTHESIS: To investigate epigenetic regulation of the plasma concentration of resistin, we performed an epigenome-wide association study for this variable and DNA methylation (DNAm) in an elderly Japanese cohort and then assessed the relation of single nucleotide polymorphisms (SNPs) associated with the plasma resistin concentration to DNAm level at identified sites. METHODS: The association of plasma resistin level with DNAm status was examined in 191 nondiabetic elderly men with the Illumina Infinium HumanMethylation450 BeadChip array. The association between DNAm status at specific sites in the flanking region of the resistin gene (RETN) and RETN mRNA abundance was then evaluated with a public data set for 1202 monocyte samples from a multi-ethnic cohort. Finally, the association of DNAm status and SNPs in the promoter region of RETN was assessed in two cohorts comprising a total of 478 Japanese individuals. RESULTS: DNAm status at cg02346997 located in the RETN promoter region showed a negative genome-wide significant association with the plasma resistin level (p = 6.02 × 10(-10)). Four DNAm sites in the RETN promoter region including cg02346997 (p = 4.23 × 10(-70)) showed a negative genome-wide significant association with RETN mRNA abundance in monocytes. Furthermore, the number of minor alleles of the RETN promoter SNPs rs34861192 and rs3219175 was negatively associated with DNAm level at cg02346997 (p = 4.43 × 10(-17)). CONCLUSIONS/INTERPRETATION: Our results suggest that RETN promoter SNPs might influence the circulating resistin level through an effect on DNAm at cg02346997 and on RETN mRNA abundance in monocytes.

Clinical Characteristics and Long-Term Outcomes of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan-Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.

Prognostic impact of combined late gadolinium enhancement on cardiovascular magnetic resonance and peak oxygen consumption in ambulatory patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Peak oxygen consumption (peak VO2) and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) are prognostic in heart failure. We investigated whether LGE-CMR and peak VO2combined had additive value in risk stratifying patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Fifty-seven DCM patients underwent CMR and cardiopulmonary exercise testing. Cardiac events were cardiac death, hospitalization for decompensated heart failure, or lethal arrhythmia. Twenty-five (44%) were LGE-positive. The median peak VO2was 18.5 mL·kg(-1)·min(-1). On multivariate analysis, positive LGE (P = .048) and peak VO2(P = .003) were independent cardiac event predictors. Cardiac event risk was significantly higher with positive LGE and peak VO2< 18.5 mL ·kg⁻¹ ·min⁻¹ than with negative LGE and peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹ (hazard ratio 12.5; 95% CI 1.57-100; P = .017). In 3 patient groups (group A: no LGE, peak VO2≥ 18.5 mL · kg⁻¹ · min⁻¹, n = 18; group B: positive LGE or peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 24; group C: positive LGE and peak VO2< 18.5 mL · kg⁻¹ · min⁻¹, n = 15) during follow-up (71 ± 32 months), group C had higher cardiac event rates than the others. CONCLUSIONS: Combined assessment of LGE-CMR and peak VO2provides additive prognostic information in ambulatory DCM.

Prognostic value of pulmonary hypertension in ambulatory patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Pulmonary hypertension (PH) because of left-sided heart disease carries a poor prognosis. We investigated whether non-ischemic dilated cardiomyopathy (DCM) with PH is associated with poor prognosis. METHODS AND RESULTS: A total of 256 consecutive DCM patients were enrolled. We measured the ratio of the maximum first derivative of left ventricular pressure (LVdP/dtmax)/systolic blood pressure and pressure half-time (T1/2) as cardiac function. Patients were allocated to 2 groups on the basis of mean pulmonary arterial pressure (mPAP), namely DCM without PH group (mPAP <25 mmHg; n=225) and DCM with PH group (mPAP ≥25 mmHg; n=31). We followed all patients for a mean of 4.3 years for the occurrence of cardiac events, defined as cardiac death or hospitalization for worsening heart failure. Cardiac events were significantly more frequent in the DCM with PH group than in the DCM without PH group (P<0.001). Multivariate Cox regression analysis revealed that mPAP ≥25 mmHg and LV end-systolic volume index were significant independent risk factors for cardiac death. Incidence of cardiac death was significantly higher in patients with DCM with PH than in those without PH [hazard ratio 11.79 (3.18-43.7), P<0.0001]. CONCLUSIONS: The presence of PH was independently associated with an increased incidence of cardiac death in ambulatory patients with DCM.

Prognostic Significance of Serum Uric Acid and Exercise Capacity in Older Adults Hospitalized for Worsening Cardiovascular Disease.

Elevated serum uric acid (sUA) is associated with the risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. When the patients were stratified by sUA into three groups (<5.3, 5.4-6.9, >7.0 mg/dL), the high-sUA group had a significantly worse peak VO2 and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low- and moderate-sUA groups (p < 0.001). When the patients were stratified by sUA into five groups (sUA < 3.9, 4.0-5.9, 6.0-7.9, 8.0-8.9, and >10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women.

Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.

Objectives: We conducted a text mining analysis of 40 years of literature on cardiac aging from PubMed to investigate the current understanding on cardiac aging and its mechanisms. This study aimed to embody what most researchers consider cardiac aging to be. Methods: We used multiple text mining and machine learning tools to extract important information from a large amount of text. Results: Analysis revealed that the terms most frequently associated with cardiac aging include "diastolic," "hypertrophy," "fibrosis," "apoptosis," "mitochondrial," "oxidative," and "autophagy." These terms suggest that cardiac aging is characterized by mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. We also revealed an increase in the frequency of occurrence of "autophagy" in recent years, suggesting that research on autophagy has made a breakthrough in the field of cardiac aging. Additionally, the frequency of occurrence of "mitophagy" has increased significantly since 2019, suggesting that mitophagy is an important factor in cardiac aging. Conclusions: Cardiac aging is a complex process that involves mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. Further research is warranted to elucidate the mechanisms of cardiac aging and develop strategies to mitigate its detrimental effects.