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This study aimed to explore the impact of cardiac rehabilitation (CR) on in vivo and ex vivo microcirculation, exercise capacity, and oxidative stress in patients with cardiovascular disease (CVD). The study included patients with acute coronary syndrome (ACS; n = 45; age, 69.0 ± 14.1 years) and heart failure (HF; n = 66; age, 77.3 ± 10.7 years) who underwent supervised CR during hospitalization. The control group comprised patients without CVD (NCVD; n = 20; age, 75.9 ± 11.2 years). In vivo microcirculatory observations using nailfold video capillary endoscopy at rest and during hyperemia, exercise capacity, and oxidative stress were assessed at baseline and 12 weeks after discharge. Baseline capillary densities were significantly lower in the ACS (5.0 ± 1.7 capillaries/mm 2 ) and HF (4.9 ± 1.7 capillaries/mm 2 ) groups than in the NCVD group (6.5 ± 1.1 capillaries/mm 2 , p < 0.01). Similarly, capillary density during reactive hyperemia was significantly lower in the ACS (5.8 ± 1.7 capillaries/mm 2 ) and HF (5.4 ± 1.8 capillaries/mm 2 ) groups than in the NCVD group (7.3 ± 1.4 capillaries/mm 2 , p < 0.01). Patients with ACS and HF had increased capillary densities at 12 weeks compared with at baseline (p < 0.05). This improvement was particularly pronounced among post-discharge outpatient CR participants (n = 20). Grip strength, exercise capacity, and oxidative stress improved at 12 weeks. Baseline capillary density changes were positively correlated with grip strength changes (r = 0.45, p < 0.001). CR significantly improved nailfold capillary density in patients with ACS and HF 12 weeks after discharge., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Killip classification has been used to stratify the risk of patients with acute myocardial infarction (AMI). There were many reports that Killip class 3 or 4 is closely associated with poor clinical outcomes. In other words, Killip class 1 or 2 is associated with favorable clinical outcomes in patients with AMI, especially when patients received primary percutaneous coronary intervention (PCI). However, some patients with Killip class 1/2 suffer from serious in-hospital complications. This study aimed to identify factors associated with serious in-hospital complications of ST-segment elevation myocardial infarction (STEMI) in patients with Killip class 1/2. The primary endpoint was serious in-hospital complications defined as the composite of in-hospital death and mechanical complications. We included 809 patients with STEMI, and divided them into the non-complication group (n = 791) and the complication group (n = 18). In-hospital death was observed in 14 patients (1.7%), and mechanical complications were observed in 4 patients (0.5%). Final TIMI flow ≤ 2 was more frequently observed in the complication group (33.3%) than in the non-complication group (5.4%) (p < 0.001). Multivariate logistic regression analysis revealed that serious in-hospital complication was associated with final TIMI flow grade ≤ 2 (Odds ratio 6.040, 95% confidence interval 2.042-17.870, p = 0.001). In conclusion, serious in-hospital complication of STEMI was associated with insufficient final TIMI flow grade in patients with Killip class 1/2. If final TIMI flow grade is suboptimal after primary PCI, we may recognize the potential risk of serious complications even when patients presented as Killip class 1/2., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Exercise intolerance is a symptom of chronic heart failure (CHF). The magnitude of exercise tolerance, as measured by peak oxygen uptake (peak VO 2 ), is strongly associated with prognosis in patients with CHF. We aimed to evaluate the factors associated with improved exercise tolerance in patients with HF. In this prospective study, we recruited patients who were diagnosed with non-ischemic cardiomyopathy between September 2017 and September 2021. All patients underwent cardiopulmonary exercise testing at discharge and 6 months after enrollment. The patients were stratified according to whether peak VO 2 was increased or not at 6 months. One hundred patients with a reduced left-ventricular ejection fraction (LVEF < 50%) were enrolled. Improvement of peak VO 2 was observed in 74 patients. In male patients, hemoglobin level was higher in the increased peak VO 2 group than in the non-increased group (15.0 ± 1.9 g/dL vs. 13.1 ± 2.1 g/dL; p < 0.01). Baseline hemoglobin level was positively correlated with the percentage change in peak VO 2 (Spearman's r = 0.248, p = 0.040). Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly less frequent in the increased peak VO 2 group than in the non-increased group (log-rank test, p = 0.032). Multivariate logistic regression analysis identified hemoglobin level as an independent predictor of improved peak VO 2 [odds ratio (OR) 1.60; 95% confidence interval (CI) 1.05-2.44; p = 0.027]. Baseline hemoglobin level is an independent predictor of improved peak VO 2 in male patients with non-ischemic cardiomyopathy., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

The effectiveness of cardiac rehabilitation (CR) in patients with cardiovascular disease requiring continuous CR from an acute care hospital to a convalescent rehabilitation hospital is unknown. Therefore, we compared the effect of CR in a rehabilitation hospital for patients with cardiovascular disease with that of those who underwent cardiovascular surgery. Sixty-nine consecutive patients were admitted to two rehabilitation hospitals for CR. Patients were classified by primary disease into two groups: patients with cardiovascular disease (cardiology group, 26 patients) and patients who underwent cardiovascular surgery (surgery group, 43 patients). Clinical information, physical function, cognitive function, activities of daily living (ADL), quality of life (QOL), amount of CR, and length of hospital stay were compared between the two groups. Compared with clinical features, age was significantly higher in the cardiology group (P < 0.001), and the preadmission Barthel index was significantly lower in the cardiology group (P = 0.025). Physical function at the time of transfer was significantly lower in the cardiology group than in the surgery group for the short physical performance battery (P < 0.001), gait speed (P = 0.005), and 6-min walking distance (P = 0.042). No significant difference was found in the amount of CR performed or the length of hospital stay, and no interaction effects were observed in improvements in physical function, exercise tolerance, or QOL. In conclusion, in rehabilitation hospitals, patients with cardiovascular disease were older, had lower preadmission ADL, and had lower a physical function at transfer than those who underwent cardiovascular surgery, but CR improved physical function and QOL to the same extent. The results suggest that the recovery of patients with cardiovascular disease may be similar to those who undergo cardiovascular surgery., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06-15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989)., (© 2022. Springer Japan KK, part of Springer Nature.)

The purpose of the present study was to develop a 60 MHz integrated backscatter intravascular ultrasound (IB-IVUS) and to evaluate its usefulness for the detection of lipid area with backward attenuation of ultrasound signal (AT) that for the prediction of post-procedural myocardial injury (PMI) after percutaneous coronary intervention (PCI). In a pathological study, images were acquired from 221 cross-sections of 18 coronary arteries from 13 cadavers obtained at autopsy. In the clinical training study, we compared non-targeted plaques in 38 patients by a previous IB-IVUS system (38 MHz) and a new IB-IVUS system (60 MHz). In the clinical testing study, we included 70 consecutive patients who underwent PCI. Serum troponin-I was measured just before and 24 h after PCI to evaluate PMI. As the % microcalcification + % cholesterol cleft area increased, the attenuation of IB values increased (r = 0.56, p < 0.001). The slopes of regression lines of the area of each tissue component between 38 and 60 MHz IB-IVUS were excellent. The lipid pool area with AT tended to be more useful than that of the conventional lipid pool area for the prediction of PMI (p = 0.11). We developed a 60 MHz IB-IVUS imaging system for tissue characterization of coronary plaques. Cutoff value of purple color was the most reliable value for the prediction of PMI., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Although glucose variability (GV) is reportedly associated with coronary plaque vulnerability, namely lipid-rich plaque, details are not fully understood. The aim of this study was to evaluate relations of GV after discharge to vulnerable plaque formation assessed by near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with and without diabetes., Methods: A total of 40 patients undergoing percutaneous coronary intervention under NIRS-IVUS guidance were included, among whom 13 (33%) had diabetes and 20 (50%) presented with acute myocardial infarction (MI). GV was evaluated by a flush glucose monitoring system, primarily with mean amplitude of glycemic excursion (MAGE). Lipid-rich plaque was assessed by maximum lipid core burden index in 4 mm (maxLCBI 4mm ) in the target lesion using NIRS-IVUS., Results: Mean MAGE and maxLCBI 4mm were 69.7 ± 25.6 mg/dl and 508.0 ± 294.9. Intra-day GV was not significantly associated with maxLCBI 4mm in the entire study population, while MAGE was correlated with maxLCBI 4mm in non-diabetic patients (r = 0.46, p = 0.02). In patients with and without acute MI presentation, no significant relations were found between MAGE and maxLCBI 4mm ., Conclusion: GV was associated with lipid core plaque formation, especially in non-diabetic patients., (© 2022. Springer Japan KK, part of Springer Nature.)

The phenomenon to heal neointimal rupture or thrombus after coronary stenting occurs as well as in native coronary artery. We investigated clinical characteristics and neointimal vulnerability of healed neointima by optical coherence tomography (OCT). We treated 67 lesions by percutaneous coronary intervention for in-stent restenosis (ISR) and conducted OCT examinations. Healed neointima was defined as neointima having one or more layers with different optical densities and a clear demarcation from underlying components. ISR with healed neointima was found in 49% (33/67) of the lesions. Compared to ISR without healed neointima, ISR with healed neointima showed significantly longer stent age (102 ± 72 vs. 31 ± 39 months, P < 0.001), lower frequency of dual antiplatelet therapy [42% (14/33) vs. 74% (25/34), P = 0.017], lower use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACE-I or ARB) [61% (20/33) vs. 91% (31/34), P = 0.028], lower usage of second-generation drug-eluting stents (DESs) [36% (12/33) vs. 63% (22/34), P = 0.029], higher usage of thick-strut stents [42% (14/33) vs. 15% (5/34), P = 0.012], larger neointimal area (6.8 ± 2.6 vs. 5.2 ± 1.8 mm 2 , P = 0.005), higher incidence of thin-cap fibroatheroma [58% (19/33) vs. 21% (7/34), P = 0.002], neointimal rupture [45% (15/33) vs. 9% (3/34), P = 0.001], and lower incidence of stent underexpansion [15% (5/33) vs. 44% (15/34), P = 0.010]. In conclusions, ISR with healed neointima was associated with neointimal vulnerability, stent age, stent type, stent strut thickness, stent expansion, antiplatelet therapy, and use of ACE-I or ARB., (© 2021. Springer Japan KK, part of Springer Nature.)

Cardiovascular events and death are more prevalent in hemodialysis (HD) patients than in the general population. However, a detailed prognostic risk stratification of HD patients with acute myocardial infarction (AMI) has not yet been performed in the modern interventional era. We examined 4509 AMI patients (89 AMI/HD and 4420 AMI/non-HD) from the Mie ACS registry and detailed prognostic analyses based on the Killip classification were performed (Cohort A). In addition, prognosis of Killip class1 AMI/HD was compared with those of 313 non-AMI/HD patients from the MIE-CARE HD study using propensity score-matching method (Cohort B). Primary endpoint was all-cause mortality for up to 2 years. All-cause death occurred in 13.0% of AMI/non-HD and 35.8% of AMI/HD during follow-up, and patients with Killip class 1 had lower 30-day and 2-year mortality than those with Killip class ≥ 2 in both AMI/non-HD and AMI/HD. Cox regression analyses identified that Killip class ≥ 2 was the strongest independent prognostic factor of 30-day mortality with a hazard ratio of 7.44 (p < 0.001), whereas both presence of HD and Killip class ≥ 2 were the independent prognostic factors of mortality for up to 2 years. In Cohort B, a propensity score-matching analysis revealed similar all-cause mortality rates between Killip class 1 AMI/HD and non-AMI/HD. In HD patients with Killip class 1 AMI, 30-day mortality was around 6%, and long-term mortality among 30-day survivors after AMI was comparable with the natural course of HD patients in the modern interventional era. Clinical trial registration: URL: https://www.umin.ac.jp/ctr/index-j.htm . UMIN000036020 and UMIN000008128., (© 2021. Springer Japan KK, part of Springer Nature.)

Left ventricular dysfunction is a pathophysiologic characteristic of heart failure. Impaired instrumental activities of daily living are associated with an elevated risk of mortality and heart failure in older adults. Nevertheless, the relationship between these activities and left ventricular function changes remains unclear. We determined whether instrumental activities of daily living are associated with subsequent left ventricular function changes in older cardiovascular disease patients. This retrospective cohort study included 383 outpatients with cardiovascular disease (74.5 ± 5.3 years, 273 males). Patients were divided according to the Frenchay activities index tertile and followed for six months after cardiovascular disease diagnosis. The left ventricular ejection fraction and annular early diastolic velocity (e') were measured for left ventricular systolic and diastolic function, respectively, at baseline and after one year. After adjusting for confounders, changes in the left ventricular ejection fraction were not significantly different. However, changes in the e' in the highest tertile group were significantly greater than in other groups. In the general linear model with multiple regression analysis, Frenchay activities index independently predicted the absolute change in the e'. In older cardiovascular disease patients, higher instrumental activities of daily living were associated with preserved left ventricular relaxation., (© 2021. Springer Japan KK, part of Springer Nature.)

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, - 8.02 ± 9.35 to - 1.62 ± 5.09 mL/min/1.73m 2  /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

With the aging society, the number of very-elderly (VE) patients with acute decompensated heart failure (ADHF) is increasing. Although tolvaptan is recommended for patients with ADHF in whom conventional diuretic therapy is ineffective, few reports exist on VE patients over 90 years of age. Therefore, we aimed to evaluate the clinical effectiveness and adverse events associated with tolvaptan in VE patients with ADHF. From January 2011 to December 2018, we retrospectively studied 180 patients with ADHF who were first administered tolvaptan during hospitalization. Patients were divided into two groups, namely, VE patients who were ≥ 90 years of age (n = 32) and not-VE patients (NVE) who were < 90 years of age (n = 148). The primary effective endpoints were the total urine volume and change in body weight. The safety endpoints evaluated were the incidence of hypernatremia (≥ 150 mEq/L) and worsening renal function (WRF) at any time during hospitalization. The median [interquartile range] patient age was 93 [91-94] years in the VE group and 80 [69-85] years in the NVE group. The mean dose of tolvaptan for the first week of administration was similar between groups (7.9 ± 5.0 mg, VE group; 7.3 ± 3.7 mg, NVE group; p = 0.52). There were no significant differences between the two groups in the total urine volume at 24 h (1901 ± 666 mL, VE group; 2101 ± 1167 mL, NVE group; p = 0.33) and that at 48 h (3707 ± 1274 mL, VE group; 4195 ± 1990 mL, NVE group; p = 0.19) and in the mean change in body weight (- 2.5 ± 2.0 kg, VE group; -2.7 ± 2.4 kg, NVE group; p = 0.70). The median duration of hospitalization was 24 [20-9] and 31 [20-42] days in the VE and NVE groups, respectively (p = 0.67). The incidence of hypernatremia (6.3% (2/32), VE group; 3.4% (5/148), NVE group; p = 0.61) and WRF (25.0% (8/32) VE group; 19.6% (29/148), NVE group; p = 0.31) was similar between the groups. In conclusion, tolvaptan has similar clinical effectiveness in increasing urine volume and decreasing body weight, without increased adverse events, in VE patients with ADHF who were ≥ 90 years of age compared to NVE patients with ADHF.

The purpose of this study was to clarify the predictive factors of activities of daily living (ADL) at discharge in elderly patients with heart failure with preserved ejection fraction (HFpEF). Participants were selected from among 598 consecutive hospitalized HF patients based on certain criteria. We investigated patient characteristics, and ADL with the motor and cognitive items of the Functional Independence Measure (FIM). We analyzed the data with the unpaired t test, Mann-Whitney U test, χ 2 test, logistic regression analysis, and receiver operating characteristic (ROC) curves. We included 154 patients for further analyses who were divided into the low ADL group (n = 75) and high ADL group (n = 79). There were significant differences between the two groups in age, long-term care insurance (LTCI) level, New York Heart Association class, creatinine level, albumin level, β-blocker, sitting, standing and walking exercise start days, length of hospital stay, and motor- and cognitive-FIM scores at admission and discharge (p < 0.05). The cutoff values of the ROC curves predicting ADL at discharge were LTCL: support level 2 (area under the curve [AUC]: 0.672, p < 0.001, sensitivity: 0.573, false-positive rate: 0.278); walking exercise start day: 4.5 days (AUC 0.694, p < 0.001, sensitivity: 0.609, false-positive rate: 0.299); motor FIM score: 34.5 points (AUC 0.710, p < 0.001, sensitivity: 0.633, false-positive rate: 0.280); and cognitive FIM score: 28.5 points (AUC 0.806, p < 0.001, sensitivity: 0.759, false-positive rate: 0.227). This study revealed several predictors of ADL at discharge and their associated cutoff values in elderly patients with HFpEF.