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Primary cardiac lymphoma is a rare entity of extranodal lymphoma and is observed with increasing frequency in immunocompromised hosts. However, a considerable proportion of cardiac lymphomas still occur in immunocompetent patients. We report the case of a 55-year-old immunocompetent Japanese man with a large amount of pericardial fluid and the presentation of heart failure secondary to primary cardiac B cell lymphoma, which was diagnosed by cytological examination of pericardial fluid and imaging. The right atrium, right ventricle and pericardium were affected by the tumour, which encased the mid/distal portion of the right coronary artery (RCA). Pretreatment optical coherence tomography of the RCA demonstrated no tumour extension into the vascular structure but a focal mural thrombus. We initiated chemotherapy (steroid therapy then COP at half dose/R-CHOP/R-CHASE) [COP (C: Cyclophosphamide, O: Oncovin, P: Prednisolone) R-CHOP (R: Rituximab, C: Cyclophosphamide, H: Doxorubicin Hydrochloride, O: Oncovin, P: Prednisolone) R-CHASE (R: Rituximab, C: Cyclophosphamide, HA: high dose Cytarabine, S: Steroid, E: Etoposide)]with administration of low-dose aspirin to prevent possible ischaemic events. The patient had a good clinical course without adverse events except for transient pericarditis.

An increased blood pressure variability (BPV) has been reported to be associated with older age and cognitive dysfunction; however, associations between increased BPV and rapid eye movement sleep behaviour disorder (RBD) has not been thoroughly investigated in patients without clinical Lewy body diseases.In frailty outpatient clinic, we evaluated ambulatory BP, RBD screening questionnaire (RBDSQ), and beat-to-beat heart rate variability during positional change from sitting to standing in 112 elderly hypertensive patients.The mean age was 81.2 ± 6.3 years (68% male). There were 15 patients who had probable RBD (RBDSQ scores ≥ 5). Patients with RBD had a greater body mass index, coefficient of variation (CV) in 24-h diastolic BP (23.5 ± 6.1 versus 18.7 ± 5.8,An increased BPV in ambulatory BP, associated with autonomic dysfunction, can be observed in patients with probable RBD even in elderly patients without clinical presentation of Lewy body diseases.

An 89-year-old woman was admitted to our hospital for subacute onset of right upper and lower limb weakness and was diagnosed with acute cerebral infarction. During rehabilitation, close observation revealed that her oxygen saturation decreased in the sitting position and improved in the recumbent position without any subjective symptoms of dyspnea. Transthoracic and transesophageal echocardiography and cardiac catheterization revealed a large patent foramen ovale with an atrial septal aneurysm with right-to-left shunting through the defect, and she was diagnosed with platypnea-orthodeoxia syndrome. Her right hemiplegia caused the trunk to collapse, so the patient slumped when in sitting position, and the trunk tilted to the right forward, resulting in an increased right-to-left shunt. Her peripheral capillary oxygen saturation improved in the upright sitting position supported by therapists. This case suggests that right hemiplegia may exacerbate the symptoms of platypnea-orthodeoxia syndrome.

An 80-year-old woman with a history of hypertrophic obstructive cardiomyopathy and Lewy body dementia was admitted to our hospital with a first episode of syncope while walking. The pressure gradient of left ventricular outflow tract (LVOT) had been stable at nearly 10 mmHg for 3 years before the admission. We evaluated the cause of syncope. Echocardiography showed that the pressure gradient of LVOT was unchanged, even in the supine position ergometer exercise test. Although the head-up tilt test revealed a drop in blood pressure of 44 mmHg systolic and 23 mmHg diastolic, she was asymptomatic during the test. The orthostatic hypotension was considered to be a manifestation of autonomic failure due to Lewy body dementia; however, it was insufficient to explain the syncope on exertion. Echocardiography in a sitting-up position showed that the pressure gradient of LVOT was exacerbated to 41 mmHg, which might be the cause of syncope while walking. Orthostatic hypotension, especially in patients with Lewy body dementia, is a common cause of syncope in the elderly. However, we should keep in mind that the exacerbation of LVOT obstruction due to posture-dependent fluid shift can be a cause of syncope in patients with hypertrophic cardiomyopathy or sigmoid-shaped interventricular septum. In such patients, echocardiography in a sitting-up position can be an effective tool to diagnose the cause of syncope.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. Methods COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. Results A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. Conclusions The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. Trial registration Clinicaltrials.jp number: JapicCTI-205238. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00517-4.

Background Peak oxygen uptake (peak VO2) is known not only as an index of aerobic fitness but also one of an index of life expectancy. Frailty, sarcopenia, and cachexia are associated with a poor prognosis and high mortality. The purpose of this study was to determine the relationships of peak VO2 with the features of sarcopenia, frailty, and cachexia, to provide insight into which might mediate the poor prognosis. Methods The first group of participants was 175 community‐dwelling older Japanese outpatients (58 men and 117 women; mean age 77.6 ± 6.4 years), in whom we assessed the features of sarcopenia, frailty, and cachexia, and measured peak VO2 during cardiopulmonary exercise. To confirm the relationships, we analysed another group of 162 participants (77.3 ± 5.5 years). Results There were significant correlations between peak VO2 and the features of sarcopenia, frailty, and cachexia, with the exception of high sensitivity C‐reactive protein. Multiple linear regression analysis for the prediction of peak VO2 (mL/min) identified following formula: predicted peak VO2 = −11.6 × age (years) + 25.5 × haemoglobin concentration (g/dL) + 114.2 × skeletal muscle mass index (kg/m2) + 8.9 × hand grip strength (kg) + 226.4 × usual walking speed (m/s) − 65.8 × fatiguability (absence 0, presence 1) − 177.4 × chronic heart failure (absence 0, presence 1) + 437.1 (R2 = 0.627, P

Minor ST-T changes on electrocardiograms are observed in patients with hypertensive heart disease with a preserved left ventricular ejection fraction (LVEF); however, the relationship between minor ST-T changes and global myocardial work on echocardiograms remains unclear. We evaluated the global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) in 186 hypertensive patients with preserved LVEF (50%) using an offline analysis system (View Pal, GE). Minor ST-T changes as well as major ST-T changes (depression in ST in lead V5 1 mV) were also evaluated by electrocardiography. The mean age was 79.4 ± 8.2 years (men 37.6%). Patients with minor and major ST-changes had a smaller absolute GLS (-20.3 ± 3.1, -18.2 ± 3.7, and -15.2 ± 5.0%, P 0.001) and a smaller constructive workload [GWI (2148 ± 486, 1938 ± 462, and 1685 ± 701 mmHg%, P = 0.002) and GCW (2419 ± 510, 2185 ± 466, and 1865 ± 702 mmHg%, P 0.001)] than those with no ST-T changes. Additionally, patients with minor and major ST-T changes had increased wasted myocardial work [GWW (87 ± 61, 105 ± 56, and 127 ± 75 mmHg%, P = 0.045)], which resulted in reductions in the myocardial work efficiency [GWE (95 ± 4, 94 ± 3, and 89 ± 12%, P 0.001)]. Even after adjustments for confounding factors, including EF, diastolic function parameters, LV hypertrophy, history of heart failure and atrial fibrillation, patients with minor ST-T changes had significantly smaller LV global constructive work in comparison to those without [GWI (2260 ± 33 vs. 2025 ± 76 mmHg%, P = 0.007) and GCW (2501 ± 45 vs. 2210 ± 105 mmHg%, P = 0.003)]. In conclusion, in hypertensive patients with preserved LVEF, minor ST-T changes on electrocardiograms were associated with reduced constructive work in the LV.

BACKGROUND The change of left ventricular function deteriorated with age because of gradual increases of blood pressure may result in increased energy loss (EL) in left ventricle (LV). The present study investigated EL in LV among hypertensive elderly patients and examined factors contributing to EL. METHODS A single-center retrospective study was performed on elderly hypertensive outpatients (≥65 years) who underwent echocardiography (N = 105). EL in the LV was measured using a vector flow mapping system, and factors affecting peak EL during the early-diastolic phase (ED-EL), late-diastolic phase (LD-EL), and systolic phase (Sys-EL) were evaluated. RESULT Mean age was 79.9 ± 6.4 years (male 43%). Mean ED-EL, LD-EL, and Sys-EL were 42.1 ± 46.7, 75.6 ± 60.2, and 40.4 ± 40.2 mJ/N/s. In a stepwise regression analysis, the E/e'(lateral) (unstandardized B = 0.005, 95%CI -0.03 to 0.007, standardized β = 0.434, P < .001) was identified as factors affecting ED-EL. The factors affecting LD-EL were E/A ratio (B = -0.122, 95%CI -0.176 to -0.068, β = -0.470, P < .001) and time velocity integral (TVI) in LVOT (unstandardized B = 0.002, 95%CI 0.000 to 0.004, β = 0.247, P = .021). The factors influencing Sys-EL were TVI in LVOT (B = 0.002, 95%CI 0.001 to 0.004, β = 0.390, P < .001), E/A ratio (B = -0.054, 95%CI -0.093 to -0.015, β = -0.258, P = .008), left ventricular outflow tract (LVOT) diameter (B = -0.006, 95%CI -0.010 to -0.002, β = -0.307, P = .006), and left ventricular mass index (B = 0.000, 95%CI 0.000 to 0.001, β = 0.208, P = .039). CONCLUSION Peak EL in the LV was higher during diastolic phase than systolic phase among elderly hypertensive patients. Peak EL both during late-diastolic phase and systolic phase was affected by systolic blood flow in LVOT and LV transmitral flow pattern.

Background Contrast-enhanced spectral detector-based computed tomography (SDCT) allows for the comprehensive and retrospective analysis. We report a case of pulmonary thromboembolism (PE) accompanied by non-ST-segment elevation myocardial infarction (NSTEMI) diagnosed by SDCT. Case summary A 72-year-old man with diabetes mellitus, hypertension, and prostate cancer suddenly developed chest and back pain and had difficulty in breathing at rest. Electrocardiography showed a right bundle branch block without significant ST-segment change. The initial serum troponin I level was 0.05 ng/mL, and the d-dimer level was 14.7 μg/mL. Spectral detector-based computed tomography showed bilateral scattered PE. After admission, his chest pain persisted, and the serum troponin I level 3 h after admission was elevated to 0.90 ng/mL. Reconstruction of SDCT images showed a perfusion defect of the posterolateral left ventricle myocardium. A coronary angiogram showed total occlusion of the obtuse marginal branch (OM); percutaneous coronary intervention was performed. Furthermore, we administered him with oral anticoagulants (OACs) for PE. Spectral detector-based computed tomography tests performed 6 months after the treatment was initiated, until when the dual antiplatelet therapy and OAC therapy were continued, showed improvement in perfusion defects of both pulmonary fields and the myocardium. His treatment was deescalated to single antiplatelet therapy and OAC, and the patient has had a good course. Discussion Non-ST-segment elevation myocardial infarction is sometimes difficult to diagnose accurately, especially in the hyper-acute phase or in the OM branch. The reconstruction of spectral images from enhanced SDCT was helpful to diagnose this unique combination of PE and NSTEMI and may be useful for evaluating therapeutic effects in such patients.

Aims Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. Methods Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-up-and-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. Results The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. Conclusions Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance. Geriatr Gerontol Int 2020; 20: 980-987.

Aim Although it is known that geriatric syndrome is associated with the development of frailty, it is not known whether an amelioration of geriatric syndrome also improves shared risk factors and frailty. Methods In total, 67 community‐dwelling older people (79.6 ± 6.5 years, 49 women) participated in this study (41 were classified as pre‐frail and 26 as frail). We analyzed indices of physical frailty and cognitive depression, exercise tolerance and health‐related quality of life as frailty related indices, and the participants completed a questionnaire regarding common geriatric symptoms (cold extremities, leg edema, breathlessness, urinary incontinence, chronic headache, chronic pain, a sense of numbness, anorexia, constipation, insomnia and skin trouble) using numeric ratings. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study (J‐CHS) criteria. The participants then underwent a far‐infrared low‐temperature sauna (FILTS) program twice a week for 3 months and the above parameters were reassessed. Results After the FILTS program, there were significant differences in usual walking speed, peak oxygen uptake, Geriatric Depression Scale‐15, health‐related quality of life and the severity of several geriatric symptoms. Of the 67 participants, 18 showed improvements in their J‐CHS frailty score, 47 showed no change and two showed reductions. Linear regression analysis showed that the change in the numeric rating of the coldness of extremities (B = −0.105, P = 0.013) and the cumulative numeric rating for geriatric syndromes (B = 0.044, P

Background: Elderly patients admitted to hospital with heart failure (HF) often have cognitive impairment, but the association between these conditions is unclear. Methods and Results: We enrolled 43 patients admitted to a geriatric hospital with HF. We evaluated echocardiography, Mini Mental State Examination (MMSE), and extracellular water/total body water (ECW/TBW) ratio (Inbody S10). Mean age was 85.1±8.0 years (range, 60–99 years) and 44.2% of the patients were men. Mean MMSE score was 20.5±5.4, with 66.7% of the patients showing cognitive impairment (MMSE ≤23). There was a significant negative correlation of MMSE score with age (r=−0.344, P=0.032), regular alcohol drinking (r=0.437, P=0.007), uric acid level (r=0.413, P=0.010), and ECW/TBW ratio (r=−0.437, P=0.007). On stepwise regression analysis including these covariates, MMSE score was significantly associated with the ECW/TBW ratio (β=0.443, P=0.009). When several echocardiography parameters (i.e., end-diastolic left ventricular volume, r=0.327, P=0.048; left atrial volume index, r=−0.411, P=0.012; and transmitral inflow A wave velocity, r=−0.625, P=0.001) were added to the model, MMSE score was found to be related to the A wave (P=0.001) and to atrial volume index (P=0.015), which are measures of diastolic function. Conclusions: In elderly patients with HF, cognitive function might be influenced by body water distribution and diastolic heart function.

Myocardial ischemia due to narrowing of the right coronary artery (RCA) may result in sinus arrhythmias, which usually present as transient sinus bradycardia with no hemodynamic instability. We report a rare case of sinus arrest with hemodynamic instability, which lasted for several months, and was caused by the occlusion of the sinus node (SN) artery following the RCA stenting. A 78-year-old woman with diabetes mellitus, hypertension, and dyslipidemia was referred to our hospital because of chest pain during activity. In her coronary angiogram, severe diffuse stenosis of the RCA was observed and intracoronary imaging using intravascular ultrasound revealed diffuse atherosclerotic plaque lesions with partial calcification and vulnerability. RCA was treated by inserting three zotarolimus-eluting stents. Immediately after these interventions, the SN artery originating from the RCA proximal to the lesion was occluded, which resulted in SN dysfunction. Significant bradycardia was observed on electrocardiogram along with low blood pressure, suggesting sinus arrest. Along with hemodynamic instability, sinus arrest lasted for several months, and permanent pacemaker implantation was needed. The plaque burden should be taken into consideration when choosing the appropriate percutaneous coronary intervention strategy because of the potential complication of sinus arrest after RCA stenting.

Background The aim of this study is to explore the prevalence and overlap of physical, cognitive, psychological, and social frailty and their negative-interrelationships. Methods We conducted a survey of people aged ≥75 years in the region with the oldest population in Japan. Frailty was divided into physical, cognitive, psychological, and social frailty, which were evaluated with the Japanese version of the Cardiovascular Health Study (J-CHS) criteria, J-CHS and the Japanese version of the Montreal Cognitive Assessment, the Geriatric Depression Scale-15 and the Lubben Social Network Scale, respectively. Results Of the 268 participants (aged 81.5 ± 4.5 years), 48.1% and 8.6% had physical prefrailty and frailty; 68.3%, 13.0%, and 5.2% had mild cognitive impairment, dementia, and cognitive frailty; 25.7% and 5.2% had depressive mood and depression as psychological frailty; and 7.8% had social frailty, respectively. Path analysis showed that social frailty was associated with psychological frailty. Psychological frailty was associated with physical frailty. Physical frailty was associated with cognitive frailty. Multiple logistic regression analysis showed that independent determinants of physical robustness were female sex, age, and psychological robustness (odds ratio (OR) = 2.166, 0.831, 3.625, respectively). Determinants of cognitive robustness were age and psychological robustness (OR = 0.837, 7.079). Determinants of psychological robustness were physical, cognitive, and social robustness (OR = 3.759, 6.829, 5.037), and the determinant of social robustness was psychological robustness (OR = 4.489), respectively. Conclusions We demonstrated the prevalence, overlap, and interrelationships of different types of frailty and clarified the factors that may help to reduce frailty.

Background: Nonspecific ST-T change in electrocardiogram can be observed in hypertensive heart disease with preserved left ventricular ejection fraction (LVEF); however, the relationship between nonspecific ST-T change and global myocardial work in echocardiography was unclear. Methods: We evaluated global longitudinal strain (GLS), GWI (global work index), GCW (global constructive work), GWW (global wasted work), GWE (global work efficiency), using offline analyzing system (View Pal, GE) in 196 hypertensive patients with preserved LVEF (>50%). Nonspecific ST-T change and major ST-T change (depression of ST in V5 lead >1mV) was also evaluated in electrocardiogram. Results: Mean age was 79.3±8.2 years (men 37.8%). Compared with patients with no ST-T change, those with nonspecific and major ST-change had a smaller absolute value of GLS (-20±3, -18±4, -14±5%, P Conclusion: In hypertensive patients with preserved LVEF, nonspecific ST-T change in electrocardiogram was associated with a reduced constructive work in LV.

Background: Although an elevated systolic blood pressure (SBP) is associated with cognitive dysfunction, BP may decrease with advanced cognitive dysfunction; therefore, we attempted to identify the turning point in the relationship between cognitive function and SBP in elderly subjects. Methods: In pooled datasets of general populations and outpatient clinics (age>65 years), in which the risk of frailty or cognitive dysfunction was assessed (N = 4076), the relationship between SBP and the Mini Mental State Examination (MMSE) score was examined. Results: Mean age was 72.5 ± 6.2 years (male 45.1%), and SBP was 133.0 ± 19.5 mmHg. In an analysis of locally weighted scatter plot smoothing, the relationship between SBP and MMSE scores changed at an MMSE score of 24 points. In subjects with preserved cognitive function (MMSE ≥24 points), MMSE scores decreased with increases in SBP (B = −0.047 per 10 mmHg increase, P = 0.002) after adjustments for age, sex, body mass index, alcohol habit, smoking status, diabetes, a history of stroke, and the geriatric nutritional index; however, in subjects with reduced cognitive function (MMSE

Background: Evidence regarding the primary prevention of coronary artery disease events by low-density lipoprotein cholesterol (LDL-C) lowering therapy in older individuals, aged ≥75 years, is insufficient. This trial tested whether LDL-C–lowering therapy with ezetimibe is useful for the primary prevention of cardiovascular events in older patients. Methods: This multicenter, prospective, randomized, open-label, blinded end-point evaluation conducted at 363 medical institutions in Japan examined the preventive efficacy of ezetimibe for patients aged ≥75 years, with elevated LDL-C without history of coronary artery disease. Patients, who all received dietary counseling, were randomly assigned (1:1) to receive ezetimibe (10 mg once daily) versus usual care with randomization stratified by site, age, sex, and baseline LDL-C. The primary outcome was a composite of sudden cardiac death, myocardial infarction, coronary revascularization, or stroke. Results: Overall, 3796 patients were enrolled between May 2009 and December 2014, and 1898 each were randomly assigned to ezetimibe versus control. Median follow-up was 4.1 years. After exclusion of 182 ezetimibe patients and 203 control patients because of lack of appropriate informed consent and other protocol violations, 1716 (90.4%) and 1695 (89.3%) patients were included in the primary analysis, respectively. Ezetimibe reduced the incidence of the primary outcome (hazard ratio [HR], 0.66; 95% CI, 0.50–0.86; P =0.002). Regarding the secondary outcomes, the incidences of composite cardiac events (HR, 0.60; 95% CI, 0.37–0.98; P =0.039) and coronary revascularization (HR, 0.38; 95% CI, 0.18–0.79; P =0.007) were lower in the ezetimibe group than in the control group; however, there was no difference in the incidence of stroke, all-cause mortality, or adverse events between trial groups. Conclusions: LDL-C–lowering therapy with ezetimibe prevented cardiovascular events, suggesting the importance of LDL-C lowering for primary prevention in individuals aged ≥75 years with elevated LDL-C. Given the open-label nature of the trial, its premature termination and issues with follow-up, the magnitude of benefit observed should be interpreted with caution. Clinical Registration: URL: https://www.umin.ac.jp . Unique identifier: UMIN000001988.

OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) is now recognized as a geriatric syndrome with multifactorial pathophysiology and clinical heterogeneity rather than a solely left ventricular diastolic dysfunction. Because the pathophysiology of HFpEF is suggested to differ by age, this study compared the clinical characteristics and prognostic factors between HFpEF patients aged 65 to 84 years and those aged 85 years or older. DESIGN Retrospective cohort study. SETTING The Tokyo CCU Network including 73 hospitals in Tokyo, Japan. PARTICIPANTS Individuals aged 65 years or older with HFpEF (N = 4305). MEASUREMENTS Very old patients were defined as those aged 85 years or older. Potential risk factors for in-hospital mortality were selected by univariate analyses, and those with a P value

Aim Orthostatic blood pressure (BP) can fall with reduced stroke volume and arterial elasticity. However, as the reason for orthostatic BP rise is unclear, we investigated the relationship of orthostatic BP rise with frailty in older patients. Methods In 169 consecutive outpatients who visited the frailty clinic, we evaluated orthostatic BP and heart rate changes (i.e. in the sitting position, just after standing up, 1 min after standing and after sitting down). Frailty was evaluated using the Kihon Checklist (KCL) established by the Ministry of Health, Labor and Welfare. Results The mean age was 77.4 ± 6.9 years, and 29% of patients had frailty with a KCL score ≥8. The systolic BP declined in both groups, but patients with frailty experienced a smaller decrease just after standing (-0.2 ± 10.3 vs -6.2 ± 11.5, P = 0.001). During standing for 1 min, elevation of systolic BP was greater in patients with frailty than in those without (8.4 ± 11.6 mmHg vs 3.2 ± 11.2 mmHg, P = 0.009). The difference in elevation of systolic BP remained significant, even after adjusting for confounding factors including systolic BP before standing (P = 0.013). In particular, the KCL score for motor function was significantly correlated with an elevation of orthostatic systolic BP after standing for 1 min, even after controlling for systolic BP before standing and confounding factors (P = 0.020). Conclusions The elevation of systolic BP after standing for 1 min was greater in patients with frailty as diagnosed by the KCL score, especially in relation to reduced motor function. Geriatr Gerontol Int 2019; 19: 525-529.

Electrocardiographic left ventricular hypertrophy (LVH) diagnosed by Cornell product and the Sokolow-Lyon voltage are associated with anatomical LVH; therefore, we investigated whether Cornell product and the Sokolow-Lyon voltage were associated with echocardiographic regional wall motion (measured by 2D-strain imaging). We reviewed data on 288 consecutive hypertensive patients who underwent both echocardiography and electrocardiography. Electrocardiographic LVH was calculated as follows: Cornell voltage, S in lead V3 + R in lead aVL; Cornell product, Cornell voltage (+0.6 mV for females) × QRS duration; and Sokolow-Lyon voltage, S in lead V1 + R in lead V5. The mean age of the subjects was 64.3 ± 13.2 years; 47.9% were men, and 65.2% were taking antihypertensive medications. Both Cornell product (r = 0.392, P < 0.001) and the Sokolow-Lyon voltage (r = 0.315, P < 0.001) were significantly related to left ventricular mass index (LVMI), and the relationship between Cornell product and LVMI (beta = 0.24, P = 0.001) was independent of the Sokolow-Lyon voltage (beta = 0.25, P < 0.001). In multivariate linear regression analysis in which the two ECG-LVH were included together, Cornell product was related to global longitudinal strain (beta = 0.24, P = 0.002), even after adjusting for the Sokolow-Lyon voltage (P = 0.835). Additionally, the Cornell voltage was related to the inner/outer ratio of circumferential strain (beta = 0.17, P = 0.033) after adjusting for the Sokolow-Lyon voltage (P = 0.318). By contrast, the Sokolow-Lyon voltage was related to the relative wall thickness and E/e' on tissue Doppler imaging, even after adjusting for Cornell product. In conclusion, Cornell product and voltage were associated with longitudinal regional wall motion and with the transmurality of regional wall motion in the short axis direction.

Aim Heart failure is increasing in Japan, in particular that with preserved ejection fraction (HFpEF) prevalent in older-aged patients. The purpose of this study was to investigate the pathophysiology during the early stage of left ventricular (LV) diastolic dysfunction by the quantitative proteome analysis of human myocardium. Methods Among 331 post-mortem autopsy patients, we selected 23 patients (aged 79 ± 9.6 years) with echocardiographic data and without major comorbidities, except hypertension. Cryopreserved autopsy tissue of the LV myocardium was subjected to proteome analysis. LV diastolic function was evaluated by echocardiographic data. Thirteen patients were classified into the impaired diastolic function (IDF) group, and 10 the normal cardiac function group. We performed comparative proteome analysis between the IDF and normal groups by isobaric tags for relative and absolute quantitation (iTRAQ) using nano-liquid chromatography-tandem mass spectrometry. Results The iTRAQ-based proteome analysis revealed 57 differentially expressed proteins in the IDF group. Molecular network analysis of differentially expressed proteins indicated that endoplasmic reticulum (ER) stress was a potentially important event. Furthermore, the expressions of proteins associated with the ER stress response, such as glucose-regulated protein 78 kDa, inositol-requiring kinase 1α and spliced X-box binding protein 1, were significantly decreased in the IDF group. Conclusions This study suggested that reduced ER stress responses were involved during the early stage of LV diastolic dysfunction. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

OBJECTIVE Unattended automated office blood pressure (AOBP) may be a better estimate of true blood pressure (BP) than conventional office BP by physicians or nurses. However, measurement of AOBP is cumbersome in general clinical practice. We compared unattended AOBP by the patients themselves using the rigid cuff in the waiting room with attended AOBP and home BP (HBP) (N = 72). METHODS Unattended AOBP by patients was measured in the waiting room using a rigid cuff with the fully automated device (Omron, HEM-907, triple BP readings taken at 1-min intervals after 5 min of rest). Attended AOBP was measured using a soft cuff by a physician in an examination room without specific resting time. HBP was measured for 5 consecutive days. RESULTS The mean age was 76.5 ± 8.6 years. The mean systolic unattended AOBP by patients, attended AOBP and HBP were 139.3 ± 16.6, 144.8 ± 17.1 and 139.1 ± 14.4 mmHg, respectively. Unattended AOBP by patients was significantly related to attended AOBP (r = 0.798; P

Background: An ideal urban network system for improving regional acute myocardial infarction (AMI) outcomes should be geographically balanced and uniform according to regional population in performance of participating hospitals. The objective of our study is to evaluate whether there is a major difference in risk-adjusted in-hospital mortality between the Tokyo Cardiovascular Care Unit (CCU) network hospitals, which cover the whole population of large cities. Methods: The study subjects were all AMI patients without cardiac arrest on arrival admitted to the Tokyo CCU network hospitals from 2009 to 2017. Risk-adjusted in-hospital mortality rates (RAMRs) were compared between the categories of each hospital-level factor. A hospital-level multivariable linear regression was modeled to analyze the association between RAMRs and hospital-level factors. A funnel plot was constructed by plotting RAMRs against hospital volumes. Results: From 2009 to 2017, there were 42,123 hospitalizations for AMI in Tokyo CCU network hospitals (n=72, as of December, 2017). There were no significant differences in RAMRs in the comparison of hospital backgrounds. Each hospital background was not significantly associated with the RAMR. Considering the 99% CI in funnel plots, only five hospitals (7.2%) were located outside the control limits. Conclusions: There was no major difference in the RAMRs between the participating hospitals within the Tokyo CCU network, despite the different hospital backgrounds.

Background: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators. Methods: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality. Results: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P=0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures. Conclusions: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators. Trial registration: UMIN-CTR identifier, UMIN000013128

Background: Frailty and sarcopenia are age-related morbid states, and a low body mass index (BMI) is a characteristic of frailty and cachexia. However, no common index for assessing these three muscle wasting states is available, making it difficult to understand the relationship among them. Peak oxygen uptake (peak VO 2 ), an index of life expectancy, may be a useful common index. Therefore, this study aimed to investigate the relationship among sarcopenia, frailty, and cachexia using age, BMI, and peak VO 2 . Methods: Participants were 175 Japanese community dwelling older adults (58 men, 117 women; 77.6 years). We assessed biochemical, physiological, and physical factors, and symptoms associated with frailty, and cachexia. Peak VO 2 was assessed with a cardiopulmonary exercise test. Participants were classified into five groups: robust, pre-frail, frail, sarcopenia, and cachexia. We compared the groups by age, BMI, and peakVO 2 with average values and 95% confidence intervals (CIs). Results: 17% (n=30) of participants were classified as robust, 40% (n=70) as pre-frail, 12% (n=21) as sarcopenia, 25% (n=44) as frail, and 6% (n=10) as cachexia. Significant differences were found in age (robust vs. frail, pre-frail vs. frail), BMI (robust vs. cachexia, pre-frail vs. cachexia, frail vs. cachexia), and peak VO 2 (robust vs. frail, robust vs. cachexia, pre-frail vs. cachexia) with average values and 95% CIs. Three dimensions among age, BMI and peak VO 2 revealed two trajectories (from robust to frailty via pre-frailty, and from robust to cachexia via sarcopenia) among muscle wasting diseases. Conclusions: This study revealed two trajectories among muscle wasting diseases.

Aims The association of vascular dysfunction and amyloid beta deposition attracted attentions for its relationship with cognitive decline. Previous studies show the correlation between the declined cardiac function and the cognitive impairment. In the present study, we analysed the association between cognitive functions and cardiac parameters in community-dwelling people with preserved ejection fraction without heart failure. Methods and results Subjects were 108 Japanese community-dwelling middle-aged and older adults with preserved ejection fraction (25 men and 83 women; mean age 74.7 years). Cardiac functional parameters at rest were assessed with B-type natriuretic peptide and echocardiography. The cardiopulmonary exercise test was used to test these parameters during exercise. Cognitive function was assessed with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Other indices were assessed biochemically, physiologically, and physically. There were significant correlations between MoCA-J score and age (r = -0.388), peak oxygen uptake (VO2 , r = 0.201), peak VO2 /heart rate (HR, r = 0.243), peak VO2 /weight (r = 0.244), peak metabolic equivalents (r = 0.244), usual walking speed (r = -0.200), and the Timed Up and Go test (r = -0.230). Multiple linear regression analysis showed peak VO2 /HR was an independent determinant of MoCA-J score after adjusting for potential confounders (B = 0.424). After 6 months of exercise training with 64 subjects, we found that the per cent change of peak VO2 /HR was related to the per cent change of MoCA-J score (r = 0.296). Conclusions These results suggested that peak VO2 /HR (an index of stroke volume at peak exercise) might be associated with cognitive impairment based on the vascular cascade hypothesis.

AIM Physical exercise improves cognitive function in people with mild cognitive impairment (MCI). However, information about whether the degree of MCI before exercise training affects improvement in cognitive function is lacking. Therefore, we aimed to investigate the cut-off value in a MCI screening tool that predicts reversal to normal cognitive function after exercise training in older adults with MCI. METHODS Participants included 112 Japanese community-dwelling older adult outpatients (37 men, 75 women; mean age 76.3 years). We administered the Japanese version of the Montreal Cognitive Assessment (MoCA-J) before and after exercise training. MCI was defined as a MoCA-J score