Symptomatic Chronic Heart Failure Patients Research Articles

Machine learning-based gait analysis to predict clinical frailty scale in elderly patients with heart failure.

Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from 7 centres between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the light gradient boosting machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen's weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs [CWK 0.866, 95% confidence interval (CI) 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively]. During a median follow-up period of 391 (inter-quartile range 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (hazard ratio 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates. Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.

Abstract 13078: Prognostic Significance of Reticulocyte Production Ability in Patients With Chronic Heart Failure

Background: Anemia is frequently observed in patients with chronic heart failure (CHF), and many studies have evaluated the association between anemia and mortality in CHF. The quality of erythropoiesis is an intrinsic aspect of pathophysiology of anemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. However, it remains unclear whether reticulocyte production ability is associated with clinical outcomes in patients with CHF. Methods: We prospectively examined 1,274 symptomatic CHF patients (mean age 71.9±13.4 years, median LVEF 50 [IQR 36-63]%) in a multicenter registry (25 sites). The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum hematocrit. Patients were divided into four groups according to the presence of WHO defined anemia and the median value of RPI. The primary outcome was composite of all-cause death and hospitalization for worsening HF. Results: During a median follow-up period of 427 (IQR 273-642) days, the primary outcome occurred in 222 (17%) patients. The group with anemia and high RPI (≥0.982, the median) showed the highest incidence of the primary outcome among the groups ( P < 0.001) (Figure A). In an anemic subgroup (n = 611), higher RPI was independently associated with increased adverse events (HR 1.67, 95% CI 1.31-2.13) adjusted for age, sex, estimated glomerular filtration rate, NT-pro BNP, hemoglobin, serum sodium and iron parameters. In this subgroup, erythrocyte counts were not significantly increased in patients with higher RPI compared to lower RPI (Figure B). Moreover, there were no significant differences on transferrin saturation and serum iron between the groups (Figure B). Conclusions: Higher reticulocyte production ability, which might reflect the impaired process of erythropoiesis, was associated with worse clinical outcomes in patients with CHF, especially with anemia.

Abstract 16327: Machine Learning-Based Prediction of Clinical Frailty Scale Based on Gait Analysis in Elderly Patients With Heart Failure

Background: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods: We prospectively examined 358 elderly (≥75 years) with symptomatic chronic HF patients (mean age 82.3±5.2 years, left ventricular ejection fraction 58 [IQR 45-67]%) from six sites between January 2019 and September 2022. The CFS was evaluated based on the modified Delphi method by 10 independent trained cardiologists as the gold standard. We obtained body-tracking motion data using OpenPose ® , a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the extremely randomized trees (ERT) model. To evaluate the performance of this model, we calculated Cohen’s weighted kappa and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. The studied patients were divided into derivation (from a university hospital) and validation (from other five sites) cohorts. Results: In the derivation (n = 181) and validation (n = 177) cohorts, the ERT model showed sufficient agreement between the actual and predicted CFSs (kappa 0.864, ICC 0.864 and kappa 0.796, ICC 0.796, respectively) ( Figure ). During a median follow-up period of 421 (IQR 280-616) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (HR 1.97, 95% CI 1.21-3.20) adjusted for the MAGGIC mortality risk prediction score, N-terminal pro-brain natriuretic peptide, and serum albumin levels. Conclusions: Machine learning-based algorithms that automatically rate the CFS are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.

MiR-568 mitigated cardiomyocytes apoptosis, oxidative stress response and cardiac dysfunction via targeting SMURF2 in heart failure rats.

Chronic heart failure (CHF), a conventional, complex, and severe syndrome, is generally defined by myocardial output inadequate to satisfy the metabolic requirements of body tissues. Recently, miR-568 was identified to be down-regulated in CHF patients' sera and negatively correlated with left ventricular mass index in symptomatic CHF patients with systolic dysfunction. Nevertheless, the role of miR-568 during CHF development remains obscure. The current study is aimed to investigate the role of miR-568 in CHF. The MTT assay, flow cytometry analysis, RT-qPCR analysis, western blot analysis and luciferase reporter assays were conducted to figure out the function and potential mechanism of miR-568 in vitro. Rats were operated with aortic coarctation to establish CHF animal model. The effects of miR-568 and SMURF2 on CHF rats were evaluated by hematoxylin-eosin staining, Masson's staining, serum index testing, cardiac ultrasound detection, and TUNEL staining assays. We discovered that miR-568 level was downregulated by H2O2 treatment in cardiomyocytes. In mechanism, miR-568 directly targeted and negatively regulated SMURF2. In function, SMURF2 overexpression reversed the effects of miR-568 on cardiac function and histological changes in vivo. Additionally, SMURF2 overexpression reversed the effects of miR-568 on the content of LDH, AST, CK and CK-MB in vivo. Moreover, SMURF2 overexpression reversed the effects of miR-568 on oxidative stress response in vivo. MiR-568 mitigated cardiomyocytes apoptosis, oxidative stress response and cardiac dysfunction via targeting SMURF2 in CHF rats. This discovery may serve as a potential biomarker for CHF treatment.

Utilization and Efficacy of Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure - A Report From the CHART-2 Study.

Background: Although cardiac resynchronization therapy (CRT) is effective for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction and wide QRS (≥120 ms), data on the use of or long-term outcomes after CRT implantation in Japan are limited.Methods and Results: We examined proper CRT utilization and outcomes in 3,447 consecutive symptomatic CHF patients registered in the CHART-2 Study. We identified 167 potentially eligible patients and divided them into 4 groups according to the presence (+) or absence (−) of an indication for and implantation of CRT: Group A (reference group), (+)indication/(+)CRT; Group B, (+)indication/(−)CRT; Group C, (−)indication/(+)CRT; and Group D, (−)indication/(−)CRT. Based on the Japanese Circulation Society guidelines, 91 patients met the eligibility for CRT implantation, with 43 (47%) of them undergoing CRT implantation. After adjusting for confounders, age was significantly associated with no CRT use (odds ratio per 5-year increase 1.46; 95% confidence interval 1.11–2.05; P=0.012). Among the 4 groups, the cumulative incidence of cardiovascular death and CHF admission were highest in Group B and lowest in Group D (P=0.029).Conclusions: In this study, only half the eligible CHF patients properly received CRT. Aging was a significant risk factor for no CRT use. Patients without CRT despite having an indication could be at higher risk of mortality and CHF admission.

Correlation between QRS duration and cardiac output measured by left ventricular outflow tract velocity in patient with cardiac resynchronization therapy

Abstract Background Cardiac resynchronization therapy (CRT) is proved as an effective treatment for moderate to severe heart failure. It reduces all-cause mortality in patients with advanced heart failure. There is strong evidence that CRT reduces mortality and hospitalization, improves cardiac function and structure in symptomatic chronic heart failure patients with optimal medical treatment, severely depressed LVEF (i.e. <35%) and complete LBBB. However 30% of patients may show negative response to CRT therapy. Therefore, optimization of CRT therapy in patients with heart failure seems to be a main subject for study in our researches. Methods of optimization includes optimization of medical therapy, control of risk factors and comorbidities, and optimization of device implantation and programming. Overall, studying the correlation between QRS duration and cardiac output will improve CRT programming optimization techniques. Aim To study the correlation between QRS duration and cardiac output measured by left ventricular outflow tract (LVOT) VTI in patients with CRT implantation. Methods Study included 100 CRT already implanted patients, they are requested to do a simple electrocardiographic and echocardiographic study. The relation between post implant QRS and cardiac output are studied among the patients. Results There was negative significant correlation between QRS duration and LVOT VTI and SVi. The optimal cut off values for optimal response to CRT using ROC curves were 130msec for post implant QRS duration and 17.1 cm for LVOT VTI. Conclusion CRT response is more in female patients with lower BSA, and without previous history of IHD or smoking. There is a significant negative correlation between QRS duration and LVOT VTI. Post implantation cut off value of QRS duration (<130) predict higher LVOT VTI and also the post implantation benefit for the patient with CRT implanted.

Evaluation of the role of enhanced external counter pulsation in patients with chronic heart failure

Background: The incidence of Chronic Heart failure (CHF) has reached epidemic proportions in developing countries. The prevalence also increases as the patient population ages. Heart failure accounts for between 5% and 10% of all hospital admissions and is the most frequent cause of hospitalization in the elderly. The aim of this single centre observational study was to find out the efficacy of EECP in improving functional capacity and LV function in symptomatic chronic heart failure patients with mild to moderate LV dysfunction irrespective of their etiology.Methods: Thirty-six symptomatic patients in NYHA class II and III were included in this study. All the patients underwent one hour EECP therapy for thirty-five sessions over a period of seven weeks. NYHA classification, six-minute walk test, two dimensional and Tissue Doppler Echocardiographic examination were done before and after EECP therapy.Results: At the end of EECP therapy there was improvement in functional class. Eleven out of thirty-six patients were asymptomatic. The mean distance covered in six-minute walk test was also significantly increased after the therapy. The Echocardiographic parameters like Ejection Fraction (EF), Systolic excursion of mitral valve annulus (S'), Ratio between mitral flow E Velocity & Mitral annular E velocity (E/E’) significantly improved after EECP.Conclusions: In this study, it was concluded that there was significant improvement in symptoms, functional capacity and LV function in Chronic Heart Failure patients after EECP therapy.

Predictors of short-term clinical response to cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment-covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. In symptomatic chronic heart failure patients (NYHA class II-IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT.

Abstract 17891: Impact of Physical Activity and Sedentary Time on Heart Failure Outcomes

Introduction: The impact of physical inactivity and sedentary time on heart failure (HF) outcomes in patients not participating in exercise program is unclear. Hypothesis: Physical inactivity and sedentary time are associated with worse HF outcomes. Methods: We analyzed data from the multicenter, HF Adherence and Retention Trial (HART) which enrolled 902 NYHA - II/III HF patients with preserved or reduced ejection fraction, followed for 36 months. Based on the mean weekly purposeful physical activity duration, patients were classified into inactive (0 min/wk), partially active (1-90 min/wk), and active (&gt;90min/wk) groups. Patients were also classified according to average daily sedentary television (TV) time into &lt;2 hrs/d, 2-4 hrs/d, and &gt;4 hrs/d groups. Study groups were propensity score matched according to 33 baseline covariates in 1:1:1 ratio. The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. Results: There were 196 inactive, 341 partially active and 365 active patients, of whom 492 (164 in each group) were successfully propensity matched. Physical inactivity was associated with higher risk of death and cardiac death than any level of physical activity, Fig 1. There was no significant difference in HF hospitalization. Furthermore, 465 subjects were propensity matched into three sedentary TV time groups (155 in each group). Sedentary TV time &gt;4 hrs/d was independently and incrementally associated with all-cause death (Δ χ 2 = 6.05; P=0.049), beyond physical activity time, Fig 1. There was no significant difference in mortality between &lt;2 and 2-4 hrs/d sedentary TV time groups, after adjusting to physical activity time, Fig 2. Conclusions: In symptomatic chronic HF patients, physical inactivity is associated with higher all-cause and cardiac mortality. Modest purposeful physical activity was associated with survival benefit. Extended sedentary time was associated incremental increased mortality.

Prognostic Impact of Subclinical Microalbuminuria in Patients With Chronic Heart Failure

Background:Microalbuminuria, traditionally defined as urinary albumin/creatinine ratio (UACR) ≥30 mg/g, is a risk factor for mortality even in patients with preserved glomerular filtration rate (GFR). The prognostic impact of subclinical microalbuminuria, however, remains unknown in patients with chronic heart failure (CHF).Methods and Results:In the Chronic Heart Failure Analysis and Registry in the Tohoku District 2 Study, we enrolled 2,039 consecutive symptomatic CHF patients (median age, 67.4 years; 68.9% male) after excluding those on hemodialysis. On classification and regression tree analysis, UACR=10.2 mg/g and 27.4 mg/g were identified as the first and second discriminating points to stratify the risk for composite of death, acute myocardial infarction, HF admission and stroke, therefore subclinical microalbuminuria was defined as UACR ≥10.2 and <27.4 mg/g. There were 506 composite endpoints (24.8%) during the median follow-up of 2.69 years. On Kaplan-Meier analysis and multivariate Cox modeling, subclinical microalbuminuria was significantly associated with increased composite endpoints with hazard ratios of 1.90 (P<0.001) and 2.29 (P<0.001) in patients with preserved (>60 ml·min-1·1.73 m-2, n=1,129) or mildly reduced eGFR (30-59.9 ml·min-1·1.73 m-2, n=789), respectively. In patients with severely reduced GFR (eGFR <30 ml·min-1·1.73 m-2, n=121), >80% had microalbuminuria or macroalbuminuria, and only 9.1% were free from any composite endpoints.Conclusions:Subclinical microalbuminuria was associated with increased risk of cardiovascular events in CHF patients with mildly reduced or preserved renal function.

Intravenous ferric carboxymaltose in iron‐deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR‐HF trial

AimsTherapy with i.v. iron in patients with chronic heart failure (CHF) and iron deficiency (ID) improves symptoms, functional capacity, and quality of life. We sought to investigate whether these beneficial outcomes are independent of anaemia.Methods and resultsFAIR-HF randomized 459 patients with CHF [NYHA class II or III, LVEF ≤40% (NYHA II) or ≤45% (NYHA III)] and ID to i.v. iron as ferric carboxymaltose (FCM) or placebo in a 2:1 ratio. We analysed the efficacy and safety according to the presence or absence of anaemia (haemoglobin ≤120 g/L) at baseline. Of 459 patients, 232 had anaemia at baseline (51%). The effect of FCM on the primary endpoints of self-reported Patient Global Assessment (PGA) and NYHA class at week 24 was similar in patients with and without anaemia [odds ratio (OR) for improvement, 2.48 vs. 2.60, P = 0.97 for PGA and 1.90 vs. 3.39, P = 0.51 for NYHA). Results were also similar for the secondary endpoints, including PGA and NYHA at weeks 4 and 12, 6 min walk test distance, Kansas City Cardiomyopathy Questionnaire overall score, and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points. Regarding safety, no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients.ConclusionsTreatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia. Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered.

ADDITION OF IVABRADINE TO CARVEDILOL REDUCES DURATION OF CARVEDILOL UPTITRATION AND IMPROVES EXERCISE CAPACITY IN PATIENTS WITH CHRONIC HEART FAILURE

Ivabradine, a specific If current inhibitor, improves prognosis in patients with chronic heart failure (CHF) and is recommended by ESC Guidelines for symptomatic CHF patients with elevated heart rate (HR) on evidence-based or maximum tolerated doses of β-blocker (BB) and RAAS antagonists. However,

Assessment of left ventricular dyssynchrony in pacing-induced left bundle branch block compared with intrinsic left bundle branch block

Although electrocardiographic and echocardiographic findings with right ventricular (RV) pacing mimic intrinsic left bundle branch block (LBBB), left ventricular (LV) mechanical activation pattern may differ. We compared mechanical activation pattern of the LV in RV-pacing-induced LBBB with intrinsic LBBB in symptomatic chronic heart failure patients. We studied 37 patients with chronic RV-pacing and 37 patients with intrinsic LBBB who were referred for cardiac resynchronization therapy. Echocardiographic study including 2D speckle tracking longitudinal strain and M-mode were performed at baseline. Patients with intrinsic LBBB were younger, had higher prevalence of ischaemic heart disease, and had more severe depressed LV function. The basal-septal segments were the earliest activated sites in 11% of patients in RV-pacing-induced LBBB compared with 30% in intrinsic LBBB (P= 0.04). The mid- and basal-lateral segments were the latest activated sites in 57% of patients in RV-pacing-induced LBBB compared with 30% in intrinsic LBBB (P = 0.03). Left ventricular dyssynchrony, using longitudinal strain, time delay ≥ 130 ms between either mid-septal or apico-septal and either basal or mid-lateral segments was present in 71% of patients with RV-pacing-induced LBBB compared with 59% in intrinsic LBBB (P = 0.03). Using M-mode, LV dyssynchrony was present in 11% of patients with RV-pacing-induced LBBB compared with 59% in intrinsic LBBB (P = 0.02). Right ventricular-pacing results in less early basal activation and more often early mid-septal and late lateral wall activation in comparison with intrinsic LBBB. Imaging techniques that only visualize the basal- or mid-part of the LV may result in a serious underestimation of dyssynchrony in patients with pacing-induced LBBB.

Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure

In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.

A Multicenter Study of Noninvasive Cardiac Output by Bioreactance During Symptom-limited Exercise

Background Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF. Methods and Results A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO 2, cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO 2 (pVO 2) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min) = 19.6 + 4·M – 2.1·NYHA + 1.9·G – 0.09·Age, where M = 1 for treadmill and 0 for bicycle and G = 1 for males and 0 for females. Similarly, pVO 2 (mL/kg/min) = 24 + 2.1·M – 2.9·NYHA + 1.26·G – 0.08·Age. VO 2 and CO were also highly correlated to each other: pCO (mL/kg/min) = 0.059 + 0.007·pVO 2 + 0.036·M – 0.025·G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO 2 (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance. Conclusion Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO 2 and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.

Abstract: S2-2 ROLES OF INFLAMMATION AND ENDOPLASMIC RETICULUM STRESS IN THE PROGRESSION AND RAPTURE OF ATHEROSCLEROTIC PLAQUES

The goal of this work was to determine whether the blockade of histamine H2receptors is beneficial for the pathophysiology of chronic heart failure (CHF).Because CHF is one of the major life-threatening diseases, we need to find a novel effective therapy. Intriguingly, our previous study, which predicts the involvement of histamine in CHF, suggests that we should test this hypothesis in patients with CHF.We selected 159 patients who received famotidine among symptomatic CHF patients for the retrospective study. We blindly selected age- and gender-matched CHF patients receiving drugs for gastritis other than histamine H2receptor blockers as a control group. For the prospective study, 50 symptomatic CHF patients were randomly divided into 2 groups. One group received famotidine of 30 mg/day for 6 months, and the other group received teprenone.In the retrospective study, famotidine of 20 to 40 mg decreased both left ventricular end-diastolic and end-systolic lengths (LVDd and LVDs, respectively) and the plasma B-type natriuretic peptide (BNP) levels (182 ± 21 vs. 259 ± 25 pg/ml, p < 0.05) with unaltered fractional shortening (FS). In a randomized, open-label study, compared with teprenone, famotidine of 30 mg prospectively decreased both New York Heart Association functional class (p < 0.05) and plasma BNP levels (183 ± 26 pg/ml vs. 285 ± 41 pg/ml, p < 0.05); this corresponded to decreasing both LVDd (57 ± 2 mm vs. 64 ± 2 mm, p < 0.05) and LVDs (47 ± 2 mm vs. 55 ± 2 mm, p < 0.05) with unaltered FS (15 ± 1% vs. 17 ± 1%). The frequency of readmission because of worsening of CHF was lower in the famotidine group (4% and 24%, p < 0.05). On the other hand, teprenone had no effects on CHF.Famotidine improved both cardiac symptoms and ventricular remodeling associated with CHF. Histamine H2receptor blockers may have therapeutic benefits for CHF.

Emerging Problems of Heart Failure Practice in Japanese Women Lessons From the CHART Study

The prognosis of patients with chronic heart failure (CHF) is poor in both men and women. However, the characteristics of, and effective treatment strategy for, female CHF patients still remain unclear. This study was designed to evaluate the prognosis and characteristics of female patients in a CHF cohort termed the Chronic Heart Failure Analysis and Registry in the Tohoku District. Of 1,278 patients registered in the cohort, the study population comprised 1,166 symptomatic CHF patients with sufficient data. As compared with male patients, female patients were more likely to be older, have preserved systolic function and non-ischemic etiology of CHF, and underuse standard CHF medications. Although a previous study showed that sex-difference was not a significant prognostic factor in CHF patients, the unadjusted survival analysis revealed an increased event rate in female patients in the present study. Multivariate analysis revealed that older age, diabetes, ventricular tachycardia and anemia were significant prognostic risks in both men and women with CHF. Female sex had a significant link with elderly CHF patients. Given the explosive increase in elderly patients in Westernized countries, further studies are needed to elucidate the evidence for treatment of female CHF patients.

Red Cell Distribution Width as a Novel Prognostic Marker in Heart Failure: Data From the CHARM Program and the Duke Databank

The goal of this study was to identify potentially novel laboratory markers of risk in chronic heart failure patients. Although a variety of prognostic markers have been described in heart failure, a systematic assessment of routine laboratory values has not been reported. All 2,679 symptomatic chronic heart failure patients from the North American CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) program had a wide range of laboratory measures performed at a core facility, enabling us to assess the relationship between routine blood tests and outcomes using a Cox proportional hazards model. We then replicated our findings in a cohort of 2,140 heart failure patients from the Duke Databank. Among 36 laboratory values considered in the CHARM program, higher red cell distribution width (RDW) showed the greatest association with morbidity and mortality (adjusted hazard ratio 1.17 per 1-SD increase, p < 0.001). Higher RDW was among the most powerful overall predictors, with only age and cardiomegaly showing a better independent association with outcome. This finding was replicated in the Duke Databank, in which higher RDW was strongly associated with all-cause mortality (adjusted hazard ratio 1.29 per 1 SD, p < 0.001), second only to age as a predictor of outcome. In 2 large contemporary heart failure populations, RDW was found to be a very strong independent predictor of morbidity and mortality. Understanding how and why this marker is associated with outcome may provide novel insights into heart failure pathophysiology.

Impact of Blockade of Histamine H2Receptors on Chronic Heart Failure Revealed by Retrospective and Prospective Randomized Studies

The goal of this work was to determine whether the blockade of histamine H2 receptors is beneficial for the pathophysiology of chronic heart failure (CHF). Because CHF is one of the major life-threatening diseases, we need to find a novel effective therapy. Intriguingly, our previous study, which predicts the involvement of histamine in CHF, suggests that we should test this hypothesis in patients with CHF. We selected 159 patients who received famotidine among symptomatic CHF patients for the retrospective study. We blindly selected age- and gender-matched CHF patients receiving drugs for gastritis other than histamine H2 receptor blockers as a control group. For the prospective study, 50 symptomatic CHF patients were randomly divided into 2 groups. One group received famotidine of 30 mg/day for 6 months, and the other group received teprenone. In the retrospective study, famotidine of 20 to 40 mg decreased both left ventricular end-diastolic and end-systolic lengths (LVDd and LVDs, respectively) and the plasma B-type natriuretic peptide (BNP) levels (182 +/- 21 vs. 259 +/- 25 pg/ml, p < 0.05) with unaltered fractional shortening (FS). In a randomized, open-label study, compared with teprenone, famotidine of 30 mg prospectively decreased both New York Heart Association functional class (p < 0.05) and plasma BNP levels (183 +/- 26 pg/ml vs. 285 +/- 41 pg/ml, p < 0.05); this corresponded to decreasing both LVDd (57 +/- 2 mm vs. 64 +/- 2 mm, p < 0.05) and LVDs (47 +/- 2 mm vs. 55 +/- 2 mm, p < 0.05) with unaltered FS (15 +/- 1% vs. 17 +/- 1%). The frequency of readmission because of worsening of CHF was lower in the famotidine group (4% and 24%, p < 0.05). On the other hand, teprenone had no effects on CHF. Famotidine improved both cardiac symptoms and ventricular remodeling associated with CHF. Histamine H2 receptor blockers may have therapeutic benefits for CHF.

Acute and Chronic Oral Magnesium Supplementation: Effects on Endothelial Function, Exercise Capacity, and Quality of Life in Patients With Symptomatic Heart Failure

Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure. The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure. Twenty-two symptomatic chronic heart failure patients were randomized to receive 800 mg oral magnesium oxide daily or placebo for 3 months. Data collected included large and small arterial elasticity/compliance, hemodynamic parameters, exercise capacity, and quality-of-life score at baseline, 1 week, and 3 months. Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo. This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients.