Ayumi Goda

Usefulness of Peak Exercise Oxygen Consumption and the Heart Failure Survival Score to Predict Survival in Patients >65 Years of Age With Heart Failure

Peak exercise oxygen consumption (Vo(2)) and the Heart Failure (HF) Survival Score (HFSS) were developed in middle-aged patient cohorts referred for heart transplantation with HF. The prognostic value of Vo(2) in patients >65 years has not been well studied. Accordingly, the prognostic value of peak Vo(2) was evaluated in these patients with HF. A retrospective analysis of 396 patients with HF >65 years with cardiopulmonary exercise testing was performed. Peak Vo(2) and components of the HFSS (presence of coronary artery disease, left ventricular ejection fraction, heart rate, mean arterial blood pressure, presence of intraventricular conduction defects, and serum sodium) were collected. Follow-up averaged 1,038 +/- 983 days. Outcome events were defined as death, implantation of a left ventricular assist device, or urgent transplantation. Patients were divided into risk strata for peak Vo(2) and HFSS based on previous cut-off points. Survival curves were derived using Kaplan-Meier analysis and compared using log-rank analysis. Survival differed markedly by Vo(2) stratum (p <0.0001), with significantly better survival rates for the low- (>14 ml/kg/min) versus medium- (10 to 14 ml/kg/min), low- versus high- (<10 ml/kg/min), and medium- versus high-risk strata (all p <0.05). Survival also differed markedly by HFSS stratum (p <0.0001), with significantly better survival rates for the low- (> or =8.10) versus medium- (7.20 to 8.09), low- versus high- (< or =7.19), and medium- versus high-risk strata (all p <0.0001). In conclusion, peak Vo(2) and the HFSS were both excellent parameters to predict survival in patients >65 years with HF.

Heart failure with preserved versus reduced left ventricular systolic function: A prospective cohort of Shinken Database 2004—2005

BACKGROUND Several hospital-based investigations have reported that a high proportion of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF). The purpose of this study was to determine the prevalence, prognosis, and predictors for mortality of Japanese HF patients with preserved versus reduced LVEF in a prospective cohort fashion. METHODS AND RESULTS Our hospital-based database including inpatients and also outpatients was used for analysis. Out of 4255 new patients, 597 patients (male/female 414/183, age 65.1+/-12.9 years) were diagnosed as having symptomatic HF at the initial visit. Among 589 HF patients undergoing echocardiography, 398 (67.6%) showed a preserved LVEF (>50%) and 191 (32.4%) had a reduced LVEF (< or =50%). Patients with preserved LVEF were older (p=0.004) and more likely to be female (p=0.002). During follow-up of an average 539 days, 34 cardiovascular deaths occurred, and patients with preserved LVEF showed a better prognosis than those with reduced LVEF (3.2% vs. 7.4% per year, p=0.0097). Multivariate Cox hazards analysis identified LVEF as an independent predictor in all HF patients. Also, separated group analysis showed that presence of chronic kidney disease was independently associated with poor prognosis irrespective of HF types. CONCLUSIONS This prospective cohort study identified prevalence and prognosis of HF in Japanese in- and outpatients, where patients with preserved LVEF showed a better prognosis than those with reduced LVEF.

Effect of Estimated Plasma Volume Reduction on Renal Function for Acute Heart Failure Differs Between Patients With Preserved and Reduced Ejection Fraction

Background—The prognostic relevance of plasma volume reduction (PVR) in acute heart failure patients remains unclear because of the confounding hemodynamic effect of left ventricular ejection fraction impairment on kidney function. Methods and Results—Subjects enrolled in the West Tokyo Heart Failure Registry were examined. The PV at admission and discharge was estimated from the subjects’ body weight and its deviation from the ideal body weight. Patients in the top tertile of estimated PVR were classified as PVR+. Of the 381 patients with acute heart failure, 181 (47.5%) had heart failure with preserved ejection fraction (HFpEF). Estimated PVR was associated with worsening renal function in the HFpEF (odds ratio, 3.28; 95% confidence interval, 1.55–6.96; P=0.002) but not in the heart failure with reduced ejection fraction cohort (odds ratio, 1.22; 95% confidence interval, 0.61–2.42; P=0.57). This association in the HFpEF cohort remained significant after adjusting for a history of hypertension and diabetes mellitus and the estimated glomerular filtration rate (odds ratio, 3.34; 95% confidence interval, 1.52–7.33; P=0.003). The use of intravenous diuretics was a significant predictor of PVR in the HFpEF and heart failure with reduced ejection fraction groups. Conclusions—The effect of estimated PVR differs by HF type, and the estimated PVR during hospitalization is a predictor of worsening renal function in patients with HFpEF but not in heart failure with reduced ejection fraction. Clinical Trial Registration—URL: http://www.umin.ac.jp/ctr/index-j.html. Unique identifier: UMIN000001549.

Utility of the Seattle Heart Failure Model in patients with cardiac resynchronization therapy and implantable cardioverter defibrillator referred for heart transplantation

BACKGROUND The Seattle Heart Failure Model (SHFM) predicts survival in heart failure but may underestimate risk in severe heart failure, and the performance has not been evaluated explicitly in patients with cardiac resynchronization therapy (CRT) and/or implantable cardioverter defibrillator (ICD) referred for heart transplantation. We aimed to assess the utility of the SHFM by validation in patients with CRT and/or ICD referred for heart transplantation. METHODS We assessed the SHFM performance in 382 patients with CRT and/or ICD referred for heart transplantation. Outcome was survival free from urgent transplantation or left ventricular assist device. Model discrimination and calibration were assessed graphically and by formal tests. RESULTS During a mean follow-up of 2.3 years, 195 events occurred. One-, 2-, and 3-year observed event-free survival was 77%, 62%, and 52%, and the observed to predicted event-free survival ratio was 0.89, 0.80, and 0.76. Calibration plots demonstrated results deviating from the ideal calibration line at 1, 2, and 3 years. The SHFM score adequately assigned patients in discrete risk strata, according to Kaplan-Meier estimated survival. Time-dependent receiver operating characteristic curve analyses demonstrated good discrimination overall, which was slightly better for 1-year (area under the curve [AUC] 0.774) compared with 2-year (AUC 0.742) and 3-year (AUC 0.728) event-free survival. CONCLUSIONS The SHFM has good discrimination but underestimates risk of adverse outcomes in patients with CRT and/or ICD referred for heart transplantation. The SHFM may be used to assess relative risk and changes over time, but when assessing absolute percentage of event-free survival, the overestimation of event-free survival should be accounted for.

Assessment of a University of California, Los Angeles 4‐Variable Risk Score for Advanced Heart Failure

Background The 4‐variable risk score from University of California, Los Angeles (UCLA) demonstrated superior discrimination in advanced heart failure, compared to established risk scores. However, the model has not been externally validated, and its suitability as a selection tool for heart transplantation (HT) and left ventricular assist device (LVAD) is unknown. Methods and Results We calculated the UCLA risk score (based on B‐type natriuretic peptide, peak VO2, New York Heart Association class, and use of angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker) in 180 patients referred for HT. The outcome was survival free from urgent transplantation or LVAD. The model‐predicted survival was compared to Kaplan‐Meiers estimated survival at 1, 2, and 3 years. Model discrimination and calibration were assessed. During a mean follow‐up of 2.1 years, 37 (21%) events occurred. One‐, 2‐ and 3‐year observed event‐free survival was 88%, 81%, and 75%, and the observed/predicted ratio was 0.97, 0.96, and 0.97, respectively. Time‐dependent receiver operating characteristic curve analyses demonstrated good discrimination overall (1‐year area under curve, 0.801; 2‐year, 0.774; 3‐year, 0.837), but discrimination between the 2 highest risk groups was poor. The difference between observed and predicted survival ranged from −14 to +17 percentage points, suggesting poor model calibration. Fairly similar results were found when the analyses were repeated in 715 patients after multivariate imputation of missing data. Conclusions The UCLA 4‐variable risk model calibration was inconsistent and high‐risk discrimination was poor in an external validation cohort. Further model assessment is warranted before widespread use.

Validation of the Get With The Guideline–Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level

BACKGROUND Detailed characteristics of patients with acute heart failure (AHF) in Japan have not been elucidated. Furthermore, international application of risk models obtained in the United States has not been validated. METHODS We evaluated the Get With The Guidelines-Heart Failure (GWTG-HF) risk score performance in AHF patients enrolled in the West Tokyo Heart Failure registry, a large, ongoing, prospective, multicenter cohort registry. Variables required for the GWTG-HF risk score were race, age, systolic blood pressure, heart rate, blood urea nitrogen level, sodium concentration, and presence of chronic obstructive pulmonary disease. Score discrimination and calibration were evaluated by the c statistic, Hosmer-Lemeshow statistic, and visual plotting. We conducted additional analyses to determine whether other variables improved the performance of the score. The primary outcome was in-hospital mortality. RESULTS In total, 1,876 patients were admitted for AHF between April 2006 and August 2014. The patients were predominantly men (60.6%), with a mean age of 73.3 ± 13.6 years. Sixty-eight (3.6%) patients died during hospitalization. The GWTG-HF risk score showed acceptable discrimination; the c statistic for in-hospital mortality in this cohort was 0.763 (95% CI, 0.700-0.826). The calibration plot showed good conformance between the predicted and observed in-hospital mortality. Notably, addition of B-type natriuretic peptide level to the conventional GWTG-HF score significantly improved the discrimination (c statistic, 0.818; 95% CI, 0.771-0.865). CONCLUSIONS The GWTG-HF risk score can be applied in Japanese AHF patients with good discrimination and calibration. Furthermore, addition of B-type natriuretic peptide level improves discrimination and could be considered in future risk models.

Current use of guideline-based medical therapy in elderly patients admitted with acute heart failure with reduced ejection fraction and its impact on event-free survival

BACKGROUND Acute heart failure (HF) is a frequently encountered cardiac condition. Its prevalence increases exponentially with age. In spite of this, elderly patients are underrepresented in clinical trials and the implementation of guideline-based medical therapy (GBMT) in them is not well established. We investigated the current use of GBMT and its effects on mortality and HF rehospitalization among elderly patients with acute HF with reduced ejection fraction (HFrEF) using data obtained from a contemporary multi-center registry. METHODS AND RESULTS We analyzed data from 1,441 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry (mean age 73.2 ± 13.6 years). Reduced ejection fraction (<45%) was noted in 803 patients (55.7%), of which 237 were aged ≥80 years (elderly group). The prescription rate of GBMT (use of renin-angiotensin system inhibitors and β-blockers at discharge) was significantly lower in the elderly than in the younger (aged < 80 years) group (46.8% vs. 66.9%, p<0.001). Although GBMT at discharge was associated with reductions in HF readmission or the composite endpoint of cardiac death and HF readmission (HR 0.49, 95% CI 0.30-0.80; and HR 0.53, 95% CI 0.32-0.89, respectively) in the younger group, this association was not observed in the elderly group (HR 1.41, 95% CI 0.68-2.92; and HR 1.54, 95% CI 0.76-3.13, respectively) CONCLUSIONS: GBMT implementation in elderly patients with HFrEF was found to be suboptimal. However, the underuse of GBMT did not appear to be responsible for poorer outcomes in elderly HFrEF patients. Further research is required to establish an ideal therapeutic approach for this population. CLINICAL TRIAL REGISTRATION URL: http://www.umin.ac.jp/icdr/index-j.html. Unique identifier: UMIN000001171.

Erythropoietin Treatment Improves Peak VO 2 and Oxygen Uptake Efficiency Slope without Changing VE vs. VCO 2 Slope in Anemic Patients

Background: While the improvement of anemia with erythropoietin (EPO) treatment increases peak VO 2 in anemic patients, the effects of EPO on minute ventilation (VE), VO 2 , and VCO 2 kinetics are not well described. Objectives: The aim of this study was to evaluate the improvement in hemodynamic, metabolic, and ventilatory response during exercise along with the improvement of anemia with EPO treatment in anemic hemodialysis patients. Methods: Thirty-seven hemodialysis patients with anemia (48.8 ± 13.6 years) received EPO (1500 or 3000 unit, 3 times a week). Parameters measured prospectively before and after EPO treatment included hemoglobin, cardiac output by dye dilution method, echocardiography, and cardiopulmonary exercise parameters. Results: With EPO treatment, hemoglobin increased from 6.4 ± 0.9 to 10.3 ± 0.9g/dl (p<0.001), with concomitant improvements of O 2 delivery at rest (from 663.8 ± 161.1 to 793.4 ± 188.5ml/min, p=0.004) and high output state (from 8.0 ± 1.6 to 5.6 ± 1.2l/min, p<0.001). Peak heart rate, peak systolic blood pressure, and peak VE did not change. Peak VO2 increased from 15.7 ± 5.3 to 18.8 ± 5.3ml/min/kg (p=0.017), and oxygen uptake efficiency slope (OUES) improved from 1,255 ± 375 to 1,517 ± 357 (p<0.001). However, VE vs. VCO 2 slope (from 34.3 ± 7.3 to 31.8 ± 7.2, p=0.86) and VE-VCO 2 curve did not change. Conclusion: The treatment of anemia improved peak VO 2 and OUES without affecting VE vs. VCO 2 slope significantly. In evaluating the efficacy of treatment for patients with renal failure and anemia, the VE vs. VO 2 relation rather than the VE vs. VCO 2 should be used.

Long-Term Prognostic Significance of Plasma B-Type Natriuretic Peptide Level in Patients With Acute Heart Failure With Reduced, Mid-Range, and Preserved Ejection Fractions

Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p <0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

Successful Treatment of Severe Right-Sided Heart Failure Due to Postoperative Constrictive Pericarditis With Tolvaptan.

The prognosis of inoperative constrictive pericarditis is poor due to subsequent severe right-sided heart failure that is refractory to conventional medical treatment. This case report describes the long-term treatment with tolvaptan, a new selective vasopression V2-receptor antagonist, was remarkably effective for inoperative constrictive pericarditis. Despite that tolvaptan was approved for the treatment of hyponatremia in Europe and the United States, the indications and treatment duration of it are not yet well established clinically. We propose that tolvaptan could offer an alternative option for the treatment of medically refractory severe right-sided heart failure such as constrictive pericarditis.