Erythropoietin response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure

AimWe aim to investigate erythropoietin (EPO) response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure.MethodsA cross-sectional study was conducted on 211 type 2 diabetes mellitus patients without advanced renal failure [estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m²]. The response of EPO to anemia of type 2 diabetic patients without advanced renal failure was compared with those of nondiabetic control subjects. Autonomic nerve function was assessed using three cardiovascular tests (deep breathing, the Valsalva maneuver, and lying-to-standing). The results of each test were scored as 0 if normal, 1 if borderline, and 2 if abnormal. Autonomic neuropathy was diagnosed when a total score of the tests was 2 or more.ResultsFifty-eight patients were anemic; compared with nonanemic patients, they had a longer duration of diabetes (16.69±10.11 vs. 10.67±8.41 years, P<.001), lower eGFR (66.43±16.30 vs. 81.74±19.49 ml/min/1.73 m², P<.001), and higher cardiovascular autonomic neuropathy score (3.17±1.95 vs. 1.79±1.72, P<.001). Serum EPO level was weakly correlated with hemoglobin (Hb) level (r=?.085, P<.001). However, the slopes of regression lines between EPO and Hb levels differed significantly between type 2 diabetic patients and nondiabetic control subjects (?0.0085 vs. ?0.255, P=.008). Multiple linear regression analysis revealed that cardiovascular autonomic neuropathy score was independently related to Hb (P<.001) or EPO level (P=.052).ConclusionsAutonomic neuropathy is associated with a blunted EPO response to anemia in type 2 diabetic patients without advanced renal failure.     

Predictive value of serum myostatin for the severity and clinical outcome of heart failure

BackgroundThe exact relationship between serum myostatin and the severity and prognosis of chronic heart failure (CHF) is unclear. In this study, we investigated the association between serum myostatin and the severity and prognosis in patients with CHF.MethodsTwo hundred and eighty-eight CHF patients and 62 healthy controls were studied. Cardiac ultrasound and serum myostatin, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were detected. CHF patients were divided into 3 groups according to tertiles of NT-proBNP or myostatin levels respectively.ResultsSerum myostatin levels were higher in CHF patients than in controls. New York Heart Association (NYHA) class IV patients had the highest levels of serum myostatin among the four NYHA classes. Compared with the low tertile NT-proBNP group, serum myostatin levels were significantly higher in the moderate and high tertile groups (15.47 ± 4.25 vs. 14.18 ± 3.69 ng/mL, p = .026; 16.28 ± 5.34 vs. 14.18 ± 3.69 ng/mL, p = .002). During 51-months follow-up, of 173 patients there were 36 deaths. Compared to survivors, nonsurvivors had significantly higher serum myostatin (18.11 ± 4.52 vs. 14.85 ± 5.11 ng/mL, p < .01). Patients in the high tertile myostatin group had lower survival rate (73.95% vs. 93.75%; p < .05) and larger number of CHF rehospitalization than those in the low tertile group. Cox regression analysis showed that serum myostatin was an independent predictor of mortality.ConclusionsSerum myostatin levels can reflect the severity of CHF and be a predictor of adverse prognosis in CHF patients.     

Clinical Outcomes of Erythropoietin Use in Heart Failure Patients With Anemia of Chronic Kidney Disease

BackgroundAnemia and chronic kidney disease are common disorders in heart failure (HF) patients and are associated with increased morbidity and mortality. This study assessed clinical outcomes associated with erythropoietin (EPO) treatment in this cardiorenal anemia syndrome (CRAS) population.Methods and ResultsThis was a retrospective cohort study of Veterans Affairs patients with CRAS from January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndrome (ACS), HF, and stroke. Multiple Cox regression modeling was used to evaluate the outcome in patients prescribed (n = 213) and not prescribed EPO (n = 1845). Adjusted incidence of mortality was statistically significantly higher in EPO than in non-EPO users (33.8% vs 19.7%; hazard ratio 1.40, 95% confidence interval 1.06–1.85; P = .02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (P = .12). Crude ACS events were documented in 18.8% and 10.8% patients (P = .001), and stroke events occurred in 22.5% and 18.3% patients (P = .14) in EPO and non-EPO groups, respectively.ConclusionsWe found that in CRAS patients, EPO use was associated with increased risk of mortality and a trend toward increased cardiovascular events. Therefore, clinicians considering EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of use.     

Effect of early correction of anemia with erythropoietin on left ventricular mass in predialysis patients: a multi-center trial

Objective To assess the effects of early correction of anemia with recombinant human erythropoietin (rHuEPO) on the development and progression of left ventricular hypertrophy (LVH) in patients with mild-to-moderate chronic renal insufficiency (CRI) who are not on hemodialysis. Methods A total of 158 patients with serum creatinine from 147μmol/L to 400μmol/L were enrolled in this prospective, multicenter study. Eighty-six patients with hemoglobin (Hb)<110g/L received rHuEPO treatment with a target Hb of > 110g/L (Group A). Forty patients with comparable Hb concentration ( <110g/L) but did not receive rHuEPO (Group B) and 32 patients with Hb≥110g/L and without rHuEPO treatment (Group C) were served as controls. Left ventricular mass index (LVMI) was evaluated by echocardiography at baseline and every 3 months for 2 years. Results There was no difference in age, gender, etiology of renal failure, blood pressure and cardiovascular risk factors among the 3 groups. At baseline, the prevalence of LVH was 72.1 % in group A, 72.5% in group B and 59.4% in group C. LVMI was inversely correlated with Hb levels (r=0.70, P<0.01). During the 2-year period, the mean LVMI decreased from 142.6±25.7g/m2 to 132.4±18.5 g/m2 in group A, while increased significantly in both group B and group C. The mean Hb concentration increased from 93.8±14.6g/L to 111.2±10.3g/L(P<0.05) in group A, but tended to decrease in group B and group C. There was no significant change of the mean blood pressure, number of anti-hypertensive drugs and serum creatinine concentrations in all 3 groups. However, patients' serum creatinine doubled more often in group B and group C than in group A. Conclusions LVH was common in predialysis CRI patients and was associated with the severity of anemia. Early intervention with rHuEPO may reverse LVH in these patients.     

Surgical ablation of atrial fibrillation in patients with congestive heart failure

BackgroundCongestive heart failure (CHF) and atrial fibrillation (AF), both of which cause morbidity and mortality, are mutually promoting diseases. We aimed to evaluate surgical AF ablation in CHF.Methods and ResultsAmong 212 patients (age 69 ± 8.8 years, 87% with persistent AF) undergoing concomitant left atrial (LA) ablation, 79 (37.3%) presented CHF (n = 62 with a left ventricular ejection fraction [LVEF] 0.31–0.45, n = 17 with an LVEF ≤ 0.30). Patients with CHF were similar to controls regarding AF duration (61 ± 65.1 months vs. 54 ± 67.2 months, not significant [NS]), LA diameter (49 ± 7.5 mm vs. 50 ± 9.2 mm, NS), and heart rate (78 ± 18.4 min⁻¹ vs. 81 ± 21.3 min⁻¹, NS), but they required more circulatory support (17.7% vs. 1.5%, P < .001) and a longer intensive care unit stay (6 ± 9.5 days vs. 4 ± 10.5 days, P = .032). At follow-up after 13 ± 7.3 months, 42 patients (66%) with CHF and 81 controls (74%, NS) were in sinus rhythm (SR) (55% and 64% without antiarrhythmic drugs, respectively, NS). Univariate and logistic regression analysis revealed that AF duration and LA diameter predicted rhythm outcome but not CHF. In patients with an LVEF of 0.30 or less, SR conversion significantly improved LVEF, New York Heart Association class, and Minnesota Living with Heart Failure score. Kaplan-Meier estimates suggested superior survival of patients with stable SR (100% vs. 73%, log-rank P < .05).ConclusionsIf patients presenting with CHF and AF require cardiac surgery, concomitant AF ablation should be considered, especially if left ventricular function is severely impaired.     

Decreased albumin is associated with elevated N-terminal pro-brain natriuretic peptide and poor long-term prognosis in patients with chronic heart failure

At present, the association between albumin, N-terminal pro-brain natriuretic peptide (NT-proBNP) and long-term prognosis in patients with chronic heart failure (CHF) is unclear. Therefore, the purpose of this study is to explore the relationship between albumin, NT-proBNP and all-cause mortality in CHF patients.Three hundred fifty two CHF patients were recruited in our study, and patients were divided into 2 groups according to the mean (37.16 g/L) of albumin concentration [low group (albumin < 37.16 g/L) and high group (albumin≥37.16 g/L)]. Differences between groups was compared by odds ratio (OR) and 95% confidence interval (CI).NT-proBNP in the high group was significantly lower than that in the low group at baseline [1811.50 (698.75–4037.00) vs 3479.50 (1538.50–7824.25), P < .001]. Spearman correlation analysis showed that there was a negative correlation between albumin and NT-pro BNP log10 transform (ρ= −0.217, P < .001). Furthermore, curve fitting further confirmed that albumin was negatively correlated with NT-proBNP. After a median follow-up of 1726 days, 90 patients in the high group occur all-cause mortality, and 98 patients in the low group occur all-cause mortality (46.88% vs 61.25%, OR = 0.29, 95% CI: 0.08–0.50). After adjusting for the selected confounding covariates by multivariate regression analysis, decreased albumin was still associated with increased all-cause mortality (high group vs low group: OR = 0.62, 95% CI: 0.39–0.97).Decreased albumin is associated with elevated NT-ProBNP and poor long-term prognosis in CHF patients. Clinicians need to pay enough attention to the nutritional status of CHF patients.     

Upregulation of Monocyte Proinflammatory Cytokine Production by C-Reactive Protein is Significantly Related to Ongoing Myocardial Damage and Future Cardiac Events in Patients With Chronic Heart Failure

BackgroundAn elevation of the cardiac troponin T (TnT) level identifies patients with ongoing myocardial damage (OMD) and at increased risk for future cardiac events in chronic heart failure (CHF). C-reactive protein (CRP) upregulates monocyte proinflammatory cytokine production and this upregulation appears to play an important role on OMD.Methods and ResultsPeripheral blood mononuclear cells (PBMCs) were stimulated by 25 μg/mL CRP in 72 patients with CHF. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 production by monocytes was measured by a specific enzyme-linked immunosorbent assay and expressed as the mean ± SD (pg·mL·10⁶ PBMCs). The patients were divided into 2 groups according to the TnT levels: 27 patients with OMD (TnT ≥0.01 ng/mL) and 45 patients without OMD. CRP-induced cytokine production was upregulated significantly more in patients with OMD than in those without OMD (TNF-α: 200.6 ± 100.4 vs. 102.1 ± 73.6 pg/mL, P < .001, IL-6: 4611.7 ± 2600.0 vs. 1451.6 ± 1193.5 pg/mL, P < .001). Multivariate Cox regression analyses revealed that CRP-stimulated monocyte production of TNF-α ≥120 pg/mL and TnT ≥0.03 ng/mL were independent predictors of cardiac events.ConclusionsThe upregulation of monocyte proinflammatory cytokine production by CRP could be significantly related to OMD and future cardiac events in CHF.     

Soluble Angiotensin-Converting Enzyme 2 in Human Heart Failure: Relation With Myocardial Function and Clinical Outcomes

BackgroundAngiotensin-converting enzyme 2 (ACE2) is an endogenous counterregulator of the renin-angiotensin system. The relationship between soluble ACE2 (sACE2), myocardial function, and clinical outcomes in patients with chronic systolic heart failure is not well established.Methods and ResultsWe measured sACE2 activity in 113 patients with chronic systolic heart failure (left ventricular ejection fraction [LVEF] ≤35%, New York Heart Association Class II-IV). Comprehensive echocardiography was performed at the time of blood sampling. We prospectively examined adverse clinical events (death, cardiac transplant, and heart failure hospitalizations) over 34 ± 17 months. Patients who had higher sACE2 plasma activity were more likely to have a lower LVEF (Spearman's r = –0.36, P < .001), greater right ventricular systolic dysfunction (r = 0.33, P < .001), higher estimated pulmonary artery systolic pressure (r = 0.35, P = .002), larger left ventricular end-diastolic diameter (r = 0.23, P = .02), and higher plasma NT-proBNP levels (r = 0.35, P < .001). sACE2 was less associated with diastolic dysfunction (r = 0.19, P = .05), and was similar between patients with ischemic and nonischemic cardiomyopathies. There was no relationship between sACE2 activity and markers of systemic inflammation. After adjusting for NT-proBNP and LVEF, sACE2 activity remained an independent predictor of adverse clinical events (HR = 1.7 [95% CI: 1.1–2.6], P = .018).ConclusionsElevated plasma sACE2 activity was associated with greater severity of myocardial dysfunction and was an independent predictor of adverse clinical events.     

Baseline Plasma NT-proBNP and Clinical Characteristics: Results From the Irbesartan in Heart Failure With Preserved Ejection Fraction Trial

BackgroundN-terminal B type natriuretic peptide (NT-proBNP) is usually elevated in heart failure (HF) patients with reduced ejection fraction (EF). Less is known about NT-proBNP in HF with preserved EF (HF-PEF). We measured baseline NT-proBNP in 3562 HF-PEF enrolled patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial.Methods and ResultsPatients with EF ≥45%, age ≥60 years, and either New York Heart Association (NYHA) II-IV symptoms with HF hospitalization (HFH) within 6 months or NYHA III-IV symptoms with corroborative evidence of HF or structural changes associated with HF-PEF. NT-proBNP (pg/mL) measured centrally using the Elecsys proBNP assay (Roche). Mean age 72 ± 7 years, 60% were women, the investigator indicated HF etiology was hypertension in 64%; the majority were in NYHA III. Medications included diuretics in 82%, angiotensin-converting enzyme inhibitor in 26%, β-blocker in 59%, and spironolactone in 15%. Median NT-proBNP was 341 pg/mL (interquartile range 135 to 974 pg/mL) and geometric mean was 354 pg/mL. In multivariate analysis, the baseline characteristics most strongly associated with higher NT-proBNP levels were atrial fibrillation (ratio of geometric mean 2.59, P < .001), NYHA IV symptoms (1.52, P < .001), lower estimated glomerular filtration rate (1.44, P < .001), and HFH hospitalization within 6 months (1.37, P < .001).ConclusionsMost HF-PEF patients have elevated NT-proBNP levels. The NT-proBNP concentrations were related to baseline characteristics generally associated with worse outcomes for HF patients.     

Soluble ST2 as a Biomarker for Detecting Stable Heart Failure With a Normal Ejection Fraction in Hypertensive Patients

BackgroundWe investigated the measurement of soluble ST2 (sST2) in stable heart failure (HF) with a normal ejection fraction (HFNEF) in hypertensive patients.Methods and ResultsEchocardiography and serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) and sST2 concentrations were evaluated in 107 hypertensive patients (65 ± 12 years, 57 male) with ejection fraction (EF) >50%. Among them, 68 patients with stable HF in functional class II and III were the HFNEF group. We found that the area under the receiver operating characteristic curve (AUC) for sST2 was 0.80 (95% CI 0.70–0.89; P < .001), relatively better than that for NT-proBNP (AUC 0.70, 95% CI 0.58–0.79; P = .003) to detect HFNEF. However, the NT-proBNP concentration, rather than sST2, was higher in HFNEF patients with functional class III (562 ± 891 vs 185 ± 242 pg/mL in functional class II; P = .009), and correlated better with mitral E/e′ (annular early diastolic velocity) (r = 0.327; P = .008) than sST2 concentrations in HFNEF patients. Multivariate analysis showed that sST2 >13.5 ng/mL was independently associated with HFNEF in hypertensive patients (odds ratio 11.7, 95% CI = 2.9–47.4; P = .001).ConclusionssST2 measurement provides diagnostic aid of stable HFNEF for hypertensive patients. Addition of NT-proBNP to sST2 could give further information regarding HF functional class and diastolic abnormality.     

Ultrafiltration is Associated With Fewer Rehospitalizations than Continuous Diuretic Infusion in Patients With Decompensated Heart Failure: Results From UNLOAD

BackgroundCompare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics.Methods and ResultsOutcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics (P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics (P < .001 UF versus bolus diuretic; P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days.ConclusionsDespite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.     

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity

Background

We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes.

Methods and results

We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15 min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1 ± 4.6 versus 64.9 ± 2.9 bursts/100 heart beats; P < 0.05) and sympathetic baroreflex impaired (2.69 ± 0.44 vs 5.25 ± 0.60% bursts/mm Hg; P < 0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8 ± 4.7 versus 82.1 ± 4.9 bursts/100 heart beats; P < 0.01) and to an increase in sympathetic baroreflex function (2.77 ± 0.45 vs 5.63 ± 0.73% bursts/mm Hg; P < 0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients.

Conclusions

CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment.     

Exercise-induced increases in oxidized low-density lipoprotein are associated with adverse outcomes in chronic heart failure

BackgroundOxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF.Methods and ResultsPlasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 ± 3.2 U/L vs 57.9 ± 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 ± 0.04 vs 0.49 ± 0.04, P ≤ .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 ± 3.2 U/L to 85.3 ± 3.0 U/L, P ≤ .001) but not in controls (57.9 ± 5.0 to 61.4 ± 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0–73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5–1438.1, P = .02).ConclusionPlasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated.     

Differences in Clinical Profile of African-American Women With Peripartum Cardiomyopathy in the United States

BackgroundPeripartum cardiomyopathy (PPCM) is a rare and heterogeneous disease with a higher prevalence in African Americans (AAs) in the USA. The clinical features and prognosis of PPCM in AAs have not been sufficiently characterized.MethodsWe studied 52 AA patients with PPCM and compared clinical characteristics and outcome with those of 104 white patients.ResultsAA patients were significantly younger (26 ± 7 vs 30 ± 6 years; P < .001), had a higher prevalence of gestational hypertension (61% vs 41%; P = .03), and were diagnosed more commonly postpartum rather then antepartum (83% vs 64%; P = .03). The rate of left ventricular (LV) recovery (LV ejection fraction [LVEF] ≥50%) was significantly lower in AAs (40% vs 61%; P = .02). AA women also had a larger LV end-diastolic diameter (57 ± 10 vs 51 ± 6 mm; P = .004) as well as lower LVEF (40% ± 16.7% vs 46% ± 14%; P = .002) at the last follow-up. Moreover, AA patients had a significantly higher incidence of the combined end points of mortality and cardiac transplantation (P = .03) and showed a strong trend (P = .09) for increased mortality.ConclusionsAA patients with PPCM in the USA have a different clinical profile and worse prognosis compared with white patients. Further research to evaluate potentially correctable causes for these differences is warranted.     

Clinical Characteristics and Outcomes of Patients With Heart Failure and Methamphetamine Abuse

BackgroundDespite a global epidemic of methamphetamine abuse, methamphetamine-associated heart failure (MethHF) remains poorly understood. We sought to evaluate characteristics and outcomes for patients with MethHF.MethodsWe reviewed the electronic health records of the University of California, San Diego, from 2005 to 2016. We compared characteristics and outcomes between 896 patients with MethHF and 20,576 patients with heart failure (HF) identified using diagnosis codes, urine toxicology, and natriuretic peptides.ResultsCompared with HF, patients with MethHF were younger (50±10 vs 67±16 years), predominantly male (72% vs 54%), and had more psychiatric and substance use comorbidities, including mood/anxiety disorders (29% vs 16%) and opioid use (44% vs 7%). MethHF had a higher 5-year HF readmission rate (64±4% vs 45±1%; hazard ratio [HR] 1.53, P < .001) and a lower 10-year total mortality rate (25±3% vs 28±1%; HR 0.85, P = .09). Predictors of poor outcomes included mood/anxiety disorders (HF readmission HR 1.41, P = .04) and opioid abuse (mortality HR 1.52, P = .04).ConclusionsPatients with MethHF are frequently encumbered by psychiatric and substance abuse comorbidities, and carry a substantial risk of HF readmission and mortality. Comprehensive efforts are needed to stem this emerging epidemic.     

Renal and Hormonal Effects of Systemic Nitric Oxide Inhibition in Patients With Congestive Heart Failure and in Healthy Control Subjects

BackgroundThe significance of basal renal nitric oxide (NO) availability in the regulation of renal perfusion and sodium excretion in human congestive heart failure (CHF) has not been described previously.Methods and ResultsWe studied the effects of acute systemic NO synthesis inhibition with N^G-monomethyl-L-arginine (L-NMMA) in 12 patients with CHF and 10 healthy control subjects (CON) in a randomized placebo-controlled study. Effect parameters were renal plasma flow (RPF), renal vascular resistance (RVR), glomerular filtration rate (GFR), urine sodium excretion and plasma levels of vasoactive hormones. L-NMMA was associated with a significant decrease in RPF (CON-LNMMA: ?13 ± 3% [P = .014]; CHF-LNMMA: ?17 ± 7% [P = .017]) and a profound increase in RVR in both CHF and CON (CON-LNMMA: +26 ± 6% [P = .009]; CHF-LNMMA: +37 ± 70% [P = .005]). Significant decreases in sodium excretion were found in both CHF-LNMMA and CON-LNMMA. Relative changes from baseline were not statistically different between CHF-LNMMA and CON-LNMMA. After L-NMMA, RPF values correlated inversely with plasma aldosterone in CHF-LNMMA (P = .01). L-NMMA induced an increase in A-type natriuretic peptide (ANP) only in CHF-LNMMA (+18 ± 8%; P = .035), which correlated significantly with basal ANP levels (P = .034).ConclusionsThere was no difference in the renal response to L-NMMA in CHF vs CON, suggesting that the impact of NO on renal perfusion and sodium excretion is maintained in stable CHF. We suggest that NO influences the release of ANP during high levels of atrial stretch in CHF.     

HE4 Serum Levels Are Associated with Heart Failure Severity in Patients With Chronic Heart Failure

Background

The novel biomarker human epididymis protein 4 (HE4) shows prognostic value in acute heart failure (HF) patients. We measured HE4 levels in patients with chronic heart failure (CHF) and correlated them to HF severity, kidney function, and HF biomarkers, and determined its predictive value.

Worsening Renal Function in Patients With Acute Decompensated Heart Failure Treated With Ultrafiltration: Predictors and Outcomes

BackgroundUltrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF.Methods and ResultsBased on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17–13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48–48.42; P = .03), and E/E′ ≥15 (OR 3.78, 95% CI 1.26–17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate.ConclusionsWRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.     

Accelerometer-Based Quantification of 6-Minute Walk Test Performance in Patients With Chronic Heart Failure: Applicability in Telemedicine

BackgroundDistance walked in the 6-minute walk test (6MWT) is an important prognostic parameter used clinically to assess functional status in patients with chronic heart failure (CHF). In this study, we investigated if alternative performance parameters with similar prognostic value can be gained from accelerometers.Methods and ResultsFifty CHF patients (age, 60.9 ± 14.0 years) were asked to perform a 6MWT while wearing 2 accelerometers and 1 pedometer. Total 6MWT step frequency (SF) and activity counts (VMU) were correlated to 6MWT distance. The accelerometer was highly accurate at quantifying SF (detected vs. observed: r = 0.99; P < .001), whereas the pedometer was unreliable below 50 m/min. VMU increased linearly with walking speed (r = 0.99), and both SF and VMU correlated strongly with 6MWT distance (VMU: r = 0.91; SF: r = 0.87, respectively; P < .001) and each other (r = 0.80, P < .001).ConclusionsAccelerometers are reliable in measuring physical performance during the 6MWT in CHF patients. Besides the simple acquisition of 6MWT distance currently used for patient assessment, accelerometers provide new data that might be useful to evaluate exercise performance during the 6MWT. This allows for routine assessment of exercise capacity in a home-based setting in the context of telemedicine.     

Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older,Obese Patients With Heart Failure With Preserved Ejection Fraction

BackgroundHeart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO₂), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire).Methods and ResultsWe compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO₂, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO₂ (β = 9.0 ± 1.6, P < .001), 6MWD (β = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (β = –23 ± 5, P = .001), even after adjusting for clinical covariates.Conclusions: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF.RegistrationNCT00959660