Inverse relationship of subjective daytime sleepiness to mortality in heart failure patients with sleep apnoea.

AIMS: Patients with sleep apnoea (SA) and heart failure (HF) are less sleepy than SA patients without HF. HF and SA both increase sympathetic nervous system activity (SNA). SNA can augment alertness. We previously showed that in HF patients, the degree of daytime sleepiness was not related to the severity of SA but was inversely related to SNA. Elevated SNA is associated with increased mortality in HF. Therefore, we hypothesized that in HF patients with SA, the degree of daytime sleepiness will be inversely related to mortality. METHODS AND RESULTS: In a prospective cohort study, 218 consecutive patients with systolic HF had overnight polysomnography. Among them, 80 subjects with SA (apnoea-hypopnoea index ≥15) were followed for a mean of 28 months to determine all-cause mortality rate. Subjective daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). During follow-up, 20 patients died. The 5 year death rate in patients with ESS less than 6 (i.e. less sleepy) was significantly higher than in patients with an ESS at or above the median of 6 (i.e. sleepier) [21.3 deaths/100 patient-years vs. 6.2 deaths/100 patient-years, unadjusted hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.20 to 7.20, P = 0.018]. After adjusting for confounding factors that included sex, history of hypertension, and mean arterial oxyhaemoglobin saturation, compared with the sleepier patients, less sleepy patients had greater risk of mortality (HR 2.56, 95% CI 1.01 to 6.47, P = 0.047). As a continuous variable, ESS scores were inversely related to mortality risk (HR 0.86, 95% CI 0.75 to 0.98, P = 0.022). CONCLUSIONS: In patients with HF and SA, the degree of subjective daytime sleepiness is inversely related to the mortality risk, suggesting that among HF patients with SA, those with the least daytime sleepiness are at greater risk of death. They may therefore have greater potential for mortality benefit from therapy of SA than those with greater daytime sleepiness.

Evaluating the confounding effects of medical therapies on potassium intake assessment in patients with heart failure.

BACKGROUND AND AIMS: Potassium-wasting (loop diuretics [LD]) and potassium-sparing (spironolactone) medications used for heart failure (HF) may alter renal potassium handling and confound the use of twenty-four-hour (24-h) urine collections as a surrogate marker for potassium intake, an effect that has been observed with dietary sodium assessment. The objective was to determine the strength of association between 24-h urine collections and weighed food records in assessing potassium intake in HF patients stratified by LD usage and spironolactone usage. METHODS AND RESULTS: Stable outpatients with HF simultaneously completed two 24-h urine collections and two weighed food records on consecutive days. Analyses compared patients stratified by LD and/or spironolactone use. Pearson's correlation and the Bland-Altman method of agreement assessed the relationship between the techniques. Overall, 109 patients (61 ± 11 yrs, 74% male) were included. The mean difference in dietary potassium estimated between 24-h urine collections and food records was -353 ± 1043 mg (p < 0.01) for all patients, with no differences between measures among subgroups. The association between the two methods was r = 0.551 (95% CI, 0.373 to 0.852, p < 0.001) for LD users; r = 0.287 (95% CI, 0.01 to 0.570, p = 0.050) for LD non-users; r = 0.321 (95% CI, 0.13 to 0.798, p = 0.043) for spironolactone users, and; r = 0.534 (95% CI, 0.331 to 0.747, p < 0.001) for spironolactone non-users. There were no significant mean biases identified as part of the Bland-Altman analysis. CONCLUSION: Among HF patients, potassium-wasting and potassium-sparing medications do not influence the agreement between the two methods in the assessment of potassium intake.

Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system.

BACKGROUND: Reduced potassium excretion caused by angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may increase the risk of hyperkalemia (serum potassium concentration >5 mmol/L) in the setting of increased potassium intake. OBJECTIVE: The purpose of this study was to assess the effect of increasing dietary potassium on serum potassium concentration in hypertensive individuals with normal renal function treated with an ACEi or ARB. We hypothesized that an increase in dietary potassium would not provoke hyperkalemia in this population despite treatment with either an ACEi or ARB. DESIGN: We conducted a controlled, parallel-design clinical trial in 20 hypertensive subjects with normal renal function treated with an ACEi or ARB, with random assignment to a usual diet or a high-potassium diet (HKD). Fruit and vegetable intake was used to increase potassium intake. Serum potassium concentration, 3-d food records, and 24-h urine collections were completed at baseline and 4 wk. RESULTS: In the usual-diet group there were no statistically significant differences for potassium excretion, intake, or serum levels at end of study compared with baseline. The HKD group had significant differences in urinary potassium excretion (83 ± 26 mmol/d at baseline compared with 109 ± 35 mmol/d at 4 wk, P = 0.01) and dietary potassium intake (3775 ± 1189 mg/d at baseline compared with 5212 ± 1295 mg/d at 4 wk, P = 0.02). Despite increased potassium intake in the HKD group, serum potassium concentrations did not significantly increase from baseline at midpoint or end of study (4.1 ± 0.6, 4.3 ± 0.3, and 4.2 ± 0.4 mmol/L, respectively). CONCLUSION: This study demonstrates that an increase in dietary potassium over a 4-wk period is safe in hypertensive subjects who have normal renal function and are receiving ACEi and/or ARB therapy. This trial was registered at www.clinicaltrials.gov as NCT02759367.

Effect of a Sodium-Restricted Diet on Intake of Other Nutrients in Heart Failure: Implications for Research and Clinical Practice.

BACKGROUND: Sodium restriction is the primary dietary therapy for heart failure (HF) patients. Currently, it is unknown if changing diets to reduce dietary sodium in HF causes secondary changes to the intake of other nutrients in this patient population already at nutritional risk. METHODS AND RESULTS: HF patients (n = 16; 52 ± 12 years old; 78% male) followed a sodium-restricted diet for 1 week. Nutritional changes were documented at baseline and after a <2,000 mg/d sodium-restricted diet, as measured by food records before baseline and each day during the study. After a 49% reduction in dietary sodium (3,626 ± 956 to 1,785 ± 696 mg/d), we observed a significant reduction in calorie (2,467 ± 748 to 1,931 ± 388 kcal/d; P < .016), carbohydrate (293 ± 108 to 232 ± 56 g/d; P = .013), calcium (995 ± 496 to 609 ± 208 mg/d; P < .004), thiamine (2.0 ± 0.8 to 1.5 ± 0.8 mg/d; P = .020), and folate (412 ± 192 to 331 ± 172 µg/d; P = .019) intakes. There was a decrease in saturated fat (32 ± 18 to 21 ± 6 g/d; P = .032) and a trend to lower total fat (89 ± 34 to 68 ± 19 g/d; P = .066) and higher potassium (1,262 ± 328 to 1,405 ± 268 mg/1,000 kcal; P = .055) intakes. CONCLUSIONS: We found multiple unintentional nutritional consequences with dietary sodium reduction in HF patients. These findings highlight the need to consider the whole diet when counseling HF patients to lower sodium intake.

Overnight Effects of Obstructive Sleep Apnea and Its Treatment on Stroke Volume in Patients With Heart Failure.

BACKGROUND: We previously showed in heart failure (HF) patients that obstructive respiratory events during sleep and generation of negative intrathoracic pressure during Mueller manoeuvres, mimicking obstructive apneas, acutely reduced stroke volume (SV). We also showed that treating obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) increased left ventricular ejection fraction over a 1-month period. We therefore hypothesized that, in HF patients, those with OSA would have greater overnight declines in SV and cardiac output (CO) than in those without sleep apnea, and that therapy of OSA using CPAP would prevent these declines. METHODS: We examined overnight percent change in SV and CO in 32 HF patients with and 28 without OSA using digital photoplethysmography. Among patients with OSA, we also examined changes in SV and CO during a CPAP titration study. RESULTS: During the baseline polysomnogram SV and CO decreased more overnight in those with OSA than in those without sleep apnea (-12.6 ± 7.7% vs -3.2 ± 6.8%; P < 0.001 and -16.2 ± 9.9% vs -3.7 ± 8.3%; P < 0.001, respectively). Overnight changes in SV and CO correlated inversely with total apnea-hypopnea index (r = -0.551; P < 0.001 and r = -0.522; P < 0.001, respectively). In 21 patients with OSA, CPAP reduced the total apnea-hypopnea index from 37.7 ± 21.4 to 15.0 ± 16.0 (P < 0.001) in association with attenuation of the overnight reduction of SV (from -14.0 ± 7.9% to -3.4 ± 9.8%; P = 0.002) and CO (from -17.2 ± 9.0% to -9.7 ± 10.7%; P = 0.042). CONCLUSIONS: In patients with HF, coexisting OSA causes overnight declines in SV and CO that are prevented through reversal of OSA by CPAP.

Presentation blood glucose and death, hospitalization, and future diabetes risk in patients with acute heart failure syndromes.

PURPOSE: The prognostic implications of blood glucose on a wide range of outcomes including early mortality, hospitalizations, and incident diabetes diagnoses have not been fully elucidated in acute heart failure syndromes (AHFS). METHODS: In a population-based cohort of 16 524 AHFS patients presenting to the emergency department (ED) in Ontario, Canada between 2004 and 2007, we performed a competing risk analysis for 30-day mortality, new diabetes diagnoses, and hospitalization outcomes. Presentation blood glucose concentrations were categorized as follows: 3.9-6.1 [referent], >6.1-7.8, >7.8-9.4, >9.4-11.1, and >11.1 mmol/L. RESULTS: Among AHFS patients without diabetes presenting to the ED (n = 9275), blood glucose >6.1 mmol/L (n = 5252, 56.6%) was associated with increased risks of all-cause death [hazard ratio (HR) range: 1.26 (95% CI 1.05-1.50) to 1.50 (95% CI 1.11-2.02)], and cardiovascular death [HR range: 1.28 (95% CI 1.03-1.59) to 1.64 (95% CI 1.16-2.33)]. Among AHFS patients with diabetes (n = 7249), presenting blood glucose >11.1 mmol/L (n = 2286, 31.5%) was associated with increased risks of all-cause death (HR 1.48, 95% CI 1.10-2.00) and diabetes-related hospitalizations (HR 1.39, 95% CI; 1.20-1.61). Presentation blood glucose >9.4 mmol/L was associated with increased risks of hospitalization for HF or cardiovascular causes [HR range: 1.09 (95% CI 1.02-1.17) to 1.15 (95% CI 1.07-1.24)] in all patients. With higher presentation blood glucose, the risk of incident diabetes diagnosis increased, with adjusted HRs of 1.61 (>6.1-7.8 mmol/L) to 3.61 (>11.1 mmol/L) among those without the condition at baseline (all P < 0.001). CONCLUSIONS: Mildly elevated presentation blood glucose was associated with early death, future diabetes, and hospitalizations for diabetes, HF, and cardiovascular causes among patients with AHFS.

Association of heart rate at hospital discharge with mortality and hospitalizations in patients with heart failure.

BACKGROUND: Heart failure (HF) is associated with a high burden of morbidity and mortality. Hospital discharge is an opportunity for identification of modifiable prognostic factors in the transition to chronic HF. METHODS AND RESULTS: We examined the association of discharge heart rate with 30-day and 1-year mortality and hospitalization outcomes in a cohort of 9097 patients with HF discharged from hospital. Discharge heart rate was categorized into predefined groups: 40 to 60 (n=1333), 61 to 70 (n=2170), 71 to 80 (n=2631), 81 to 90 (n=1700), and >90 bpm (n=1263). There was a significant increase in all-cause 30-day mortality with adjusted odds ratios of 1.59 (95% confidence interval [CI], 1.18-2.14; P=0.003) for discharge heart rates 81 to 90 bpm and 1.56 (95% CI, 1.13-2.16; P=0.007) for heart rates>90 bpm when compared with the reference group (heart rates, 61-70 bpm). Cardiovascular death risk at 30 days was also higher with adjusted odds ratio 1.59 (discharge heart rates, 81-90 bpm; 95% CI, 1.09-2.33; P=0.017) and 1.65 (discharge heart rates, >90 bpm; 95% CI, 1.09-2.48; P=0.017). One-year all-cause mortality (adjusted odds ratio, 1.41; 95% CI, 1.16-1.72; P<0.001) and cardiovascular death (adjusted odds ratio, 1.47; 95% CI, 1.12-1.92; P=0.005) were higher with discharge heart rates>90 bpm when compared with the reference group (heart rates, 40-60 bpm). Readmissions for HF (adjusted hazard ratio, 1.26; 95% CI, 1.04-1.54; P=0.021) and cardiovascular disease (adjusted hazard ratio, 1.29; 95% CI, 1.08-1.54; P=0.004) within 30 days were also higher with discharge heart rates>90 bpm. CONCLUSIONS: Higher discharge heart rates were associated with greater risk of all-cause and cardiovascular mortality≤1-year follow-up and an elevated risk of 30-day readmission for HF and cardiovascular disease.

Differing relationship of nocturnal fluid shifts to sleep apnea in men and women with heart failure.

BACKGROUND: In men with heart failure, nocturnal rostral fluid shift is associated with an overnight increase in the neck circumference (NC) and with severity of obstructive sleep apnea. Because the prevalence of obstructive sleep apnea is lower in women than in men with heart failure, we hypothesized that less fluid would shift into the neck in association with less severe obstructive sleep apnea in women than in men with heart failure. METHODS AND RESULTS: In 35 men and 30 women with heart failure, we assessed overnight changes in NC (ΔNC) and leg fluid volume before and after polysomnography. The severity of obstructive sleep apnea was assessed by the apnea-hypopnea index. Although the changes in leg fluid volume did not differ significantly between men and women (-131 ± 90 versus -180 ± 132 mL, P=0.081), in women, ΔNC was smaller (P<0.001) than in men. Furthermore, although in men, changes in leg fluid volume correlated inversely with ΔNC (r=-0.755, P<0.001) and apnea-hypopnea index (r=-0.765, P<0.001), it did not in women. CONCLUSIONS: Despite no difference in overnight displacement of fluid from the legs compared with in men, in women, less of this fluid reached the neck, and unlike men, there was no relationship between changes in leg fluid volume and either ΔNC or apnea-hypopnea index. These findings suggest a differing relationship between overnight fluid shift from the legs and severity of obstructive sleep apnea in women than in men with heart failure.

Prediction of heart failure mortality in emergent care: a cohort study.

BACKGROUND: Heart failure contributes to millions of emergency department (ED) visits, but hospitalization-versus-discharge decisions are often not accompanied by prognostic risk quantification. OBJECTIVE: To derive and validate a model for acute heart failure mortality applicable in the ED. DESIGN: Clinical data abstraction with development of a broadly applicable multivariate risk index for 7-day death using initial vital signs, clinical and presentation features, and readily available laboratory tests. SETTING: Multicenter study of 86 hospitals in Ontario, Canada. PATIENTS: Population-based random sample of 12 591 patients presenting to the ED from 2004 to 2007. MEASUREMENTS: Death within 7 days of presentation. RESULTS: In the derivation cohort (n = 7433; mean age, 75.4 years [SD, 11.4]; 51.5% men), mortality risk increased with higher triage heart rate (adjusted odds ratio [OR], 1.15 [95% CI, 1.03 to 1.30] per 10 beats/min) and creatinine concentration (OR, 1.35 [CI, 1.14 to 1.60] per 1 mg/dL [88.4 µmol/L]), and lower triage systolic blood pressure (OR, 1.52 [CI, 1.31 to 1.77] per 20 mm Hg) and initial oxygen saturation (OR, 1.16 [CI, 1.01 to 1.33] per 5%). Nonnormal serum troponin levels (OR, 2.75 [CI, 1.86 to 4.07]) were associated with increased mortality risk. Areas under the receiver-operating characteristic curves of the multivariate model were 0.805 for the derivation data set (bootstrap-corrected, 0.811) and 0.826 for validation data set (n = 5158; mean age, 75.7 years [SD, 11.4]; 51.6% men). In the derivation cohort, a multivariate index score stratified 7-day mortality with rates of 0.3%, 0.3%, 0.7%, and 1.9% in quintiles 1 to 4, respectively. Mortality rates in the 2 highest risk groups were 3.5% and 8.2% in deciles 9 and 10, respectively. LIMITATION: Left ventricular ejection fraction was not included in the model. CONCLUSION: A multivariate index comprising routinely collected variables stratified mortality risk with high discrimination in a broad group of patients with acute heart failure presenting to the ED. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Relationship between sodium intake and sleep apnea in patients with heart failure.

OBJECTIVES: The purpose of this study was to test the hypothesis that severity of sleep apnea (SA), assessed by frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index [AHI]), is related to sodium intake in patients with heart failure (HF). BACKGROUND: Dependent edema and overnight rostral fluid shift from the legs correlate with the AHI in patients with HF in whom excessive sodium intake can cause fluid retention. METHODS: Sodium intake was estimated by food recordings in 54 HF patients who underwent overnight polysomnography. RESULTS: Thirty-one of the 54 patients had SA, and their mean sodium intake was higher than that in those without SA (3.0 ± 1.2 g vs. 1.9 ± 0.8 g, p < 0.001). There was a significant correlation between the AHI and sodium intake (r = 0.522, p < 0.001). Multivariate analysis showed that the significant independent correlates of the AHI were sodium intake, male sex, and serum creatinine level. CONCLUSIONS: These findings suggest that in patients with HF, sodium intake plays a role in the pathogenesis of SA.

Prediction of emergent heart failure death by semi-quantitative triage risk stratification.

OBJECTIVES: Generic triage risk assessments are widely used in the emergency department (ED), but have not been validated for prediction of short-term risk among patients with acute heart failure (HF). Our objective was to evaluate the Canadian Triage Acuity Scale (CTAS) for prediction of early death among HF patients. METHODS: We included patients presenting with HF to an ED in Ontario from Apr 2003 to Mar 2007. We used the National Ambulatory Care Reporting System and vital statistics databases to examine care and outcomes. RESULTS: Among 68,380 patients (76±12 years, 49.4% men), early mortality was stratified with death rates of 9.9%, 1.9%, 0.9%, and 0.5% at 1-day, and 17.2%, 5.9%, 3.8%, and 2.5% at 7-days, for CTAS 1, 2, 3, and 4-5, respectively. Compared to lower acuity (CTAS 4-5) patients, adjusted odds ratios (aOR) for 1-day death were 1.32 (95%CI; 0.93-1.88; p = 0.12) for CTAS 3, 2.41 (95%CI; 1.71-3.40; p<0.001) for CTAS 2, and highest for CTAS 1: 9.06 (95%CI; 6.28-13.06; p<0.001). Predictors of triage-critical (CTAS 1) status included oxygen saturation <90% (aOR 5.92, 95%CI; 3.09-11.81; p<0.001), respiratory rate >24 breaths/minute (aOR 1.96, 95%CI; 1.05-3.67; p = 0.034), and arrival by paramedic (aOR 3.52, 95%CI; 1.70-8.02; p = 0.001). While age/sex-adjusted CTAS score provided good discrimination for ED (c-statistic = 0.817) and 1-day (c-statistic = 0.724) death, mortality prediction was improved further after accounting for cardiac and non-cardiac co-morbidities (c-statistics 0.882 and 0.810, respectively; both p<0.001). CONCLUSIONS: A semi-quantitative triage acuity scale assigned at ED presentation and based largely on respiratory factors predicted emergent death among HF patients.

Post-trial period surveillance for randomised controlled cardiovascular studies: submitted protocols, consent forms and the role of the ethics board.

BACKGROUND: The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. OBJECTIVES: The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. METHODS: An observational study of protocols of randomised trials of chronic therapies for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. RESULTS: 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. CONCLUSIONS: The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised.

ß-blockade restores muscle sympathetic rhythmicity in human heart failure.

BACKGROUND: Muscle sympathetic nerve firing rate increases as chronic heart failure (CHF) progresses, yet its oscillation, particularly within the frequency range encompassing 0.13 Hz, diminishes. The current study tested the hypothesis that chronic therapy with lipophilic ß-adrenoceptor antagonists augments the modulation of muscle sympathetic nerve activity variability (MSNAV) at this frequency range. METHODS AND RESULTS: In 21 CHF angiotensin converting enzyme (ACE) inhibitor-treated patients (age: 53 ± 2, ejection fraction: 20 ± 2%), MSNA was recorded before and after 4 months of ß-blockade with either metoprolol (up to 50mg b.i.d.) or carvedilol (up to 25mg b.i.d.). Harmonic MSNAV was assessed by coarse graining spectral analysis. Both drugs lowered heart rate similarly (-13 ± 2 beats/min; P < 0.001) but neither affected MSNA burst frequency (-7 ± 4 bursts/min, not significant). Before ß-blockade, harmonic MSNA power in the region encompassing 0.13 Hz was essentially absent. Beta-blockade increased the mean values for total power (from 0.00 to 0.50 Hz; 5.2 ± 0.8 to 6.8 ± 1.2U(2); P < 0.001) and for harmonic MSNA spectral power across the 0.1-0.22 Hz frequency range (from 0.48 ± 0.10 to 1.50 ± 0.32 U(2), F = 12.2; P < 0.001). Both carvedilol and metoprolol had a similar effect. CONCLUSIONS: In patients with CHF receiving ACE inhibitors, adding a ß-adrenoceptor antagonist restores low and high frequency harmonic oscillations in MSNA. Beta-1 antagonism is sufficient to achieve this response. Augmented modulation of sympathetic outflow could contribute to the beneficial effects of ß-blockade in CHF on sudden death and disease progression.

Relation of periodic leg movements during sleep and mortality in patients with systolic heart failure.

Periodic leg movements during sleep (PLMs) are a disorder characterized by regularly recurring movements of the legs during sleep. Although PLMs are common in patients with heart failure (HF), their clinical significance is unknown. The aim of this study was to determine whether, in patients with HF, PLMs are associated with increased mortality risk. In a prospective cohort study, 218 consecutive patients with systolic HF newly referred to an HF clinic from 1997 to 2004 who underwent overnight polysomnography, regardless of symptoms or signs of sleep disorders, were enrolled. The frequency of PLMs per hour of sleep was quantified as the PLM index (PLMI). Patients were classified as either normal (PLMI <5) or abnormal (PLMI ≥5). Eighty-one of the patients (37%) had PLMIs ≥5. During a mean follow-up period of 32.9 months, complete follow-up data were obtained in 95%. Patients with PLMIs ≥5 were older and had lower left ventricular ejection fractions and higher New York Heart Association classes than patients with PLMIs <5. The mortality rate was significantly higher in patients with PLMIs ≥5 than those with PMLIs <5 (10.4 vs 3.4 deaths/100 patient-years, p = 0.002). After adjusting for significant confounding factors, the presence of PLMI ≥5 remained a significant independent risk for death (hazard ratio 2.42, 95% confidence interval 1.16 to 5.02, p = 0.018). In conclusion, in patients with systolic HF, the presence of PLMI ≥5 is associated with an increased mortality risk, but these findings do not establish a cause-effect relation.

A high-sodium diet is associated with acute decompensated heart failure in ambulatory heart failure patients: a prospective follow-up study.

BACKGROUND: A low-sodium diet is an accepted treatment of patients with heart failure (HF), although minimal evidence exists on the appropriate amount of sodium intake for this population. Certain HF guidelines have liberalized dietary sodium recommendations, which actually exceed guidelines for healthy adults. OBJECTIVES: We tested the hypothesis that high sodium intake is related to acute decompensated HF (ADHF) in ambulatory HF patients. Secondary outcomes included all-cause hospitalization and mortality. DESIGN: We prospectively enrolled medically stable, ambulatory patients with systolic HF (n = 123; mean ± SD age: 60 ± 13 y) from 2 outpatient HF clinics from 2003 to 2007. Baseline estimates of dietary sodium and other nutrient intakes were obtained from two 3-d food records. RESULTS: The median follow-up time was 3.0 y. Mean (±SD) sodium intakes were 1.4 ± 0.3, 2.4 ± 0.3, and 3.8 ± 0.8 g Na/d in the lower, middle, and upper tertiles, respectively. Cumulative ADHF event rates at 3 y were 12 ± 6%, 15 ± 7%, and 46 ± 11% in the low, middle, and upper tertiles, respectively (log-rank P = 0.001). For ADHF, the upper tertile was associated with an adjusted hazard ratio of 2.55 (95% CI: 1.61, 4.04; P < 0.001). Time-to-event probabilities were significant for mortality (log-rank P = 0.022) but not for all-cause hospitalization (log-rank P = 0.224). The high-sodium tertile was associated with an adjusted hazard ratio of 1.39 (95% CI: 1.06, 1.83; P = 0.018) for all-cause hospitalization and 3.54 (95% CI: 1.46, 8.62; P = 0.005) for mortality. CONCLUSIONS: To our knowledge, this study provides the first prospective evidence that ambulatory HF patients who consume higher amounts of sodium are at greater risk of an ADHF event. These data provide support for more stringent sodium intake guidelines than those currently recommended for HF patients.

Cardiac-specific sympathetic activation in men and women with and without heart failure.

BACKGROUND: Clinical outcomes for cardiovascular syndromes such as heart failure differ between men and women. OBJECTIVE: To seek phenotypic evidence for sex-differences in cardiac-specific sympathetic nervous system activation, as abnormal sympathetic nervous system activation is a key pathophysiological mechanism in heart failure (HF). METHODS: Patients who underwent evaluation of cardiac norepinephrine spillover (CNESP) using radiotracer methodology were identified retrospectively, and included in the analysis if they met criteria for either a normal left ventricular (NLV) function group, or systolic HF group, defined as an LV ejection fraction <40% and NYHA class II-III symptoms. Within each group a matched cohort analysis, identifying two control men for each woman, was performed. RESULTS: 166 subjects were identified, 48 within the NLV function group and 118 within the HF group. In the NLV function group, 12 women were matched for age to 24 men. Women had significantly higher NE concentrations in coronary sinus plasma. When normalised to total body NE spillover (CNESP:TBNESP), women had significantly higher values than men (CNESP:TBNESP, 6±3% in women vs 3±3% in men, p<0.05). In the HF group, 20 women were matched for age, date of study and presence of coronary disease to 39 men. There were no differences in comorbidities, drugs or haemodynamic measurements. Both CNESP and CNESP:TBNESP were significantly higher in women with HF than in men (CNESP 264±191 in women vs 182±110 in men, CNESP:TBNESP 9±6% in women vs 4±2% in men, p<0.05 for both). CONCLUSION: In patients with and without HF, women exhibit increased cardiac-specific sympathetic activation. Sexual dimorphism in cardiac autonomic physiology and its relationship to disease merits further investigation.

Evaluation of 2 methods for sodium intake assessment in cardiac patients with and without heart failure: the confounding effect of loop diuretics.

BACKGROUND: Twenty-four-hour urine collections are considered the optimal method for sodium intake assessment. Whether a diagnosis of heart failure (HF) or the use of loop diuretic (LD) therapy for HF compromises the validity of 24-h urine collections as a surrogate marker for sodium intake is unknown. OBJECTIVE: The objective was to determine the strength of association between 24-h urine collections and food records for sodium intake assessment in non-HF cardiac patients and in HF patients stratified by LD usage. DESIGN: Food records and 24-h urine collections were simultaneously completed for 2 consecutive days. Correlation coefficients and the Bland-Altman method of agreement described the relation between the techniques. RESULTS: Non-HF cardiac patients (n = 96; mean ± SD age: 65 ± 11 y), HF patients who were not taking an LD (n = 47; 62 ± 11 y), and HF patients who were taking an LD (n = 62; age: 60 ± 12 y) were included. Correlation coefficients for sodium intake between food records and urine collections were r = 0.624 (P < 0.001) for non-HF cardiac patients and r = 0.678 (P < 0.001) for HF patients who were not taking an LD. However, no significant association (r = 0.132, P = 0.312) was observed for HF patients who were taking LDs. The 95% limits of agreement between the non-HF cardiac patients and the HF patients who were not taking LDs were similar but were ≈50% wider for HF patients who were taking LDs. CONCLUSIONS: For the assessment of sodium intake, food records agree well with 24-h urine collections in non-HF patients with cardiovascular disease and in HF patients who are not receiving LD but not for HF patients who are taking LDs. Therefore, food records may provide a better estimate of sodium intake in HF patients who are receiving LD therapy.

Diuretic dose and long-term outcomes in elderly patients with heart failure after hospitalization.

BACKGROUND: The array of outcomes according to longitudinal furosemide doses in heart failure (HF) have not been evaluated. We examined the relationship of dynamic furosemide dose with mortality and hospitalizations for cardiovascular disease and renal dysfunction. METHODS: Among elderly patients with HF (>or=65 years) newly discharged from hospital, dynamic furosemide exposure was determined by examining dose fluctuations up to 5 years of follow-up using the Ontario Drug Benefit pharmacare database. Dynamic furosemide exposures were classified as low dose (LD; 1-59 mg/d), medium dose (MD; 60-119 mg/d), or high dose (HD; >or=120 mg/d). Outcomes were assessed by modeling furosemide exposure as a time-dependent covariate. RESULTS: Among 4,406 patients (78.4 +/- 7.0 years; 50.5% male), 46% changed furosemide dose categories within 1 year, and 63% changed dose categories over the follow-up period. High-dose furosemide patients were younger, were mostly male, and exhibited more ischemic or valvular disease, diabetes, atrial fibrillation, hypotension, hyponatremia, and higher baseline creatinine than LD. Compared with LD, MD exposure was associated with increased mortality with adjusted hazard ratio 1.96 (95% CI 1.79-2.15), whereas HD exposure conferred greater mortality risk with hazard ratio 3.00 (95% CI 2.72-3.31) after multiple covariate adjustment (both P < .001). Adjusted risks of hospitalization for HF (MD: 1.24 [95% CI 1.12-1.38] and HD: 1.43 [95% CI 1.26-1.63]), renal dysfunction (MD: 1.56 [95% CI 1.38-1.76] and HD: 2.16 [95% CI 1.88-2.49]), and arrhythmias (MD: 1.15 [95% CI 1.03-1.30] and HD: 1.45 [95% CI 1.27-1.66]) were also higher with increasing furosemide exposure. CONCLUSION: Exposure to higher furosemide doses is associated with worsened outcomes and is broadly predictive of death and morbidity.