Abdul Al-Hesayen

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.

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Focus Update: Anemia, Biomarkers, and Recent Therapeutic Trial Implications

The 2014 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides discussion on the management recommendations on 3 focused areas: (1) anemia; (2) biomarkers, especially natriuretic peptides; and (3) clinical trials that might change practice in the management of patients with heart failure. First, all patients with heart failure and anemia should be investigated for reversible causes of anemia. Second, patients with chronic stable heart failure should undergo natriuretic peptide testing. Third, considerations should be given to treat selected patients with heart failure and preserved systolic function with a mineralocorticoid receptor antagonist and to treat patients with heart failure and reduced ejection fraction with an angiotensin receptor/neprilysin inhibitor, when the drug is approved. As with updates in previous years, the topics were chosen in response to stakeholder feedback. The 2014 Update includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers to best manage patients with heart failure.

Nutritional Inadequacies in Patients with Stable Heart Failure

Sodium restriction is the primary nutritional strategy in heart failure; however, other diet-related concerns may also occur. We characterized dietary intake among stable patients with heart failure and a non-heart-failure cardiac control group to quantify and determine prevalence of inadequate micronutrient intake. Two 3-day food records were completed by 123 patients with heart failure and 58 controls. A subset of each group provided two 24-hour urine collections. Mean intake of sodium (2,540+/-1,122 vs 2,596+/-1,184 mg/day) and potassium (3,190+/-980 vs 3,114+/-828 mg/day) was similar between the heart failure and control groups. Prevalence of inadequate potassium intake was 94% among patients with heart failure and 91% among controls. More than 50% in each group had inadequate intakes of calcium, magnesium, folate, and vitamins D and E. In stable patients with heart failure, sodium intake was not excessive. However, we demonstrated widespread dietary inadequacies of other vitamins and minerals. These findings highlight the importance of diet beyond that of sodium restriction.

Role of KATP Channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts

Rationale: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. Objective: We addressed the hypotheses that there is regional disease-related expression of KATP channels in human cardiomyopathic hearts and that KATP channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. Methods and Results: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 &mgr;mol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. KATP subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (&Dgr;ERPTransmural=ERPEpicardium−ERPEndocardium) was verified with pacing protocols. &Dgr;ERPTransmural in control was 5±2 ms and increased to 36±5 ms with ischemia. This effect was greatly attenuated by glibenclamide (&Dgr;ERPTransmural for glibenclamide+ischemia=4.9±4 ms, P=0.019 versus control ischemia). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.

Selective versus nonselective β-adrenergic receptor blockade in chronic heart failure: differential effects on myocardial energy substrate utilization

Non‐selective and selective β‐blockers have been shown to improve outcomes in chronic heart failure (CHF). Recent data suggests the non‐selective β‐blockers have a more favourable effect on outcomes than β1‐selective agents. We sought to examine the differential effects of non‐selective versus selective β‐blockade on myocardial substrate utilization in patients with CHF.

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update: Focus on Rehabilitation and Exercise and Surgical Coronary Revascularization

The 2013 Canadian Cardiovascular Society Heart Failure Management Guidelines Update provides focused discussions on the management recommendations on 2 topics: (1) exercise and rehabilitation; and (2) surgical coronary revascularization in patients with heart failure. First, all patients with stable New York Heart Association class I-III symptoms should be considered for enrollment in a tailored exercise training program, to improve exercise tolerance and quality of life. Second, selected patients with suitable coronary anatomy should be considered for bypass graft surgery. As in previous updates, the topics were chosen in response to stakeholder feedback. The 2013 Update also includes recommendations, values and preferences, and practical tips to assist the clinicians and health care workers manage their patients with heart failure.

The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure

Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase‐5 inhibition on sympathetic activity in this population has not been evaluated.

Cardiac sympathetic activation in patients with pulmonary arterial hypertension.

Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 ± 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 ± 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 ± 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 ± 2.2 vs. 1.5 ± 0.9 pmol/ml; P < 0.01) but similar to that seen in those with CHF (3.3 ± 1.4; P = NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure.

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.

The Effects of Dobutamine on Cardiac Sympathetic Activity in Patients With Congestive Heart Failure

OBJECTIVES The goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. BACKGROUND Increased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. METHODS Seven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. RESULTS Systemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/- 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 +/- 22 pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 +/- 43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). CONCLUSIONS Dobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.