The prognostic significance of serum sodium in a population undergoing cardiac resynchronisation therapy.

PURPOSE: To determine the prognostic implications of changes towards hyponatremia at varying time-points in the treatment of patients undergoing cardiac resynchronisation therapy (CRT). METHODS: A retrospective series of 249 patients was studied from 2002 to 2013. The population was categorized on the basis of serum sodium profile at baseline, at 1 month and at 6 month follow up visits following successful CRT implantation. The composite endpoint was all-cause mortality and heart failure hospitalisation (defined by the need for intravenous diuretic therapy) following CRT implantation. RESULTS: A total of 249 patients (67.8±12.5 years; NYHA class III/IV 75; LVEF 27.2±8.8%) were followed up for a median of 5.5 years. Hyponatremia at baseline, 1 month or 6 months follow up did not predict the composite endpoint. 26% of patients showed hyponatremia at baseline prior to CRT implantation, while it was present in 19.9% of patients 1 month (p=0.003) and in 16% (p<0.001) 6 months after CRT implantation. There was a significantly worse outcome for those patients who developed hyponatremia 6 months after CRT implantation. In multivariate analysis, the intake of loop diuretics (HR 1.76 [1.04-2.95], p=0.03) and renal impairment (urea>7.0mmol/l) (HR 1.61 [1.05-2.46], p=0.03) at baseline were associated with an increased risk of unplanned heart failure hospitalisation and all-cause mortality after CRT implantation. CONCLUSIONS: A change towards hyponatremia when observed 6 months after CRT implantation may predict a worse clinical outcome. Additionally, renal impairment and higher diuretic doses are associated with an increased risk of mortality in the population analysed.

In-hospital treatment and outcomes of heart failure in specialist and non-specialist services: a retrospective cohort study in the elderly.

BACKGROUND: Heart failure is common in the elderly and is associated with high rates of hospitalisation, readmission and mortality. International guidelines however are not frequently implemented in this population. METHODS: We retrospectively studied the clinical profile, investigations, treatment on discharge, length of hospital stay, readmission rate and mortality in 261 patients, aged ≥75 years, with a discharge diagnosis of heart failure. Clinical frailty was estimated using the Canadian Study of Health and Aging clinical frailty scale. RESULTS: Hypertension (64%), atrial fibrillation (50.6%) and ischaemic heart disease (46%) were common, and 75.6% of patients were clinically vulnerable or frail. 23.5% of admitters had an inpatient echocardiogram and 20% of patients had at least one readmission episode for heart failure. On discharge, 64.6% of admissions were treated with an ACE inhibitor or angiotensin II receptor antagonist, 49.3% with a ß blocker and 28.7% with an aldosterone receptor antagonist (ARA). Patients discharged from cardiology wards were more likely to receive a ß blocker (p<0.05) versus care of elderly (COE) wards and readmitters were more likely to receive an ARA (p<0.05) versus patients with a single admission. In total, 34 inpatient deaths were recorded (13%) and 80 deaths (30.7%) were recorded long-term (median follow-up 337 days). Long-term mortality was significantly lower in single admitters versus readmitters (p<0.0001) and in those managed on cardiology wards versus COE wards (p<0.05). CONCLUSIONS: Compared with patients hospitalised on geriatric wards, those admitted to cardiology units were discharged more frequently with recommended medications and had a lower long-term mortality.

Post-procedural arterial hypertension: implications for clinical outcome after transcatheter aortic valve implantation.

BACKGROUND AND AIM OF THE STUDY: Persistent arterial hypertension (HT) has been associated with increased morbidity and mortality after surgical aortic valve replacement (AVR). The impact of increased blood pressure (BP) after transcatheter aortic valve implantation (TAVI) has not yet been fully elucidated. METHODS: The mean systolic and diastolic BP after TAVI were calculated from the last 10 non-invasive recordings performed before discharge in 176 patients. The primary end-point was symptomatic improvement after 6-12 months according to BP control at the time of discharge. RESULTS: In patients with controlled BP (<140/90 mmHg), the symptomatic response after TAVI was significantly better compared to patients with uncontrolled BP (> or =140/90 mmHg), as reflected by NYHA functional class (+1.4 +/- 0.8 versus +0.8 +/- 1.0, p = 0.002) and six-minute walk test (6-MWT) distance improvement (+100 +/- 71 m versus +30 +/- 64 m, p < 0.001) at 6-12 months' follow up. A 10 mmHg decrease in systolic BP was associated with an 18 m increase in 6-MWT distance (p = 0.001). In addition, reverse left ventricular (LV) remodeling was significantly impaired in uncontrolled BP individuals, as reflected by regression of LV mass (-15 +/- 61 g versus -37 +/- 54 g, p = 0.041) and relative wall thickness (-0.02 +/- 0.09 versus -0.07 +/- 0.1, p = 0.01). Cumulative all-cause and cardiovascular mortality were significantly lower in patients with controlled BP compared to those with uncontrolled BP (6.5% versus 16%, p = 0.04; cardiovascular 3.7% versus 11.6%, p = 0.035). CONCLUSION: Uncontrolled HT after TAVI may contribute to diminished symptomatic improvement.

Distribution and neurochemical characterization of neurons within the nucleus of the solitary tract responsive to serotonin agonist-induced hypophagia.

Pharmacological compounds enhancing serotonergic tone significantly decrease food intake and are among the most clinically efficacious treatments for obesity. However, the central mechanisms through which serotonergic compounds modulate feeding behavior have not been fully defined. The primary relay center receiving visceral gastrointestinal information in the central nervous system is the nucleus of the solitary tract (NTS) in the caudal brainstem. Here we investigated whether the classic anorectic serotonin receptor agonist m-chloro-phenylpiperazine (mCPP) enhances the activity of metabolically sensitive NTS neurons. Using c-fos immunoreactivity (FOS-IR) as a marker of neuronal activation in rats, we observed that mCPP significantly and dose-dependently activated a discrete population of caudal NTS neurons at the level of the area postrema (AP). In particular, this pattern of FOS-IR induction was consistent with the location of catecholamine-containing neurons. Dual-labeling performed with FOS-IR and the catecholamine biosynthetic enzyme tyrosine hydroxylase (TH) revealed that mCPP induced FOS-IR in 83.7% of TH-IR containing neurons in the NTS at the level of the AP. The degree of activation of TH neurons was strongly negatively correlated with food intake. Moreover, this activation was specific to catecholamine neurons, with negligible induction of cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), or neurotensin neurons. NTS catecholaminergic neurons relay visceral gastrointestinal signals to both the lateral hypothalamus (LHA) and paraventricular nucleus of the hypothalamus (PVH), where these signals are integrated into autonomic and hormonal responses regulating food intake. The data presented here identify a novel mechanism through which a serotonin receptor agonist acting in the caudal brainstem may regulate ingestive behavior.