Clinical Outcomes of 1625 Patients With Primary Aldosteronism Subtyped With Adrenal Vein Sampling.

We sought to measure the clinical benefits of adrenal venous sampling (AVS), a test recommended by guidelines for primary aldosteronism (PA) patients seeking surgical cure, in a large registry of PA patients submitted to AVS. Data of 1625 consecutive patients submitted to AVS in 19 tertiary referral centers located in Asia, Australia, Europe, and North America were collected in a large multicenter international registry. The primary end points were the rate of bilateral success, ascertained lateralization of PA, adrenalectomy, and of cured arterial hypertension among AVS-guided and non AVS-guided adrenalectomy patients. AVS was successful in 80.1% of all cases but allowed identification of unilateral PA in only 45.5% by the criteria in use at each center. Adrenalectomy was performed in 41.8% of all patients and cured arterial hypertension in 19.6% of the patients, 2-fold more frequently in women than men (P<0.001). When AVS-guided, surgery provided a higher rate of cure of hypertension than when non-AVS-guided (40.0% versus 30.5%; P=0.027). Compared with surgical cases, patients treated medically needed more antihypertensive medications (P<0.001) and exhibited a higher rate of persistent hypokalemia requiring potassium supplementation (4.9% versus 2.3%; P<0.01). The low rate of adrenalectomy and cure of hypertension in PA patients seeking surgical cure indicates suboptimal AVS use, possibly related to issues in patient selection, technical success, and AVS data interpretation. Given the better outcomes of AVS-guided adrenalectomy, these results call for actions to improve the diagnostic use of this test that is necessary for detection of surgical PA candidates. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01234220.

Electrical stimulation for the treatment of obstructive sleep apnoea: a review of the evidence.

INTRODUCTION: Obstructive sleep apnoea is an increasingly prevalent clinical condition with significant impact on individuals and public health. Continuous positive airway pressure therapy is the standard treatment, but adherence is limited and alternative treatments are needed. In this context, non-invasive and invasive methods for the electrical stimulation of upper airway dilator muscles have been demonstrated to be effective in selected patients. Areas covered: This review will cover investigations on the clinical effects, safety, and tolerability of non-invasive and invasive electrical stimulation of the upper airway for the management of obstructive sleep apnoea. Following a search of the relevant literature published on PubMed this review is focused mainly on data obtained from randomized clinical trials and clinical studies. Expert commentary: The available evidence provides a rationale to consider upper airway electrical stimulation as treatment for selected patients with obstructive sleep apnoea, who have poor adherence or experience difficulties with continuous positive airway pressure therapy. Non-invasive stimulation using transcutaneous electrodes and implantable hypoglossal nerve stimulator technologies may provide an alternative to continuous positive airway pressure for the treatment of obstructive sleep apnoea via restoration of neuromuscular tone and improved upper airway patency.

Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a loss of neuromuscular tone of the upper airway dilator muscles while asleep. This study investigated the effectiveness of transcutaneous electrical stimulation in patients with OSA. PATIENTS AND METHODS: This was a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed OSA. Patients were randomly assigned to one night of sham stimulation and one night of active treatment. The primary outcome was the 4% oxygen desaturation index, responders were defined as patients with a reduction >25% in the oxygen desaturation index when compared with sham stimulation and/or with an index <5/hour in the active treatment night. RESULTS: In 36 patients (age mean 50.8 (SD 11.2) years, male/female 30/6, body mass index median 29.6 (IQR 26.9-34.9) kg/m(2), Epworth Sleepiness Scale 10.5 (4.6) points, oxygen desaturation index median 25.7 (16.0-49.1)/hour, apnoea-hypopnoea index median 28.1 (19.0-57.0)/hour) the primary outcome measure improved when comparing sham stimulation (median 26.9 (17.5-39.5)/hour) with active treatment (median 19.5 (11.6-40.0)/hour; p=0.026), a modest reduction of the mean by 4.1 (95% CI -0.6 to 8.9)/hour. Secondary outcome parameters of patients' perception indicated that stimulation was well tolerated. Responders (47.2%) were predominantly from the mild-to-moderate OSA category. In this subgroup, the oxygen desaturation index was reduced by 10.0 (95% CI 3.9 to 16.0)/hour (p<0.001) and the apnoea-hypopnoea index was reduced by 9.1 (95% CI 2.0 to 16.2)/hour (p=0.004). CONCLUSION: Transcutaneous electrical stimulation of the pharyngeal dilators during a single night in patients with OSA improves upper airway obstruction and is well tolerated. TRIAL REGISTRATION NUMBER: NCT01661712.

Decongestion in acute heart failure.

Congestion is a major reason for hospitalization in acute heart failure (HF). Therapeutic strategies to manage congestion include diuretics, vasodilators, ultrafiltration, vasopressin antagonists, mineralocorticoid receptor antagonists, and potentially also novel therapies such as gut sequesterants and serelaxin. Uncertainty exists with respect to the appropriate decongestion strategy for an individual patient. In this review, we summarize the benefit and risk profiles for these decongestion strategies and provide guidance on selecting an appropriate approach for different patients. An evidence-based initial approach to congestion management involves high-dose i.v. diuretics with addition of vasodilators for dyspnoea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade with thiazide diuretics or natriuretic doses of mineralocorticoid receptor antagonists. Vasopressin antagonists may improve aquaresis and relieve dyspnoea. If diuretic strategies are unsuccessful, then ultrafiltration may be considered. Ultrafiltration should be used with caution in the setting of worsening renal function. This review is based on discussions among scientists, clinical trialists, and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from 30 November to 1 December 2012.

Molecular biology based assessment of green tea effects on oxidative stress and cardiac remodelling in dialysis patients.

BACKGROUND & AIMS: Cardiovascular disease, the most common cause for morbidity and mortality in end-stage renal disease (ESRD), has prompted the exploration of multiple approaches to improve outcomes. Cardiovascular risk factors such as oxidative stress (OxSt) and cardiac remodelling are common in ESRD and dialysis patients. Green tea (GT) is well recognized as reducing OxSt. This 6 months study evaluated in 20 ESRD patients under chronic dialysis, the effect of GT treatment (1 g/day as commercially available capsule) on cellular and plasma OxSt and proliferation related markers using a molecular biology approach. METHODS: Mononuclear cell p22(phox), Haeme Oxygenase (HO)-1 protein expression, and phosphorylated ERK1/2 status were evaluated in dialysis patients at baseline, after 3 and 6 months of GT treatment by Western blot analysis and plasma oxLDL by ELISA. Cardiac remodelling was assessed by echocardiographic left ventricular (LV) mass determination at baseline and at the end of the study. RESULTS: GT treatment reduced p22(phox) and pERK1/2 from baseline while HO-1 increased. At baseline, LV mass correlated with both p22(phox) and oxLDL. GT treatment decreased LV mass from baseline, which correlated with oxLDL. 9 patients had LV hypertrophy at baseline, which, at 6 months, was normalized in 5 and reduced in 3, showing a parallel decrease of p22(phox), pERK1/2, oxLDL and increase of HO-1. CONCLUSIONS: Treatment with GT decreased the expression of OxSt-related proteins tightly associated with cardiovascular disease and decreased LV mass. It appears highly likely that the addition of GT can provide a benefit in terms of cardiovascular protection in dialysis patients.

Prevention of hypertension, cardiovascular damage and endothelial dysfunction with green tea extracts.

BACKGROUND: We investigated the effect of green tea extract (GTE) in arterial hypertension with high oxidative stress. Angiotensin (Ang) II induces endothelial dysfunction (ED) that is crucial for the development of atherosclerosis and hypertension. METHODS: Male Sprague-Dawley rats, 13 weeks old, randomly assigned to drinking water with or without GTE (6 mg/mL) received a vehicle, a high (700 microg/kg/d) or a low (350 microg/kg/d) Ang II dose for 13 days, by osmotic mini-pumps. Blood pressure (BP) was measured with telemetry. After sacrifice, left ventricular (LV) mass index, small mesenteric artery media-to-lumen ratio, and concentration-response curves of phenylephrine-precontracted arteries to acetylcholine were evaluated. The effect of the superoxide dismutase (SOD-1) analog tempol on artery responses to acetylcholine was assessed. Oxidative stress was measured by plasma hydroperoxides and nitrotyrosine levels. The mRNA of heme oxygenase 1 (HO-1), NADPH oxidase endothelial p22(phox) subunit, and SOD-1 was also measured in the aorta. RESULTS: Compared with vehicle high Ang II increased BP, LV mass index, media-to-lumen ratio, and hydroperoxide radicals. The GTE blunted these increases, prevented the increase in HO-1, p22(phox), and SOD-1 mRNA in aorta caused by Ang II, and reduced them below baseline levels. Low Ang II dose increased BP values and plasma hydroperoxides only during the first week. Both Ang II doses shifted rightward the curves to acetylcholine; this was prevented in vivo by GTE and abolished in vitro by tempol. CONCLUSIONS: The GTE prevented hypertension and target organ damage induced by a high Ang II dose, likely by prevention or scavenging of superoxide anion generation.

Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk women.

OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more detrimental in women than in men, but it is unknown whether this applies to high-risk women. We therefore investigated the association of hyperhomocysteinemia with coronary artery disease (CAD) and cardiovascular mortality in high-risk women referred for CAD, both in the total population and in the hypertensive and normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary centre. INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T polymorphism. CAD was defined as a modified Duke Index score greater than 0; hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women, respectively, without differences between CAD and non-CAD women. By the ATPIII criteria, 92.2% of the women were in the highest risk class and 55% had CAD; however, no association of tHcy with the CAD score was found. After a median follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular causes. Women with high tHcy levels showed the worst all-cause and cardiovascular death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the hypertensive cohort only women with hyperhomocysteinemia showed increased cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk women and adversely affects their prognosis, although it is unrelated to the CAD atherosclerotic burden.

Is homocysteine important as risk factor for coronary heart disease?

AIM: Homocysteine (Hcy), a sulfur-containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular disease. In this paper we review available knowledge on the pathways leading to synthesis and degradation of Hcy, as well as on the genetic and environmental factors affecting its plasma levels, focussing on its potential role in the development of coronary heart disease. DATA SYNTHESIS: Hyperhomocysteinemia (HHcy) is determined by genetic and environmental factors and represents a modifiable cardiovascular risk factor since vitamin supplementation has been shown to effectively lower plasma homocysteine levels. While case-control and cross-sectional studies consistently showed an association of HHcy with cardiovascular disease, prospective studies have given conflicting results. Thus, the role of HHcy in the development of coronary heart disease is still under debate. Furthermore, it remains unclear which patients should be screened for HHcy and treated to correct HHcy. CONCLUSIONS: Available information collectively suggests that although HHcy can be regarded as a minor risk factor for coronary heart disease, it interacts with other risk factors in triggering new events in patients with known CAD. Thus, the treatment of mild HHcy with folate supplementation is appropriate in particular in high risk patients or patients with established CAD who do not present with the "traditional" risk factors.