Renal function in advanced heart failure

Despite recent advances with neurohormonal antagonists and devices, the prognosis of patients with advanced heart failure (HF) remains grave. Renal dysfunction is a common comorbid condition in HF and is associated with adverse outcomes. Current evidence indicates that intrinsic renal disease and inflammation in HF makes the kidney susceptible to hemodynamic compromise and congestion and contributes to a great extent to the development of renal dysfunction. Relief of congestion requires combination treatment with diuretics, neurohormonal antagonists, and occasionally vasodilators as well as inotropes. However, high doses of diuretics may accelerate the development of renal dysfunction by increasing neurohumoral activity and inducing renal structural and functional changes. Ultrafiltration should be reserved for patients with true diuretic resistance. Finally, early identification of the "patient at risk" remains a challenging issue and is limited by the currently used conventional parameters of renal function. However, novel biomarkers of acute kidney ischemia and/or injury are emerging and promise to become a diagnostic option for this patient population.     

Obesity,inflammation, and heart failure: links and misconceptions

Heart Failure Reviews - Obesity has been linked with heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF). This link has been attributed to obesity-induced metabolic...     

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes

BACKGROUND: Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS: This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. RESULTS: Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. CONCLUSION: The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.     

Intestinal metabolism promotes regional differences in apical uptake of indinavir: coupled effect of P-glycoprotein and cytochrome P450 3A on indinavir membrane permeability in rat

The purpose of this study was to investigate transport and metabolism contributions to low indinavir permeability in rat ileum and enhanced drug permeability in the jejunum. Permeability models utilized included single pass in situ rat intestinal perfusion and rat intestinal tissue mounted in Ussing chambers. Intestinal metabolism was measured by fractional appearance of metabolite (F(met)), determined as the percentage of the predominant metabolite M6 over luminal loss of indinavir in the perfusion model. Among the results, indinavir exhibited bidirectional transport across rat ileum. Verapamil and cyclosporin A inhibited net flux by 37 and 38%, respectively. Intestinal metabolism of indinavir was most significant in upper jejunum (F(met) = 65.78 +/- 19.02%), decreasing in midjejunum (F(met) = 31.58 +/- 5.63%). M6 was not detectable in ileum or colon. Western blot analysis of rat intestinal mucosal tissue samples confirmed that the axial expression of CYP3A was consistent with the regional pattern of formation of M6. Intestinal metabolism was saturable and could be inhibited by the CYP3A inhibitor, ketoconazole. A low luminal concentration of indinavir (1 microM) was associated with high F(met) (87.90 +/- 14.30%), whereas a high luminal concentration of indinavir (50 microM) was associated with low F(met) (35.84 +/- 11.59%). In the presence of ketoconazole, both F(met) and permeability of indinavir were reduced in the jejunum. These results suggest that 1) intracellular metabolism of indinavir enhances apical uptake of indinavir in the rat jejunum as a function of the increased concentration gradient generated across the epithelial cell membrane and 2) the efflux transporter P-glycoprotein limits apical uptake of indinavir in the ileum, resulting in low apparent permeability.     

Pathogenesis of chronic heart failure: cardiovascular aging,risk factors,comorbidities, and disease modifiers

Heart Failure Reviews - Chronic heart failure (HF) is rare in the young and common in the elderly in the Western world. HF in the young is usually due to specific causes, predominantly or...     

A 2-Year Psychological Autopsy Study of Completed Suicides in the Athens Greater Area,Greece

ObjectiveTo study the characteristics of a sample of suicide victims from the Athens Greater Area using the psychological autopsy method for the first time in Greece.MethodsWe studied all recorded cases of completed suicide for the 2-year time period November 2007-October 2009 collecting data from the victims'' forensic records as well as from the completion of a psychological autopsy questionnaire.Results335 persons were recorded as suicide victims. We contacted relatives of 256 victims interviewing those of 248 of them (96.9%). The differences regarding sex, marital and employment status between our sample and the general population were statistically significant (p<0.001). The male/female ratio was 3:1. Comparatively more victims were divorced, separated or single and a greater proportion were pensioners or unemployed. 26.0% of the victims had history of prior attempts (64.4% once, 20.3% twice and 15.3% more times). 42.6% were taking psychiatric medication-significantly more women than men according to blood tests; 14.2% had been hospitalized in a psychiatric clinic the year prior to their death. 84.8% have deceased at the place of suicide and 15.2% died in the hospital; 80.3% died indoors and 19.7% outdoors. Men died primarily by hanging or shooting by a firearm while women preferred jumping from height instead (p<0.001). As many as 48.8% had expressed their intention to die to their relatives; 26.6% left a suicide note.ConclusionOur study has shown that the psychological autopsy method is applicable and widely accepted yielding results comparable to the international literature. Specific parameters associated with suicide have been studied for the first time in Greece.