Continuous ultrafiltration for congestive heart failure: the CUORE trial.

BACKGROUND: There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload. METHODS AND RESULTS: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33). CONCLUSIONS: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Continuous ultrafiltration for congestive heart failure: the CUORE trial.

Background: There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.Methods and Results: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; = 27). The primary endpoint of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 4.5 and 7.9 ± 5.0 kg, respectively;P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002).Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).Conclusions: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

Uricaemia and ejection fraction in elderly heart failure outpatients.

BACKGROUND: Preliminary data suggest that serum uric acid (SUA) could be involved in the prognosis of chronic heart failure (HF). The aim of our study was to test the relationship between SUA and left ventricular ejection fraction (EF%) in a cohort of elderly hypertensive outpatients with chronic HF. DESIGN: We consecutively enrolled 487 elderly outpatients (M = 59·8%; F = 40·2%; mean age: 72 ± 11 years old) affected by mild-to-moderate hypertensive and/or ischaemic HF, evaluating the relationship between SUA and EF%. RESULTS: In an univariate analysis, SUA was inversely related with EF%: B = -4·392, 95% CI -5·427 to -3·357, P < 0·001. After adjustment for a large number of variables in a multivariate analysis, the value of EF% was best predicted by SUA (B = -3·005, 95% CI -4·386 to -1·623, P < 0·001), log brain natriuretic peptide (BNP: B = -2·341, 95% CI -3·137 to -1·248, P < 0·001) and mean arterial pressure (MAP: B = 0·241, 95% CI 0·047 to 0·435, P = 0·015). A separate analysis by estimated glomerular filtration rate (eGFR) levels confirmed the inverse relationship between SUA and EF% in patients with normal renal function. A separate analysis by sex confirmed that SUA and log BNP were significant strong predictors of EF% in men, but not in women where the best predictors were log BNP, MAP and body mass index. The predicting role of SUA was apparently independent of eGFR and use of diuretics. CONCLUSION: Serum uric acid seems to be inversely related to EF% in male elderly patients with HF after adjustment for the several confounding factors. This observation supports a primary negative effect of SUA on left ventricular function that warrants further investigations.

Management and outcomes of calf deep vein thrombosis in patients with contraindication to full anticoagulation due to bleeding.

BACKGROUND: This prospective observational study was aimed at assessing early outcomes of inpatients with isolated distal deep vein thrombosis (IDDVT) and coexisting bleeding. METHODS: Patients received enoxaparin 4000 units daily or intermediate doses, and ultrasound surveillance (US). Primary outcomes were extension to the popliteal vein (PDVT) or symptomatic pulmonary embolism (PE), bleeding complications during the treatment and the composite of PDVT and bleeding complications. Secondary outcomes were recurrent IDDVTs and death. RESULTS: 90/95 patients completed the study period (30 days). PDVT occurred in 2/41 (4.9%) and in 3/45 (6.7%) subjects receiving enoxaparin 4000 units and intermediate doses respectively (OR 1.39; 95% CI: 0.22-11; P=0.72). PE occurred in only one of the 4 untreated subjects (25% vs. 0 patients taking enoxaparin 4000 units or intermediate doses; P=1.0). Recurrent IDDVTs occurred in 29 subjects (32.2%), more frequently during enoxaparin 4000 (19/29, 65.5%). Four patients died (4.4%). Bleeding complications occurred in 8 subjects (8.9%), all treated with intermediate doses (0 vs. 17.8%; P=1.0). Enoxaparin 4000 units significantly reduced the risk of the composite outcome compared with higher doses (4.9% vs. 24.4%; OR 6.31; 95% CI: 1.56-42.65; P=0.02). Major trauma significantly increased the risk of PDVT (OR 20.92; 95% CI: 2.82-427.51, P=0.01; logistic regression P=0.01). Patients with major trauma are also at increased bleeding risk (OR 5; 95% CI: 1.06-23.76, P=0.04; logistic regression P=0.03). CONCLUSIONS: Enoxaparin 4000 units daily, supported by US, may be an option for selected patients.

Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up.

BACKGROUND: The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function. METHODS: In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure. RESULTS: The presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; P = .027/P = .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, P = .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, P = .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, P <.002). CONCLUSIONS: Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.

Calf deep vein thrombosis: frequency, therapeutic management, early outcomes and all-causes mortality in a cohort of hospitalized patients.

BACKGROUND: Isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. METHODS: We performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. This study aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. RESULTS: Among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2% and 0.7% respectively. 19% of IDDVT patients died compared to 25.5% of PDVT subjects (OR=0.72; 95% CI=0.44-1.17; P=0.19). In IDDVT patients, age ≥80, cancer and intracranial bleeding increased the risk of death (OR=2; 95% CI=1.07-3.75, P=0.001; OR=8.47; 95% CI=3.28-21.88, P=0.0000003; OR=2.33; 95% CI=1.18-4.58, P=0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (P=0.031; OR=16.11; 95% CI=0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR=8.28, 95% CI=2.07-33 P=0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR=0.07; 95% CI=0.009-0.61, P=0.007), and all-causes mortality (OR=0.37; 95% CI=0.17-0.8; P=0.02), without a significant increase of bleeding. CONCLUSIONS: Among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.

Central hemodynamics in risk assessment strategies: additive value over and above brachial blood pressure.

Although the clinical relevance of brachial blood pressure (BP) measurement for cardiovascular (CV) risk stratification is nowadays widely accepted, this approach can nevertheless present several limitations. Pulse pressure (PP) amplification accounts for the notable increase in PP from central to peripheral arterial sites. Target organs are more greatly exposed to central hemodynamic changes than peripheral organs. The pathophysiological significance of local BP pulsatility, which has a role in the pathogenesis of target organ damage in both the macro- and the microcirculation, may therefore not be accurately captured by brachial BP as traditionally evaluated with cuff measurements. The predictive value of central systolic BP and PP over brachial BP for major clinical outcomes has been demonstrated in the general population, in elderly adults and in patients at high CV risk, irrespective of the invasive or non-invasive methods used to assess central BP. Aortic stiffness, timing and intensity of wave reflections, and cardiac performance appear as major factors influencing central PP. Great emphasis has been placed on the role of aortic stiffness, disturbed arterial wave reflections and their intercorrelation in the pathophysiological mechanisms of CV diseases as well as on their capacity to predict target organ damage and clinical events. Comorbidities and age-related changes, together with gender-related specificities of arterial and cardiac parameters, are known to affect the predictive ability of central hemodynamics on individual CV risk.

Central hemodynamics for risk reduction strategies: additive value over and above brachial blood pressure.

Reduction strategies of blood pressure, as a modifiable cardiovascular risk, are currently based on office assessment of brachial artery blood pressure. However, antihypertensive treatment based on brachial BP values reduces cardiovascular risk but cannot completely reverse the hypertension-induced risk of morbidity events. As is well known, BP varies in different arterial systems and invasive and non-invasive studies have demonstrated that brachial BP does not necessarily reflect central aortic BP. Emerging evidences now suggest that central pressure may predict cardiovascular diseases better than brachial BP; moreover, it may differently respond to certain antihypertensive drugs. The potential effects beyond peripheral BP control may be due to specific protective properties of different antihypertensive drugs in affecting central aortic pressure and arterial stiffness. Although data on direct cardiovascular benefit impact of central blood pressure treatment in randomized clinical trials are still lacking, it is likely that the improvement of quality of care and the individualized assessment of the hypertension-associated cardiovascular risk are achievable with the use of central hemodynamics. Therefore, basing antihypertensive treatment guidance on central pressures rather than on peripheral blood pressure may be the key for future antihypertensive strategies.