Alberto Palazzuoli

Epidemiology of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference

Sean M. Bagshaw, Dinna N. Cruz, Nadia Aspromonte, Luciano Daliento, Federico Ronco, Geoff Sheinfeld, Stefan D. Anker, Inder Anand, Rinaldo Bellomo, Tomas Berl, Ilona Bobek, Andrew Davenport, Mikko Haapio, Hans Hillege, Andrew House, Nevin Katz, Alan Maisel, Sunil Mankad, Peter McCullough, Alexandre Mebazaa, Alberto Palazzuoli, Piotr Ponikowski, Andrew Shaw, Sachin Soni, Giorgio Vescovo, Nereo Zamperetti, Pierluigi Zanco, Claudio Ronco and for the Acute Dialysis Quality Initiative (ADQI) Consensus Group

Time‐dependent effect of statins on platelet function in hypercholesterolaemia

Background Reduction of platelet activity induced by statins has been described as a positive effect exerted by such molecules on vascular thrombotic events. However, the relations among cholesterol (LDL‐C) reduction, the timing of the antiplatelet effect, the involved mechanisms and the doses of each statin able to reduce platelet function are not actually well known. The aim of our study was to evaluate the impact of simvastatin (20 mg day−1), atorvastatin (10 mg day−1), fluvastatin (40 mg day−1) and pravastatin (40 mg day−1) on platelet function in hypercholesterolaemic subjects with relation to (LDL‐C), oxidized‐LDL (ox‐LDL) and antiport mechanism modifications.

Cardiorenal Syndromes: An Executive Summary from the Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

The cardiorenal syndrome (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded into five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type 1 = acute worsening of heart function leading to kidney injury and/or dysfunction; CRS type 2 = chronic abnormalities in heart function leading to kidney injury or dysfunction; CRS type 3 = acute worsening of kidney function leading to heart injury and/or dysfunction; CRS type 4 = chronic kidney disease leading to heart injury, disease and/or dysfunction, and CRS type 5 = systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Definition and classification of Cardio-Renal Syndromes: workgroup statements from the 7th ADQI Consensus Conference

Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Brunkhorst FM et al. Acute renal failure in patients with severe sepsis and septic shock a significant independent risk factor for mortality: results from the German Prevalence Study. Van Biesen W et al. Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study. et al. Prognostic factors in acute re-nal failure due to sepsis. Results of a prospective multicentre study. Brain natriuretics peptide: a marker of myo-cardial dysfunction and prognosis during severe sepsis. Persistent preload defect in severe sepsis despite fluid loading: a longitudinal echocardiographic study in patients with septic shock. Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study. Troponin as a risk factor for mortality in critically ill patients without acute coronary syndromes. Chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study. Am J Cardiol 2007; 99: 393–398 72. Hillege HL, van Gilst WH. Accelerated decline and prognostic impact of renal function after myocardial infarction and the benefits of ACE inhibition: the CATS randomized trial.

Erythropoietin as a treatment of anemia in heart failure: Systematic review of randomized trials

BACKGROUND Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure. METHODS An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613). RESULTS Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (-0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (-226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure-related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited. CONCLUSION Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.

Platelet hyperactivity after statin treatment discontinuation

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure

Recent studies have shown that carvedilol therapy in patients with heart failure improves clinical outcome and survival, however, the effects of such treatment on left cardiac morphology and function in elderly patients with severe heart failure has not been widely studied.

Anaemia in heart failure: a common interaction with renal insufficiency called the cardio‐renal anaemia syndrome

Background:  Although many studies have found a high prevalence of anaemia in patients with congestive heart failure (CHF), few have carefully examined the relationship between the CHF and the prevalence of anaemia and chronic renal insufficiency (CRI). Patients with advanced renal failure, significant anaemia, diffuse atherosclerosis, respiratory disease and more elderly patients have been systematically excluded from the great majority of the randomised clinical trials.

Transesophageal echocardiography for identifying potential cardiac sources of embolism in patients with stroke.

Abstract Pathologies of cerebral circulation are one of the most frequent causes of mortality and morbidity among the populations of Western countries. The incidence of ischemic events presumed to have a cardioembolic origin varies from 13% to 34% in the largest international multi-center studies. However, some authors have reported an incidence of general cardiogenic stroke ranging from 23% to 36% in younger patients. Transesophageal echocardiography (TEE) is a useful investigation for identifying cardiac sources of embolism in patients without vascular alterations involving the carotid and vertebral districts.This study comprised 73 patients with unexplained stroke who were investigated by both transthoracic echocardiography (TTE) and TEE. Vascular echocolor sonography had been performed in all of them with negative results. TEE demonstrated: atrial or ventricular thrombosis in 6 Patients (8%), intracavitary neoplasm in 2 (2%), spontaneous echocontrast in 11 (13%), valve strands in 6 (7%), complex aortic plaque in 10 (11%), patency of the foramen ovale in 17 (19%), atrial septal aneurysm in 9 (11%), dystrophy and mitral calcifications in 9 (11%). In the other 18 patients, TEE did not reveal any anomalies. Definite sources of stroke (clots and tumors) were identified in 14% of all the lesions; however, the majority (86%) were potential sources.A comparison of the two echocardiographic techniques demonstrated a greater sensitivity and specificity of TEE. Although TEE was superior to TTE for identifying and evaluating potential embolic sources, we found both methods to be useful and would advise performing TTE before TEE. While TTE is not capable of identifying the majority of anomalies, it does provide useful information to guide subsequent transesophageal investigations.

Prevalence of risk factors, coronary and systemic atherosclerosis in abdominal aortic aneurysm: comparison with high cardiovascular risk population.

Background: Abdominal aortic aneurysm (AAA) is considered a manifestation of atherosclerosis, however there are epidemiologic, biochemical, and structural differences between occlusive atherosclerosis and AAA. The pathogenesis of AAA involves several factors, first of all destruction of collagen and elastin in the aortic wall. Classical risk factors may influence the evolution and development of AAA, though no consistent association has been found. Aims of the study were to evaluate associations between risk factors and to establish the prevalence of carotid, peripheral vascular and coronary atherosclerosis in patients with AAA. Methods: We studied 98 patients with AAA (Group 1) awaiting surgery compared with high cardiovascular risk population having two or more risk factors (n = 82 Group 2). We evaluated traditional risk factors and we studied by eco-doppler and echocardiography the presence of carotid peripheral and coronaric atherosclerosis in two groups. Results: We found a higher incidence of AAA in males (p < 0.01). The prevalence of infrarenal AAA was significantly higher than suprarenal AAA (81 vs 17 p < 0.001). No differences in total cholesterol (199 ± 20 vs. 197 ± 25 mg/dl), low-density lipoprotein (142 ± 16 vs. 140 ± 18 mg/dl), triglycerides (138 ± 45 vs. 144 ± 56 mg/dl), glycemia (119 ± 15 vs. 122 ± 20 mg/dl), and fibrinogen (388 ± 154 vs. 362 ± 92 mg/dl) were found between groups. We demonstrated significant differences for cigarette smoking (p < 0.002), systolic and diastolic blood pressure (150 ± 15 vs. 143 ± 14 mmHg and 88 ± 6 vs. 85 ± 7 mmHg, p < 0.0001 and p < 0.05, respectively) and high sensititivity C reactive protein (2.8 ± 1.3 vs. 1.3 ± 0.7 mg/dl, p < 0.001). High-density lipoprotein (HDL) cholesterol levels were significant greater in Group 1 than Group 2 (p < 0.003). Subgroups of patients with AAA and luminal thrombus showed higher fibrinogen levels (564 ± 235 vs. 341 ± 83 mg/dl, p < 0.001) and lower HDL than in controls (46.6 ± 6.5 vs. 52.1 ± 7.8 mg/dl, p < 0.01). We did not find any difference in body mass index, or prevalence of coronary and peripheral atherosclerosis between groups. Conversely, we found higher prevalence of carotid atherosclerosis in Group 2 (9% vs. 25%, p < 0.004). Conclusion: Our AAA patients had fewer and different risk factors respect to patients with atherosclerosis. Only elevated blood pressure, C reactive protein, and smoking showed a significant association with AAA. Atherosclerosis in other arterial districts did not differ respect to subjects with high cardiovascular risk. Our results confirm the hypothesis that AAA and atherosclerosis are two different pathological entities with different risk profiles.