Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Perioperative heart failure in coronary surgery and timing of intra-aortic balloon pump insertion.

BACKGROUND: Perioperative heart failure (HF) in coronary operations is accompanied by a high operative mortality rate. An intra-aortic balloon pump (IABP) is often used to treat this syndrome. The correct timing for IABP insertion after completion of the operation has not yet been investigated. The aim of this study was to investigate the operative mortality in perioperative HF patients who had undergone coronary operations with respect to the early or the late use of IABP. METHODS: This is a retrospective study including 7,270 patients who had undergone coronary surgery with or without associated procedures. A population of patients with perioperative HF was extracted and analyzed with respect to the use of drugs, intra-operative or post-operative IABP to treat this condition. RESULTS: A total of 1,051 (14.5%) patients had perioperative HF. The mortality rate in this group was 13.5%. Early (intra-operative) IABP insertion was performed in 123 patients. In contrast, 928 patients were treated with inotropic drugs only, and, of these patients, 59 developed a drug-refractory HF requiring late IABP insertion. Operative mortality was significantly (P=0.001) higher in patients requiring late (64.4%) vs. early (41.5%) IABP insertion. Independent risk factors for developing a drug-refractory HF were age, pre-operative serum creatinine value and an associated mitral valve procedure. CONCLUSIONS: Postponing the use of IABP may be deleterious in patients with drug-refractory HF. In the presence of the three factors independently associated with the risk of a drug-refractory HF, early IABP insertion is suggested.

Effects of fenoldopam infusion in complex cardiac surgical operations: a prospective, randomized, double-blind, placebo-controlled study.

AIM: Fenoldopam mesylate is a short-acting dopamine-1 agonist that has been suggested to be a possible reno-protective agent in patients undergoing cardiac surgery. The present study is a prospective, randomized, double-blind placebo controlled trial conducted to determine the effects of fenoldopam in a population of patients undergoing complex cardiac operations. METHODS: Eighty subjects undergoing complex cardiac operations with cardiopulmonary bypass (CPB) were enrolled in the study. Patients were randomly assigned either to the fenoldopam (0.1 microg . kg-1. min-1) or the placebo group. Fenoldopam infusion started at the onset of CPB and was maintained for the first twelve postoperative hours. CPB parameters and renal outcome data were collected. RESULTS: Patients in the fenoldopam group had higher oxygen delivery during CPB and a significantly lower perfusion pressure, although this parameter was still within the normal range. Blood lactate concentrations during CPB were similar in the two groups. Urine output during and after CPB did not differ between groups, nor did the renal function parameters. There was a significantly higher rate of acute kidney injury (AKI) in the placebo group (10% vs 0%). In the subgroup of patients requiring inotropic support for more than 48 hours, renal function parameters were significantly better, the peak arterial blood lactate was significantly lower, and the major morbidity rate was significantly lower (36% vs 100%) for patients who received fenoldopam. CONCLUSION: Fenoldopam improves the quality of perfusion during CPB. In patients receiving catecholamines to treat a postoperative low cardiac output state, fenoldopam significantly improves renal function and prevents AKI and major morbidity.

Living without aprotinin: the results of a 5-year blood saving program in cardiac surgery.

BACKGROUND: After 20 years of regular use in cardiac surgery patients, aprotinin has recently been withdrawn from the market due to many concerns about its safety. For a number of reasons aprotinin has not been available in Italy since 1998. The present study presents an aprotinin-free treatment protocol applied at our institution during the last 5 years, and aims to verify the results of this protocol in terms of allogeneic blood product transfusions, postoperative blood loss and surgical re-exploration rate. METHODS: Retrospective study on 7988 consecutive patients who underwent cardiac surgery during the years 2003-2007. All the patients received specific hemostasis/coagulation management based on (a) routine use of tranexamic acid, (b) heparin dose-response monitoring, thromboelastography, platelet (PLT) function analysis in a select population of patients, and (c) use of fresh frozen plasma (FFP), PLTs, and desmopressin according to the hemostasis/coagulation profile. Data retrieved from the institutional database were quantity of packed red cells (PRCs), FFP, PLT transfusion rate, blood loss in the first 12 postoperative hours, and surgical re-exploration rate. RESULTS: PRCs were transfused in 40.4% of patients (with higher rates for selected high-risk subpopulations), FFP in 12.9% and PLTs in 2.6%. Surgical re-exploration rate was 3.7%. With respect to historical controls, a significant reduction of PRCs and FFP transfusions was obtained using closed circuits, point of care coagulation tests, and combination of the two. CONCLUSION: This aprotinin-free blood saving program is an effective strategy for allogeneic blood products transfusion containment.