Right ventricular dysfunction in chronic heart failure: clinical laboratory and echocardiographic characteristics. (the RIVED-CHF registry).

BACKGROUND: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated. METHODS: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study. RESULTS: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact. CONCLUSIONS: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321).

Usefulness of Combined Ultrasound Assessment of E/e' Ratio, Pulmonary Pressure, and Cava Vein Status in Patients With Acute Heart Failure.

Congestion is poorly investigated by ultrasound scans during acute heart failure (AHF) and systematic studies evaluating ultrasound indexes of cardiac pulmonary and systemic congestion during early hospital admission are lacking. We aimed to investigate the prevalence of ultrasound cardiac pulmonary and systemic congestion in a consecutive cohort of hospitalized patients with AHF, analyzing the relevance of each ultrasound congestion component (cardiac, pulmonary, and systemic) in predicting the risk of death and rehospitalization. This is a prospective research study of a single center that evaluates patients with an AHF diagnosis who are divided according to the left ventricular ejection fraction in patients with heart failure with preserved ejection fraction or reduced ejection fraction. We performed a complete bedside echocardiography and lung ultrasound analyses within the first 24 hours of hospital admission. The ultrasound congestion score was preliminarily established by measuring the following parameters: cardiac congestion, which was defined as the contemporary presence of E/e' >15 and pulmonary systolic pressure >35 mm Hg and the pulmonary congestion, defined as the total B-line number >25 at the lung ultrasound performed in 8 chest sites; moreover, the systemic congestion was defined if the inferior vena cava (IVC) was >21 mm and if it was associated with a reduced inspiratory collapse >50%. We thoroughly assessed 230 patients and evaluated their results. Of these patients, 135 had heart failure with reduced ejection fraction and there were 95 patients with heart failure with preserved ejection fraction; 122 patients experienced adverse events during the 180-day follow-up. The receiver operating characteristic curve analysis showed that the tricuspid annular peak systolic excursion (TAPSE) (area under the curve [AUC] 0.34 [0.26 to 0.41], p <0.001), E/e' (AUC 0.62 [0.54 to 0.69], p = 0.003), and IVC (AUC 0.70 [0.63 to 0.77], p <0.001) were all significantly related to poor prognosis detection. The univariate Cox regression analysis revealed that cardiac congestion in terms of E/e' and pulmonary systolic pressure (hazard ratio [HR] 1.49 [1.02 to 2.17], p = 0.037), TAPSE (HR 0.90 [0.85 to 0.94], p <0.001), and systemic congestion (HR 2.64 [1.53 to 4.56], p <0.001) were all significantly related to the 180-day outcome. After adjustment for potential confounders, only TAPSE (HR 0.92 [0.88 to 0.98], p = 0.005) and IVC (HR 1.92 [1.07 to 3.46], p = 0.029) confirmed their prognostic role. The multivariable analysis of multiple congestion levels in terms of systemic plus cardiac (HR 1.54 [1.05 to 2.25], p = 0.03), systemic plus pulmonary (HR 2.26 [1.47 to 3.47], p <0.001), and all 3 congestion features (HR 1.53 [1.06 to 2.23], p = 0.02) revealed an incremental prognostic role for each additional determinant. In conclusion, among the ultrasound indexes of congestion, IVC and TAPSE are related to adverse prognosis, and the addition of pulmonary and cardiac congestion indexes increases the risk prediction accuracy. Our data confirmed that right ventricular dysfunction and systemic congestion are the most powerful predictive factors in AHF.

Aortic banding and endovascular aneurysm repair in a case of juxtarenal aortic aneurysm with unsuitable infrarenal neck.

The proximal aortic neck is one of the limiting factors for endovascular aneurysm repair (EVAR) and represents a crucial factor for success or failure of the procedure. In contrast to open surgery, where a clamp can be placed suprarenally but the repair performed infrarenally, EVAR requires a good infrarenal neck for durable fixation and seal. In a high-risk surgical 79-year-old patient with juxtarenal aortic aneurysm with unsuitable infrarenal neck, a hybrid procedure was chosen: juxtarenal aortic banding and EVAR. The banding allowed a successful EVAR by reshaping the juxtarenal aneurysmal aortic segment, hence converting a previously untreatable anatomy into a treatable one.

Protein S-100B as biochemical marker of brain ischemic damage after treatment of carotid stenosis.

BACKGROUND: S-100 protein is a family of low molecular weight proteins found in vertebrates characterized by two calcium binding sites of the helix-loop-helix ("EF-hand type") conformation. There are at least 21 different types of S-100 proteins. The name is derived from the fact that the protein is 100% soluble in ammonium sulfate at neutral pH. Protein S-100B was investigated as a marker of brain ischemic damage after treatment of carotid stenoses. METHODS: Between December 1, 2009 and December 1, 2010, S-100B protein was monitored in 76 patients after carotid artery stenting (CAS) and in 24 patients after carotid endarterectomy (CEA). In each patient, multiple samples were taken: before the procedure (basal sample), immediately after CAS or CEA, 60 minutes after CAS or CEA, and daily during the hospital stay. Evaluation of S-100B was carried out by blind assessment. Patients underwent pre- and postoperative diffusion-weighted magnetic resonance imaging or computed tomographic scan. RESULTS: An S-100B coefficient of variation higher than the established cut-off was detected in 16 patients: three affected by postoperative stroke, two patients with minor stroke, and one patient with fatal stroke; 12 patients presented with uneventful neurological outcome and positive brain imaging; and there was one false positive case. No false negative cases occurred. The postoperative protein S-100B level lowered to basal level in 15 patients: within 24 hours in the 12 patients with the uneventful outcome (and positive brain imaging) and in the false positive case; and after 120 and 144 hours, respectively, in the two patients with minor stroke. In the patient with fatal stroke, protein S-100B never returned to the preoperative level. CONCLUSIONS: In patients with an increased S-100B coefficient of variation, the diffusion-weighted magnetic resonance imaging was positive for ischemic brain lesions, except for one patient who was reported as a false positive case. The postoperative S-100B protein level decreased within 24 hours in the uneventful neurological cases and in the false positive case, whereas long-lasting postoperative increased values of the S-100B protein were observed in patients with poor neurological outcomes.

Detection of familial hypercholesterolemia in a cohort of children with hypercholesterolemia: results of a family and DNA-based screening.

The diagnosis of familial hypercholesterolemia (FH) in unselected children is difficult due to the frequent overlap of cholesterol values in affected and non-affected and the paucity of physical signs. Nevertheless, detection and treatment of FH in childhood has been advocated to prevent atherosclerosis in these patients. Here, we report the results of a screening program in a cohort of 157 unrelated, hypercholesterolemic (HC) children (age range 2-15 years; mean 8.3+/-3.4 years) carried out by a combination of family study and molecular analysis of the LDLR gene. On the basis of the familial phenotype, 27 (17.2%) were classified as probable FH and 49 (31.2%) as affected by FCHL. Among probable FH children, 14 (51.8%) carried mutant LDLR alleles, giving an overall 8.9% prevalence of FH. Most of LDLR variants were already reported, but three new mutations G266C, T368M, and D451Y were identified. Beside increased TC and LDL-C (p<0.001), FH children showed decreased HDL-C (p<0.05) and higher prevalence of family history of CAD when compared to non-FH children. None presented tendon xanthomas. We estimated that LDL-C >3.9 mmol/L was the best cut off value for diagnosing FH in these children, showing 79% sensitivity and 71.0% specificity. We propose the use of a LDL-C cut off level associated with a family study to identify FH among HC children.

Early increase of oxidative stress and soluble CD40L in children with hypercholesterolemia.

OBJECTIVES: The aim of the study was to analyze the behavior of oxidative stress and its interplay with CD40L, a protein that is implicated in atherosclerosis, in hypercholesterolemic children. BACKGROUND: Oxidative stress has been suggested to play a major role in premature atherosclerosis. METHODS: Forty-one children with hypercholesterolemia (mean age 9.28 +/- 0.5 years) and 40 children with normocholesterolemia (mean age 9.02 +/- 0.69 years) were matched for gender and age. Within each group, children were classified as having or not having a family history of cardiovascular disease. Serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, and plasma levels of soluble CD40L (sCD40L) were measured in each child. In a subgroup of children with high (n = 8) or normal (n = 8) levels of serum cholesterol, platelet p38 mitogen-activated protein (MAP) kinase phosphorylation, a protein involved in the activation of nicotinamide adenine dinucleotide phosphate oxidase, was determined. RESULTS: Children with hypercholesterolemia had higher values of 8-OHdG and sCD40L compared with control subjects (0.55 +/- 0.06 ng/ml vs. 0.21 +/- 0.02 ng/ml, p < 0.001 and 0.55 +/- 0.04 ng/ml vs. 0.19 +/- 0.03 ng/ml, p < 0.001, respectively). A significant correlation between 8-OHdG and sCD40L was observed in children with high (r = 0.676, p < 0.001) or normal (r = 0.878, p < 0.001) levels of cholesterol. Children with a family history of cardiovascular disease tended to have higher values of 8-OHdG and sCD40L, but the difference was not significant. Analysis of platelet p38 MAP kinase showed that it was phosphorylated more in children with hypercholesterolemia compared with control subjects (36.8 +/- 5.8 AU vs. 8.0 +/- 4.5 AU, p < 0.001 respectively). CONCLUSIONS: Children with hypercholesterolemia have an early increase of oxidative stress that may be responsible for up-regulation of CD40L and potentially predispose to premature atherosclerosis.

Effect of dietary supplementation with glucomannan on plasma total cholesterol and low density lipoprotein cholesterol in hypercholesterolemic children.

AIM: This paper evaluates the effect of the adjunct of the hydrosoluble fiber glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children, during a randomized controlled trial, to reduce plasma cholesterol. METHODS: All the subjects recruited underwent an 8-week run in diet period; a Step-One-Diet was prescribed. After that, they were randomly allocated to one of two groups: Step-One-Diet only (control), and Step-One-Diet plus glucomannan in gelatine capsules. After another 8 weeks of treatment, the results were compared within and between the two groups. RESULTS: Glucomannan treated group showed decreased values in plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) vs. control group after 8 weeks of treatment. The percentage decrease showed a statistically significant difference between sex groups. Decreases were observed in favor of female vs. male children in TC (24% vs. 9%) and LDL-C (30% vs. 9%). CONCLUSIONS: These results suggest that glucomannan may represent a rationale adjunct to diet therapy in primary prevention in high risk hypercholesterolemic children.