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Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment. [ABSTRACT FROM AUTHOR]

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment. [ABSTRACT FROM AUTHOR]

Cryptogenic strokes account for about 25% to 40% of total ischemic strokes, and 1 of the 3 of these have a patent foramen ovale (PFO). A meta-analysis concerning the effectiveness and safety of PFO closure in cryptogenic strokes or transient ischemic attacks (TIAs) was performed. We systematically searched Medline, Embase, and the Cochrane Library through April 2018. Eligible studies were randomized clinical trials. Primary and secondary end points were, respectively, stroke or TIA and stroke recurrences. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for all end points using fixed- and random-effects meta-analyses. Data were included from 6 trials involving 3560 patients. In the pooled analysis, PFO closure was superior to medical treatment for both primary (RR: 0.39; 95% CI: 0.18-0.82; P < .02) and secondary end points (RR: 0.58; 95% CI: 0.44-0.76; P < .001). Transcatheter closure significantly increased the risk of new-onset atrial fibrillation (AF; RR: 5.74; P < .001). Percutaneous closure is superior to medical treatment in reducing stroke and TIA recurrence, even if with a significant risk increasing for new-onset AF. These findings suggest that transcatheter closure is indicated in patients with cryptogenic strokes and large PFO. [ABSTRACT FROM AUTHOR]

Femtosecond pulsed laser deposition, carried out in high vacuum, leads the ablation of any target material, producing a plume of nano-drops which are deposited on a substrate as particles, preserving the parent material composition. The deposited nanoparticles (NPs) exhibit a characteristic disk-shape with a major diameter ranging from 5 nm up to 60 nm and a thickness ranging from 1 nm up to 10 nm. Also when the particles form a thick layer, they remain separated by an interface of free volume. This characteristic morphology of the deposited films gives an interplay of interparticle and intraparticle physical correlations which deeply differentiates their properties from those of similar nanogranular films deposited by other techniques. This investigation is focused on the influence of the novel structural conditions on the coupling between strain and magnetization, and/or strain and resistivity, in Co50 Fe50 NP films deposited on Kapton substrate. Due to the NP nature of the films, these couplings are substantially different from standard magnetostrictive and piezoresistive effects. Magnetization and resistivity versus applied strain were studied, thus evidencing novel elastoresistive and elastomagnetic functionalities and evaluating their relative sensitivities. The limits and potentiality for the application of the new NP magnetic films in microelectromechanical systems (MEMS) will be briefly discussed. [ABSTRACT FROM AUTHOR]

Aims: Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT). Methods: Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction ≥15% at 6 months. Results: All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 ± 4 mm vs 20 ± 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 ± 14 mmHg vs 27 ± 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 ± 6 cm2 vs 16 ± 3 cm2 P < 0.001), RV end-systolic area (RVESA 16 ± 6 cm2 vs 8 ± 2 cm2, P = 0.001), and RV fractional area change (30 ± 12% vs 48 ± 8%, P < 0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSE ≤14 mm and the population was stratified into two groups based on baseline TAPSE ≤ or > 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001). Conclusions: Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline. [ABSTRACT FROM AUTHOR]

Abstract: Background: Experimentally, vagal stimulation (VS) is protective in chronic heart failure (HF). In man, VS is used in refractory epilepsy but has never been used in cardiovascular diseases. Increased sympathetic and reduced vagal activity predict increased mortality in HF. Aims: This pilot study assessed feasibility and safety and tested possible efficacy of chronic VS in HF patients. Methods: We studied 8 patients (mean age 54 years). CardioFit (BioControl Medical), a VS implantable system delivering pulses synchronous with heart beats through a multiple contact bipolar cuff electrode, was used. VS was started 2–4 weeks after implant, slowly raising intensity; patients were followed 1, 3 and 6 months thereafter. Results: All procedures were successful: as sole surgical side effect, one patient had transient hoarseness. VS was well tolerated, with only mild side effects (cough and sensation of electrical stimulation). There was a significant improvement in NYHA class, Minnesota quality of life® (from 52±14 to 31±18, p <0.001), left ventricular end-systolic volume (from 208±71 to 190±83 ml, p =0.03), and a favourable trend toward reduction in end-diastolic volume. Conclusions: This novel approach to the treatment of patients with HF is feasible, and appears safe and tolerable. The preliminary efficacy results appear promising. These findings suggest the opportunity to proceed with a larger multicentre study. [Copyright &y& Elsevier]

Abstract: Background: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective I f current inhibitor) in advanced HF patients. Aims: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function. Methods and results: Ten NYHA class III patients (50±12 years, LV ejection fraction 21±7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90′, followed by 0.05–0.075 mg/kg in the subsequent 90′. Baseline HR was 93±8 bpm, cardiac index (CI) 2.2±0.6 l/min⁎m2; LV stroke volume 44±11 ml and systolic work 39±13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68±9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66±17 ml) and 53% (to 58±20 g) at 4 h. No serious adverse events occurred. Conclusion: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the rate of return to work after transplantation and its determinants in a clinically-stable population of patients transplanted and followed-up at a single institution in Italy. Methods: 151 thoracic organ transplant recipients (72 lung, 79 heart) were examined. Patients were asked about daily activities, level of education, employment and clinical condition. A six-minute walking test was performed with measurement of dyspnoea using the Borg scale. Quality of Life was evaluated with the SF-36 and GHQ questionnaires. Results: Before transplantation 131 patients (87%), (70 heart and 61 lung) worked. After transplantation, 51 patients (39%) went back to work and 3 more started working. We found that younger age, a better quality of life (mainly in the mental domain), having had an occupation previously (particularly as an entrepreneur/freelancer), and having been off work for less than 24 months, were independent predictors of return to work. Conclusions: Considering their good, objective and subjective, functional status, some patients who could have returned to work, chose not to. Identifying factors which affect return to work might help health professionals to adopt the best course of treatment and psychological support in order to fulfil this goal; however, return to work should not be considered as the only expression of a patient''s real psychophysical condition. [Copyright &y& Elsevier]

Abstract: Background: Patients with AL amyloidosis often present with signs of congestive heart failure. Aim: This study was prospectively designed to assess the significance of RV dysfunction in AL amyloidosis. Methods and results: Seventy-four patients with biopsy proven AL amyloidosis underwent a thorough echocardiographic evaluation. A tricuspid annular plane systolic excursion (TAPSE) <17 mm was taken as marker of RV dysfunction. Plasma NT-proBNP determinations were performed in all cases. RV function was normal in 60 patients and reduced in 14 patients. Patients with RV dysfunction had thicker left ventricular (LV) walls (p <0.01), lower LV end-diastolic volumes (p <0.01), lower LV ejection fraction (p <0.01) and more frequently a restrictive LV filling pattern (p <0.01). RV dimensions and RV free wall thickness were not significantly different in the two groups. A thick interventricular septum and a reduced TAPSE were associated with high NT-proBNP levels (both p <0.01). Seven patients died during a median follow-up period of 19 months; TAPSE <17 mm was the only echocardiographic parameter associated with poor survival. Conclusion: In patients with AL amyloidosis, RV dysfunction is associated with more severe involvement of the left ventricle, higher plasma levels of NT-proBNP and with poor prognosis. [Copyright &y& Elsevier]

Background. Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. Aims: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. Methods and results: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and αB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon–intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. Conclusions: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical. [Copyright &y& Elsevier]

Aims The study aimed at evaluating the prevalence of interventricular and intraventricular contractile dyssynchrony in heart failure patients with either normal or prolonged QRS duration. [ABSTRACT FROM PUBLISHER]

Aims To investigate celiac disease (CD) and related co-morbidity in patients with familial and sporadic cardiomyopathy and in their relatives.Methods and results We screened anti-human-tissue-transglutaminase (IgA and IgG anti-h-tTG) and anti-endomysial antibodies (AEAs) in 238 consecutive adult patients with inherited or sporadic dilated cardiomyopathy (DCM), 418 relatives, and 2000 healthy blood donors. HLADQ2-DQ8 was tested in tTG-positive subjects. The IgA-tTG-positive patients with cardiomyopathy underwent duodenal biopsy. Twenty-six subjects were tTG-positive: five DCM patients (2.1%), two of 28 (7.1%) and three of 390 (0.7%) relatives with and without echocardiographic abnormalities respectively, and 16 controls (0.8%). Twenty-two of 26 subjects were AEA-positive, and 25 HLA-positive. Of the five patients with cardiomyopathy and biopsy-proven CD, four suffered iron-deficiency anaemia. Two CD-positive DCM patients and two tTG-positive relatives were from families with inherited disease in which CD did not co-segregate with DCM.Conclusions The higher prevalence of CD in patients with sporadic or inherited DCM, and of tTG-positive serology in relatives with echocardiographic abnormalities, suggests that immune-mediated mechanisms are active in subsets of patients/families. However, gluten intolerance cannot be considered causative since CD seems to be associated but not co-segregated with DCM in familial cases. [ABSTRACT FROM PUBLISHER]

Background: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic betablocker therapy. Methods: We studied 26 patients (21 males and five females) with a mean age of 58 ± 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. Results: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. Conclusions: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) mutations have been causally linked with cardiomyopathies, both dilated (DCM) and hypertrophic. We identified the T12297C mutation in the mtDNA-tRNA[sup Leu(CUN)] of a 36-year-old male patient diagnosed with DCM. The mutation was heteroplasmic, with high amount (88%) of mutant DNA in the myocardium, and was absent in normal (n=120) and disease (n=150) controls. It affects a highly conserved nucleotide (adjacent to the anticodon triplet) that allows the phospho-ribose backbone to turn and form the loop. The potential pathological role of T12297C mutation is further supported by its recent identification in another unrelated Italian family with DCM associated with endocardial fibroelastosis. In the variable loop of the same tRNA, our patient also carried the A12308G transition that is debated as pathological mutation or neutral polymorphism in progressive external ophthalmoplegia: the two defects could exert a synergistic effect on the tRNA structure and function. The endomyocardial biopsy study showed abnormal ring-like mitochondria and occasional cytochrome c oxydase negative myocytes. Overall, the heteroplasmy, the highly conserved position of the mutated nucleotide, the absence of the mutation in large series of diseased and normal controls, and the cardiac mitochondrial changes support a causative link of the mutation with the disease. [ABSTRACT FROM AUTHOR]

Donor-to-Recipient Decremental Conduction of AK We describe the unique case of a heart transplant patient with type I atrial fibrillation that arose in the donor atrium during a late acute rejection episode and conducted to the recipient atrium with second-degree type I local block. After internal cardio-version, programmed stimulation showed bidirectional decremental conduction across the suture line with nearly equal atrioatrial interval, whereas the recipient atrium showed progressively delayed intra-atrial conduction. These findings strongly suggest that the mechanism of atrioatrial conduction may he electrical propagation along viable myocardium bridging the surgical scar and that the electrophysiologic characteristics of the recipient atrium are involved in decremental conduction across the suture line. [ABSTRACT FROM AUTHOR]

A case of endomyocardial fibrosis in a patient with idiopathic hypereosinophilic syndrome is reported and discussed. The authors draw attention to the importance of both echocardiography (two-dimensional and Doppler) and nuclear magnetic resonance in the detection of cardiac involvement due to this rare pathology. Moreover, these imaging techniques appear to be valuable in the evaluation of effects of medical treatment. Therapy with corticosteroids alone has shown no reliable effectiveness in reducing the absolute eosinophil count. A combined immunosuppressive treatment with use of hydroxyurea is required. [ABSTRACT FROM AUTHOR]

A response by Carmelo Libetta, Vincenzo Sepe, Manuela Zucchi et al to a letter to the editor about their article on intermittent haemodiafiltration in refractory congestive heart failure is presented.

A letter to the editor is presented in response to the article "Standard Hemodiafiltration Improves Diuretic Responsiveness in Advanced Congestive Heart Failure," by Carmelo Libetta, Vincenzo Sepe, Manuela Zucchi, Carlo Campana, and Antonio Dal Canton in the December 15, 2005 issue.