Paolo Ferrero

Prognostic scores in heart failure — Critical appraisal and practical use

Survival in patients with heart failure in the last two decades has significantly improved, owing to availability of new drugs, devices, and technologies. However, these new therapeutic tools are often costly and not without attendant risks. Thus, accurate and reproducible risk stratification is required to assess appropriateness of therapy. Although a growing body of evidence has characterized various predictors of poor outcomes, the application of comprehensive prognostic models in clinical practice remains limited. Herein, we critically evaluate the utility of prognostic scores in heart failure, discussing the strategies to select the most efficient and appropriate risk estimator in the individual patient.

Selective-site pacing in paediatric patients: a new application of the Select Secure system

AIMSnThe aim of this study was to evaluate the feasibility and reliability of selective-site pacing by means of a new lead system in a paediatric population. This lead system is composed of a 4.1 Fr, active-fixation lead and a steerable catheter that allows easy positioning in selective sites.nnnMETHODS AND RESULTSnThirty young patients (mean age 9.0 +/- 4.5 years, range 2-16 years) received a single- (10) or dual- (20) chamber pacemaker. The 3830 lead was implanted successfully in the targeted chambers in all patients. The selective RV sites of pacing in 26 of the patients were: 18 mid-septum, 5 outflow tract, 1 low-septum, and 2 LEVO-RV-Apex. In all patients, an intracardiac loop was left in order to avoid stretching of the lead with growth. Mean follow-up duration was 11 +/- 10 months. Atrial sensing and pacing thresholds were 3.2 +/- 1.7 mV and 0.8 +/- 0.6 V at 0.5 ms at implantation and 3.4 +/- 2.1 mV and 0.6 +/- 0.3 V at 0.5 ms at follow-up. Ventricular sensing and pacing thresholds were 12.1 +/- 4.9 and 0.7 +/- 0.4 V at 0.5 ms on implantation and 12.7 +/- 6.1 mV and 0.8 +/- 0.5 V at 0.5 ms at follow-up (P = NS). No adverse events were reported.nnnCONCLUSIONnSelect Secure is a promising system for selective-site pacing in children.

Novel approaches to the post-myocardial infarction/heart failure neural remodeling

The review aims to discuss the role of nerve growth factor (NGF) as a potential novel biomarker in post-myocardial infarction (MI) and in heart failure (HF), with a specific focus on neural remodeling and sprouting processes occurring after tissue damage. Many experimental data show that MI induces nerve sprouting, leading to increased sympathetic outflow and higher risk of ventricular arrhythmias and sudden cardiac death. In this framework, cardiac and circulating NGF might be an indicator of the innervation process and neural remodeling: it dramatically increases after MI, while it declines along with advanced HF and ventricular dysfunction. The bimodal behavior of NGF in acute and chronic settings leads to the speculation that NGF modulation may be a pharmacological target for intervention in different stages of the ischemic heart disease. Specifically, a fascinating possibility is to support or to inhibit NGF receptors, in order to prevent negative cardiac remodeling after MI and consequent ventricular dysfunction.

Curative ablation in a 12-month-old baby with severe ventricular systolic dysfunction and incessant ventricular tachycardia

Cardiomyopathies in the paediatric population portend a poor prognosis being characterized by a particularly accelerated and therapy refractory clinical course.1,2 Recognition and effective treatment of potential secondary causes may play a crucial role, leading to recovery in a not negligible proportion of cases. Left-ventricular dysfunction associated with wide QRS tachycardia is a quite common presentation, depicting two possible clinical pictures: ventricular tachycardia complicating idiopathic cardiomyopathy and primary tachycardiomyopathy. The distinction between the two might be pivotal, particularly in the paediatric population since, recognition of a tachycardiomyopathy must prompt an aggressive rhythm control. In this context, the role of the conduction system is being recognized in many incessant tachycardias with or without an underlying structural heart disease.3,4 The two most clinically relevant scenarios are fascicular tachycardia and junctional ectopic tachycardia (JET).5 The former is usually sustained by a reentry within a diseased Purkinjie network or involving the surrounding ventricular myocardium. The latter is thought to be caused by abnormal automaticity within the atrioventricular junction, and thus usually display a narrow QRS. Although JET is more frequently associated with a known structural injury such as myocarditis or post-operative status, still it should be kept in mind in the differential diagnosis, since isolated-idiopathic cases have been described as well.6 These arrhythmias, when displaying an incessant course may be responsible for systolic impairment, independent of their specific individual prognosis.7 We are describing a case of a 12-month-old baby that presented with a severe systolic dysfunction and almost incessant wide QRS tachycardia causing rapidly worsening heart failure despite full medical therapy. The arrhythmia was finally diagnosed as idiopathic left-ventricular fascicular tachycardia (ILVT) at the invasive electrophysiologic study, and transcatheter ablation through transseptal route was performed. The procedure turned out to be effective both in eliminating the …

Ranolazine in Heart Failure With Preserved Left Ventricular Ejection Fraction and Microvascular Dysfunction: Case Report and Literature Review

Heart failure with a normal or nearly preserved left ventricular (LV) ejection fraction (HFpEF) may represent more than 50% of heart failure cases. Despite HFpEF is being increasingly recognized, there is still a lack of information regarding of its potential pharmacological treatment. Patients with HFpEF are more frequently elderly, female, hypertensive and diabetic. Microvascular dysfunction (MVD) may be involved during the development of HFpEF mainly because of comobidities including hypertension and diabetes. Diastolic dysfunction is seen in 30–70% of patients with type 2 diabetes: the likely mechanisms include altered endothelial function, defective energy metabolism, and microvascular disease. MVD is also estimated to be more common in women. Women with angina, evidence of ischemia by stress testing, and no obstructive coronary artery disease (CAD) by angiography frequently have MVD which carries an adverse prognosis for cardiovascular events including myocardial infarction, stroke, heart failure, and sudden cardiac death. There are an estimated 2–3 million women in the United States with MVD: in this patient population persistent angina, despite treatment with nitrates, beta‐ blockers, and calcium channel blockers, remains a therapeutic challenge. MVD and myocardial ischemia are known to be associated with reduced adenosine triphosphate fluxes and decreased energy supply, resulting in disturbances of intracellular ion homeostasis of cardiac myocites. Disruption of this electrolyte balance leads to abnormally elevated intracellular levels of sodium and calcium, which are thought to contribute to the discrepancy between myocardial oxygen demand and supply. The increase of intracellular sodium concentrations is mediated by either late activation or failing channel closure of the inward sodium current (INa), which mainly happen in pathological states, such as ischemia, oxidative stress, myocardial stretch, and left ventricular hypertrophy. Previous studies demonstrated that the increase of sodium current is mainly associated to a reduced net cytosolic calcium efflux, leading to higher degree of diastolic stiffness, diastolic coronary vascular compression and, consequently, diastolic dysfunction. Ranolazine reduces the sodium‐dependent calcium overload via inhibition of the late INa and thus improves diastolic tone and oxygen handling during myocardial ischemia. This molecular mechanism is associated to a symptomatic relief of chronic angina without affecting heart rate or systolic blood pressure, therefore ranolazine has been widely used for ischemic patients not only as an add‐on therapy. New experimental studies in mouse models documented a potential role of ranolazine in reversing diastolic dysfunction oxidative stress‐mediated, showing a direct effect on myofilaments and contractile apparatus. So far, no data have been published on the influence of ranolazine in HFpEF and MVD. In this case report, we describe the beneficial effect of ranolazine in an ischemic HFpEF patient symptomatic for dyspnea. The Journal of Clinical Pharmacology 53(6) 665–669

Beneficial effects of adaptive servo-ventilation on natriuretic peptides and diastolic function in acute heart failure patients with preserved ejection fraction and sleep-disordered breathing

PurposeAdaptive servo-ventilation (ASV) is a ventilator algorithm able to correct breathing through anticyclic support of breathing in patients with central sleep apnea (CSA). So far, very few data exist regarding the role of ASV on acute heart failure with preserved ejection fraction (HFpEF).MethodsWe performed a single-center prospective, randomized, case-control study in consecutive acute HFpEF (left ventricle ejection fraction, LVEF ≥u200945%) patients with sleep-disordered breathing (SDB, apnea–hypopnea index, AHI >u200915/h) and prevalence of CSA.ResultsWe included ten consecutive patients randomized for ASV on top of standard therapy for acute heart failure (group 1) versus standard care alone (group 2). ASV therapy significantly reduced AHI and CSA. An improvement in cardiac diastolic function was seen in group 1 compared to group 2 (E/E’ 17.5 to 9.6, pu2009<u20090.02 vs 18.5 to 14.5, pu2009=u20090.4). Brain natriuretic peptide (BNP) markedly decreased in cases, but not in controls (298 to 84xa0pg/ml, pu2009<u20090.02 vs 280 to 120xa0pg/ml, pu2009=u20090.06). Right ventricle (RV) function significantly improved in group 1, differently from group 2.ConclusionsAn acute use of ASV seems effective in reducing BNP and improving diastolic and RV function in acute HFpEF patients with SDB and CSA, compared to standard treatment.

Exercise Hemodynamic and Functional Capacity After Mitral Valve Replacement in Patients With Ischemic Mitral Regurgitation: A Comparison of Mechanical Versus Biological Prostheses

Background: In patients with ischemic mitral regurgitation requiring mitral valve replacement (MVR), the choice of the prosthesis type is crucial. The exercise hemodynamic and functional capacity performance in patients with contemporary prostheses have never been investigated. To compare exercise hemodynamic and functional capacity between biological (MVRb) and mechanical (MVRm) prostheses. Methods and Results: We analyzed 86 consecutive patients with ischemic mitral regurgitation who underwent MVRb (n=41) or MVRm (n=45) and coronary artery bypass grafting. All patients underwent preoperative resting echocardiography and 6-minute walking test. At follow-up, exercise stress echocardiography was performed, and the 6-minute walking test was repeated. Resting and exercise indexed effective orifice areas of MVRm were larger when compared with MVRb (resting: 1.30±0.2 versus 1.19±0.3 cm2/m2; P=0.03; exercise: 1.57±0.2 versus 1.18±0.3 cm2/m2; P=0.0001). The MVRm had lower exercise systolic pulmonary arterial pressure at follow-up compared with MVRb (41±5 versus 59±7 mmu2009Hg; P=0.0001). Six-minute walking test distance was improved in the MVRm (pre-operative: 242±43, post-operative: 290±50 m; P=0.001), whereas it remained similar in the MVRb (pre-operative: 250±40, post-operative: 220±44 m; P=0.13). In multivariable analysis, type of prosthesis, exercise indexed effective orifice area, and systolic pulmonary arterial pressure were joint predictors of change in 6-minute walking test (ie, difference between baseline and follow-up). Conclusions: In patients with ischemic mitral regurgitation, bioprostheses are associated with worse hemodynamic performance and reduced functional capacity, when compared with MVRm. Randomized studies with longer follow-up including quality of life and survival data are required to confirm these results.

Leadless pacemaker implantation in a patient with complex congenital heart disease and limited vascular access

Management of rhythm related issues might be particularly challenging in patients with congenital heart disease due to complex anatomy and restricted vascular access. The leadless technology appears a suitable and attractive alternative for this population. We describe a patient with single ventricle physiology who successfully underwent implantation of a leadless pacemaker.