Cristina Balla

Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin.

Cardiac resynchronization therapy (CRT) has been introduced to treat drug refractory chronic heart failure (CHF). Apelin, the endogenous ligand of the APJ receptor, is under evaluation for its potential role in human CHF pathophysiology. This study aims to assess whether biventricular pacing affects plasma apelin levels in patients with severe CHF.

Plasma osteopontin reveals left ventricular reverse remodelling following cardiac resynchronization therapy in heart failure

BACKGROUND Cardiac resynchronization therapy (CRT) promotes left ventricular (LV) reverse remodelling and affects myocardial collagen turnover in heart failure (HF) patients. Osteopontin (OPN) is a matrix glycoprotein required for the activation of fibroblasts upon TGF-β1 stimulation. In humans, plasma OPN and OPN-expressing lymphocytes correlate with the severity of HF. We sought to evaluate whether plasma OPN and TGF-β1 reflect LV reverse remodelling following CRT. METHODS Eighteen patients (12 men, mean age 65 ± 11 years) undergoing CRT were studied. Patients underwent baseline clinical and echocardiographic evaluation, and assessment of plasma OPN and TGF-β1. The evaluation was repeated 8.5 ± 4 months after device implantation. Eight healthy age- and sex-matched subjects served as controls. RESULTS In HF patients, baseline plasma OPN and TGF-β1 were higher as compared to control subjects (OPN: 99 ± 48 vs 59 ± 22 ng/ml; p<0.05; TGF-β1: 15.9 ± 8.0 vs 9.3 ± 5.6 ng/ml; p<0.05). At follow-up, 12 patients responded to CRT and showed LV reverse remodelling, whereas 6 did not. Plasma OPN decreased in CRT responders (108 ± 47 vs 84 ± 37 ng/ml; p=0.03) and increased in non-responders (79 ± 58 vs 115 ± 63 ng/ml; p<0.01). TGF-β1 showed a trend towards reduction in responders (17.5 ± 8.7 vs 10.2 ± 8.9 ng/ml; p=0.08) and was unchanged in non-responders. A significant correlation (r=-0.56; p=0.01) was found between relative changes of LVESV and plasma OPN. CONCLUSIONS CRT-induced LV reverse remodelling is reflected by changes in plasma OPN. Circulating OPN may represent a marker of LV dilation/impairment and an indicator of the response to HF therapies promoting LV reverse remodelling.

Nodo- and fasciculoventricular pathways: Electrophysiological features and a proposed diagnostic algorithm for preexcitation variants

Introduction Fasciculoventricular and nodoventricular pathways (FVP and NVP) are uncommon preexcitation variants that can be misleading during electrophysiology studies (EPSs), and differentiating them could be challenging. In this article, we describe 2 representative cases and then we present various electrophysiological features and phenomenon encountered in patients with these particular accessory pathways (APs).

Atrial Natriuretic Peptide Single Nucleotide Polymorphisms in Patients with Nonfamilial Structural Atrial Fibrillation

Background Atrial natriuretic peptide (ANP) has antihypertrophic and antifibrotic properties that are relevant to AF substrates. The -G664C and rs5065 ANP single nucleotide polymorphisms (SNP) have been described in association with clinical phenotypes, including hypertension and left ventricular hypertrophy. A recent study assessed the association of early AF and rs5065 SNPs in low-risk subjects. In a Caucasian population with moderate-to-high cardiovascular risk profile and structural AF, we conducted a case-control study to assess whether the ANP -G664C and rs5065 SNP associate with nonfamilial structural AF. Methods 168 patients with nonfamilial structural AF and 168 age- and sex-matched controls were recruited. The rs5065 and -G664C ANP SNPs were genotyped. Results The study population had a moderate-to-high cardiovascular risk profile with 86% having hypertension, 23% diabetes, 26% previous myocardial infarction, and 23% left ventricular systolic dysfunction. Patients with AF had greater left atrial diameter (44 ± 7 vs. 39 ± 5 mm; P < 0.001) and higher plasma NTproANP levels (6240 ± 5317 vs. 3649 ± 2946 pmol/mL; P < 0.01). Odds ratios (ORs) for rs5065 and -G664C gene variants were 1.1 (95% confidence interval [CI], 0.7-1.8; P = 0.71) and 1.2 (95% CI, 0.3-3.2; P = 0.79), respectively, indicating no association with AF. There were no differences in baseline clinical characteristics among carriers and noncarriers of the −664C and rs5065 minor allele variants. Conclusions We report lack of association between the rs5065 and -G664C ANP gene SNPs and AF in a Caucasian population of patients with structural AF. Further studies will clarify whether these or other ANP gene variants affect the risk of different subpheno-types of AF driven by distinct pathophysiological mechanisms.

The apelin/APJ system: From vascular biology to heart failure

Apelin, the endogenous ligand of the G protein-coupled APJ receptor, displays several activities on the cardiovascular system. Indeed, recent studies support the notion that the apelin/APJ system is involved in key mechanisms that are relevant to fluid homeostasis, blood pressure control and cardiac contractility. This paper reviews our current knowledge on the physiological properties and potential clinical significance of apelin and APJ receptor.

Angiotensin Receptor Antagonists to Prevent Sudden Death in Heart Failure: Does the Dose Matter?

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.

Negative concordance pattern in bipolar and unipolar recordings: An additional mapping criterion to localize the site of origin of focal ventricular arrhythmias.

BACKGROUND The relevance of the temporal relationship between a unipolar electrogram (UEGM) and a bipolar electrogram (BEGM) in determining the site of origin (SOO) of focal arrhythmias has been largely demonstrated. OBJECTIVE We sought to demonstrate that a negative concordance in the initial forces of these EGMs is also helpful in predicting the SOO of premature ventricular contractions (PVCs). METHODS Mapping and radiofrequency (RF) ablation were performed in 41 patients with symptomatic PVCs in the absence of structural heart disease. Simultaneous recordings of the minimally filtered (0.5-500 Hz) UEGM and filtered BEGM (30-500 Hz) were analyzed at 247 mapping sites, where RF was attempted. EGMs of 63 mechanically induced PVCs were separately analyzed as a validation group. All ablation sites had a QS pattern in the UEGM. Acute PVC suppression was defined as a complete disappearance of ventricular ectopic beats after a 60-second pulse of RF. RESULTS RF ablation obtained PVC suppression (RF+) in 33 of 247 sites (13.3%). A negative concordance pattern (NCP) during the initial 20 ms of both UEGM and BEGM was observed in 31 of 33 (94%) RF+ sites compared with 10 of 214 (4%)RF- sites (P < .0001). The NCP criterion demonstrated to be an additional powerful predictor of acute RF success with sensitivity, specificity, positive predictive value, and negative predictive value of 94%, 95%, 76%, and 99%, respectively. Similarly to RF+ sites, the NCP was observed in 60 of 63 sites (95.2%) in the mechanical PVC group. CONCLUSION An NCP in both UEGM and BEGM may be an additional criterion that helps to localize the SOO of focal ventricular arrhythmias.

Low-dose angiotensin receptor blockers as an alternative to ACE-inhibitors increase the risk of appropriate ICD interventions in heart failure

doi:10.1016/j.ijcard.2010.04.057 established that right ventricle provides powerful influential signals to the prognosis of the patients with systolic heart failure[3]. However, in the study by Monteiro et al., no information was provided concerning right heart chambers, failure of which is thought to be quite common in patients with advanced heart failure. Furthermore, it was previously shown that right ventricle could be the source of higher natriuretic peptides [4], as it was shown in the table of the current paper that higher CA-125 levels were associated with higher natriuretic peptides. Unfortunately, no information was present concerning pericardial effusion, where similar cellular source might be secreting the substance, either in the paper. We think right heart should not be omitted in this scenario, though, CA-125 was simply stratifying the risk. Because, there may be further risk categories. Since, mesothelial cells are thought to be the major source of CA-125 levels, it is not surprising to observe that failure of right heart could bring about increased serum levels up on further hemodynamic load on splanchnic bed, where there is abundance of these cells. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].

Extracellular matrix remodelling in myocardial hypertrophy and failure: focus on osteopontin

Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.

Ventricular tachycardia as the first manifestation of disease: An element with different clinical settings

Introduction Ventricular tachycardia is defined as an arrhythmia with a rate at least 100 bpm for three or more consecutive beats that originates below the His bundle in the conduction system, ventricular muscle or in combination of both tissues independently of atrial and atrioventricular nodal conduction. Ventricular tachycardia is described as monomorphic when a single QRS morphology indicates a stable sequence of depolarization while ventricular tachycardia is polymorphic if multiple sites of origin and a variable sequence of activation produce a continuous changing in the QRS morphology. If sustained ( 30 s) form, ventricular tachycardia may produce hemodynamic compromise or cardiac arrest. Even if nonsustained, it can be associated with invalidating symptoms and, if incessant, can lead to deterioration of cardiac function.