Nicola Vitulano

Leukotrienes in Atherosclerosis: New Target Insights and Future Therapy Perspectives

Atherosclerosis represents an important chronic inflammatory process associated with several pathophysiological reactions in the vascular wall. The arachidonic acid, released by phospholipase A2, is an important substrate for the production of a group of lipid mediators known as leukotrienes, which induce proinflammatory signaling through the activation of specific BLT and CysLT receptors. The interaction of these substances in the vascular wall determines important morphological alterations like the early lipid retention and the accumulation of foam cells, the development of intimal hyperplasia, and advanced atherosclerotic lesions, and it plays an important role in the rupture of atherosclerotic plaque. Many studies regarding myocardial ischemia and reperfusion show that leukotriene signaling may be involved in the development of ischemic injury. For these, reasons both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested for inducing beneficial effects at different stages of the atherosclerosis process and may represent a new therapeutic target in the treatment of atherosclerotic vessel diseases, in particular in acute coronary syndrome.

Ivabradine: Beyond heart rate control

Chronic stable angina pectoris (CSAP) usually occurs in patients with coronary artery disease (CAD) that affects one or more large epicardial arteries. It results when myocardial perfusion is insufficient to meet cardiac metabolic demand. Elevated heart rate (HR) is an important factor in the development of myocardial ischemia and angina pectoris. The pharmacologic agents most commonly administered in the treatment of CSAP are β-blockers and calcium channel blockers (CCBs). However, the use of β-blockers is limited by poor compliance related to contraindications and comorbidities, especially in elderly patients. Ivabradine is a new selective HR-lowering agent that selectively inhibits the pacemaker current If in the sinus atrial node. In several randomized controlled trials, ivabradine 5–10 mg twice daily has demonstrated equivalent anti-ischemic and anti-anginal activity to β-blockers and CCBs, with a good safety and tolerability profile. Although ivabradine has been shown not to improve cardiac outcomes in patients with stable CAD and left ventricular systolic dysfunction, it may be used to reduce the incidence of CAD outcomes in a subgroup of patients with HR ≥70 bpm. The aim of this short review is to summarize the use of ivabradine in the treatment of CSAP, and its potential utility in atherosclerosis, primitive and dilatative cardiomyopathy, and arrhythmias, such as postural tachycardia syndrome and inappropriate sinus tachycardia, where exclusive lowering of elevated HR may prove beneficial.

Aliskiren, the First Approved Renin Inhibitor: Clinical Application and Safety in the Treatment of Hypertension

Hypertension is one of the most important risk factors for, and causes of, cardiovascular disease. The difficulty in achieving a normal blood pressure range in some patients makes the rate of cardiovascular disease high. For some years renin-angiotensin system inhibitors such as angiotensin-converting enzyme (ACE) and angiotensin receptor blockade have been objects of interest for treatment of cardiovascular disease. Aliskiren, the first approved renin inhibitor to reach the market, is a low molecular weight, orally active, hydrophilic nonpeptide molecule, which blocks angiotensin I generation. However it might also become a reasonable therapeutic choice in a broad number of clinical conditions, as stable coronary artery disease, cerebrovascular and cardiorenal disease, diabetes, and peripheral arterial disease. The aim of this review is to describe the effectiveness and safety of aliskerin in the treatment of hypertension.

Aliskiren: beyond blood pressure reduction

Importance of the field: Hypertension is one of the most important risk factors and causes of cardiovascular disease (CVD). From some years, renin-angiotensin-aldosterone system (RAAS) inhibitors such angiotensin converting enzyme (ACE) and angiotensin receptor blockade (ARB) have been of interest, not only for better blood pressure (BP) control but also for their involvement in the mechanisms of various organ functions. Areas covered in this review: The aim of this review is to focus on the effectiveness and safety of aliskiren beyond the treatment of hypertension. What the reader will gain: Aliskiren, the first approved renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks angiotensin I generation. Because of its mechanism of action, aliskiren may offer the additional opportunity to inhibit progression of atherosclerosis at tissue level and the potential to be useful in a wide spectrum of conditions. However, we will discuss how it might become a reasonable therapeutic choice also in a broad number of clinical conditions, sharing an increased cardiovascular risk as stable coronary artery disease (CAD), microvascular and cardio-renal disease, diabetes, and peripheral arterial disease (PAD). Take home message: Therapy of hypertension through a better blockade of RAAS may be the first step in also achieving interesting results in the complications that hypertension causes in several organs.

Technology update: intracardiac echocardiography – a review of the literature

The development of new imaging tools helps in better investigation of cardiac structures and function by showing detailed images during interventional procedures. Intracardiac echocardiography plays a pivotal role as an intraoperative real-time imaging tool during invasive cardiac procedures. Initially, this echocardiographic technique was particularly useful when transthoracic image quality was insufficient and to avoid general anesthesia for transesophageal imaging. Nowadays, intracardiac echocardiography is routinely used in several cardiac invasive laboratories to support several types of procedures, such as extraction and implantation of cardiac devices, electrophysiological mapping, ablation, and endomyocardial biopsies. This review gives an overview of the basic principles of intracardiac echocardiography and examines its applications in the different settings of invasive cardiology.

Inflammatory markers in heart failure: hype or hope?

Heart failure is a growing global epidemic that involves in its pathophysiology a proinflammatory state. Since the first description of elevated cytokine levels in this setting, there has been increasing interest in understanding the role of these molecules in left-ventricular remodeling and function. Over the years, intense research on the ‘cytokine theory’ of heart failure has allowed evaluation of the role of inflammatory biomarkers not only as pathogenetic mediators, but also as potential tools in the diagnosis and risk stratification of heart failure patients. Whereas current evidence does not support the use of inflammatory biomarkers for the diagnosis of heart failure, the assessment of their levels and the connection between their changes and changes in clinical status and prognosis has been well validated. At present, the utility of anti-inflammatory therapies in heart failure is still debated, since trials of anti-inflammatory agents in this setting have pointed out controversial results. On the contrary, established treatments of heart failure, including &bgr;-blockers, renin–angiotensin system antagonists, and aldosterone-receptor blockers seem able to act by modulating cytokine expression, suggesting a new role for these molecules in guiding heart failure therapy. Therefore, the binomial topic of heart failure and inflammation still has a number of fields not completely explored: our aim is to update current knowledge and future perspectives.

Ranolazine: Beyond the Treatment of Chronic Stable Angina Pectoris

The aims in the treatment of angina are relief of pain and prevention of disease progression through risk reduction. A number of patients may have contraindications or remain unrelieved from anginal discomfort with conventional drugs. Among newer alternatives, ranolazine indirectly prevents the intracellular calcium overload involved in cardiac ischemia and it is a considered as a valid addition to traditional treatments. Recent findings showed potential positive side effect of ranolazine in the treatment of arrhythmias. This review gives an overview of the basic principles of ranolazine in the treatment of myocardial ischemia and examines its applications in the new field of anti-arrhythmic effects.

Should every Patient with Heart Failure be Investigated for Sleep Apnea Syndrome

Should every Patient with Heart Failure be Investigated for Sleep Apnea Syndrome? The increasing interest in the field of sleep medicine during the whole twentieth century is principally due to the involvement of sleep-related disordered breathing (SDB) in cardiovascular disease. Disorders of a physiological phenomenon such as sleep lead to important changes in state of quiescence of the cardiovascular, respiratory and metabolic systems during the night. Consequences of SDB (microawakening, sleep fragmentation, hypoxemia) represent important harmful triggers on the cardiovascular system, above all in patients suffering by inability of the heart to provide an adequate output such as for heart failure (HF) patients. SDB and HF may be related to each other in a bidirectional way from epidemiologic and physiopathologic point of view.

Continuous positive airway pressure treatment in addition to optimal medical therapy for ventricular ectopy in a patient with heart failure and sleep-related breathing disorder

In this report we describe the case of a 56-year-old man with a medical history of onset of asthenia, palpitations and dyspnoea for mild efforts. After a negative ergometric test for myocardial ischaemia and 24-h Holter monitoring showing frequent ventricular premature beats, but an echocardiogram with significant dilation and dysfunction of the left ventricle, coronary angiography was performed and did not show haemodynamically significant stenosis. Regarding the anamnesis of snoring, daytime sleepiness and the relationship between sleep-related breathing disorder and cardiovascular disease, we performed a cardiorespiratory sleep study that indicated a diagnosis of sleep-related breathing disorder with prevalent obstructive apnoea. In addition to optimal medical therapy for cardiovascular disease, the patient began therapy with continuous positive airway pressure during the night. This showed a considerable decrease in ventricular premature beats (VPBs) during the night, a better control of ventricular ectopy during the day and a better compliance with medical therapy.

Collateral findings during computed tomography scan for atrial fibrillation ablation: Let’s take a look around

The growing number of atrial fibrillation catheter ablation procedures warranted the development of advanced cardiac mapping techniques, such as image integration between electroanatomical map and cardiac computed tomography. While scanning the chest before catheter ablation, it is frequent to detect cardiac and extracardiac collateral findings. Most collateral findings are promptly recognized as benign and do not require further attention. However, sometimes clinically relevant collateral findings are detected, which often warrant extra diagnostic examinations or even invasive procedure, and sometimes need to be followed-up over time. Even though reporting and further investigating collateral findings has not shown a clear survival benefit, almost all the working groups providing data on collateral findings reported some collateral findings eventually coming out to be malignancies, sometimes at an early stage. Therefore, there is currently no clear agreement about the right strategy to be followed.