Prevention of thromboembolism after a fracture: is aspirin enough?

Venous thromboembolism (VTE) is a serious complication that can arise during and after hospitalization, particularly following surgery under general anaesthesia. Particularly at risk are major orthopaedic surgical procedures such as elective knee or hip replacement and the treatment of hip fractures. In these patients, current guidelines recommend (low or low-moderate level of evidence) aspirin as a possible alternative to anticoagulant therapy for the prophylaxis of long-term venous thromboembolism after an initial period with anticoagulant drugs. Several randomized trials and meta-analyses demonstrate no significant differences in the risk of VTE when comparing aspirin with anticoagulants. However, it must be considered that most recommendations are based on elective orthopaedic surgery and that trials after fractures have excluded patients at high thrombotic risk. Consequently, the overall incidence of major clinical events (death and pulmonary embolism) was ∼1% with wide confidence margins in even large non-inferiority studies. The incidence of asymptomatic VTE, especially distal, appears to be higher with aspirin. Patient preference and lower costs could play an important role in the choice in favour of aspirin.

The point on the electronic cigarette more than 10 years after its introduction.

Electronic cigarettes (e-cigarettes) are battery-powered devices containing a liquid based on propylene glycol or vegetable glycerin, compounds which, when vaporized, act as a vehicle for nicotine, flavours, and other chemical components. These devices have been marketed without clear evidence of risks, long-term safety, and efficacy as a means of traditional smoking cessation. Recent clinical studies have shown how the use of the e-cigarette, combined with adequate psychological support, can be effective in reducing traditional smoking but not nicotine addiction. However, meta-analyses of observational studies have not confirmed this efficacy. Several studies have also highlighted an increase in sympathetic tone, vascular stiffness, and endothelial dysfunction, all factors associated with an increased cardiovascular risk. Clinicians, therefore, should carefully monitor the possible risks to public health deriving from the use of e-cigarettes and should discourage non-smokers and adolescents from using such devices. Finally, particular attention should be paid to smokers so that the combined use of electronic and traditional cigarettes can be limited as much as possible.

Real-Life Indications to Sacubitril/Valsartan Treatment in Patients With Chronic Systolic Heart Failure.

OBJECTIVE: International guidelines recommend the introduction of sacubitril/valsartan (Entresto) in patients with heart failure (HF) and reduced ejection fraction (EF), who remain symptomatic, despite optimal uptitrated therapy. The purpose of the following analysis is to verify the real-life eligibility for sacubitril/valsartan in a population of patients suffering from chronic HF, regularly monitored in a single HF clinic and treated according to guideline-directed medical therapy (GDMT). METHODS: From a total of 1070 patients regularly monitored in our HF Clinic between January 2011 and September 2017, the clinical records of 224 patients with HF and reduced EF on optimized GDMT were retrospectively analyzed. RESULTS: Of 224 analyzed patients, 75 improved their EF or were asymptomatic after uptitration of GDMT during follow-up; 50 were not on angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for different reasons; 13 patients had systolic blood pressure ≤100 mm Hg, so they were not eligible for sacubitril/valsartan introduction. The remaining patients were still symptomatic (NYHA ≥2), and therefore, sacubitril/valsartan introduction was indicated in these 86 patients (38.4%) of 224 enrolled. CONCLUSION: In patients with HF and reduced EF, where GDMT is appropriately achieved, indication to sacubitril/valsartan treatment is around 38%.

Pathophysiological Mechanisms and Correlates of Therapeutic Pharmacological Interventions in Essential Arterial Hypertension.

Treating arterial hypertension (HT) remains a hard task. The hypertensive patient is often a subject with several comorbidities and metabolic abnormalities. Clinicians everyday have to choose the right drug for the single patient among the different classes of antihypertensives. Apart from lowering blood pressure, a main therapeutic target should be that of counteracting all the possible pathophysiological mechanisms involved in HT itself and in existing/potential comorbidities. All the ancillary positive and negative effects of the administered drugs should be considered: in particular, since hypertensive patients are often glucose intolerant/diabetic, carrier of serum lipids disorder, have already developed atherosclerotic diseases and endothelial dysfunction, they should not be treated with drugs negatively interfering with these conditions but with molecules that, if possible, improve them. The main pathophysiological mechanisms and correlates of therapeutic pharmacological interventions in essential HT are reviewed here.

Current experimental and early investigational agents for cardiac fibrosis: where are we at?

INTRODUCTION: Myocardial fibrosis (MF) is induced by factors activating pro-fibrotic pathways such as acute and prolonged inflammation, myocardial ischemic events, hypertension, aging process, and genetically-linked cardiomyopathies. Dynamics and characteristics of myocardial fibrosis development are very different. The broad range of myocardial fibrosis presentations suggests the presence of multiple potential targets. AREA COVERED: Heart failure treatment involves medications primarily aimed at counteracting neurohormonal activation. While these drugs have demonstrated efficacy against MF, not all specifically target inflammation or fibrosis progression with some exceptions such as RAAS inhibitors. Consequently, new therapies are being developed to address this issue. This article is aimed to describe anti-fibrotic drugs currently employed in clinical practice and emerging agents that target specific pathways, supported by evidence from both preclinical and clinical studies. EXPERT OPINION: Despite various preclinical findings suggesting the potential utility of new drugs and molecules for treating cardiac fibrosis in animal models, there is a notable scarcity of clinical trials investigating these effects. However, the pathology of damage and repair in the heart muscle involves a complex network of interconnected inflammatory pathways and various types of immune cells. Our comprehension of the positive and negative roles played by specific immune cells and cytokines is an emerging area of research.

Clinical and functional effects of beta-blocker therapy discontinuation in patients with biventricular heart failure.

BACKGROUND: Nearly two-thirds of patients with heart failure with reduced ejection fraction (HFrEF) have right ventricular dysfunction, previously identified as an independent predictor of reduced functional capacity and poor prognosis. Beta-blocker therapy (ß-BT) reduces mortality and hospitalizations in patients with HFrEF and is approved as first-line therapy regardless of concomitant right ventricular function. However, the exact role of sympathetic nervous system activation in right ventricular dysfunction and the potential usefulness (or harmfulness) of ß-BT in these patients are still unclear. OBJECTIVES: The aim of the study is to evaluate the medium-term effect of ß-BT discontinuation on functional capacity and right ventricular remodelling based on cardiopulmonary exercise testing (CPET), echocardiography and serum biomarkers in patients with clinically stable biventricular dysfunction. METHODS: In this single-centre, open-label, prospective trial, 16 patients were enrolled using the following criteria: patients were clinically stable without signs of peripheral congestion; NYHA II-III while on optimal medical therapy (including ß-BT); LVEF 40% or less; echocardiographic criteria of right ventricular dysfunction. Patients were randomized 1 : 1 either to withdraw (group 0) or continue (group 1) ß-BT. In group 0, optimal heart rate was obtained with alternative rate-control drugs. Echo and serum biomarkers were performed at baseline, after 3 and 6 months; CPET was performed at baseline and 6 months. Mann--Whitney U test was adopted to determine the relationships between ß-BT discontinuation and effects on right ventricular dysfunction. RESULTS: At 6 months' follow up, S' DTI improved (ΔS': 1.01 vs. -0.92 cm/s; P = 0.03), while estimated PAPs (ΔPAPs: 0.8 vs. -7.5 mmHg; P = 0.04) and echo left ventricular-remodelling (ΔEDVi: 19.55 vs. -0.96 ml/mq; P = 0.03) worsened in group 0. In absolute terms, the only variables significantly affected by ß-BT withdrawal were left ventricular EDV and ESV, appearing worse in group 0 (mean EDVi 115 vs. 84 ml/mq; mean ESVi 79 vs. 53.9 ml/mq, P = 0.03). No significant changes in terms of functional capacity were observed after ß-BT withdrawal. CONCLUSION: In HFrEF patients with concomitant right ventricular dysfunction, ß-BT discontinuation did not produce any beneficial effects. In addition, despite maintenance of optimal heart rate control, ß-BT discontinuation induced worsening of left ventricular remodelling. Our study corroborates the hypothesis that improvement in left ventricular function may likewise be a major determinant for improvement in right ventricular function, reducing pulmonary wedge pressure and right ventricular afterload, with only a marginal action of its negative inotropic effect. In conclusion, ß-BT appears beneficial also in heart failure patients with biventricular dysfunction.

Pharmacological treatment options for hypertrophic cardiomyopathy: high time for evidence.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, affecting over one million individuals in Europe. Hypertrophic cardiomyopathy patients often require pharmacological intervention for control of symptoms, dynamic left ventricular outflow obstruction, supraventricular and ventricular arrhythmias, and microvascular ischaemia. Current treatment strategies in HCM are predicated on the empirical use of long-standing drugs, such as beta-adrenergic and calcium blockers, although with little evidence supporting their clinical benefit in this disease. In the six decades since the original description of the disease, <50 pharmacological studies enrolling little over 2000 HCM patients have been performed, the majority of which were small, non-randomized cohorts. As our understanding of the genetic basis and pathophysiology of HCM improves, the availability of transgenic and preclinical models uncovers clues to novel and promising treatment modalities. Furthermore, the number of patients identified and followed at international referral centres has grown steadily over the decades. As a result, the opportunity now exists to implement adequately designed pharmacological trials in HCM, using established as well as novel drug therapies, to potentially intervene on the complex pathophysiology of the disease and alter its natural course. Therefore, it is timely to review the available evidence for pharmacological therapy of HCM patients, highlight the most relevant gaps in knowledge, and address some of the most promising areas for future pharmacological research, in an effort to move HCM into the era of evidence-based management.

Metabolic Approaches for the Treatment of Dilated Cardiomyopathy.

In dilated cardiomyopathy (DCM), where the heart muscle becomes stretched and thin, heart failure (HF) occurs, and the cardiomyocytes suffer from an energetic inefficiency caused by an abnormal cardiac metabolism. Although underappreciated as a potential therapeutic target, the optimal metabolic milieu of a failing heart is still largely unknown and subject to debate. Because glucose naturally has a lower P/O ratio (the ATP yield per oxygen atom), the previous studies using this strategy to increase glucose oxidation have produced some intriguing findings. In reality, the vast majority of small-scale pilot trials using trimetazidine, ranolazine, perhexiline, and etomoxir have demonstrated enhanced left ventricular (LV) function and, in some circumstances, myocardial energetics in chronic ischemic and non-ischemic HF with a reduced ejection fraction (EF). However, for unidentified reasons, none of these drugs has ever been tested in a clinical trial of sufficient size. Other pilot studies came to the conclusion that because the heart in severe dilated cardiomyopathy appears to be metabolically flexible and not limited by oxygen, the current rationale for increasing glucose oxidation as a therapeutic target is contradicted and increasing fatty acid oxidation is supported. As a result, treating metabolic dysfunction in HF may benefit from raising ketone body levels. Interestingly, treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) improves cardiac function and outcomes in HF patients with or without type 2 diabetes mellitus (T2DM) through a variety of pleiotropic effects, such as elevated ketone body levels. The improvement in overall cardiac function seen in patients receiving SGLT2i could be explained by this increase, which appears to be a reflection of an adaptive process that optimizes cardiac energy metabolism. This review aims to identify the best metabolic therapeutic approach for DCM patients, to examine the drugs that directly affect cardiac metabolism, and to outline all the potential ancillary metabolic effects of the guideline-directed medical therapy. In addition, a special focus is placed on SGLT2i, which were first studied and prescribed to diabetic patients before being successfully incorporated into the pharmacological arsenal for HF patients.

[The fact about e-cigarettes and cardiovascular risk]. / Il punto su sigarette elettroniche e rischio cardiovascolare.

Electronic cigarettes (e-cigarettes) are battery-powered devices containing a liquid based on propylene glycol or vegetable glycerin. These compounds, when vaporized, act as a vehicle for nicotine, flavors, and other chemical components. These devices have been marketed without clear evidence of risks, long-term safety, and efficacy. Toxicological data show lower plasma concentrations of carbon monoxide and other cancer-inducing substances as compared to traditional smoking. However, several studies have highlighted an increase in sympathetic tone, vascular stiffness, and endothelial dysfunction, all factors associated with cardiovascular risk that, however, is largely inferior to the cardiovascular risk related to traditional smoking. Recent clinical studies have shown how the use of e-cigarettes, combined with adequate psychological support, can be effective in reducing traditional smoking but not nicotine addiction. New policy directives are focusing on the possibility to ban some deleterious products in favor of the use of low-nicotine devices able to promote smoking cessation and reducing the risk of addiction, especially in young people. The use of e-cigarettes among smokers might be promoted with the specific aim of facilitating smoke cessation, but non-smokers and adolescents should be warned against using such devices. Finally, particular attention should be paid to smokers so that the combined use of electronic and traditional cigarettes can be limited as much as possible.

Vasostatin-1 as a potential novel circulating biomarker in patients with chronic systolic heart failure: A pilot study.

BACKGROUND AND AIMS: Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF. MATERIALS AND METHODS: The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events. RESULTS: CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events. CONCLUSION: In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Role of cardiological specialistic evaluation in patients with chest pain presenting in the emergency department.

AIMS: Aim of this study was to evaluate the impact of cardiological and echocardiographic evaluation in addition to a standard clinical and instrumental approach on diagnostic and prognostic accuracy in patients presenting in the emergency department (ED) with chest pain (CP). Acute coronary syndromes, pulmonary embolism and acute aortic syndromes (AAS) (triple-rule-out/TRO) were considered. METHODS: From 7040 patients presenting with CP from 1 January 2015 to 31 December 2017, we randomly selected a sample of 1119. We retrospectively evaluated the clinical course and definitive diagnosis according to the ED final report. A 6-month follow-up to assess incident acute cardiovascular events was made by telephone interview in discharged patients; in hospitalized patients, clinical records were analyzed to evaluate the appropriateness of admissions. Diagnostic and prognostic accuracy wasd estimated through sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, according to the presence or absence of cardiological and echocardiographic consultation. RESULTS: Complete information of 1099 patients out of 1119 was retrieved. Seven hundred and eighty-eight patients (71.70%) had been discharged, eight inappropriately (0.73%). Three hundred eleven (28.30%) had been hospitalized, 14 (1.27%) inappropriately. Diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% PPV and 99% NPV, with an overall accuracy of 98.00%. In patients evaluated by the cardiologist in addition to the ED physician (n = 387) we observed an improvement of sensitivity and NPV at the expense of specificity. Among improperly discharged patients, 7/8 had normal troponin, 7/8 normal ECG and only 1 was evaluated by a cardiologist. Only one inappropriately hospitalized patient was not evaluated by a cardiologist. CONCLUSIONS: Early consultation with a cardiologist and echocardiography improves clinical judgment in doubtful cases of CP, increasing diagnostic performance mainly by reducing inappropriate patient discharge and guaranteeing a low rate of inappropriate hospitalizations.

Resting cardiac energy metabolism is inversely associated with heart rate in healthy young adult men.

BACKGROUND: 31-Phosphorus-magnetic resonance spectroscopy may provide pathophysiological insights into the high-energy phosphate metabolism of the myocardium as measured by phosphocreatine to adenosine triphosphate (PCr/ATP) ratio. Aim of the present study was to determine in vivo the relation between cardiac PCr/ATP ratio and heart rate in normal male subjects. METHODS: One hundred twelve apparently healthy, young male individuals (age 34 ± 10 years) were prospectively evaluated. They underwent cardiac cine magnetic resonance imaging to assess left ventricular (LV) function and morphology and 3D-ISIS (31)P-magnetic resonance spectroscopy of the LV to assess the PCr/ATP ratio (a recognized in vivo marker of myocardial energy metabolism). Data were analyzed after segregation by tertiles of the resting PCr/ATP ratio. RESULTS: A significant inverse association between PCr/ATP ratios and resting heart rate was observed (Spearman ρ: r=-0.37; P < .0001). PCr/ATP ratios were also inversely associated with body mass index, diastolic blood pressure, wall mass and with insulin resistance, but in multiple regression analysis heart rate was found to be independently related to PCr/ATP. CONCLUSIONS: The present study shows that resting heart rate is proportionally lower across tertiles of increasing PCr/ATP ratio of the LV in apparently healthy young male individuals, supporting the hypothesis that heart rate is a major determinant of cardiac energy stores. These findings may explain the prognostic role of heart rate in the general population as evidenced by previous large epidemiological studies.

Case report of cardiogenic shock in COVID-19 myocarditis: peculiarities on diagnosis, histology, and treatment.

BACKGROUND: The year 2020 was dramatically characterized by SARS-CoV-2 pandemic outbreak. COVID-19-related heart diseases and myocarditis have been reported. CASE SUMMARY: A 45-year-old healthy male was admitted to the intensive care unit of our hospital because of cardiogenic shock. A diagnosis of COVID-19 infection and myocarditis was done. We present here several peculiarities about diagnostic workup, myocardial histological findings, choice of treatment, and the patient clinical course at 3 and 8 months of follow-up. DISCUSSION: COVID-19 myocardial damage and myocarditis are mainly linked to the cytokine storm with mild myocardial inflammatory infiltrate and very unusual platelet microclots in the setting of the microvascular obstructive thrombo-inflammatory syndrome. Counteracting the inflammatory burden with an interleukine-1 inhibitor appeared safe and led to a dramatic and stable improvement of cardiac function.

Sudden Cardiac Death in Patients with Heart Disease and Preserved Systolic Function: Current Options for Risk Stratification.

Sudden cardiac death (SCD) is the leading cause of cardiovascular mortality in patients with coronary artery disease without severe systolic dysfunction and in heart failure with preserved ejection fraction. From a global health perspective, while risk may be lower, the absolute number of SCDs in patients with left ventricle ejection fraction >35% is higher than in those with severely reduced left ventricle ejection fraction (defined as ≤35%). Despite these observations and the high amount of available data, to date there are no clear recommendations to reduce the sudden cardiac death burden in the population with mid-range or preserved left ventricle ejection fraction. Ongoing improvements in risk stratification based on electrophysiological and imaging techniques point towards a more precise identification of patients who would benefit from ICD implantation, which is still an unmet need in this subset of patients. The aim of this review is to provide a state-of-the-art approach in sudden cardiac death risk stratification of patients with mid-range and preserved left ventricular ejection fraction and one of the following etiologies: ischemic cardiomyopathy, heart failure, atrial fibrillation or myocarditis.

Cardiac fibrosis: emerging agents in preclinical and clinical development.

INTRODUCTION: Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-ß), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing. AREA COVERED: This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerging pathway-specific agents in preclinical and clinical development [phase I and II-concluded or ongoing trials]. We performed a PubMed, Embase and Google Scholar research including original articles, systematic reviews, ongoing and completed trials using combinations of keywords such as 'myocardial fibrosis', 'reverse remodeling', 'RAAs', 'therapy'. EXPERT OPINION: A variety of preclinical evidences suggest that new drugs and molecules are potentially useful to target cardiac fibrosis and improve left ventricular function, reduce infarct size and scars, delay incident heart failure and cardiac dysfunction in animal models. However, there are very few clinical trials investigating the effect of such drugs in this setting, as well as a lack of new engineered molecules for specific targets.

Hyperhidrosis: the neglected sign in heart failure patients.

Profuse sweating is a symptom often reported by cardiological patients and could be also an early phenomenon of adaptation or rather cardiac maladaptation in the context of incipient heart failure (HF). By definition, in HF patients the low cardiac output causing reduced renal blood supply and reduced pressure in the arterial baroreceptors activate compensatory mechanisms such as the RAAS and the adrenergic autonomic nervous system. The retention of fluids caused by the decompensation of heart-kidney system could generate a reactive hyperhidrosis and even anticipate an incipient decompensation and might prevent manifest volume overload. Moreover, in HF patients the overactive sympathetic nervous system generates an increase in the reabsorption of fluids in the kidney, on the other hand it generates a signaling to the sweat glands to induce a dispersion of fluids, with loss of sodium and chlorine at the glandular ductal level. Finally sweat gland production physiology during physical activity is also altered in HF patients. This review is focused on sweating and its pathophysiological role in heart failure. Although all the mechanisms underlying this phenomenon are not fully understood, there are interesting connections that might explain this fluid elimination as a wise and sophisticated way to prevent incipient heart failure crisis. Future research could be focused on studying new drugs that selectively would be able to promote fluid elimination by this specific way in patients suffering from heart failure.

Right ventricular endomyocardial biopsy in patients with cardiac magnetic resonance showing left ventricular myocarditis.

AIMS: The aim of this study was to evaluate the sensitivity of right ventricular endomyocardial biopsy (EMB) in myocarditis patients with cardiac magnetic resonance (CMR) and electroanatomical mapping (EAM) showing left ventricular abnormalities. METHODS: We performed right ventricular EMB in 144 consecutive patients (66% men, age 43 ±â€Š15 years) with acute symptoms and CMR-proved diagnosis of left ventricular myocarditis. Right ventricular EMB sensitivity has been evaluated in patients with different localization and extension of abnormal substrate at both CMR and -- when performed -- EAM. Abnormal substrate was defined, respectively, by late gadolinium enhancement (LGE) and low-voltage areas (LVAs). RESULTS: Globally, right ventricular EMB sensitivity was 87.5%. EMB-negative cases had significantly smaller fragment sizes (cumulative area 2.8 ±â€Š1.7 vs. 3.8 ±â€Š1.8 mm2, P = 0.023), and lower LGE surface extension (24.7 ±â€Š14.2 vs. 38.5 ±â€Š20.2%, P = 0.006) and transmurality (32.0 ±â€Š26.1 vs. 49.3 ±â€Š22.6, P = 0.003). Right ventricular EMB sensitivity in patients with LGE involving both right ventricular and interventricular septum (IVS), isolated right ventricular or IVS, and remote left ventricular areas (n = 10, 49 and 67 cases) was 83.3, 84.4 and 90.5%, respectively (P = 0.522). Overall, 34 patients (23.6%) underwent EAM. On the basis of EAM, right ventricular EMB sensitivity was 85.3%: in detail, it was 50.0, 88.2 and 86.7% in patients with both right ventricular and IVS, isolated right ventricular/IVS and distant left ventricular involvement (n = 2, 17 and 15, respectively, P > 0.05). Sample size area was the only factor associated with right ventricular EMB sensitivity (hazard ratio = 1.6/mm2, 95% confidence interval 1.1-2.4, P = 0.013). CONCLUSION: Right ventricular EMB is still an accurate technique to confirm diagnosis in patients with CMR-proved left ventricular myocarditis. In particular, provided there is an adequate sample size, its sensitivity is comparable among patients with heterogeneous LGE or LVA localization.

[Present trends and controversies in the use of beta-blockers in cardiovascular diseases]. / Beta-bloccanti e sistema cardiovascolare: attuali acquisizioni e controversie.

In this paper we summarize present trends and controversies in the use of beta-blockers in cardiovascular diseases. Beta-blockers are catecolamine competitive inhibitors and act through alpha and beta adrenergic receptors blockade. Different agents have a dose-dependent affinity for different beta adrenergic receptors (beta 1, beta 2, beta 3) which is less with higher doses. The most important therapeutic effects of beta-blockers are on cardiovascular system, where they act as negative chronotropic and inotropic agents, lowering cardiac work and improving oxygen demand /supply ratio. Clinical indications are numerous. For their anti-ischemic activity beta-blockers are used as anti-anginal drugs and in acute and previous myocardial infarction for preventing total and cardiovascular mortality. Combined use of beta-blockers and ACE inhibitors slows down heart failure progression and reduces cardiovascular mortality. Beta-blockers are useful in treating focal atrial tachycardia and supra ventricular paroxysmal tachycardia, by reducing sinus node automaticity and delay atrio-ventricular conduction; they also prevent sudden cardiac death and ventricular tachycardia associated with increased sympathetic activity. There is no indication in treating primary non-complicated hypertension with beta-blockers as first-line drugs. Different metabolic effects of selective and non-selective beta-blockers are actually debated. In conclusion, beta-blockers have indication in the treatment of many cardiovascular diseases. Further studies are needed for better understanding the differences in cardiac and peripheral beta-blockers effects depending on their selectivity.

Atrial fibrillation in hypertrophic cardiomyopathy: pathophysiology, diagnosis and management.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, representing a leading cause of sudden cardiac death in the young and a prevalent cause of heart failure and stroke. Atrial fibrillation (AF) is frequently associated with HCM with a reported prevalence of about 20% to 25%. AF genesis is multifactorial, mostly genetically determined or secondary to hemodynamic alterations. AF has also a negative impact on HCM patients' prognosis because it may lead to an increased incidence of heart failure or stroke. We currently have several strategies which can be used during atrial fibrillation episodes and to prevent the arrhythmic recurrences.

Safety and efficacy of doxazosin as an "add-on" antihypertensive therapy in mild to moderate heart failure patients.

OBJECTIVE: Doxazosin treatment has been discouraged in hypertensive patients in order to prevent heart failure (HF) development. However, this drug is still prescribed as an "add-on" medication to achieve a better blood pressure (BP) control. The aim of this study was to evaluate the safety and efficacy of doxazosin as an "add-on" medication in HF patients with uncontrolled hypertension. METHODS AND RESULTS: We reviewed our HF clinic files to collect patient variables recorded at baseline and during follow-up visits in patients receiving, or not, doxazosin. We compared HF-related hospitalization rates and all-cause and cardiovascular mortality rates between patients on doxazosin and those not on doxazosin. We constructed cumulative risk curves for time to first event (HF-related hospitalization and/or death) for both groups of patients. Fifty-two HF patients had been prescribed doxazosin. At baseline, several relevant variables were unevenly distributed between patients receiving doxazosin and those not receiving doxazosin (N=122), such as left ventricular ejection fraction (LVEF) and NYHA class. HF-related hospitalization and death rates were similar between patients on doxazosin and those not on doxazosin at the end of the follow-up. Even after adjustment for all potentially confounding variables, doxazosin was not associated with HF-related hospitalization and/or death. Doxazosin significantly reduced BP, but did not affect NYHA class. CONCLUSIONS: Doxazosin, "on top" of other antihypertensive treatments was safe and effective, and did not appear to be associated with HF-related hospitalization and mortality rates in our patients with mild/moderate HF.