Cardiovascular effects of doping substances, commonly prescribed medications and ergogenic aids in relation to sports: a position statement of the sport cardiology and exercise nucleus of the European Association of Preventive Cardiology.

The use of substances and medications with potential cardiovascular effects among those practicing sports and physical activity has progressively increased in recent years. This is also connected to the promotion of physical activity and exercise as core aspects of a healthy lifestyle, which has led also to an increase in sport participation across all ages. In this context, three main users' categories can be identified, (i) professional and amateur athletes using substances to enhance their performance, (ii) people with chronic conditions, which include physical activity and sport in their therapeutic plan, in association with prescribed medications, and (iii) athletes and young individuals using supplements or ergogenic aids to integrate their diet or obtaining a cognitive enhancement effect. All the substances used for these purposes have been reported to have side effects, among whom the cardiovascular consequences are the most dangerous and could lead to cardiac events. The cardiovascular effect depends on the type of substance, the amount, the duration of use, and the individual response to the substances, considering the great variability in responses. This Position Paper reviews the recent literature and represents an update to the previously published Position Paper published in 2006. The objective is to inform physicians, athletes, coaches, and those participating in sport for a health enhancement purpose, about the adverse cardiovascular effects of doping substances, commonly prescribed medications and ergogenic aids, when associated with sport and exercise.

Lower dose direct oral anticoagulants and improved survival: A combined analysis in patients with established atherosclerosis.

BACKGROUND: Antithrombotic/anticoagulation effects of direct oral anticoagulants (DOACs) are dose-dependent. However, recent observations suggest that administering lower dose DOACs may better protect against all-cause mortality. We investigated whether, in patients with established atherosclerosis, DOAC dose selection would affect the risk of all-cause mortality. METHODS: We performed a structured literature research for controlled trials allowing random assignment to a lower dose DOAC, a higher dose DOAC, or control therapy in patients with established atherosclerosis. Pooled risk ratios (RRs) of all-cause mortality in lower and higher dose DOACs versus control therapy were estimated using a random-effect model. RESULTS: Atherosclerosis manifested as acute coronary syndrome (n=17,220), stable coronary (CAD) and/or peripheral artery disease (PAD) (n=27,395) or CAD associated with atrial fibrillation (n=4,510). Antithrombotic doses of rivaroxaban (2.5 mg or 5.0 mg BID) or dabigatran (50 mg, 75 mg, 110 mg, or 150 mg, BID) were tested in three trials versus single or dual antiplatelet control therapy, whereas anticoagulation doses of edoxaban (30 mg or 60 OD) were tested versus warfarin in one trial. Compared to control, patients receiving lower dose (RR 0.80, 95% CI 0.73-0.89, p<0.0001, I²=0%), but not those receiving higher dose DOACs (RR 0.95, 95% CI 0.87-1.05, p=0.3074, I²=0%), had a significant reduction of all-cause mortality. Benefit from lower dose DOACs remained after sensitivity analysis or direct comparison with higher dose DOACs (RR 0.84, 95% CI 0.76-0.93, p=0.0009, I²=0%). CONCLUSIONS: Within antithrombotic/anticoagulation regimens of DOAC administration, selection of lower dose appears to protect from all-cause mortality in patients with established atherosclerosis.

Quinidine-A legacy within the modern era of antiarrhythmic therapy.

Quinidine has a very long history as antiarrhythmic medication. The alkaloid has been used in the treatment of almost all cardiac arrhythmias, especially atrial fibrillation, since the early twentieth century. Despite decreases in clinical prescription over the last two decades, mainly due to side effects like pro-arrhythmia, leading to increased mortality and to the availability of newer anti-arrhythmic drugs and catheter ablation, Quinidine remains an invaluable drug in the modern era of antiarrhythmic therapy. We present a review of the pharmacological properties of quinidine and its pivotal therapeutic role in the treatment of life-threatening arrhythmic storms in patients with congenital arrhythmogenic syndromes like Brugada's syndrome, early repolarization syndrome, short QT syndrome and idiopathic ventricular fibrillation.

Clinical and electrocardiographic features of complete heart block after blunt cardiac injury: A systematic review of the literature.

The underlying mechanisms and temporal course of complete heart block (CHB) after blunt cardiac injuries (BCIs) are poorly understood, and a systematic analysis of available data is lacking. In this systematic review, PubMed was searched for publications of reported cases of CHB-BCI analyzing clinical findings, electrocardiographic features, temporal course, and outcomes. Case reports on CHB-BCI were available for 50 patients, mainly secondary to traffic or sport accidents. A fatal outcome occurred in 10 of 50 (20%) of patients, while a structural damage of the atrioventricular (AV) conductive system was evident in 4 of 8 (50%) of necropsy studies. Clinical manifestation of CHB-BCI occurred within 72 hours of injury in 38 of 47 (∼80%) of patients, and 1:1 AV conduction was restored within 7-10 days in about half of early survivors. Permanent pacemaker implantation was indicated in 22 of 42 (∼50%) of early survivors because of recurrent or permanent CHB. Cardiac troponins, when analyzed, were elevated in 12 of 13 (∼90%) of patients, and electrocardiographic features of aberrancy were present in 29 of 40 (>70%) of patients. In conclusion, CHB secondary to BCI is associated with 20% mortality mainly occurring in the early posttraumatic period and most of the deaths are due to or triggered by this malignant arrhythmia. Recurrent or permanent CHB requiring pacemaker implantation occurs in ∼50% of survivors. A structural damage of the AV conductive system can be found in 50% of necropsy studies.

Commotio Cordis and complete heart block: Where is the block level?

Ventricular fibrillation is typically the initial arrhythmia in commotio cordis following precordium impacts that occur within an electrically vulnerable period of the cardiac cycle. Conversely, complete heart block is very rare in this context, and its mechanism and temporal course are poorly understood. The presented case concerns a 12-year-old boy, athletic skier, who developed a transient complete heart block following commotio cordis. The electrocardiographic features, the proposed block level and mechanisms of complete heart block following commotio cordis are discussed.

Left atrial work in patients with stable chronic heart failure: factors associated and prognostic role.

BACKGROUND: Limited information is available on left atrial (LA) work in chronic heart failure (CHF) patients. We evaluated correlates and prognostic role of LA work in 243 CHF patients using as reference for normal LA work values 230 healthy controls. METHODS: Left atrial work was assessed by computation of LA kinetic energy (LAKE) from the formula: 0.5 × m × A(2) where m is LA stroke volume × blood density, and A is transmitral Doppler peak atrial velocity. The prespecified primary endpoint of the study was major cardiovascular (CV) events, a composite endpoint defined as CV death + hospitalization for heart failure (HF). RESULTS: Left atrial kinetic energy was 3.9 ± 2.7 in CHF patients and 2.6 ± 1.4 Kdynes/m(2) in controls (P < 0.001). Abnormally high LAKE (>5.4 Kdynes/m(2) = mean + 2 SD of the controls) was found in 19% of CHF patients and 4% of controls (P < 0.001). LAKE was independently associated with an increased shortening of left ventricular (LV) longitudinal fibers and renal dysfunction. CV death or hospitalization for decompensated HF occurred in 66% and 20% of patients with abnormally high and normal LAKE, respectively (P < 0.001). Abnormally high LAKE, not LA size, was an independent predictor of events hazard ratio (HR) 3.92 [95% CI 1.96-7.84] together with renal dysfunction and lower LV ejection fraction. CONCLUSION: In CHF patients, LAKE is significantly higher than in healthy controls, the prevalence of abnormally high LAKE is near fivefold higher in the former than in the latter. LAKE depends on systolic LV and renal function and is a strong predictor of CV death and hospitalization for HF. LA work has an incremental prognostic value over LA size.

Italian cardiological guidelines for sports eligibility in athletes with heart disease: part 1.

In Italy the existence of a law on health protection of competitive sports since 1982 has favored the creation and the revision of these cardiological guidelines (called COCIS), which have reached their fourth edition (1989-2009). The present article is the second English version, which has summarized the larger version in Italian. The experience of the experts consulted in the course of these past 20 years has facilitated the application and the compatibility of issues related to clinical cardiology to the sports medicine field. Such prolonged experience has allowed the clinical cardiologist to acquire knowledge of the applied physiology of exercise and, on the other hand, has improved the ability of sports physicians in cardiological diagnostics. All this work has produced these guidelines related to the judgment of eligibility for competitive sports in the individual clinical situations and in the different cardiovascular abnormalities and/or heart disease. Numerous arguments are debated, such as interpretation of the athlete's ECG, the utility of a preparticipation screening, arrhythmias, congenital heart disease, cardiomyopathies, arterial hypertension, ischemic heart disease and other particular issues.

Italian cardiological guidelines for sports eligibility in athletes with heart disease: part 2.

In Italy the existence of a law on health protection of competitive sports since 1982 has favored the creation and the revision of these cardiological guidelines (called COCIS), which have reached their fourth edition (1989-2009). The present article is the second English version, which has summarized the larger version in Italian. The experience of the experts consulted in the course of these past 20 years has facilitated the application and the compatibility of issues related to clinical cardiology to the sports medicine field. Such prolonged experience has allowed the clinical cardiologist to acquire knowledge of the applied physiology of exercise and, on the other hand, has improved the ability of sports physicians in cardiological diagnostics. All this work has produced these guidelines related to the judgment of eligibility for competitive sports in the individual clinical situations and in the different cardiovascular abnormalities and/or heart disease. Numerous arguments are debated, such as interpretation of the athlete's ECG, the utility of a preparticipation screening, arrhythmias, congenital heart disease, cardiomyopathies, arterial hypertension, ischemic heart disease and other particular issues.

Prognostic stratification by conventional echocardiography of patients with aortic stenosis: the "CAIMAN-ECHO score".

BACKGROUND AND AIM: Surgery is not recommended in asymptomatic patients with aortic stenosis (AS). However, prognosis of these patients is worse than retained. We built a simple score (named by the acronym "CAIMAN") for stratifying asymptomatic patients with AS according to the different risk for cardiovascular events. MATERIAL AND METHODS: Data from 141 patients with moderate-to-severe AS followed up for 36 months were analyzed. The end point "outcome" was defined as death of all causes or aortic valve replacement imposed by symptoms or hospital admission for myocardial infarction and/or heart failure. The score was validated in 143 patients prospectively recruited in 2 different centers. RESULTS: The 40 events occurred in the original cohort were associated with higher aortic transvalvular peak jet velocity, calcium score, and observed/predicted left ventricular (LV) mass ratio. Based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score 1-3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, 3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. After a mean period of 28 ± 18 months, event-free survival was 18%, 42%, 91%, and 96% in the 4 quartiles of echo score. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. CONCLUSIONS: The CAIMAN-ECHO score is a simple and feasible tool useful for an accurate prognostic stratification of patients with asymptomatic moderate-to-severe AS.

[Subcutaneous implantable cardioverter-defibrillators]. / Il defibrillatore "leadless"

Transvenous implantable cardioverter-defibrillators (ICD) for the primary and secondary prevention of sudden cardiac death due to ventricular tachycardia/fibrillation have led to a significant improvement in survival in high-risk populations. Although conventional transvenous ICD therapy is currently widely used, it is associated with severe intra- and perioperative complications related to the use of transvenous leads, mostly occurring late after implantation. The recent introduction of a new ICD system with fully subcutaneous sensing and shocking capabilities has provided a valuable therapeutic option for special patient groups, allowing to identify and stop malignant ventricular arrhythmias while discriminating them from high-rate supraventricular tachyarrhythmias. This has also given us the opportunity to analyze the advantages and limitations of both implantable lifesaving electrical therapies. In the present paper, the technical characteristics of subcutaneous ICDs are described along with the recent advances in clinical and experimental research that have led to the introduction of these devices into clinical practice (over 1000 patients have been treated worldwide since 2009). Subcutaneous ICDs are indicated for both primary and secondary prevention of cardiac arrest in patients at risk for acquired or congenital arrhythmogenic diseases, including those with an underlying genetic molecular mechanism, provided that they do not require antibradycardia or antitachycardia pacing or cardiac resynchronization therapy, which represent the main limitations of these new devices. A subcutaneous ICD system has the advantage of avoiding the need for transvenous leads, making its implantation or removal much simpler without requiring fluoroscopic guidance. In addition, subcutaneous ICDs can be used in children, young subjects and athletes, and in all patients for whom venous access may be difficult to achieve.

Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation.

OBJECTIVES: The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design. BACKGROUND: Due to its I(f) blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. METHODS: Twenty-one patients were randomized to receive placebo (n=10) or ivabradine 5 mg twice daily (n=11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. RESULTS: After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p<0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88±11 beats/min to 76±11 beats/min, p=0.011), on standing (from 108±12 beats/min to 92±11 beats/min, p<0.0001), during 24 h (from 88±5 beats/min to 77±9 beats/min, p=0.001), and during effort (from 176±17 beats/min to 158±16 beats/min, p=0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. CONCLUSIONS: In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia.

Analysis of circumferential and longitudinal left ventricular systolic function in patients with non-ischemic chronic heart failure and preserved ejection fraction (from the CARRY-IN-HFpEF study).

Heart failure with preserved left ventricular ejection fraction (HFpEF) is implicitly attributed to diastolic dysfunction, often recognized in elderly patients with hypertension, diabetes, and renal dysfunction. In these patients, left ventricular circumferential and longitudinal shortening is often impaired despite normal ejection fraction. The aim of this prospective study was to analyze circumferential and longitudinal shortening and their relations in patients with nonischemic HFpEF. Stress-corrected midwall shortening (sc-MS) and mitral annular peak systolic velocity (S') were measured in 60 patients (mean age 73 ± 13 years) with chronic nonischemic HFpEF in stable New York Heart Association functional class II or III and compared to the values in 120 healthy controls and 120 patients with hypertension without HFpEF. Sc-MS was classified as low if <89% and S' as low if <8.5 cm/s (the 10th-percentile values of healthy controls). Isolated low sc-MS was detected in 46% of patients with HFpEF, 27% of patients with hypertension, and 2% of controls; isolated low S' was detected in 11% of patients with HFpEF, 7% of patients with hypertension, and 5% of controls; and combined low sc-MS and low S' was detected in 26% of patients with HFpEF, 9% of patients with hypertension, and 5% of controls (HFpEF vs others, all p values <0.001). Thus, any alteration of systolic function was found in 83% of patients with HFpEF. The relation between sc-MS and S' was nonlinear (cubic). Changes in S' within normal values corresponded to negligible variations in sc-MS, whereas the progressive decrease below 8.5 cm/s was associated with substantial decrease in sc-MS. In conclusion, circumferential and/or longitudinal systolic dysfunction is present in most patients with HFpEF. Circumferential shortening normalized by wall stress identifies more patients with concealed left ventricular systolic dysfunction than longitudinal shortening.

Analysis of left ventricular systolic function by midwall mechanics in patients with obstructive sleep apnoea.

AIMS: midwall mechanics reveal systolic dysfunction in obese and hypertensive patients with concentric left ventricular (LV) geometry, which is frequently detected in subjects with obstructive sleep apnoea (OSA). Midwall mechanics have never been studied in these patients, who frequently experience heart failure (HF). METHODS AND RESULTS: we analysed midwall stress-shortening relations by echocardiography in 150 controls and 200 patients with OSA (age 62 ± 13 years) without known cardiac disease. On the basis of the severity of OSA, patients were divided into mild OSA (n = 63), moderate OSA (n = 70), and severe OSA (n = 67). LV stress-corrected midwall shortening (scMS) was considered low if <87% in men and <90% in women. scMS was similar in controls and mild OSA (90 ± 13 and 91 ± 18%, respectively) and significantly lower in moderate and severe OSA (83 ± 14 and 83 ± 15%; all P < 0.001 vs. controls and mild OSA). Prevalence of low scMS was 40 and 39% in controls and mild OSA (P=NS), 62% in moderate and 61% in severe OSA (both P < 0.001 vs. controls and mild OSA). In logistic regression analysis, low scMS was associated with moderate-severe OSA (OR 3.82, P < 0.001) independent of significant associations with diabetes (OR 5.06, P < 0.01), LV hypertrophy (OR 1.89, P = 0.01), and LV concentric geometry (OR 2.79, P < 0.001). CONCLUSION: midwall mechanics are impaired in more than half of middle-aged patients with OSA without known cardiac disease. Moderate-severe OSA predicts LV systolic dysfunction independent of diabetes, LV hypertrophy, and concentric geometry. These relations may in part explain the increased rate of HF and cardiovascular events in these patients.

Chronic kidney disease elicits excessive increase in left ventricular mass growth in patients at increased risk for cardiovascular events.

BACKGROUND: The hemodynamic alterations induced by the impairment of renal function explain only in part the development of left ventricular hypertrophy in patients with chronic kidney disease (CKD), who are theoretically exposed to an inappropriate high growth of left ventricular mass (iLVM) due to the activation of neuro-hormonal stressors. Few data are available on the relations between iLVM and renal function. STUDY DESIGN AND MEASUREMENTS: Three hundred and forty individuals at increased risk for cardiovascular events underwent assessment of renal function by the estimation of glomerular filtration rate (eGFR) and echocardiography: 227 patients had stages 1-2 CKD (eGFR ≥60 ml/min per 1.73 m), and 113 stages 3-5 (eGFR <60 ml/min per 1.73 m). LVM was predicted in each patient from height, sex and stroke work using a validated equation. iLVM was defined as LVM more than 28% of the predicted value. Sixty-eight healthy individuals served as controls. RESULTS: iLVM was detected in seven controls (10%) and in 146 study patients (43%). There was an inverse relation between observed/predicted LVM ratio and eGFR (r 0.54, P < 0.001). In linear regression analysis, iLVM was related to eGFR (ß 0.40), relative wall thickness (ß 0.29), diabetes (ß 0.14), and maximal left atrial volume (ß 0.25) (all P < 0.001). Prevalence of iLVM was 10% in patients in stage-1 CKD, 31% in stage 2, 67% in stage 3, and 100% in stages 4 and 5. CONCLUSION: In patients at increased risk for cardiovascular events, iLVM is strongly related to the presence and magnitude of CKD. Further longitudinal studies are needed to evaluate the prognostic value of the coexistence of iLVM and CKD.

J wave, QRS slurring, and ST elevation in athletes with cardiac arrest in the absence of heart disease: marker of risk or innocent bystander?

BACKGROUND: QRS-ST changes in the inferior and lateral ECG leads are frequently observed in athletes. Recent studies have suggested a potential arrhythmogenic significance of these findings in the general population. The aim of our study was to investigate whether QRS-ST changes are markers of cardiac arrest (CA) of unexplained cause or sudden death in athletes. METHODS AND RESULTS: In 21 athletes (mean age, 27 years; 5 women) with cardiac arrest or sudden death, the ECG recorded before or immediately after the clinical event was compared with the ECG of 365 healthy athletes eligible for competitive sport activity. We measured the height of the J wave and ST elevation and searched for the presence of QRS slurring in the terminal portion of QRS. QRS slurring in any lead was present in 28.6% of cases and in 7.6% of control athletes (P=0.006). A J wave and/or QRS slurring without ST elevation in the inferior (II, III, and aVF) and lateral leads (V(4) to V(6)) were more frequently recorded in cases than in control athletes (28.6% versus 7.9%, P=0.007). Among those with cardiac arrest, arrhythmia recurrences did not differ between the subgroups with and without J wave or QRS slurring during a median 36-month follow-up of sport discontinuation. CONCLUSIONS: J wave and/or QRS slurring was found more frequently among athletes with cardiac arrest/sudden death than in control athletes. Nevertheless, the presence of this ECG pattern appears not to confer a higher risk for recurrent malignant ventricular arrhythmias.

Sports and arrhythmias: a report of the International Workshop Venice Arrhythmias 2009.

This article is a report of an international symposium, endorsed by the Section on Sports Cardiology of the European Association for Cardiovascular Prevention and Rehabilitation, the Italian Society of Sports Cardiology, and the Italian Federation of Sports Medicine, which was held within the 11th International Workshop on Cardiac Arrhythmias (Venice Arrhythmias 2009, Venice, Italy, October 2009). The following main topics were discussed during the symposium: the role of novel diagnostic examinations to assess the risk of sudden death in athletes, controversies on arrhythmic risk evaluation in athletes, controversies on the relationship between sports and arrhythmias, and controversies on antiarrhythmic treatment in athletes.

Severe obstructive sleep apnea elicits concentric left ventricular geometry.

BACKGROUND: Obstructive sleep apnea (OSA) has several negative effects on the heart including increase in myocardial end-systolic stress, venous return and sympathetic activity, all potential stimuli of left ventricular (LV) hypertrophy. The impact of the severity of OSA on LV geometry is unknown. We hypothesized that OSA is related to concentric LV geometry. METHODS: One hundred and fifty-seven patients with suspected OSA underwent echocardiography, ambulatory 24-h blood pressure and ECG monitoring. On the basis of the severity of OSA, patients were divided into controls, mild OSA and moderate/severe OSA (apnea-hypopnea index <5, 5-15 and >15/h, respectively). Patients with LV hypertrophy were defined as LV mass at least 49.2 g/m2.7 for men and at least 46.7 for women. Relative wall thickness of at least 0.43 identified patients with concentric LV geometry. RESULTS: Patients with moderate/severe OSA (n = 86) had a higher body mass index and a higher prevalence of paroxysmal atrial fibrillation than those (n = 51) with mild OSA and controls (n = 20). Prevalence of hypertension, diabetes, obesity, LV mass and blood pressure did not differ between the groups. Relative wall thickness was positively related to apnea-hypopnea index (r = 0.30; P = 0.003) and the prevalence of concentric LV geometry was 20% in controls, 12% in mild OSA and 58% in moderate/severe OSA (P < 0.001). In logistic regression analysis concentric LV geometry was associated with moderate/severe OSA [odds ratio (OR) 7.6, P < 0.001], low stress-corrected midwall shortening (OR 3.38, P = 0.004), and higher body mass index (OR 1.09, P = 0.03). CONCLUSIONS: Moderate/severe OSA is associated with high prevalence of concentric LV geometry. This increased prevalence may in part explain the increased rate of cardiovascular events in these patients.

[Atrial fibrillation and flutter in athletes]. / La fibrillazione e il flutter atriale nell'atleta.

Atrial fibrillation (AF) is one of the most frequent findings in the general population, with an incidence of about 0.1% per year and a mean prevalence of 0.95%. However, prevalence values are known to vary with age, being very low (0.1-0.2%) in subjects less than 55 years old, the age group comprising the greatest number of individuals who practice sport at various levels. Long-term, regular, intense physical training determines an increase in vagal tone, leading to bradycardia, and during physical activity, particularly competitive sport, a marked release of catecholamines occurs as a result of both the intense physical effort and the emotional stress involved in competition. Both these adaptive phenomena on the part of the autonomous nervous system may promote the development of AF. Heart diseases with a certain degree of severity are not generally compatible with sport, unless the activity undertaken involves a low expenditure of energy and is noncompetitive. In any case, in the presence of AF, the arrhythmia must be well controlled and well tolerated during performance of the activity.

[Drugs and athletic activity: do they fit together?]. / Quanto sono compatibili i farmaci con l'attività atletica.

Competitive sports eligibility, mandatory for the Italian law in all age classes, from young to master athletes, involves millions of subjects, who are at risk during their sport career both for prescription and illicit drugs (or banned substances included in the World Anti-Doping Agency list, annually updated). These drugs may interfere with adrenergic hyperactivation related to athletic activity and can bring to unfavorable cardiovascular effects, such as arrhythmias, coronary artery disease, myocarditis, pericarditis, heart failure, ion channel disease. Moreover, numerous compounds may reduce athletic performance. Cardiovascular side effects are more frequently reported when drug co-administration is performed, which occurs frequently. Drug co-administration may have a higher risk when a common metabolic pathway is used (i.e. P450 hepatic cytochrome), and inhibition or induction effects modify plasma drug levels. One of the most important problems remains for combination of drugs that might be torsadogenic. Therefore, it is mandatory to be aware of pharmacokinetic properties, mechanisms of action, side effects and interactions between drugs and competitive sports activities; moreover, possible clinical, instrumental (i.e. ECG) or laboratory markers should be pointed out in order to recognize a possible toxic effect and subsequently interrupt or modify drug administration and/or assumption.