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.

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.

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.

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.

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.

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.

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.

Radiofrequency catheter ablation of atrial fibrillation in athletes referred for disabling symptoms preventing usual training schedule and sport competition.

INTRODUCTION: Atrial fibrillation (AF) may occasionally affect athletes by impairing their ability to compete, and leading to noneligibility at prequalification screening. The impact of catheter ablation (CA) in restoring full competitive activity of athletes affected by AF is not known. The aim of our study was to investigate the effectiveness of CA of idiopathic AF in athletes with palpitations impairing physical performance and compromising eligibility for competitive activities. METHODS AND RESULTS: Twenty consecutive competitive athletes (all males; 44.4 +/- 13.0 years) with disabling palpitations on the basis of idiopathic drug-refractory AF underwent 46 procedures (2.3 +/- 0.4 per patient) according to a prospectively designed multiprocedural CA approach that consolidates pulmonary veins (PV) isolation through subsequent steps. Preablation, effort-induced AF could be documented in 13 patients (65%) during stress ECG and significantly reduced maximal effort capacity (176 +/- 21 W), as compared with patients with no AF during effort (207 +/- 43 W, P < 0.05). At the end of CA protocol, which also included ablation of atrial flutter (AFL) in 7 patients, 18 (90.0%) patients were free of AF and two (10.0%) reported short-lasting (minutes) episodes of palpitations during 36.1 +/- 12.7 months follow-up. Compared with preablation, postablation maximal exercise capacity significantly improved (from 183 +/- 32 to 218 +/- 20 W, P < 0.02). All baseline quality of life (QoL) parameters pertinent to physical activity significantly improved (P < 0.05) at the end of CA protocol. All athletes obtained reeligibility and could effectively reinitiate sport activity. CONCLUSIONS: AF, alone or in combination with AFL, may significantly impair maximal effort capacity thereby limiting competitive performance. Multiple PV isolation proved very effective in these patients to restore full competitive activity and allow reeligibility.

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.

Changes in plasma N-terminal proBNP levels and ventricular filling pressures during intensive unloading therapy in elderly with decompensated congestive heart failure and preserved left ventricular systolic function.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels depend on left ventricular (LV) filling pressures and correlate with the state of neurohormonal modulation in patients with congestive heart failure (CHF). In these subjects, therapy of decompensated CHF can determine acute changes in BNP levels. METHODS AND RESULTS: We defined the sequential pattern of N-terminal (T) proBNP in elderly with decompensated CHF and preserved LV systolic function undergoing intensive unloading therapy, assessed the prevalence of patients who significantly reduced NTproBNP at the end of treatment, and verified the relations between changes in NTproBNP and ventricular filling pressures. NTproBNP was measured in 30 patients hospitalized for worsening CHF with LV ejection fraction >50% at admission and after 2 to 4 and 6 to 8 days from the start of treatment. Patients who exhibited a reduction in NTproBNP >35% from baseline to 8-day evaluation were defined as "responders." Twelve healthy subjects matched for age and sex were used as controls. NTproBNP was significantly higher in CHF patients than controls in all time points, to a greater extent in baseline evaluation (2982 [lower/upper quartile 1273/8146] versus 235 [150/280] pg/mL). A progressive, linear reduction of NTproBNP was detected in CHF patients during unloading. At Day 8, 18 patients (60%) resulted in "responders," whereas 12 (40%) were "nonresponders." The former could be predicted through higher pulmonary artery wedge pressure at baseline. Surprisingly, ventricular filling pressures similarly declined in responders and non responders. At Day 8, NTproBNP was yet 7-fold higher in CHF patients than controls. CONCLUSION: Intensive unloading therapy is associated with a significant short-term reduction in NTproBNP in elderly with CHF and preserved LV systolic function. This behavior is progressive and linear during the first week and parallels a reduction in ventricular filling pressures which, however, does not differ between patients who significantly reduce NTproBNP and those who do not. Thus the short-term changes in NTproBNP during intensive unloading therapy in our patients do not depend only on the acute improvement in hemodynamic conditions.

Prospective assessment of late conduction recurrence across radiofrequency lesions producing electrical disconnection at the pulmonary vein ostium in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation (AF) undergoing radiofrequency (RF) electrical disconnection of multiple pulmonary veins (PVs), the incidence of late conduction recurrences has not been systematically determined. METHODS AND RESULTS: Using a prospectively designed, multistep approach, we aimed at assessing the correlation between acute achievement and chronic maintenance of electrical conduction block across RF lesions disconnecting the distal tract of the PV in 43 patients (52.3+/-8.2 years) with AF. Forty-one left superior (LS), 42 right superior (RS), 25 left inferior (LI), and 9 right inferior (RI) PVs were targeted during 108 EP procedures (2.6+/-0.5 per patient). Seventeen patients underwent 2 procedures, 23 patients underwent 3 procedures, and 3 patients underwent 4 procedures. During the first attempt, electrical disconnection was achieved in 112 PVs (95.7%). During a next procedure (time interval, 4.6+/-1.9 months), conduction recurrence was observed in 32 of 39 LSPVs (82.1%), 29 of 40 RSPVs (72.5%), 20 of 24 LIPVs (83.3%), and 7 of 9 RIPV (77.8%). After reablation at gap sites, a later procedure (time interval, 5.1+/-2.4 months) revealed a second recurrence in 13 of 22 LSPVs (59.1%) and 14 of 19 RSPVs (73.7%). CONCLUSIONS: Conduction recurrence across disconnecting RF lesions can be observed in approximately 80% of cases 4 months after ablation. After reablation, similar recurrence rates are observed 5 months later. This high rate of late conduction recurrence may contribute significantly to AF recurrence in patients undergoing catheter ablation aiming at disconnection of multiple PVs.

Arrhythmogenic effects of illicit drugs in athletes.

Cardiac arrhythmias are among the most important causes of non-eligibility to sports activities, and may be due to different causes (cardiomyopathies, myocarditis, coronary abnormalities, valvular diseases, primary electrical disorders, abuse of illicit drugs). The list of illicit drugs banned by the International Olympic Committee and yearly updated by the World Anti-Doping Agency includes the following classes: stimulants, narcotics, anabolic agents (androgenic steroids and others such as beta-2 stimulants), peptide hormones, mimetics and analogues, diuretics, agents with an antiestrogenic activity, masking agents. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal or not, even in healthy subjects with no previous history of cardiac diseases. Therefore, given the widespread abuse of illicit drugs among athletes, in the management of arrhythmic athletes the cardiologist should always take into consideration the possibility that the arrhythmias be due to the assumption of illicit drugs (sometimes more than one type), especially if no signs of cardiac diseases are present. On the other hand, in the presence of latent underlying arrhythmogenic heart disease including some inherited cardiomyopathies at risk of sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic effects.

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.

[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.

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.

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.

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.