Fragmented and delayed electrograms within fibrofatty scar predict arrhythmic events in arrhythmogenic right ventricular cardiomyopathy: results from a prospective risk stratification study.

BACKGROUND: Islets of myocytes within fibrofatty scars represent the substrate for reentrant ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Electroanatomic mapping can reliably identify such areas. OBJECTIVE: To prospectively test the association between late and fragmented electrograms within scar and arrhythmic events in patients with ARVC. METHODS: High-density right ventricle electroanatomic mapping was performed in 32 patients with ARVC without history of cardiac arrest or sustained ventricular arrhythmias. Standard definitions of electroanatomic scars and fragmented, isolated, and very late potentials were used. All patients received an implantable cardioverter-defibrillator for the primary prevention of sudden death. RESULTS: After a mean follow-up of 25 ± 7 months, 12 (38%) patients received appropriate implantable cardioverter-defibrillator shock for sustained ventricular arrhythmias. With the exception of a higher rate of previous syncope (P = .053), patients with arrhythmic events at follow-up did not differ from those who remained free from arrhythmic events in terms of other clinical variables, including cardiac magnetic resonance findings. Electroanatomic scars were present in all patients. The distribution and extent of electroanatomic scars were similar in the 2 groups (38 ± 25 cm(2) vs 33 ± 20 cm(2); P = .51). However, patients with implantable cardioverter-defibrillator shock had a higher prevalence of fragmented electrograms (92% vs 20%; P <.001), of isolated late potentials (75% vs 20%; P = .004), and of very late potentials (67% vs 25%; P = .030). Fragmented electrograms were the only variable independently associated with arrhythmic events at follow-up (hazard ratio 21; P = .015). CONCLUSION: The presence of fragmented and delayed electrograms within the scar predicts arrhythmic events in ARVC.

Imaging of scar in patients with ventricular arrhythmias of right ventricular origin: cardiac magnetic resonance versus electroanatomic mapping.

INTRODUCTION: Assessment of late gadolinium enhancement (LGE) at cardiac magnetic resonance is often used to detect scar in patients with arrhythmias of right ventricular (RV) origin. Recently, electroanatomic mapping (EAM) has been shown to reliably detect scars corresponding to different cardiomyopathic substrates. We compared LGE with EAM for the detection of scar in patients with arrhythmias of RV origin. METHODS AND RESULTS: Thirty-one patients with RV arrhythmias and biopsy-proven structural heart disease (18 ARVC and 13 myocarditis), and 5 with idiopathic RV outflow tract arrhythmias underwent LGE analysis and EAM with scar validation through EAM-guided endomyocardial biopsy. EAM scars were present in 23 (64%) patients (all with structural heart disease), whereas LGE was present only in 12 (33%). In 2 cases, EAM provided a false-positive diagnosis of a small scar in the basal perivalvular area. LGE correctly diagnosed EAM scar in 48% of patients, resulting in high positive (92%) but low negative (50%) predictive values. The distribution of LGE was significantly associated with the distribution of EAM scars (P < 0.001 in the free wall, P = 0.003 in the outflow tract, and P = 0.023 in the posterior/inferior wall). Presence of LGE reflected a higher extension of EAM scars (34.4 ± 16.5% vs 7.9 ± 10.1% of the RV area, P < 0.001). At receiver operating characteristic (ROC) analysis, an extension of scar ≥20% of the RV area was the best cut-off value to detect LGE (sensitivity 83%, specificity 92%). Of note, LGE missed 10 of 11 (91%) patients with EAM scars <20% of RV area. CONCLUSIONS: LGE is significantly less sensitive than EAM in identifying RV cardiomyopathic substrates. Absence of LGE does not rule out the presence of small scars, and EAM with biopsy should be considered to increase the diagnostic yield.

Aliskiren: beyond blood pressure reduction.

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

Right ventricular substrate mapping using the Ensite Navx system: Accuracy of high-density voltage map obtained by automatic point acquisition during geometry reconstruction.

BACKGROUND: Contact point-to-point electroanatomic mapping (Pt-Map) is a validated tool to evaluate right ventricular (RV) substrate. When using the EnSite NavX system (St. Jude Medical, St Paul, Minnesota), geometry reconstruction by dragging the mapping catheter (Geo-Map) allows for quicker acquisition of a large number of points and better definition of anatomy, but it is not validated for substrate mapping. OBJECTIVE: This study evaluates the feasibility and accuracy of Geo-Map. METHODS: Thirteen patients (mean age 38 +/- 12 years) with RV arrhythmias and an apparently normal heart underwent cardiac magnetic resonance imaging (MRI), Pt-Map, and Geo-Map. The 2 maps were compared in terms of mapping procedural time, radiation time, and total number of points acquired. We finally compared the number and characteristics of low-potential areas on each patient's Pt-Map, Geo-Map, and cardiac MRI. RESULTS: Geo-Map required significantly shorter mapping and radiation times in comparison to Pt-Map (12.4 +/- 4.6 vs. 31.9 +/- 10.1 and 5.8 +/- 2.1 vs. 12.1 +/- 3.9, P <.001). Furthermore, Geo-Map was based on a significantly higher density of points in comparison to Pt-Map (802 +/- 205 vs. 194 +/- 38, P <.001). Taking into consideration the total number of RV regions analyzed, the Pt-Map and Geo-Map disagreed in 2 of 65 (3%) regions (P = NS), which only Geo-Map identified as low-potential areas and indeed corresponded to wall motion abnormalities on MRI. CONCLUSION: Voltage maps obtained through RV geometry acquisition have accuracy comparable to that of conventional point-by-point mapping in detecting low-voltage areas, have a good correlation with MRI wall motion abnormalities, and allow a significant reduction in procedural time and x-ray exposure.

Risk of arrhythmias in myotonic dystrophy: trial design of the RAMYD study.

OBJECTIVE: Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block. METHODS/DESIGN: More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00127582. CONCLUSION: The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.

High prevalence of myocarditis mimicking arrhythmogenic right ventricular cardiomyopathy differential diagnosis by electroanatomic mapping-guided endomyocardial biopsy.

OBJECTIVES: We evaluated the diagnostic contribution and the therapeutic and prognostic implications of 3-dimensional electroanatomic mapping (EAM)-guided endomyocardial biopsy (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: ARVC is a frequent cause of life-threatening ventricular arrhythmias and sudden death in young people. The value of current diagnostic criteria and the role of imaging techniques and EMB are still debated. METHODS: We studied 30 consecutive patients (17 male, mean age 43 +/- 17 years) with a noninvasive diagnosis of ARVC according to current criteria. All patients underwent 3-dimensional EAM-guided EMB. RESULTS: Twenty-nine (97%) of 30 patients presented an abnormal voltage map. Histology and immunohistochemistry confirmed the diagnosis of ARVC in 15 patients, and showed active myocarditis according to Dallas criteria in the remaining 15 patients. Patients with ARVC were not distinguishable on the basis of clinical features, presence, and severity of structural and functional right ventricular abnormalities and 3-dimensional EAM findings. On the basis of clinical and histological features, a cardioverter-defibrillator was implanted in 13 patients with biopsy-proven ARVC and in 1 patient only with myocarditis. At a mean follow-up of 21 +/- 8 months, 7 (47%) patients with ARVC experienced a recurrence of symptomatic sustained ventricular arrhythmias with appropriate defibrillator intervention in all cases. All patients with myocarditis remained asymptomatic and free from arrhythmic events. CONCLUSIONS: Right ventricular myocarditis frequently mimics ARVC. Three-dimensional EAM-guided EMB is a safe and effective tool in differential diagnosis and in the selection of the most appropriate therapeutic strategy.

Long-term follow-up of patients with cardiac syndrome X treated by spinal cord stimulation.

OBJECTIVE: To assess the long-term effect of spinal cord stimulation (SCS) in patients with refractory cardiac syndrome X (CSX). METHODS: A prospective, controlled, long-term follow-up was performed of 19 patients with CSX with refractory angina who underwent SCS (SCS group, 5 men, mean (SD) age 60.9 (8.5) years); 9 comparable patients with CSX who refused SCS treatment (3 men, mean (SD) age 60.9 (8.8) years) constituted the control group. Clinical and functional status were assessed at the time of screening for SCS indication (basal evaluation) and at a median (range) follow-up of 36 (15-82) months. RESULTS: The two groups at baseline did not show any difference in clinical characteristics and angina status. All indicators of angina status (angina episode frequency, duration and short-acting nitrate use) improved significantly at follow-up in the SCS group (p<0.001) but not in controls. Functional status, as assessed by the Seattle Angina Questionnaire and a visual analogue scale for quality of life, improved at follow-up in the SCS group (p<0.001 for all scales) but not in controls. Exercise tolerance, exercise-induced angina and ST segment changes also significantly improved in the SCS group but not in controls. CONCLUSIONS: Data show that SCS can be a valid form of treatment for long-term control of angina episodes in patients with refractory CSX.

Effect of spinal cord stimulation on spontaneous and stress-induced angina and 'ischemia-like' ST-segment depression in patients with cardiac syndrome X.

AIMS: A significant number of patients with cardiac syndrome X (CSX) present frequent episodes of severe chest pain, refractory to maximal multi-drug therapy. A few, small, uncontrolled data suggested that spinal cord stimulation (SCS) may have favourable clinical benefits in these patients. METHODS AND RESULTS: We studied 10 CSX patients who were being treated by SCS for refractory angina pectoris for 17+/-16 months (median 8). Patients were randomized to either continue or withdraw SCS for a period of 3 weeks and were then crossed over to the other condition for a further 3-week period. During each 3-week period patients kept a detailed diary of angina episodes occurring in the last 2 weeks of each phase. Furthermore, at the end of each 3-week period, angina status was also assessed by Seattle Angina Questionnaire (SAQ), a 0-100 visual analogue scale (VAS), and patients underwent 24-h Holter monitoring (HM) and echocardiographic dobutamine stress test (DST). Compared with the withdrawal phase, SCS reduced the number (P=0.01), duration (P=0.022), and severity (P=0.011) of angina episodes, and nitrate consumption (P=0.042). SAQ scores (P< or =0.013 for all) and VAS (P<0.001) were also improved, the number of episodes of ST-segment depression on HM was decreased (P=0.014), and time to angina (P=0.045) and to 1 mm ST-segment depression (P=0.04) during DST were both prolonged by SCS. CONCLUSIONS: Our data point out that SCS may be an effective form of treatment in patients with CSX suffering from frequent angina episodes significantly impairing quality of life (QOL) and refractory to maximally tolerated drug therapy.

A randomized comparison of alternative techniques to achieve coronary sinus cannulation during biventricular implantation procedures.

INTRODUCTION: Biventricular pacing system implantation is a time-consuming and challenging procedure. A critical step in biventricular pacemaker implantation is coronary sinus (CS) cannulation. CS cannulation can be achieved either using dedicated guiding catheters (guiding catheter alone positioning strategy, GCA) or with the aid of an electrophysiology catheter advanced inside the guiding catheter (electrophysiology catheter aided positioning strategy, EPA). AIM OF THE STUDY: To evaluate whether the EPA technique is useful for reducing CS cannulation time compared to a conventional GCA technique. METHODS: Thirty-four consecutive patients were randomly assigned to the GCA (18 patients) or EPA (16 patients) CS cannulation strategy. RESULTS: Time to successful catheterization of CS was 5.0 +/- 2.4 min in the EPA group versus 10.1 +/- 5.4 min in the GCA group p = 0.004. Fluoroscopy time was 4.6 +/- 2.3 min in the EPA group versus 9.2 +/- 4.9 min in the GCA group p = 0.004. Total contrast dye volume to search and engage the CS ostium was 0.0 ml in the EPA group versus 14.3 +/- 3.4 ml in the GCA group p < 0.001. CONCLUSIONS: Cannulation of CS with the adjunct of an electrophysiology catheter to dedicated delivery systems significantly reduces procedural time, fluoroscopy time and contrast dye volume compared to a conventional strategy.

Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris.

The treatment of patients with angina pectoris refractory to medical therapy and unsuitable for revascularization procedures has yet not been well standardized. Previous retrospective studies and small prospective studies have suggested beneficial effects of spinal cord stimulation (SCS) in these patients. We created a Prospective Italian Registry of SCS to evaluate the short- and long-term clinical outcome of patients who underwent SCS device implantation because of severe refractory angina pectoris. Overall, 104 patients were enrolled in the registry (70 men, aged 68 +/- 17 years), most of whom (83%) had severe coronary artery disease. Average follow-up was 13.2 +/- 8 months. Overall, 17 patients (16%) died, 8 (8%) due to cardiac death. Among clinical variables, only age was found to be significantly associated both with total mortality (p = 0.04) and cardiac mortality (p = 0.02) on Cox regression analysis. A significant improvement of anginal symptoms (> or =50% reduction of weekly anginal episodes, compared with baseline) occurred in 73% of patients, and Canadian Cardiovascular Society angina class improved by > or =1 class in 80% and by > or =2 classes in 42% of patients, with a relevant reduction in the rate of hospital admission and days spent in the hospital because of angina (p <0.0001 for both). No life-threatening or clinically serious complications were observed. The most frequent side effect consisted of superficial infections, either at the site of puncture of electrode insertion or of the abdominal pocket, which occurred in 6 patients. In conclusion, our prospective data point out that SCS can be performed safely and is associated with a sustained improvement of anginal symptoms in a relevant number of patients with refractory stable angina pectoris.