Frequency Of Ventricular Arrhythmias Research Articles

Nature and Nurture in Arrhythmogenic Right Ventricular Cardiomyopathy - A Clinical Perspective.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterised by frequent ventricular arrhythmias and slowly progressive predominant RV dysfunction. Up to two-thirds of ARVD/C patients have mutations in genes encoding the cardiac desmosome. Mutations in other genes are increasingly recognised. Inheritance of ARVD/C is generally autosomal dominant with reduced age-related penetrance and significant variable expressivity. While the full explanation for this phenotypic heterogeneity remains unclear, there is increasing evidence that exercise plays a major role in disease penetrance and arrhythmic risk. The disproportionate representation of athletes among ARVD/C patients has long been noted. Recently, the association of exercise with earlier onset and more severe arrhythmic and structural disease has been documented. This article reviews current evidence regarding the association of genotype, exercise and clinical outcomes and discusses the emerging paradigm in which genetic predisposition and environmental factors (exercise) interact around a threshold for phenotypic expression of ARVD/C.

Heart rate and arrhythmia frequency of normal cats compared to cats with asymptomatic hypertrophic cardiomyopathy

ObjectivesTo compare heart rate and arrhythmia frequency and complexity in a normal population of cats to a population of cats with hypertrophic cardiomyopathy (HCM). Animals17 cats with HCM and 15 cats with normal echocardiograms. MethodsResults for echocardiography, electrocardiography, Doppler blood pressure, and 24-h Holter monitoring were compared between groups. ResultsThere was no difference in heart rate between HCM cats and normal cats regardless of modality used. All (17/17) HCM cats had ventricular arrhythmias (geometric mean 124 complexes/24 h) with 82% (14/17) exhibiting complex arrhythmias (couplets, triplets, or ventricular tachycardia). Most (14/15) normal cats had ventricular arrhythmias (geometric mean 4 complexes/24 h), but only 20% (3/15) exhibited complexity. HCM cats had significantly more total ventricular complexes, ventricular premature complexes and accelerated idioventricular rhythm than normal cats (P < 0.0001, P < 0.0001, and P = 0.01, respectively). Eighty eight percent (15/17) of HCM cats had supraventricular arrhythmias (geometric mean 9 complexes/24 h) with 23% (4/17) exhibiting complexity. Sixty percent (9/15) of normal cats had supraventricular arrhythmias (geometric mean 1 complex/24 h) with 13% (2/15) exhibiting complexity. Cats with hypertrophic cardiomyopathy had significantly more supraventricular complexes than normal cats (P = 0.0148). ConclusionCats with asymptomatic HCM have more frequent and complex ventricular and supraventricular arrhythmias than normal cats but do not have different overall heart rates compared to normal cats. Further studies are needed to determine if these arrhythmias are associated with an increased risk of sudden cardiac death or influence long-term survival.

Is there any influence of elevated diastolic blood pressure on ventricular arrhythmias in hypertensive patients with left ventricular hypertrophy?

Cardiologia CROATICA Objective: To investigate the prevalence of ventricular arrhythmias in a patient with isolated systolic hypertension (ISHT) and left ventricular hypertrophy (LVH) in comparison to patients with systolic and diastolic hypertension and LVH. Patients and Methods: 192 (87 men) patients with essential hypertension and LVH were divided into two groups: 98 patients with ISHT and 94 patients with systolic and diastolic hypertension. After discontinuing all medications for a period of 48 hours, the blood pressure was measured, electrocardiography, echocardiography, Holter monitoring and bicycle ergometry were performed. The number of ventricular arrhythmias was recorded. Antihypertensive drugs and the duration of previous treatment were taken into consideration. Results: Isolated systolic hypertension (systolic blood pressure >140 mmHg and diastolic blood pressure <90 mmHg) was recorded in 98 patients (51%), 47 men and 51 women (Table 1). The frequency of ventricular arrhythmias did not differ according to Lowns classification categories I-II and IIIIV in patients with and without isolated systolic hypertension (Table 2). There was no difference in the treatment duration between the groups (p=0.858), or in the type of the applied medication. We found 44% complex ventricular arrhythmias in patients with ISHT. No significant difference was found in the frequency of ventricular arrhythmias between the groups that were observed. Conclusions: No significant difference was found in the frequency of ventricular arrhythmias in patients with isolated systolic hypertension and LVH in comparison to patients with systolic and diastolic hypertension and LVH. Diastolic blood pressure does not seem to have any influence on the frequency of ventricular arrhythmias in such patients.

Expressão fenotípica da miocardiopatia hipertrófica e realce tardio na ressonância magnética cardíaca

Introduction and AimThe prognostic value of late gadolinium enhancement (LGE) for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the subject of disagreement. We set out to examine the association between clinical and morphological variables, risk factors for sudden cardiac death and LGE in HCM patients. MethodsFrom a population of 78 patients with HCM, we studied 53 who underwent cardiac magnetic resonance. They were divided into two groups according to the presence or absence of LGE. Ventricular arrhythmias and morbidity and mortality during follow‐up were analyzed. ResultsPatients with LGE were younger at the time of diagnosis (p=0.046) and more often had a family history of sudden death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037) and volume (p=0.035), and more often presented a restrictive pattern of diastolic dysfunction (p=0.011) with a higher E/É ratio (p=0.003) and left ventricular systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the association between LGE and previous echocardiographic findings: greater left atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left ventricular ejection fraction (p=0.056). Patients with LGE more often had an implantable cardioverter‐defibrillator (ICD) (p=0.015). At follow‐up, no differences were found in the frequency of ventricular arrhythmias, appropriate ICD therapies or mortality. ConclusionsThe presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in this population. However, larger studies are required to confirm its independent association with clinical events.

Phenotypic expression in hypertrophic cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance

Introduction and AimThe prognostic value of late gadolinium enhancement (LGE) for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the subject of disagreement. We set out to examine the association between clinical and morphological variables, risk factors for sudden cardiac death and LGE in HCM patients. MethodsFrom a population of 78 patients with HCM, we studied 53 who underwent cardiac magnetic resonance. They were divided into two groups according to the presence or absence of LGE. Ventricular arrhythmias and morbidity and mortality during follow-up were analyzed. ResultsPatients with LGE were younger at the time of diagnosis (p=0.046) and more often had a family history of sudden death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037) and volume (p=0.035), and more often presented a restrictive pattern of diastolic dysfunction (p=0.011) with a higher E/E′ ratio (p=0.003) and left ventricular systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the association between LGE and previous echocardiographic findings: greater left atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left ventricular ejection fraction (p=0.056). Patients with LGE more often had an implantable cardioverter-defibrillator (ICD) (p=0.015). At follow-up, no differences were found in the frequency of ventricular arrhythmias, appropriate ICD therapies or mortality. ConclusionsThe presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in this population. However, larger studies are required to confirm its independent association with clinical events.

Radiofrequency Ablation of Frequent Ventricular Arrhythmia Guided by Multielectrode Array Catheter

Introduction and objective: The non-contact mapping system with expandable balloon catheter allows ventricular arrhythmiamapping with few ectopic beats. The aim of this study was to analyze ablation results with this system.Methods: Patients with ventricular arrhythmia were prospectively and consecutively studied with the non-contact mappingsystem.Results: The study included 10 patients, 8 women, with mean age of 45 years (range: 27 to 65). Arrhythmia origin was rightventricular outflow tract in 8 patients, right ventricular inflow tract in 1 and left ventricular outflow tract in 1. Acute successwas obtained in 9/10 patients (90%). Mean follow-up was 6 months (range 1 to 16); 8 patients continued with obliteratedarrhythmia without medication and 1 patient required pharmacologic treatment. The only complication was femoralarteriovenous fistula.Conclusions: The non-contact mapping system allows a highly efficient and safe approach of right ventricular arrhythmias.Future studies with more patients and comparing with other methods may confirm these results.

Lack of efficacy of radiofrequency catheter ablation in Andersen-Tawil syndrome: are we targeting the right spot?

Andersen–Tawil syndrome (ATS) is associated with a high arrhythmic burden as demonstrated recently by Delannoy et al .1 in this Journal . Almost all subjects (91%) had very frequent ventricular arrhythmias [>10 000 premature ventricular contractions (PVCs)/day] including episodes of bigeminy and non-sustained ventricular tachycardia. As in other hereditary sudden cardiac death syndromes, it seems appropriate to eliminate these arrhythmias by means of radiofrequency catheter ablation (RFCA). To our knowledge, there is no publication …

Evaluation of Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis

Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using the Tp-e interval and Tp-e/QT ratio in patients with rheumatoid arthritis (RA), and to assess the relation with inflammation. Ninety-six patients (72 females, 24 males; mean age 43.8±11.8 years) with RA and 50 controls (35 females, 15 males; mean age 44.2±11.1 years) were included. From the 12-lead electrocardiogram, Tp-e interval and Tp-e/QT ratio were measured. Blood samples were taken for erythrocyte sedimentation rate (ESR) and plasma levels of C-reactive protein (CRP). These parameters were compared between groups. The relationship between ventricular repolarization and inflammation was assessed by Pearson correlation coefficients. Tp-e interval and Tp-e/QT ratio were increased in RA patients compared to the controls (72.6±8.2 vs 66.4±8.5 ms, 0.20±0.02 vs 0.18±0.02; p<0.001 and p<0.001, respectively). The Tp-e interval was significantly correlated with CRP, ESR, and disease activity score (DAS-28) (r=0.56, p<0.001, r=0.57, p<0.001, and r=0.29, p=0.02, respectively). The Tp-e/QT ratio was also correlated with CRP, ESR, and DAS-28 score (r=0.43, p<0.001, r=0.53, p<0.001, and r=0.25, p=0.03, respectively). In RA patients, the increased frequency of ventricular arrhythmias may be explained by increased indexes of ventricular repolarization and their relationship with inflammation.

Diagnostic Value of Cardiac Magnetic Resonance in Patients with Frequent Ventricular Arrhythmia and Normal Doppler Echocardiography

IntroductionFrequent ventricular arrhythmia can be a primary electrical disturbance or may beassociated to cardiomyopathy. The prognostic and therapeutic impact depends onthe presence of structural heart disease. Transthoracic Doppler echocardiographyhas been the most important complementary study to evaluate the presence of cardiacstructural abnormalities.ObjectivesThe aims of this study were to determine the ability of cardiac magnetic resonanceimaging to detect structural heart disease in patients with normal Doppler echocardiogramand to assess the incidence of adverse cardiovascular events during followup.MethodsThe study included 66 consecutive patients with frequent ventricular arrhythmiadefined as > 5000 ventricular extrasystoles in 24-hour Holter monitoring, ventriculartachycardia or resuscitated cardiac respiratory arrest with normal Dopplerechocardiogram. All patients underwent cardiac magnetic resonance imaging to assesscardiomyopathies.ResultsFifty-seven percent of patients had structural heart disease. The most prevalentdiagnosed pathologies were myocarditis sequelae, non-compacted myocardium andsubendocardial infarction scar. At mean follow-up of 24 ± 22 months, the incidenceof adverse cardiovascular events was 6.06 %. The number of ventricular extrasystoleswas higher in patients with abnormal cardiac magnetic resonance.DiscussionThis work demonstrates that in patients with frequent ventricular arrhythmia andnormal Doppler echocardiogram, gadolinium cardiac magnetic resonance imagingcan detect structural heart disease in more than half of the cases. Patients with frequentventricular arrhythmia during Holter monitoring, normal Doppler echocardiogramand mild alterations in the magnetic resonance present low risk of cardiovascularevents.

Valor diagnóstico de la resonancia magnética cardíaca en pacientes con arritmia ventricular frecuente y ecocardiograma Doppler normal

Valor diagnóstico de la resonancia magnética cardíaca en pacientes con arritmia ventricular frecuente y ecocardiograma Doppler normal

Catheter Ablation for Ventricular Tachycardia in Structural Heart Disease

The management of ventricular tachyarrhythmias has changed significantly over the past several decades. The advent of readily available implantable cardioverter defibrillators (ICDs) has had the greatest effect, with important mortality effects in patients with ventricular tachycardia and structural heart disease. ICDs have been shown to reduce sudden death in patients with ischemic and nonischemic cardiomyopathies; evidence of adverse consequences of ICD shocks, however, is mounting. In addition to the negative effects on patient-reported quality of life, anxiety, and depression, frequent ventricular arrhythmias and ICD shocks have also been associated with increased mortality. It is therefore important to identify and implement effective ventricular tachycardia-suppressive strategies. Antiarrhythmic drugs represent one such method, but are challenged by unfavourable side effect profiles and proarrhythmic risk. Catheter ablation of ventricular tachycardia is now a well-accepted intervention, which has been demonstrated to reduce recurrent arrhythmias. Questions persist regarding the optimal role for ablation compared with drug therapy.

Effect of Statin Therapy In Ventricular Arrhythmias In Patient With Acute Anterior Myocardial Infarction

Background: Though statins are widely used in acute coronary syndrome (ACS), there is a paucity of information on the efficacy of high dose statin therapy in reducing the incidence of ventricular arrhythmias after acute myocardial infarction. Arrhythmias are relatively common in acute myocardial infarction (AMI) anterior, and sometimes progress to cardiac arrest. This study was planned to evaluate the role of high dose atorvastatin therapy in prevention of ventricular arrhythmias after acute anterior myocardial infarction. Methods: This study was conducted in NICVD from December 2010 to October 2011. Total 200 patients with newly diagnosed acute anterior myocardial infarction who received thrombolytic therapy were included in the study. They were divided into two groups. Group I (n=100) was selected for high dose atorvastatin therapy and group II (n=100) was selected for conventional doses of atorvastatin therapy. 24 hours Holter monitoring was performed 48 hours after hospital admission to evaluate arrhythmia. Results: Majority of the patients belonged to age range of 40 to 59 years with a male predominance. Patient characteristics regarding age, sex, drug use, risk factors for ventricular arrhythmia, body mass index, left ventricular ejection fraction were similar in two study groups. There was no electrolyte imbalance or renal impairment in any patient in either group. A significant difference in frequency of ventricular arrhythmias was found between the two groups. Ventricular premature beats were found in 66% patients in group I and 97% patients in group II (p=0.001) whereas non sustained ventricular tachycardia were observed in 0% and 4% in group I and group II respectively. Conclusion: High dose atorvastatin therapy is associated with lower frequency of ventricular arrhythmias after acute anterior myocardial infarction. Cardiovascular Journal Volume 6, No. 1, 2013, Page 37-42 DOI: http://dx.doi.org/10.3329/cardio.v6i1.16113

Ventricular arrhythmias before and after transcatheter aortic valve implantation

Purpose: Transcatheter aortic valve implantation (TAVI) is a therapeutic option for patients with severe aortic stenosis at high surgical risk. Although the procedure is associated with a reduction in total mortality, there is no data in the literature regarding the variability in the incidence of ventricular arrhythmias (VAs) after TAVI. The aim of this study is to assess the incidence of VAs before and after TAVI and to identify the prognostic value of these arrhythmias. Methods: We enrolled 239 patients at high surgical risk who underwent TAVI at our institution between June 2007 and December 2011. Eighty-two patients were excluded from our study for the following reasons: presence of permanent pacemaker (PPM) before the procedure (n=24, 10%), new PPM implant after the procedure (n=25, 10.5%), death during the period follow-up (n=31 pcs, 13%). A total of 157 patients were included in our analysis. The presence of VAs was evaluated in all patients recording a 24-hrs Holter monitoring before the procedure and after 1, 6 and 12 months. VAs were classified according to the classification of Lown in 5 grades: absence of ventricular ectopic beats (VEB) (grade 0); VEB occasional and isolated, less than 30/h (grade 1); VEB isolated and frequent higher than 30/h (grade 2); VEB multifocal (grade 3); presence of pairs (grade 4a); ventricular tachycardia (grade 4b). Results: Before the procedure, isolates VEB (grade 1-2) were present in 54.1% of patients (n=76). Among these patients, only 20 (12.7%) had frequently VEB, more than 30/h. Complex VAs (grade 3-4) were present in 22.3% of the population (multifocal VEB in 10 pts, 6.3%; pairs in 11 pts, 7%, ventricular tachycardia in 14 pts, 8.9%). One month after the procedure, we observed an increased incidence of arrhythmias of grade 2 (n 22, 17.5%), and complex arrhythmias grade 3 (n=37 pts, 23.6%). The follow-up at 6 and 12 months showed a significant reduction in the frequency of VAs in each group. In particular, after 1 year of the procedure, only 37% of patients had isolates VEB (n=41 group 1, n=6 group 2), while the frequency of complex arrhythmias was reduced to 14.6% (multifocal VEB in 11 pts, 7% couples 7 pts, 4.5% and ventricular tachycardia in 5 pts, 3.2%). Conclusion: We observed an increase in the incidence and severity of VAs immediately after TAVI. However, this increase was transient. The long-term follow-up showed a significant reduction in the frequency of complex VAs. This may be related to the benefits determined by valve replacement on left ventricular function.

Has late gadolinium enhancement an incremental value for management of patients with hypertrophic cardiomyopathy?

Purpose: Some authors suggest the presence of fibrosis, identified with Late Gadolinium Enhancement (LGE) in Cardiac Magnetic Resonance (CMR), can be related to the subject arrhythmogenic risk in patients (P) with Hypertrophic Cardiomyopathy (HCM). We aim to examine the association between clinical-morphological variables, risk factors for sudden cardiac death and LGE findings in a population with HCM. Methods: From a population of 74 HCM P, we studied 55 P (51% male; age 63±18 years) who performed CMR. They were divided in 2 groups: LGE+ (with LGE; n=25; 45.5%) and LGE- (without LGE; n=30; 54.5%). Follow-Up (FU) regarding ventricular arrhythmias and Mortality (M) was done. Results: HCM diagnosis was done at a younger age (53±17 vs 61±17; p=0.051) in LGE+. No differences were found regarding gender, cardiovascular risk factors, previous syncope, NYHA class, ambulatory medication, identification of HCM mutation, electrocardiographic criteria for left ventricular hypertrophy or atrial fibrillation. LGE+ more often had family history of sudden death (32% vs 3.4%; p=0.008) and known coronary artery disease (12.0% vs 0%; p=0.088). They also presented a trend towards higher NTproBNP values (5151±7882 vs 1489±2422, p=0.089). Blood pressure response during exercise test was similar. Regarding echocardiogram LGE+ had higher interventricular septum (IVS) thickness (18.8±5.1 vs 15.9±3.09; p=0.017) and left atrium (LA) volume (102.1±33.7 vs 85.4±32.9, p=0.078); more often presented a restrictive pattern of diastolic dysfunction (8.7% vs 4.2%; p=0.021) with a higher E/E' relation (16.5±7.6 vs 12.0±5.9; p=0.022); and left ventricular systolic impairment (24.0% vs 3.3%; p=0.039). No differences were found concerning HCM phenotype, presence of obstruction or mitral regurgitation severity. CMR reinforced the association between LGE+ and previously echocardiographic findings: higher LA volume (32.88±3.6 vs 29.3±5.2; p=0.034); IVS thickness (21.3±4.1 vs 17.9±2.8; p=0.001) and left ventricle ejection fraction (64.1±8.9 vs 68.0±8.6; p=0.064). LGE+ more often had an implantable cardioverter defibrillator (ICD) (36.0% vs 6.7%, p=0.006). At FU (32.0±74.4 months), no differences were found regarding the frequency of ventricular arrhythmias, appropriated ICD therapies or mortality. Conclusions: In this population the presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in HCM patients. However its independent association to clinical events requires the study of larger populations, so it can be interpreted as having an incremental value for risk stratification of these P.

Local delivery of thrombolytics before thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention - the dissolution randomized trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520).

High-resolution electrocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in Boxer dogs

To evaluate the reliability of high-resolution electrocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in Boxers, 20 dogs with no structural cardiac alterations at echocardiographic examination were grouped on the basis of frequency of ventricular arrhythmias, evaluated by 24-hour ambulatory ECG, and undergoing a high-resolution electrocardiography. High frequency QRS duration, duration of terminal QRS complex less than 40µV (LAS40) and root mean square voltage of the terminal 40 milliseconds of the QRS complex (RMS40) were measured. Differences in high-resolution ECG variables were not observed between groups. Therefore, the results of this investigation suggest that high-resolution electrocardiography is not a useful method for the diagnosis of arrhythmogenic right ventricular cardiomyopathy in Boxers without detectable myocardial alterations or systolic dysfunction.

Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive myocardial loss, with fibro-fatty replacement, and high frequency of ventricular arrhythmias that can lead to sudden cardiac death. ARVC is a genetically determined disorder, usually caused by point mutations in components of the cardiac desmosome. Conventional mutation screening of ARVC genes fails to detect causative mutations in about 50% of index cases, suggesting a further genetic heterogeneity. We performed a genome-wide linkage study and a copy number variations (CNVs) analysis, using high-density SNP arrays, in an ARVC family showing no mutations in any of the desmosomal genes. The CNVs analysis identified a heterozygous deletion of about 122 kb on chromosome 12p11.21, including the entire plakophilin-2 gene and shared by all affected family members. It was not listed on any of available public CNVs databases and was confirmed by quantitative real-time PCR. This is the first SNP array-based genome-wide study leading to the identification of a CNV segregating with the disease phenotype in an ARVC family. This result underscores the importance of performing additional analysis for possible genomic deletions/duplications in ARVC patients without point mutations in known disease genes.

Recurrent orthostatic syncope due to left atrial and left ventricular collapse after a continuous-flow left ventricular assist device implantation

Left ventricular assist devices (LVADs) have become an established treatment for patients with advanced heart failure as a bridge to transplantation or for permanent support as an alternative to heart transplantation. Continuous-flow LVADs have been shown to improve outcomes, including survival, and reduce device failure compared with pulsatile devices. Although LVADs have been shown to be a good option for patients with end-stage heart failure, unanticipated complications may occur. We describe dynamic left atrial and left ventricular chamber collapse related to postural changes in a patient with a recent continuous-flow LVAD implantation.

Provocative tests and electrophysiological study in athletes

Provocative tests can be divided into three main categories: first-level or screening tests, consisting basically of step test, which all athletes undergo during pre-participation screening; second-level tests, which include exercise test (simple or cardiopulmonary), performed on the basis of specific clinical indications or for the assessment of functional capacity; and third-level tests, consisting of complex methods such as myocardial scintigraphy and stress echo (or exercise echo), which are performed in subjects adequately selected according to clinical characteristics or to the results of first- and second-level tests. The electrophysiological endocavitary study has specific indications in sustained or frequent ventricular arrhythmias, while it is not useful in diagnostic evaluation of athletes with supraventricular arrhythmias, where it has been replaced in most cases by transesophageal electrophysiological study.

462 Simvastatin in the Setting of INOS Deletion Improves Survival in Mice With Ventricular Hypertrophy Secondary to Calcineurin Overexpression

Overexpression of calcineurin (CN) causes cardiac hypertrophy and arrhythmic deaths secondary to either heart block or ventricular tachyarrhythmias (VT). Statins have been reported to prevent the development of left ventricular hypertrophy (LVH) in some experimental models and in patients with heart disease. We have previously reported that simvastatin prevented VT associated with CN overexpression but did not improve survival or modify the magnitude of LVH. Inducible nitric acid (NO) synthase (INOS) has been implicated in cardiac injury. Here, we tested the hypothesis that simvastatin would improve survival in transgenic mice with CN overexpression and INOS deletion. Double recombinant mice with CN overexpression and INOS deletion were treated daily with 2mg/kg simvastatin (n=10) or placebo (n=11) up to 270 days of age. ECGs were monitored for 5 minutes every 10 days commencing at age 35 days. Heart rate, P-R interval, AV block and spontaneous VT were compared between groups at ages 46 and 126 days. Heart weight, heart septum thickness and left ventricle wall thickness were compared between groups at death. Survival was also compared between the two groups. Simvastatin did not significantly reduce cardiac mass or dimensions. Simvastatin improved survival in the INOS-CN mice (Figure) and increased resting heart rate. Simvastatin did not modify AV conduction or magnitude of heart block but tended to reduce ventricular arrhythmia frequency. Tabled 1View Large Image Figure ViewerDownload (PPT) Simvastatin treatment improved survival in double recombinant INOS deletion x CN mice in the absence of structural remodeling. The mechanism(s) of improved survival will require further study.