Frequent Ventricular Ectopy Research Articles

Safety and effectiveness of intravenous procainamide in patients with frequent ventricular ectopics during cardiac magnetic resonance scanning: a way to ensure high quality imaging

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiac magnetic resonance (CMR) imaging in patients with frequent ventricular arrhythmias provides significant diagnostic and prognostic information but is challenging due to artefacts. In patients with occasional ventricular premature contractions (VPCs), arrhythmia rejection algorithms can be used to acquire good quality cine images at the expense of longer breath-hold times. However, arrhythmia sorting in not practical in cases of frequent VPCs; other options include triggered data acquisition which compromises image quality or use of low temporal and spatial resolution ‘real-time’ imaging. Purpose The aim of our study was to examine the safety and effectiveness of the class Ia antiarrhythmic medication procainamide for suppressing ventricular ectopy and acquiring high quality CMR images. Methods 50 consecutive patients (mean age 48 ± 16 years; 52% female) with a high burden of VPCs during CMR scanning were included in the study. Procainamide was administered on the scanner table prior to CMR scanning at intermittent intravenous bolus doses of 50 mg every minute, until suppression of VPCs was achieved or a maximum dose of 10 mg/kg was reached. Blood pressure was measured every minute and there was continuous monitoring of heart rate and ECG trace. CMR studies were performed on a 1,5T Magnetom Avanto scanner using a standard cardiac protocol. Results The average dose of procainamide administered was 567 ± 197 mg (range 200-1000 mg). Procainamide successfully suppressed VPCs in 82% of patients (20 patients with complete suppression and 21 with significant reduction); 7 patients had minimal suppression of VPCs, while there was no effect of procainamide in only 2 patients. Baseline blood pressure (BP) was mildly reduced (mean change systolic BP -12 ± 9 mmHg; diastolic BP -4 ± 9 mmHg) but none of the patients developed symptomatic hypotension. Baseline heart rate (HR) was relatively unchanged (baseline 75 ± 11 beats per minute (bpm) – peak procainamide HR 74 ± 12 bpm (mean HR change -1 ± 6 bpm). None of the patients developed pathological ECG changes. CMR scan had normal findings in 42% of the patients, 26% had non-ischemic cardiomyopathy, in 16% the most likely diagnosis was VPC-related cardiomyopathy, 14% had previous myocarditis, and 1 patient had dual pathology (dilated cardiomyopathy with previous myocardial infarction). Mean left ventricular ejection fraction was 55% ± 9%. Conclusion We propose the bolus intravenous administration of procainamide prior to CMR scanning as a safe and effective alternative approach for suppressing VPCs and acquiring high quality images in patients with frequent ventricular arrhythmias and normal or only mildly impaired left ventricular function. Further studies are needed to assess its safety and effectiveness in larger patient cohorts, including also patients with ventricular systolic impairment.

Bolus Intravenous Procainamide in Patients with Frequent Ventricular Ectopics during Cardiac Magnetic Resonance Scanning: A Way to Ensure High Quality Imaging.

Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients (age 53.0 [42.0–58.0]; 52% female, left ventricular ejection fraction 55 ± 9%) were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced (mean change systolic BP −12 ± 9 mmHg; diastolic BP −4 ± 9 mmHg), while the baseline heart rate (HR) remained relatively unchanged (mean HR change −1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function.

Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study.

CKD is associated with sudden cardiac death and atrial fibrillation (AF). However, other types of arrhythmia and different measures of the burden of arrhythmias, such as presence and frequency, have not been well characterized in CKD. To quantify the burden of arrhythmias across CKD severity in 2257 community-dwelling adults aged 71-94 years, we examined associations of major arrhythmias with CKD measures (eGFR and albuminuria) among individuals in the Atherosclerosis Risk in Communities study. Participants underwent 2 weeks of noninvasive, single-lead electrocardiogram monitoring. We examined types of arrhythmia burden: presence and frequency of arrhythmias and percent time in arrhythmias. Of major arrhythmias, there was a higher prevalence of AF and nonsustained ventricular tachycardia among those with more severe CKD, followed by long pause (>30 seconds) and atrioventricular block. Nonsustained ventricular tachycardia was the most frequent major arrhythmia (with 4.2 episodes per person-month). Most participants had ventricular ectopy, supraventricular tachycardia, and supraventricular ectopy. Albuminuria consistently associated with higher AF prevalence and percent time in AF, and higher prevalence of nonsustained ventricular tachycardia. When other types of arrhythmic burden were examined, lower eGFR was associated with a lower frequency of atrioventricular block. Although CKD measures were not strongly associated with minor arrhythmias, higher albuminuria was associated with a higher frequency of ventricular ectopy. CKD, especially as measured by albuminuria, is associated with a higher burden of AF and nonsustained ventricular tachycardia. Additionally, eGFR is associated with less frequent atrioventricular block, whereas albuminuria is associated with more frequent ventricular ectopy. Use of a novel, 2-week monitoring approach demonstrated a broader range of arrhythmias associated with CKD than previously reported.

Left main coronary trunk spasm due to accidental catheter ablation in the artery ostium

The results of the examination and treatment of a patient with frequent ventricular ectopy are presented in the article. During ablation of an ectopic focus in the left coronary sinus of the aorta, as a result of dislocation of the ablation catheter, a spasm of the left coronary artery has been diagnosed and successfully managed.

A novel SCN5A gene mutation causing LQT3 with unique phenotype in a large canadian kindred

Abstract Background SCN5A gene mutations are associated with diverse clinical phenotypes including Long QT (LQT) Syndrome, Brugada Syndrome, progressive conduction system disease and cardiomyopathy. Objective We identified a novel SCN5A variant (T731I) in a pedigree affected by QT prolongation and ventricular arrhythmia. Clinical phenotype and co-segregation with genotype within the pedigree were characterized. Methods Family members were invited to attend clinics held in their indigenous community. All subjects underwent a history, physical exam, 12 lead ECG and had blood samples collected for genetic testing. Patients were assessed by an adult or pediatric cardiologist and genetic counselors over a six year period. There were 86 females and 69 males ranging in age from 1 to 82 years (mean 36 years) at the time of first assessment. ECG analysis was performed by a cardiac electrophysiologist blinded to patient identity and genotype. The QTc was calculated using Bazett's formula. Results One hundred and fifty five family members were evaluated (86 (55%) female; mean age 36 years (range 1 to 82 years). Mean QTc was 461 + 21 ms for the gene positive group and 419 + 22 ms for the gene negative group (P<0.001) (Figure). There was no significant difference in age or sex between the gene positive and gene negative groups. Gene positive family members were also noted to have low right atrial p waves and frequent unifocal ventricular ectopy and non-sustained monomorphic ventricular tachycardia. One gene positive individual developed dilated cardiomyopathy with high burden ventricular tachycardia and required cardiac transplantation. Conclusion This novel SCN5A variant co-segregated with an abnormal phenotype consisting of significant QTc prolongation, low atrial rhythm, and ventricular arrhythmia. This pedigree highlights the phenotypic heterogeneity of SCN5A gene mutations and the importance of cascade family screening to identify at risk family members. Figure 1. QTc intervals Funding Acknowledgement Type of funding source: None

Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene

Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P=0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P=0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P<0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (P=0.07). TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.

Genetic Loss of IK1 Causes Adrenergic-Induced Phase 3 Early Afterdepolariz ations and Polymorphic and Bidirectional Ventricular Tachycardia.

Arrhythmia syndromes associated with KCNJ2 mutations have been described clinically; however, little is known of the underlying arrhythmia mechanism. We create the first patient inspired KCNJ2 transgenic mouse and study effects of this mutation on cardiac function, IK1, and Ca2+ handling, to determine the underlying cellular arrhythmic pathogenesis. A cardiac-specific KCNJ2-R67Q mouse was generated and bred for heterozygosity (R67Q+/-). Echocardiography was performed at rest, under anesthesia. In vivo ECG recording and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type (WT) littermate controls and R67Q+/- mice. IK1 measurements, action potential characterization, and intracellular Ca2+ imaging from isolated ventricular myocytes at baseline and after adrenergic stimulation were performed in WT and R67Q+/- mice. R67Q+/- mice (n=17) showed normal cardiac function, structure, and baseline electrical activity compared with WT (n=10). Following epinephrine and caffeine, only the R67Q+/- mice had bidirectional ventricular tachycardia, ventricular tachycardia, frequent ventricular ectopy, and/or bigeminy and optical mapping demonstrated high prevalence of spontaneous and sustained ventricular arrhythmia. Both R67Q+/- (n=8) and WT myocytes (n=9) demonstrated typical n-shaped IK1IV relationship; however, following isoproterenol, max outward IK1 increased by ≈20% in WT but decreased by ≈24% in R67Q+/- (P<0.01). R67Q+/- myocytes (n=5) demonstrated prolonged action potential duration at 90% repolarization and after 10 nmol/L isoproterenol compared with WT (n=7; P<0.05). Ca2+ transient amplitude, 50% decay rate, and sarcoplasmic reticulum Ca2+ content were not different between WT (n=18) and R67Q+/- (n=16) myocytes. R67Q+/- myocytes (n=10) under adrenergic stimulation showed frequent spontaneous development of early afterdepolarizations that occurred at phase 3 of action potential repolarization. KCNJ2 mutation R67Q+/- causes adrenergic-dependent loss of IK1 during terminal repolarization and vulnerability to phase 3 early afterdepolarizations. This model clarifies a heretofore unknown arrhythmia mechanism and extends our understanding of treatment implications for patients with KCNJ2 mutation.

Heart rhythm during episodes ofcollapse in boxers with frequent orcomplex ventricular ectopy.

To describe heart rhythm during collapse events in boxer dogs using ambulatory electrocardiogram and determine the predictive value of frequent or complex ventricular ectopy for collapse associated with ventricular tachycardia. A total of 659 ambulatory electrocardiogram recordings from 429 boxer dogs were identified from a database in the UK. Summary statistics described the frequency and complexity of ventricular ectopy during all recordings, recordings in which collapse occurred and associated boxer demographics. Positive predictive values were calculated to investigate whether frequent ventricular ectopy was useful to predict heart rhythm during episodes of collapse. Of the 659 ambulatory electrocardiogram recordings, 250 recordings showed <50 single ventricular beats (Group 1), and frequent (≥50) or complex ventricular ectopy were observed in 409 recordings (Group 2). A total of 90 collapse events were observed in 72 ambulatory electrocardiograms from 68 dogs, comprising 30 dogs in Group 1 and 38 dogs in Group 2. In both groups, sinus rhythm was the most frequent collapse rhythm, followed by neurally mediated collapse and then ventricular tachycardia. The proportion of dogs that displayed ventricular tachycardia-associated episodic collapse given that they had frequent (≥50) or complex ventricular ectopy in the study population was 0.11 [95% confidence interval=0.01 to 0.21]. These results challenge the preconception that UK boxer dogs with collapse will have ventricular tachycardia and, consequently, the authors recommend definitive diagnosis of the cause of episodic collapse to guide selection of therapeutic drugs.

195 A Case Of Mitral Annular Disjunction Presenting With Ventricular Arrhythmia

Mitral annular disjunction (MAD) arrhythmic syndrome has been previously described but under-recognised in clinical practice.View Large Image Figure ViewerDownload Hi-res image Download (PPT) We present a case of a 35-year-old female who was intubated and ventilated following out of hospital cardiac arrest requiring 6 minutes of cardiopulmonary resuscitation and 2 synchronized electrical cardioversion. Medical history is significant for known bileaflet mitral valve prolapse, mild mitral regurgitation with preserved systolic function. She has Hashimoto’s thyroiditis-on thyroxine and stable myasthenia gravis. Inpatient monitoring revealed frequent ventricular ectopy with multiple episodes of non-sustained ventricular tachycardia managed with amiodarone. Transthoracic Echocardiography (TTE) revealed mitral annular disjunction (MAD). Contrast Cardiac MRI (MRC) confirmed significant MAD measuring 10mm and significant lateral annular movement of approximately 2cm with typical curling movement of posterolateral wall. There was no focal early or late gadolinium enhancement. MRC findings of mildly dilated left ventricle with moderate LV systolic dysfunction and LVEF of 38% corresponds with TTE. Her CT coronary angiogram excluded coronary artery disease. She proceeded to insertion of an automated implantable cardioverter defibrillator and commencement of heart failure therapy with weaning of amiodarone. She has remained well since the index presentation with no device therapies. This case illustrates an example of MAD and associated risk of increased life-threatening arrhythmia. Management of this complex entity is uncertain and new research is needed to inform clinicians on how to best treat these patients.

LEFT MAIN CORONARY TRUNK SPASM DUE TO ABLATION CATHETER DISLOCATION IN ITS OSTIUM DURING ECTOPIC FOCUS ABLATION IN AORTIC LEFT CORONARY SINUS

The results of the examination and treatment of a patient with frequent ventricular ectopy are presented in the article. During ablation of an ectopic focus in the left coronary sinus of the aorta, as a result of dislocation of the ablation catheter, a spasm of the left coronary artery has been diagnosed.

5163Predictors of adverse cardiovascular events in patients with truncating variants in the filamin c (flnc) gene

Abstract Background Truncating variants in Filamin C (FLNCtv) are associated with arrhythmogenic (AC) and dilated cardiomyopathies (DCM). Affected patients are reported to demonstrate a high incidence of arrhythmic and heart-failure related cardiovascular events. The aim of this study was to determine factors that predict adverse events in mutation carriers. Methods The study cohort comprised 168 FLNCtv carriers followed at 19 European centres. Baseline and longitudinal follow-up clinical data were collected. The primary endpoint was a composite of sudden cardiac death (SCD), aborted SCD, appropriate implantable cardioverter-defibrillator (ICD) shock, cardiac transplantation (HTx) and mortality from end-stage heart failure (ESHF). Results 47 different pathogenic or likely-pathogenic FLNCtv were identified in 60 unrelated probands. In those with baseline and longitudinal data (160 patients; 57 probands), 114 (71.3%) patients exhibited evidence of cardiac disease at initial evaluation. Gene penetrance was 85% by the age of 40 years. During a median follow-up of 1.5 years (IQR 4.1), 24 individuals (15%) reached the primary endpoint – 16 arrhythmic (SCD/aborted SCD/ICD shock) and 8 heart failure (ESHF/HTx) related-events. Univariable predictors at baseline evaluation of the composite primary endpoint included proband status (HR 4.0, 95% CI: 1.5–10.9, p=0.01), symptoms of dyspnoea (HR 2.8, 95% CI: 1.2–6.4, p=0.02), LV systolic dysfunction (LVSD) (HR 12.4, 95% CI: 2.9–53.2, p=0.001), frequent ventricular ectopy (VE&gt;500) on 24-hour Holter (HR 9.3, 95% CI: 1.2–74.7, p=0.04) and the presence of late gadolinium enhancement on CMR (HR 8.9, 95% CI: 1.2–68.5, p=0.04). Multivariable analysis identified LVSD (LVEF &lt;50%) at baseline as an independent predictor of the primary endpoint with a hazard ratio of 8.6 (95% CI: 1.8–41.5, p=0.007). ROC analysis using LV systolic dysfunction to predict the primary endpoint demonstrated an area under the curve of 0.84 (95% CI: 0.76–0.91, p&lt;0.001) and identified an optimal LVEF “cut-off” of 47% for predicting adverse events with a Youden's index of 0.61 (sensitivity 0.91; specificity 0.70). Kaplan-Meier plot to demonstrate freedom Conclusions LVSD is associated with an over 8-fold increase in the hazard of a primary endpoint event in FLNCtv gene carriers indicating that these patients should be considered for implantable cardioverter-defibrillator (ICD) implantation, optimal heart failure medical therapy and close clinical follow-up. Acknowledgement/Funding NIHR Biomedical Research Centre; Instituto de Salud Carlos III; DETECTIN-HF project; Wellcome Trust;CIBERCV; EU Regional Development Fund; FEDER.

Gradient variability in hypertrophic cardiomyopathy: New insights from computer‐assisted, high fidelity, rest and exercise hemodynamic analysis

ObjectivesThis study examines the intrapatient variability in peak instantaneous left ventricular outflow tract (LVOT) gradients and aortic pulse pressures during rest, exercise, and after ventricular ectopy.BackgroundAlthough the variability in LVOT gradients in patients with hypertrophic cardiomyopathy (HCM) is well known, the predictors of such variation are not. We hypothesized that quantitative invasive analysis of gradient variation could identify useful predictors of maximal gradients.MethodsVariability in continuously recorded, high‐fidelity left ventricular and aortic pressure waveforms were evaluated by computer‐assisted analysis in the resting state (N = 659 beats) and during supine exercise (N = 379 beats) in a symptomatic patient with a resting LVOT gradient >30 mmHg and frequent ventricular ectopy.ResultsAt rest, the peak left ventricular and aortic pressures at the time of the peak instantaneous LVOT gradient for all sinus and postectopic beats followed consistent regression slopes characterizing the potential energy loss between the LV cavity and aorta. During exercise, similar regression slopes were identified, and these converged with the resting slopes at the point of the maximal measured LVOT gradient. Component analysis of the LVOT gradient suggests that resting beat‐to‐beat variability provides information similar to post‐ectopic pressures for predicting maximal gradients in obstructive‐variant HCM.ConclusionsOur study suggests that computer‐assisted analysis of hemodynamic variability in HCM may prove useful in characterizing the severity of obstruction. Further study is warranted to confirm the reproducibility and utility of this finding in a population with clinically significant exercise‐induced gradients.

Ventricular Arrhythmias in the Patient with a Structurally Normal Heart.

Ventricular arrhythmias (VAs) are among the most common cardiac rhythm disturbances encountered in clinical practice. Patients presenting with frequent ventricular ectopy or sustained ventricular tachycardia represent a challenging and worrisome clinical scenario for many practitioners because of concerning symptoms, frequent associated acute hemodynamic compromise, and the adverse prognostic implications inherent to these cases. While an underlying structural or functional cardiac abnormality, metabolic derangement, or medication toxicity is often readily apparent, many patients have no obvious underlying condition, despite a comprehensive diagnostic evaluation. Such patients are diagnosed as having an idiopathic VA, which is a label with specific implications regarding arrhythmia origin, prognosis, and potential for pharmacologic and invasive management. Further, a subset of patients with otherwise benign idiopathic ventricular ectopy can present with polymorphic ventricular tachycardia and ventricular fibrillation, adding a layer of complexity to a clinical syndrome previously felt to have a benign clinical course. Thus, this review seeks to highlight the most common types of idiopathic VAs with a focus on their prognostic implications, underlying electrophysiologic mechanisms, unique electrocardiographic signatures, and considerations for invasive electrophysiologic study and catheter ablation. We further address some of the data regarding idiopathic ventricular fibrillation with respect to the heterogeneous nature of this diagnosis.

Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis.

Mitral valve prolapse (MVP) is commonly observed as a benign finding. However, the literature suggests that it may be associated with sudden cardiac death (SCD). We performed a meta-analysis and systematic review to determine the: (1) prevalence of MVP in the general population; (2) prevalence of MVP in all SCD and unexplained SCD; (3) incidence of SCD in MVP and (4) risk factors for SCD. The English medical literature was searched for: (1) MVP community prevalence; (2) MVP prevalence in SCD cohorts; (3) incidence SCD in MVP and (4) SCD risk factors in MVP. Thirty-four studies were identified for inclusion. This study was registered with PROSPERO (CRD42018089502). The prevalence of MVP was 1.2% (95% CI 0.5 to 2.0) in community populations. Among SCD victims, the cause of death remained undetermined in 22.1% (95% CI 13.4 to 30.7); of these, MVP was observed in 11.7% (95% CI 5.8 to 19.1). The incidence of SCD in the MVP population was 0.14% (95% CI 0.1 to 0.3) per year. Potential risk factors for SCD include bileaflet prolapse, ventricular fibrosis complex ventricular ectopy and ST-T wave abnormalities. The high prevalence of MVP in cohorts of unexplained SCD despite low population prevalence provides indirect evidence of an association of MVP with SCD. The absolute number of people exposed to the risk of SCD is significant, although the incidence of life-threatening arrhythmic events in the general MVP population remains low. High-risk features include bileaflet prolapse, ventricular fibrosis, ST-T wave abnormalities and frequent complex ventricular ectopy. PROSPERO (CRD42018089502).

CONGENITAL MUSCULAR DYSTROPHIES: P.334Recessive loss-of-function mutations in ITGA7 cause cardiac arrhythmia with or without structural cardiomyopathy and respiratory muscle weakness

Integrin α7 encoded by ITGA7 is highly expressed in skeletal and cardiac muscle and contributes to sarcolemmal stability by binding to laminin α2. Three unrelated patients were previously reported with ITGA7-linked congenital muscular dystrophy. Here, we report three patients from two unrelated families presenting with adult-onset cardiac arrhythmia and respiratory weakness due to recessive null mutations in ITGA7. Patient I, a 51-year-old male presented with delayed motor milestones, stridor since birth, cardiac arrhythmia (frequent ventricular ectopy, non-sustained ventricular tachycardia and premature conduction disease) requiring ICD at 46 years. Cardiac MRI showed basal septal hypertrophy and fibrosis. Examination showed focal wasting of medial gastrocnemii and respiratory impairment. EMG was myopathic. Two other male siblings also reported cardiac symptoms. Patient IIa, a 61-year-old female presented at 49 years with febrile respiratory distress requiring mechanical ventilation and tracheostomy. She had a history of atrial flutter, left bundle branch block and atrioventricular block requiring a pacemaker. She presented with further episodes of relapsing respiratory insufficiency. Examination showed mild weakness of ankle dorsiflexion (MRC 4+) and vocal cord paresis. EMG was myopathic. Muscle ultrasound showed widespread hyperechogenicity in the limb muscles. Patient IIb, her female sibling aged 55 presented with chronic hypoventilation. She had mild limb weakness. Presently she uses nocturnal non-invasive ventilation. Quadriceps biopsies (PI and PIIa) revealed non-specific myopathic changes. Next generation sequencing revealed a homozygous c.806_818del [p.S269fs] variant (PI) and two canonical splice site variants (PIIa, PIIb), (c.2357+1G>A [r.spl?] and c.2278-1G>A [r.spl?]) in ITGA7. Immunostaining revealed absent sarcolemmal integrin α7 labeling in both biopsies. Evaluation of α7-integrin-null mice showed a mild progressive myopathy with mainly diaphragmatic involvement and similar pathological features. Patients with predominant respiratory weakness and/or cardiac arrhythmias with or without structural cardiomyopathy should be screened for mutations in ITGA7.

Use of Advanced Cardiac Imaging in the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy

A 22-year-old male student presented to his general practitioner with chest discomfort and palpitations. There were no exertional symptoms or syncope and no family history of cardiac disease or sudden death. Cardiovascular examination was unremarkable. Echocardiogram demonstrated sinus bradycardia with epsilon waves in the inferior leads and abnormal T-wave morphology in the anterior leads. Seven beats of non–sustained ventricular tachycardia and frequent ventricular ectopy were present during cardiac monitoring. Transthoracic echocardiography demonstrated a dilated, dyskinetic right ventricle (RV) with systolic impairment (Figure 1) and impaired RV ventricular strain (Figure 2). There was mildly reduced left ventricular (LV) systolic function (LV ejection fraction 52%). Computed tomography coronary angiogram established normal coronary anatomy. Cardiac magnetic resonance imaging revealed segmental LV and RV dysfunction with regional fibrosis in both ventricles, predominantly affecting the right (RV ejection fraction 37%). There was severe dilatation of the RV (end diastolic volume 156 mL/m2; (Figure 3). The mid-inferior, mid-distal RV free wall, and RV outflow tract were akinetic. Post–gadolinium delayed enhancement was consistent with a non–ischaemic aetiology. The main differentials were arrhythmogenic right ventricular cardiomyopathy and cardiac sarcoidosis, the latter was excluded with a negative positron emission tomography scan. A subcutaneous implantable defibrillator was implanted for primary prevention of sudden cardiac death and the patient was started on ramipril 2.5 mg and bisoprolol 1.25 mg. He is being followed-up regularly and remains well. Proband genetic testing and family screening of first-degree relatives for arrhythmogenic right ventricular cardiomyopathy has been advised. This case illustrates the incremental value of multimodality imaging in the diagnosis of this rare but potentially life-threatening condition. Figure 2 View Large Image Figure Viewer Download Hi-res image Figure 3 View Large Image Figure Viewer Download Hi-res image

Radiofrequency Ablation in Frequent Ventricular Ectopy

Radiofrequency Ablation in Frequent Ventricular Ectopy

Predictors and Therapy of Cardiomyopathy Caused by Frequent Ventricular Ectopy.

The aim of this review is to describe predictors and therapeutic principles for PVC-induced cardiomyopathy. PVC-induced cardiomyopathy is a treatable condition resulting in a reversible form of cardiomyopathy. PVC-induced cardiomyopathy has only recently been recognized as an entity that causes a reversible form of cardiomyopathy. The mechanism of development of PVC-induced cardiomyopathy has not yet been elucidated, although dyssynchrony appears to play a major role. Multiple factors have been described that are independently associated with PVC-induced cardiomyopathy. Predictors of PVC-induced cardiomyopathy include PVC prevalence, epicardial origin, male gender, longer symptom duration and asymptomatic status, presence of interpolated PVCs, lack of circadian variability, and a broader PVC-QRS width. In the presence of cardiomyopathy, work-up for structural heart disease and its etiology should be performed, followed by aggressive attempts at PVC reduction. There is evidence that ablation therapy is superior to medical therapy for frequent PVCs, but treatment decisions need to be individualized depending on the patients symptoms, PVC prevalence, PVC origin, patients comorbidities, and patient preference. The potential of sudden cardiac death associated with the presence of structural heart disease needs to be recognized, and appropriate risk stratification is mandatory.

Long-term prognostic significance of right bundle-branch morphology ventricular ectopy induced during stress test in patients with intermediate to high probability of coronary artery disease

Stress-induced right bundle-branch block morphology ventricular ectopy (SI-RBVE) may be caused by left ventricular myocardial anomalies. While frequent ventricular ectopy (FVE) has been linked to poor outcomes, the prognostic value of SI-RBVE has not been established. The study aims to determine whether SI-RBVE is associated with increased mortality. Three hundred forty-three patients with an intermediate to high probability of coronary artery disease were prospectively included. Patients were referred for a single-photon emission computed tomography and underwent a stress test according to standard protocols. Stress-induced right bundle-branch block morphology ventricular ectopy (VE) was defined as one or more induced premature beats with positive predominance in V1. Frequent VE was defined as the presence of seven or more ventricular premature beats per minute or any organized ventricular arrhythmia. During a mean follow-up of 4.5 ± 1.3 years, 59 deaths occurred. The death rate was higher in the SI-RBVE group (23.4% vs. 14.0%, P = 0.021). Age [odds ratio (OR) = 1.09 (95% CI: 1.06-1.13), P < 0.001] and peripheral artery disease [OR = 2.47 (95% CI: 1.35-4.50) P = 0.003] were independent factors of mortality, but single-photon emission computed tomography findings were not. There was an interaction between SI-RBVE and left ventricular ejection fraction (LVEF). In patients with LVEF > 50%, SI-RBVE was an incremental risk factor for mortality [OR = 2.83 (95% CI: 1.40-5.74), P = 0.004]. Stress-induced right bundle-branch block morphology VE patients also presented higher rates of known coronary artery disease, ischaemia, scar, and ST-segment changes. Frequent VE was not related to mortality. Stress-induced right bundle-branch block morphology VE is associated with an increased mortality in patients with preserved LVEF.

The effect of mitral valve surgery on ventricular arrhythmia in patients with bileaflet mitral valve prolapse

BackgroundBileaflet mitral valve prolapse (biMVP) is associated with frequent ventricular ectopy (VE) and malignant ventricular arrhythmia. We examined the effect of mitral valve (MV) surgery on VE burden in biMVP patients. MethodsWe included 32 consecutive patients undergoing MV surgery for mitral regurgitation secondary to biMVP between 1993 and 2012 at Mayo Clinic who had available pre- and post-operative Holter monitoring data. Characteristics of patients with a significant reduction in postoperative VE (group A, defined as >10% reduction in VE burden compared to baseline) were compared with the rest of study patients (group B). ResultsIn the overall cohort, VE burden was unchanged after the surgery (41 interquartile range [16, 196] pre-surgery vs. 40 interquartile range [5186] beats/hour [bph] post-surgery; P = 0.34). However, in 17 patients (53.1%), VE burden decreased by at least 10% after the surgery. These patients (group A) were younger than the group B (59 ± 15 vs. 68 ± 7 years; P = 0.04). Other characteristics including pre- and postoperative left ventricular function and size were similar in both groups. Age <60 years was associated with a reduction in postoperative VE (odds ratio 5.8; 95% confidence interval, 1.1–44.7; P = 0.03). Furthermore, there was a graded relationship between age and odds of VE reduction with surgery (odds ratio 1.9; 95% confidence interval 1.04–4.3 per 10-year; P = 0.04). ConclusionsMV surgery does not uniformly reduce VE burden in patients with biMVP. However, those patients who do have a reduction in VE burden are younger, perhaps suggesting that early surgical intervention could modify the underlying electrophysiologic substrate.