Ventricular Electrical Instability Research Articles

Diagnosis of arrhythmogenic cardiomyopathy: 20 years of progress and innovation

Arrhythmogenic cardiomyopathy (CMA) is a cardiac disease characterized by non-ischemic ventricular scarring and electrical instability. The diagnosis of CMA still remains challenging today and requires the use of a set of criteria, since no single diagnostic test represents the gold standard. The first diagnostic criteria were defined and disseminated in 1994 and then revised in 2010, focusing mainly on right ventricular involvement. In 2019, an international panel of experts identified the limitations of the previous diagnostic criteria. The 2020 Padua criteria included a specific pathway for the diagnosis of left ventricular variants and emphasized the need for the use of cardiac magnetic resonance imaging in the characterization of myocardial scarring. These criteria were further refined and published in 2023 as European Task Force (TF) criteria, thus gaining international recognition.Exploring the history of CMA and its diagnosis, in this review we analyze the changes and progress in the 20 years that have occurred from the first version of the criteria in 1994 to the latest in European TF of 2023, highlighting the evolution of our knowledge of the pathobiology and morpho-functional characteristics of the disease. One of the most relevant updates is undoubtedly the introduction of the concept of "scarring/arrhythmogenic cardiomyopathy", a definition that enhances the main features of the pathology and emphasizes the multiplicity of phenotypes and clinical presentations independent of etiology.

The 2023 European Task Force Criteria for Diagnosis of Arrhythmogenic Cardiomyopathy: Historical Background and Review of Main Changes.

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disease featured by non-ischemic myocardial scarring linked to ventricular electrical instability. As there is no single gold-standard test, diagnosing ACM remains challenging and a combination of specific criteria is needed. The diagnostic criteria were first defined and widespread in 1994 and then revised in 2010, approaching and focusing primarily on right ventricular involvement without considering any kind of left ventricular variant or phenotype. Years later, in 2020, with the purpose of overcoming previous limitations, the Padua Criteria were introduced by an international expert report. The main novel elements were the introduction of specific criteria for left ventricular variants as well as the use of cardiac magnetic resonance for tissue characterization and scar detection. The last modifications and refinement of these criteria were published at the end of 2023 as the European Task Force criteria, by a "head-quarter" of ACM international experts, proving the emerging relevance of this condition besides its difficult diagnosis. In this review, emphasizing the progress in understanding the aetiology of the cardiomyopathy, an analysis of the new criteria is presented. The introduction of the term "scarring/arrhythmogenic cardiomyopathy" sets an important milestone in this field, underlying how non-ischemic myocardial scarring-typical of ACM-and arrhythmic susceptibility could be the main pillars of numerous different phenotypic variants regardless of etiology.

Impact of short-term exercise training on QT dispersion and double product in diabetic patients after surgical aortic valve replacement

Abstract Background QT dispersion (QTd) represents the heterogeneity in the repolarization of the ventricular myocardium and electrical instability of the myocardium, reflecting the increased tendency towards ventricular arrhythmias. Abnormally high QTd has been correlated with risk of cardiac death. Purpose The aim of this study was to establish the influence of short-term exercise training on QT dispersion and double product (DP), in diabetic patients after surgical aortic valve replacement (SAVR). Methods The study involved 147 patients after SAVR, in the sinus rhythm without AV blocks or branch blocks. Average age of patients was 59.3 years. 45 patients were with diabetes mellitus, and 102 were without diabetes. Patients were similar as to age and baseline stress test duration. In all subjects clinical examination, standard ECG and exercise test on treadmill according to Bruce protocol, were performed and after that patients were included in program of physical training for three weeks. Patients were instructed to follow a training program using the bicycle ergometer (10 min, 2 times a day), gymnastic exercises and walking. The patients continued to take the same medicaments in same doses. From standard ECG corrected QT dispersion (QTdc) was calculated. Results Before starting with the program of physical training, patients with diabetes had significantly higher values of QTdc (83.4 ± 15.3 vs 74.6 ± 16.9 ms; p<0.005) in comparison to those without diabetes. After three weeks, significant reduction of QTdc was found (from 83.4 ± 15.3 to 77.3 ± 15.4 ms; p<0.02 in patients with diabetes and from 74.6 ± 16.8 to 68.7 ± 17.1 ms; p<0.005 in patients without diabetes). After three weeks, significant reduction of DP was found (from 11763.8 ± 779.9 to 11314.8 ± 635.8 beat/min x mmHg; p<0.005 in patients with diabetes and from 114376.4 ± 792.3 to 10034.2 ± 521.3 beat/min x mmHg; p<0.001 in patients without diabetes). In diabetic patients, after program of physical training, significant reduction of glycemia was found (from 7.0 ± 2.3 to 5.9 ± 1.5 mmol/L; p<0.005), of total cholesterol from 5.2 ± 1.3 to 4.6 ± 1.1 mmol/L (p<0.025), of LDL cholesterol from 3.2 ± 0.8 to 2.8 ± 0.6 mmol/L (p<0.05). After three weeks, both groups of patients in the exercise test reached a significantly longer time (p<0.001). Conclusions The study showed that patients with diabetes have a higher value QTdc, probably due to diffuse interstitial fibrosis. Short-term exercise training has favourable effects on QT dispersion and double product in patients after SAVR. In patients without diabetes physical training had more favourable effects on the followed parameters. Physical training led to the significant decrease of myocardial oxygen uptake at rest and probably decreased the possibility of arrhythmia events.

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent “non-ischemic” myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the “Padua criteria” were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other “non-scarring” myocardial disease. The “ring-like’ pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

Predictive value of the frontal QRS-T angle for a permanent pacemaker requirement in patients undergoing transcatheter aortic valve implantation.

Despite recent advances, the requirement for permanent pacemaker (PPM) implantation after transcatheter aortic valve implantation (TAVI) remains high. The frontal QRS-T angle (fQRS-Ta) indicates ventricular electrical instability as well as ventricular depolarization and repolarization heterogeneity. The predictive value of fQRS-Ta for the PPM requirement after TAVI is lacking. Therefore, we aimed to investigate the predictive value of baseline fQRS-Ta for the requirement of PPM after TAVI. This is a retrospective study conducted at a single tertiary care center. The patients were divided into two groups: those who required a pacemaker (PPM group) and those who did not (No-PPM group). The optimal fQRS-Ta cut-off value for predicting a PPM requirement was determined by using receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to determine the independent predictors of post-TAVI PPM placement. Final study population consisted of 184 patients. The mean age of the patients was 79.41 ± 7.88 years, and 61% (n = 113) were women. Twenty-seven patients who required PPM after TAVI were considered as the 'PPM group'. The baseline frontal QRS and T axes did not differ between the groups, but the fQRS-Ta was significantly higher in the PPM group. ROC analysis performed for the prediction of post-TAVI PPM need, the fQRS-Ta cut-off value was found to be 100.5 with a sensitivity of 74.1% and a specificity of 60.5% [AUC (95% CI): 0.637 (0.520 - 0.755), p: 0.023]. In multivariate analysis, age [HR (95% CI): 1.071 (1.005 - 1.142), p: 0.034] and fQRS-Ta [HR (95% CI): 2.509 (1.084 - 6.399), p: 0.044] were identified as independent risk factors for PPM requirement after TAVI. This study demonstrated that age and baseline fQRS-Ta were independent predictors of PPM requirements after TAVI in patients with aortic stenosis.

Ventricular conduction improvement after pericardial fat reduction triggered by rapid weight loss in subjects with obesity undergoing bariatric surgery.

Obesity is considered a major cardiovascular risk factor. The excess of pericardial fat (PF) in patients with obesity has been associated with a variety of electrocardiographic alterations. In previous studies, we demonstrated that rapid weight loss and bariatric interventions result in decreased PF. The aim of this study is to report the changes in PF after bariatric surgery and its effect on ventricular conduction. US hospital, academic institution. A linear measurement of PF thickness on computed tomography scans was obtained for 81 patients, as well as a retrospective review of electrocardiographic changes before and after bariatric surgery. We compared the changes in PF thickness and electrocardiographic components before and after procedures. Common demographics and co-morbidities were collected along with lipid profiles preoperative and postoperative. A total of 81 patients had electrocardiograms done before and 1 year after bariatric surgery. Females comprised 67.9% (n = 55), and the average age for our population was 55.07 ± 14.17 years. Pericardial fat thickness before surgery was 5.6 ± 1.84 and 4.5 ± 1.62 mm after surgery (P = .0001). Ventricular conduction (QT and QT corrected [QTc] intervals) showed a significant improvement from 438.7 + 29 before to 426.8 + 25.3 after bariatric surgery (P = .006). We found a statistically significant association between the decrease in PF and the decrease in QTc intervals (P = .002). Obesity is a risk factor for arrhythmias and sudden cardiac death. Bariatric surgery and its effect on PF produce an improvement in ventricular conduction, which may reduce the ventricular electrical instability in patients with obesity.

Mitral and tricuspid annulus disjunction frequently coexist

Abstract Background Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus, frequently found in patients with high-risk arrhythmogenic mitral valve prolapse syndrome. It is unknown whether the annulus disjunction extends to the right side of the heart as tricuspid annulus disjunction (TAD), and whether it is associated with right ventricular electrical instability. Purpose We aimed to explore the presence of TAD, and if extended annulus disjunction was associated with ventricular arrhythmias. Methods We included patients with previously described MAD assessed by cardiac magnetic resonance imaging (CMR) in an ambispective cohort study. MAD and TAD was defined as ≥1 mm separation between the respective atrial wall-valve leaflet junction and the top of the ventricular myocardium. TAD was assessed in the lateral and inferior right ventricular free wall by means of the 4-chamber and right ventricular 2-chamber views, respectively. MAD circumference was assessed by a CMR study protocol with six left ventricular long axis views separated by 30 degrees. Mitral valve prolapse was defined as ≥2 mm superior displacement of any part of the mitral leaflets beyond the mitral annulus. Ventricular arrhythmias were defined as aborted cardiac arrest or non-sustained/sustained ventricular tachycardias recorded by electrocardiogram (ECG), stress ECG or Holter monitoring. Results We included 92 patients with MAD (62% female, age 47±16 years, 71% mitral valve prolapse). TAD was found in 48 (52%) patients, both in the lateral (n=40, 83%) and inferior (n=30, 63%) right ventricular free wall. Patients with TAD were older (age 51±16 years vs. 43±14 years, p=0.01), had greater MAD circumference (168±56° vs. 117±62°, p=0.001) and greater MAD distance (9.2±2.9 mm vs. 6.4±2.8 mm, p<0.001). Additionally, patients with TAD had more frequently mitral valve prolapse (40 patients [85%] vs. 25 patients [57%], p=0.003), whereas similar frequency of bileaflet prolapse (17 patients [39%] vs. 10 patients [39%], p=0.99). Ventricular arrhythmias had occurred in 38 (41%) patients, who were younger (age 40±14 years vs. 52±15 years, p<0.001) and had less frequently TAD (14 patients [37%] vs. 34 patients [63%], p=0.01; univariate odds ratio 0.34 [0.15–0.81], p=0.02). However, TAD was not associated with ventricular arrhythmias when adjusted for age (multivariate odds ratio 0.46 [0.18–1.15], p=0.10). Conclusions TAD by CMR was highly prevalent in patients with MAD and was a marker of severe annulus disjunction and mitral valve prolapse. TAD was not associated with more ventricular arrhythmias. This novel marker warrants further research to explore the clinical implications of right-sided annulus disjunction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council

Diagnostic Overlap Between Arrhythmogenic Right Ventricular Dysplasia And Myocarditis

Background Arrhythmogenic Right Ventricular Dysplasia (ARVD) is inherited cardiomyopathy with an estimated prevalence of 1 in 5000 people. Case 20 years old male with no PMH had out of hospital cardiac arrest while playing basketball. Bystander CPR was started immediately, and ROSC was achieved after 2 shocks for Vfib. He was intubated immediately on arrival at the nearest ER. A bedside echo showed biventricular failure with LVEF of 5-10%. The patient was taken for an urgent LHC that showed normal coronary arteries. An IABP was placed and he was transferred to our hospital for advanced heart failure therapies. Physical examination was remarkable for intubated and sedated patient with no JVD, and extremities were warm to touch. EKG showed normal sinus rhythm with T wave inversions in V1-V3 lead, normal QTc (Figure 1). He underwent emergent RHC with endomyocardial biopsy which showed RA of 18 mmHg, RV of 36/14 mmHg, PA of 33/18 mmHg, PCWP of 20 mmHg, CO/CI of 2.52/1.24 and PA sat of 48%. Cardiogenic shock conference was initiated, and the decision was made to proceed with VA-ECMO. The biopsy showed inflammatory infiltrate including macrophages, neutrophils, T cells, and focal associated myocyte damage but no giant cells or lymphoid aggregates (Figure 1). This was concerning for acute fulminant myocarditis vs another inflammatory process. He started showing signs of hemodynamic and echocardiographic recovery on day 2 without requiring immunosuppressive medications. VA-ECMO was decannulated on day 3 and extubated on day 4. He was diagnosed as myocarditis and discharged on day 7 with full LVEF recovery but RV remained dilated with reduced function. A cardiac MRI done 1 week later ruled out myocarditis. On follow up visit one month later, he is asymptomatic. His echo shows dyskinetic and dilated RV with PLAX RVOT of 33 mm with normal LV (Figure 1). Genetic testing showed PKP2 mutation. Hence, the diagnosis was ultimately modified to ARVD. He is now referred for an ICD implantation and advised abstinence from competitive sports. Discussion ARVD presents a diagnostic challenge since diseases like myocarditis, sarcoidosis, and dilated cardiomyopathy can act as mimics. Our patient met three major criteria from the 2010 International Task Force Guidelines, including EKG, echo, and genetic mutation; hence meeting requirements for definitive diagnosis of ARVD. ARVD can lead to sudden cardiac death due to ventricular electrical instability. Conclusion ARVD poses diagnostic challenge, a high index of clinical suspicion is required. Initially, ARVD can present similarly to myocarditis on histopathology. VA-ECMO can be utilized as bridge to recovery in critically ill patients with ARVD.

Modulation of activated astrocytes in the hypothalamus paraventricular nucleus to prevent ventricular arrhythmia complicating acute myocardial infarction

BackgroundSympathetic overactivation after acute myocardial infarction (AMI) contributes to ventricular arrhythmia (VA). Paraventricular nucleus (PVN) of the hypothalamus may play an important role on this context, however, the mechanisms remain unknown. In this study, we investigated whether inhibition of activated astrocytes in the PVN could reduce VA in rats with AMI. MethodsThe anesthetized rats were randomly divided into four groups of sham-operated, AMI, AMI + vehicle and AMI + fluorocitrate (FCA). Electrocardiogram was continuously recorded. RNA sequencing, sympathetic nerve activity (heart rate variability and norepinephrine levels) and ventricular electrical instability (ventricular effective refractory period and ventricular fibrillation inducibility) were measured. Furthermore, brain tissues were extracted to detect expression of inflammatory cytokines (IL-6, and TNF-α), astrocyte and neuro activation. ResultsRNA sequencing analysis showed that functions of differentially expressed genes in the PVN of AMI rats were significantly enriched in immune system- and neuroactive-related pathways, along with enhance expression of cytokines and Glial fibrillary acidic protein (GFAP). We further characterized that astrocytes were activated in PVN and intervention of activation astrocytes by FCA significantly inhibited sympathetic nerve activity and decreased the incidence of VA and ventricular electrical instability in rats with AMI. Moreover, FCA significantly attenuated neurons activation and downregulated expression of inflammatory cytokines in the PVN. ConclusionsInhibition of activated astrocytes in the PVN could reduce VA occurrence and improve ventricular electrical instability in AMI rats by central neuro-immune pathway. These findings suggest that astrocytes are a potential target for prevention and treatment of VA complicating AMI.

3075Global longitudinal strain and mechanical dispersion in the general population aged 50–64 years – results from the echocardiography study of the Swedish CArdioPulmonary bioImage Study (SCAPIS)

Abstract Background The Swedish CArdioPulmonary bioImage Study (SCAPIS) was initiated to improve understanding of underlying mechanisms in order to prevent cardiovascular and pulmonary disease. 30 000 individuals aged 50–64 years, randomly selected from the general population, were included in the study. Six-thousand-eight-hundred of the individuals underwent transthoracic echocardiography. Global longitudinal strain (GLS) and mechanical dispersion (MD) are novel echocardiographic measures of left ventricular (LV) systolic function and electrical instability reflecting risk for malignant arrhythmia, respectively. Previous studies suggest that the limit of normal for GLS is −16% and that MD >70 ms may be associated with increased risk for malignant arrhythmias. GLS and MD have, however, not before been investigated in a large population-based study. Purpose The purpose of this first project within the SCAPIS echocardiography study is to determine the prevalence of impaired GLS and MD in the general population aged 50–64 years. Methods GLS and MD, defined as mean peak longitudinal strain of the 18 LV segments and standard deviation of time-to-peak strain for the 18 LV segments, respectively, were analysed using a commercially available software. For group comparisons, the independent-samples t-test, the Mann-Whitney U-test or One Way Analysis of Variance with the Bonferroni post hoc test were performed. Values are mean±standard deviation. Results 1850 examinations have so far been reviewed, whereof image quality was considered adequate for strain analysis in 1480 individuals (80%). Image quality, assessed as the number of visually assessable LV segments, was better for the second half of the examinations, as compared to the first half (p<0.001). Of the 1480 individuals where GLS and MD were assessed, 51% were women and mean age was 57±4.4 years with no difference in age between the sexes (p=ns). Mean GLS was −20±2% and men had significantly more negative (p<0.001) GLS values than women (−21±2% vs. −19±2%). There was no significant difference (p=ns) in GLS when comparing individuals aged 50–54, 55–59 or 60–64 years, respectively. GLS values were less negative than −16% in 1.9% of the study population. Mean MD was 41±12 ms with no significant difference (p=ns) between the sexes. MD was significantly lower (p<0.001) among individuals aged 50–54 years, as compared to those aged 55–59 or 60–64 years, respectively. MD was >70 ms in 1.6% of the study population. Conclusions These preliminary data from the SCAPIS echocardiography study suggest that, in the general population aged 50–64 years, 1.9% have impaired GLS and 1.6% have increased MD, which is possibly associated with a higher risk for malignant arrhythmias. Men had more negative GLS values than women and MD was lower in the lowest age tertile. Further analyses are ongoing. Acknowledgement/Funding The Swedish Heart and Lung Foundation. Grants from Linkoping University. ALF-grants from the Swedish government (LIO-700841).

Changes of QT Dispersion in Patients Suffering from Aluminium Phosphide Poisoning (Rice Pill).

BACKGROUND:Aluminium phosphide (ALP) or rice pill is a substance used in developing countries due to its low cost as pesticides. The availability of this substance has been lead to an increased rate of the use of this toxic inorganic compound for suicide. Complications are considered to be dose-related toxicity and hospitalisation time, varying from hemodynamic disorder, hypoglycemia, hyperglycemia, shock, cardiotoxicity, pulmonary and renal failures. The consumption of this substance is one of the major causes of mortality due to heart arrhythmia. QT dispersion represents a regional difference in ventricular repolarisation and electrical instability of the heart.AIM:The purpose of this study was to investigate the effect of ALP poisoning on QT dispersion.METHODS:In this study, 70 patients with ALP poisoning were enrolled, and 10 patients were excluded due to the exclusion criteria. QT dispersion rate was calculated in 60 patients using the standard electrocardiography at the time of referral. The above data were compared with the control group, which included 40 subjects with normal coronary angiography, and without cardiovascular risk factors.RESULTS:The findings presented herein indicated a significant correlation between QT dispersion and control group (P < 0.0.5). There was a significant relationship between the severity of acidosis and the patient’s tablets –taking a number (P < 0.05). However, there was no relationship between QT dispersion with the severity of acidosis and mortality in patients.CONCLUSION:Because there is no CAD risk factor in the population, it can be concluded that increase in QT dispersion in these individuals can be due to ALP poisoning; nevertheless, this is not considered to be a factor in increasing the morbidity of these patients.

Stimulation of Epicardial Sympathetic Nerves at Different Sites Induces Cardiac Electrical Instability to Various Degrees

The cardiac sympathetic nerves distribute across cardiac tissues with uneven density. Yet, to what extent this anatomical heterogeneity affects electrical activity of the left ventricle is largely unknown. Dogs were randomized into non-stimulation control (NC), posterior basal-stimulation (PB), anterior superior-stimulation (AS), apical part-stimulation (AP) group. The epicardial sympathetic nerves at different sites along their distribution were with electrical stimulation (ES) for 4 hours except in the NC group. The myocardial effective refractory period (ERP), ventricular fibrillation threshold (VFT) and density of sympathetic nerves were recorded. Compared with ES at other places, the stimulation at PB site significantly shortened ERP (left ventricular anterior and posterior walls; PB group, 118 ± 4 ms, 106 ± 2 ms; Versus NC group, 155 ± 3.5 ms, 160 ± 3 ms; p < 0.01) and VFT (PB group, 11.5 ± 1.5 V; Versus NC group, 20.5 ± 0.9 V; p < 0.01), and induced remarkable regeneration of the cardiac sympathetic nerves, hence influencing electrical activity of the left ventricle to the most extent. Our study demonstrates that the degree of induced ventricular electrical instability is correlated tightly with the density of sympathetic nerves around ES site, and PB site is a potential target for modulating ventricular electrical activity to the maximal extent.

Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.

BackgroundModulation of the autonomic nervous system (ANS) has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.MethodsTwenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT) and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43) and tyrosine hydroxylase (TH). The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.ResultsFour weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05). Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05). The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05). However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV), left atrial diameter (LA), ejection fraction (EF).ConclusionsSummarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

Decreased risk of ventricular arrhythmias with treatment of nebivolol in patients with coronary slow flow

Coronary slow-flow (CSF) is an angiographic phenomenon characterised by delayed opacification of vessels in the absence of any evidence of obstructive epicardial coronary disease. QT interval dispersion (QTD) reflects regional variations in ventricular repolarisation and cardiac electrical instability and has been reported to be longer in patients with CSF. To examine QT duration and dispersion in patients with CSF and the effects of nebivolol on these parameters. The study population included 67 patients with angiographically proven normal coronary arteries and CSF, and 38 patients with angiographically proven normal coronary arteries without associated CSF. The patients were evaluated with 12-lead electrocardiography, and echocardiography before and three months after treatment with nebivolol. Compared to the control group QTcmax and QTcD were significantly longer in patients with CSF (p = 0.036, p = 0.019, respectively). QTcD significantly correlated with the presence of CSF (r = 0.496, p < 0.001). QTcmax (p = 0.027), QTcD (p = 0.002), blood pressure (p = 0.001), and heart rate (p < 0.001) values significantly decreased after treatment with nebivolol. Coronary slow flow is associated with increased QTD. Nebivolol reduced increased QTD in patients with CSF after three months.

2015 update on the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy.

This review will discuss the recent advances in the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Since the first detailed clinical description of the disease in 1982, we have learned much about the genetics, pathophysiology, diagnosis, and management of ARVC. We now appreciate that pathogenic mutations in desmosomal genes are the most common genetic finding. Although the right ventricle is mostly affected, left ventricular involvement is being increasingly recognized. Electrical instability precipitating sudden cardiac death often presents before structural abnormalities, and therefore early accurate diagnosis is of utmost importance. The broad spectrum of phenotypic variation, age-related penetrance, and lack of a definitive diagnostic test make the clinical diagnosis challenging. The diagnosis is made by fulfilling the 2010 Task Force criteria. Today, genetic testing and cardiac MRI play an important role in the diagnosis. Implantable cardioverter defibrillator implantation is the only lifesaving therapy available today for a subset of patients. In patients with recurrent ventricular arrhythmias, epicardial catheter ablation has demonstrated improved outcomes compared with endocardial ablation. Exercise restriction may delay the progression of disease. ARVC is predominantly associated with mutations in desmosomal genes with incomplete penetrance and variable expressivity. Ventricular electrical instability is the hallmark of ARVC, often occurring before structural abnormalities. Goals in the evaluation and management of ARVC are early diagnosis, risk stratification for sudden cardiac death, minimizing ventricular arrhythmias, and delaying the progression of disease.

Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death

Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular electric instability remains elusive. The cardiac pathology registry of 650 young adults (≤40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re-examined. Forty-three patients with MVP (26 females; age range, 19-40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28-43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects (P<0.001), with a regional distribution overlapping the histopathology findings in SCD cases. MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.

Abnormal T2-STIR magnetic resonance in hypertrophic cardiomyopathy: a marker of advanced disease and electrical myocardial instability.

BackgroundMyocardial hyperintensity on T2-weighted short-tau inversion recovery (STIR) (HyT2) cardiac magnetic resonance (CMR) images has been demonstrated in patients with hypertrophic cardiomyopathy (HCM) and is considered a sign of acute damage. The aim of the current study was to evaluate the relationship between HyT2 and both a) markers of ventricular electrical instability and b) clinical and CMR parameters.MethodsSixty-five patients underwent a thorough clinical examination, consisting of 24-h ECG recording and CMR examination including functional evaluation, T2-STIR images and late gadolinium enhancement (LGE).ResultsHyT2 was detected in 27 patients (42%), and subjects with HyT2 showed a greater left ventricle (LV) mass index (p<0.001), lower LV ejection fraction (p = 0.05) and greater extent of LGE (p<0.001) compared to those without HyT2. Twenty-two subjects (34%) presented non-sustained ventricular tachycardia (NSVT) on the 24-h ECG recording, 21 (95%) of whom exhibited HyT2. Based on the logistic regression analysis, HyT2 (odds ratio [OR]: 165, 95% CI 11–2455, p<0.001) and LGE extent (1.1, 1.0–1.3, p<0.001) served as independent predictors of NSVT, while the presence of LGE was not associated with NSVT occurrence (p = 0.49). The presence of HyT2 was associated with lower heart rate variability (p = 0.006) and a higher number of arrhythmic risk factors (p<0.001).ConclusionsIn HCM patients, HyT2 upon CMR examination is associated with more advanced disease and increased arrhythmic burden.

Electrocardiography changes in bipolar patients during long-term lithium monotherapy

ObjectiveCardiovascular side effects of lithium have been reported to occur mainly at higher-than-therapeutic serum levels. We aimed to investigate the impact of the long-term lithium use on electrocardiogram (ECG) parameters in association with the serum levels in patients with bipolar disorder (BD) and in healthy controls (HCs) serving as the reference group. MethodsThe study sample consisted of 53 euthymic BD type I patients on lithium monotherapy at therapeutic serum levels (M=0.76, S.D.=0.14, range=0.41–1.09 mmol/l) for at least 12 months and 45 HCs. A 12-lead surface ECG was obtained from all participants at resting state for at least half an hour for 5-min recording. Heart-rate, Pmax, Pmin, QRS interval, QT dispersion, QT dispersion ratio (QTdR) and Tpeak-to-end interval (TpTe) were measured. ResultsRegression analyses revealed that QTdR (B=14.17, P=.001), TpTe (B=18.38, P<.001), Pmax (B=17.84, P<.001) and Pmin (B=25.10, P<.001) were increased in BD patients who were on chronic lithium treatment than in HCs after controlling for age, sex and strict Bonferroni correction for multiple testing. There were no associations between serum lithium levels and ECG parameters. ConclusionOur findings suggest that the use of lithium is associated with both atrial and ventricular electrical instability, even when lithium levels are in the therapeutic range.

The Effect of Aortic Coarctation Surgical Repair on QTc and JTc Dispersion in Severe Aortic Coarctation Newborns: A Short-Term Follow-Up Study

Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. In our previous study, we showed a significant increase of QTc-D and JTc-D in newborns with isolated severe aortic coarctation, electrocardiographic parameters that clinical and experimental studies have suggested could reflect the physiological variability of regional and ventricular repolarization and could provide a substrate for life-threatening ventricular arrhythmias. The aim of the current study was to evaluate the effect of surgical repair of CoA on QTc-d, JTc-d in severe aortic coarctation newborns with no associated congenital cardiac malformations. The study included 30 newborns (18M; 70+/-12 h old) affected by severe congenital aortic coarctation, without associated cardiac malformations. All newborns underwent to classic extended end-to-end repair. Echocardiographic and electrocardiographic measurements were performed in each patient 24 h before and 24 h after the interventional procedure and at the end of the follow-up period, 1 month after the surgical correction. All patients at baseline, 24 h and one month after CoA surgical repair did not significantly differ in terms of heart rate, weight, height, and echocardiographic parameters. There were no statistically significant differences in QTc-D (111.7+/-47.4 vs 111.9+/-63.8 ms vs 108.5+/-55.4 ms; P=0.4) and JTc-D (98.1+/-41.3 vs 111.4+/-47.5 vs 105.1+/-33.4 ms; P=0.3) before, 24 h and 1 month after CoA surgical correction. In conclusions, our study did not show a statistically significant decrease in QTc-D and JTc-D, suggesting the hypothesis that the acute left ventricular afterload reduction, related to successful CoA surgical correction, may not reduce the ventricular electrical instability in the short-term follow-up.

Impact of the presence and amount of myocardial fibrosis by cardiac magnetic resonance on arrhythmic outcome and sudden cardiac death in nonischemic dilated cardiomyopathy

Current risk stratification for sudden cardiac death (SCD) in nonischemic dilated cardiomyopathy (NIDC) relies on left ventricular (LV) dysfunction, a poor marker of ventricular electrical instability. Contrast-enhanced cardiac magnetic resonance has the ability to accurately identify and quantify ventricular myocardial fibrosis (late gadolinium enhancement [LGE]). To evaluate the impact of the presence and amount of myocardial fibrosis on arrhythmogenic risk prediction in NIDC. One hundred thirty-seven consecutive patients with angiographically proven NIDC were enrolled for this study. All patients were followed up for a combined arrhythmic end point including sustained ventricular tachycardia (VT), appropriate implantable cardioverter-defibrillator (ICD) intervention, ventricular fibrillation (VF), and SCD. LV-LGE was identified in 76 (55.5%) patients. During a median follow-up of 3 years, the combined arrhythmic end point occurred in 22 (16.1%) patients: 8 (5.8%) sustained VT, 9 (6.6%) appropriate ICD intervention, either against VF (n = 5; 3.6%) or VT (n = 4; 2.9%), 3 (2.2%) aborted SCD, and 2 (1.5%) died suddenly. Kaplan-Meier analysis revealed a significant correlation between the LV-LGE presence (not the amount and distribution) and malignant arrhythmic events (P < .001). In univariate Cox regression analysis, LV-LGE (hazard ratio [HR] 4.17; 95% confidence interval [CI] 1.56-11.2; P = .005) and left bundle branch block (HR 2.43; 95% CI 1.01-5.41; P = .048) were found to be associated with arrhythmias. In multivariable analysis, the presence of LGE was the only independent predictor of arrhythmias (HR 3.8; 95% CI 1.3-10.4; P = .01). LV-LGE is a powerful and independent predictor of malignant arrhythmic prognosis, while its amount and distribution do not provide additional prognostic value. Contrast-enhanced cardiac magnetic resonance may contribute to identify candidates for ICD therapy not fulfilling the current criteria based on left ventricular ejection fraction.