Identification of the pathogenic effects of missense variants causing PRKAG2 cardiomyopathy.

BACKGROUND: Pathogenic missense variants in PRKAG2, the gene for the gamma 2 regulatory subunit of adenosine monophosphate-activated protein kinase (AMPK), cause severe progressive cardiac disease and sudden cardiac death, named PRKAG2 cardiomyopathy. In our previous study, we reported a E506K variant in the PRKAG2 gene that was associated with this disease. This study aimed to functionally characterize the three missense variants (E506K, E506Q, and R531G) of PRKAG2 and determine the possible effects on AMPK activity. METHODS: The proband was clinically monitored for eight years. To investigate the functional effects of three missense variants of PRKAG2, in vitro mutagenesis experiments using HEK293 cells with wild and mutant transcripts and proteins were comparatively analyzed using quantitative RT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay. RESULTS: In the long-term follow-up, the proband was deceased due to progressive heart failure. In the in vitro experimental studies, PRKAG2 was overexpressed after 48 h of transfection in three mutated cells, after which the expression levels of PRKAG2 were regressed to the level of wild-type cells in 3-weeks stably transformed cells, except for the cells with E506K variant. E506K, E506Q, and R531G variants had caused a reduction in the AMPK activity and resulted in the formation of cytoplasmic glycogen deposits. CONCLUSION: Three missense variants that alter AMPK activity affect a residue in the CBS4 domain associated with ATP/AMP-binding. Detailed information on the influence of PRKAG2 pathogenic variants on AMPK activity would be helpful to improve the treatment and management of patients with metabolic cardiomyopathy.

Comparison of electrophysiological characteristics of right- and left-sided Mahaim-type accessory pathways.

AIMS: Mahaim-type accessory pathways (MAPs) are generally right-sided due to the embryological differentiation, but left-sided localization is also possible. This study aims to compare the clinical and electrophysiological characteristics of right- and left-sided MAPs. METHODS: Of 251 patients diagnosed with AP by electrophysiological study between November 2015 and February 2020, 12 patients with MAP were included (right sided n = 8, left sided n = 4). MAP was diagnosed if; (1) no retrograde conduction; (2) anterograde decremental conduction; (3) adenosine sensitivity; and (4) Mahaim potential at successful ablation site were present. RESULTS: Ten of twelve MAPs were clustered on the lateral walls of the mitral (n = 3, 75%) and tricuspid annuli (n = 7, 87.5%). Right-sided MAPs were mostly long pathways extending toward the conduction system whereas left-sided MAPs were short extending toward the neighboring myocardium. For right- and left-sided APs, the median QRS times were 129 and 156 ms (p = .042), the median VAbl -RVApex intervals were -12 and 64 ms (p = .007), the median QRS-V(His) intervals were 16 and 86 ms (p = .120), and the median VAbl -QRS interval was -8 and 12 ms (p = .017), respectively. Coexistence of dual atrioventricular node physiology was observed only in right-sided APs (n = 3, 37.5%). CONCLUSION: MAPs are more typically located on the right but may rarely be seen on the left. Catheter ablation was associated with high success without complications.

Psychological correlates of COVID-19 conspiracy beliefs and preventive measures: Evidence from Turkey.

COVID-19 pandemic has led to popular conspiracy theories regarding its origins and widespread concern over the level of compliance with preventive measures. In the current preregistered research, we recruited 1088 Turkish participants and investigated (a) individual differences associated with COVID-19 conspiracy beliefs; (b) whether such conspiracy beliefs are related to the level of preventive measures; and (c) other individual differences that might be related to the preventive measures. Higher faith in intuition, uncertainty avoidance, impulsivity, generic conspiracy beliefs, religiosity, and right-wing ideology, and a lower level of cognitive reflection were associated with a higher level of belief in COVID-19 conspiracy theories. There was no association between COVID-19 conspiracy beliefs and preventive measures while perceived risk was positively and impulsivity negatively correlated with preventive measures. We discuss the implications and directions for future research.

Value of latent outflow obstruction to predict clinical course of patients with hypertrophic cardiomyopathy.

Objective The frequency, significance and prognostic value of left ventricle obstruction (LVO) induced with provocation (latent LVO) is controversial for hypertrophic cardiomyopathy (HC) patients. This study was designed to assess the value of latent LVO in predicting the clinical course in 101 patients with HC. Methods and results Patients were followed for a mean of 82 ± 48 months (range 2 to 148 months) for clinical end points defined as a composite of cardiovascular death resuscitated cardiac arrest, appropriate defibrillator shock or hospitalization due to worsening of heart failure symptoms. Presence of LVO (hazard ratio 3.63; 95% confidence interval, 1.85 to 7.12; P = 0.0001) and log NT-proBNP levels (hazard ratio, 1.40; 95% confidence interval, 1.14 to 1.72; P = 0.001) were the independent variables associated with an increased risk of experiencing clinical end points. HC patients with latent LVO have a trend toward decreased survival when compared with HC patients without LVO (log rank P = 0.027), but better survival than patients with resting LVO (log rank P = 0.007). HC patients with NT-proBNP levels <1,000 pg/ml had also better survival. LVO and NT-proBNP levels are the major determinants of clinical end points in patients with HC. Conclusions Evaluation of patients without resting LVO to demonstrate latent obstruction is of critical importance in respect of outcome and selection of patients for septal reduction therapies, so routine provocative testing with physiological exercise and measurement of NT-proBNP is recommended in this patient population for risk stratification.

ICD function and dysfunction in patients with arrhythmogenic cardiac diseases: the role of home monitoring.

BACKGROUND: Since their implementation in clinical practice, remote home monitoring systems (HM) have undoubtedly become an added value in patients with implantable devices for cardiac rhythm management. The aim of this study was to investigate the impact of HM on clinical management and outcome in patients with channelopathies and other arrhythmogenic diseases who received an implantable cardioverter defibrillator (ICD). METHODS: Fifty-four patients (age 6 months--74 years) were followed by means of HM in our ICD clinic. Alerts and/or device-related clinical events were analysed in all patients and subsequent clinical decisions were made if indicated. RESULTS: During an average observation time of 27 months, 46 alerts were received from 32 different patients. Five patients (9%) received appropriate therapies for life-threatening arrhythmias and four patients (8%) inappropriate therapies because ofT wave oversensing or supraventricular tachycardias. Three patients had alerts due to electrical noise (two on the atrial, one on the ventricular channel). Overall, 18 alerts (39%) required a modification of the pharmacological therapy or the programming of the device. Mean anticipation of clinical visits based on the alerts was 92.6 +/- 56 days (median 97, interquartile range 50-150). CONCLUSION: HM substantially improves the clinical management of patients with cardiac arrhythmogenic disease by early recognition of device-related inappropriate therapies and subsequent anticipation of treatment adaptation.

Effective health communication depends on the interaction of message source and content: two experiments on adherence to COVID-19 measures in Türkiye.

OBJECTIVE: Following the COVID-19 outbreak, authorities recommended preventive measures to reduce infection rates. However, adherence to calls varied between individuals and across cultures. To determine the characteristics of effective health communication, we investigated three key features: message source, content, and audience. METHODS: Using a pre-test and two experiments, we tested how message content (emphasizing personal or social benefit), audience (individual differences), message source (scientists or state officials), and their interaction influence adherence to preventive measures. Using fliers advocating preventive measures, Experiment 1 investigated the effects of message content and examined the moderator role of individual differences. Experiment 2 presented the messages using news articles and manipulated sources. RESULTS: Study 1 found decreasing adherence over time, with no significant impact from message content or individual differences. Study 2 found messages emphasizing 'protect yourself' and 'protect your country' to increase intentions for adherence to preventive measures. It also revealed an interaction between message source and content whereby messages emphasizing personal benefit were more effective when they came from healthcare professionals than from state officials. However, message source and content did not affect vaccination intentions or donations for vaccine research. CONCLUSION: Effective health communication requires simultaneous consideration of message source and content.

The roles of social norms and leadership in health communication in the context of COVID-19.

The global struggle with the COVID-19 pandemic has lasted for almost three years. Although national and local leaders have often called on the public to comply with preventive measures through health communication, large sections of society sometimes violated precautions and did not adequately follow these calls. We propose that social norms and leaders' identity entrepreneurship characteristics could be essential in effective health communication. In line with this notion, we investigated the effects of social norm types and leadership on complying with preventive measures, the intention to be vaccinated, and prosocial behavioral tendency through a high-powered experiment that focused on three factors: leadership quality (presence/lack of entrepreneurship), descriptive norm (supportive/obstructive), and injunctive norm (supportive/obstructive). Results showed that when support for injunctive and descriptive norms was present, people tended to more readily adhere to preventive measures, get vaccinated, and engage in prosocial behavior. There was also a significant effect of the interaction between descriptive and injunctive norms on compliance with preventive measures. The compliance level was highest when both norm types were supportive and lowest when both were obstructive. The effect decreased in the discrepant norms condition, where one type of norm was supportive and the other obstructive. There is also a significant interaction between leadership and the descriptive norm, indicating that a combination of an entrepreneur leader and a supportive descriptive norm increases compliance with the preventive measure. We discussed the role of leadership and social norms in effective health communication.

Verification of pulmonary vein isolation during single transseptal cryoballoon ablation: a comparison between the classical circular mapping catheter and the inner lumen mapping catheter.

AIMS: Cryoballoon ablation has proven very effective in achieving pulmonary vein isolation (PVI). The novel Achieve inner lumen mapping catheter designed to be used in conjunction with the cryoballoon, serves as both a guidewire and a mapping catheter. To our knowledge, this is the first study comparing the latter to verification of electrical isolation with the 'traditional' circular mapping catheter. METHODS AND RESULTS: We assigned 40 consecutive patients matched for age and left atrial diameter suffering of paroxysmal atrial fibrillation to cryoballoon PVI using either the circular mapping catheter or the Achieve as a mapping catheter. Duration of procedure as well as fluoroscopy times were significantly lower in the Achieve group than in the circular mapping catheter group (111 ± 14 min vs. 126 ± 13 min, P < 0.005 and 22 ± 5 min vs. 29 ± 4 min, P < 0.0001, respectively). There were no significant differences between both groups in terms of mean degree of occlusion, mean minimal temperatures, and PVI. Pulmonary vein isolation could be documented by real-time recordings in 55% of veins in the Achieve group with mean time to isolation of 65 ± 23 s. CONCLUSION: Cryoballoon ablation in conjunction with the novel Achieve is feasible, safe, and affords PVI in nearly all veins in similar proportions to the approach with the traditional guidewire. Furthermore, if compared to the procedure with the circular mapping catheter, cryoballoon ablation with the Achieve is significantly faster and associated to shorter fluoroscopy times.

Isolating the pulmonary veins as first-line therapy in patients with lone paroxysmal atrial fibrillation using the cryoballoon.

AIMS: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Nowadays, catheter-based ablative approaches are mainly reserved for drug-refractory patients. However, the value of an ablative therapy as a first-line alternative remains elusive. The aim of our study was to analyse the acute procedural success and clinical outcome of patients with lone paroxysmal AF undergoing cryoballoon ablation (CBA) as first-line treatment. METHODS AND RESULTS: Eighteen individuals (mean age 44 ± 9 years, range 23-61 years, 15 males) with lone paroxysmal AF preferring a catheter-based treatment to drug treatment as first-line therapy were consecutively enrolled in our study. Mean left atrial size was 39 ± 4 mm and mean left ventricular ejection fraction 58 ± 3%. After a mean of 2.4 CBA (range 2-4) applications pulmonary vein (PV) isolation could be demonstrated in 70 (97%) PVs. Additional lesions with a focal ablation catheter were needed to isolate one right inferior pulmonary vein and one left superior pulmonary vein in two different patients. At the end of the procedure, all (100%) PVs were isolated. After a 2-month blanking period, 16 patients (89%) were free of symptomatic AF recurrence at a mean follow-up of 14 ± 9 months and without antiarrhythmic drugs (AADs). CONCLUSION: Cryoballoon ablation in patients with lone paroxysmal AF yields a high acute efficacy rate with a great chance of being free of symptomatic AF recurrence without antiarrhythmic drugs on a mid-term follow-up period, when offered as a first-line treatment.

Added value of transoesophageal echocardiography during transseptal puncture performed by inexperienced operators.

AIMS: Transseptal puncture (TP) appears to be safe in experienced hands; however, it can be associated with life-threatening complications. The aim of our study was to demonstrate the added value of routine use of transoesophageal echocardiography (TEE) for the correct positioning of the transseptal system in the fossa ovalis, thus potentially preventing complications during fluoroscopy-guided TP performed by inexperienced operators. METHODS AND RESULTS: Two hundred and five patients undergoing pulmonary vein isolation procedure (PVI) for drug-resistant paroxysmal or persistent atrial fibrillation were prospectively included. When the operator (initially blinded to TEE) assumed that the transseptal system was in a correct position according to fluoroscopical landmarks, the latter was then checked with TEE unblinding the physician. If necessary, further refinement of the catheter position was performed. Refinement >10 mm, or in case of catheter pointing directly at the aortic root or posterior wall were considered as major repositioning. Thirty-four patients required major repositioning. Regression analysis revealed age (P: 0.0001, Wald: 12.9, 95% confidence interval: 1.04-1.16), left atrial diameter (P: 0.01, Wald: 6.6, 95% confidence interval: 1.04-1.34), previous PVI (P: 0.01, Wald: 6.3, 95% confidence interval: 1.31-8.76), and atrial septal thickness (P: 0.03, Wald: 4.5, 95% confidence interval: 1.05-3.4) as independent predictors of major revision with TEE. CONCLUSION: Routine 2D TEE in addition to traditional fluoroscopic TP appears to be very useful to guide the TP assembly in a correct puncture position and thus, to avoid TP-related complications. However, further randomized prospective comparative studies are necessary to support these suggestions.

Pulmonary vein isolation during cryoballoon ablation using the novel Achieve inner lumen mapping catheter: a feasibility study.

AIMS: Cryoballoon (CB) ablation has proven very effective in achieving pulmonary vein isolation (PVI). The Achieve catheter (AC) is a novel inner lumen catheter designed to be used in conjunction with the CB, which serves the double purpose of a guidewire and a mapping catheter. We aimed to evaluate the feasibility of CB ablation in conjunction with the novel AC, in terms of PVI and safety in a series of patients affected by drug resistant paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Seventy patients (49 male) affected by paroxysmal AF were assigned to CB PVI using the AC as a mapping catheter. Patients underwent loop-Holter monitoring 1, 3 and 6 months after ablation. Isolation occurred in 98% of PVs with the CB-AC association without having switching to a regular guidewire. Pulmonary vein isolation could be documented by real-time (RT) recordings in 47% (132) of veins. Time to isolation was significantly longer in PVs exhibiting early left atrium-PV reconnection if compared with veins with sustained isolation (117 ± 25 s vs. 59 ± 25 s; P< 0,005). No serious complications occurred; four transient phrenic nerve palsies occurred all resolving completely before the end of the procedure. CONCLUSION: Cryoballoon ablation in conjunction with the novel AC is feasible, safe, and most importantly affords PVI in nearly all veins without having to switch to a regular guidewire. However, RT recordings could be documented in only 47% of pulmonary veins.

Recent Status in Brugada Syndrome.

Brugada syndrome was first described in 1992 as right precordial ST-segment elevation in patients with structurally normal hearts and sudden cardiac death. Brugada Syndrome is one of the most common reasons for sudden cardiac death (4-12%) and is a hereditary disease with an autosomal dominant pattern of transmission with nearly 300 pathogenic variants in 19 responsible genes published. The present review focuses on the diagnosis, genetics, risk stratification, and management of patients with Brugada Syndrome.

Situational factors shape moral judgements in the trolley dilemma in Eastern, Southern and Western countries in a culturally diverse sample.

The study of moral judgements often centres on moral dilemmas in which options consistent with deontological perspectives (that is, emphasizing rules, individual rights and duties) are in conflict with options consistent with utilitarian judgements (that is, following the greater good based on consequences). Greene et al. (2009) showed that psychological and situational factors (for example, the intent of the agent or the presence of physical contact between the agent and the victim) can play an important role in moral dilemma judgements (for example, the trolley problem). Our knowledge is limited concerning both the universality of these effects outside the United States and the impact of culture on the situational and psychological factors affecting moral judgements. Thus, we empirically tested the universality of the effects of intent and personal force on moral dilemma judgements by replicating the experiments of Greene et al. in 45 countries from all inhabited continents. We found that personal force and its interaction with intention exert influence on moral judgements in the US and Western cultural clusters, replicating and expanding the original findings. Moreover, the personal force effect was present in all cultural clusters, suggesting it is culturally universal. The evidence for the cultural universality of the interaction effect was inconclusive in the Eastern and Southern cultural clusters (depending on exclusion criteria). We found no strong association between collectivism/individualism and moral dilemma judgements.

Pulmonary vein ostium shape and orientation as possible predictors of occlusion in patients with drug-refractory paroxysmal atrial fibrillation undergoing cryoballoon ablation.

AIMS: No specific data are available on the influence of pulmonary vein (PV) anatomy and shape on cryoballoon ablation (CA) catheter efficacy in delivering cryothermal energy and, consequently, in obtaining PV isolation. METHODS AND RESULTS: Among a larger series of patients (68) with drug-refractory paroxysmal atrial fibrillation who underwent CA in our department, 52 patients were included in our study. All of them had a multislice cardiac computed tomography (MSCT) before the procedure. We retrospectively evaluated their MSCT scans focusing our attention on PV ovality and orientation in the frontal plane. A fair inverse association was documented between the ovality index of the left PVs and the degree of occlusion (r=-0.486 and P<0.003 for the LSPV and r=-0.360 and P=0.033 for the LIPV), whereas no association was found between the ovality index of the right PVs and the degree of occlusion (r=-0.283 and P=0.083 for the RSPV and r=0.235 and P=0.093 for RIPV). Nevertheless, a strong inverse association was found between the orientation of the PV ostia and the degree of occlusion in each vein (r=-0.804 and P<0.001 for the LSPV, r=-0.415 and P=0.013 for LIPV, r=-0.798 and P<0.001 for the RSPV, and r=-0.867 and P<0.001 for RIPV). CONCLUSION: Pulmonary vein ostium shape and orientation evaluated by MSCT proved to be useful in predicting the degree of occlusion obtained during CA.

Ventricular repolarization changes for a single heart beat after short periods of ventricular pacing.

We report two patients with apical hypertrophic cardiomyopathy who had repolarization changes for a single sinus beat after short periods of right ventricular apical pacing during invasive electrophysiological study.

Pacemakers do not always tell the truth: diagnosis of ventricular tachycardia for supraventricular tachycardia on pacemaker telemetry.

Pacemaker telemetry reflects algorithm-dependent interpretations about the cardiac rhythm. For these data to be useful, it is necessary to recognize the limitations of each algorithm and its interactions with pacing and sensing parameters. We report on a case in which pacemaker Holter recording showed several episodes of nonsustained supraventricular tachycardia which were erroneously classified as ventricular tachycardia.

Atrial fibrillation ablation: a single center comparison between remote magnetic navigation, cryoballoon and conventional manual pulmonary vein isolation.

BACKGROUND: The aim of the study was to compare in our center the effect of different ablation techniques on intermediate term freedom from atrial fibrillation (AF) or atrial tachycardia (AT) in patients affected by refractory AF. METHODS AND RESULTS: We retrospectively selected 94 patients who underwent AF ablation in our electrophysiological laboratory from June 2007 to December 2009. 29 patients underwent manual circumferential pulmonary vein isolation (mCPVI), 35 underwent remote magnetic navigation assisted CPVI (rmtCPVI) and 30 cryoballoon CPVI (cCPVI). Antiarrhythmic drugs were systematically stopped 2 months after the procedure (end of the "blanking period"). At a mean follow-up of 12,64 ± 6,41 months (range 2-31), the success rate for mCPVI group was 65.5% (19 patients), 66.7 % (20 patients) for the rmtCPVI group and 65.7 % (23 patients) for the cCPVI group (p = 0.625). Procedural and fluoroscopy times were significantly reduced in the cCPVI group (both p < 0.001). Univariate Cox regression showed that no clinical variables were independently associated with recurrence. CONCLUSIONS: In our center's experience cCPVI and rmtCPVI have been demonstrated to be as effective as mCPVI. cCPVI seemed to be associated with lower procedural and fluoroscopy times.

Cryoballoon ablation for paroxysmal atrial fibrillation in septuagenarians: a prospective study.

AIMS: To evaluate the effects of pulmonary vein isolation (PVI) in terms of feasibility, safety and success rate on a midterm follow-up period in septuagenarians undergoing ablation with the Arctic Front Cryoballoon for atrial fibrillation (AF). METHODS AND RESULTS: We prospectively enrolled 21 patients aged 70 years or older (14 male; age 73 ± 2.5 years) elected to circumferential PVI with the 28mm cryoballoon for symptomatic drug resistant paroxysmal AF. A total number of 82 pulmonary veins (PV) were evidenced. Successful isolation could be obtained in all 82 (100%) PV ostia at the end of procedure. No major complication occurred during procedure. At a mean follow-up of 11.5 ± 4.7 months following ablation, 62% of patients did not present recurrence of atrial arrhythmias. CONCLUSION: Cryoballoon ablation may be feasible and safe in older patients. Moreover a large proportion of the latter did not present AF recurrence during follow-up.

Advanced Age, Female Gender and Delay in Pacemaker Implantation May Cause TdP in Patients With Complete Atrioventricular Block.

AIM: We aimed to report the clinical features related to torsades de pointes (TdP) in patients with complete AV block (CAVB). METHODS: Patients with CAVB who were admitted to our instituition between January 2007 and January 2010 were retrospectively evaluated in terms of the occurence of TdP. The clinical features were compared in patients with and without TdP using the software of SPSS. RESULTS: Sixty-four patients were determined to have CAVB. Three of them had documented episodes of TdP. All three patients experiencing TdP were females, whereas 48% of the patients with CAVB were females. The mean age of patients with TdP was significantly greater than the mean age of the other patients (85 ±3 vs. 78±7.6, respectively; p<0.05). In our archives, bradycardia exposure time could be determined in only 49 patients without TdP. Among them, just 10 patients had been exposed to bradycardia over 48 hours, whereas all of the 3 patients with TdP had been exposed to bradycardia over 48 hours (p<0.05). Additionally, in two patients with TdP, we demonstrated that QT and QTc prolongation increases as the duration of bradycardia is extended. Furthermore, all patients with TdP had notched T waves in the ECG on the occurrence day of TdP, whereas they did not have any notched T wave in their ECG on the admission day. CONCLUSION: Among the patients with CAVB, elderly females are more susceptible to development of TdP. Delay in institution of physiological heart rate leads to further QT prolongation and thereby to TdP. Besides QT prolongation, the finding of T wave notching on ECG may also have a predictive value for TdP.

Chronic cigarette smoking affects left and right ventricular long-axis function in healthy young subjects: a Doppler myocardial imaging study.

OBJECTIVE: Cigarette smoking is one of the major risk factors for coronary artery disease. However, chronic smoking has additional cardiac adverse effects independent of coronary atherosclerosis. We assessed the possible effects of chronic smoking on left and right ventricular (LV, RV) long-axis function using Doppler myocardial imaging (DMI). METHODS: Forty otherwise healthy smokers (mean age = 26+/-3 years) and 40 age-matched nonsmoking controls enrolled. Standard echocardiography protocol was followed by DMI. Peak systolic (V(S)), early (V(E)) and late diastolic (V(A)) velocities, peak systolic strain (S), and strain rate (SR) were measured from septal, lateral, and RV free walls. RESULTS: The baseline characteristics of two groups were similar. There were significant differences regarding Doppler myocardial velocity, S, and SR indices. Septal V(E) (P < 0.04), S (P < 0.0001) and SR (P < 0.02) were significantly reduced in smokers. For both lateral and RV free wall, V(S) (P < 0.003, P < 0.002, respectively), V(E) (P < 0.0001, P < 0.002, respectively), S (P < 0.0001 for both), and SR (P < 0.0001, P < 0.002, respectively) were significantly reduced in smokers. There were significant correlations between the amount of smoking and septal, lateral, and RV free wall S and SR. CONCLUSIONS: Chronic cigarette smoking causes alterations in long-axis systolic and diastolic functions of right and left ventricles in healthy young subjects. These changes can be accurately detected with Doppler myocardial velocity and SR imaging.