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Histopathologic findings in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) are replacement of the normal myocardium with fatty and fibrous elements with preferential involvement of the right ventricle. The right ventricular fibrosis can be visualised by post-gadolinium delayed enhancement inversion recovery imaging (DE imaging). We compared the image quality of three different gradient echo MRI sequences for short axis DE imaging of the right ventricle (RV). We retrospectively analysed MRI scans performed between February 2005 and December 2008 in 97 patients (mean age: 41.2 years, 67% men) suspected of ARVC/D. For DE imaging either a 2D Phase Sensitive (PSIR), a 2D (2D) or a 3D (3D) inversion recovery sequence was used in respectively 38, 32 and 27 MRI-examinations. The RV, divided in 10 segments, was assessed for image quality by two radiologists in random sequence. A consensus reading was performed if results differed between the two readings. Image quality was good in 24% of all segments in the 3D group, 66% in the 2D group and 79% in the PSIR group. Poor image quality was observed in 51% (3D), 10% (2D), and 2% (PSIR) of all segments. Exams were considered suitable for clinical use in 7% of exams in the 3D group, 75% of exams in the 2D group and 90% of exams of the PSIR group. Breathing-artifacts occurred in 22% (3D), 59% (2D) and 53% (PSIR). Motion-artifacts occurred in 56% (3D), 28% (2D) and 29% (PSIR). Post-gadolinium imaging using the PSIR sequence results in better and more consistent image quality of the RV compared to the 2D and 3D sequences. [ABSTRACT FROM AUTHOR]

Background- Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding 5 desmosomal proteins are found in ~=50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt ARVD/C index patients, so follow-up data on relatives are scarce. Methods and Results- One hundred forty-nine ARVD/C index patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria and 302 relatives from 93 families (282 asymptomatic; 135 male patients; age, 44±13 years) were clinically and genetically characterized. DNA analysis comprised sequencing of plakophilin-2 (PKP2), desmocollin-2, desmoglein-2, desmoplakin, and plakoglobin and multiplex ligation-dependent probe amplification to identify large deletions in PKP2. Pathogenic mutations were found in 87 index patients (58%), mainly truncating PKP2 mutations, including 3 cases with multiple mutations. Multiplex ligation-dependent probe amplification revealed 3 PKP2 exon deletions. ARVD/C was diagnosed in 31% of initially asymptomatic mutation-carrying relatives and 5% of initially asymptomatic relatives of index patients without mutation. Prolonged terminal activation duration was observed more than negative T waves in V(1) to V(3), especially in mutation-carrying relatives <20 years of age. In 45% of screened families, >=1 affected relatives were identified (90% with mutations). Conclusions- Pathogenic desmosomal gene mutations, mainly truncating PKP2 mutations, underlie ARVD/C in the majority (58%) of Dutch index patients and even 90% of familial cases. Additional multiplex ligation-dependent probe amplification analysis contributed to discovering pathogenic mutations underlying ARVD/C. Discovering pathogenic mutations in index patients enables those relatives who have a 6-fold increased risk of ARVD/C diagnosis to be identified. Prolonged terminal activation duration seems to be a first sign of ARVD/C in young asymptomatic relatives. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to determine the spectrum and prevalence of "background genetic noise" in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and to determine genetic associations that can guide the interpretation of a positive test result.Background: ARVC is a potentially lethal genetic cardiovascular disorder characterized by myocyte loss and fibrofatty tissue replacement of the right ventricle. Genetic variation among the ARVC susceptibility genes has not been systematically examined, and little is known about the background noise associated with the ARVC genetic test.Methods: Using direct deoxyribonucleic acid sequencing, the coding exons/splice junctions of PKP2, DSP, DSG2, DSC2, and TMEM43 were genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy controls of various ethnicities. Eighty-two additional ARVC cases were obtained from published reports, and additional mutations were included from the ARVD/C Genetic Variants Database.Results: The overall yield of mutations among ARVC cases was 58% versus 16% in controls. Radical mutations were hosted by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutations versus a similar 21% of ARVC cases. Relative to controls, mutations in cases occurred more frequently in non-Caucasians, localized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within PKP2 and DSG2.Conclusions: This study is the first to comprehensively evaluate genetic variation in healthy controls for the ARVC susceptibility genes. Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutations should be interpreted in the context of race and ethnicity, mutation location, and sequence conservation. [ABSTRACT FROM AUTHOR]

Competing Interests: None.

Background: Reducing wasteful practices optimizes value in medicine. Docusate lacks treatment efficacy yet is widely prescribed. This quality improvement project aimed to de-implement docusate in place of a new evidence-based order set., Methods: This is an ambidirectional study of inpatient laxative orders from 2018 to 2022 ​at one institution. We stratified docusate data by service/unit to target prospective deimplementation initiatives. A new evidence-based constipation order set was embedded in Cerner., Results: There were 701,732 docusate orders across 75 services on 68 units. Top docusate ordering services were Trauma, Obstetrics and Hospitalist. Docusate administration rates were higher than for other laxatives. Our efforts reduced docusate orders by 44% over 4 months. PEG and senna orders increased by 58% and 35%., Conclusion: Docusate has no efficacy yet is widely prescribed. A structured de-implementation strategy can drive systematic change by leveraging technology and applying multidisciplinary improvement efforts. Our work removed docusate from the inpatient formulary., Competing Interests: Declaration of competing interest This work has not been published previously and is not under consideration for publication elsewhere. This publication is approved by all authors. This publication did NOT include any generative AI and AI-assisted technologies in the writing process. The authors declare that they have NO affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. This project was undertaken as a quality improvement and program evaluation initiative and as such does not constitute human subjects research and was waived institutional review board review., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Pulsed field ablation (PFA) was recently introduced for the treatment of symptomatic atrial fibrillation (AF) with the claim of selectively ablating the myocardium while sparing surrounding tissues. We present our initial experience with a PFA catheter for pulmonary vein isolation (PVI) and describe procedural findings and peri-procedural safety of the first 100 patients., Materials and Methods: We investigated 100 patients treated for symptomatic AF using the FARAWAVE PFA catheter (Farapulse, Menlo Park, CA, USA) between July 2021 and March 2022. Procedure workflow and electrophysiological findings at the time of ablation, peri-procedural complications, and operator learning curves are described., Results: The mean age of patients was 62.9 ± 9.4 years, 62% were male subjects and 80% had paroxysmal AF. The median CHA 2 DS 2 -VASc score was 1.5 (IQR: 1.0-2.0) and the mean left atrial volume index was 35.7 ± 9.6 ml/m2. In 88 (88%) patients, PVI alone was performed and in 12 (12%) patients additional ablation of the posterior wall was performed. 3D-electroanatomic mapping was performed in 18 (18%) patients. Procedures without mapping lasted for 52.3 ± 16.6 min. The mean number of applications per pulmonary vein (PV) was 8.1 ± 0.6. In all patients (100%), all PVs were confirmed to be isolated. The learning curves of the two operators who performed > 20 procedures showed a negligible variation of performance over time and practice did not significantly predict procedure time [Operator 1 (senior): R 2 = 0.034, p = 0.35; Operator 2 (junior): R 2 = 0.004, p = 0.73]. There was no difference between the procedure times between senior and junior operators (Operator 1: 46.9 ± 9.7 min vs. Operator 2: 45.9 ± 9.9 min; p = 0.73). The only complications observed were two cases of bleeding at the site of percutaneous access., Conclusion: Our initial experience shows that use of the PFA catheter for pulmonary vein isolation (PVI) is safe, fast, and easy to learn., Competing Interests: Author HG received a speaker fee from Biosense Webster. Author YB received research grants (to department) from AtriCure and Medtronic, and a speaker fee from AtriCure and Circle. He was also a proctor for Abbott, Biosense Webster, and Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Magni, Mulder, Groenveld, Wiesfeld, Tieleman, Cox, Van Gelder, Smilde, Tan, Rienstra and Blaauw.)

Research regarding cross-behavioral relationships between the cognitive mechanisms motivating health behavior change is lacking for cancer survivors. This study investigated these relationships to inform the development of multiple health behavior change (MHBC) interventions for this at-risk population. Eligible participants included cancer survivors attending an intake appointment for smoking cessation services. This cross-sectional survey study assessed participants' self-efficacy and motivation (stage of change) for smoking cessation and exercise, as well as self-reported health behaviors. Analyses evaluated cross-behavioral associations between cognitive mechanisms and their relationships with smoking and exercise behaviors. Seventy-six participants completed the survey questionnaire. The correlation between self-efficacy scores for smoking cessation and exercise was statistically significant ( r = .45, 95% CI [.09, .67]), as were correlations between self-efficacy and reported levels of exercise (( r = .44, 95% CI [.20, .65]) strenuous); (( r = .36, 95% CI [.12, .59]) moderate), exercise self-efficacy and smoking behavior ( r = -.27, 95% CI [-.46, -.05]), and smoking self-efficacy and smoking behavior ( r = -0.41, 95% CI [-.61, -.18]). For cancer survivors, associations between exercise self-efficacy and smoking cessation self-efficacy may offer an opportunity to leverage MHBC; specifically, this positive association may facilitate exercise intervention in survivors seeking smoking cessation services..

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time-activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

For cancer survivors, who also often present with co-existing health conditions, exercise testing is often performed using submaximal protocols incorporating linear heart rate response for estimating the cardiorespiratory capacity and assessing exercise tolerance. However, use of beta-blocker medications, during sub-maximal protocols based on linear HR response can be problematic. Rating of perceived exertion (RPE), which takes into account an individual's overall perception of effort, can be used as a complementary tool that does not rely solely on the heart rate response to increased workload. We compared heart rate response (VO 2 HR) and self-rating of perceived exertion (VO 2 RPE) in a graded submaximal exercise test (GXT) in 93 endometrial cancer survivors. The results of the GXT were stratified according to whether participants were taking beta-blocker (BB) medications or not (non-BB). Among non-BB participants, there was no difference between the mean VO 2 HR and the mean VO 2 RPE estimates of cardiorespiratory capacity (mlO 2/ /kg/min) (20.4 and 19.3, respectively; p = 0.166). Among BB participants, the mean VO 2 HR approached significant difference than the mean VO 2 RPE (21.7 mlO 2/ /kg/min and 17.6 mlO 2/ /kg/min, respectively; p = 0.087). Bland-Altman plots for both methods showed a proportional bias for the non-BB group; but not the BB group. Our results suggest that sub-maximal protocols based on Borg's Rating of Perceived exertion (RPE) produce differing results from sub-maximal protocols based on HR response when applied to clinical population taking BB medications. Using RPE instead of HR for participants on BB medications may be a better method for assessing the exercise tolerance for estimating the cardiorespiratory capacity in sub-maximal exercise testing.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) and obesity are prevalent in cancer survivors and decrease quality of life; however, the impact of the co-occurrence of these conditions has garnered little attention. This study investigated differences between obese and non-obese cancer survivors with CIPN and predictors of symptom burden and pain., Methods: Patients with CIPN were administered the MD Anderson Symptom Inventory and a modified version of pain descriptors from the McGill Pain Inventory. Independent t tests assessed group differences between obese and non-obese survivors, and linear regression analyses explored predictors of patient outcomes., Results: Results indicated a significant difference in symptom severity scores for obese (M = 32.89, SD = 25.53) versus non-obese (M = 19.35, SD = 16.08) patients (t(37.86) = -2.49, p = .02). Significant differences were also found for a total number of pain descriptors endorsed by obese (M = 4.21, SD = 3.45) versus non-obese (M = 2.42, SD = 2.69) participants (t(74) = -2.53, p = .01). Obesity was a significant predictor of symptom severity and total pain descriptors endorsed. Other significant predictors included age and months since treatment., Conclusions: Cancer survivors with CIPN and co-occurring obesity may be more at risk for decreased quality of life through increased symptom severity and pain compared to non-obese survivors. This paper identified risk factors, including obesity, age, and months since treatment, that can be clinically identified for monitoring distress in CIPN patients. Future research should focus on the longitudinal relationship between obesity and CIPN, and robust interventions to address the multifaceted issues faced by cancer survivors.

The thermodynamic temperature of the point of inflection of the melting transition of Re-C, Pt-C and Co-C eutectics has been determined to be 2747.84 ± 0.35 K, 2011.43 ± 0.18 K and 1597.39 ± 0.13 K, respectively, and the thermodynamic temperature of the freezing transition of Cu has been determined to be 1357.80 ± 0.08 K, where the ± symbol represents 95% coverage. These results are the best consensus estimates obtained from measurements made using various spectroradiometric primary thermometry techniques by nine different national metrology institutes. The good agreement between the institutes suggests that spectroradiometric thermometry techniques are sufficiently mature (at least in those institutes) to allow the direct realization of thermodynamic temperature above 1234 K (rather than the use of a temperature scale) and that metal-carbon eutectics can be used as high-temperature fixed points for thermodynamic temperature dissemination. The results directly support the developing mise en pratique for the definition of the kelvin to include direct measurement of thermodynamic temperature., (© 2016 The Author(s).)

Background: Effective, broad-reaching channels are important for the delivery of health behavior interventions in order to meet the needs of the growing population of cancer survivors in the United States. New technology presents opportunities to increase the reach of health behavior change interventions and therefore their overall impact. However, evidence suggests that older adults may be slower in their adoption of these technologies than the general population. Survivors' interest for more traditional channels of delivery (eg, clinic) versus new technology-based channels (eg, smartphones) may depend on a variety of factors, including demographics, current health status, and the behavior requiring intervention., Objective: The aim of this study was to determine the factors that predict cancer survivors' interest in new technology-based health behavior intervention modalities versus traditional modalities., Methods: Surveys were mailed to 1871 survivors of breast, prostate, and colorectal cancer. Participants' demographics, diet and physical activity behaviors, interest in health behavior interventions, and interest in intervention delivery modalities were collected. Using path analysis, we explored the relationship between four intervention modality variables (ie, clinic, telephone, computer, and smartphone) and potential predictors of modality interest., Results: In total, 1053 respondents to the survey (56.3% response rate); 847 provided complete data for this analysis. Delivery channel interest was highest for computer-based interventions (236/847, 27.9% very/extremely interested) and lowest for smartphone-based interventions (73/847, 8.6%), with interest in clinic-based (147/847, 17.3%) and telephone-delivered (143/847, 16.9%) falling in between. Use of other technology platforms, such as Web cameras and social networking sites, was positively predictive of interest in technology-based delivery channels. Older survivors were less likely to report interest in smartphone-based diet interventions. Physical activity, fruit and vegetable consumption, weight status, and age moderated relationships between interest in targeted intervention behavior and modality., Conclusions: This study identified several predictors of survivor interest in various health behavior intervention delivery modalities. Overall, computer-based interventions were found to be most acceptable, while smartphones were the least. Factors related to survivors' current technology use and health status play a role in their interest for technology-based intervention versus more traditional delivery channels. Future health behavior change research in this population should consider participants' demographic, clinical, and lifestyle characteristics when selecting a delivery channel. Furthermore, current health behavior interventions for older cancer survivors may be best delivered over the Internet. Smartphone interventions may be feasible in the future following further adoption and familiarization by this particular population., (©Emily C Martin, Karen Basen-Engquist, Matthew G Cox, Elizabeth J Lyons, Cindy L Carmack, Janice A Blalock, Wendy Demark-Wahnefried. Originally published in JMIR Cancer (http://cancer.jmir.org), 11.02.2016.)

Objective: Depression and reduced quality of life are often reported in patients with upper-extremity lymphedema secondary to breast cancer treatment. Little is known about how pain and body image influence depression in patients with lymphedema. The current study examined the association of pain intensity and body integrity beliefs with depressive symptoms and the extent to which body image dissatisfaction mediated these associations., Methods: A cross-sectional sample of patients with lymphedema secondary to breast cancer treatment completed self-report questionnaires of pain, body image, and depressive symptoms. Hierarchical regression analyses and tests of mediation were conducted to examine the associations among the variables of interest., Results: Pain intensity and body integrity beliefs were positively associated with depressive symptoms. Further, body image dissatisfaction mediated the relationship between pain and depressive symptoms, indicating that higher levels of pain led to higher states of body image dissatisfaction, which, in turn, led to greater depressive symptoms. Body image dissatisfaction also mediated the relationship between body integrity beliefs and depressive symptoms, suggesting that greater body integrity beliefs led to higher dissatisfaction with one's body and subsequently to greater depressive symptoms., Conclusions: Our findings provide preliminary evidence that pain intensity and body image are important factors in understanding depressive symptoms in patients with lymphedema. Clinical implications include screening for pain and body image concerns in this population to identify patients who are in distress. Counseling interventions targeting body image dissatisfaction can also be potentially helpful for patients with lymphedema., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: Vigorous physical activity (PA) has been promoted for improving cardiorespiratory fitness (CRF). However, therapeutic techniques designed to engage participants in vigorous PA have fallen short; one reason for this may be the unpleasant physical sensations associated with vigorous exercise (e.g., temporary shortness of breath and mild muscle soreness). Mindfulness and acceptance-based therapies such as Acceptance and Commitment Therapy (ACT) may be helpful at improving adherence to vigorous PA levels. In this open clinical trial, we sought to demonstrate the feasibility and acceptability of a mindfulness- and acceptance-based intervention for increasing CRF in sedentary adults and to generate initial outcomes data., Design: Participants ( N =24) engaged in a 10-week fitness walking program while attending regular group sessions based on ACT., Main Outcome Measures and Results: The feasibility and acceptability of the intervention were demonstrated through high levels of walking adherence (89.30%) and group session attendance (85.50%). A large significant decrease in total 1-mile walk test time [ t (18)=4.61, p =.0002, d =.64] and a moderate significant increase in estimated VO 2max [ t (18)=-4.05, p =.0007, d =-.43] were observed. Analyses indicated a large significant increase in exercise-related experiential acceptance [ t (18)=-9.19, p <.0001, d =-2.09]., Conclusion: This study demonstrates the feasibility and acceptability of an ACT-based intervention for supporting participation in vigorous PA in sedentary individuals.

Inadequate statistical power to detect treatment effects in health research is a problem that is compounded when testing for mediation. In general, the preferred strategy for increasing power is to increase the sample size, but there are many situations where additional participants cannot be recruited, necessitating the use of other methods to increase statistical power. Many of these other strategies, commonly applied to analysis of variance and multiple regression models, can be applied to mediation models with similar results. Additional predictors or blocking variables will increase or decrease statistical power, however, depending on whether these variables are related to the mediator, the outcome, or both. The effect of these two methods on the power for tests of mediation is illustrated through the use of simulations. Implications for health researchers using these methods are discussed., (© The Author(s) 2013.)

Inhibitory control and sensitivity to reward are relevant to the food choices individuals make frequently. An imbalance of these systems can lead to deficits in decision-making that are relevant to food ingestion. This study evaluated the relationship between dietary behaviors - binge eating and consumption of sweetened beverages and snacks - and behavioral control processes among 198 adolescents, ages 14 to 17. Neurocognitive control processes were assessed with the Iowa Gambling Task (IGT), a generic Go/No-Go task, and a food-specific Go/No-Go task. The food-specific version directly ties the task to food cues that trigger responses, addressing an integral link between cue-habit processes. Diet was assessed with self-administered food frequency and binge eating questionnaires. Latent variable models revealed marked gender differences. Inhibitory problems on the food-specific and generic Go/No-Go tasks were significantly correlated with binge eating only in females, whereas inhibitory problems measured with these tasks were the strongest correlates of sweet snack consumption in males. Higher BMI percentile and sedentary behavior also predicted binge eating in females and sweet snack consumption in males. Inhibitory problems on the generic Go/No-Go, poorer affective decision-making on the IGT, and sedentary behavior were associated with sweetened beverage consumption in males, but not females. The food-specific Go/No-Go was not predictive in models evaluating sweetened beverage consumption, providing some initial discriminant validity for the task, which consisted of sweet/fatty snacks as no-go signals and no sugar-sweetened beverage signals. This work extends research findings, revealing gender differences in inhibitory function relevant to behavioral control. Further, the findings contribute to research implicating the relevance of cues in habitual behaviors and their relationship to snack food consumption in an understudied population of diverse adolescents not receiving treatment for eating disorders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

As a result of the complex nature of operating multi-station national air quality networks it is rare that complete data sets are produced from these networks. The reliance of most air quality legislation on the assessment of measured annual average concentrations against target or limit concentrations necessitates the use of methods to calculate an annual average value and the uncertainty in this value in the absence of a complete data set for the year in question. Standard procedures exist for performing these calculations, but it is not clear how effective these are when data having low time resolution are collected and missing data accounts for large periods of the year. This paper investigates the influence of these deficiencies using data from UK air quality networks in the form of monthly average concentrations for polycyclic aromatic hydrocarbons and for metals in the PM10 phase of ambient air. Whilst the standard methods currently employed produce good results on average, for individual cases the uncertainty in the annual average calculated when data is missing may be appreciably different from that obtained when full knowledge of the distribution of the data is known. These effects become more apparent as the quantity of missing data increases.

Objective: The objective of this paper is to describe baseline differences between obese and non-obese endometrial cancer survivor in anthropometrics, exercise behavior, fitness, heart rate and blood pressure, and quality of life, and to analyze whether the effect of a home-based exercise intervention on these outcomes differed for obese and non-obese participants., Methods: One hundred post-treatment Stage I-IIIa endometrial cancer survivors participated in a single arm 6month study in which they received a home-based exercise intervention. Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured every two months, and quality of life (QOL) and psychological distress were measured at baseline and 6months., Results: Adjusting for potential confounders, at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher systolic blood pressure (p=.018), and lower physical functioning (p<.001) and ratings of general health (p=.002), and more pain (p=.037) and somatization (.002). Significant improvements were seen in exercise behavior, resting heart rate, systolic blood pressure, and multiple QOL domains over the course of the intervention. Obese survivors had less improvement in exercise behavior and cardiorespiratory fitness than non-obese survivors, but there were no differences with regard to improvements in QOL and stress., Conclusions: Home based exercise interventions are beneficial to endometrial cancer survivors, including those whose BMI is in the obese range. While obese survivors have lower levels of physical activity and fitness, they experienced similar activity, fitness, quality of life and mental health benefits. Exercise should be encouraged in endometrial cancer survivors, including those who are obese., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently associated with desmosomal mutations. However, nondesmosomal mutations may be involved. The aim of this study was to assess the contribution of a phospholamban (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force criteria (TFC). In 142 Dutch patients (106 men, mean age 51 ± 13 years) with proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known desmosomal genes (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene were screened. After genetic analysis, phenotypic characteristics of desmosomal versus PLN mutation carriers were compared. In 59 of 142 patients with ARVD/C (42%), no desmosomal mutation was found. In 19 of 142 patients (13%), the PLN founder mutation c.40&#95;42delAGA (p.Arg14del) was identified. PLN mutation carriers more often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p = 0.017) left ventricular impairment, whereas desmosomal mutation carriers had more solitary right ventricular abnormalities. The revised TFC included 21 of 142 patients with proven ARVD/C who did not meet the 1994 TFC, including 7 PLN mutation carriers. In conclusion, there is a substantial contribution of PLN mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of patients (19 of 59) with genetically unexplained proven ARVD/C, this nondesmosomal mutation was found. PLN mutation carriers have ARVD/C characteristics, including important right ventricular involvement, and additionally more often low-voltage electrocardiograms, inverted T waves in the left precordial leads, and left ventricular involvement., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Causal inference continues to be a critical aspect of evaluation research. Recent research in causal inference for statistical mediation has focused on addressing the sequential ignorability assumption; specifically, that there is no confounding between the mediator and the outcome variable., Objectives: This article compares and contrasts three different methods for assessing sensitivity to confounding and describes the graphical depiction of these methods., Design: Two types of data were used to fully examine the plots for sensitivity analysis. The first type was generated data from a single mediator model with a confounder influencing both the mediator and the outcome variable. The second was data from an actual intervention study. With both types of data, situations are examined where confounding has a large effect and a small effect., Subjects: The nonsimulated data were from a large intervention study to decrease intentions to use steroids among high school football players. We demonstrate one situation where confounding is likely and another situation where confounding is unlikely., Conclusions: We discuss how these methods could be implemented in future mediation studies as well as the limitations and future directions for these methods.

The consequences of missing data during air quality monitoring activities and the calculation of the annual average mass concentration of ambient pollutants are discussed. Possible strategies for mitigating totally and partially missing data during given measurement periods are presented and evaluated. A mathematical description of a preferred method for the determination of annual average concentration using the simple mean, and not using time weighting to account for missing data, is justified. It is hoped this discussion paper will provoke debate in the air quality community about the best way to assess measured concentrations of ambient pollutants against legislative values.

Background: Arrhythmogenic cardiomyopathy (AC) is considered a predominantly right ventricular (RV) desmosomal disease. However, left-dominant forms due to desmosomal gene mutations, including PKP2 variant c.419C>T, have been described. Recently, a nondesmosomal phospholamban (PLN) mutation (c.40&#95;42delAGA) has been identified, causing dilated cardiomyopathy and arrhythmias., Objective: To gain more insight into pathogenicity of the PKP2 variant c.419C>T by cosegregation analysis of the PKP2 variant c.419C>T vs the PLN mutation c.40&#95;42delAGA., Methods: A Dutch family (13 family members, median age 49 years, range 34-71 years) with ventricular tachycardia underwent (1) meticulous phenotypic characterization and (2) screening of 5 desmosomal genes (PKP2, DSC2, DSG2, DSP, JUP) and PLN., Results: Six family members fulfilled 2010 AC Task Force Criteria. Seven had signs of left ventricular (LV) involvement (inverted T waves in leads V4-V6, LV wall motion abnormalities and late enhancement, and reduced LV ejection fraction), including 6 family members with proven AC. The PKP2 variant c.419C>T was found as a single variant in 3 family members, combined with the PLN mutation c.40&#95;42delAGA in 3 others. PLN mutation was found in 9 family members, including the 6 with AC and all 7 with LV involvement. The PLN mutation c.40&#95;42delAGA was found as a single mutation in 6, combined with the PKP2 variant c.419C>T in 3 others. A low-voltage electrocardiogram was seen in 4 of 9 PLN mutation-positive subjects. None of the family members with the single PKP2 variant showed any sign of RV or LV involvement., Conclusions: The PLN mutation c.40&#95;42delAGA cosegregates with AC and with electrocardiographic and structural LV abnormalities. In this family, there was no evidence of disease-causing contribution of the PKP2 variant c.419C>T., (Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Arrhythmogenic cardiomyopathy (AC) is closely associated with desmosomal mutations in a majority of patients. Arrhythmogenesis in patients with AC is likely related to remodeling of cardiac gap junctions and increased levels of fibrosis. Recently, using experimental models, we also identified sodium channel dysfunction secondary to desmosomal dysfunction., Objective: To assess the immunoreactive signal levels of the sodium channel protein NaV1.5, as well as connexin43 (Cx43) and plakoglobin (PKG), in myocardial specimens obtained from patients with AC., Methods: Left and right ventricular free wall postmortem material was obtained from 5 patients with AC and 5 controls matched for age and sex. Right ventricular septal biopsies were taken from another 15 patients with AC. All patients fulfilled the 2010 revised Task Force Criteria for the diagnosis of AC. Immunohistochemical analyses were performed using antibodies against Cx43, PKG, NaV1.5, plakophilin-2, and N-cadherin., Results: N-cadherin and desmoplakin immunoreactive signals and distribution were normal in patients with AC compared to controls. Plakophilin-2 signals were unaffected unless a plakophilin-2 mutation predicting haploinsufficiency was present. Distribution was unchanged compared to that in controls. Immunoreactive signal levels of PKG, Cx43, and NaV1.5 were disturbed in 74%, 70%, and 65% of the patients, respectively., Conclusions: A reduced immunoreactive signal of PKG, Cx43, and NaV1.5 at the intercalated disks can be observed in a large majority of the patients. Decreased levels of Nav1.5 might contribute to arrhythmia vulnerability and, in the future, potentially could serve as a new clinically relevant tool for risk assessment strategies., (Copyright © 2013 Heart Rhythm Society. All rights reserved.)

Aims: To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM)., Methods and Results: We screened a cohort of 97 ARVC and 257 DCM unrelated index patients for PLN mutations and evaluated their clinical characteristics. PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Haplotype analysis revealed a common founder, estimated to be between 575 and 825 years old. A low voltage electrocardiogram was present in 46 % of R14del carriers. Compared with R14del- DCM patients, R14del+ DCM patients more often demonstrated appropriate implantable cardioverter defibrillator discharge (47 % vs. 10 % , P < 0.001), cardiac transplantation (18 % vs. 2 % , P < 0.001), and a family history for sudden cardiac death (SCD) at < 50 years (36 % vs. 16 % , P = 0.007). We observed a similar pattern in the ARVC patients although this was not statistically significant. The average age of 26 family members who died of SCD was 37.7 years. Immunohistochemistry in available myocardial samples revealed absent/depressed plakoglobin levels at intercalated disks in five of seven (71 %) R14del+ ARVC samples, but in only one of nine (11 %) R14del+ DCM samples (P = 0.03)., Conclusions: The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC. R14del+ patients diagnosed with DCM showed an arrhythmogenic phenotype, and SCD at young age can be the presenting symptom. These findings support the concept of 'arrhythmogenic cardiomyopathy'.

Arrhythmogenic cardiomyopathy (AC) has originally been described as a disorder characterized by fibrofatty replacement of the myocardium, primarily of the right ventricle (RV), and ventricular tachyarrhythmias, sudden death, and at a late stage progressive heart failure. Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD/C) was the previous name of the disease. However, similar histopathologic changes are also found in the left ventricle (LV). AC is also considered a hereditary disease. Recent molecular genetic studies provide accumulating evidence that fibrofatty replacement is preceded by mutation-related desmosomal changes. Desmosomal dysfunction may lead to mechanical and thereafter electrical uncoupling, ultimately resulting in conduction delay. This activation delay and conduction block, provide a substrate for re-entrant mechanisms and thereby ventricular tachycardia (VT). The gold standard for AC diagnosis is demonstration of transmural fibrofatty replacement in cardiac tissue obtained by autopsy or surgery. To facilitate diagnosis in clinical practice, an international Task Force defined in 1994 a set of criteria (TFC) based on electrocardiographic, functional and morphologic features, and family history. These criteria have recently been revised. Routine 12-lead electrocardiography is one of the most important tools for AC diagnosis in all stages of the disease. Even in the absence of other markers in the early concealed stage of the disease, in line with early slow conduction and electrical uncoupling ECG analysis may contribute to early diagnosis. Activation delay and site of origin of VT are reflected in various characteristics of the surface 12-lead electrocardiogram. Since the ECG is easy to obtain, this technique is particularly useful, for both diagnosis and follow up of disease progression.

Background: The overt stage of arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is preceded by a concealed stage with minor or no signs of disease. However, sudden death may occur in this early phase. Deformation imaging may contribute to early diagnosis. The aims of this study were to compare the diagnostic accuracy of the conventional (1994) versus the recently published (2010) new echocardiographic criteria for ARVD/C and to evaluate the additional value of echocardiographic tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic carriers of pathogenic ARVD/C mutations., Methods: Fourteen asymptomatic first-degree relatives of ARVD/C probands (the ARVD/C-r group; mean age, 38.0 ± 13.2 years) with a pathogenic plakophilin-2 mutation and a group of age-matched controls (n = 56; mean age, 38.2 ± 12.7 years) were included at a 1:4 ratio. A complete echocardiographic evaluation (dimensions, global systolic parameters, and visual assessment and deformation imaging of the RV free wall including Doppler tissue imaging and two-dimensional strain echocardiography) was obtained. Peak systolic strain less negative than -18% and/or postsystolic shortening (postsystolic index > 15%) in any RV segment was considered abnormal., Results: RV dimensions in the ARVD/C-r group were similar to those in controls (RV outflow tract, 15.4 ± 2.9 vs 14.4 ± 1.9 mm/m(2), P = NS; RV inflow tract, 18.6 ± 2.6 vs 19.1 ± 2.6 mm/m(2), P = NS), and global systolic parameters were moderately reduced (tricuspid annular plane systolic excursion, 20.0 ± 3.2 vs 23.9 ± 2.8 mm, P = .001; RV fractional area change, 40.3 ± 8.4 vs 40.6 ± 7.1, P = NS). According to task force criteria, 57% of the ARVD/C-r group and 29% of controls were classified as abnormal when applying the 1994 criteria and 29% and 4% when applying the 2010 criteria, respectively. Doppler tissue imaging and two-dimensional strain deformation (and strain rate) values were reduced in the ARVD/C-r group in the basal and mid RV segments compared with controls (P < .001). In the ARVD/C-r group, peak systolic strain less negative than -18% was seen in six patients (43%), postsystolic strain in nine (64%), and either abnormality in 10 (71%), almost exclusively in the basal segment; these findings were observed in none of the controls., Conclusions: The 2010 criteria for ARVD/C improve specificity, whereas sensitivity is significantly reduced in this asymptomatic population. In contrast, echocardiographic deformation imaging detects functional abnormalities in the subtricuspid region in 71% of asymptomatic carriers of a pathogenic plakophilin-2 mutation, while regional deformation was normal in all control subjects, indicating superiority of both sensitivity and specificity with these new modalities., (Copyright © 2012. Published by Mosby, Inc.)

Background: Cardiac magnetic resonance (CMR) evaluation of athletes for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is complicated by overlapping features such as right ventricular (RV) volume increase. The revised ARVC/D diagnostic Task Force Criteria (TFC) incorporate cut-off values for RV ejection fraction (EF) and RV end-diastolic volume (EDV) on CMR., Design: To distinguish ARVC/D patients from athletes we compared CMR ventricular volumes, function, TFC cut-off values, and LV/RV ratios since athletes show proportionate, and ARVC/D patients disproportionate, changes in LV and RV., Methods: Quantitative CMR parameters of 33 ARVC/D patients (64% male, mean age 45.4 years, diagnosed by revised TFC), 66 healthy athletes and 66 healthy non-athletes (sex and age matched) were compared using revised TFC and new cut-off values representing LV/RV balance., Results and Conclusions: Absolute values for ARVC/D patients/athletes/non-athletes were: in males, RV EDV 149/133/106 ml/m(2), ratio EDV LV/RV 0.70/0.91/0.93, RV EF 34/52/54%, LV EF 48/57/58%, ratio EF LV/RV 1.49/1.10/1.09; and in females, RV EDV 115/115/91 ml/m(2), ratio EDV LV/RV 0.86/0.94/0.97, RV EF 43/54/58%, LV EF 52/57/61%, ratio EF LV/RV 1.23/1.08/1.04 (p-values < 0.05). Areas under the ROC-curve are 0.68 (RV EDV index), 0.84 (LV/RV EDV ratio) and 0.93 (RV EF), demonstrating significantly (p < 0.001) better performance of RV EF and LV/RV EDV ratio. If a wall motion abnormality is present (observed in 30 ARVC/D patients and not in healthy subjects), RV EF can help distinguish ARVC/D from physiological cardiac adaptation in athletes on CMR whereas RV EDV index cannot. A good alternative in athletes is the LV/RV EDV ratio, representing normal proportionate adaptation of both ventricles.

Arrhythmogenic cardiomyopathy (AC) is characterised by myocardial fibrofatty tissue infiltration and presents with palpitations, ventricular arrhythmias, syncope and sudden cardiac death. AC is associated with mutations in genes encoding the desmosomal proteins plakophilin-2 (PKP2), desmoplakin (DSP), desmoglein-2 (DSG2), desmocollin-2 (DSC2) and junctional plakoglobin (JUP). In the present study we compared 28 studies (2004-2011) on the prevalence of mutations in desmosomal protein encoding genes in relation to geographic distribution of the study population. In most populations, mutations in PKP2 showed the highest prevalence. Mutation prevalence in DSP, DSG2 and DSC2 varied among the different geographic regions. Mutations in JUP were rarely found, except in Denmark and the Greece/Cyprus region.

Objectives: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index patients, a genetic predisposition is demonstrated. The purpose of this study was to examine a plakophilin-2 (PKP2) splice site mutation, c.2489+4A>C, identified in 4 separately ascertained Dutch ARVD/C families., Methods: Genealogical studies and comprehensive screening of 5 desmosomal genes were undertaken. Reverse transcriptase PCR (RT-PCR) and subsequent sequencing was performed., Results: An A-to-C change (c.2489+4A>C) near the splice donor site of intervening sequence 12 of PKP2 was found in all 4 families. Based on pedigree data and haplotype sharing, a common ancestor should be situated more than 7 generations ago. RT-PCR demonstrated the presence of aberrant messenger RNA. Clinical manifestations ranged from severe disease to nonpenetrance in elderly mutation carriers., Conclusions: This founder mutation in PKP2 is predicted to lead to the presence of a dysfunctional PKP2 protein, whereas most truncating mutations are expected to lead to loss of protein. Mutation carriers displayed a wide range of disease severity, suggesting that PKP2 mutations alone are not sufficient to cause disease, which results in the variable expression and incomplete penetrance characteristic of ARVD/C mutations., (Copyright © 2012 S. Karger AG, Basel.)

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.Arg79X mutation in PKP2 has been identified in Europe and North America and has been functionally characterised. We evaluated the prevalence of the p.Arg79X mutation in PKP2 in the Dutch population., Methods: Twelve index patients and 41 family members were evaluated in three university hospitals in the Netherlands. The diagnosis of ARVC/D was established according to the recently revised Task Force Criteria. Segregation of the p.Arg79X mutation was studied and haplotypes were reconstructed to determine whether the p.Arg79X mutation was a recurrent or a founder mutation., Results: The p.Arg79X mutation in PKP2 was identified in 12 index patients. Haplotype analysis revealed a shared haplotype among Dutch p.Arg79X mutation carriers, indicating a common founder. Six index patients (50%) had a first- or second-degree relative who had died of sudden cardiac death below 40 years of age. At age 60, only 60% of the mutation carriers had experienced any symptoms. There was no significant difference in symptom-free survival and event-free survival between men and women., Conclusion: We have identified the largest series of patients with the same desmosome gene mutation in ARVC/D reported to date. This p.Arg79X mutation in PKP2 is a founder mutation in the Dutch population. The phenotypes of PKP2 p.Arg79X mutation carriers illustrate the clinical variability and reduced penetrance often seen in ARVC/D. (Neth Heart J 2010;18:583-91.).

ResearcherS used two behavioral prompts to compare increases in safety belt use: a Click It or Ticket prompt or a Flash-for-Life prompt. Participants were 1,822 unbuckled drivers exiting two student parking lots of a large university. Research assistants identified unbuckled drivers, flashed one of the two prompts, and recorded whether drivers buckled after the prompt and the drivers' facial expressions and hand gestures. Findings and implications are discussed.

Background: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) Diagnostic Task Force Criteria (TFC) proposed in 1994 are highly specific but lack sensitivity. A new international task force modified criteria to improve diagnostic yield. A comparison of diagnosis by 1994 TFC versus newly proposed criteria in 3 patient groups was conducted., Methods and Results: In new TFC, scoring by major and minor criteria is maintained. Structural abnormalities are quantified and TFC highly specific for ARVD/C upgraded to major. Furthermore, new criteria are added: terminal activation duration of QRS > or = 55 ms, ventricular tachycardia with left bundle-branch block morphology and superior axis, and genetic criteria. Three groups were studied: (1) 105 patients with proven ARVD/C according to 1994 TFC, (2) 89 of their family members, and (3) 39 patients with probable ARVD/C (ie, 3 points by 1994 TFC). All were screened for pathogenic mutations in desmosomal genes. Three ARVD/C patients did not meet the new sharpened criteria on structural abnormalities and thereby did not fulfill new TFC. In 62 of 105 patients with proven ARVD/C, mutations were found: 58 in the gene encoding Plakophilin2 (PKP2), 3 in Desmoglein2, 3 in Desmocollin2, and 1 in Desmoplakin. Three patients had bigenic involvement. Ten additional relatives (11%) fulfilled new TFC: 9 (90%) were female, and all carried PKP2 mutations. No relatives lost diagnosis by application of new TFC. Of patients with probable ARVD/C, 25 (64%) fulfilled new TFC: 8 (40%) women and 14 (56%) carrying pathogenic mutations., Conclusions: In this first study applying new TFC to patients suspected of ARVD/C, 64% of probable ARVD/C patients and 11% of family members were additionally diagnosed. ECG criteria and pathogenic mutations especially contributed to new diagnosis. Newly proposed TFC have a major impact in increasing diagnostic yield of ARVD/C.

Background: This study aimed to evaluate the prevalence and type of mutations in the major desmosomal genes, Plakophilin-2 (PKP2), Desmoglein-2 (DSG2), and Desmocollin-2 (DSC2), in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients. We also aimed to distinguish relevant clinical and ECG parameters., Methods and Results: Clinical evaluation was performed according to the Task Force Criteria (TFC). We analyzed the genes in (a) 57 patients who fulfilled the ARVD/C TFC (TFC+), (b) 28 patients with probable ARVD/C (1 major and 1 minor, or 3 minor criteria), and (c) 31 patients with 2 minor or 1 major criteria. In the TFC+ ARVD/C group, 23 patients (40%) had PKP2 mutations, 4 (7%) had DSG2 mutations, and 1 patient (2%) carried a mutation in DSC2, whereas 1 patient (2%) had a mutation in both DSG2 and DSC2. Among the DSG2 and DSC2 mutation-positive TFC+ ARVD/C probands, 2 carried compound heterozygous mutations and 1 had digenic mutations. In probable ARVD/C patients and those with 2 minor or 1 major criteria for ARVD/C, mutations were less frequent and they were all heterozygous. Negative T waves in the precordial leads were observed more (P<0.002) among mutation carriers than noncarriers and in particular in PKP2 mutation carriers., Conclusions: Mutations in DSG2 and DSC2 are together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C patients. Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation is less likely to cause a full-blown ARVD/C phenotype. Negative T waves on ECG were prevalent among mutation carriers (P<0.002).

Background: Desmosomal changes, electric uncoupling, and surviving myocardial bundles in fibrofatty tissue characterize arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Resultant activation delay is pivotal for reentry and thereby ventricular tachycardia (VT). Current task force criteria (TFC) for diagnosis have limited sensitivity. The aim of this study was to assess the diagnostic value of additional criteria on activation delay and VT to improve identification of affected individuals., Methods and Results: ECG criteria were studied, while off drugs, in 50 index patients with proven ARVD/C according to TFC (TFC > or = 4 points) and 33 patients with probable ARVD/C (TFC 3 points, or TFC3), being 21 index patients and 12 family members of proven ARVD/C patients. Newly proposed additional criteria are (1) prolonged terminal activation duration in V(1)-V(3), an indicator of activation delay, (2) VT with left bundle-branch block morphology and superior axis, and (3) multiple VT morphologies. All index patients were screened for mutations in ARVD/C-related genes encoding desmosomal proteins. Altogether, 23 of 33 (70%) TFC3 patients fulfilled ARVD/C diagnosis when newly proposed criteria were applied additionally to current TFC. VT with left bundle-branch block morphology and superior axis or multiple VT morphologies were recorded in 12 and 9 of 33 TFC3 patients, respectively, all being index patients. When applying prolonged terminal activation duration additionally to TFC on depolarization/conduction abnormalities, 14 (42%) TFC3 patients fulfilled ARVD/C diagnosis. Results were not significantly different between mutation carriers and noncarriers., Conclusions: Adding the newly proposed criteria to current TFC for ARVD/C will improve identification of affected individuals importantly, independent of outcome of DNA analyses.

Background: The aim of this study was to determine the accuracy of new quantitative echocardiographic strain and strain-rate imaging parameters to identify abnormal regional right ventricular (RV) deformation associated with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)., Methods: A total of 34 patients with ARVD/C (confirmed by Task Force criteria) and 34 healthy controls were prospectively enrolled. Conventional echocardiography, including Doppler tissue imaging (DTI), was performed. Doppler and two-dimensional strain-derived velocity, strain, and strain rate were calculated in the apical, mid, and basal segments of the RV free wall., Results: RV dimensions were significantly increased in patients with ARVD/C (RV outflow tract 19.3+/-5.2 mm/m2 vs 14.1+/-2.2 mm/m2, P<.001; RV inflow tract 23.4+/-4.8 mm/m2 vs 18.8+/-2.4 mm/m2, P<.001), whereas left ventricular dimensions were not significantly different compared with controls. Strain and strain rate values were significantly lower in patients with ARVD/C in all 3 segments. All deformation parameters showed a higher accuracy to detect functional abnormalities compared with conventional echocardiographic criteria of dimensions or global systolic function. The lowest DTI strain value in any of the 3 analyzed segments showed the best receiver operating characteristics (area under the curve 0.97) with an optimal cutoff value of -18.2%., Conclusions: DTI and two-dimensional strain-derived parameters are superior to conventional echocardiographic parameters in identifying ARVD/C. This novel technique may have additional value in the diagnostic workup of patients with suspected ARVD/C.

Intercalated discs are the membrane sites where individual cardiomyocytes are connected to each other. Adherens-, desmosomal-, and gap junctions are situated in the intercalated disc and ensure mechanical coupling between cells and enable propagation of electrical impulses throughout the heart. A number of cardiac disorders, for example arrhythmogenic right ventricular dysplasia/cardiomyopathy, have been described in which an impaired mechanical coupling leads to electrical dysfunction, with occurrence of fatal arrhythmias. In this article the interaction between electrical and mechanical coupling is explored by reviewing studies performed in patients, animals, and in vitro. In these studies the effect of changes in protein composition of a mechanical junction on the electrical junction, and vice versa were investigated. It is shown that impaired electrical coupling does not change mechanical coupling. However, impaired mechanical coupling largely affects electrical coupling.