Heart Disease Arrhythmias Research Articles

Clinical Efficacy and Cardiac Function Analysis of Zhigancao Decoction Combined With Metoprolol in the Treatment of Coronary Heart Disease Arrhythmias

Objective: To explore the clinical effect and cardiac function of moxibustion licorice decoction combined with metoprolol in the treatment of coronary heart disease arrhythmia. Method: 92 patients with coronary heart disease and arrhythmia admitted from January 2022 to December 2023 were selected as the analysis subjects. Divide into a control group and an observation group using envelope randomization method. The former is treated with metoprolol, while the latter is treated with moxibustion licorice soup and metoprolol. Compare clinical efficacy, cardiac function, heart rate variability, and adverse reactions. The total effective rate of the observation group treatment was 95.65%, which was higher than that of the control group 82.61% (X2=4.039, P=0.044); The LVESD and CO levels in the observation group were lower than those in the control group, while the LVEF and LVEDD levels were higher than those in the control group (P<0.05); The number of atrial premature beats and ventricular premature beats at 24 hours in the observation group was lower than that in the control group, and the levels of SDNN and SDANN were higher than those in the control group (P<0.05); The incidence of adverse reactions in the observation group was 6.52%, which was lower than that in the control group (X2=4.389, P=0.036). Conclusion: For patients with coronary heart disease and arrhythmia, moxibustion with licorice decoction combined with metoprolol has a clear effect, can improve heart function, reduce myocardial contractility, and is relatively safe.

Efficacy, safety, and economy of shensongyangxin capsules for the treatment of coronary heart disease arrhythmia: a meta-analysis of randomized controlled trials.

Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled trials of SSYX was reported in the treatment of Coronary heart disease arrhythmia in China. However, these experiments have not been systematically evaluated by economics. The purpose of this study was to assess the efficacy, safety, and economy of the SSYX in the treatment of arrhythmia in patients with coronary heart disease. With "Shensong Yangxin Capsules" "Coronary Heart Disease" "Coronary Atherosclerotic Heart Disease"and "Arrhythmia" as the subject words, the relevant journals and conference papers were searched manually in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, PubMed, Web Of Science, CBM, Embase and The Cochrane Library. The literature of randomized controlled trials of SSYX in the treatment of coronary heart disease arrhythmia was searched until November 2022. All data were analyzed using RevMan 5.3 Sotware and combined with cost-effectiveness for economic evaluation. Twenty randomized controlled trials were included in this study, with a total of 2011 cases. The meta-analysis showed that the therapeutic effect of SSYX-metoprolol is superior to that of metoprolol alone. SSYX is superior to amiodarone in improving the total clinical effective rate, reducing the incidence of adverse reactions, and reducing the junction premature beats. There was no significant difference between the SSYX and amiodarone in the curative effect of ECG, ventricular premature complexes, and atrial premature beats. The results of pharmacoeconomics show that SSYX has a cost-effectiveness advantage in treating coronary heart disease arrhythmia. Single-factor sensitivity analysis also confirmed the stability of the results. In summary, SSYX has a curative effect, safety, and economy in treating coronary heart disease arrhythmia.

Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure.

Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats. MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization. PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (P=0.007). PF4618433 improved stroke volume (P=0.031) and cardiac output (P=0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (P=0.002) and fractional shortening (P=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (P=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI. Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.

Pediatric Electrophysiology Device Needs: A Survey from the Pediatric and Congenital Electrophysiology Society Taskforce on Pediatric-Specific Devices.

Background There are few US Food and Drug Administration (FDA)-approved devices specifically aimed at the pediatric patient with arrhythmia. This has led to a high off-label utilization of devices in this vulnerable population. The Pediatric and Congenital Electrophysiology Society (PACES), the international organization representing pediatric and congenital heart disease arrhythmia specialists, developed a task force to comprehensively address device development issues relevant to pediatric patients with congenital arrhythmia. Methods and Results As a first step, the taskforce developed a 26-question survey for the pediatric arrhythmia community to assess providers' understanding of the FDA approval process, specifically in regard to pediatric labeling. There were 92/211 respondents (44%) with a >90% completion rate. The vast majority of respondents believed there was a paucity of devices available for children (96%). More than 60% of respondents stated that they did not understand the FDA regulatory process and were not aware of whether the devices they used were labeled for pediatric use. Conclusions Pediatric electrophysiologists are keenly aware of the deficit of available pediatric devices for their patients. The majority do not understand the FDA approval process and could benefit from additional educational resources regarding this. A collaborative forum including PACES, FDA, patients and their families, and Industry would be an important next step in clarifying opportunities and priorities to serve this vulnerable population.

TARGETING TUMOR NECROSIS FACTOR (TNF) IN ATRIAL STRETCH-DEPENDENT ADVERSE ATRIAL REMODELING AND VALVULAR ATRIAL FIBRILLATION IN A MOUSE MODEL OF AORTIC REGURGITATION

TARGETING TUMOR NECROSIS FACTOR (TNF) IN ATRIAL STRETCH-DEPENDENT ADVERSE ATRIAL REMODELING AND VALVULAR ATRIAL FIBRILLATION IN A MOUSE MODEL OF AORTIC REGURGITATION

Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease.

The ryanodine receptor (RyR2) has a critical role in controlling Ca2+ release from the sarcoplasmic reticulum (SR) throughout the cardiac cycle. RyR2 protein has multiple functional domains with specific roles, and four of these RyR2 protomers are required to form the quaternary structure that comprises the functional channel. Numerous mutations in the gene encoding RyR2 protein have been identified and many are linked to a wide spectrum of arrhythmic heart disease. Gain of function mutations (GoF) result in a hyperactive channel that causes excessive spontaneous SR Ca2+ release. This is the predominant cause of the inherited syndrome catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, rare hypoactive loss of function (LoF) mutations have been identified that produce atypical effects on cardiac Ca2+ handling that has been termed calcium release deficiency syndrome (CRDS). Aberrant Ca2+ release resulting from both GoF and LoF mutations can result in arrhythmias through the Na+/Ca2+ exchange mechanism. This mini-review discusses recent findings regarding the role of RyR2 domains and endogenous regulators that influence RyR2 gating normally and with GoF/LoF mutations. The arrhythmogenic consequences of GoF/LoF mutations will then be discussed at the macromolecular and cellular level.

Study on Effective Nursing Methods of Senile Coronary Heart Disease Arrhythmia and Its Influence on Nursing Quality

Study on Effective Nursing Methods of Senile Coronary Heart Disease Arrhythmia and Its Influence on Nursing Quality

P320 LEFT DOMINANT ARRHYTHMOGENIC CARDIOMYOPATHY: HOW TO STRATIFY THE ARRHYTHMIC RISK? EARLY ONSET CLINICAL CASE

Abstract Introduction Arrhythmogenic cardiomyopathy (ACM) is a genetic disease characterized by the progressive replacement of myocardiocytes by fibroadipose tissue that becomes a susbstrate for ventricular arrhythmias with risk of sudden cardiac death. Arrhythmogenic cardiomyopathy can manifest itself through three different phenotypes: the classic phenotype, the most frequent, involving only the right ventricle, the biventricular variant with possible right or left dominance and the rare variant involving only the left ventricle. We present a case of left ventricular arrhythmogenic cardiomyopathy. Case Report 16–year–old male patient in complete physical well–being, with no significant medical history and a negative family history of heart disease and/or sudden cardiac death (Fig. 1). He practiced competitive sports for years with periodic medical–sports visits. In 2017, ventricular extrasystole was detected on the electrocardiogram, for which he performed cardiological investigations. On electrocardiogram: sinus rhythm with QRS fragmented into DIII and aVL and negative T waves from V4 to V6 (Fig. 2). On transthoracic echocardiography, evidence of normal cavity dimensions, ejection fraction at lower normal limits (42%) and left ventricular trabeculation, in the absence of significant valvulopathy. He then performed a cardiac MRI that showed: left ventricle moderately dilated and hypokinetic with widespread alterations of myocardial signal secondary to fibroadipose replacement phenomena, configuring a picture of left ventricular dilation and dysfunction referable to arrhythmogenic left ventricular cardiomyopathy (Fig. 3). The patient was also subjected to genetic analysis aimed at searching for mutations of genes involved in arrhythmic heart disease, which was negative. In light of the absence of conclusive scientific evidence on the implantation of a defribrillator in primary prevention in clinical–instrumental cases such as the present, the risk of infection and the risk of inappropriate discharges, it was proposed the implantation of a loop–recorder in order to monitor and record any arrhythmic events, starting beta–blocker therapy. The possibility of continuing competitive physical activity was therefore denied. Conclusions Currently, guidelines on ACM and diagnostic criteria focus mainly on the right variant, so there are no clear indications to stratify arrhythmic risk in left ventricular ACM.

P170 VALUE OF ELECTROCARDIOGRAPHIC SCREENING FOR EARLY DETECTION OF ARRHYTHMIC AND MALIGNANT HEART DISEASE IN CHILDREN

Abstract Background Twelve–lead electrocardiography (ECG) is a tool that can identify cardiac conduction abnormalities that predispose to sudden cardiac death (SCD) in completely asymptomatic subjects. The rate of sudden cardiac death in childhood is estimated at 1–1.5 cases per 100,000 individuals and 10–15% of events occur during physical activity. We evaluated the importance of the electrocardiogram performed in childhood in the early diagnosis of asymptomatic electrocardiographic changes suggestive for electrical or structural heart disease potentially at risk of sudden death. Materials and Methods we analyzed 623 patients aged 0–16 years who were referred to the pediatric arrhythmology clinic in Padua Hospital between October 2013 and March 2020. Patients were referred to our second–level clinic after a first electrocardiographic alteration found out in ECG screening performed for sports activity. All patients were evaluated with clinical history and ECG. Then, depending on the suspected pathology, Holter ECG, ergometric test, echocardiogram, MRI were performed for adequate risk stratification. Results Of the 623 patients evaluated, 393 (63%) were referred by sports medicine, 179 (29%) by the hospital pediatric clinic or family pediatrician, and 51 patients (8%) were referred for familiarity. 45% of patients (280) were referred for suspected WPW; 124 patients (20%) for many BEV and suspected ARVD; 85 patients (14%) for suspected long QT, 31 patients (5%) for suspected Brugada pattern; 7 patients (1%) for suspected CPVT; 8 patients (1%) for electrocardiographic changes with suspected HCM; 1 patient (0.01%) for suspected short QT and 88 patients (14%) for other arrhythmic disorders not at risk of sudden death. The diagnosis of WPW was confirmed in 280 patients (100%), LQTS in 45 patients (52%), SQTS in 1 patient (100%), S. of Brugada in 8 patients (25%), CPVT in 5 patients (71%), HCM in 8 patients (100%) and ARVD in 6 patients (5%). Conclusions Our study demonstrates that electrocardiographic screening in childhood allows early diagnosis and treatment of life–threatening arrhythmic heart disease.

Clinical Analysis of 24h Holter ECG in the Diagnosis of Coronary Heart Disease Arrhythmia

Clinical Analysis of 24h Holter ECG in the Diagnosis of Coronary Heart Disease Arrhythmia

Lymphoma Patients Treated without Anthracyclines Have Negligible Risk of Cardiotoxicity: A Nationwide Cohort Study

▪AbstractObjective: For more than two decades,CHOP (and later R-CHOP) has been the standard frontline treatment for diffuse large b-cell lymphoma (DLBCL). However, anthracycline-based chemotherapy regimens increase risk of cardiotoxicity with congestive heart failure (HF) being the best documented cardiovascular complication of anthracycline use. However, cardiotoxicity has also been associated with other chemotherapeutic drugs. In this nationwide cohort study, we compared the incidence of development of HF in patients with DLBCL or follicular lymphoma (FL) treated with or without anthracyclines.Methods: DLBCL and FL patients > 16 years both receiving anthracycline in the form of R-CHOP/CHOEP or non-anthracycline chemotherapy regiments were identified in the Danish National Lymphoma Registry (LYFO) from 2000-2012. Anthracycline exposed patients were required to receive ≥3 cycles of R-CHOP or R-CHOEP upfront. The non-anthracycline exposed patients consisted of patients receiving non-anthracycline containing chemotherapy (such as CVP, CEOP and Bendamustine). Exclusion criteria were i) treatment with chemo therapy regimens more intensive than R-CHOP/CHOEP, ii) up-front high dose autologous stem cell transplantation and iii) the following heart comorbidities prior to the beginning of the study: HF (ICD-10 code: “I50”), Ischemic Heart Disease (ICD-10 code: “I20-I25”), Arrhythmic Heart Disease (ICD-10 code: “I48-I49”) and Cardiomyopathy (ICD-10 code: “I42”). Information on heart comorbidities in our study population were retrieved from the Danish National Patient Registry. Patient follow-up started from 30 days after ended chemotherapy to minimize confounding by early HF on the planned number of R-CHOP treatments. Follow-up ended when HF occurred, on the day of emigration from Denmark, day of death or the end of the study on 31th. December 2014, whichever came first. Univariate and multivariable cox regression analyses were performed to assess the association between cumulative anthracycline treatments and HF (adjusted analysis included gender, age, Ann Arbor stadium, radiotherapy, comorbidities and type of lymphoma). Cumulative R-CHOP treatments were stratified into groups of “3-5”, “6” and “>6” treatments. Cumulative incidence curves were computed to illustrate risk of HF over time according to number of treatments.Results: The study included 2,696 patients; 2,007 received anthracycline and 689 received non-anthracycline containing chemotherapy. In total, 1979 patients were diagnosed with DLBCL and 717 with follicular lymphoma. Anthracycline users were slightly younger (median age 64.03 vs 65.2 years (p-value <0.01)), received radiotherapy more often (21.03% vs 6.82% (p-value <0.01)) and were more frequently diagnosed with DLBCL (87.94% vs 31.06% (p-value <0.01)) (table 1). For patients not treated with anthracycline, the cumulative risk of HF within 1, 5 and 8 years were 0%, 0.89% and 1.77%, respectively. For patients treated with 3- 5 cycles of R-CHOP/CHOEP, the corresponding cumulative risk were 0.54%, 4.58% and 5.18%. For patients treated with 6 cycles, the cumulative risks were 1.02%, 4.49% and 8.02 % and for patients treated with >6 cycles, the cumulative risks were 4.01 %, 7.86% and 9.33% (fig 1).Compared to patients receiving non-anthracycline containing chemotherapy (reference), patients receiving anthracycline containing chemotherapy had a higher risk of developing HF during follow-up with adjusted hazard ratio (HR) of 3.73 (95% CI 1.38-10.09) for patients receiving 3-5 cycles, 4.38 (95% CI 1.83-10.48) for patients receiving 6 cycles, and 8.22 (95% CI 3.50-19.31) for patients receiving >6 cycles of anthracycline treatment.Conclusion: This present studyconfirms that inclusion of anthracyclines in a multi-agent chemotherapy regimen is responsible for the increased risk of HF observed after treatment for lymphoma and that the rate of HF is correlated to the number of treatment cycles. Patients treated without anthracyclines had a negligible risk of HF supporting the safety of these regimens in patients considered at substantial risk of cardiotoxicity. [Display omitted] DisclosuresJørgensen:Roche: Research Funding. Poulsen:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. El-Galaly:Roche: Other: Travel funding; Takeda: Other: Travel funding.

Value of electrocardiographic screening for the early diagnosis of arrhythmic and malignant heart disease in pediatric age

Abstract Funding Acknowledgements Type of funding sources: None. Background The 12-lead electrocardiogram (ECG) is an instrument that can identify cardiac conduction system abnormalities that predispose to sudden cardiac death (SCD) in completely asymptomatic subjects. The rate of sudden cardiac death in pediatric age is estimated to be around 1-1.5 cases per 100.000 individuals, and 10-15% of events occur during physical activity. We evaluated the importance of the electrocardiogram performed in pediatric age in the early detection of asymptomatic electrocardiographic alterations, suggestive for the presence of electrical or structural heart disease potentially at risk for sudden death. Materials and Methods We analyzed 623 patients between 0 and 16 years of age who were sent to the second level pediatric arrhythmology clinic in Padua Hospital between October 2013 and March 2020. The patients were redirected at our clinic after a first finding of electrocardiographic alterations, following ECG performed before the beginning of sport activity, suspected of life-threatening pathologies. The following parameters were evaluated of all patients: clinical suspect of sending the pediatric arrhythmology clinic and electrocardiogram. Then, depending on the type of pathology suspected, the following diagnostic tests were carried out to confirm the clinical suspicion, and if confirmed, to carry out an adequate risk stratification: Holter ECG, ergometric Results Among the evaluated population (623 patients), 393 patients (63%) were sent to the pediatric arrhythmology clinic by sports medicine, 179 (29%) were sent by clinical o family pediatrician, and 51 patients (8%) were sent after ECG performed at hospital facilities for familiarity. The majority, 280 patients (45%), were sent for suspected WPW; 124 patients (20%) were sent for BEV and suspected ARVD; 85 patients (14%) for suspected long QT, 31 patients (5%) for suspected Brugada Pattern; 7 patients (1%) suspected CPVT; 8 patients (1%) for electrocardiographic changes with suspected HCM; 1 patient (0.01%) suspected shortened QT, and 88 patients (14%) for other arrhythmic disorders not at risk of sudden death. The diagnosis of WPW was confirmed in 280 patients, LQTS in 45 patients, SQTS in 1 patient, S. di Brugada in 8 patients, CPVT in 5 patients, HCM in 8 patients and ARVD in 6 patients. Conclusions Our study shows that the electrocardiographic screening already in pediatric age allows the diagnosis and subsequent early treatment of life-threatening arrhythmic heart diseases.

Efficacy of Metoprolol Succinate Sustained Release Tablets Combined with Wenxin Granules in the Treatment of Coronary Heart Disease Arrhythmia

Objective: To explore the effect of metoprolol succinate sustained-release tablets combined with Wenxin Granules in the treatment of coronary heart disease patients with arrhythmia. Methods: The research objects were 50 patients with arrhythmia who were treated in our hospital from September 2019 to September 2020. According to different treatment methods, they were divided into observation group (Wenxin Granule + metoprolol succinate treatment) and control group (metoprolol succinate treatment), 25 cases in each group. The curative effects of the two groups were compared. Results: After treatment, there was no significant difference in rnn50, RMSSD, sdnni and SDANN between the two groups (P&gt;0.05). Compared with the control group, the SDNN in the observation group was higher than that in the control group (P&lt; 0.05); Before treatment, there was no significant difference in the above indexes between the two groups (P&gt;0.05); The effective rates of the observation group and the control group were 92.00% and 68.00% respectively, and the curative effect of the observation group was higher than that of the control group (P&lt; 0.05); There was no significant difference in the incidence of adverse reactions between the two groups (P&gt; 0.05). Conclusion: In the treatment of patients with coronary heart disease and arrhythmia, Wenxin Granule Combined with metoprolol succinate sustained-release tablets has significant effect, which can effectively improve the dynamic electrocardiogram indexes of patients, improve the clinical efficacy, and has high safety.

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1-3 According to Individuals' Gender, Age, and QTc Intervals: A Network Meta-analysis.

Long QT syndrome (LQTS) is an arrhythmic heart disease caused by congenital genetic mutations, and results in increased occurrence rates of polymorphic ventricular tachyarrhythmias and sudden cardiac death (SCD). Clinical evidence from numerous previous studies suggested that beta blockers (BBs), including atenolol, propranolol, metoprolol, and nadolol, exhibit different efficacies for reducing the risk of cardiac events (CEs), such as syncope, arrest cardiac arrest (ACA), and SCD, in patients with LQTS. In this study, we identified relevant studies in MEDLINE, PubMed, embase, and Cochrane databases and performed a meta-analysis to assess the relationship between the rate of CEs and LQTS individuals with confounding variables, including different gender, age, and QTc intervals. Moreover, a network meta-analysis was not only established to evaluate the effectiveness of different BBs, but also to provide the ranked efficacies of BBs treatment for preventing the recurrence of CEs in LQT1 and LQT2 patients. In conclusion, nadolol was recommended as a relatively effective strategy for LQT2 in order to improve the prognosis of patients during a long follow-up period.

Comparative Evaluation of Ambulatory Electrocardiogram and Routine Electrocardiogram in Patients with Coronary Heart Disease Arrhythmia

Comparative Evaluation of Ambulatory Electrocardiogram and Routine Electrocardiogram in Patients with Coronary Heart Disease Arrhythmia

Multi-nodal nano-actuator pacemaker for energy-efficient stimulation of cardiomyocytes

There is continuous interest in maximizing the longevity of implantable pacemakers, which are effective in remedying and managing patients with arrhythmic heart disease. This paper accordingly first proposes miniature actuating nanomachines that inter-connect with individual cardiomyocytes and then deeply explores their energy expenditure when performing basic cardiomyocyte stimulation tasks. Since evoked electrical impulses from a number of actuated cardiomyocytes could coordinate contraction throughout the remaining heart muscle and lead to a heart beat, the miniature actuating nanomachines acting synchronously form a conceptual multi-nodal nano-actuator pacemaker network. Rectangular-, sine-, half-sine-, and sawtooth stimulation pulses with varying configurations are considered for actuation of a single isolated in-silico cardiomyocyte by each of the nanomachines. Computer optimization methods with energy consumption as a cost function are utilized to configure preferable stimulation signals in terms of numbers of stimulation sessions/pulses, pulse amplitudes, and duration. In addition, the simulation data are compared with experimental data obtained using in-vitro mouse cardiomyocytes. Among the considered waveforms, half-sine pulses that lead to actuation of a single cardiomyocyte consume minimum energy. None of the used sequences with multiple stimulation pulses reduces the overall energy expenditure of cell stimulation when compared to a single pulse stimulation.

Establishing 24-hour Holter reference intervals for clinically healthy puppies

Normal Holter reference intervals have not been established for dogs <1 year of age. This lack of Holter reference intervals inhibits the ability to screen puppies for early indicators of heart disease, especially in breeds that have inherited cardiac arrhythmias (e.g. German Shepherd Dogs) or a high incidence of arrhythmic heart disease (e.g. Boxer dogs). The objective of this project was to establish Holter minimum, average, and maximum heart rates and incidence of arrhythmias in clinically healthy dogs <1 year of age and to compare these results to previously reported Holter data for their adult counterparts.Forty-four client-owned clinically healthy puppies between 12 and 51 weeks of age were prospectively studied. Age was determined by date of birth and corroborated by dental examination. Puppies were deemed healthy based on history and physical examination. Puppies with heart murmurs underwent echocardiographic examination. Dogs with physiologic heart murmurs were included. Twenty-four hour ECG recordings were obtained using a digital Holter system.The median (interquartile range) Holter minimum, average, and maximum heart rates were 51 bpm (43–60 bpm), 99 bpm (85–113 bpm), and 274 bpm (257–291 bpm), respectively. The median for ventricular and supraventricular arrhythmias was 0. Ventricular and supraventricular premature complexes were identified in 4/44 (9%) and 6/44 (13%) puppies, respectively. Second degree atrioventricular block was identified in 2/44 puppies (5%). Overall, minimum, average, and maximum Holter heart rates of puppies are higher than adult dogs. The incidence of ventricular and supraventricular premature complexes in puppies is similar to adult dogs.

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K+ current by different G-protein coupled receptors.

Elevated angiotensin II (Ang II) and sympathetic activity contributes to a high risk of ventricular arrhythmias in heart disease. The rapidly activating delayed rectifier K+ current (IKr ) carried by the hERG channels plays a critical role in cardiac repolarization, and decreased IKr is involved in increased cardiac arrhythmogenicity. Stimulation of α1A -adrenoreceptors or angiotensin II AT1 receptors is known to inhibit IKr via PKC. Here, we have identified the PKC isoenzymes mediating the inhibition of IKr by activation of these two different GPCRs. The whole-cell patch-clamp technique was used to record IKr in guinea pig cardiomyocytes and HEK293 cells co-transfected with hERG and α1A -adrenoreceptor or AT1 receptor genes. A broad spectrum PKC inhibitor Gö6983 (not inhibiting PKCε), a selective cPKC inhibitor Gö6976 and a PKCα-specific inhibitor peptide, blocked the inhibition of IKr by the α1A -adrenoreceptor agonist A61603. However, these inhibitors did not affect the reduction of IKr by activation of AT1 receptors, whereas the PKCε-selective inhibitor peptide did block the effect. The effects of angiotensin II and the PKCε activator peptide were inhibited in mutant hERG channels in which 17 of the 18 PKC phosphorylation sites were deleted, whereas a deletion of the N-terminus of the hERG channels selectively prevented the inhibition elicited by A61603 and the cPKC activator peptide. Our results indicated that inhibition of IKr by activation of α1A -adrenoreceptors or AT1 receptors were mediated by PKCα and PKCε isoforms respectively, through different molecular mechanisms.

Characterization of the Connexin45 Carboxyl-Terminal Domain Structure and Interactions with Molecular Partners

Mechanisms underlying the initiation and persistence of lethal cardiac rhythms are of significant clinical and scientific interests. Gap junctions are principally involved in forming the electrical connections between myocytes, and changes in distribution, density, and properties are consistent characteristics in arrhythmic heart disease. Therefore, understanding the structure and function of gap junctions during normal and abnormal impulse propagation are essential in the control of arrhythmias. For example, Cx45 is predominately expressed in the specialized myocytes of the impulse generation and conduction system. In both ventricular and atrial human working myocytes, Cx45 is present in very low quantities. However, a reduction in Cx43 coupled with an increased Cx45 protein levels within the ventricles have been observed after myocardial infarction and end-stage heart failure. Cx45 may influence electrical and/or metabolic coupling as a result of pathophysiological overexpression. Our goal was to identify mechanisms that could cause cellular coupling to be different between the cardiac connexins. Based upon the conserved transmembrane and extracellular loop segments, our focus was on identifying features within the divergent cytoplasmic portions. Here, we biophysically characterize the carboxyl-terminal domain of Cx45 (Cx45CT). Purification revealed the possibility of oligomeric species, which was confirmed by analytical ultracentrifugation experiments. Sedimentation equilibrium and circular dichroism studies of different Cx45CT constructs identified one region of α-helical structure (A333-N361) that mediates CT dimerization through hydrophobic contacts. Interestingly, the binding affinity of Cx45CT dimerization is 1000-fold stronger than Cx43CT dimerization. Cx45CT resonance assignments were also used to identify the binding sites and affinities of molecular partners involved in the Cx45 regulation; although none disrupted dimerization, many of these proteins interacted within one intrinsically disordered region (P278-P285). This domain has similarities with other cardiac connexins, and we propose they constitute a master regulatory domain, which contains overlapping molecular partner binding, cis-trans proline isomerization, and phosphorylation sites.

Pregnancy complicated by heart disease in Nepal

ObjectiveTo investigate the prevalence, characteristics and maternal and perinatal outcomes of pregnancies complicated by heart disease.DesignProspective single-centre registry.SettingTertiary care teaching hospital in eastern Nepal.PatientsPregnant women presenting to the antenatal clinic...