Utilization of Electrocardiographic P-wave Duration for AV Interval Optimization in Dual-Chamber Pacemakers

Background

Empiric programming of the atrio-ventricular (AV) delay is commonly performed during pacemaker implantation. Transmitral flow assessment by Doppler echocardiography can be used to find the optimal AV delay by Ritter''s method, but this cannot easily be performed during pacemaker implantation. We sought to determine a non-invasive surrogate for this assessment. Since electrocardiographic P-wave duration estimates atrial activation time, we hypothesized this measurement may provide a more appropriate basis for programming AV intervals.

Methods

A total of 19 patients were examined at the time of dual chamber pacemaker implantation, 13 (68%) being male with a mean age of 77. Each patient had the optimal AV interval determined by Ritter''s method. The P-wave duration was measured independently on electrocardiograms using MUSE® Cardiology Information System (version 7.1.1). The relationship between P-wave duration and the optimal AV interval was analyzed.

Results

The P-wave duration and optimal AV delay were related by a correlation coefficient of 0.815 and a correction factor of 1.26. The mean BMI was 27. The presence of hypertension, atrial fibrillation, and valvular heart disease was 13 (68%), 3 (16%), and 2 (11%) respectively. Mean echocardiographic parameters included an ejection fraction of 58%, left atrial index of 32 ml/m², and diastolic dysfunction grade 1 (out of 4).

Conclusions

In patients with dual chamber pacemakers in AV sequentially paced mode and normal EF, electrocardiographic P-wave duration correlates to the optimal AV delay by Ritter''s method by a factor of 1.26.     

Shortening of atrioventricular delay at increased atrial paced heart rates improves diastolic filling and functional class in patients with biventricular pacing

Background

Use of rate adaptive atrioventricular (AV) delay remains controversial in patients with biventricular (Biv) pacing. We hypothesized that a shortened AV delay would provide optimal diastolic filling by allowing separation of early and late diastolic filling at increased heart rate (HR) in these patients.

Methods

34 patients (75 ± 11 yrs, 24 M, LVEF 34 ± 12%) with Biv and atrial pacing had optimal AV delay determined at baseline HR by Doppler echocardiography. Atrial pacing rate was then increased in 10 bpm increments to a maximum of 90 bpm. At each atrial pacing HR, optimal AV delay was determined by changing AV delay until best E and A wave separation was seen on mitral inflow pulsed wave (PW) Doppler (defined as increased atrial duration from baseline or prior pacemaker setting with minimal atrial truncation). Left ventricular (LV) systolic ejection time and velocity time integral (VTI) at fixed and optimal AV delay was also tested in 13 patients. Rate adaptive AV delay was then programmed according to the optimal AV delay at the highest HR tested and patients were followed for 1 month to assess change in NYHA class and Quality of Life Score as assessed by Minnesota Living with Heart Failure Questionnaire.

Results

81 AV delays were evaluated at different atrial pacing rates. Optimal AV delay decreased as atrial paced HR increased (201 ms at 60 bpm, 187 ms at 70 bpm, 146 ms at 80 bpm and 123 ms at 90 bpm (ANOVA F-statistic = 15, p = 0.0010). Diastolic filling time (P < 0.001 vs. fixed AV delay), mitral inflow VTI (p < 0.05 vs fixed AV delay) and systolic ejection time (p < 0.02 vs. fixed AV delay) improved by 14%, 5% and 4% respectively at optimal versus fixed AV delay at the same HR. NYHA improved from 2.6 ± 0.7 at baseline to 1.7 ± 0.8 (p < 0.01) 1 month post optimization. Physical component of Quality of Life Score improved from 32 ± 17 at baseline to 25 ± 12 (p < 0.05) at follow up.

Conclusions

Increased heart rate by atrial pacing in patients with Biv pacing causes compromise in diastolic filling time which can be improved by AV delay shortening. Aggressive AV delay shortening was required at heart rates in physiologic range to achieve optimal diastolic filling and was associated with an increase in LV ejection time during optimization. Functional class improved at 1 month post optimization using aggressive AV delay shortening algorithm derived from echo-guidance at the time of Biv pacemaker optimization.     

Novel insights on effect of atrioventricular programming of biventricular pacemaker in heart failure – a case series

Background

Echocardiography plays an integral role in the diagnosis of congestive heart failure including measurement of left heart pressure as well as mechanical dyssynchrony.

Methods

In this report we describe novel therapeutic uses of echo pulsed wave Doppler in atrioventricular pacemaker optimization in patients who had either not derived significant symptomatic benefit post biventricular pacemaker implantation or deteriorated after deriving initial benefit. In these patients atrioventricular optimization showed novel findings and improved cardiac output and symptoms.

Results

In 3 patients with Cheyne Stokes pattern of respiration echo Doppler showed worsening of mitral regurgitation during hyperpneac phase in one patient, marked E and A fusion in another patient and exaggerated ventricular interdependence in a third patient thus highlighting mechanisms of adverse effects of Cheyne Stokes respiration in patients with heart failure. All 3 patients required a very short atrioventricular delay programming for best cardiac output. In one patient with recurrent congestive heart failure post cardiac resynchronization, mitral inflow pulse wave Doppler showed no A wave until a sensed atrioventricular delay of 190 ms was reached and showed progressive improvement in mitral inflow pattern until an atrioventricular delay of 290 ms. In 2 patients atrioventricular delay as short as 50 ms was required to allow E and A separation and prevent diastolic mitral regurgitation. All patients developed marked improvement in congestive heart failure symptoms post echo-guided biv pacemaker optimization.

Conclusion

These findings highlight the value of echo-guided pacemaker optimization in symptomatic patients post cardiac resynchronization treatment.     

A quantitative description of normal AV nodal conduction curve in man.

The AV nodal conduction curve generated by the atrial extrastimulus technique has been described only qualitatively in man, making clinical comparison of known normal curves with those of suspected AV nodal dysfunction difficult. Also, the effects of physiological and pharmacological interventions have not been quantifiable. In 50 patients with normal AV conduction as defined by normal AH (less than 130 ms), normal AV nodal effective and functional refractory periods (less than 380 and less than 500 ms), and absence of demonstrable dual AV nodal pathways, we found that conduction curves (at sinus rhythm or longest paced cycle length) can be described by an exponential equation of the form delta = Ae-Bx. In this equation, delta is the increase in AV nodal conduction time of an extrastimulus compared to that of a regular beat and x is extrastimulus interval. The natural logarithm of this equation is linear in the semilogarithmic plane, thus permitting the constants A and B to be easily determined by a least-squares regression analysis with a hand calculator.     

Functional mathematical model of dual pathway AV nodal conduction

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.     

Pacemaker Dependency after Cardiac Surgery: A Systematic Review of Current Evidence

Background

Severe postoperative conduction disturbances requiring permanent pacemaker implantation frequently occur following cardiac surgery. Little is known about the long-term pacing requirements and risk factors for pacemaker dependency in this population.

Methods

We performed a systematic review of the literature addressing rates and predictors of pacemaker dependency in patients requiring permanent pacemaker implantation after cardiac surgery. Using a comprehensive search of the Medline, Web of Science and EMBASE databases, studies were selected for review based on predetermined inclusion and exclusion criteria.

Results

A total of 8 studies addressing the endpoint of pacemaker-dependency were identified, while 3 studies were found that addressed the recovery of atrioventricular (AV) conduction endpoint. There were 10 unique studies with a total of 780 patients. Mean follow-up ranged from 6–72 months. Pacemaker dependency rates ranged from 32%-91% and recovery of AV conduction ranged from 16%-42%. There was significant heterogeneity with respect to the definition of pacemaker dependency. Several patient and procedure-specific variables were found to be independently associated with pacemaker dependency, but these were not consistent between studies.

Conclusions

Pacemaker dependency following cardiac surgery occurs with variable frequency. While individual studies have identified various perioperative risk factors for pacemaker dependency and non-resolution of AV conduction disease, results have been inconsistent. Well-conducted studies using a uniform definition of pacemaker dependency might identify patients who will benefit most from early permanent pacemaker implantation after cardiac surgery.     

Atrioventricular Block Subsequent to Intraoperative Device Closure Atrial Septal Defect with Transthoracic Minimal Invasion; A Rare and Serious Complication

Objectives

Atrioventricular block (AVB) is a infrequent and serious complication after percutaneous ASD closure. In this study, we report on the incidence of AVB associated with intraoperative device closure of the ASD with transthoracic minimal invasion, and the outcomes of this complication in our center.

Methods

Between May 2006 and January 2011, a total of 213 secundum-type ASD patients were accepted in our hospital for intraoperative and transthoracic device closure with a domestic occluder. All patients were assessed by real-time transthoracic echocardiography (TTE) and electrocardiograph (ECG).

Results

All patients were occluded successfully under this approach. Immediate postprocedure third-degree AVB was observed in two patients. Since heart rates were in the range of about 50 to 55 beats per minute, no intervention was needed except for close observation for one patient. Another patient who recovered sinus rhythm intermittently during the operation was fitted with a temporary pacemaker. Approximately one week following glucocorticoid treatment, the AVB resolved spontaneously in these two patients. Mobitz type II AVB occurred in three patients during the procedure. Two patients developed post-operative cardiac arrest and were rescued successfully with cardiopulmonary resuscitation. One other patient changed to Mobitz type I AVB after three days. During the follow-up period, which ranged from six months to five years, no further occurrence of AVB was found.

Conclusions

Intraoperative and transthoracic device closure of secundum ASDs with domestic occluder resulted in excellent closure rate. AVB is an infrequent but serious complication during and after device closure of a secundum ASD. AVB is a complication that warrants greater attention and long-term follow-up.     

Relationship between temperature change and the requirement for a permanent pacemaker implantation in bradyarrhythmias

Some cardiovascular diseases are associated with seasonal or meteorological factors. We tried to identify the relationship between meteorological parameters and the requirement for a permanent pacemaker (PPM) implantation for advanced sinus node dysfunction (SND) and atrioventricular block (AVB). This study enrolled 656 patients (67% male, age = 76 ± 11 years) who underwent a PPM implantation due to SND or AVB from January 2004 to December 2008. Using daily temperature, barometric pressure, humidity, and daylight hour records from Taipei, we evaluated the effect of these meteorological parameters within different time periods on the occurrence of SND and AVB. There were 355 patients in the SND group and 301 in the AVB group. In the AVB group, more patients presented in the spring than in other seasons (P = 0.003). In the SND group, there was no relationship with the seasons (P = 0.137). The proportion of patients with AVB did not depend on the average temperature, barometric pressure, humidity, or daylight hours within 3, 7, and 14 days prior to admission (P = NS). A temperature change of greater than 11°C within 30 days prior to admission was associated with a significantly higher proportion of patients with advanced AVB compared to those with advanced SND (P = 0.009). Extreme change in temperature was the most independent predictor of the development of advanced AVB. The peak occurrence of advanced AVB was in the spring. The occurrence of advanced AVB was associated with extreme temperature changes within 30 days, especially in the spring.     

Digitalis Does not Improve Left Atrial Mechanical Dysfunction After Successful Electrical Cardioversion of Chronic Atrial Fibrillation

This study was designed to investigate whether administration of digitalis could improve mechanical function of left atrial appendage (LAA) and left atrium prospectively in patients with atrial stunning. Fifty-four consecutive patients in whom atrial stunning was observed immediately after cardioversion of chronic atrial fibrillation (AF) were randomized into digitalis or control group for 1 week following cardioversion. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were performed prior to, immediately following, 1 day after and 1 week after cardioversion to measure transmitral flow velocity and LAA flow velocity. Electrical cardioversion of AF elicited significantly slower left atrial appendage peak emptying velocity (LAA-PEV) and peak filling velocity (LAA-PFV) immediately following cardioversion in both groups. 1 day post cardioversion, there were no significant differences in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or left atrial appendage ejection fraction (LAA-EF) between digitalis and control groups. 1 week post cardioversion, no significant differences were found in transmitral E wave, A wave, E/A ratio, LAA-PEV, LAA-PFV or LAA-EF between the two groups. The occurrence rates of spontaneous echo contrast were not significantly different between digitalis and control groups one day and one week post cardioversion. In conclusion, digitalis did not improve left atrial and appendage mechanical dysfunction following cardioversion of chronic AF. Digitalis did not prevent the development of spontaneous echo contrast in left atrial chamber and appendage. This may be due to the fact that digitalis aggravates intracellular calcium overload induced by chronic AF and has a negative effect on ventricular rate.     

A partial agonist of the A(1)-adenosine receptor selectively slows AV conduction in guinea pig hearts

The use of full agonists of the A(1)-adenosine receptor (A(1)-ADOR) as antiarrhythmic agents is limited by their actions to cause high-grade atrioventricular (AV) block, profound bradycardia, atrial fibrillation, and vasodilation. It may be possible to avoid these undesired actions by use of partial agonists. We determined the effects of CVT-2759, a potential partial agonist of A(1)-ADORs, on guinea pig hearts. CVT-2759 (0.1-100 microM) increased the S-H interval of the isolated heart from 45 +/- 1 to 60 +/- 3 ms (P < 0. 01) with a half-maximal effect at 3.1 microM. CVT-2759 did not cause second-degree AV block. CVT-2759 significantly attenuated the actions of the full agonists N(6)-cyclopentyladenosine and adenosine. CVT-2759 caused a moderate slowing of atrial rate by 10 microM. In contrast, CVT-2759 was a full agonist to decrease cAMP content of rat adipocytes and Fischer rat thyroid line 5 cells. Results of radioligand binding assays indicated that CVT-2759 stabilized a high-affinity, G protein-coupled state of the A(1)-ADOR in membranes prepared from rat adipocytes but not in membranes prepared from the guinea pig brain. The results suggest that a weak A(1)-ADOR agonist, such as CVT-2759, may be useful to slow AV nodal conduction and thereby ventricular rate without causing AV block, bradycardia, atrial arrhythmias, or vasodilation.     

Tp-e间期、P波离散度对室性心律失常病情的预测价值

摘要 目的：探讨Tp-e间期、P波离散度(Pd)对室性心律失常病情的预测价值。方法：2016年6月到2018年6月选择在本院诊治的心绞痛患者110例,所有患者都给予动态心电图检查,记录Tp-e间期、Pd值与室性心律失常发生情况。随访患者的心绞痛复发情况,并判定预测价值。结果：在110例患者中,发生室性心律失常48例(失常组),发生率为43.6 %,其中偶发室早21例、频发室早19例、室早4例、心室颤动3例、室性心动过速1例。失常组的Tp-e间期、Pd值都显著高于非失常组(P<0.05)。随访至今,失常组的心绞痛复发率为45.8 %,显著低于对照组的8.1 %(P<0.05)。在失常组中,单因素与多因素logistics回归分析显示Tp-e间期、Pd都为影响患者心绞痛复发的重要因素(P<0.05)。ROC曲线分析显示Tp-e间期、Pd预测心绞痛复发的敏感性与特异性都在85.0 %以上。结论：心绞痛合并室性心律失常患者多伴随有Tp-e间期、Pd增加,也会增加患者的复发率,Tp-e间期、Pd对预测室性心律失常复发情况具有重要价值。     

永久起搏器程控在心房颤动诊断中的临床应用及意义

摘要 目的：探究永久起搏器程控在心房颤动诊断中的临床应用及意义。方法：选择78例我院收治的心房颤动患者随机分为程控组和非程控组2组,其中观察组患者给与永久起搏器程控诊断,非程控组则仅给植入永久起搏器,但非程控。对比分析两组患者基本资料、房颤负荷、心房与心室起搏比、心房结构重构及左心功能、P波结果;比较永久起搏器程控诊断与临床诊断结果的差异,分析永久起搏器程控在心房颤动诊断敏感度。结果：程控组和非程控组患者的男女比例、年龄、心率失常的类型、存在的基础性疾病以及使用过的治疗药物比较,差异均无统计学意义（P>0.05）;程控组和非程控组患者的房颤负荷、VP值和P波最小时限均显著小于非程控组,AP值、P波最大时限和P波离散度则显著大于非程控组（P<0.05）;程控组和非程控组患者的LAD、RAD、LVEDD和LVEF值在植入前和植入后均不存在显著性差异（P>0.05）。与临床诊断结果比较可以发现,永久起搏器程控对心房颤动检出率为97.44 %,且永久起搏器程控应用于诊断心房颤动敏感度高达98.72 %。结论：对心房颤动患者采用永久起搏器程控进行诊断,可以在心电图检查的各项指标结果上对患者的心房颤动给与准确的判断,具有较高的临床应用价值,值得临床推广使用。     

Predictors and frequency of conduction disturbances after open-heart surgery

Introduction

The risk of developing conduction disturbances after coronary bypass grafting (CABG) or valvular surgery has been well established in previous studies, leading to permanent pacemaker implantation in about 2% to 3% of patients, and in 10% of patients undergoing repeat cardiac surgery. We sought to determine the incidence, features and predictors of conduction disorders in the immediate post-operative period of patients subjected to open-heart surgery, and the need for permanent pacemaker implantation.

Material and Method

We prospectively studied 374 consecutive patients who underwent open-heart surgery in our institution: coronary artery bypass (CABG) (n=128), Mitral valve replacement(MVR)(n=18), aortic valve replacement(AVR) (n=21), MVR and AVR(n=56), repair of ventricular septal defect (VSD) (n=51), repair of tetralogy of Fallot (TOF) (n=57),CABG and valvular surgery (n=6), others (n=37).

Results

Among 374 patients included in our study (mean age 34.46±25.68; 146 males), 192 developed new conduction disorders: symptomatic sinus bradycardia in 8%, atrial fibrillation with slow ventricular response (AF) in 4.5%, first-degree atrioventricular block (AVB)in 6.4%, second-degree AVB in 0.3%, third-degree AVB in 7%, new right bundle branch block (RBBB) in 33%, and new left bundle branch block (LBBB) in 2.1%. In 5.6% patients, a permanent pacemaker was implanted, 47.6% of them underwent valvular surgery. In 44.1% of patients the conduction defects occurred in the first 48 hr. after surgery. In CABG group, 29.7% of patients developed new conduction disturbances; the most common of them was symptomatic sinus bradycardia. After valvular surgery 44.2% of patients developed conduction disturbances, of those the most common was atrial fibrillation with slow ventricular response . After VSD and TOF repair, the most common conduction disturbance was new RBBB. Perioperative myocardial infarction (MI) occurred in 1.9% of patients. The occurrence conduction disturbance was compared with patient age, sex, occurrence of perioperative MI, ejection fraction (EF), postoperative use of ß-adernergic receptor blocking agents and digitalis and type of cardiac surgery. By regression analysis there was a correlation between type of surgery and new conduction defects, being significant for CABG and TOF repair. Only the occurrence of perioperative MI was related to PPM implantation.

Conclusion

Irreversible AVB requiring a PPM is an uncommon complication after open-heart surgery. Peri-operative MI is a risk factor.     

A novel strategy to treat vaso-vagal syncope: Cardiac neuromodulation by cryoballoon pulmonary vein isolation

BackgroundClinical management of vaso-vagal syncope (VVS) remains challenging since no therapy has proven to completely prevent VVS recurrence.ObjectiveThe purpose of this study was to analyze the mid-term outcome of cryoballoon (CB) cardioneuroablation achieved by pulmonary vein isolation (PVI) in patients with VVS.MethodsPatients who underwent CB cardioneuroablation in our centers between January 2014 to June 2018 were included. All patients had a history of VVS or pre-syncope despite therapeutic attempts with medical and/or pacing treatments. Patients were excluded in case of structural heart diseases, cerebrovascular diseases or suspected drug-related syncope. Both heart rate (HR) and atrio-ventricular (AV) interval were analyzed on the 12-lead electrocardiogram (ECG) the day before the procedure, the day after, and in the follow-up.ResultsIn total, 26 patients (76.9% males, 37.5 ± 9.0 years old) were included. All patients underwent a successful procedure with the 28 mm second-generation Arctic Front Advance CB. No major complication occurred. At a mean follow-up of 20.1 ± 11.6 months the freedom from VVS or reflex pre-syncope was 83,7%, with 22 patients free from any clinical recurrence. Basal HR significantly increased the day after the procedure (57.2 bpm vs 78.3 bpm, p < 0.001), while at the final follow-up it stabilized at a value halfway between the 2 previous ones (69.8 bpm, p = 0.0086). The AV interval didn’t modify significantly after the procedure.ConclusionEndocardial autonomic denervation achieved by CB PVI appears to be an effective and safe treatment option for patients with refractory VVS and reflex pre-syncope.     

Hemodynamic Changes following Aortic Valve Bypass: A Mathematical Approach

Aortic valve bypass (AVB) has been shown to be a viable solution for patients with severe aortic stenosis (AS). Under this circumstance, the left ventricle (LV) has a double outlet. The objective was to develop a mathematical model capable of evaluating the hemodynamic performance following the AVB surgery. A mathematical model that captures the interaction between LV, AS, arterial system, and AVB was developed. This model uses a limited number of parameters that all can be non-invasively measured using patient data. The model was validated using in vivo data from the literature. The model was used to determine the effect of different AVB and AS configurations on flow proportion and pressure of the aortic valve and the AVB. Results showed that the AVB leads to a significant reduction in transvalvular pressure gradient. The percentage of flow through the AVB can range from 55.47% to 69.43% following AVB with a severe AS. LV stroke work was also significantly reduced following the AVB surgery and reached a value of around 1.2 J for several AS severities. Findings of this study suggest: 1) the AVB leads to a significant reduction in transvalvular pressure gradients; 2) flow distribution between the AS and the AVB is significantly affected by the conduit valve size; 3) the AVB leads to a significant reduction in LV stroke work; and 4) hemodynamic performance variations can be estimated using the model.     

Utility of Epinephrine Levels in Determining Adrenal Vein Cannulation During Adrenal Venous Sampling for Primary Aldosteronism

ObjectiveIn patients with primary aldosteronism, adrenal venous sampling (AVS) is performed to determine the presence of unilateral or bilateral adrenal disease. During AVS, verification of catheter positioning within the left adrenal vein (AV) and the right AV by comparison of AV and inferior vena cava (IVC) cortisol levels can be variable. The objective of this study was to determine the utility of AV epinephrine levels in assessing successful AV cannulation.MethodsThis was a single institution, retrospective review of patients who underwent AVS with cosyntropin stimulation for primary aldosteronism between 2009 and 2018. Successful cannulation of the AV was defined by an AV/IVC cortisol ratio selectivity index (SI) ≥3:1. Epinephrine thresholds to predict catheter placement in the AV were determined using logistic regression. The calculated epinephrine thresholds were compared with previously published thresholds.ResultsAVS was performed on 101 consecutive patients and, based on the SI, successful cannulation of the left AV and right AV occurred in 98 (97%) and 91(90%) patients, respectively. The calculated optimal epinephrine threshold to predict AV cannulation was 364 pg/mL (sensitivity, 92.1%; specificity, 94.6%) and the calculated optimal AV/IVC epinephrine ratio threshold was 27.4, (sensitivity, 92.1%; specificity, 91.3%). Among the 14 patients with failed AV cannulation, 3 patients would have been considered to have successful AVS using AV epinephrine levels >364 pg/mL and AV/IVC epinephrine ratio >27.4 thresholds.ConclusionObtaining 2 right AV samples routinely as well as AV and IVC epinephrine levels during AVS could prevent unnecessary repeat AVS in patients with failed AV cannulation based on cortisol-based SI <3:1.     

A G613A missense in the Hutchinson’s progeria lamin A/C gene causes a lone,autosomal dominant atrioventricular block

Background

LMNA/C mutations have been linked to the premature aging syndrome Hutchinson’s progeria, dilated cardiomyopathy 1A, skeletal myopathies (such as the autosomal dominant variant of Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy), Charcot-Marie-Tooth disorder type 2B1, mandibuloacral dysplasia, autosomal dominant partial lipodystrophy, and axonal neuropathy. Atrioventricular block (AVB) can be associated with several cardiac disorders and it can also be a highly heritable, primitive disease.One of the most common pathologies associated with AVB is dilated cardiomyopathy (DCM), which is characterized by cardiac dilatation and reduced systolic function. In this case, onset has been correlated with several mutations in genes essential for the proper maturation of cardiomyocytes, such as the gene for lamin A/C. However, no clear genotype–phenotype relationship has been reported to date between LMNA/C mutations and cardiomyopathies.

Results

DNA and medical histories were collected from (n?=?11) members of different generations of one family, the proband of which was implanted with a pacemaker for lone, type II AVB. Exome sequencing analysis was performed on three relatives with AVB, and the mutations therein identified validated in a further three AVB-affected family members.In the initial three AVB family members, we identified 10 shared nonsynonymous single-nucleotide variations with a rare or unreported allele frequency in the 1000 Genomes Project database. Follow-up genetic screening in the additional three affected relatives disclosed a correlation between the lone AVB phenotype and the single-nucleotide polymorphism rs56816490, which generates an E317K change in lamin A/C. Although this mutation has already been described by others in a DCM-affected proband with familiarity for AVB and sudden death, the absence of DCM in our large, AVB-affected family is indicative of genotype–phenotype correlation between rs56816490 and a familial, autosomal dominant form of lone AVB.

Conclusions

Screening for G613A in LMNA/C in patients with lone AVB and their relatives might prevent sudden death in families affected by AVB but without familiarity for DCM. Lone AVB is an age-related disease caused by mutations in LMN A/C gene rather than a complication of DCM.

     

A new method for localizing the landmark of axillary vein and its application

BackgroundAxillary vein puncture is a popular puncture site for pacemaker implantation. However, due to the lacking of body surface markers, the current puncture method is too complicated and affect the popularization and application of axillary vein puncture. Here, we performed a new body surface landmark to make the blind axillary vein puncture simple and easy.MethodsThe study population included 30 patients referred for pacemaker implantation using axillary vein puncture. Digital subtraction angiography (DSA) was used to determine the direction and the surface landmarks of the axillary vein. Medial cusp of thoracic triangle and the coracoid process were directly touched with fingers. The puncture point was about 1 cm below the coracoid, and the needle tip pointed to the medial cusp of thoracic triangle with the angle of 30–60°.ResultsThere was little variation in distribution of axillary vein. The body surface landmark of the junction of the axillary vein and the subclavian vein is on the medial cusp of thoracic triangle. In these 30 patients, blind axillary vein puncture was successful obtained in all patients. There was no pneumothorax and inadvertent arterial puncture. The pacemaker lead wire was placed smoothly. Moreover, the pacemaker pocket was ideally positioned when cut along the puncture point.ConclusionsBlind axillary vein access using the body surface landmark of the thoracic triangle is an effective method for pacemaker implantation and can obvious avoid the complications usually observed with the traditional subclavian vein approach.     

Doppler-echocardiographic characteristics of left ventricular function in patients with pseudoexfoliation glaucoma: a preliminary report

Glaucoma is associated with an increased incidence of cardiovascular disease and risk factors. The aim of the study was to assess the left ventricular (LV) function in patients with pseudoexfoliation (PEX) glaucoma using doppler-echocardiographic examinations. Two-dimensional and pulsed Doppler echocardiography of transmitral flow was performed in 21 patients with (PEX) glaucoma and 24 controls. LV systolic contraction and ejection were assessed using the LV ejection fraction (EF) and fractional shortening (FS). LV diastolic filling assessed parameters were: early, fast diastolic filling (E wave), late diastolic filling (A wave), ratio E/A, velocity time integral E wave (VTIE) and A wave (VTIA), their ratio (VTIE /VTIA), pressure at the end of filling (LVEDP) and a pulmonary capillary wedge pressure (PCWP). A significant difference was found concerning LV filling flow parameters in E, E/A, VTIA and ratio VTIA/ VTIE. No significant difference was found in EF, FS, A, VTIE, LVEDP and PCWP tested parameters. Our study indicates the possibility of slightly impaired diastolic function of LV in patients with PEX glaucoma assessed by Doppler-echocardiographic examinations.