Peripheral Biomarker for Vascular Disorders.

Atherosclerosis is the underlying cause of most myocardial infarction (MI) and ischaemic stroke episodes. An early sign of atherosclerosis is hypertrophy of the arterial wall. It is known that increased intima media thickness (IMT) is a non-invasive marker of arterial wall alteration, which can easily be assessed in the carotid arteries by high-resolution B-mode ultrasound. Similarly, the other key element of MI and ischaemic strokes is the N-methyl-D-aspartate (NMDA) receptor which is an ionotropic glutamate receptor that mediates the vast majority of excitatory neurotransmission in the brain. NMDA activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. A special enzyme, serine racemase (SR), is required for the conversion of L-serine into D-serine, and alterations in SR activities lead to a variety of physiological and pathological conditions ranging from synaptic plasticity to ischemia, MI, and stroke. The amount of D-serine available for the activation of glutamatergic signalling is largely determined by SR and we have developed ways to estimate its levels in human blood samples and correlate it with the IMT. This research based short communication describes our pilot study, which clearly suggests that there is a direct relationship between the SR, D-serine, and IMT. In this article, we will discuss whether the activity of SR can determine the future consequences resulting from vascular pathologies such as MI and stroke.

Prevalence and predictors of electrocardiogram abnormalities among athletes.

Background Existing evidence, predominantly from Western countries, has demonstrated that athletes' hearts undergo structural, physiological, and electrical changes, leading to abnormal electrocardiogram readings that are said to be training-related. Athletes with non-training-related electrocardiographic abnormalities risk developing sudden cardiac death. The lack of studies on this issue in the Asian population warrants further exploration. Therefore, the aim of this study was to estimate the prevalence and predictive factors contributing to electrocardiogram abnormalities among athletes in Brunei. Methods A descriptive cross-sectional study was conducted on 100 athletes (median age 25.2 years) in 10 sporting disciplines, whose electrocardiogram readings and essential information was obtained. Results The prevalence of an abnormal electrocardiogram was 52% (95% confidence interval: 42.0%-62.0%), comprising training-related changes in 49% (95% confidence interval: 39.0%-59.0%) and non-training-related changes in 3% (95% confidence interval: 0.4%-6.4%). Athletes with a higher body mass index were 3.3-times (95% confidence interval: 1.47-9.58) more likely to have abnormal electrocardiogram readings. Athletes <25-years old (odds ratio = 0.25, 95% confidence interval: 0.07-0.81) and those who trained with low dynamic intensity (odds ratio = 0.33, 95% confidence interval: 0.12-0.93) were significantly less likely to have electrocardiogram abnormalities. Conclusions This is the first study reporting abnormal electrocardiograms among athletes in Brunei, which provides important information to relevant agencies involved in the preparation of Asian athletes for domestic or international competitions, particularly those with a higher body mass index and low dynamic training intensity.

Initial experience with a leadless pacemaker (Micra™) implantation in a low volume center in South East Asia.

Aim: The Micra™ Transcatheter Pacing System is a leadless pacemaker that has been introduced recently. We share our experience in a low volume center and the use of right ventricular angiography (RVA) during implantation. Materials & methods: Patients underwent Micra implantation and RVA was performed to predetermine the implant site.Results: Nine patients underwent Micra implantation. The most common indication was atrial fibrillation with bradycardia. The device was implanted at apical-septum in seven and mid-septum in two. The procedure time ranged from 30 to 100 min and fluoroscopic time 4-18 min. Pacing parameters remained stable after 1-month follow-up. Conclusion: The Micra implantation technique can be easily learnt. RVA was helpful in selecting an appropriate site for the Micra implant.

Implant of a left atrial appendage occluder device (Watchman) and leadless pacing system (Micra) through the same venous access in a single sitting.

A left atrial appendage occluder device (Watchman) and leadless pacemaker (Micra) was implanted from a single right femoral vein access in a 73-year-old female patient with persistent atrial fibrillation and symptomatic tachy-brady syndrome and unable to take oral anticoagulants. Standard methods of implantation were followed for both procedures. The Watchman device was implanted first followed by dilatation of the same venous access site in order to implant Micra transcatheter pacing system. The patient tolerated the procedures well and there were no complications. At the end of 1 month, both the devices were found to be working well.

Early experience with attain stability, an activefixation LV lead: virtues and pitfalls.

BACKGROUND: Appropriate left ventricle (LV) lead placement is integral to successful cardiac resynchronization therapy (CRT). Lead dislodgement and phrenic nerve stimulation (PNS) are major obstacles. A recent trial of an active fixation LV lead (Attain Stability 20066, Medtronic Inc., Tilburg, the Netherlands) has shown promising results. We share our initial experience with this novel active fixation LV lead. METHODS: A Medtronic active fixation lead 20066 was used in eight consecutive patients for CRT. An optimal site was chosen and recommended maneuvers were applied for lead fixation. Push and pull maneuvers were used to test stability. RESULTS: There were two initial dislodgements after which we used a transvalvular insertion (TVI) tool that was used in the hemostatic valve during rotation of the lead so that the torque was easily transmitted to the tip. It also allowed better tactile feedback during push-pull tests. There were no further dislodgements in the subsequent six patients. However, in one patient the lead could not be unscrewed due to the tip getting wedged at a distal smaller vein. Repositioning of the LV lead was done in three patients due to PNS or pacing issues. The median time for LV lead placement was 16.5 minutes (interquartile range 9-25 minutes). CONCLUSION: The Medtronic Attain Stability 20066 active fixation LV lead can potentially be implanted at any pacing site avoiding PNS and providing better stability. The learning curve is short and additional tricks can be learnt to improve success. Use of TVI while the lead is rotated is beneficial.

Possible targets of therapy for catecholaminergic polymorphic ventricular tachycardia. - Insight from a theoretical model -.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a serious disease with a high mortality but its management is limited. The aim of this study was to investigate specific target sites for therapy in order to find potential management strategies for CPVT. METHODS AND RESULTS: The mutant Ryanodine receptor 2 (RyR2) with reduced stored-overloaded-induced Ca²âº release (SOICR) threshold was incorporated into the Luo-Rudy dynamic (LRd) cell model to elucidate the underlying pathologies of CPVT. The simulations reveal that ß-adrenergic stimulation increased the Ca²âº load in cardiac myocyte, which facilitates spontaneous SR Ca²âº leakage, resulting in triggered arrhythmias. Varied blockade (from 0% to 90%) in specific ion channels, including the Na⁺/Ca²âº exchanger (I(NaCa)), fast Na⁺ channel (I(Na)), RyR2 receptor (I(rel)), Ca²âº-ATPase (SERCA) (I(up)) or L-type Ca²âºchannel (I(Ca(L))),was performed to simulate the action of specific drugs on target sites. Blockade of the I(NaCa) (≤ 10% blockade), in contrast to the I(up) (≤ 30% blockade), I(Ca(L)) and I(Na) (≤40% blockade), and followed by I(rel) (≤ 80% blockade), was most effective in suppressing the triggered arrhythmias in CPVT. Specifically, dual blockade of I(Ca(L))/I(up), I(Na)/I(rel) or I(Ca(L))/I(rel) had a synergistic effect in CPVT management. CONCLUSIONS: Blockade of I(NaCa) appears to be the most efficacious target for CPVT management. Dual blockade of I(Ca(L))/I(up), I(Na)/I(rel) or I(Ca(L))/I(rel) has a synergistic effect in CPVT treatment.

Recoordination rather than resynchronization predicts reverse remodeling after cardiac resynchronization therapy.

BACKGROUND: Mechanical discoordination as studied by magnetic resonance imaging has been shown to be a better predictor of left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT) compared with mechanical dyssynchrony. MATERIALS AND METHODS: This study assessed the value of acute recoordination derived from speckle-tracking echocardiography for predicting response to CRT compared with acute resynchronization. Thirty patients with heart failure scheduled for CRT were studied at baseline, immediately after CRT, and after 6 months of CRT. Acute recoordination after CRT was indexed by an acute reduction in radial discoordination index (RDI), defined as the ratio of average myocardial thinning to thickening during the ejection phase. RESULTS: CRT responders were defined as those patients whose LV end-systolic volume decreased by >or= 15% at the 6-month follow-up. Immediately after CRT, the responders (n = 18) demonstrated a significant reduction in RDI (P < .001), which was sustained at the 6-month follow-up (P < .001). The nonresponders, however, did not show a significant change in RDI after CRT. LV reverse remodeling at the 6-month follow-up was significantly correlated with acute recoordination (r = 0.75, P < .001) but weakly correlated with acute resynchronization (r = 0.43; P = .02). CONCLUSIONS: Receiver operating characteristic analysis revealed that acute recoordination provided the best separation for prediction of CRT responders compared with acute resynchronization, baseline dyssynchrony, or baseline discoordination. LV recoordination after CRT is an acute phenomenon and predicts response to CRT at 6-month follow-up better than resynchronization.

Pacing-related acute pulmonary edema and mechanical asynchrony illustrated by three-dimensional echocardiography.

Sick sinus syndrome with symptomatic bradycardia is an indication for a permanent pacemaker. Either a single (AAIR) or dual-chamber (DDDR) pacemaker can be implanted in these patients with normal atrioventricular nodal function. This report presents a 92-year-old male with right ventricular apical pacing related recurrent acute pulmonary edema and mechanical asynchrony demonstrated by three-dimensional echocardiogram. Although three-dimensional echocardiography has been available for many years, it has seldom been applied to evaluate pacing-related intraventricular asynchrony. The systolic asynchrony index for this patient was 6.7% during AAIR pacing mode and 22% during DDDR pacing mode.

Brugada-like electrocardiographic pattern and ventricular fibrillation in a patient with primary hyperparathyroidism.

There are several causes for ST segment abnormalities in leads V1 to V3. Hypercalcaemia and Brugada syndrome are among them. Both are known to produce ventricular arrhythmia, albeit only rare cases have been reported with documented evidence of ventricular arrhythmias in association with a hypercalcaemic crisis but none when hypercalcaemic coexists with Brugada syndrome. We describe a patient with primary hyperparathyroidism who presented with ventricular fibrillation, and the ECG showed changes similar to Brugada syndrome. The provocation test with flecainide was conducted twice. This was positive, both before and after parathyroidectomy when serum calcium and parathormone levels had normalized. The patient was treated for hypercalcaemia and underwent parathyroidectomy. This is the first report of oral flecainide test unmasking the diagnostic coved Brugada ECG pattern in a patient with primary hyperparathyroidism and raising attention to hypercalcaemia as a potential trigger for life-threatening arrhythmia in Brugada syndrome.

Myocardial ischemia and ventricular fibrillation: pathophysiology and clinical implications.

Ventricular fibrillation (VF) and myocardial ischemia are inseparable. The first clinical manifestation of myocardial ischemia or infarction may be sudden cardiac death in 20-25% of patients. The occurrence of potentially lethal arrhythmia is the end result of a cascade of pathophysiological abnormalities that result from complex interactions between coronary vascular events, myocardial injury, and changes in autonomic tone, metabolic conditions and ionic state of the myocardium. It is also related to the time from the onset of ischemia. Within the first few minutes there is abundant ventricular arrhythmogenesis usually lasting for 30 min. Triggers for ischemic VF occur at the border zone or regionally ischemic heart. The border zone of ischemia is the predominant site of fragmentation. Acute ischemia opens K(ATP) channels and causes acidosis and hypoxia of myocardial cells leading to a large dispersion in repolarization across the border zone. Abnormalities of intracellular Ca2+ handling also occur in the first few minutes of acute myocardial ischemia and may be an important cause of arrhythmias in human coronary artery disease. Substrate on the other hand transforms triggers into VF and serves to maintain it through fragmentation of waves in the ischemic zone. Thrombin levels, stretch, catecholamine, genetic predisposition, etc. are some of these factors. Reentry models described are spiral wave reentry, 3 dimensional rotors, reentry around 'M' cells and figure-of-eight reentry. Continuing efforts to better understand these arrhythmias will help identify patients of myocardial ischemia prone to arrhythmias.

Recurrent postcardiac injury syndrome mimicking cardiac perforation following transvenous pacing: An unusual presentation.

We report a case of recurrent postcardiac injury syndrome (PCIS) after pacemaker lead insertion. Each episode was attended by hemorrhagic pleuro-pericardial effusion with drop in hemoglobin levels leading us to consider cardiac perforation and subject the patient to surgical pericardiotomy. However, no perforation or active bleeding was detected on exploration. This unusual case illustrates the occurrence of PCIS following pacemaker lead insertion, mimicking cardiac perforation. This entity should be considered in patients who, after pacemaker lead insertion, develop pericardial and pleural effusion associated with markers of inflammation.

Biplane assessment of left ventricular function during atrial fibrillation at beats with equal subsequent cycles.

BACKGROUND: Prior study has demonstrated that the biplane single-beat method could be used to assess left ventricular function during atrial fibrillation at a beat with equal subsequent cycles. The study was to test whether we could improve the method by measuring a few beats with equal subsequent cycles and cycle-length limits. METHODS: In 75 patients with atrial fibrillation, stroke volume and ejection fraction were determined from simultaneous biplane views of left ventricle for 20 beats using a matrix-array transducer and a biplane Simpson's rule. The influence of cycle lengths on the values of systolic parameters at beats with equal subsequent cycles was examined from the plot of normalized parameters (measured values/average values) against cycle lengths. The values of 1 to 3 beats with equal subsequent cycles and cycle-length limits were averaged and compared with the average values over 20 beats by Bland-Altman and mean percentage difference analysis. The variability of repeat measurements was evaluated in 10 patients. RESULTS: The systolic parameters measured at beats with cycle lengths shorter than 500 ms were usually far below the average values. Agreement and mean percentage difference analysis revealed improved accuracy when 2 or 3 beats with cycle-length limits (>500 ms) were used for assessment. As the variability of averaging 2 or 3 beats is no greater than that of repeat measurements, both methods are equally good. CONCLUSIONS: Accurate assessment of left ventricular systolic function in atrial fibrillation can be obtained by averaging 2 beats with equal subsequent cycles and cycle-length limits (>500 ms).

Refinement on single-beat determination of left ventricular systolic function in patients with atrial fibrillation.

Single-beat determination of left ventricular systolic function at a beat with equal subsequent cardiac cycles has been proposed as an accurate method in atrial fibrillation. However, there has still been substantial variability between the values calculated from beats with equal subsequent cycles. Therefore, some refinement on the single-beat method is needed. In 100 patients with atrial fibrillation, Doppler aortic flow time-velocity integral was determined for at least 20 consecutive cardiac cycles. The values at beats with equal subsequent cardiac cycles were chosen and compared with the average values over all cardiac cycles. The values at beats with cycle lengths shorter than 500 milliseconds were usually far below the average values over all cardiac cycles. Bland-Altman agreement analysis revealed improved accuracy by gradually narrowing the range of the limits of agreement when 2 or 3 beats with equal subsequent cycles and cycle lengths longer than 500 milliseconds were used for evaluation.

Pleomorphic ventricular tachycardia: an uncommon presentation in idiopathic left ventricular tachycardia.

Idiopathic left ventricular tachycardia (ILVT) is a distinct entity that arises in the left ventricle, may have reentrant mechanism and is verapamil-sensitive. Pleomorphism as defined by multiple ventricular tachycardia morphologies is usually associated with either coronary artery disease or cardiomyopathy but very rare in cases of ILVT. In this case report, we describe an unusual case of ILVT with two ECG morphologies of the opposite axis that were successfully eliminated with radiofrequency ablation. The successful ablation sites were closely located to each other in the left lower ventricular septum.

Unusual features of an idiopathic ventricular tachycardia arising from the left ventricular outflow tract.

We encountered a 40-year-old man with recurrent symptomatic palpitations manifested as monomorphic ventricular tachycardia (VT) of a right bundle branch block (RBBB) pattern with an inferior frontal axis. Physical examination, chest roentgenogram, and echocardiogram were unremarkable. The VT could be provoked by treadmill exercise testing. Electrophysiologic study revealed that the VT could be reproducibly initiated with either atrial or ventricular pacing at cycle lengths between 500 and 400 ms. With overdrive ventricular pacing, the VT could be terminated. Of note was the observation that intravenous adenosine was not effective, but intravenous verapamil could interrupt the VT. The VT was pace mapped to be arising from a site at the left ventricular outlet tract (LVOT). Notably, during pace mapping, the pacing spike was immediately followed by the beginning of the paced QRS complex, and during VT, there was no time delay between the earliest local activation and the onset of QRS complex. Furthermore, there was no mid-diastolic activity or Purkinje potential that could be recorded during sinus rhythm and VT. Subsequently, the VT was successfully ablated with radiofrequency energy as guided by pace mapping. In summary, an idiopathic VT arising from the LVOT was found to be cycle lengths- and catecholamine-dependent, adenosine-insensitive but verapamil responsive. These unusual features suggest that either microreentry or triggered activity could be the underlying mechanism.

Simultaneous biplane single-beat assessment of left ventricular systolic function in patients with atrial fibrillation.

Left ventricular systolic function was studied in 40 patients with atrial fibrillation using a matrix-array transducer, which enables 2 simultaneous orthogonal views to be obtained in a biplane mode. Bland-Altman analysis showed excellent correlation and agreement between the systolic parameters of a single beat with identical RR1 and RR2 intervals and the measured average value over all cardiac cycles.

Electrophysiological characteristics of accessory pathways with prolonged retrograde conduction.

Electrophysiological characteristics of an accessory pathway (AP) with a long ventriculoatrial (VA) interval (arbitrarily defined as > or = 50 ms and absence of continuous electrical activity) and no retrograde decremental property are described in this study. Fifteen patients (group 1) were compared with 171 patients with normal VA conduction (group 2). Mean VA conduction time was 77 +/- 24 versus 34 +/- 12 ms in group 1 versus group 2, respectively. Group 1 patients were older (55 +/- 14 vs 40 +/- 14 years), the male to female ratio was higher (2.8 vs 1.6), and APs were more prevalent on the right (60%) but manifest APs were lower (20% vs 54%) compared to group 2 patients (P < 0.05 in all cases). QRS morphology during induced atrioventricular reciprocating tachycardia was identical in both groups but the tachycardia cycle length was longer in group 1 (373 +/- 29 vs 344 +/- 50 ms, P < 0.05). Retrograde AP block cycle length and effective refractory period were greater in group 1 (362 +/- 59 vs 293 +/- 57 ms; 330 +/- 58 vs 273 +/- 55 ms, both P < 0.05). Adenosine (up to 18 mg) and verapamil (5-10 mg) failed to block the VA conduction via AP during ventricular pacing. In group 1 the number of radiofrequency lesions for a successful ablation were significantly less (3 +/- 2 vs 6 +/- 5, P < 0.05). In conclusion, APs with a long VA interval and no decremental retrograde conduction have electrophysiological characteristics that are different from those with a short VA interval. Role of aging deserves further exploration.

Atrioventricular nodal reentry tachycardia with multiple AH jumps: electrophysiological characteristics and radiofrequency ablation.

This article describes the additional use of incremental atrial burst pacing (A1A1) and double atrial extrastimulation with a predefined fast pathway conducted A2 (A1A2A3), rather than single atrial extrastimulation (A1A2) only, to characterize typical atrioventricular nodal reentrant tachycardia (AVNRT). The authors noted an additional 32% of patients had multiple anterograde AV nodal physiology demonstrated when A1A1 or A1A2A3 protocols were deployed compared to more conventional A1A2 protocols. The A2H2max (449 +/- 147 vs 339 +/- 94 ms) and A3H3max (481 +/- 120 vs 389 +/- 85 ms) were higher in 31 patients where multiple jumps in the AV nodal conduction curve were obtained (group 1) compared to 192 patients where only single jump was obtained (group 2) (both P < 0.01). Postablation, the degree of reduction of A2H2max (49%) and A3H3max (50%) in group 1 was greater than in group 2 (38% and 42%, respectively, P < 0.05). In seven of group 1 patients in whom A1A2A3 stimulation was required to reveal multiple jumps, the A2H2max remained unchanged after ablation (237 +/- 89 vs 214 +/- 59, P > 0.05). A3H3max was the only parameter that shortened significantly after ablation. Generally, successful ablation resulted in loss of multiple discontinuities in A1A1/A1H1 or A2A3/A3H3 curves. In conclusion, a combination of A1A2, A1A1, and A1A2A3 are required to fully elucidate AVNRT. Significant shortening of AHmax or loss of multiple jumps after ablation indicates successful elimination of AVNRT in these patients.

Prolonged ventricular asystole, sinus arrest, and paroxysmal atrial flutter-fibrillation: an uncommon presentation of vasovagal syncope.

We described a 55-year-old woman with recurrent syncope, complete atrioventricular (AV) block, sparsely scattered idioventricular beats lasting for 56 seconds, and long sinus arrest recorded during the syncopal episode. Paroxysmal atrial flutter-fibrillation was also presented during Holter electrocardiograph (ECG) monitoring without clinical symptom. During tilt test, atrial flutter with variable AV block was induced and the patient suddenly passed out. The vasovagal syncope was successfully treated with a DDD permanent pacemaker with a rate drop response algorithm. Vasovagal syncope with concomitant ventricular asystole and sinus arrest is rare. Aggressive management with permanent pacemaker is strongly advocated in malignant vasovagal syncope.

Atrial fibrillation: new horizons.

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. The understanding of the pathophysiology of AF has changed drastically during the last several decades. Recent observations have challenged the concept of the multiple circuit reentry model in favor of single focus or single circuit reentry models. Atrial electrical dysfunction provides a favorable substrate and transmembrane ionic currents are key determinants. Interest has also been generated in the role of angiotensin converting enzyme (ACE) inhibition in reversing the electrical and structural remodeling. Reverting to the sinus rhythm seems to be the best way for reverse remodeling of atria during atrial fibrillation. Antiarrhythmic drugs (AADs) are only modestly effective. Of these amiodarone seems to provide the most benefits. Drugs like verapamil and ACE inhibitors may also help as adjuvant therapies in the reverse remodeling of atria. Nonpharmacological methods have been used to control both rate and rhythm for patients with AF. Recently, there has been a surge in interest to focal ablation of atrial foci. Focal sources of AF are commonly found in pulmonary veins (PV). Ablation in pulmonary veins through identification of the earliest endocardial activation has met with variable success. Anatomical approaches have involved circumferential radiofrequency ablation of pulmonary vein ostia using novel techniques such as balloon based circumferential ultrasound ablation system and circular cryoablation catheter. Most recently the segmental approach is preferred because the myocardial fibers surrounding the PV are not continuous. Segments where musculature is present can be identified using high frequency depolarization signals recorded through multi-electrode loop catheter or even conventional catheters.