Electrical Remodeling In Patients Research Articles

Quantitative analysis of fractionated electrogram area of left atrium during right atrial pacing as an indicator of left atrial electrical remodeling in patients with atrial fibrillation

AbstractBackgroundThe clinical significance of left atrial local electrogram fractionation after restoration of sinus rhythm in patients with atrial fibrillation (AF) has not been elucidated.MethodsWe evaluated ultrahigh‐resolution maps of the left atrium (LA) during RA pacing acquired after pulmonary vein isolation in 40 patients with AF. The association between low‐voltage area (LVA, <0.5 mV), fractionated electrogram area (FEA, the highlighted area with LUMIPOINT™ Complex Activation), the interval from onset of LA activation to wavefront collision at the mitral isthmus (LA activation time), and wave propagation velocity (WPV) was evaluated quantitatively.ResultsThe total LVA, total FEA with ≥5.0 peaks or ≥7.0 peaks were 7.0 ± 7.9 cm2, 15.9 ± 12.9 cm2, and 5.2 ± 7.5 cm2, respectively. These areas were predominantly observed in the anteroseptal region. Total LVA, total FEA with ≥5.0 peaks, and total FEA with ≥5.0 peaks in the normal voltage area (NVA: ≥0.5 mV) correlated with LA activation time (R = 0.69, 0.75, and 0.71; each p < .0001). In the anterior wall, these areas correlated with regional mean WPV (R = −0.75, −0.83, and − 0.55; each p < .0001) and the extent of slow conduction area (SCA) with WPV <0.3 m/s (R = 0.89, 0.84, 0.33; p < .0001 for LVA and FEA, p < .05 for FEA located in NVA). The anterior wall FEA with ≥7.0 peaks and that in the NVA showed a better correlation in predicting anterior wall SCA (R = 0.92 and 0.86, each p < .0001).ConclusionQuantitative analysis of FEA together with LVA may facilitate the assessment of LA electrical remodeling.

Lower cardiorespiratory fitness is associated with left atrial structural, functional and electrical remodelling in patients with symptomatic atrial fibrillation

Abstract Background Preserved cardiorespiratory fitness (CRF) is associated with improved rhythm control in patients with symptomatic atrial fibrillation (AF). However, the pathophysiological features associated with low cardiorespiratory fitness are not well described. Purpose Evaluate the association between cardiorespiratory fitness and structural, functional and electroanatomical features of the left atrium (LA) amongst patients with symptomatic AF. Methods Consecutive patients with symptomatic paroxysmal or persistent AF undergoing AF ablation were recruited. CRF was assessed objectively by peak oxygen consumption (VO2peak) assessed during maximal cycle ergometry. Invasive assessment of LA remodelling involved direct assessment of resting LA pressures (LAP), LA stiffness during saline infusion and LA electrical function using high-density electroanatomical maps. Non-invasive assessment involved 2D transthoracic echocardiography at rest and during exercise. The association between VO2PEAK and atrial parameters were determined using multivariable linear regression models adjusted for age and sex. Results In total, 110 participants were recruited. Mean age was 63±11 and 74.5% of the cohort was male. In adjusted analyses, higher VO2PEAK was associated with lower mean LAP (p<0.001) and invasively assessed LA stiffness (p=0.005). On non-invasive testing, VO2PEAK was positively associated with left atrial emptying fraction (LAEF) (p=0.001) and reservoir strain (p<0.001) at rest. During exercise, VO2PEAK remained associated with LAEF (p<0.001) and LA reservoir strain (p=0.007). Higher VO2peak was positively associated with LA bipolar voltages (p=0.035) but not LA conduction velocities (p=0.131) or LA fractionation (p=0.452) Conclusions In patients with symptomatic AF, lower cardiorespiratory fitness is independently associated with extensive LA remodelling involving impaired LA haemodynamics, increased LA stiffness, LA mechanical dysfunction and LA electrical remodeling.

Atrial electrical remodeling and function after transcatheter aortic valve replacement in patients with aortic stenosis.

To examine reverse atrial electrical remodeling in patients with aortic stenosis (AS) after trans-catheter aortic valve replacement (TAVR). In 65 consecutive patients with severe AS (83 ± 4years, 47 (72.3%) females), we analyzed ECG records for the P wave duration (PWD) in lead II and P-terminal force (PTFV1) in V1, and measured cardiac dimensions and function by echocardiography (ECHO) following TAVR. Biomarkers were measured to assess myocardial injury by TAVR. TAVR was successfully performed without major complications: the aortic valve area increased from 0.62 ± 0.14 cm2 to 1.52 ± 0.24cm2, and the trans-aortic pressure gradient decreased from 58.4 ± 15.9mmHg to 15.0 ± 19.6mmHg. PWD and PTFV increased immediately after TAVR and returned to the pre-TAVR levels on the next day. Then, the PWD declined toward 6months after TAVR non-significantly in all patients, but significantly in 25 patients with baseline PWD ≥ 130ms (P = 0.039). PTFV1 showed no long-term change. Improvement was observed in the ejection fraction, all thickness of the left ventricle and in the left atrial dimensions on ECHO. After recovery from transient aggravation by TAVR procedure, PWD reversed slowly, and the change was significant in those with baseline PWD ≥ 130ms while change in PTFV1 was not significant at 6months of follow-up. ECHO showed a reversal of remodeling in the left ventricle and in the left atrial dimension after TAVR.

Predictors for the prolonged R wave peak time among patients with arterial hypertension.

Hypertension (HT) is prevalent in the general population and is associated with significant cardiovascular adverse events. Major structural and electrical remodeling occurs in the ventricular myocardium in response to the pressure overload. Increased left ventricular mass (LVM) and myocardial fibrosis contribute to the prolongation of the R wave peak time (RWPT), which may indicate electrical remodeling in patients with HT. We evaluated predictors for prolonged RWPT among patients with a previous diagnosis of HT. Consecutive patients who had a previous diagnosis of arterial HT and presented to the cardiology clinic for routine visit were included in the study. The standard 12-lead surface electrocardiography (ECG) and transthoracic echocardiography (TTE) was performed on all the patients included in the study for evaluating RWPT and the epicardial fat tissue (EFT). The upper limit for the RWPT was accepted as 40 milliseconds (ms). Between February 2019 and February 2020, 453 patients were screened; and of these, 237 were included in the study. The mean age was 62.1±11.2 years, and 41.8% of the included patients were men. The mean RWPT of the study population was 41.9±10.8. The RWPT was prolonged in 55 patients, and the remaining 172 patients had normal RWPT. In the univariate analysis, EFT (Odds ratio [OR] 1.222; 95% confidence interval [CI] 1.077-1386; p=0.002), the left ventricular mass index (LVMI) (OR 1.011; 95% CI 1.001-1.021; p=0.026), and fragmented QRS (fQRS) (OR 2.679; 95% CI 1.433-5.004; p=0.002) were associated with a prolonged RWPT. Multivariate analysis revealed that only EFT (OR 1.211; 95% CI 1.061-1.383; p=0.005) and fQRS (OR 2.796; 95% CI 1.459-5.359; p=0.002) predicted prolonged RWPT. Among the patients with HT, EFT and fQRS predicted prolonged RWPT. These findings may suggest that compared with increased LVM, myocardial fibrosis had a more significant impact on ventricular activation time.

The extent of complex fractionated atrial electrograms in the left atrium reflects age-related electrical remodeling in patients with persistent atrial fibrillation.

BackgroundsAlterations in the atrial structure and function associated with aging result in electric remodeling of the left atrium (LA) in patients with persistent atrial fibrillation (AF). We performed this study to evaluate the influence of age on electric remodeling as assessed by the extent of complex fractionated atrial electrograms (CFAEs) in the LA.MethodsA total of 122 patients (mean age, 55.9 ± 10.4 years; range, 31‐79; 106 males) who underwent catheter ablation for drug‐refractory persistent AF were included in the study. The extent of CFAE was measured by CFAE area and its index (CFAE area/LA surface area × 100) using three‐dimensional automated software of NavX system.ResultsThe mean value of CFAE extent was significantly different among age groups; the CFAE area decreased significantly with increasing age (30 seconds [43.2 ± 14.5 mm2] vs 40 seconds [28.6 ± 6.0 mm2] vs 50 seconds [22.8 ± 3.4 mm2] vs 60 seconds [15.3 ± 2.6 mm2] vs 70 seconds [10.3 ± 3.2 mm2]; P = .010). A similar significant decrease was observed in the CFAE area index (30 seconds [22.9 ± 7.4] vs 40 seconds [14.9 ± 3.4] vs 50 seconds [10.4 ± 1.6] vs 60 seconds [6.9 ± 1.2] vs 70 seconds [4.6 ± 1.4]; P = .002). Age had a significantly negative correlation with the CFAE area (r = −0.322, P < .001) and CFAE area index (r = −0.357, P < .001).ConclusionsIncreasing age is associated with electric remodeling in the LA characterized by a decrease in the extent of CFAE area and its index.

Chronic B-Type Natriuretic Peptide Therapy Prevents Atrial Electrical Remodeling in a Rabbit Model of Atrial Fibrillation.

Atrial fibrillation (AF) is an important and growing clinical problem. Current pharmacological treatments are unsatisfactory. Electrical remodeling has been identified as one of the principal pathophysiological mechanisms that promote AF, but there are no effective therapies to prevent or correct electrical remodeling in patients with AF. In AF, cardiac production and circulating levels of B-type natriuretic peptide (BNP) are increased. However, its functional significance in AF remains to be determined. We assessed the hypotheses that chronic BNP treatment may prevent the altered electrophysiology in AF, and preventing AF-induced activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) may play a role. Forty-four rabbits were randomly divided into sham, rapid atrial pacing (RAP at 600 beats/min for 3 weeks), RAP/BNP, and sham/BNP groups. Rabbits in the RAP/BNP and sham/BNP groups received subcutaneous BNP (20 μg/kg twice daily) during the 3-week study period. HL-1 cells were subjected to rapid field stimulation for 24 hours in the presence or absence of BNP, KN-93 (a CaMKII inhibitor), or KN-92 (a nonactive analog of KN-93). We compared atrial electrical remodeling-related alterations in the ion channel/function/expression of these animals. We found that only in the RAP group, AF inducibility was significantly increased, atrial effective refractory periods and action potential duration were reduced, and the density of ICa, L and Ito decreased, while IK1 increased. The changes in the expressions of Cav1.2, Kv4.3, and Kir2.1 and currents showed a similar trend. In addition, in the RAP group, the activation of CaMKIIδ and phosphorylation of ryanodine receptor 2 and phospholamban significantly increased. Importantly, these changes were prevented in the RAP/BNP group, which were further validated by in vitro studies. Chronic BNP therapy prevents atrial electrical remodeling in AF. Inhibition of CaMKII activation plays an important role to its anti-AF efficacy in this model.

Regulation of the TRPC1 channel by endothelin-1 in human atrial myocytes

Our recent study demonstrated that the nonselective cation current mediated by the transient receptor potential canonical 1 (TRPC1) channel is activated by endothelin-1 (ET-1) in human atrial myocytes; however, the related signal molecules involved are unknown. The purpose of this study was to investigate how the TRPC1 channel is regulated by ET-1 and whether it is upregulated in human atria from patients with atrial fibrillation (AF). Whole-cell patch technique and molecular biology techniques were used in the study. The ET-1-evoked TRPC1 current was inhibited by the ET-1 type A (ETA) receptor antagonist BQ123 and the ET-1 type B (ETB) receptor antagonist BQ788 as well as the protein kinase C inhibitor chelerythrine. ETA receptor-mediated TRPC1 channel activity was selectively inhibited by the phosphoinositide-3-kinase inhibitor wortmannin, while ETB receptor-mediated TRPC1 activity was inhibited by the phospholipase C inhibitor U73122. The messenger RNAs and proteins of the TRPC1 channel and ETA receptor, but not the ETB receptor, were significantly upregulated in atria from patients with AF. The basal TRPC1 current increased in AF myocytes, and the response to ET-1 was greater in AF myocytes than in sinus rhythm myocytes. ET-1 induced a delayed repolarization in 20% of AF myocytes. These results demonstrate for the first time that TRPC1 activation by ET-1 is mediated by protein kinase C through the distinct phospholipids pathways phosphoinositide-3-kinase and phospholipase C and that the TRPC1 channel and ETA receptor are upregulated in AF atria, which are likely involved in atrial electrical remodeling in patients with AF.

Evidence of cardiac electrical remodeling in patients with Huntington disease.

ObjectiveAlthough Huntington's disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement.Materials and MethodsWe measured conventional and advanced resting ECG indices. Thirty‐one subjects with a confirmed huntingtin gene mutation and 31 age‐ and gender‐matched controls were included. The HD subjects were divided into four groups based on their Unified Huntington Disease Rating Scale (UHDRS) motor score.ResultsWe detected changes in advanced ECG variables connected with electrical ventricular remodeling (t test, p < 0.01). The increase in the unexplained part of both QT variability and the standard deviation of normal‐to‐normal QT intervals, presumably reflecting beat‐to‐beat changes in repolarization, was most pronounced. Further, both variables correlated with the product of the cytosine–adenine–guanine (CAG) triplets’ repeat length and the subjects’ age (CAP), the former R = 0.423 (p = 0.018) and the latter R = 0.499 (p = 0.004). There was no correlation between the CAP score and any of variables representing autonomic nervous system activity.ConclusionsBoth autonomic nervous system dysfunction and cardiac electrical remodeling are present in patients with HD. The changes in advanced ECG variables observed in the study evolve with HD progression. The increased values of QT unexplained variability may be a marker of temporal inhomogeneity in ventricular repolarization associated with malignant ventricular arrhythmias.

Inflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source

About one third of ischaemic strokes are classified as embolic strokes of undetermined source (ESUS). A silent atrial fibrillation (AF) may play a pathogenic role in these strokes and P wave dispersion (PWD), representing an electrocardiographic (ECG) predictor for paroxysmal AF, thereby a potential marker of covert cardioembolism, was found to be increased in cryptogenic stroke. Furthermore, current evidence links AF to inflammation: inflammatory markers, such as high-sensitive C-reactive protein (hsCRP), have been related to the development and persistence of AF, possibly by promoting atrial remodelling. The aim of this study was to evaluate whether a relationship between PWD and hsCRP in patients with ESUS exists, in order to highlight a possible role for inflammation in the atrial electric remodelling, that predisposes to AF. We enrolled 174 patients (91 males, 83 females; mean age 69±13years) with ESUS. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. P wave dispersion and hsCRP were measured in all subjects. A significant positive correlation was found between hsCRP and PWD (Spearman r: 0.35, p<0.0001). In patients with high PWD (>40 msec; n=102), hsCRP was three-fold higher than in patients with normal PWD (≤40 msec; n=72)(1.57±2.9 vs 0.42±0.4mg/dl, p=0.0005). Our results show increased hsCRP levels in cryptogenic stroke patients with high PWD. These findings provide support for the hypothesis that systemic inflammation plays a role in a fraction of patients with ESUS, by increasing AF risk via atrial electric remodelling.

Previous use of Statins and Atrial Electrical Remodeling in Patients with Cryptogenic Stroke.

In the general population the leading cause of cardioembolic stroke is atrial fibrillation (AF). A silent AF is also the possible cause of many cryptogenic strokes. P wave dispersion (PWD), a predictor of AF, has been proposed as a marker of silent AF occurrence in these strokes. PWD correlates with high-sensitive C-reactive protein levels reflecting the role of inflammation in promoting a slowed and inhomogeneous atrial conduction. Statins have a multitude of additional effects beyond lipid lowering, in particular anti-inflammatory effects that may influence atrial conduction. The aim of this study was to evaluate the effects of previous statin use on PWD in patients with cryptogenic stroke, in order to highlight a possible role for statins in preventing atrial conduction alterations that predispose to AF. We enrolled 131 patients (67 males, 64 females; mean age 69±13 years) with cryptogenic stroke. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. PWD was measured in all subjects. Patients previously treated with statins (n: 34) had lower PWD and P index values in comparison with no-statin group (41.7±12.2 vs 48.7±15.2 ms, p=0.01, and 14.2±3.7 vs 16.5±5.3 ms, p=0.02, respectively). Our results show lower PWD values in cryptogenic stroke patients previously treated with statins. These findings provide support to the hypothesis that statins may play a role in modulating atrial electrophysiological and structural properties, preventing the occurrence of a slowed and heterogeneous atrial conduction and finally, reducing the occurrence of AF.

Electrical remodelling in patients with iatrogenic left bundle branch block.

Left bundle branch block (LBBB) is induced in approximately one-third of all transcatheter aortic valve implantation (TAVI) procedures. We investigated electrophysiological remodelling in patients with TAVI-induced LBBB. This retrospective study comprises 107 patients with initially narrow QRS complex of whom 40 did not and 67 did develop persistent LBBB after TAVI. 12-lead electrocardiograms (ECGs) taken before TAVI, within 24 hours ('acute'), and 1-12 months after TAVI ('chronic') were used to reconstruct vectorcardiograms. From these vectorcardiograms, QRS and T-wave area were calculated as comprehensive indices of depolarization and repolarization abnormalities, respectively. TAVI-induced LBBB resulted in significant acute depolarization and repolarization changes while further repolarization changes were observed with longer lasting LBBB. The amount of long-term repolarization changes (remodelling) was highly variable between patients. The change in T-wave area between acute and chronic LBBB ranged from +57% to - 77%. After dividing the LBBB cohort into tertiles based on the change in T-wave area, only baseline QRS area was larger in the tertile with no significant change in T-wave area. During longer lasting LBBB, the spatial vector gradient (SVG) changed orientation towards the direction of the QRS-vector, indicating that later-activated regions developed shorter action potential duration. This study in patients with TAVI-induced LBBB shows that repolarization changes develop within months after onset of LBBB, and that these changes are highly variable between individual patients.

The impact of cryoballoon-based catheter ablation on left atrial structural and potential electrical remodeling in patients with paroxysmal atrial fibrillation.

While atrial fibrillation (AF) begets AF via structural, contractile, and electrical remodeling, it was shown that successful radiofrequency ablation of AF has effectively reversed left atrial (LA) remodeling. However, there was little data regarding the efficacy of cryoablation on LA remodeling. Herein, we aimed to assess the impact of cryoablation on LA structural and potential electrical remodeling in paroxysmal AF patients. A total of 41 symptomatic patients with non-valvular paroxysmal AF underwent their first catheter ablation via cryoballoon technique. All patients had transthoracic echocardiography before, 6 and 12 months after cryoablation. LA volume index (LAVI), left intra-, right intra-, and inter-atrial electromechanical conduction delay (AEMD) were calculated in all patients. Postprocedural first 3 months was accepted as blanking period. All 179 pulmonary veins were isolated successfully in 41 patients with no major complication. During median 18 months (12-20 months) follow-up, recurrent atrial arrhythmia was found in nine patients (21.9%). In multivariate Cox regression analysis, only early recurrence was found as the independent predictor of late recurrence. At 12th month visit compared to baseline, there was no change in LAVI (p = 0.647) but significant increase in left intra- and inter-AEMD (p < 0.05). However, in non-recurrent group, both LAVI (30.63 ± 3.6 to 28.42 ± 3.63, p < 0.001), left intra-AEMD (18.75 ± 8.77 to 12.5 ± 4.65, p < 0.001), and inter-AEMD (25.2 ± 13.2 to 18.84 ± 8.52, p < 0.001) were significantly decreased. Our study findings revealed that successful cryoballoon-based AF ablation yields LA structural and potential electrical reverse remodeling. However, LA remodeling process cannot be halted by cryoablation in patients with AF recurrence during follow-up.

第2回 不整脈薬物治療フォーラム 慢性心不全患者における心房の電気的リモデリングに対するアンジオテンシン変換酵素阻害薬の効果について

第2回 不整脈薬物治療フォーラム 慢性心不全患者における心房の電気的リモデリングに対するアンジオテンシン変換酵素阻害薬の効果について

Functional transient receptor potential canonical type 1 channels in human atrial myocytes

Transient receptor potential (TRP) channels are not well understood in human atrium, and the present study was therefore designed to investigate whether TRPC channels would mediate the nonselective cation current reported previously and are involved in the formation of store-operated Ca(2+) entry (SOCE) channels in human atrial myocytes using approaches of whole-cell patch voltage-clamp, RT-PCR, Western blotting, co-immunoprecipitation, and confocal scanning approaches, etc. We found that a nonselective cation current was recorded under K(+)-free conditions in human atrial myocytes, and the current was inhibited by the TRP channel blocker La(3+). Thapsigargin enhanced the current, and its effect was suppressed by La(3+) and prevented by pipette inclusion of anti-TRPC1 antibody. Endothlin-1 and angiotensin II enhanced the current that could be inhibited by La(3+). Gene and protein expression of TRPC1 channels were abundant in human atria. In addition, mRNA and protein of STIM1 and Orai1, components of SOCE channels, were abundantly expressed in human atria. Co-immunoprecipitation analysis demonstrated an interaction of TRPC1 with STIM1 and/or Orai1. Ca(2+) signaling mediated by SOCE channels was detected by a confocal microscopy technique. These results demonstrate the novel evidence that TRPC1 channels not only mediate the nonselective cation current, but also form SOCE channels in human atria as a component. TRPC1 channels can be activated by endothelin-1 or angiotensin II, which may be involved in the atrial electrical remodeling in patients with atrial fibrillation.

Reverse atrial electrical remodelling induced by continuous positive airway pressure in patients with severe obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and mortality, including atrial arrhythmias. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; its impact on atrial electrical remodelling has not been fully investigated. Signal-averaged p-wave (SAPW) duration is an accepted marker for atrial electrical remodelling. The objective of this study is to determine whether CPAP induces reverse atrial electrical remodelling in patients with severe OSA. Consecutive patients attending the Sleep Disorder Clinic at Kingston General Hospital underwent full polysomnography. OSA-negative controls and severe OSA were defined as apnoea-hypopnea index (AHI) < 5 events/hour and AHI ≥ 30 events/hour, respectively. SAPW duration was determined at baseline and after 4-6 weeks of CPAP in severe OSA patients or without intervention controls. Nineteen severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum oxygen saturation were 41.4 ± 10.1 events/hour and 80.5 ± 6.5 % in severe OSA patients and 2.8 ± 1.2 events/hour and 91.4 ± 2.1 % in controls. At baseline, severe OSA patients had a greater SAPW duration than controls (131.9 ± 10.4 vs 122.8 ± 10.5 ms; p = 0.02). After CPAP, there was a significant reduction of SAPW duration in severe OSA patients (131.9 ± 10.4 to 126.2 ± 8.8 ms; p < 0.001), while SAPW duration did not change after 4-6 weeks in controls. CPAP induced reverse atrial electrical remodelling in patients with severe OSA as represented by a significant reduction in SAPW duration.

175 Cavotricuspid isthmus dependent atrial flutter in adults with congenital heart disease - single centre experience over a decade

AHI 30 events/hour, respectively. In severe OSA patients, SAPW was determined preand post-intervention with CPAP. In OSA-negative controls, SAPW was recorded at baseline and 4-6 weeks thereafter without any intervention. RESULTS: A total of 17 severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum O2 saturation were 40.4 12 events/hour and 80.2 6.9% in severe OSA patients and 2.9 1.4 events/hour and 90.7 2.8% in controls. Baseline BMI was different between severe OSA patients and controls (35 4.7 vs 27.3 5.8; P 0.001). At baseline, severe OSA patients had a greater SAPW duration than controls (131.1 8.4ms vs 122.7 9.5 ms; P 0.05). After CPAP intervention, there was a significant reduction of SAPW duration in severe OSA patients (127.4 8ms vs 131.1 8.4ms; P 0.001). In controls, SAPW duration did not change within 4-6 weeks. CONCLUSION: CPAP induced reverse atrial electrical remodeling in patients with severe OSA as represented by a significant reduction in P-wave duration.

Relationship between mechanical and electrical remodelling in patients with cardiac resynchronization implanted defibrillators

Cardiac resynchronization therapy (CRT) is associated with reverse left ventricular (LV) remodelling. However, the effects of CRT-induced mechanical remodelling on electrical remodelling, and the occurrence of ventricular arrhythmias have not been clearly established. We studied the relationship between mechanical remodelling, electrical remodelling, and the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapy 1 year after CRT. We analysed data from 45 patients who underwent ICD-CRT implantation at our centre. Significant LV reverse remodelling was defined by a minimum 10% decrease in the LV end-diastolic diameter (LVEDd) at 1 year of follow-up. Electrocardiographic indices of dispersion of repolarization [QTc, Tpeak-Tend (Tp-e) and their dispersion] were measured immediately and 1 year post-CRT implantation. The occurrence of appropriate ICD therapy was noted for each patient. Patients with (n= 21) and without (n= 24) significant LV reverse remodelling had similar baseline characteristics. At 1 year of follow-up, patients with mechanical reverse LV remodelling exhibited a significant decrease in QTc (505 ± 42 vs. 485 ± 52 ms, P < 0.05) and Tp-e (107 ± 26 vs. 92 ± 22 ms, P < 0.0001). However, patients without mechanical LV reverse remodelling exhibited a significant increase in QT dispersion (29 ± 43 vs. 98 ± 47 ms, P = 0.002) and Tp-e dispersion (22 ± 21 vs. 54 ± 36 ms, P = 0.0001). Finally patients with mechanical LV reverse remodelling experienced a lower rate of ICD therapy (P = 0.0025) after a mean follow-up of 19 months. Reverse LV mechanical remodelling is associated with reversal of electrical remodelling and a lower rate of appropriate ICD therapy following CRT.

ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: Implications for electrical remodeling

The angiotensin-converting enzyme (ACE) gene contains a common polymorphism based on the insertion (I) or deletion (D) of a 287-bp intronic DNA fragment. The D allele is associated with higher ACE activity and thus higher angiotensin II levels. Angiotensin II stimulates cardiac fibrosis and conduction heterogeneity. The purpose of this study was to determine whether the ACE I/D polymorphism modulates cardiac electrophysiology. Three different cohorts of patients were studied: 69 patients with paroxysmal lone atrial fibrillation (AF), 151 patients with structural heart disease and no history of AF, and 161 healthy subjects without cardiovascular disease or AF. Patients taking drugs that affect cardiac conduction were excluded from the study. ECG parameters during sinus rhythm were compared among the ACE I/D genotypes. The ACE I/D polymorphism was associated with the PR interval and heart block in the lone AF cohort. In multivariable linear regression models, the D allele was associated with longer PR interval in the lone AF and heart disease cohorts (12.0-ms and 7.1-ms increase per D allele, respectively). P-wave duration showed a similar trend, with increase in PR interval across ACE I/D genotypes in the lone AF and heart disease cohorts. The ACE D allele is associated with electrical remodeling in patients with lone AF and in those with heart disease, but not in control subjects. ACE activity may play a role in cardiac remodeling after the development of AF and heart disease.

The beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors on atrial electrical remodeling in patients with essential hypertension

Background: Stroke volume (SV) and heart rate (HR), determining cardiac output (CO), are crucial hemodynamic parameters determining training adoptions to endurance training. In soccer, aerobic power as well as intermittent exercise performance varies significantly among level of competition as well as playing position. In this study cohort study we thought to determine the hemodynamic changes following a standardized soccer-specific exercise in female soccer players at the soccer field using a portable non-invasive hemodynamic monitoring tool. Methods: A non-invasive, portable continuous wave (CW) Doppler-based ultrasound system (USCOM, Sydney, Australia) was used to assess HR, SV, CO, and cardiac index (CI) using a suprasternal approach after a soccer specific exercise (5-vs-2-gameplay over 5 min) in an elite female soccer team of the German Fussball Bundesliga (15 females, 22.3±3.6 years). Results: 30 s after the peak exercise the mean HR increased significantly (121±26 /min vs 56±11 /min, pb0.05), while SV did not change significantly (75±25 ml vs. 80±13 ml, n.s.). CO increased significantly (9.2±4.1 l/min vs. 4.5±1.1 l/min) as did CI (5.3±2.1 l/min/m vs. 2.6±0.6 l/min/m, pb0.05). Conclusion: Elite female soccer players increase cardiac output after 5-vs-2-gameplay on average to 10 l/min, in single cases up to 18 l/min 30 s after peak exercise. Therefore significant peak hemodynamic demands are encountered in soccer game play. The increase of cardiac output is by far more achieved by an increase of the heart rate than by stroke volume changes in most of the female soccer players. On field hemodynamic exercise testing is feasible using the USCOM in elite soccer. © 2007 Elsevier Ireland Ltd. All rights reserved.

Aging and Sinoatrial Node Dysfunction

In the century since the discovery by Keith and Flack of the sinoatrial node in the mole heart, a detailed mosaic of its cellular, anatomic, and electrophysiological properties has emerged. The human sinus node has been found to be anatomically constant and well localized, occupying an approximately 10-mm subepicardial region on the sulcus terminalis at the superior cavo–atrial junction.1 Histologically, its ultrastructure of central P cells (likely corresponding to the leading pacemaker site) and outer transitional zone merging with surrounding atrial myocardium have been well characterized.1 Great progress also has been made in defining the ionic mechanisms responsible for the sinoatrial action potential and its spontaneous pacemaker activity, including important contributory roles for I Ca,L, I k, and the funny current, I f.1 This morphologically discrete, unifocal sinus node is not the exclusive force behind clinical sinus rhythm, however. Detailed animal and human mapping has demonstrated that normal cardiac pacemaker activity is widely distributed in the right atrium. In the human atrium, the pacemaker complex extends for up to 75 mm along the long axis of the sulcus terminalis and precaval band.2 At times, even left atrial pacemakers may be active during normal sinus rhythm.2 Graduated differential sensitivity to adrenergic and vagal inputs exists along the integrated pacemaker complex such that superior sites tend to dominate during periods of sympathetic drive, whereas inferior sites are activated by increased parasympathetic tone. Increasing the complexity, each sinus beat may have multicentric origin, and the nature of conduction out of the node also seems to be variable in response to autonomic tone.2 The presence of a diffuse pacemaker complex …