Sinus node pacemaker shift: a phenomenon induced by premature atrial stimulation in man?

The aim of this study was to investigate whether premature atrial stimulation is able to induce a shifting of the sinus node pacemaker. For this purpose we compared, in 18 patients, the curve of sinus node function obtained with Strauss' method with that resulting from the scanning, with premature atrial stimulation, of the first returning cycle following a single premature induced atrial beat. We found that the length of the compensatory phase (zone I) evaluated on the curve resulting from the scanning of the first returning cycle following the single premature induced atrial beat was shorter (15%) than that observed with the original Strauss method. In addition, an inverse relationship between the shortening of the compensatory zone and the estimated sinoatrial conduction time was observed. This result could be accounted for by one of the following explanations: 1) a change in the sinoatrial conduction or in the sinus pacemaker automaticity; 2) sinus node reentry; 3) sinus node pacemaker shift. Even if there is no direct evidence either to prove or to exclude one or more of these explanations, sinus node pacemaker shift seems to be the most convincing explanation.     

Preventive pacemaker stimulation in atrial fibrillation

Preventive pacing algorithms and the use of alternative or multifocal pacing sides are new approaches for treatment of paroxysmal atrial tachyarrhythmias. However, present data are not sufficient to define a new indication for pacemaker implantation in patients with refractory atrial fibrillation. Yet, preventive pacing should be predominantly performed either in patients with an established pacemaker indication or during controlled study projects. In patients undergoing cardiac surgery, biatrial overdrive pacing using temporary epicardial wires can be recommended for prevention of postoperative atrial fibrillation.     

Analysis of sino-atrial conduction in man using premature atrial stimulation.

Sino-atrial conduction was investigated using premature atrial depolarization in 25 patients seven of whom had sino-atrial block. The results obtained in this investigation were evaluated plotting the test cycle (expressed as difference between the basic sinus cycle and the test cycle as a percentage of the basic sinus cycle) as a function of the return cycle (expressed as difference between the return cycle and the basic cycle as a percentage of the basic sinus cycle). In normal subjects, premature atrial depolarizations elicited in the last 10-20% of the spontaneous sinus cycle, produced a progressive prolongation of the return cycle and the points correlating the return cycle index to the test cycle index fell above the diagonal of the plotting system. After earlier premature atrial depolarizations, the return cycle remained of the same length, and the points correlating the return cycle index to the test cycle index fell along a line parallel to the y-axis ('plateau'). The mean value of the returning cycles (as expressed above) corresponding to the test cycles (as evaluated above) included in the first 5% of the 'plateau' can be defined as 'the sino-atrial conduction index'. This index, the sum of conduction into and out of the sinus node, was found to range from 79 to 185 ms. By assuming similar anterograde and retrograde conduction, the sino-atrial conduction time ranged from 39.5 to 97.5 ms (mean value=70 ms). In the patients with sino-atrial block, fully compensatory pauses were observed for atrial premature depolarizations elicited up to the last 25-35% of the atrial cycle, and a slow and progressive divergence from the diagonal of the plotting system was seen instead of the 'plateau'. In these patients the sino-atrial conduction index ranged from 151 to 297 ms (mean 253 ms). By assuming similar antegrade and retrograde conduction, the sino-atrial conduction time ranged from 75.5 to 148.5 ms (mean value=126.5 ms) with a statistically significant difference with respect to normal subjects (P=0.001).     

Corticosteroid-induced stimulation of atrial natriuretic peptide in man

Previously, we reported elevated plasma immunoreactive ANP (irANP) levels from the 2nd to the 9th day of administering either prednisone, 50 mg/day, or 9 alpha-fludrocortisone acetate (9 alpha F), 0.6 mg/day, to normal humans. To investigate the course of plasma irANP levels during the first 48 h of corticosteroid administration, 9 healthy men (mean age +/- SEM, 24 +/- 1 years) received in randomised sequence A) a 4-h iv infusion of prednisolone sodium tetrahydrophthalate followed by oral administration of prednisone for 2 days; or B) a 4-h infusion of aldosterone followed by oral administration of 9 alpha F for 2 days. Basal supine plasma irANP levels averaged 32 +/- 5 ng/l in study A and 30 +/- 6 ng/l in study B; they were unchanged or even deceased up to 24 h of glucocorticoid or mineralocorticoid administration, but rose (P less than 0.01) to 56 +/- 9 and 62 +/- 12 ng/l at 48 h, respectively, of the two interventions. During glucocorticoid treatment, blood pressure (BP) and indices of the sodium-fluid volume state were unchanged after 48 h. During 9 alpha F administration, body weight increased (1.1 +/- 0.3%, P less than 0.001), whereas urinary sodium excretion (63 +/- 7%, P less than 0.001), hematocrit (4.1 +/- 1.1%, P less than 0.001), and plasma renin activity (38 +/- 4%, P less than 0.001) decreased. Conclusions: The increase in circulating irANP at 48 h of administration of either a glucocorticoid or a mineralocorticoid demonstrates a distinct but slow response of the ANP system to these corticosteroids in normal humans.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man.

BACKGROUND: In animal studies, atrial fibrillation has been shown to shorten the atrial refractory period and impair its rate adaptation. However, little is known about the effects of chronic atrial fibrillation on atrial electrophysiology and its recovery course in humans. METHODS AND RESULTS: Nineteen patients, mean age 64 +/- 14 years, with chronic atrial fibrillation of more than six months duration were included in this study. All of them were successfully converted to sinus rhythm with an external defibrillator. Atrial effective refractory periods at right atrial appendage and distal coronary sinus were determined with five pacing cycle lengths (300, 400, 500, 600 and 700 ms) at 30 min after cardioversion and once a day for four days. The atrial conduction properties, including P wave duration of surface ECG, and right and left atrial conduction times, were also measured at the same time interval. Twenty age-matched patients without a history of atrial tachyarrhythmia were evaluated as controls. In comparison with controls, chronic atrial fibrillation significantly shortened the atrial effective refractory period, impaired its rate adaptation response, especially at distal coronary sinus, and depressed the conduction properties of atria. The atrial conduction properties did not change during the four-day follow-up period; however, the atrial effective refractory period was gradually prolonged and its rate adaptation response improved after restoration of sinus rhythm. CONCLUSIONS: In humans, chronic atrial fibrillation significantly shortened the atrial effective refractory period, and impaired its rate adaptation response. Restoration and maintenance of sinus rhythm could reverse these electrophysiological changes.     

Temporal changes in atrial refractoriness following DC cardioversion of persistent atrial fibrillation in man.

AIMS: Studies have demonstrated shortening of the atrial effective refractory period (ERP) after episodes of atrial fibrillation (AF). This is termed atrial remodelling. It is unclear whether restoration of SR after persistent AF in patients with a clinical substrate results in reversal of this shortening and whether this is maintained long term. METHODS AND RESULTS: The ERP was determined at mid-lateral right atrial wall (MLRA) and right atrial appendage (RAA) at 600 ms and 400 ms drive cycle lengths and at basic sinus cycle length in 81 patients with persistent AF immediately, 24 h and 2 weeks following external DC cardioversion. All atrially active drugs were stopped for at least 5 half lives. (1) Prolongation of the ERP was observed at both atrial sites and all cycle lengths up to 24 h post cardioversion (p < 0.0001). (2) However, between 24 h and 2 weeks a subsequent shortening occurred in the ERP returning it to near post cardioversion levels. (3) The ERP was significantly longer at 24 h post cardioversion in patients who remained in SR for 2 weeks or longer compared with those who reverted to AF. CONCLUSION: Prolongation of the atrial ERP occurred following restoration of SR in persistent AF patients but was not maintained and displayed a biphasic pattern such that by 2 weeks the ERP had returned to baseline values. Despite this finding, a longer ERP at 24 h post cardioversion was associated with maintenance of SR in the medium-term.     

永久起搏器植入术后早期心房穿孔一例

患者男,23岁,因“反复发作性头晕半年”收入院,有“慢性胃病”史2年。外院心电图示：心房颤动（房颤）伴缓慢心室率（房颤时最长RR间期5．8s）,应用异丙肾卜腺素后复查心电图示窦性心律（62次／min）。入院后查电解质、肝肾功能、超敏C反应蛋白、     

Newly detected atrial fibrillation following dual chamber pacemaker implantation

Introduction: Pacemaker (PPM)-detected atrial high-rate episodes (AHREs) of even 5-minute duration may identify patients at increased risk for stroke and death. In this study, we sought to determine the incidence of newly detected atrial fibrillation (AF defined as an AHRE ≥5 minutes) in patients following dual-chamber PPM implantation and to define the clinical predictors of developing AF.
Methods and Results: We evaluated 262 patients (142 male; age 74 ± 12 years) without documented AF who underwent PPM implantation for sinus node dysfunction (n = 122) or atrioventricular block (n = 140). Information regarding patient demographics, cardiovascular diseases, and medication history was obtained. The cumulative percentages of ventricular pacing as well as the frequency, duration, and time to first episode of an AHRE were also determined. During follow-up of 596 ± 344 days, an AHRE ≥5 minutes was detected in 77 (29%) patients. Of these, 47 (61%) patients had an AHRE ≥1 hour, 22 (29%) patients had an AHRE ≥1 day, and 12 (16%) patients had an AHRE ≥1 week. An AHRE ≥5 minutes was seen in 24% and 34% of patients at 1 year and 2 years, respectively. Among patients with sinus node dysfunction, ≥50% cumulative ventricular pacing was the only significant predictor of an AHRE ≥5 minutes (HR 2.2; CI 1.0–4.7; P = 0.04).
Conclusions: Within 1 year of PPM implantation, AF is detected in 24% of patients without history of AF. In patients with sinus node dysfunction, ≥50% cumulative right ventricular pacing is associated with a 2-fold increase in risk of developing AF.     

DDD(R)术后新发心房颤动的特点及预后

目的探讨无心房颤动(简称房颤)病史患者植入双腔起搏器术后新发房颤的特点及临床预后。方法入选2013年6月到2015年2月在上海中山医院植入双腔起搏器且术前无房颤病史的患者为研究对象。研究中将起搏器记录到的持续5 min以上且心房率≥180次/分的快速房性心律失常事件定义为房颤。结果 219例患者(88例窦房结功能障碍,131例为房室传导阻滞)纳入研究,平均随访(884±180)天,共有56例(26%)发生房颤,其中31例(55%)无任何症状。多因素回归分析发现冠心病合并房颤更容易出现症状(OR 8.168;CI 1.155～15.928;P=0.038)。研究发现房颤发生率在不同性别及年龄段(年龄<65岁,65岁≤年龄≤75岁,年龄≥75岁)无明显差异。56例新发房颤患者仅3例接受抗凝治疗。新发房颤患者脑梗死的发病率明显高于未发生房颤患者[16%(9/56) vs 1%(2/163),P<0.05]。结论起搏器术后房颤发生率高,且多无症状,应加强对起搏器发现的房颤患者的抗凝治疗以降低其并发症。     

Analysis of the interpolation phenomenon in man evaluated by premature atrial stimulation.

After early premature atrial stimulations, returning cycles shorter than the basic cycle were observed in 25 patients. In 4 of them sinus echoes were seen to occur after premature atrial stimulation coupling intervals shorter than those able to induce completely interpolated beats. Such a sequence is unexpected if we suggest a sino-atrial entrance block for explaining the interpolation phenomenon. An alternative explanation can be postulated assuming that all these early premature beats are sinus node re-entries and that the completely interpolated beat is only a sinus re-entry fortuitously occurring at an appropriate interval.     

Temporal patterns of paroxysmal atrial fibrillation following DDDR pacemaker implantation

Paroxysmal atrial fibrillation (AF) episodes have been reported to be randomly distributed. However, because patients are not always symptomatic, it has been difficult to study temporal patterns of AF. Newer implantable pulse generators have data-logging capabilities that permit the detection and analysis of temporal patterns of AF. This study tested the hypothesis that AF episodes occur in clusters over time and that these episodes are not randomly distributed in individual patients. The date and time of 582 episodes of AF were recorded from the data logs of 16 patients with a Medtronic Thera DR followed 6 weeks and 6 and 12 months after pulse generator implant. The probability of AF recurrence and the interevent intervals between successive episodes of AF were fitted to monoexponential and Weibull distributions. A Weibull distribution best described the nonrandom distribution of AF for 67% of follow-up visits. Temporal clustering of AF (interevent intervals <24 hours) declined during follow-up (95 ± 10%, 90 ± 11%, and 74 ± 28% at the 6-week and 6- and 12-month visits, respectively; p <0.05). The average duration of an episode of AF tended to increase over time (0.31 hour, 95% confidence intervals [CI] 0.17 to 0.58 hours; 0.36 hours, 95% CI 0.17 to 0.78 hours; 0.65 hours, 95% CI 0.29 to 1.45 hours [p = 0.07] at the 6-week and 6- and 12-month visits, respectively). Paroxysmal AF recurrence is nonrandomly distributed over the long term in many patients. The temporal patterns of AF change over time after pacemaker implantation. This has implications for the selection of study end points in AF clinical trials.     

Sinoatrial transmission and atrial invasion during normal rhythm in the rabbit heart.

Intracellular microelectrodes and small unipolar leads applied to endocardial surface of the right atrium in vitro were used to study the complex extracellular wave patterns recorded from the neighborhood of the cardiac pacemaker during spontaneous activity. Sinus activity propagated slowly toward the site of atrial invasion on the venous border of the crista terminalis. Atrial activation was marked by a primary negative wave that appeared 20-40 msec after pacemaker firing. Two sources of complex multiphasic waves were found. First, potentials from transitional sinus tissue propagated toward the atrium and caused low-voltage waves that preceded and slurred the onset of the atrial initial negativity. Second, bundles and layers of the crista terminalis muscle were excited asynchronously around the invasion region, as if cross-connections were infrequent. Waves originating from this source occurred after the firing of the invasion site. No extracellular wave could be associated with the firing of the true pacemaker cells. The sinoatrial ring bundle (SARB) yielded a discrete biphasic deflection along most of its way toward the coronary sinus. This potential appeared most frequently after that of the adjoining cristal muscle, raising questions about the functional role of the SARB as an internodal preferential pathway.     

Glucocorticoid and mineralocorticoid stimulation of atrial natriuretic peptide release in man

To investigate the influence of a mineralocorticoid and a glucocorticoid on plasma immunoreactive atrial natriuretic peptide (irANP) and possible functional correlates, eight normal men received in random order 9 alpha-fludrocortisone acetate (9 alpha F; 0.6 mg/day), prednisone (50 mg/day), and placebo each for 9 days. Their diet contained 130 mmol sodium and 75 mmol potassium daily. The mean supine plasma irANP levels were similar on days 2, 4, and 9 of placebo treatment [25 +/- 10 (+/- SE), 27 +/- 5, and 27 +/- 6 pmol/L, respectively]. Mean plasma irANP levels were 76 +/- 42 (P less than 0.05), 89 +/- 34, and 93 +/- 29 pmol/L (P less than 0.01), respectively, on days 2, 4, and 9 during 9 alpha F administration, and 68 +/- 37 (P less than 0.05), 83 +/- 41, and 48 +/- 18 pmol/L on the same days during prednisone administration. Compared with the placebo period, sodium intake minus urinary output during 9 alpha F administration averaged +41 mmol at the time of blood sampling on day 2, +112 mmol on day 4, and +149 mmol on day 9; body weight was unchanged on day 2 and increased by 0.7 and 1.1 kg on days 4 and 9, respectively. Escape from 9 alpha F-induced renal sodium retention occurred on days 5 and 6. During prednisone administration, sodium intake minus urinary output and body weight did not change. Plasma volume and BP rose significantly during 9 alpha F (P less than 0.05) but not during prednisone administration. Plasma renin, aldosterone, and norepinephrine (NE) decreased during 9 alpha F treatment (P less than 0.05 to less than 0.01); during prednisone treatment, plasma aldosterone levels were lower on day 9 only. Cardiovascular pressor responsiveness to angiotensin II was enhanced during 9 alpha F but not prednisone administration, while blood pressure reactivity to NE was not significantly modified. These findings demonstrate that 9 alpha F and prednisone in high doses provoke remarkably similar increases in plasma irANP, but that the glucocorticoid-induced rise in plasma irANP is due to a mechanism other than sodium and volume retention.     

Coupled secretion of gastric lipase and pepsin in man following pentagastrin stimulation.

Secretion patterns of gastric lipase and pepsin were studied in duodenal ulcer patients before and after vagotomy and in healthy subjects following continuous administration of pentagastrin in graded doses. The lipase output increased in response to pentagastrin stimulation in similar fashion as that of pepsin. The output of the two enzymes were correlated with each other and with hydrogen ion output. Evaluation of dose-response relationships showed that in duodenal ulcer patients the secretion of gastric lipase and pepsin is more sensitive to pentagastrin stimulation than that of hydrogen ions.     

Atrial stimulation and intranodal migration of sinus pacemaker in man (author's transl)

In order to demonstrate, in man, sinus node pacemaker shift following atrial stimulation, we compared, in 26 patients, the curve of sinus node function obtained with Strauss' method with that resulting by the scanning with premature atrial stimulation of the first returning cycle following either a single premature atrial induced beat (140 ms shorter than the basic cycle) (group A), or a train of 8 consecutive atrial beats induced with a rate slightly faster (10 beats/m) than the control sinus rhythm (group B). Assuming that no changes in sinus pacemaker automaticity or in sinoatrial conduction occur owing to atrial stimulation, curves with the same shape should be observed if the site of the dominant pacemaker remains unchanged: whereas, different lengths of the compensatory phase (zone I) should be expected if an intranodal pacemaker shift occurs. For evaluating the length of the compensatory zone (zone I), we calculate, on the curve of the sinus node function, the mean value of the relation points included in the first third of the reset zone (zone II). According to our results, the length of the compensatory phase (zone I) evaluated on the curve resulting by the scanning of the first returning cycle following either a single premature atrial induced beat (group A), or eight consecutive atrial beats (group B) was shorter than that observed with the original Strauss' method (10% and 18% respectively). However, only in the group B, this difference was statistically significant. In addition, a significant inverse relationship between the shortening of the compensatory zone and the sinoatrial conduction index was also observed. Considering that our results have been corrected in such way as to repeal eventual changes in sinus pacemaker automaticity or sinoatrial conduction following atrial stimulation, the shortening of the compensatory zone, we have observed in our patients, strongly suggests an intranodal sinus pacemaker shift. If we assume that this result could represent an indirect evidence of this phenomenon, some clinical implications may follow: 1) another limitation, in addition to others known (intraatrial conduction delay, sinus arrhythmia, changes in sinus node automaticity, difference between retrograde and antegrade conduction time) could decrease the accuracy of atrial stimulation techniques in the estimation of the sinoatrial conduction time; 2) sinus pacemaker shift following atrial stimulation, may induce an understimulation of the true sinoatrial conduction time; however, according to our results, the error is generally small, so that it does no preclude the usefulness of atrial stimulation techniques in the evaluation of sinoatrial conduction; 3) the more evident and significant shortenings of the compensatory phase occurred with atrial pacing technique: this finding could explain why shorter sinoatrial conduction times are generally observed with Narula's method in comparison with Strauss' method.     

Direct stimulation of the sinus node in man. A possible explanation for an unusual finding during premature atrial stimulation.

An atypical behavior of the postextrasystolic pauses was observed in a 19-yr-old patient studied by His bundle electrography and programmed premature atrial stimulation. In the normal case there is a prolongation of the postextrasystolic pauses compared to the spontaneous cycle length allowing calculation of sinoatrial conduction time (SACT). In this case there were constant postextrasystolic pauses during the whole range of prematurity which were identical to the spontaneous cycle length. It is suggested that the catheter tip was accidentally positioned at the sinus node itself. The lengths of the spontaneous cycles, of the return cycles, and of the postreturn cycles showed no significant differences. Thus, one may assume that sinus node automaticity was not influenced in this case.     

Ventricular capture by anodal pacemaker stimulation.

This report describes the case of an 86-year-old male with syncopal paroxysmal 2:1 atrioventricular block and a single chamber VVI pacemaker programmed to bipolar sensing and unipolar pacing. After recurrence of syncope, a complete loss of ventricular capture with regular ventricular sensing was observed on ECG; fluoroscopic examination suggested perforation of the right ventricle by the helix of the implanted screw-in lead. Reprogramming the pacemaker to bipolar pacing/sensing resulted in regular ventricular capture and sensing, suggesting effective anodal stimulation from the ring electrode permitting complete non-invasive palliation.     

心房内不同刺激部位对窦房结恢复时间测定的影响

选取病态窦房结综合征患者23例，比较分别刺激其高位右房（HRA）和房间隔右侧面下部（AS）时的窦房结恢复时间（SNRT）。结果显示，刺激HRA与刺激AS的SNRT在个体有不同，但在整体则无统计学差异。提示心房内刺激部位对临床检测SNRT无明显影响。