Europace Advance Access published May 20, 2015
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv098
Atrial standstill in sinus node disease due to extensive atrial fibrosis: impact on dual chamber pacemaker implantation 1 Department of Cardiology, Charite´ Berlin Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; 2Department of Cardiology, University Hospital, Technical University Aachen RWTH, Pauwelstrasse 30, 52074 Aachen, Germany; and 3Kardiologie an der Rudower Chaussee, Rudower Chausee 9, 12489 Berlin, Germany
Received 19 January 2015; accepted after revision 17 March 2015
Aims
Atrial standstill is characterized by the absence of atrial activity. We report about a series of cases, in which conventional atrial pacemaker lead implantation in patients with symptomatic sinus node disease failed due to lack of excitable right atrial tissue, thus, prompting the diagnosis of atrial standstill. We hypothesized that mapping of the atria with subsequent identification of myocardium still amenable to atrial pacing would allow dual chamber pacemaker implantation. ..................................................................................................................................................................................... Methods and In four patients, atrial lead implantation failed. In these patients, spontaneous or fibrillatory electrical activity was absent but the atria could not be captured despite high stimulation voltages at conventional atrial sites. We suspected partial or results complete atrial standstill and subsequently confirmed this hypothesis by conventional (n ¼ 1) or electroanatomical mapping (n ¼ 3). Areas of fibrotic tissue were present in all patients as identified by lack of spontaneous electrical activity and inability of local electrical capture via the mapping catheter. Surviving atrial tissue, which could be electrically captured with subsequent conduction of activity to the atrioventricular (AV) node, was present in three patients. Successful targeted atrial lead implantation at these sites was achieved in all these patients. Isolated sinus node activity without conduction to the atria was found in one patient. ..................................................................................................................................................................................... Conclusion Partial atrial standstill may be present and prevent atrial lead implantation in patients with sinus node disease. In these patients, recognition of partial atrial standstill and identification of surviving muscular islets with connection to the AV node by mapping studies may still allow synchronous AV sequential pacing.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial standstill † Sinus node † Pacemaker † Atrial mapping
Introduction Atrial standstill is a condition characterized by the absence of electrical and mechanical atrial activity1 and was first described by Cushny.2 Atrial standstill may not be recognized as such because differentiation from bradyarrhythmia due to sick sinus syndrome or permanent atrial fibrillation with low amplitude or lack of fibrillatory waves in surface electrogram recordings is sometimes difficult. Depending on the spatial distribution and temporal courses, atrial standstill has been classified as partial or total and as intermittent or permanent.3,4 Digitalis glycosides or quinidine intoxication,
hyperkalaemia, hypoxia, or myocardial infarction may temporarily cause atrial standstill.5 – 7 Permanent atrial standstill is characterized by severe morphological changes with fibrosis and cell death,8 and may be accompanied by reduced expression of atrial natriuretic peptide, especially in its permanent form.9 The latter is often found not only after valve replacement or in combination with organic heart disease but also in patients with systemic muscular disease. In some patients, atrial standstill is observed after longstanding atrial fibrillation.10 Of note, substantial left atrial fibrosis can be found during electrogram mapping in patients undergoing left atrial ablation of atrial fibrillation. Recently, magnetic resonance imaging has also
* Corresponding author. Tel: +49 30 8445 2231; fax: +49 30 8445 77 2231, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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Barbara Bellmann 1,2*, Mattias Roser 1, Bogdan Muntean 1, Verena Tscholl 1, Patrick Nagel 1, Michael Schmid 2, and Patrick Schauerte 2,3
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What’s New? † Electroanatomical mapping of the right atrium may identify surviving right atrial sites amenable for permanent atrial stimulation in patients with atrial standstill. † Sick sinus syndrome and atrial standstill may share a common underlying pathology of fibrosis. † This report describes how an underlying fibrotic process affects the sinus node and the right atrium thus raising the hypothesis that sinus node disease may be at least partially due to a systemic fibrotic process of the atria.
Methods From 1996 to 2012, right atrial standstill was suspected in four of 1200 consecutive patients undergoing dual chamber pacemaker implantation, due to the lack of a discrete local atrial electrogram at typical right atrial lead implantation sites (right atrial appendage, right atrial lateral wall) combined with the inability to pace the atria from these sites. The first pacemaker implantation took much longer as a standard dual chamber pacemaker operation. The time
Results The mean age was 60 + 17 years. One of the four patients was female. All patients suffered from arterial hypertension and two of them from diabetes mellitus type II. All baseline data are shown in Table 1.
Table 1 Baseline data Patient 1
Patient 2
Patient 3
Patient 4
Male
+
+
2
+
Female Age (years)
2 65
2 36
+ 64
2 76
...............................................................................................................................................................................
Coronary heart disease
2
+
2
2
LV EF (%) Atrial fibrillation
40 +
50 +
64 2
60 2
Arterial hypertension
+
+
+
+
Aortic stenosis Diabetes mellitus type II
+ 2
2 2
2 2
2 +
Hypercholesterolaemia
+
2
+
+
Nicotin abuse Positive family history
+ +
+ +
2 +
+ +
Left atrium dimension (cm2)
Enlarged No quantification
39
34
42
Right atrium dimension (cm2)
Enlarged No quantification
37
34
40
RVSD (mmHg)
52 + ZVD
30 + ZVD
28 + ZVD
49 + ZVD
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revealed large atrial scar areas possibly as a consequence of atrial fibrillation.11 We report about a series of cases with symptomatic sinus node disease, in which right atrial pacemaker lead implantation failed owing to the inability to capture right atrial tissue at conventional right atrial sites. We suspected that partial right atrial standstill might be present and hypothesized that mapping of the atria, with subsequent identification of myocardium still amenable to atrial pacing would allow dual chamber pacemaker implantation with sequential atrioventricular (AV) electrical and mechanical activation.
of procedure was 82 –124 min before a VVI-pacemaker was implanted. To establish the diagnosis of sinus node disease, the following criteria and tests were performed: resting electrocardiogram, Holter ECG, or continuous ECG monitoring to evaluate the dynamics of spontaneous heart rate, exercise stress testing unless patients were unable to perform treadmill testing. During electrophysiological studies: mapping of the right atrium and sinus node recovery time in patients with spontaneous atrial electrical activity and particularly sinus node area for spontaneous atrial activity an the absence of atrial fibrillatory wavelets were perfomed. In these patients, subsequent conventional (n ¼ 4) and electroanatomical (n ¼ 3) mapping of the right atrium was performed. The electrophysiological study was scheduled in the mean 5 (+3) days later after VVI-pacemaker implantation. No patient left the hospital in the time between VVIpacemaker implantation and the mapping of the right atrium. For the atrial mapping, we used an electrophysiological recording system (Pulmocard) and deflectable electrode catheter (TORQR, 5 French, Medtronic). In three patients, an additional mapping system (CARTO XP Navigation System, Biosense) was utilized. The target values during mapping were a sensing .1 mV and pacing thresholds ,2 V/0.5 ms. During electroanatomical mapping the threshold for scar tissue was set to local voltages ,0.5 mV indicating the presence of scar tissue. The second criterion for scar tissue was the inability of atrial myocardial electrical capture at that site during pacing attempts with an output of 6 V. After successful dual chamber implantation a follow-up for a minimum of 12 months was realized.
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Atrial standstill due to extensive atrial fibrosis
Complete right atrial standstill with preserved but impaired sinus node function
Table 2 Diagnosis of sinus node disease Patient 1
Patient 2
Patient 3
Patient 4
Slow regular rhythm with wide QRS complexes, no visible P-waves or atrial fibrillatory waves in surface ECG. Lack of increase of heart rate during Holter or continuous telemetric ECG recording.
+
+
+
+
+
+
+
+
Treadmill stress testing revealed chronotropic incompetence.
n.d.
+
+
+
No spontaneous atrial activity in the right atrium or sinus node area during EP-mapping and testing.
+
+
+
+
...............................................................................................................................................................................
Figure 1 Constant heart frequency and loss of P-waves in the Holter monitor.
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In 1996, a 65-year-old man was admitted to the hospital with signs of severe right and left heart failure. He had diabetes mellitus type II since 1988, while paroxysmal atrial fibrillation occurred since 1992. On admission, the 12-channel-electrocardiogram (ECG) showed a regular rhythm of 46 beats per minute (bmp) with narrow QRS complexes but lack of visible atrial fibrillatory waves or P-waves (Table 2). Holter monitoring revealed a constant heart rate 50 bpm (Figure 1). The patient was on angiotensin-converting enzymeinhibitor (ACE-inhibitor), diuretics and digoxin, with digoxin levels being in the normal range (1.2 mg/ml). Echocardiography revealed severe aortic stenosis with a mean gradient of 42 mmHg (calculated aortic valve orifice area of 0.7 cm2). Left ventricular ejection fraction was moderately reduced (ejection fraction 40%). Doppler measurement of the mitral and tricuspid valves did not show A-waves. Bradyarrhythmia during atrial fibrillation was suspected but due to the lack of fibrillatory waves in the surface ECG an electrophysiological study was scheduled after
short-term discontinuation of digoxin (48 h). Catheter mapping of the right atrium was performed with a deflectable electrode catheter (Torqr, 5 French, Medtronic) using an electrophysiological recording system (Pulmocard, filter 50 Hz, gain 8). At any right atrial site including the ostium of coronary sinus, discrete atrial electrograms or fibrillatory activity could be recorded. Likewise, pacing at a cycle length of 500 ms with increasing output up to 28 mA did not result in atrial capture at any of these sites. Only at a discrete area at the anterolateral high right atrium, spontaneous atrial activity at a cycle length of 1200 ms was identified. Pacing at a cycle length of 1100 ms resulted in local atrial capture, which was not conducted to the rest of the atria. This was confirmed by mapping of the right atrium with a second electrode catheter (bipolar 5 mm spaced mapping catheter: EP.XT, Bard) and by a lack of discernible surface ECG P-waves. In addition, the ventricular rate did not change during pacing at this site, which was taken as evidence for a lack of atrial conduction to the AV node. Owing to the location of this area and the spontaneous low rate depolarization, sinus node activity was suspected. In order to evaluate spontaneous recovery after overdrive suppression, the sinus node recovery time was determined at twice the local capture threshold revealing a maximal corrected recovery time of 1530 ms.
Page 4 of 8 A rate adaptive permanent right ventricular pacemaker was implanted and programmed at a lower rate limit of 60 bpm. An aortic valve replacement was not performed because of recurrent epistaxis, requiring recurrent blood transfusions and a logistic EuroSCORE II of 21.20%. During 6 years of follow-up until the patient’s death, the percentage of right ventricular pacing was 100%. Routine testing for spontaneous electrical activity during follow-up in the pacemaker clinic revealed a junctional escape rhythm with narrow QRS complexes at a rate of 30–35 bpm but no P-waves or fibrillatory waves in the surface ECG.
A 36-year-old male patient complained about dizziness in 2009. Surface ECG on admission showed a narrow QRS rhythm of 43 bmp, but without discernible P-waves prompting the diagnosis of a junctional escape rhythm (Table 2). There was a history of coronary heart disease with previous ST elevation myocardial infarction in 2007 and subsequent percutaneous coronary intervention of the right coronary artery which was patent during a control catheterization in 2008. The patient suffered from paroxysmal atrial fibrillation since 2007. The patient was on therapy with an ACE-inhibitor, a statin (simvastatin) and aspirin. Betablocker therapy was stopped in 2008 because of bradycardia and chronotropic incompetence. Treadmill stress testing revealed chronotropic incompetence; the heart frequency did not increased adequately (fixed heart rate at 45 bpm). Pulmonary function test showed normal results. Systolic left ventricular function was slightly reduced with an ejection fraction of 50% and no A-waves could be detected during Doppler echocardiography of the mitral and tricuspid valve. Because of the junctional escape rhythm and suspected sinus node arrest, the patient underwent dual pacemaker implantation. During the initial implant procedure, no atrial capture and no atrial sensing was obtained at several typical sites for right atrial lead implantation (RAA, high and lateral right atrium). Thus, atrial lead implantation was deferred and a single chamber pacemaker was implanted. Because of the young age of the patient, the case underwent internal discussion and these findings triggered a differential diagnosis of right atrial standstill. A subsequent electrophysiological examination was scheduled to confirm this diagnosis and eventually identify surviving right atrial sites at which atrial pacing could still be achieved. During intracardiac mapping with an electroanatomical mapping system (Biosense Webster CARTO XP), an isolated regular electrical activity in the sinus node area at the high right atrium with a cycle length of 1600 ms was detected. Owing to the atrial fibrosis the excitation of the sinus node was limited to the region of the high right atrium. The rest of the atrium was excited retrograde by the junctional escape beats, at a faster cycle length of 1000 ms. Voltage mapping showed extensive scarring of the lateral right atrium with preserved voltage levels only at the septal right atrium. At this site, atrial pacing with a threshold of 1 V/0.4 ms resulted in atrial capture and subsequent 1 : 1 AV conduction. Incremental pacing revealed an antegrade Wenckebach point at a cycle length of 600 ms. Sensing was 2.0 V.
In a second operation, the atrial lead was implanted at the previously identified septal right atrium with a pacing threshold of 1 V/0.4 ms. Sensing was 1.5 V. Pacing from this site yielded visible electrical atrial activity as judged by the presence of P-waves in surface ECGs and also mechanical atrial activity as reflected by A-waves across the tricuspid and mitral valve during Doppler echocardiography. During the 3 years of follow-up, atrial pacing thresholds remained stable and there were preserved P-waves in the surface ECG and A-waves across both AV valves. The atrial and right ventricular pacing percentage was 91.6% at a programmed AV delay of 280 ms and a lower rate limit of 60 bmp (Table 3).
Partial right atrial standstill In 2011, a 64 year-old women was admitted because of symptomatic bradycardia. The ECG revealed a regular rhythm at 19 bmp with narrow QRS complexes and no obvious P-waves (Table 2). Echocardiography showed normal systolic left ventricular function (64%). A-waves were absent during Doppler examination of the mitral and tricuspid valve. The atria were enlarged (right atrium: 34 cm2, left atrium: 34 cm2). There was a history of arterial hypertension and hypercholesterolaemia, treated with an ACE-inhibitor and simvastatin. Cardiac stress magnetic resonance imaging (MRI) and laboratory findings were normal. Treadmill testing showed chronotropic incompetence (fixed heart rate at 42 bpm). Pulmonary function test delivered good results. Sinus node arrest was suspected and the patient was scheduled for dual chamber pacemaker implantation. Meanwhile, a temporary pacemaker was provided due to intermittent haemodynamic instability. Magnetic resonance imaging and echocardiography were realized before the temporary pacemaker was placed. During pacemaker implantation, atrial lead implantation failed due to insufficient atrial sensing (,1 mV) and the inability to pace the right atrium from high and lateral right atrial sites even at high output (6 V/1.5 ms). Thus, a permanent right ventricular pacing lead was implanted and connected with a dual chamber pacemaker and the patient was referred for a subsequent electrophysiological study for suspected right atrial standstill.
Table 3 Follow-up after 12 months Case 1
Case 2
Case 3
Case 4
60/bpm VVI
60/bpm DDD
60/bpm DDD
60/bpm DDD
Atrial sensing
–
3.5 mV
2.2 mV
5.4 mV
Ventricular sensing Atrial pacing threshold
9.8 mV –
11.4 mV 1.0 V/ 0.4 ms
5.4 mV 0.6 V/ 0.4 ms
12.8 mV 0.5 V/ 0.4 ms
Ventricular pacing threshold
0.5 V/ 0.4 ms
0.5 V/ 0.4 ms
1.5 V/ 0.4 ms
0.75 V/ 0.4 ms
Mode switch Atrial pacing fraction Ventricular pacing fraction
– –
34% 95%
0% 100%
0% 81%
100%
10%
4%
18.5%
................................................................................ Lower rate limit Mode
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Partial right atrial standstill with sinus node arrest and impaired atrioventricular conduction
B. Bellmann et al.
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Atrial standstill due to extensive atrial fibrosis
Figure 2 (A) 3D-Map in LAO. (B) 3D-Map (CARTO) in LAO 308. The red area demonstrates scar. (C) 3D-Map (CARTO) of the posterior atrium. (D) Post-operative X-ray. The atrial lead is placed at the posterior wall of the right atrium. At this place atrial stimulation was possible. SVC, Superior vena cava; IVC, inferior vena cava; CS, coronary sinus; MV: mitral annulus.
Electroanatomical mapping with an electroanatomical mapping system (Biosense Webster CARTO 3) of the right atrium confirmed the diagnosis of a partial atrial standstill. There were no waves of atrial fibrillation. A small band of tissuewith preserved voltagewas found at the posterior wall of the right atrium which extended to the AV node (Figure 2). Probatory pacing from this area was possible at 1.5 V/0.4 ms. The antegrade Wenckebach cycle length was 500 ms. In a second implantation procedure a permanent atrial lead was placed at the septal right atrium. Intraoperative testing yielded a sensing of 2.1 mV and a pacing threshold of 0.6 V/ 0.4 ms. During pacing P-waves were present in surface in the ECG and discrete A-waves were detected across the mitral and tricuspid valve during Doppler echocardiography (Figure 3). Before atrial lead implantation, the percentage of right ventricular pacing was 100% but decreased to 1% after dual chamber pacemaker implantation. Stable sensing and pacing threshold values were obtained during a 12 months follow-up.
Partial right atrial standstill and sinus node arrest In January 2012, a 76-year-old man was admitted because of recurrent syncopes; 12-lead ECG showed a slow regular rhythm with wide QRS complexes, no visible P-waves or atrial fibrillatory waves in surface ECG spontaneous rate 42 bpm (Table 2). P-waves
were missed. The patient was on ACE-inhibitor and diuretics for treatment of arterial hypertension and on metformin because of diabetes mellitus type II. Underlying coronary artery disease was excluded by coronary angiogram. Echocardiography showed normal systolic left ventricular function (60%). A treadmill stress test showed chronotropic incompetence (fixed heart rate at 46 bpm). Pulmonary function test delivered physiological results. Dual chamber pacemaker implantation was attempted but atrial lead positioning failed due to insufficient sensing (,1 mV) and/or pacing (threshold .5 V/1.5 ms) at several high right atrial sites including the RAA and at the free wall of the right atrium lateral sites during pacing from coronary sinus (Figure 4). A dual chamber pacemaker connected to a right ventricular lead was implanted at the high right ventricular septum and the patient underwent an electrophysiological study subsequently. Electroanatomical mapping of the right atrium showed ubiquitous atrial low voltage with sensing values , 0.9 mV with a cut of 0.5 mV to define scar (Figure 4). A circumscriptive area of 2 cm at the ostium of the coronary sinus was the single right atrial site at which a sensing of 2.5 mV and a pacing capture threshold of 1.3 V /0.4 ms were obtained. No isolated sinus node activity was detected at higher or lateral atrial sites. In a second operation, the atrial lead was positioned at this site with reasonable sensing (2.6 mV) and a pacing values with a threshold of 1.2 V/0.4 ms. Thereafter, during atrial stimulation P-waves could be documented in the surface ECG and A-waves were visible across the AV valves during Doppler echocardiography. During 12-month followup, the right ventricular pacing percentage was 23% while the atria were paced at 99% at a programmed lower rate limit of 60 bpm (Table 4).
Long-term follow-up (n 5 4) The mean follow-up was 3.5 years. In the follow-up period all measured data were stable (Table 3). The first patient died after 6 years. During 6 years follow-up there were no changes in the measurements. The percentage of right ventricular pacing was 100%. All other patients are still well. The right ventricular pacing rate is still
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Figure 3 Echocardiogram after atrial lead implantation and atrial stimulation with A- and E-waves.
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Table 4 Results before and directly after dual chamber pacemaker implantation and coding of the dual chamber pacemakers Lower rate limit pacemaker
Right ventricular pacing fraction (single chamber)
AV delay
Atrial/right ventricular pacing fraction (dual chamber)
PR interval under atrial stimulation
Stimulation frequency
No atrial lead 300 ms
No atrial lead 92%/92%
Not measurable 280 ms
– 60 bmp
............................................................................................................................................................................... Case 1 Case 2
60 bmp 60 bmp
100% 93%
Case 3
60 bmp
100%
250 ms
100%/1%
190 ms
60 bmp
Case 4
60 bmp
80%
250 ms
99%/23%
170 ms
60 bmp
low (,20%). There were no dislocations of leads. Programmed mode switch at all patients is an atrial rate of 171 bpm. Only one patient showed paroxysmal atrial fibrillation. Under treatment with amiodarone the burden of atrial fibrillation was 15%.
Discussion Clinically, atrial standstill is difficult to differentiate from sinus arrest as both may be characterized by irregular slow escape rhythm in the surface ECG, loss of P-waves and absent fibrillatory atrial waves. In cases of sinus node arrest and (regular) escape rhythm partial atrial standstill must be suspected prior to pacemaker implant in order to raise the physician’s awareness of this disease entity. This could lead the implanting cardiologist to attempt alternative and less common atrial lead implantation sites in order to achieve synchronous AV pacing. If this does not succeed a second procedure guided by prior electroanatomical mapping of the atria might be considered. This report describes how an underlying fibrotic process affects the sinus node and the right atrium, thus raising the hypothesis that sinus node disease may be at least partially due to a systemic fibrotic process of the atria. There are few reports on the pathophysiology of atrial standstill. Fibroelastosis and fatty infiltration of the atrial wall has been described.12 In patients with atrial standstill pacemaker implantation may be required because of symptomatic, permanent bradycardia.13 In many of these patients, single chamber stimulation is chosen for
therapy due to the lack of atrial capture.14 In this report, we provide electrophysiological evidence that right atrial standstill may be extensive involving the sinus node, but also the AV node: In two out of four cases, preserved but impaired sinus node activity was observed while sinus node arrest was found in two patients. In patients with preserved sinus node activity, nodal activity was abnormal with either markedly prolonged cycle length or prolonged sinus node recovery time. In both cases, the sinus node activity was not conducted to the atria as documented by a lack of P-waves in surface ECG, mapping of the right atrium or lack of A-waves during Doppler echocardiography of both AV valves. In addition, AV conduction was impaired in one patient. Of note, in two patients there was a history of previous atrial fibrillation. In fact, patchy atrial scarring may lead to anatomical obstacle delaying or blocking atrial electrical activation and increase anisotropy of the atria. This may promote re-entrant circuits facilitating the development of atrial tachycardia and atrial fibrillation. It is important to mention that, scarring of the atrial wall has been described in patients undergoing atrial fibrillation ablation.11 So far, it is not clear, whether atrial fibrillation is the cause, or in part, consequence of atrial fibrosis. There is experimental evidence that atrial fibrosis may be secondary to atrial fibrillation due to rapid cellular activation and apoptosis.15 The current report raises the opportunity to believe that atrial fibrosis per itself may be a factor, which affects atrial electrophysiology and the function of the sinus and AV node and not just
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Figure 4 (A) 3D-MAP (CARTO) in LAO. The low lateral right atrium is the target region for the atrial lead. The red area demonstrates scar. (B) 3D-Map (CARTO) of the right lateral atrium. (C) 3D-Map (CARTO) of the left lateral atrium. (D) Post-operative fluoroscpoy. High septal ventricular lead and right atrial lead in low lateral right atrium (LAO).
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Atrial standstill due to extensive atrial fibrosis
be achieved allowing at least partial atrial mechanical contribution to diastolic ventricular filling. However, although atrial contraction was present after dual chamber pacemaker implantation as demonstrated by the presence of A-waves during Doppler echocardiography, full atrial contractility may still have been impaired due to the underlying atrial fibrosis.
Limitations and unresolved issues This study is descriptive and comprises a low number of patients. In one patient, digoxin was only discontinued 48 h prior to pacemaker implantation. In fact, a functional effect of digoxin on sinus node function might have been present. Likewise, digoxin (even being within normal plasma levels) might have contributed to electrical standstill. Nevertheless, the detailed findings provide novel insights into atrial and sinus node pathology and thus is hypothesis generating. We do not know the long-term stability of atrial pacing at the surviving atrial islets. As atrial fibrosis is a progressive disease, loss of capture at the pacing sites may occur in long term. The mean follow-up of this study (3.5 years) and the low number of patients does not allow clarifying this issue. Mapping was restricted to the right atrium. Thus, we do not know the extent of atrial standstill in the left atrium. However, the presence of A-waves across the mitral valves after atrial lead implantation provides some evidence for a presence of viable left atrial tissue. Likewise in one patient, right atrial electroanatomical mapping was performed during pacing from the coronary sinus, which indicates surviving left atrial tissue. It remains unclear whether partial atrial standstill or fibrosis is more common in patients with sinus node disease as currently suspected. Possibly, the underlying atrial pathology is simply not recognized due to sufficient pacing thresholds during atrial lead implantation, which is typically implanted in the more muscular right atrial appendage.
Conclusion In patients with suspected symptomatic sick sinus syndrome and regular escape rhythms partial right atrial standstill may be present, especially if enlarged atria are present during echocardiography thus preventing successful right atrial lead implantation. Recognition of this prior to pacemaker implantation might guide the implanting physician to search more extensively for alternative right atrial pacing sites during the operation. In selected patients electroanatomical mapping of the right atrium prior to pacemaker implantation may identify surviving right atrial sites amenable for permanent synchronous AV stimulation. Sick sinus syndrome and atrial standstill may share a common pathology. Conflict of interest: none declared.
References 1. Wooliscroft J, Tuna N. Permanent atrial standstill: the clinical spectrum. Am J Cardiol 1982;49:2037 – 41. 2. Cushny A. Optical isomerism, and the mechanism of drug action. J Hist Biol 1975;8: 145 –65. 3. Rodrı´guez Reyes H, Cruz Cruz F, Iturralde Torres P, de Micheli A, Gonza´lez Hermosillo JA. Persistent atrial paralysis: reported of 2 cases. Arch Inst Cardiol Mex 1997;67:498 –502. 4. Nakamoto K. Relation between the duration of pancardiacasystole and the postasystolic atrial cycle and the effects of orciprenaline on the atrioventricular
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secondary to systolic heart failure or valvular heart disease (except Patient 1 with aortic stenosis). The presence of pulmonary hypertension in two patients and upper normal values in the other two patients raise the opportunity that pulmonary hypertension partially contributed to right atrial fibrosis and standstill. One might argue that the number of such cases is low as only four patients were identified in a higher volume centre (1200 dual chamber pacemakers between 1996 and 2012). However, it seems very likely that in many instances of atrial scarring and partial standstill atrial fibrillation develops due to anisotropic conduction thus masking the underlying atrial pathology and its potential impact on sinus and AV nodal function. In fact, two patients in this report had a history of previous atrial fibrillation. The findings of the four cases presented herein demonstrate that preoperative recognition of signs of potential atrial standstill like regular slow escape rhythm, lack of atrial fibrillatory waves might drive a change in procedural approach in these patients. This could include the information of the implanting physician of potentially present partial atrial standstill thus leading to more detailed search for alternative pacing sites. In patients with enlarged atria, indicative for atriale fibrosis, an electrophysiological mapping study might be considered prior to pacemaker implantation to confirm the diagnosis of partial atrial standstill and to identify potential implantation sites to decrease the possibility of a second implantation procedure. The inability to pace the atria from standard atrial sites during pacemaker implantation then led to the recognition of atrial standstill which could be confirmed by subsequent electrophysiological studies. These mapping studies also revealed that fibrosis involved the sinus and AV nodal area as a progressive disease. The patients in this report offered the unique opportunity to study sinus and AV nodal function during partial or complete right atrial standstill, thus unrevealing the involvement of both nodes in advanced stages of this disease. This is additional evidence that sinus node disease may not always be a primary disease entity, but secondary to changes of the surrounding atrial tissue.16 In fact, it has for long been recognized, that atrial fibrillation may occur secondary to sick sinus syndrome possibly due to atrial dilatation and increased atrial pressure, which may facilitate the development of atrial fibrillation. However, pacemaker implantation does only partially reduce the likelihood for atrial fibrillation.17 In view of the findings of this study, the hypothesis may be raised that atrial fibrillation develops in part as consequence of a more diffuse atrial disease involving the sinus node, rather than being linked solely to sinus nodal dysfunction. Atrial fibrosis is a typical age related process in otherwise healthy men. Of note, above the age of 55 years fibrosis increases by 1% per year in normal man.18 Besides the fact that the patients of this study were of advanced age, all of them had a history of arterial hypertension and 50% were diabetic, both conditions known to promote cardiac fibrosis.19 This may have considerably contributed to the extent of fibrosis observed during the mapping studies. How do we cope with bradycardia secondary to atrial standstill? This report describes how mapping of the atria allows to identify surviving areas of the right atrium at which pacing with AV conduction can successfully re-establish synchronous AV conduction. It confirms reports of Arimoto et al. 20 and extends them by providing long-term follow-up data. This approach is advantageous as right ventricular apical pacing with left branch bundle block morphology may be avoided (Table 2). Furthermore, AV synchronous conduction can
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11.
13. Park SR, Kwak CH, Kang YR, Seo MK, Kang MK, Cho JH et al. Implantable cardioverter-defibrillator implantation in a patient with atrial standstill. Yonsei Med J 2009;50:156–9. 14. Yaminisharif J, Moezzi A. Atrial standstill: a rare case. J. Teheran Heart Center 2011;6: 152 –4. 15. De Jong AM, Maass AH, Oberdorf-Maass SU, De Boer RA, Van Gilst WH, Van Gelder IC. Cyclical stretch induces structural changes in atrial myocytes. J Cell Mol Med 2013;17:743 –53. 16. Kottkamp H. Human atrial fibrillation substrate: towards a specific fibrotic atrial cardiomyopathy. Eur Heart J 2013;34:2731 –8. 17. Silva R, Pereira T, Martins V. Effectiveness of atrial antitachycardia pacing in the treatment of paroxysmal atrial fibrillation in patients with pacemakers. Rev Port Cardiol 2014;33:781 –8. 18. Verheule S, Tuyls E, van Hunnik A, Kuiper M, Schotten U, Allessie M. Fibrillatory conduction in the atrial free walls of goats in persistent and permanent atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:590 –9. 19. Dewire J, Khurram IM, Pashakhanloo F, Spragg D, Marine JE, Berger RD et al. The association of pre-existing left atrial fibrosis with clinical variables in patients referred for catheter ablation of atrial fibrillation. Clin Med Insights Cardiol 2014;19:25 –30. 20. Arimotoa T, Sukekawa H, Takayama S, Ikeno E, Takeishi Y, Kubota I. Electroanatomical mapping in partial atrial standstill for visualization of atrial viability and a suitable pacing site. Pacing Clin Electrophysiol 2008;31:509 –12.
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12.
conduction in a patient with 2: 1 A-V block and intermittent cardiac standstill. Jpn Circ J 1969;33:823 –32. Wolff L, White PD. Auricular fibrillation. Results of seven year’s experience with quinidine sulphate therapy (1921 –1928). Arch Intern Med 1928;43:653. Surawicz B. Electrolytes and the electrocardiogram. Am J Cardiol 1963;12:656. James TN. Myocardial infarction and atrial arrhythmias. Circulation 1961;24:761. Chavez I, Brumlik J, Sodi-Pallares D. Sobre un caso de paralisis auricular permenente con degeneracion del nodulo de Keith Flack. Arch Inst Cardiol Mex 1946; 16:159 – 81. Seino Y, Shimai S, Ibuki C, Itoh K, Takano T, Hayakawa F. Distubed secretion of atrial natriuretic peptide in patients with persistent atrial standstill: endocrinologic silence. J Am Coll Cardiol 1991;18:459 –63. Tu¨rkog˘lu C, Aliyev F, Celiker C, Fıratlı I. Permanent atrial standstill with irregular junctional ectopic rhythm mimicking atrial fibrillation. Turk. Kardiyol Dern Ars 2011; 39:55 –8. Higuchi K, Akkaya M, Akoum N, Marrouche NF. Cardiac MRI assessment of atrial fibrosis in atrial fibrillation: implications for diagnosis and therapy. Heart 2013; 100:590–6. Rosen KM, Rahimtoola SH, Gunnar RM, Lev M. Transient and persistent atrial standstill with His bundle lesions. Electrophysiologic and pathologic correlations. Circulation 1971;44:220–36.
B. Bellmann et al.
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv098
Atrial standstill in sinus node disease due to extensive atrial fibrosis: impact on dual chamber pacemaker implantation 1 Department of Cardiology, Charite´ Berlin Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; 2Department of Cardiology, University Hospital, Technical University Aachen RWTH, Pauwelstrasse 30, 52074 Aachen, Germany; and 3Kardiologie an der Rudower Chaussee, Rudower Chausee 9, 12489 Berlin, Germany
Received 19 January 2015; accepted after revision 17 March 2015
Aims
Atrial standstill is characterized by the absence of atrial activity. We report about a series of cases, in which conventional atrial pacemaker lead implantation in patients with symptomatic sinus node disease failed due to lack of excitable right atrial tissue, thus, prompting the diagnosis of atrial standstill. We hypothesized that mapping of the atria with subsequent identification of myocardium still amenable to atrial pacing would allow dual chamber pacemaker implantation. ..................................................................................................................................................................................... Methods and In four patients, atrial lead implantation failed. In these patients, spontaneous or fibrillatory electrical activity was absent but the atria could not be captured despite high stimulation voltages at conventional atrial sites. We suspected partial or results complete atrial standstill and subsequently confirmed this hypothesis by conventional (n ¼ 1) or electroanatomical mapping (n ¼ 3). Areas of fibrotic tissue were present in all patients as identified by lack of spontaneous electrical activity and inability of local electrical capture via the mapping catheter. Surviving atrial tissue, which could be electrically captured with subsequent conduction of activity to the atrioventricular (AV) node, was present in three patients. Successful targeted atrial lead implantation at these sites was achieved in all these patients. Isolated sinus node activity without conduction to the atria was found in one patient. ..................................................................................................................................................................................... Conclusion Partial atrial standstill may be present and prevent atrial lead implantation in patients with sinus node disease. In these patients, recognition of partial atrial standstill and identification of surviving muscular islets with connection to the AV node by mapping studies may still allow synchronous AV sequential pacing.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial standstill † Sinus node † Pacemaker † Atrial mapping
Introduction Atrial standstill is a condition characterized by the absence of electrical and mechanical atrial activity1 and was first described by Cushny.2 Atrial standstill may not be recognized as such because differentiation from bradyarrhythmia due to sick sinus syndrome or permanent atrial fibrillation with low amplitude or lack of fibrillatory waves in surface electrogram recordings is sometimes difficult. Depending on the spatial distribution and temporal courses, atrial standstill has been classified as partial or total and as intermittent or permanent.3,4 Digitalis glycosides or quinidine intoxication,
hyperkalaemia, hypoxia, or myocardial infarction may temporarily cause atrial standstill.5 – 7 Permanent atrial standstill is characterized by severe morphological changes with fibrosis and cell death,8 and may be accompanied by reduced expression of atrial natriuretic peptide, especially in its permanent form.9 The latter is often found not only after valve replacement or in combination with organic heart disease but also in patients with systemic muscular disease. In some patients, atrial standstill is observed after longstanding atrial fibrillation.10 Of note, substantial left atrial fibrosis can be found during electrogram mapping in patients undergoing left atrial ablation of atrial fibrillation. Recently, magnetic resonance imaging has also
* Corresponding author. Tel: +49 30 8445 2231; fax: +49 30 8445 77 2231, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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Barbara Bellmann 1,2*, Mattias Roser 1, Bogdan Muntean 1, Verena Tscholl 1, Patrick Nagel 1, Michael Schmid 2, and Patrick Schauerte 2,3
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What’s New? † Electroanatomical mapping of the right atrium may identify surviving right atrial sites amenable for permanent atrial stimulation in patients with atrial standstill. † Sick sinus syndrome and atrial standstill may share a common underlying pathology of fibrosis. † This report describes how an underlying fibrotic process affects the sinus node and the right atrium thus raising the hypothesis that sinus node disease may be at least partially due to a systemic fibrotic process of the atria.
Methods From 1996 to 2012, right atrial standstill was suspected in four of 1200 consecutive patients undergoing dual chamber pacemaker implantation, due to the lack of a discrete local atrial electrogram at typical right atrial lead implantation sites (right atrial appendage, right atrial lateral wall) combined with the inability to pace the atria from these sites. The first pacemaker implantation took much longer as a standard dual chamber pacemaker operation. The time
Results The mean age was 60 + 17 years. One of the four patients was female. All patients suffered from arterial hypertension and two of them from diabetes mellitus type II. All baseline data are shown in Table 1.
Table 1 Baseline data Patient 1
Patient 2
Patient 3
Patient 4
Male
+
+
2
+
Female Age (years)
2 65
2 36
+ 64
2 76
...............................................................................................................................................................................
Coronary heart disease
2
+
2
2
LV EF (%) Atrial fibrillation
40 +
50 +
64 2
60 2
Arterial hypertension
+
+
+
+
Aortic stenosis Diabetes mellitus type II
+ 2
2 2
2 2
2 +
Hypercholesterolaemia
+
2
+
+
Nicotin abuse Positive family history
+ +
+ +
2 +
+ +
Left atrium dimension (cm2)
Enlarged No quantification
39
34
42
Right atrium dimension (cm2)
Enlarged No quantification
37
34
40
RVSD (mmHg)
52 + ZVD
30 + ZVD
28 + ZVD
49 + ZVD
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revealed large atrial scar areas possibly as a consequence of atrial fibrillation.11 We report about a series of cases with symptomatic sinus node disease, in which right atrial pacemaker lead implantation failed owing to the inability to capture right atrial tissue at conventional right atrial sites. We suspected that partial right atrial standstill might be present and hypothesized that mapping of the atria, with subsequent identification of myocardium still amenable to atrial pacing would allow dual chamber pacemaker implantation with sequential atrioventricular (AV) electrical and mechanical activation.
of procedure was 82 –124 min before a VVI-pacemaker was implanted. To establish the diagnosis of sinus node disease, the following criteria and tests were performed: resting electrocardiogram, Holter ECG, or continuous ECG monitoring to evaluate the dynamics of spontaneous heart rate, exercise stress testing unless patients were unable to perform treadmill testing. During electrophysiological studies: mapping of the right atrium and sinus node recovery time in patients with spontaneous atrial electrical activity and particularly sinus node area for spontaneous atrial activity an the absence of atrial fibrillatory wavelets were perfomed. In these patients, subsequent conventional (n ¼ 4) and electroanatomical (n ¼ 3) mapping of the right atrium was performed. The electrophysiological study was scheduled in the mean 5 (+3) days later after VVI-pacemaker implantation. No patient left the hospital in the time between VVIpacemaker implantation and the mapping of the right atrium. For the atrial mapping, we used an electrophysiological recording system (Pulmocard) and deflectable electrode catheter (TORQR, 5 French, Medtronic). In three patients, an additional mapping system (CARTO XP Navigation System, Biosense) was utilized. The target values during mapping were a sensing .1 mV and pacing thresholds ,2 V/0.5 ms. During electroanatomical mapping the threshold for scar tissue was set to local voltages ,0.5 mV indicating the presence of scar tissue. The second criterion for scar tissue was the inability of atrial myocardial electrical capture at that site during pacing attempts with an output of 6 V. After successful dual chamber implantation a follow-up for a minimum of 12 months was realized.
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Atrial standstill due to extensive atrial fibrosis
Complete right atrial standstill with preserved but impaired sinus node function
Table 2 Diagnosis of sinus node disease Patient 1
Patient 2
Patient 3
Patient 4
Slow regular rhythm with wide QRS complexes, no visible P-waves or atrial fibrillatory waves in surface ECG. Lack of increase of heart rate during Holter or continuous telemetric ECG recording.
+
+
+
+
+
+
+
+
Treadmill stress testing revealed chronotropic incompetence.
n.d.
+
+
+
No spontaneous atrial activity in the right atrium or sinus node area during EP-mapping and testing.
+
+
+
+
...............................................................................................................................................................................
Figure 1 Constant heart frequency and loss of P-waves in the Holter monitor.
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In 1996, a 65-year-old man was admitted to the hospital with signs of severe right and left heart failure. He had diabetes mellitus type II since 1988, while paroxysmal atrial fibrillation occurred since 1992. On admission, the 12-channel-electrocardiogram (ECG) showed a regular rhythm of 46 beats per minute (bmp) with narrow QRS complexes but lack of visible atrial fibrillatory waves or P-waves (Table 2). Holter monitoring revealed a constant heart rate 50 bpm (Figure 1). The patient was on angiotensin-converting enzymeinhibitor (ACE-inhibitor), diuretics and digoxin, with digoxin levels being in the normal range (1.2 mg/ml). Echocardiography revealed severe aortic stenosis with a mean gradient of 42 mmHg (calculated aortic valve orifice area of 0.7 cm2). Left ventricular ejection fraction was moderately reduced (ejection fraction 40%). Doppler measurement of the mitral and tricuspid valves did not show A-waves. Bradyarrhythmia during atrial fibrillation was suspected but due to the lack of fibrillatory waves in the surface ECG an electrophysiological study was scheduled after
short-term discontinuation of digoxin (48 h). Catheter mapping of the right atrium was performed with a deflectable electrode catheter (Torqr, 5 French, Medtronic) using an electrophysiological recording system (Pulmocard, filter 50 Hz, gain 8). At any right atrial site including the ostium of coronary sinus, discrete atrial electrograms or fibrillatory activity could be recorded. Likewise, pacing at a cycle length of 500 ms with increasing output up to 28 mA did not result in atrial capture at any of these sites. Only at a discrete area at the anterolateral high right atrium, spontaneous atrial activity at a cycle length of 1200 ms was identified. Pacing at a cycle length of 1100 ms resulted in local atrial capture, which was not conducted to the rest of the atria. This was confirmed by mapping of the right atrium with a second electrode catheter (bipolar 5 mm spaced mapping catheter: EP.XT, Bard) and by a lack of discernible surface ECG P-waves. In addition, the ventricular rate did not change during pacing at this site, which was taken as evidence for a lack of atrial conduction to the AV node. Owing to the location of this area and the spontaneous low rate depolarization, sinus node activity was suspected. In order to evaluate spontaneous recovery after overdrive suppression, the sinus node recovery time was determined at twice the local capture threshold revealing a maximal corrected recovery time of 1530 ms.
Page 4 of 8 A rate adaptive permanent right ventricular pacemaker was implanted and programmed at a lower rate limit of 60 bpm. An aortic valve replacement was not performed because of recurrent epistaxis, requiring recurrent blood transfusions and a logistic EuroSCORE II of 21.20%. During 6 years of follow-up until the patient’s death, the percentage of right ventricular pacing was 100%. Routine testing for spontaneous electrical activity during follow-up in the pacemaker clinic revealed a junctional escape rhythm with narrow QRS complexes at a rate of 30–35 bpm but no P-waves or fibrillatory waves in the surface ECG.
A 36-year-old male patient complained about dizziness in 2009. Surface ECG on admission showed a narrow QRS rhythm of 43 bmp, but without discernible P-waves prompting the diagnosis of a junctional escape rhythm (Table 2). There was a history of coronary heart disease with previous ST elevation myocardial infarction in 2007 and subsequent percutaneous coronary intervention of the right coronary artery which was patent during a control catheterization in 2008. The patient suffered from paroxysmal atrial fibrillation since 2007. The patient was on therapy with an ACE-inhibitor, a statin (simvastatin) and aspirin. Betablocker therapy was stopped in 2008 because of bradycardia and chronotropic incompetence. Treadmill stress testing revealed chronotropic incompetence; the heart frequency did not increased adequately (fixed heart rate at 45 bpm). Pulmonary function test showed normal results. Systolic left ventricular function was slightly reduced with an ejection fraction of 50% and no A-waves could be detected during Doppler echocardiography of the mitral and tricuspid valve. Because of the junctional escape rhythm and suspected sinus node arrest, the patient underwent dual pacemaker implantation. During the initial implant procedure, no atrial capture and no atrial sensing was obtained at several typical sites for right atrial lead implantation (RAA, high and lateral right atrium). Thus, atrial lead implantation was deferred and a single chamber pacemaker was implanted. Because of the young age of the patient, the case underwent internal discussion and these findings triggered a differential diagnosis of right atrial standstill. A subsequent electrophysiological examination was scheduled to confirm this diagnosis and eventually identify surviving right atrial sites at which atrial pacing could still be achieved. During intracardiac mapping with an electroanatomical mapping system (Biosense Webster CARTO XP), an isolated regular electrical activity in the sinus node area at the high right atrium with a cycle length of 1600 ms was detected. Owing to the atrial fibrosis the excitation of the sinus node was limited to the region of the high right atrium. The rest of the atrium was excited retrograde by the junctional escape beats, at a faster cycle length of 1000 ms. Voltage mapping showed extensive scarring of the lateral right atrium with preserved voltage levels only at the septal right atrium. At this site, atrial pacing with a threshold of 1 V/0.4 ms resulted in atrial capture and subsequent 1 : 1 AV conduction. Incremental pacing revealed an antegrade Wenckebach point at a cycle length of 600 ms. Sensing was 2.0 V.
In a second operation, the atrial lead was implanted at the previously identified septal right atrium with a pacing threshold of 1 V/0.4 ms. Sensing was 1.5 V. Pacing from this site yielded visible electrical atrial activity as judged by the presence of P-waves in surface ECGs and also mechanical atrial activity as reflected by A-waves across the tricuspid and mitral valve during Doppler echocardiography. During the 3 years of follow-up, atrial pacing thresholds remained stable and there were preserved P-waves in the surface ECG and A-waves across both AV valves. The atrial and right ventricular pacing percentage was 91.6% at a programmed AV delay of 280 ms and a lower rate limit of 60 bmp (Table 3).
Partial right atrial standstill In 2011, a 64 year-old women was admitted because of symptomatic bradycardia. The ECG revealed a regular rhythm at 19 bmp with narrow QRS complexes and no obvious P-waves (Table 2). Echocardiography showed normal systolic left ventricular function (64%). A-waves were absent during Doppler examination of the mitral and tricuspid valve. The atria were enlarged (right atrium: 34 cm2, left atrium: 34 cm2). There was a history of arterial hypertension and hypercholesterolaemia, treated with an ACE-inhibitor and simvastatin. Cardiac stress magnetic resonance imaging (MRI) and laboratory findings were normal. Treadmill testing showed chronotropic incompetence (fixed heart rate at 42 bpm). Pulmonary function test delivered good results. Sinus node arrest was suspected and the patient was scheduled for dual chamber pacemaker implantation. Meanwhile, a temporary pacemaker was provided due to intermittent haemodynamic instability. Magnetic resonance imaging and echocardiography were realized before the temporary pacemaker was placed. During pacemaker implantation, atrial lead implantation failed due to insufficient atrial sensing (,1 mV) and the inability to pace the right atrium from high and lateral right atrial sites even at high output (6 V/1.5 ms). Thus, a permanent right ventricular pacing lead was implanted and connected with a dual chamber pacemaker and the patient was referred for a subsequent electrophysiological study for suspected right atrial standstill.
Table 3 Follow-up after 12 months Case 1
Case 2
Case 3
Case 4
60/bpm VVI
60/bpm DDD
60/bpm DDD
60/bpm DDD
Atrial sensing
–
3.5 mV
2.2 mV
5.4 mV
Ventricular sensing Atrial pacing threshold
9.8 mV –
11.4 mV 1.0 V/ 0.4 ms
5.4 mV 0.6 V/ 0.4 ms
12.8 mV 0.5 V/ 0.4 ms
Ventricular pacing threshold
0.5 V/ 0.4 ms
0.5 V/ 0.4 ms
1.5 V/ 0.4 ms
0.75 V/ 0.4 ms
Mode switch Atrial pacing fraction Ventricular pacing fraction
– –
34% 95%
0% 100%
0% 81%
100%
10%
4%
18.5%
................................................................................ Lower rate limit Mode
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Partial right atrial standstill with sinus node arrest and impaired atrioventricular conduction
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Atrial standstill due to extensive atrial fibrosis
Figure 2 (A) 3D-Map in LAO. (B) 3D-Map (CARTO) in LAO 308. The red area demonstrates scar. (C) 3D-Map (CARTO) of the posterior atrium. (D) Post-operative X-ray. The atrial lead is placed at the posterior wall of the right atrium. At this place atrial stimulation was possible. SVC, Superior vena cava; IVC, inferior vena cava; CS, coronary sinus; MV: mitral annulus.
Electroanatomical mapping with an electroanatomical mapping system (Biosense Webster CARTO 3) of the right atrium confirmed the diagnosis of a partial atrial standstill. There were no waves of atrial fibrillation. A small band of tissuewith preserved voltagewas found at the posterior wall of the right atrium which extended to the AV node (Figure 2). Probatory pacing from this area was possible at 1.5 V/0.4 ms. The antegrade Wenckebach cycle length was 500 ms. In a second implantation procedure a permanent atrial lead was placed at the septal right atrium. Intraoperative testing yielded a sensing of 2.1 mV and a pacing threshold of 0.6 V/ 0.4 ms. During pacing P-waves were present in surface in the ECG and discrete A-waves were detected across the mitral and tricuspid valve during Doppler echocardiography (Figure 3). Before atrial lead implantation, the percentage of right ventricular pacing was 100% but decreased to 1% after dual chamber pacemaker implantation. Stable sensing and pacing threshold values were obtained during a 12 months follow-up.
Partial right atrial standstill and sinus node arrest In January 2012, a 76-year-old man was admitted because of recurrent syncopes; 12-lead ECG showed a slow regular rhythm with wide QRS complexes, no visible P-waves or atrial fibrillatory waves in surface ECG spontaneous rate 42 bpm (Table 2). P-waves
were missed. The patient was on ACE-inhibitor and diuretics for treatment of arterial hypertension and on metformin because of diabetes mellitus type II. Underlying coronary artery disease was excluded by coronary angiogram. Echocardiography showed normal systolic left ventricular function (60%). A treadmill stress test showed chronotropic incompetence (fixed heart rate at 46 bpm). Pulmonary function test delivered physiological results. Dual chamber pacemaker implantation was attempted but atrial lead positioning failed due to insufficient sensing (,1 mV) and/or pacing (threshold .5 V/1.5 ms) at several high right atrial sites including the RAA and at the free wall of the right atrium lateral sites during pacing from coronary sinus (Figure 4). A dual chamber pacemaker connected to a right ventricular lead was implanted at the high right ventricular septum and the patient underwent an electrophysiological study subsequently. Electroanatomical mapping of the right atrium showed ubiquitous atrial low voltage with sensing values , 0.9 mV with a cut of 0.5 mV to define scar (Figure 4). A circumscriptive area of 2 cm at the ostium of the coronary sinus was the single right atrial site at which a sensing of 2.5 mV and a pacing capture threshold of 1.3 V /0.4 ms were obtained. No isolated sinus node activity was detected at higher or lateral atrial sites. In a second operation, the atrial lead was positioned at this site with reasonable sensing (2.6 mV) and a pacing values with a threshold of 1.2 V/0.4 ms. Thereafter, during atrial stimulation P-waves could be documented in the surface ECG and A-waves were visible across the AV valves during Doppler echocardiography. During 12-month followup, the right ventricular pacing percentage was 23% while the atria were paced at 99% at a programmed lower rate limit of 60 bpm (Table 4).
Long-term follow-up (n 5 4) The mean follow-up was 3.5 years. In the follow-up period all measured data were stable (Table 3). The first patient died after 6 years. During 6 years follow-up there were no changes in the measurements. The percentage of right ventricular pacing was 100%. All other patients are still well. The right ventricular pacing rate is still
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Figure 3 Echocardiogram after atrial lead implantation and atrial stimulation with A- and E-waves.
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Table 4 Results before and directly after dual chamber pacemaker implantation and coding of the dual chamber pacemakers Lower rate limit pacemaker
Right ventricular pacing fraction (single chamber)
AV delay
Atrial/right ventricular pacing fraction (dual chamber)
PR interval under atrial stimulation
Stimulation frequency
No atrial lead 300 ms
No atrial lead 92%/92%
Not measurable 280 ms
– 60 bmp
............................................................................................................................................................................... Case 1 Case 2
60 bmp 60 bmp
100% 93%
Case 3
60 bmp
100%
250 ms
100%/1%
190 ms
60 bmp
Case 4
60 bmp
80%
250 ms
99%/23%
170 ms
60 bmp
low (,20%). There were no dislocations of leads. Programmed mode switch at all patients is an atrial rate of 171 bpm. Only one patient showed paroxysmal atrial fibrillation. Under treatment with amiodarone the burden of atrial fibrillation was 15%.
Discussion Clinically, atrial standstill is difficult to differentiate from sinus arrest as both may be characterized by irregular slow escape rhythm in the surface ECG, loss of P-waves and absent fibrillatory atrial waves. In cases of sinus node arrest and (regular) escape rhythm partial atrial standstill must be suspected prior to pacemaker implant in order to raise the physician’s awareness of this disease entity. This could lead the implanting cardiologist to attempt alternative and less common atrial lead implantation sites in order to achieve synchronous AV pacing. If this does not succeed a second procedure guided by prior electroanatomical mapping of the atria might be considered. This report describes how an underlying fibrotic process affects the sinus node and the right atrium, thus raising the hypothesis that sinus node disease may be at least partially due to a systemic fibrotic process of the atria. There are few reports on the pathophysiology of atrial standstill. Fibroelastosis and fatty infiltration of the atrial wall has been described.12 In patients with atrial standstill pacemaker implantation may be required because of symptomatic, permanent bradycardia.13 In many of these patients, single chamber stimulation is chosen for
therapy due to the lack of atrial capture.14 In this report, we provide electrophysiological evidence that right atrial standstill may be extensive involving the sinus node, but also the AV node: In two out of four cases, preserved but impaired sinus node activity was observed while sinus node arrest was found in two patients. In patients with preserved sinus node activity, nodal activity was abnormal with either markedly prolonged cycle length or prolonged sinus node recovery time. In both cases, the sinus node activity was not conducted to the atria as documented by a lack of P-waves in surface ECG, mapping of the right atrium or lack of A-waves during Doppler echocardiography of both AV valves. In addition, AV conduction was impaired in one patient. Of note, in two patients there was a history of previous atrial fibrillation. In fact, patchy atrial scarring may lead to anatomical obstacle delaying or blocking atrial electrical activation and increase anisotropy of the atria. This may promote re-entrant circuits facilitating the development of atrial tachycardia and atrial fibrillation. It is important to mention that, scarring of the atrial wall has been described in patients undergoing atrial fibrillation ablation.11 So far, it is not clear, whether atrial fibrillation is the cause, or in part, consequence of atrial fibrosis. There is experimental evidence that atrial fibrosis may be secondary to atrial fibrillation due to rapid cellular activation and apoptosis.15 The current report raises the opportunity to believe that atrial fibrosis per itself may be a factor, which affects atrial electrophysiology and the function of the sinus and AV node and not just
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Figure 4 (A) 3D-MAP (CARTO) in LAO. The low lateral right atrium is the target region for the atrial lead. The red area demonstrates scar. (B) 3D-Map (CARTO) of the right lateral atrium. (C) 3D-Map (CARTO) of the left lateral atrium. (D) Post-operative fluoroscpoy. High septal ventricular lead and right atrial lead in low lateral right atrium (LAO).
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Atrial standstill due to extensive atrial fibrosis
be achieved allowing at least partial atrial mechanical contribution to diastolic ventricular filling. However, although atrial contraction was present after dual chamber pacemaker implantation as demonstrated by the presence of A-waves during Doppler echocardiography, full atrial contractility may still have been impaired due to the underlying atrial fibrosis.
Limitations and unresolved issues This study is descriptive and comprises a low number of patients. In one patient, digoxin was only discontinued 48 h prior to pacemaker implantation. In fact, a functional effect of digoxin on sinus node function might have been present. Likewise, digoxin (even being within normal plasma levels) might have contributed to electrical standstill. Nevertheless, the detailed findings provide novel insights into atrial and sinus node pathology and thus is hypothesis generating. We do not know the long-term stability of atrial pacing at the surviving atrial islets. As atrial fibrosis is a progressive disease, loss of capture at the pacing sites may occur in long term. The mean follow-up of this study (3.5 years) and the low number of patients does not allow clarifying this issue. Mapping was restricted to the right atrium. Thus, we do not know the extent of atrial standstill in the left atrium. However, the presence of A-waves across the mitral valves after atrial lead implantation provides some evidence for a presence of viable left atrial tissue. Likewise in one patient, right atrial electroanatomical mapping was performed during pacing from the coronary sinus, which indicates surviving left atrial tissue. It remains unclear whether partial atrial standstill or fibrosis is more common in patients with sinus node disease as currently suspected. Possibly, the underlying atrial pathology is simply not recognized due to sufficient pacing thresholds during atrial lead implantation, which is typically implanted in the more muscular right atrial appendage.
Conclusion In patients with suspected symptomatic sick sinus syndrome and regular escape rhythms partial right atrial standstill may be present, especially if enlarged atria are present during echocardiography thus preventing successful right atrial lead implantation. Recognition of this prior to pacemaker implantation might guide the implanting physician to search more extensively for alternative right atrial pacing sites during the operation. In selected patients electroanatomical mapping of the right atrium prior to pacemaker implantation may identify surviving right atrial sites amenable for permanent synchronous AV stimulation. Sick sinus syndrome and atrial standstill may share a common pathology. Conflict of interest: none declared.
References 1. Wooliscroft J, Tuna N. Permanent atrial standstill: the clinical spectrum. Am J Cardiol 1982;49:2037 – 41. 2. Cushny A. Optical isomerism, and the mechanism of drug action. J Hist Biol 1975;8: 145 –65. 3. Rodrı´guez Reyes H, Cruz Cruz F, Iturralde Torres P, de Micheli A, Gonza´lez Hermosillo JA. Persistent atrial paralysis: reported of 2 cases. Arch Inst Cardiol Mex 1997;67:498 –502. 4. Nakamoto K. Relation between the duration of pancardiacasystole and the postasystolic atrial cycle and the effects of orciprenaline on the atrioventricular
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secondary to systolic heart failure or valvular heart disease (except Patient 1 with aortic stenosis). The presence of pulmonary hypertension in two patients and upper normal values in the other two patients raise the opportunity that pulmonary hypertension partially contributed to right atrial fibrosis and standstill. One might argue that the number of such cases is low as only four patients were identified in a higher volume centre (1200 dual chamber pacemakers between 1996 and 2012). However, it seems very likely that in many instances of atrial scarring and partial standstill atrial fibrillation develops due to anisotropic conduction thus masking the underlying atrial pathology and its potential impact on sinus and AV nodal function. In fact, two patients in this report had a history of previous atrial fibrillation. The findings of the four cases presented herein demonstrate that preoperative recognition of signs of potential atrial standstill like regular slow escape rhythm, lack of atrial fibrillatory waves might drive a change in procedural approach in these patients. This could include the information of the implanting physician of potentially present partial atrial standstill thus leading to more detailed search for alternative pacing sites. In patients with enlarged atria, indicative for atriale fibrosis, an electrophysiological mapping study might be considered prior to pacemaker implantation to confirm the diagnosis of partial atrial standstill and to identify potential implantation sites to decrease the possibility of a second implantation procedure. The inability to pace the atria from standard atrial sites during pacemaker implantation then led to the recognition of atrial standstill which could be confirmed by subsequent electrophysiological studies. These mapping studies also revealed that fibrosis involved the sinus and AV nodal area as a progressive disease. The patients in this report offered the unique opportunity to study sinus and AV nodal function during partial or complete right atrial standstill, thus unrevealing the involvement of both nodes in advanced stages of this disease. This is additional evidence that sinus node disease may not always be a primary disease entity, but secondary to changes of the surrounding atrial tissue.16 In fact, it has for long been recognized, that atrial fibrillation may occur secondary to sick sinus syndrome possibly due to atrial dilatation and increased atrial pressure, which may facilitate the development of atrial fibrillation. However, pacemaker implantation does only partially reduce the likelihood for atrial fibrillation.17 In view of the findings of this study, the hypothesis may be raised that atrial fibrillation develops in part as consequence of a more diffuse atrial disease involving the sinus node, rather than being linked solely to sinus nodal dysfunction. Atrial fibrosis is a typical age related process in otherwise healthy men. Of note, above the age of 55 years fibrosis increases by 1% per year in normal man.18 Besides the fact that the patients of this study were of advanced age, all of them had a history of arterial hypertension and 50% were diabetic, both conditions known to promote cardiac fibrosis.19 This may have considerably contributed to the extent of fibrosis observed during the mapping studies. How do we cope with bradycardia secondary to atrial standstill? This report describes how mapping of the atria allows to identify surviving areas of the right atrium at which pacing with AV conduction can successfully re-establish synchronous AV conduction. It confirms reports of Arimoto et al. 20 and extends them by providing long-term follow-up data. This approach is advantageous as right ventricular apical pacing with left branch bundle block morphology may be avoided (Table 2). Furthermore, AV synchronous conduction can
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5. 6. 7. 8.
9.
10.
11.
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