Electrophysiologic Evaluation of Sinus Node Function in Patients with Sinus Node Dysfunction HAROLD C. STRAUSS, M.D., C.M., J. THOMAS BIGGER, JR., M.D., ALAN L. SAROFF, M.D., AND ELSA-GRACE V. GIARDINA, M.D. SUMMARY Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and sinoatrial block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the time of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated "sinoatrial conduction time" exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a

value equal to 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + I SDd in 13/19 (68%) patients. Nineteen patients received I mg atropine intravenously and mean cycle length decreased by 19%, from 891 ± 175.8 msec to 718 ± 182.9 msec. Graded infusion of isoproterenol was employed in 19 patients; four patients required an infusion rate greater

INTEREST IN SINUS NODE DYSFUNCTION has grown in recent years with identification of electrocardiographic criteria for sick sinus syndrome.1-6 Reports have appeared describing the clinical features'-" or electrophysiologic studies36-46 or postmortem findings in this group of patients.15, 16, 21, 30, 47-51 Although the electrocardiographic criteria for diagnosis of sick sinus syndrome have gained wide acceptance, the evaluation of such patients in the clinic can often be difficult, particularly when a patient does not have full blown features of the syndrome. Symptomatology is not only importantly related to the severity of the bradyarrhythmia(s) but also is related to the nature and severity of the tachyarrhythmia(s) and to the coexistence of cerebrovascular and cardiac disease. A variety of interventions have been offered as a means of identifying sinus node dysfunction,37 40-42, 52 but at present it is not clear that they do anything more than identify those patients with overt features of the sick sinus syndrome. Interpretations of data derived from the use of these interventions are facilitated by consideration of data obtained from in vitro electrophysiologic studies.53 In the rabbit heart, electrical activity in the sinus node is generated by automatic pacemaker cells and the impulse so formed propagates toward the crista terminalis to activate the atrium.53 Hence, in the rabbit, and presumably in man, absence of atrial depolarization can reflect disturbance of sinus node automaticity and/or sinoatrial conduction. Thus, it may be useful to employ electrophysiologic tests which assess both sinus node automaticity and sinoatrial conduc-

tion in order to characterize the nature of the physiologic disturbance in individual patients. Despite the numerous descriptions of patients with sinus node dysfunction, there are no complete detailed electrophysiologic studies of this group of patients available. Such information could be expected to further our understanding of the underlying electrophysiologic mechanisms, and thus provide a more rational basis for pharmacologic therapy in this group of patients. It was the purpose of this study to evaluate patients with sinus node dysfunction in an attempt to gain insight into the clinical features of these patients and the electrophysiologic mechanisms that underlie disturbances of sinus node function.

than 28.3 ng/kg/min to produce a 20% decrease in spontaneous sinus cycle length. These data would indicate that a variety of interventions are required to characterize the disturbance of sinus node automaticity and sinoatrial conduction in patients with sinus node dysfunction.

Methods Twenty symptomatic patients with sinus node dysfunction, who were in sinus rhythm at the time of electrophysiologic study, comprise the study group. The patients' ages ranged from 32 to 87 years (mean age 66.2 years). Informed consent was obtained in all patients. History, physical examination, chest X-ray and ECG were performed prior to detailed electrophysiologic study and each patient was classified according to New York Heart Association classification.54 Sinus bradycardia was evaluated on the basis of its severity and considered to be either persistent or intermittent. Sinus bradycardia was classified as persistent if the range of sinus rhythm recorded at rest during the hospitalization remained below 60 beats/min. It was considered to be minimal if rates ranged between 50 and 59 beats/min; moderate between 40 and 49 beats/min; and severe if the rate fell below 40 beats/min during the period of hospitalization. At the time of study the patients were in a resting, nonsedated, postabsorptive state. Throughout the procedure a solution of 5% dextrose and water was slowly infused through an indwelling catheter placed in the left antecubital vein. Two 4F bipolar electrodes (stimulating and recording) were passed, under fluoroscopic control, via a right antecubital vein into position in the right atrium, as previously described.42 A 6F tripolar catheter passed per-

From the Departments of Medicine and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York, and Duke University Medical Center, Durham, North Carolina. Presented in part at the 44th Scientific Sessions of the American Heart Association, Anaheim, California, November 1971. Supported in part by a Grant-in-Aid from the New York Heart Association, USPHS grants HL 12738, HL 07541, HL 05736, HL 15190, HL 05864, HL 50709, and HL 70204, and in part by the Cardiac Intensive Care Unit Fund of the Presbyterian Hospital of New York City and the Chernow Foundation. Also supported by a Pharmaceutical Manufacturers Association Foundation Faculty Development Award in Clinical Pharmacology. Address for reprints: Harold C. Strauss, M.D., Box 3845, Duke University Medical Center, Durham, North Carolina 27710. Received September 3, 1975; revision accepted for publication December 18, 1975.

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CIRCULATION

764

cutaneously via the right femoral vein was used to record the His bundle electrogram in 15 patients.5 Filter settings for the atrial electrogram recordings were 4-1000 Hz and for the His bundle electrogram recordings, 40-1000 Hz. Signals from body-surface ECG, atrial and His bundle electrodes, along with 100 and 1000 msec time marks (Tektronix-type 184 time mark generator) were simultaneously recorded on FM magnetic tape and displayed on an Electronics for Medicine multichannel oscillograph. Following a 15-20 min stabilization period, control recordings were obtained. Thereafter, in 19/20 patients, programmed premature stimuli were introduced via the stimulating atrial electrode during spontaneous sinus rhythm, as previously described.42 In this way atrial premature stimuli were introduced after every eighth spontaneous sinus cycle. Stimuli were introduced late in atrial diastole and moved progressively earlier in 5-10 msec decrements, until the entire atrial diastolic period was scanned.42 A two minute stabilization period followed the period of premature atrial stimulation. Twenty consecutive cycles for control pre-pacing cycle length were obtained during the second minute. In 19/20 patients the atria were paced for 60 sec, at constant cycle lengths of 860, 660, 540, 460, 400 and 353 msec. The intervals between pacing were 60-90 sec. During the pacing periods the rhythm was carefully monitored to ensure complete atrial capture. Five minutes after termination of atrial pacing, an isoproterenol infusion was started. The solution of isoproterenol HCl (2 ,g/ml) and 5% dextrose and water was infused into the dextrose and water infusate at a constant rate. Every five minutes infusion rates were increased by 0.25 ml/min. The rate of infusion was increased until the patient complained of chest pain, developed more than 3-5 ventricular premature depolarizations/min, or until a maximal rate of 120 beats/min was reached. Recordings used in the analysis of cycle length were obtained during the final minute of the infusion period. Following discontinuation of isoproterenol infusion, the patient's rate was allowed to return to control values over a period of 30-50 minutes, then 1 mg of atropine sulfate was given intravenously. Cycles recorded during the fifth minute following atropine administration were used for analysis of cycle length. The data were transferred to photographic paper for analysis using an Electronics for Medicine recorder at paper speeds of 100 and 150 mm/sec. Twenty consecutive spontaneous sinus cycles obtained following the initial stabilization period were analyzed for determination of P-P, P-V, A-H, H-V intervals. Atrial activation for the P-V interval was determined from the earliest onset of atrial activity that was detectable in lead II or in the atrial electrogram recording. Atrial (A), His bundle (H) and ventricular (V) activations for A-H, H-V intervals were determined from the onset of the rapid voltage change in the His bundle electrogram recording. P wave and QRS durations were obtained from analysis of ten consecutive lead II cycles. When the spontaneous sinus cycle was interrupted by an atrial premature depolarization (APD), the following four consecutive atrial intervals were measured: 1) spontaneous cycle length (AIAJ), i.e., the interval between the last two spontaneous sinus P waves that preceded the APD; 2) the test cy-

VOL. 53, No. 5, MAY 1976

cle (A,A2), i.e., the interval between the last spontaneous sinus P wave and the APD; 3) the return cycle (A2A3), i.e., the interval between the APD and the following P wave; and 4) the spontaneous sinus cycle immediately following the return cycle (A3A4). The atrial intervals used in the analysis of the response to APDs were determined using earliest activation detected. The number of A,A, cycles analyzed corresponded to the number of programmed APDs elicited in any given patient and ranged from 30 to 240 (average 135). Definitions

The A2A2 interval that followed different A,A2 intervals was not constant but was related to the coupling interval of A2 in a predictable manner which then permitted subdivision of atrial diastole into different zones (fig. 1). The estimated "sinoatrial conduction time" (the sum of retrograde and antegrade sinoatrial conduction time) was considered to be prolonged if it exceeded 215 msec, a value that represented the sum of the mean + I SD (169 + 46 msec) in a series of 20 patients without sinus node dysfunction.56 Unlike our previous study,42 the derived value of the esA SAN SAJ ATRIUM

T

1,

1,

A

A

A

A

A

K

4d

I

i

Al c

Al

a\

i

Ii

A2

A3

A4

IIrj I Al

Al

Al

Al A2

Ag

At A2

A2

A3

A4

A4

A3

D A3

II

A4

FIGURE 1. Diagramatic representation of Zones I-IV. In each panel a ladder diagram is shown with hypothesized activity in the sinus node (SAN) and sinoatrial junction (SAJ) designated by dashed lines. A trial activity is depicted by solid lines. For purpose of comparison, five spontaneous beats are shown in panel A. In panel B a late atrial premature depolarization (APD-A2) elicited in Zone I collides with the emerging sinus node impulse and is followed by a compensatory return cycle (A2A3), so that A1A2 + A2A3 = 2 A,A,. In panel C an APD elicited in Zone II resets the sinus node causing A2A, to be less than compensatory so thai A1A2 + A2A3 < 2 A,A, and A2A3 > A,A,. In panel D an APD elicited in Zone III is presumably blocked between the atrium and the sinus node, resulting in its being interpolated, so that AIA2 + A2A3 . A,A, with A2A3 < A,A,. Thus, A2A3 in Zone III is less than A,A, and A2A3 in Zone IH is greater than A,A,. However, in a few instances, intermediate responses have been noted. In panel E an APD elicited in Zone IV is followed by a shorter than anticipated A2A3 cycle, so that A1A2 + A2A3 < A1A1. The A2A3 cycles identified with Zones I-IV had A3 responses that had sinus P waves (upright P waves in leads I and IH).

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EVALUATION OF SINUS NODE FUNCTION/Strauss, Bigger, Saroff, Giardina

timated sinoatrial conduction time was not divided by a factor of two. The functional refractory period of the atrioventricular conduction system (shortest V1-V2 interval) determined during spontaneous sinus rhythm was considered to be prolonged if it exceeded 460 msec, a value that represented the sum of the mean + I SD (419 + 41 msec) in a series of 19 patients with heart disease, but with normal QRS duration and heart rates of 70-100 beats/min.57 The value of the first escape cycle following termination of pacing was considered to be prolonged if it exceeded a value equal to 1.3 x the mean value of the control spontaneous sinus cycle length + 101 msec, a value that represented the slope of the regression line (1.3 X) + Y intercept (46 msec) +1 SD (estimated to be 55 msec) in a plot of the maximum first escape cycle length against the control spontaneous sinus cycle length.36 The chronotropic response to atropine was considered to be abnormal if the mean cycle length decreased by less than 17%, a value that represented the mean decrease from control heart rate - I estimated SD (34% - 17%) in a series of 39 patients ranging in age from 40 to 79 years without known

systemic disease.58 The chronotropic response to isoproterenol was considered to be abnormal if the infusion rate required to produce a 20% decrease in cycle length exceeded 28.3 ng/kg/min, a value that represented the sum of mean + 1 SD (21.0 + 7.3 ng/kg/min) derived from this study group. Results

765

ventricular conduction disturbance. Five patients (25%) had prolonged QRS complexes: in two this was due to left bundle branch block, in two to right bundle branch block. Nine of 20 (45%) patients had artificial pacemaking systems implanted after electrophysiologic study. Six of the nine patients had dizziness, faintness or syncope; three patients had angina and/or congestive heart failure. Symptoms disappeared in five patients and decreased in frequency in three patients. One patient died 24 days postoperatively, six other patients died 5-30 months following pacemaker implantation; thus, 78% of those treated with artificial pacemaker implantation died within 30 months. Pacemaker systems were not implanted in 11 patients. Nine of this latter group of patients are alive 28-47 months following study and one died four months following electrophysiologic study. One patient was lost to follow-up. Electrophysiological Intervals

Electrophysiological intervals obtained during the control period revealed that 10/20 (50%) patients, at the time of study, had a mean cycle length that was greater than 1000 msec. The P wave duration was greater than 120 msec in 13/20 (65%) of the patients. The P wave was upright in ECG leads I and II in all 20 patients. QRS duration was greater than 120 msec in 4/20 (25%) patients. The mean P-V interval was greater than 210 msec in 7/20 (35%) patients. In this group of seven patients a His bundle electrogram recording was obtained in six and the H-V interval was greater than 55 msec in three patients. Two patients with a prolonged H-V interval had no associated QRS widening.

Clinical Features

Clinical information on the 20 patients who form the basis of this report is shown in table 1. The patients seen for evaluation had a variety of noncardiac problems. Twelve of the 20 patients were male and 13 were white. Presenting symptoms included dizziness (9/20), syncope (5/20), cerebrovascular accident (2/20), chest pain (7/20) and one patient was asymptomatic. Eleven patients had persistent sinus bradycardia, seven patients had intermittent sinus bradycardia, and two patients did not have sinus bradycardia. Sinus bradycardia was severe in two, moderate in ten, and minimal in six patients. Seven patients had paroxysmal episodes of supraventricular tachyarrhythmias prior to study. Sinus pauses were observed in three patients and sinoatrial block was observed in one patient (No. 16). The etiologies of the heart disease were as listed in table 1. Cardiomegaly was present in 14/20 (70%) patients. Using the New York Heart Association classification,54 four patients were judged as having an uncompromised status (class 1); eight patients had a slightly compromised status (class 2); seven patients had a moderately compromised status (class 3); and one patient had a severely compromised status (class 4). Eleven patients had some abnormality of atrioventricular nodal and/or intraventricular conduction. Nine of our patients (45%) had first degree atrioventricular block (table 1). Eight of 20 patients (40%) had an intraventricular conduction disturbance. Seven patients (35%) had QRS complexes that demonstrated marked left axis deviation; in three patients this was the only manifestation of an intra-

Effects of Atrial Premature Depolarizations

The atrial responses to premature atrial stimuli were analyzed in 19/20 patients. In all 19 patients the normalized values of the return cycles (A2A3/A,A,) were plotted as a function of the normalized values of the test cycles (A,A,/A,A,) and in such graphs one to four zones were identified in 16/19 patients (table 2, figs. 2-4). In three of 19 patients the responses to atrial premature depolarizations were so variable as to preclude further analysis. Scatter in the distribution of data points was moderate in five patients (fig. 2) and minimal in the remaining patients ( 1/19) (figs. 3 and 4). Zone I, in which atrial premature depolarizations are usually followed by compensatory return cycles, was identified in all 16 patients who were analyzed. In two patients, atrial premature depolarizations introduced late in atrial diastole were followed by greater than compensatory return cycles as shown in figure 5. The greater than compensatory A2A3 cycles are described as occurring in Zone I and were associated with a similar prolongation of A3A4 cycles. The inner limit of Zone I was defined by the transition to Zone II in the graphs (figs. 2-5) and coincided with the appearance of less than compensatory A2A3 cycles as manifested by points falling below the compensatory line. This occurred in 13/16 patients. In the two patients with greater than compensatory A2A3 cycles in Zone I, the transition to a "plateau" response was discrete and at this point the transition between Zone I and II was so identified (fig. 5). Thus, the transition from Zone I to II ranged between 66.6% and 94.7% of the A,A, interval in 15/16 patients

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766

CIRCULATION

VOL. 53, No. 5, MAY 1976

TABLE 1. Clinical Features Patient

1 KM

Age (yr) and sex

82 F 7_

-

Chief complaint

Dizziness, syncope, _

_,

r

-7

I sided weakness

Heart rate in

hospital

Am monit 41-75 b/min with block APDs

Diagnosis

1. L hemisphere CVA

Pacemaker

Fo!low-up

Yes

Dizziness absent. Died after 27 months

2. Heart disease a) Etiol unknown, HT

b) Min cardiomegaly c) SB & NSR with blocked APDs 1st deg AVB, I-Mod SB

d) Status-2 2 AZ

81 M

Dizziness, atypical chest pain

ECG 50-60/mi

(N

=

2)

1. Heart disease

Refused

a) Etiol unknown

spells

c) SB, IAB, RBBB, P-Min SB

d) Status-2 3 AL

76 M

4 MB

82 M

Marked dizziness anid ECG 38-45/min (N = 5) weakness

1. Heart disease

Marked dizziness ECG 48-54/min Med: Digoxin 0/25 mg (N = 6) Chlorothiazide

1. Basilar art insuff 2. Heart disease

500

5 TB

6 CJ

mg

61 M

Syncope, chest pain, ECG 65-78/min dyspnea (N = 6) Med: Digoxin 0/2.5 mg Furosemide 40 mg Reserpine 0/25 mg

72

Dizziness, weakness, dyspnea

MI

7 MP

32 M

8 MM

68 F

9 RE

87 F

10 VB

71 F

ECG 50-56/min

Yes

a) Coronary atherosclerosis b) Old lat wall MI, Min cardiomegaly c) IAB, P-sev SB d) Status-3 a) Coronary atherosclerosis, Hr, AS b) Min cardiomegaly, AS c) IAB, 1st deg AVB, MLAD, P-Mod SB d) Status-3 1. S/P R CVA (1966) 2. Heart disease a) Etiology unknown, HT b) Marked cardiomegaly c) Sinus pauses 2° digoxin & reserpine, 1st deg AVB, IVCD, MLAD, CHF d) Status-3 1. Heart disease

a) Coronary atherosclerosis b) Min cardiomegaly, apical MI c) SB Parox A fib, IAB, 1st deg AVB, MLAD, CHF, P-Min SB, BTS d) Status-3 Dizziness, syncope ECG 58-78/min 1. Heart disease none detectable Atypical chest pain (N = 2) c) I-Min SB d) Status-1 Chest pain, dyspnea ECG 48-65/min 1. Heart disease (N = 3) Parox A flutter a) Etiology unknown Med: Digoxin 0/25 mg 2 sec. sinus pauses b) Mod cardiomegaly c) SB, Parox A flutter, IAB, Mesantoin 300 mg 1st deg AVB, MLAD, CHF, I-Mod SB, BTS, Sinus pauses d) Status-3 Dizziness, dyspnea ECG 35-55 1. Basilar art insuff (N =3) Med: Digoxin 0/125 2. Heart disease a) Coronary atherosclerosis mg Furosemide b) Mod cardiomegaly, MR 40 mg c) SB, SA, alt with A fib, IAB, 1st deg AVB, CHF Aldactone 50 mg P-Sev SB, BTS Ephedrine, d) Status-4 isoproterenol Recurrent dyspnea ECG 45-55/min 1. Heart disease 5) 2° Parox A fib (N a) Coronary atherosclerosis Digoxin 0/25 mg BID b) Mod cardiomegaly, MR 2° pap m Furosemide 80 mg QOD dysfunction, MI c) SB, Parox A fib, IAB, CHF with parox pulm edema, P-Mod SB, BTS d) Status-3

Recurrent dizzy ECG 48-60/min (N = 7) A&W after 47 months Dizziness absent for 46 months

Yes

Dizziness absent. Died after 12 months

Yes

Syncope absent. CHF worsened. Died after 3 months*

No

Intermittent dizziness and dyspnea. ECG 52-72/min

(N = 6)

A&W on digoxin after 45 months No

Lost to follow-up

Yes

Died postop.

Yes

Symptoms decreased in frequency Died after 30 months

Yes

Symptoms decreased in frequency on digoxin Died after 24 months

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EVALUATION OF SINUS NODE FUNCTION/Strauss, Bigger, Saroff, Giardina

Patient

11 IB

12 WO

Age (yr) and sex

73 M

69 M

Chief complaint

Heart rate in hospital

ECG 48-78 dyspnea x 3 wk (N = 4) A flutter (310:155) SB post cardioversion

Asympt bradycardia & VPDs

ECG 55-60/min (N = 2)

13 CC

66 F

Deep inspir sinus Syncope, dyspnea Med: Digoxin 0/25 mg CL 680-2200 msec Furosemide 40 ECG 70-90/min mg QOD (N = 4) SVT (120/min) A flutter (295/min

14 JJ

49 M

ECG 41-60/min Dyspnea Med: Digoxin 0/25 mg (N = 15) Furosemide 40 mg

15 LH

59 M

Atypical chest pain Palpitations

16 MA

49 F

ECG 58-68/min Atypical chest pain (N = 3) Spontaneouis SA block Med: Isosorbide dinitrate

17 CW

51 F

Syncope L sided weakness Med: Aldomet 250 mg QID Synthroid 100

18 DL

69 F

Dizziness

ECG 48-55/min (N = 3)

ECG 43-50/min (N = 3)

Diagnosis

P?acemaker

1. Heart disease a) Etiol unknown b) Min cardiomegaly c) SB, with parox A flutter-fib, CHF, I-Mod SB, BTS d) Status-I 1. Heart disease a) Coronary atherosclerosis b) ASMI c) SB, IAB, 1st deg AVB, freq. VPDs, I-Min SB, BTS d) Status-1 1. Aneurysm of abd aorta & iliac artery 2. Heart disease a) Etiol unknown c) NSR with APDs, VPDs, sinus pause,SVT, A flutter, IAB d) Status-2 1. S/P R CVA (1968) 2. Heart disease a) Coronary atherosclerosis b) Mod cardiomegaly, MI c) SB, IAB, 1st deg AVB, ventricular asynergy, LBBB, CHF, LV failure, P-Mod SB d) Status-3 1. Heart disease a) Etiol unknown b) Min cardiomegaly c) SB, IAB, rate related LBBB, MLAD, mod. VPDs, P-Mod SB d) Status-i 1. Heart disease a) Etiol unknown b) Anat nl c) SB. SA block, I-Min. SB d) Status-2 1. R CVA 2. Heart disease a) HT c) SB, P-Mod SB d) Status-2

No

1. Heart disease a) Etiol unknown b) Min cardiomegaly c) SB, P-Min SB d) Status-2 1. Heart disease a) Coronary atherosclerosis b) Min cardiomegaly c) SB, IAB, P-Mod SB d) Status-2 1. Heart disease a) RHD inactive, S/P SBE treated, MR/MS b) Mod cardiomegaly, MR/MS c) SB, IAB, 1st deg AVB, IVCD, MLAD, Parox A fib, I-Mod SB, BTS d) Status-2

No

767

Follow-up

P 46-66/min after 29 months A fib after 35 monthscardioversion,

digoxin No

A flutter-fib after 27 months- cardioversion, digoxin

A&W after 34 months P 50-60/min No

Syncope absent on digoxin & furosemide Died after 4 months

Yes

No complaints on digoxin, furosemide & dyrenium after 33 months

No

Recurrent atypical chest pain after 32 months

No

On propranolol & probanthine, symptoms

No

un-

changed after 29 months On hydralazine & aldomet, no complaints after 29 months

mg

19 ET

62 M

20 WJ

65 M

ECG 50-55/min

(N = 2) Palpitations Med: Digoxin 0/25 mg Chlorothiazide 500 mg ECG 48-60/min Chest pain T freq (N = 4) x 6 wk

Dizziness, weakness

Am monit

Parox A fib

43-70/min Sinus with freq

Med: Digoxin 0/375 mg

APDs & mod

VPDs

No

On digoxin & chlorthiazide, dizziness unchanged after 28 months (ECG

55-60/min) On propranolol & probanthine, symptoms unchanged after 28 months

No

CHF & chest pain on digoxin

Faintness after 16 months P 36-45/min pacemaker inserted Cardiac arrest, died after 21 months

*Postmortem findings: diffuse interstitial myocardial fibrosis. Abbreviations: Etiol = etiology; Anat = anatomy; A = alive; W = well; Am monit = ambulatory monitoring; N1 = normal; AS = aortic stenosis; BTS - bradyeardia-tachyeardia syndrome; CHF = congestive heart failure; HT = hypertension; MI = myocardial infarction; MR = mitral regurgitation; SVT = supraventricular tachycardia; TIA = transient ischemic attack; SB = sinus bradycardia; NSR = normal sinus rhythm; A fib = atrial fibrillation; A flutter = atrial flutter; AVB = AV block; (M) LAD = (marked) left axis deviation; IAB = intra atrial block; IVCD = intraventricular conduction dis= left bundle branch block; VPD = ventricular branch block; LBBB turbance; RBBB = right bundle Downloaded from http://circ.ahajournals.org/ by guest on Aprilpremature 28, 2015depolarization. Medications are given in dose/day unless otherwise stated.

VOL. 53, No. 5, MAY 1976

ClIRCULATION

768

(table 2). In these 15 patients at the transition between Zones I and II, the A2A3 cycle was 24-278 msec longer than the A1A1 cycle. In one patient, Zone II responses were never elicited and this patient had a markedly prolonged Zone L.42

Earlier in diastole, atrial premature depolarizations were followed by less than compensatory return cycles which were greater than the spontaneous sinus cycle (A,A,) (table 2, figs. 1-5). The inner limit of Zone II was defined by the

TABLE 2. Responses to Premature Atrial Stimuli

(rane). (msec)

Pt. no. 1

2 3

Zone Ila responses

Al A, SD

Limts of zones

t.

966

33.3

(868-1041) N = 66 1225 i 16.1 (1165-1288) N = 97 1447

IV

I

II

71.7-

50.8-

106.-5

71.7

89.1100.0

47.489.1

38.447.5

82.9102.3

36.082.9

29.439.0

69.7100.0

42.569.7

82.8100.0

43.474.3

36.247.3

73.5100.0

40.273.5

-

48.9-

-

-

-

-

-

III

*Diast limits

Al

53.062.0

959

%

71.0-

85.0

A4

4 MiSo i

(msec) i

32.8 N = 12 1232 18.0 N = 17

132.6 3.49

So i

Slope of

A3 A4

\2 X'I3 ± A1 A2 '7o

sD

SACT

-0.189

102.7 3.60

-

0.7.)6

101.3 1.76

-

105

-

202

112.6

1..50

313

103.7

(1277-1742) N = 97 4

5

6

1176

-

43.4

(1032-1274) N = 120 748 - 12.9 (725-803) N = 101 871

-

31.8

(744-936) N = 215 7

774

-

46.1

(676-977) N = 125 8

949

-

48.9

-

65.080.0

117.1 3.26

-

-

0.036

102.4 2.18

140.7 2.62

-

-0.106

110.0 1.84

876

125.7

-

-0.347

225

2.82

101.9 1.75

-

23.5 N = 48 759 i

-

0.239

119.3 10.86

-

122

1179 50.0

N 59.0

69.0

30.2-t i52.8

61.071.0 61.073.0

101.1

-

94.5104.6

34.3 94.5

94.7102.2

46.094.7

72.2100.0 80.2-

23

=

754

-

17.2 N = 18

=

135.3 2.98

18.9

N

(809-1099) = 103

-

232

29

/464

N 10

1200

38.6

(1136-1289) N = 108 11

857

-

20.4

(744-960) N = 133 12

1001

-

67.8

(703-1150) N 177

67.0-

1200

87.0

39.1

N -

-

46.372.2

-

-

43.3-

-

103.0

46.280.2

47.0

-

86.6101.8

34.0 86.6

83.9103.7

31.883.9

81.0 101.2

34.481.0

70.0103.5

36.1-

93.2101.6

32.593.2

74.090.0

60.070.0

699

-

13.3

(655-731) N 30

60.080.0

=

14

1194

65.6

(1075-1381) N 146

-

-

68.086.0

=

15

1023

-

72.7

(843-1247) N - 131 16

848

-

83.0

(765-1017) N

17$

=

30.746.2

29.3-t 34.7

56.083.0 64.080.0

-

148

1050

107.2 3.69

-0.071

102.5 2.30

107.7 3.57

-0.354

102.2 3.98

127.6 3.40

0.263

101.8 4.74

284

-0.355

100.3 0.69

146

0.090

102.2 4.74

-

161

86

30

875 45.8

N = 36 1028 55.2

-

67

N= 21

=

13

-

703

-

4.9 N = 8 1199 44.7 N = 21 987 42.1 N = 23 856 50.5 N = 20

120.7 4.02

-

113.4 i 5.20

-

121.5 5.64

-

-0.403

102.2 4.39

-

212

119.6 2.97

-

0.015

103.9 2.66

-

168

131.3 5.14

-

-0.494

107.5 4.08

-

373

106.4 4.32

-

-0.196

100.7 4.43

i

84

112.0

(853-1394) N 18

=

1167

240 -

69.0

(947-1446) N 19

=

1313

N 20

1245

-

182 -

53.7

(1157-1443) =

-

70.0

192

-

57.069.0 72.092.0

1192 45.8 N = 43 1318 49.1 N = 45

195.4

(868-1642) N

=

151

*Diastolic limits defines the limits of diastole or AiA1 cycle during which A2A3 and AsA4 cycles were used for analysis of Zone Ila responses. tThe beats designated as sinus node echo beats in patients Nos. 6 and 15 had a P wave configuration that was similar to sinus beats although decreased in amplitude in ECG leads I and II and a high to low right atrial sequence that was similar for the normal and echo In patient No. 15 the latency of the test depolarization eliciting the echo response increased from 35 msec (late in diastole) to 65 msee and intraatrialbeats. conduction time. as measured from onset of atrial activity to rapid atrial deflection, increased from 25 to 120 msec. $Patient No. 17 had atrioventricular junctional echo beats.

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EVALUATION OF SINUS NODE FUNCTION/Strauss, Bigger, Saroff, Giardina earliest atrial premature depolarization that produced a Zone II response. In our 16 patients this value ranged between 28.1% and 50.8% of the A1A2 interval. Having defined the limits of Zone II in each graph, this zone was divided into thirds and the last third of Zone II, adjacent to Zone I, (Ila) was used for further analysis. The diastolic limits of the Zone IIa responses used for analysis are listed in table 2. In our 15/16 patients the mean values of the Ila A2A3 cycles ranged between 106.1% and 143.0% of the AIA, cycle and were 59 to 373 msec longer than the A,A1 cycle. The differences between the A2A3 and A1A1 cycles were used as the values that most closely approximated the sum of antegrade and retrograde sinoatrial conduction times (SACT = A2A2 - A,A,). In two patients (Nos. 5 and 7) with greater than compensatory A2A3 cycles 200

Pattent 12(WO)

A

769

in Zone I, the A3A4 cycle was subtracted from the A2A3 cycle to derive the sinoatrial conduction time (SACT = A2A3 - A3A4). The SACT exceeded 215 msec in 6/16 (38%) patients. Two patients (Nos. 5 and 8) with sinus pauses had values of SACT that exceeded 215 msec, and in one patient (No. 8) the value greatly exceeded 215 msec.43 Zone III responses (figs. 3 and 4) occurred in 5/16 patients (31%). The ranges are shown in table 2. In one patient (No. 19) Zone II and Zone III responses could not be differentiated. Zone IV responses occurred in only two patients (13%) (Nos. 6 and 15) (table 2, fig. 3). Atrioventricular junctional echo beats were seen in one patient

(No. 17). Sinoatrial and Atrioventricular Refractory Periods

As premature stimuli were used to scan the spontaneous atrial cycles the refractory periods of the sinoatrial junction Patient 6 (CJ)

180-

I

I

I

< .o

04

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