ARRNYTNMIAS AND CDNDUCTIDN DlSlURBANCES
Treatment of Ventricular Arrhythmias by United States Cardiologists: a Survey Before the Cardiac Arrhythmia Suppression Trial Results Were Available Joel Morganroth, MD, J. Thomas Bigger, Jr., MD, and Jeffrey L. Anderson, MD TodefhethepractkebabttsofUnitedStates WdidOgiStSuldtlKttW!dlMdOfVentriwlsr
srrhythdas, a random sample of 1,DDD of 12,DDD car&&tstswassentapretestedquertSwuire. Afterfobwup procedurer, =-,of
aakddly-based, whldl18%wem lmpitai-based d S3% were -.
28% were
Attitudesabaut~rrbytbmk~therapyforthe treahed of ventrk&r antrythiar were hftuand sevedty of cardiac dir-bywofsymptomsandthetypeof -=,hV ventrkuhr afhyttnnlar. In WI suvey, only 1% of treatedpatkntswithasymptomatk ~compkXe,MdfBOblWtdiSiztz!zr
ease,but17%treatedaKfhpathtsifunrurtained v~tacbycardiawaspresent.mrate~cardiotogistshcrearedto38%wlmn camnary utw disease with left ve flalcthwaspnranthpanentswithasymptomptie Ventricuhr
dys-
ptWldWecOmpkX~The~Of
any car&at dtsease and symptomatk venWadar a&ytbmias Wsed the treaMeMrateto0Dto lOO%.Apt~~xhnatetySO%ot rewadhgphysidanstreatedpat&ntscomparsbletotbecardbc
ArTimythmia~Trialstudypopula8on with antiambythdc drugs. Beta blockers were the mostcomnnmurtivrhythnkdnqgdaucbosenar the most mte initw therapy in new patknts whereasno-witbv-&ythmias. giststbaughtthatamkdaronewasappropriateto tnitiatehnewpatkntswithtm&norpotsntidly InaiigMnt ventrkuk r arrhythmia& as many as 33 to43%ofcardkW&woutduseamMafonefur refractwy pathts with swh ambyttdas, a response unltradktofy to the approved labeling for this dw. Lesstbanonehdtof~recogntzetbe ligb potential organ toxicity for qulnidhe, procainbetieved that a&and tocaM&. w adarrhytinnkagemtswithdauIAandICactim~ wereequalty~ytbmkinpatkMswitbpotenventrk&r ant\ytbmias. Anttarww rbyttdc drugs were hi&ted only in-hcqital by dOUt2StOSO%Off2dkbgiStS.Eketrophyrkiogk testing was hays used by 83% of cardktogistsforev~ofsustahedvenMculartacbycwlicr;33%nevarusedswhtesthgforpatknts v-ar amhythmiis. fipotwmcrlignant intbeseresuttsbasedon ThenWStVnOdmerenccH
40
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65
Thus, signifkant lade of CoMensu existsontbs toxicity of antiarrhytlwnii dfugs, use of ekctrophyddogk testhg and in- versus out+f-bospiM dug initlattan. At the time of the survey,,most cardiologiststreatedpatkntswitbasymptomatkand symptomatkpot~malignurtv~arlhythmi,althoughIhhiti~-OftheC~Trial hdkate recondiacAlThythmiasqBpmsh sideration for therapy h ruch patknts. (Am J Cardtol lSSD;eS~40-48)
lthough a consensusexistsabout the management of patients with either benign or malignant ventricular arrhythmias, the management of the large group of patients with potentially malignant ventricular arrhythmias is controversial.*,* An example of the potentially malignant group is the postmyocardial infarction patient with minimally symptomatic or asymptomatic ventricular ectopy. It was hoped.that the Cardiac Arrhythmia SuppressionTrial (CAST), which began in June 1987, would determine whether antiarrhythmic drug suppressionof asymptomatic or mildly symptomatic ventricular premature complexes (WCs) with or without unsustained ventricular tachycardia (VT) would significantly decreasethe at-rhythmic death rate.3It is expectedthat the practice patterns of cardiologists will evolvewith new information from clinical trials and with the availability of new antiarrhythmic drugs. To measurethe practice of United Statescardiologists in regard to ventricular arrhythmia management, we conducted a survey before releaseof the interim results of CAST.
A
MEmoDs ll~ w A 4-page questionnaire was developedunder the name “National Arrhythmia Survey” to evaluate the indications for treatment of ventricular From the Center of Excellencefor CardiovascularStudies of the Graduate Health System and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;College of Physiciansand Surgeonsof Columbia University, New York, New York; and LDS Hospital and the University of Utah School of Medicine, Salt Lake City, Utah. Manuscript receivedAugust 1.1989,revisedmanuscriptreceived and acceptedAugust 31,1989. Address for reprints: Joel Morganroth, MD, Center of Excellence for CardiovascularStudies,the Graduate Hospital, One Graduate Plaza, Philadelphia, Pennsylvania19146.
TABLE Ill Ratings of the Efficacy of Antiarrhythmic
Drugs for Potentially Malignant or Malignant Ventricular Arrhythmias (% of 252 Cardiologists)
TABLE I Use of Antiarrhythmic Drugs by Patient Group, Arrhythmia Type and Symptoms (% of 252 Cardiologists) Asymptomatic
Symptomatic
Cardiac Status
VPC
vpc+VT-n
VPC
VPC t VT-n
VT-S
No heart disease No CAD, LVEF O.40 CAD, LVEF CO.40 AMI within 6 months SymptomaticCHF
1 21 13 38 41 36
17 61 51 76 79 73
66 80 80 88 90 86
88 96 97 98 98 96
100 100 100 100 100 100
Potentially
Malrgnant
MalIgnant
Hgh
Moderate
Low
Low
?
Quinidrne Procarnamide Disopyramrde
34 36 18
60 59 67
6 5 13
?
0 28 030 211
57 57 58
14 13 27
1 0 4
Mexiletine Tocainrde
26 15
49 52
23 29
220 413
44 42
33 41
3 4
Encainide Ftecainide
65 73
26 21
4 3
540 3 45
43 39
11 12
6 4
fl blockers
8
37
54
1
3
17
78
2
Amiodarone
71
7
3
19 85
9
1
4
Hugh Moderate
TAME II Sequence of Antiarrhythmic
Drugs by Ventricular Patients (% of 252
Arrhythmia Class in Symptomatic Cardiologists)
? = don’t know.
Not Appropriate for New Pabents but Not Reserved for Refractory Cases
Appropriate to Initiate in New Patients
TABLE IV Ratings of the Noncardiac Adverse Effects of Antiarrhythmic Drugs (% of 252 Cardiologists)
Resewed Only for Refractory Cases
Adverse Effects High
Medium
Quinrdine Procainamide Disopyramide
70 54 65
24 38 25
0 14
Mexitetine Tocarnrde
39 59
11 13
6 8
Encainide Ftecainide
2
1
1
33
43
76
B
PM
M
B
PM
M
B
Quinidine Procainamide Disopyramide
68 65 42
78 78 53
90 90 64
20 23 36
15 16 28
7 7 22
7 6 12
3 3 10
1 1 4
Mexitetine Tocainide
45 31
53 41
93 47
34 31
32 29
6 26
12 15
9 13
Encainide Ftecainide
42 39
51 45
61 59
35 35
33 37
29 29
16 18
Bbkckers
80
80
38
11
12
26
0
0
7
4
6
14
Amiodarone
6 - bewgn. M = mafgnant:
PM = potenhally
PM
Organ Toxraty Low
?
High
Medium
Low
?
6
0
31
38
10
0
21
23
31 31 54
0 0 2
43 30
14 5
4 6
9 37
32 31
55 28
4 4
15 17
41 43
39 36
5 4
6 13
31 29
57 54
6 4
p blockers
37
39
24
0
2
17
81
0
Amiodarone
94
3
1
2
95
2
1
2
M
a 040
38
mahenant.
arrhythmias based on the presenceand degreeof heart disease,symptoms and type of arrhythmia. The questionnaire provided specific definitions for arrhythmia classification and for symptoms. In addition, the currently available antiarrhythmic drugs approved by the Food and Drug Administration in the United States were listed alphabetically in the questionnaire (although reported herein by antiarrhythmic class). We sought to determine cardiologists’ attitudes about indications for treatment and the relative degrees,of efficacy, noncardisc adverse effects, probability of organ toxic effects, proarrhythmia and negative inotropic features of antiarrhythmic drugs. Information also was obtained on how cardiologists usedelectrophysiologic testing in their practice. We pretested the questionnaire using 20 cardiologists and revised the questionnaire basedon this pretest to enhanceits clarity (Appendix). A marketing research firm, Anderson, Neibuhr and Associates, handled the logistics of mailing the questionaires and data tabulation. cdkttlonndUNlYdSrA p=d% list of approximately 12,000 actively practicing cardiol-
ogists representedthe initial database for selection of the sample population. From the list, a random sample of 1,000 cardiologists was selectedby a digital computer. The survey was conducted from May to November 1988.The questionnaire was sent to the 1,000 cardiologists with a cover letter by first class mail with a preaddressedpostage-paid return envelope. Cardiologists who did not respond were sent 3 additional follow-up reminders with a secondcopy of the questionnaire. An option for a telephone interview to complete the survey also was offered. The completed surveys were transferred to magnetic tape for computer analysis and were quality controlled for data verification. The Statistical Packagefor the Social Scienceswas used in the analysis. RESULTS Questionnaires were returned by 252 of the 1,000 cardiologists sampled (25%). Generalization of the data to all cardiologists should be performed cautiously due to this responserate. Of the cardiologists responding, 53% said their practice was office-based,29% were hospital-based and 18%were academically-based.TwentyTHE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1990
41
TABLE V Ranking of Major Cardiovascular
Adverse Effects of Antiarrhythmic
Proarrhythmia in Patients with Potentially Malignant Ventricular Arrhythmias
Proarrhythmia in Patients with Malignant Ventricular Arrhythmias
High
Mod
Low
Quinidine Procainamida
38 24
42 50
Disopyramide
16
48
19 25 33
Mexdetine
12
42
Tocainide
12
39
?
Aggravation of Congestive Heart Failure
High
Mod
Low
1 1 3
46 35 37
42
10 12 14
2
51 44
42 42
4 7
18 18
46 45
?
High
Mod
Low
?
11 9 88
44 52 9
43 37 1
2
2 5
29 29
7 8
5 5
38 37
53 51
4 7
2 2
Encainide
33
45
19
Fkainide
43
39
16
3 2
54 57
36 22
6 5
4 3
18 64
45 25
33 9
4 2
B blockers
2
12
85
1
15
23
55
7
88
6
2
1
Amiiarone
14
29
45
12
20
32
37
11
14
37
43
6
one percent of the respondents lived in the Western United States, 26% in the Midwest, 23% in the Northeast and 30% in the South. Table I lists the cardiologists’ responsesto the survey’s first question, in which their decisionsto use antiarrhythmic therapy were related to the presenceand severity of cardiac disease,type of arrhythmia and degree of symptoms. Whereas 1% of cardiologists routinely prescribed antiarrhythmic drugs for patients without heart disease and asymptomatic VPCs, 17% treated such patients if unsustained VT was present. In asymp tomatic patients, the type of ventricular arrhythmia and the severity of cardiac disease were each of approximately equal importance in treatment decisions (columns 3 and 4 in Table I). When symptoms and heart diseasewere present, >80% of cardiologists gave treatment. The questionnaire subgroupsthat relate closely to the patient population being studied in the CAST are those with acute myocardial infarction within 6 months or coronary artery diseasewith ejection fraction
Treatment of Ventricular Arrhythmias by United States Cardiologists: a Survey Before the Cardiac Arrhythmia Suppression Trial Results Were Available Joel Morganroth, MD, J. Thomas Bigger, Jr., MD, and Jeffrey L. Anderson, MD TodefhethepractkebabttsofUnitedStates WdidOgiStSuldtlKttW!dlMdOfVentriwlsr
srrhythdas, a random sample of 1,DDD of 12,DDD car&&tstswassentapretestedquertSwuire. Afterfobwup procedurer, =-,of
aakddly-based, whldl18%wem lmpitai-based d S3% were -.
28% were
Attitudesabaut~rrbytbmk~therapyforthe treahed of ventrk&r antrythiar were hftuand sevedty of cardiac dir-bywofsymptomsandthetypeof -=,hV ventrkuhr afhyttnnlar. In WI suvey, only 1% of treatedpatkntswithasymptomatk ~compkXe,MdfBOblWtdiSiztz!zr
ease,but17%treatedaKfhpathtsifunrurtained v~tacbycardiawaspresent.mrate~cardiotogistshcrearedto38%wlmn camnary utw disease with left ve flalcthwaspnranthpanentswithasymptomptie Ventricuhr
dys-
ptWldWecOmpkX~The~Of
any car&at dtsease and symptomatk venWadar a&ytbmias Wsed the treaMeMrateto0Dto lOO%.Apt~~xhnatetySO%ot rewadhgphysidanstreatedpat&ntscomparsbletotbecardbc
ArTimythmia~Trialstudypopula8on with antiambythdc drugs. Beta blockers were the mostcomnnmurtivrhythnkdnqgdaucbosenar the most mte initw therapy in new patknts whereasno-witbv-&ythmias. giststbaughtthatamkdaronewasappropriateto tnitiatehnewpatkntswithtm&norpotsntidly InaiigMnt ventrkuk r arrhythmia& as many as 33 to43%ofcardkW&woutduseamMafonefur refractwy pathts with swh ambyttdas, a response unltradktofy to the approved labeling for this dw. Lesstbanonehdtof~recogntzetbe ligb potential organ toxicity for qulnidhe, procainbetieved that a&and tocaM&. w adarrhytinnkagemtswithdauIAandICactim~ wereequalty~ytbmkinpatkMswitbpotenventrk&r ant\ytbmias. Anttarww rbyttdc drugs were hi&ted only in-hcqital by dOUt2StOSO%Off2dkbgiStS.Eketrophyrkiogk testing was hays used by 83% of cardktogistsforev~ofsustahedvenMculartacbycwlicr;33%nevarusedswhtesthgforpatknts v-ar amhythmiis. fipotwmcrlignant intbeseresuttsbasedon ThenWStVnOdmerenccH
40
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 65
Thus, signifkant lade of CoMensu existsontbs toxicity of antiarrhytlwnii dfugs, use of ekctrophyddogk testhg and in- versus out+f-bospiM dug initlattan. At the time of the survey,,most cardiologiststreatedpatkntswitbasymptomatkand symptomatkpot~malignurtv~arlhythmi,althoughIhhiti~-OftheC~Trial hdkate recondiacAlThythmiasqBpmsh sideration for therapy h ruch patknts. (Am J Cardtol lSSD;eS~40-48)
lthough a consensusexistsabout the management of patients with either benign or malignant ventricular arrhythmias, the management of the large group of patients with potentially malignant ventricular arrhythmias is controversial.*,* An example of the potentially malignant group is the postmyocardial infarction patient with minimally symptomatic or asymptomatic ventricular ectopy. It was hoped.that the Cardiac Arrhythmia SuppressionTrial (CAST), which began in June 1987, would determine whether antiarrhythmic drug suppressionof asymptomatic or mildly symptomatic ventricular premature complexes (WCs) with or without unsustained ventricular tachycardia (VT) would significantly decreasethe at-rhythmic death rate.3It is expectedthat the practice patterns of cardiologists will evolvewith new information from clinical trials and with the availability of new antiarrhythmic drugs. To measurethe practice of United Statescardiologists in regard to ventricular arrhythmia management, we conducted a survey before releaseof the interim results of CAST.
A
MEmoDs ll~ w A 4-page questionnaire was developedunder the name “National Arrhythmia Survey” to evaluate the indications for treatment of ventricular From the Center of Excellencefor CardiovascularStudies of the Graduate Health System and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania;College of Physiciansand Surgeonsof Columbia University, New York, New York; and LDS Hospital and the University of Utah School of Medicine, Salt Lake City, Utah. Manuscript receivedAugust 1.1989,revisedmanuscriptreceived and acceptedAugust 31,1989. Address for reprints: Joel Morganroth, MD, Center of Excellence for CardiovascularStudies,the Graduate Hospital, One Graduate Plaza, Philadelphia, Pennsylvania19146.
TABLE Ill Ratings of the Efficacy of Antiarrhythmic
Drugs for Potentially Malignant or Malignant Ventricular Arrhythmias (% of 252 Cardiologists)
TABLE I Use of Antiarrhythmic Drugs by Patient Group, Arrhythmia Type and Symptoms (% of 252 Cardiologists) Asymptomatic
Symptomatic
Cardiac Status
VPC
vpc+VT-n
VPC
VPC t VT-n
VT-S
No heart disease No CAD, LVEF O.40 CAD, LVEF CO.40 AMI within 6 months SymptomaticCHF
1 21 13 38 41 36
17 61 51 76 79 73
66 80 80 88 90 86
88 96 97 98 98 96
100 100 100 100 100 100
Potentially
Malrgnant
MalIgnant
Hgh
Moderate
Low
Low
?
Quinidrne Procarnamide Disopyramrde
34 36 18
60 59 67
6 5 13
?
0 28 030 211
57 57 58
14 13 27
1 0 4
Mexiletine Tocainrde
26 15
49 52
23 29
220 413
44 42
33 41
3 4
Encainide Ftecainide
65 73
26 21
4 3
540 3 45
43 39
11 12
6 4
fl blockers
8
37
54
1
3
17
78
2
Amiodarone
71
7
3
19 85
9
1
4
Hugh Moderate
TAME II Sequence of Antiarrhythmic
Drugs by Ventricular Patients (% of 252
Arrhythmia Class in Symptomatic Cardiologists)
? = don’t know.
Not Appropriate for New Pabents but Not Reserved for Refractory Cases
Appropriate to Initiate in New Patients
TABLE IV Ratings of the Noncardiac Adverse Effects of Antiarrhythmic Drugs (% of 252 Cardiologists)
Resewed Only for Refractory Cases
Adverse Effects High
Medium
Quinrdine Procainamide Disopyramide
70 54 65
24 38 25
0 14
Mexitetine Tocarnrde
39 59
11 13
6 8
Encainide Ftecainide
2
1
1
33
43
76
B
PM
M
B
PM
M
B
Quinidine Procainamide Disopyramide
68 65 42
78 78 53
90 90 64
20 23 36
15 16 28
7 7 22
7 6 12
3 3 10
1 1 4
Mexitetine Tocainide
45 31
53 41
93 47
34 31
32 29
6 26
12 15
9 13
Encainide Ftecainide
42 39
51 45
61 59
35 35
33 37
29 29
16 18
Bbkckers
80
80
38
11
12
26
0
0
7
4
6
14
Amiodarone
6 - bewgn. M = mafgnant:
PM = potenhally
PM
Organ Toxraty Low
?
High
Medium
Low
?
6
0
31
38
10
0
21
23
31 31 54
0 0 2
43 30
14 5
4 6
9 37
32 31
55 28
4 4
15 17
41 43
39 36
5 4
6 13
31 29
57 54
6 4
p blockers
37
39
24
0
2
17
81
0
Amiodarone
94
3
1
2
95
2
1
2
M
a 040
38
mahenant.
arrhythmias based on the presenceand degreeof heart disease,symptoms and type of arrhythmia. The questionnaire provided specific definitions for arrhythmia classification and for symptoms. In addition, the currently available antiarrhythmic drugs approved by the Food and Drug Administration in the United States were listed alphabetically in the questionnaire (although reported herein by antiarrhythmic class). We sought to determine cardiologists’ attitudes about indications for treatment and the relative degrees,of efficacy, noncardisc adverse effects, probability of organ toxic effects, proarrhythmia and negative inotropic features of antiarrhythmic drugs. Information also was obtained on how cardiologists usedelectrophysiologic testing in their practice. We pretested the questionnaire using 20 cardiologists and revised the questionnaire basedon this pretest to enhanceits clarity (Appendix). A marketing research firm, Anderson, Neibuhr and Associates, handled the logistics of mailing the questionaires and data tabulation. cdkttlonndUNlYdSrA p=d% list of approximately 12,000 actively practicing cardiol-
ogists representedthe initial database for selection of the sample population. From the list, a random sample of 1,000 cardiologists was selectedby a digital computer. The survey was conducted from May to November 1988.The questionnaire was sent to the 1,000 cardiologists with a cover letter by first class mail with a preaddressedpostage-paid return envelope. Cardiologists who did not respond were sent 3 additional follow-up reminders with a secondcopy of the questionnaire. An option for a telephone interview to complete the survey also was offered. The completed surveys were transferred to magnetic tape for computer analysis and were quality controlled for data verification. The Statistical Packagefor the Social Scienceswas used in the analysis. RESULTS Questionnaires were returned by 252 of the 1,000 cardiologists sampled (25%). Generalization of the data to all cardiologists should be performed cautiously due to this responserate. Of the cardiologists responding, 53% said their practice was office-based,29% were hospital-based and 18%were academically-based.TwentyTHE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1990
41
TABLE V Ranking of Major Cardiovascular
Adverse Effects of Antiarrhythmic
Proarrhythmia in Patients with Potentially Malignant Ventricular Arrhythmias
Proarrhythmia in Patients with Malignant Ventricular Arrhythmias
High
Mod
Low
Quinidine Procainamida
38 24
42 50
Disopyramide
16
48
19 25 33
Mexdetine
12
42
Tocainide
12
39
?
Aggravation of Congestive Heart Failure
High
Mod
Low
1 1 3
46 35 37
42
10 12 14
2
51 44
42 42
4 7
18 18
46 45
?
High
Mod
Low
?
11 9 88
44 52 9
43 37 1
2
2 5
29 29
7 8
5 5
38 37
53 51
4 7
2 2
Encainide
33
45
19
Fkainide
43
39
16
3 2
54 57
36 22
6 5
4 3
18 64
45 25
33 9
4 2
B blockers
2
12
85
1
15
23
55
7
88
6
2
1
Amiiarone
14
29
45
12
20
32
37
11
14
37
43
6
one percent of the respondents lived in the Western United States, 26% in the Midwest, 23% in the Northeast and 30% in the South. Table I lists the cardiologists’ responsesto the survey’s first question, in which their decisionsto use antiarrhythmic therapy were related to the presenceand severity of cardiac disease,type of arrhythmia and degree of symptoms. Whereas 1% of cardiologists routinely prescribed antiarrhythmic drugs for patients without heart disease and asymptomatic VPCs, 17% treated such patients if unsustained VT was present. In asymp tomatic patients, the type of ventricular arrhythmia and the severity of cardiac disease were each of approximately equal importance in treatment decisions (columns 3 and 4 in Table I). When symptoms and heart diseasewere present, >80% of cardiologists gave treatment. The questionnaire subgroupsthat relate closely to the patient population being studied in the CAST are those with acute myocardial infarction within 6 months or coronary artery diseasewith ejection fraction
