Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy

Left Ventricular Dysfunction Due to Atrial Fibrillation in Patients Initially Believed to Have Idiopathic Dilated Cardiomyopathy Martha Grogan, MD, Hugh C. Smith, MD, Bernard J. Gersh, MB,ChB, DPhil, and Douglas L. Wood, MD

Ten patients aged 22 to 80 years (median 57) with severe left ventricular (LV) dysfunction and atrial fhuillation (AF) wtth rapid ventrkular response were evalwted after therapy. Because most patients were unaware of their arrhythmia, duration was usually unknown. All patients had heart failure symptoms; 9 presented with New York Heart Association class III or IV disability, and 1 with class II disability. Initial LV ejection fraction ranged from 12 to 30% (median 25). No pattent had symptomatic coronary artery disease (4 underwent anglography). Myocarditts and infiltrative processes were excluded by biopsy in 5 patients. All patients were constdered hdttally to have idtopathic dilated cardiomyopathy wtth secondary AF. Ventricular rate was controlled in all patients, with &us rhythm restored in 5. At fdlow-up (median 30 months, range 3 to 56), all pattentr were asymptomattc. W ejection fraction after treatment ranged from 40 to 64% (median 52). It is conch&d that in some patients initially considered to have idiopathic dilated cardiomyopathy, AF with rapid ventricular response may be the primary cause rather than the consequence of severe LV dysfunction. LV dysfunction may be completely reversible with ventricular rate control. (Am J Cardiol1992;69:1570-1573)

he clinical entity of reversible left ventricular (LV) dysfunction secondaryto chronic tachycardia is now well-documented,i-7and in most patients, the underlying arrhythmia was supraventricular tachycardia. The deleteriouseffectsof chronic tachycardia on LV function have beenhighlighted further by an animal model of congestiveheart failure produced by rapid atria1 or ventricular pacing.8-16Despite reports of “tachycardia-induced cardiomyopathy,” atria1 fibrillation (AF) in the absenceof other heart diseaseis generally considereda benign entity, although 2 recent case reports suggestedthe contrary.i7J8 We report on 10 patients who had congestive heart failure, severe global LV hypokinesia and AF with a rapid ventricular response.The admitting diagnosisof all patients was “idiopathic” dilated cardiomyopathy with secondary AF. All 10 patients had marked improvement in LV function and complete resolution of the symptoms of heart failure with ventricular rate control.

T

METHODS Ten patients were identified from our clinical practice between 1985to 1990with AF and congestiveheart failure. A systematicreview of all patients with AF and LV dysfunction seen during thii time period was not performed. All patients presented with AF, rapid ventricular response,symptoms and physical findings of congestiveheart failure, and evidenceof LV dysfunction by echocardiographyor left ventriculography. Anatomic valvular heart diseasewas excluded by clinical evaluation and e&cardiography. Alcoholic heart disease was excluded by history, and absenceof clinical and laboratory evidence of alcohol abuse. Four patients (aged 36 to 61 years) underwent coronary angiography, and 5 underwent endomyocardial biopsy. Awarenessof dysrhythmia and duration of AF were assessedin all patients. New York Heart Association functional class,was determined before and after treatment. Medical records were reviewed for type of treatment, initial heart rate, heart rate after treatment, and length of follow-up. The initial ejection fraction was determined from echocardiographicdimensions in 8 patients by using a modified Quinones method.19LV measurementswere obtained as an averageof 25 beatsduring AF and of 3 From the Division of Cardiovascular D&easesand Internal Medicine, beatsduring sinus rhythm. In 2 patients, the initial ejecMayo Clinic and Mayo Foundation,Rochester,Minnesota.Manuscript tion fraction was obtained by biplane LV angiography, receivedNovember 19,1991;revisedmanuscriptreceivedand accepted using a Simpson’sRule.2oAll follow-up determinations February 20.1992. Addressfor reprints: Hugh C. Smith, MD, Mayo Clinic, 200 First of ejection fraction were performed using echocardiography. Street SW, Rochester,Minnesota 55905. 1570

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69

JUNE 15, 1992

TABLE I Clinical Characteristics of 10 Patients with Atrial Fibrillation and Congestive Heart Failure

I

Follow-Up Initial Initial NYHA

Ejection Fraction

Heart Rate

& Sex

Functional Class

Initial Heart Rate

(beatslmin)

(%)

(beatslmin)

Rhythm

Ejection Fraction (%I

22F 36M

III IV

175 140

25

66

AF

52

Amiodarone (digoxin, enalapril)

2

29

50

SR

52

3

38M

Ill

180

12t

50

AF

40

4 5 6

53F 55F 58M

Ill IV Ill

120 150 150

28 20 24

70 80 60

SR AF

61 54 52

7 8

6OF 60M

III

140 130

28

IV

23t

50 50

AF SR

50 64

9

61M 8OF

Ill II

140 120

25 30

60 70

SR

50 60

DC cardioversion (digoxin, quinidine) DC cardioversion (digoxin, quinidine, nifedipine) DC cardioversion (digoxin, enalapril) Amiodarone (digoxin, lisinopril) Digoxin, encainide (diltiazem, captopril, u-methyldopa) Amiodarone (diltiazem) DC cardioversion (digoxin, lisinopril, flecainide) Amiodarone (captopril, digoxin) Digoxin, propranolol

Age (yr)

Pt. 1

10

SR

AF

Type of

Treatment*

Duration (mos.) 30 22 35 30 56 14 44 30 3 21

‘Primary treatment that led to ventricular rate control or conversion to sinus rhythm is noted; other cardiac medications (with exception of diuretics) used at time of follow-up are in parentheses. tEjection fraction determined byventriculography, rather than echocardiography. AF = atrial fibrillation; DC = direct-current: NYHA = New York Heart Association; SR = sinus rhythm.

RESULTS Clinical characteristics of akaldulr-. the 10 patients are listed in Table I. All patients had little or no awarenessof palpitations or dysrhythmia, despite initial ventricular rates of 120 to 180 beats/min (median 140); consequently, the duration of AF could not be determined reliably. Most patients sought medical attention only when symptomsof heart failure developed. Nine patients presented with New York Heart Association class III or IV symptoms,and 1 with class II. The types of treatments used are listed in Table I. Four patients were maintained in normal sinus rhythm, 3 in normal sinus rhythm with intermittent AF, and 3 in AF with a controlled ventricular rate. Patient 10 had Tj thyrotoxicusis with secondaryAF. With rate control, her LV ejection fraction increased from 30 to 60% at 8-month follow-up, despitecontinued marked suppression of thyroid-stimulating hormone. Consequently, the LV dysfunction was most likely due to uncontrolled AF rather than to any direct effect of thyroid hormone. Patients 1 and 6 had poorly controlled hypertension at presentation. Although afterload reduction (angioten&converting enzyme inhibitors) may have contributed to improved ventricular function, the magnitude of improvement (>lOO%) was unlikely the result of afterload reduction alone. Patients 4, 5 and 8 had mild hypertension and received angiotensin-converting enzyme inhibitors. These 3 patients had no echocardiographic evidenceof hypertensive heart disease,and marked improvement of LV function was not accompaniedby significant change in blood pressure. w B Results of coronary angiography were normal in 3 patients. One patient had a significant stenosis(80?&of the diameter) of the distal circumflex artery, but no angina, evidenceof infarction, or regional wall motion abnormalities. He did not receive antianginal treatment. The 6 patients (aged 22 to 80 l

years) who did not undergo coronary angiography did not have symptomsor risk factors for coronary disease and did not receive treatment for ischemia that could accOuntfor the observedimprovement. hdomyoeuacll biopsy: Endomyocardial biopsy was performed in 5 patients. The results of these biop sies were negative for myocarditis (according to the Dallas criteria*‘) and any infiltrative processes.In the remaining 5 patients, there were no systemicsymptoms or clinical findings suggestiveof myocarditis or infiltrative processes. Ev~ofleftv~ functkn: Ejection fraction before and after treatment, corresponding heart rate, and rhythm are listed in Table I. Initial median LV ejection fraction ranged from 12 to 30% (median 25). With treatment, ejection fraction doubled (range 40 to 64% median 52). The serial follow-up LV ejection fractions of 3 patients are shown in Figures 1 to 3, becausethey provide insight into the relation betweenatrial rhythm, ventricular rate and LV function. An example of the decreasein heart size with treatment is shown in the chest radiographs in Figure 4. Fdkw-up: Follow-up ranged from 3 to 56 months (median 30). The 7 patients who remained asymptomatic maintained sinus rhythm or AF with controlled ventricular response.Three patients had recurrent AF with rapid ventricular response; all 3 had recurrent symptomsof heart failure, again without being aware of the dysrhythmia. DISCUSSION In the last 40 years, congestiveheart failure in association with chronic sustained supraventricular tachycardia was reported in several small series and single case reports.lS7These reports suggestedthat chronic, uncontrolled tachycardia may result in severeglobal LV dysfunction that may resolve completely over a period of several months with rate control. In some patients, permanent damage could occur.3 Our initial review of

VENTRICULAR DYSFUNCTION DUE TO ATRIAL FIBRILIATION

1571

the prior 40 years of literature yielded only 3 reports of AF and reversible heart failure.i7J8+**However, further review revealed that AF alone was suggestedas the cause of dilated cardiomyopathy in previously normal hearts as long ago as 1913.23Similar reports were published from 1930 to 1949,24-27followed by a 40-year hiatus. In 1949,Phillips and Levine27describedthe first series of patients with AF and reversible heart failure

and concluded that “auricular fibrillation per se may produce cardiac dilatation and progressive congestive failure . . . a truly reversible type of heart failure.” Severalmechanismsof tachycardia-induced LV dysfunction have been proposed, including depletion of high-energy phosphatestores,*activation of the sympathetic nervous and renin-angiotensin systems,9,10 depletion of atria1 natriuretic factor,” and myocardial isch-

60 52 40

FIGURE 1. hial ejecUon fracthm (EF) in 36.yeJaMldmanwho~lwoek

EF, %

zgfggp$gys

20

0 Heart rate

initial

4 days

2 months

AF 75*

SR 80

SR 80

SR 60

60

60

8 months

rospanseof14Gbeatshbl.Flrst2studk -~kkmtkalleftvontrkduejectbnfractlenqsecondwasporfomlodafbrcomenbn to#husrhythm (SR). Mahed impownrant was seen at 2. and8-monthfoSowup,doepRosl* hoartratosfor1studl8s.

(0-N *Heart

rate 140 one week earlier

60

FIGURE 2. Sedal ejectiam fractions (EF) in 8G-year-oldwomanwhowasinatddiilwbtlon(AF)foraU~ sbldloe.Mo4ost ~WiBSSOOll8f-

40

EF, %

temlmadhofratecmtrol,withretumto nomldvelMdar-at4monthfol-

20

bw-lp.Ratocontdabno~ln&a-

motlchpmvmedlnejectbnfractbn without8nydmngeinhyUm.

0 Heart rate (O-4

Initial

1 month

4 months

8 months

AF 120

AF 70

AF 76

AF 70

61

60

52 40

EF, % 20

0 Heart rate

Initial

3 months

51 months

AF 150

AF 75

AF 140

56 months

SR 80

W-4 1572

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69

JUNE 15. 1992

FlGURE4.Decreaeincardiacsizewith -i6-bydlestr3dbi--n&). um.Lt?ft,atrw fibddbnwiullaw twspmm ot a75 beawn; aliibrimhwnh-venbiaJar rate ot 66 beats/min.

dgw, alli-

emia with depressedcontractility. l 2~13 LV hypertrophy, diastolic dysfunction and ventricular remodeling have been described in the experimental animal mode1.14-l6 We report the first series of patients with AF and reversible cardiomyopathy since that of Phillips and Levine.27All our patients presentedwith AF and LV dysfunction, and although a normal heart before AF cannot be proved, all echocardiogramsafter treatment were normal. All patients had little or no awarenessof AF. Such patients may be particularly prone to develop LV dysfunction becauseof prolonged, unrecognizedand untreated rapid heart rates, Most patients had only modeat improvement immediately after rate control, with gradual improvement occurring during a l- to 12month period; this gradual improvement, despitesimilar heart rates (Figures 1 and 2), argues strongly that the initially decreasedejection fraction measurement was not an artifact of heart rate alone. Factors other than rate control may have contributed to the improved LV function in our patients. Treatment for hypertension, use of angiotensin-converting enzymeinhibitors, and other therapiesfor heart failure may have been partially responsible for the improvement in LV function. However, the overall magnitude of improvement in LV function makes it unlikely that these therapies were the major cause of the ob served clinical response. Our conclusions are strikingly similar to those of Phillips and Levine2740 years ago. AF with rapid ventricular responsemay be a primary causerather than a secondaryeffect of severeLV dysfunction. Recognition of this entity has important diagnostic, therapeutic and prognostic implications, becausesustainedAF is not uncommon, and the associatedcardiomyopathy may be completely reversible.

REFERENCES 1. Packer DL, Bardy GH, Worley SJ, Smith MS, Cobb FR, Coleman E, Gallagher JJ, German LD. Tachycardia-inducedcardiomyopathy:a reversibleform of left ventricular dysfunction. Am J Cardiol 1986;57:563-570. 2. Giorgi LV. Hartzler Go, Hamaker WR. Incessantfocal atria1tachycardia: a surgically remediable cause of cardiomyopathy. J Thorac Cardiwosc Surg 1984;87:466-469.

3. McLaran CJ, Gersh BJ, SugrueDD, Hammill SC, SewardJB, Holmes DR Jr. Tachycardia induced myocardial dysfunction: a reversible phenomenon?Br Heart J 1985;53:323-327.

4. Claibome TS. Auricular tachycardia with auriculoventricular block of 12years

duration in a 16-year-oldgirl. Am Hear? J 1950;39:444-450. 5. ShachnowN, Spellman S, Rubin I. Persistentsupraventricular tachycardia: case report with review of literature. Circulation 1954;10:232-236. 6. KeaneJF, Plauth WH Jr, Nadas AS. Chronic ectopic tachycardia of infancy and childhood. Am Heart J 1972;84:748-757. 7. Engel TR, Bush CA, Schaal SF. Tachycardia-aggravatedheart disease.Ann Intern Med 1974;80:384-388.

6. Coleman HN III, Taylor RR, Pool PE, Whipple GH, Cove8 JW, RossJ Jr, Braunwald E. Congestiveheart failure following chronic tachycardia.Am Heart J 1971;81:79C-798, 9, RieggerAJG, Liebau G. The renin-angiotensin-aldosterone system,antidiuretic hormoneand sympatheticnerveactivity in an experimentalmodelof congestive heart failure in the dog. C/in .Sci 1982;62:465-469. 10. Riegger GAJ, Liebau G, Holzschuh M, Witkowski D, Steilner H, Kochsiek K. Role of the renin-angiotensinsystemin the developmentof congestiveheart failure in the dog as assessedby chronic converting-enzymeblockade. Am J Cardiol 1984;53:614-618. 11. Armstrong PW, Stopps TP, Ford SE, and de Bold AJ. Rapid ventricular pacing in the dog: pathophysiologicstudiesof heart failure. Circulation 1986;

74:1075-1084. 12. Moe GW, Stopps TP, Howard RJ, Armstrong PW. Early recovery from heart failure: insights into the pathogenesisof experimental chronic pacing-induced heart failure. J Lab Clin Med 1988;112:426-432. 13. Corday E, Gold H, de Vera LB, Williams JH, Fields J. Effect of the cardiac arrhythmias on the coronary circulation. Ann Intern Med 1959;50:535-553. 14. Tomita M, Spinale FG, Crawford FA, Zile MR. Changesin left ventricular volume, mass,and function during the developmentand regressionof supraventricular tachycardia-inducedcardiomyopathy:disparity betweenrecovery of systolic versusdiastolic function. Circulation 1991;83:635-644. 15. Spinale FG, Hendrick FA, Crawford FA, Smith AC, Hamada Y, Carabdo BA. Chronic supraventricular tachycardia causesventricular dysfunction and subendccardialinjury in swine. Am J Physiol 1990;259:H218-H229. 16. Weber KT, Pick R, Silver MA, Moe GW, Janicki JS, Zucker IH, Armstrong PW. Fibrillar collagenand remodelingof dilated canineleft ventricle. Circulation 1990;82:1387-1401. 17. Peters KG, Kienzle MG. Severe cardiomyopathy due to chronic rapidly conductedatrial fibrillation: completerecovery after restoration of sinusrhythm. Am J A4ed 1988;85:242-244. 16. SarembockIJ, Horack AR, CommerfordPJ.Tachycardia-inducedreversible left ventricular dysfunction: a report of 2 cases.S A/r &fed J 1988;73:484-485. 19. QuinonesMA, WaggonerAD, Reduto LA, Nelson JG, Young JB, Winters WL Jr, Ribeiro LG, Miller RR. A new, simplified and accurate method for determining ejection fraction with two-dimensionalechocardiography.Circulation 1981;64:744-753. 20. ChapmanCB, Baker 0, ReynoldsJ, Bonte FJ. Use of biplane cinefluorog raphy for measurementof ventricular volume. Circulation 1958;18:1105-1117. 21. Aretz HT. Billingham ME, EdwardsWD, Factor SM, Fallon JT, FenoglioJJ Jr, OlsenEG, SchoenFJ. Myocarditis. A histopathologicdefinition and classitication. Am J Cardiouax Pathol 1987;1:3-14. 22. Rosenqvist M, Lee MA, Moulinier L, Springer MJ, Abbott JA, Wu J, LangbergJJ, Griffin JC, ScheinmanMM. Long-term follow-up of patientsafter transcatheterdirect current ablation of the atrioventricular junction. J Am CON Cardiol 1990;16:1467-1474. 23. GossageAM, Hicks JAB. On auricular fibrillation. Q J Med 1913;6: 435-440. 24. ParkinsonJ, Campbell M. Paroxysmalauricular fibrillation: a record of two hundred patients. Q J Med 1930;24:67-100.

26. Brill IC. Auricular fibrillation with congestivefailure andno other evidenceof organic heart disease.Am Heart J 1937;13:175-182. 26. Brill IC. Congestiveheart failure arising from uncontrolledauricular Iibrillation in the otherwise normal heart: follow-up noteson a previously reported case. Am J Med 1947;2:544-547.

27. Phillips E. Levine SA. Auricular tibrillation without other evidenceof heart disease:a causeof reversible heart failure. Am J Med 1949;7:478-489.

VENTRICULAR DYSFUNCTION DUE TO ATRIAL FIBRILLATION

1573