Tachycardia-Induced Cardiomyopathy: Atrial Fibrillation and Congestive Heart Failure

Cardiology Grand Rounds from

The diagnosis of TIC is often made retrospectively as the patient clinically and hemodynamically improves with rate or rhythm control.

University of North Carolina at Chapel Hill

Case Report

Tachycardia-Induced Cardiomyopathy: Atrial Fibrillation and Congestive Heart Failure Editors George A. Stouffer, MD Daniel J. Lenihan, MD Stamatios Lerakis, MD Richard G. Sheahan, MD

Authors Jeff P. Steinhoff, MD Richard G. Sheahan, MD

ABSTRACT: Tachycardia-induced cardiomyopathy occurs as a result of prolonged, excessive heart rates. Ventricular function may improve significantly upon control of the heart rate. We present a case of a patient with atrial fibrillation with rapid ventricular response who showed a dramatic improvement in left ventricular function following AV nodal ablation and insertion of a pacemaker. We also review the history and pathophysiology of tachycardia-induced cardiomyopathy. KEY INDEXING TERMS: Cardiomyopathy; Tachycardia; Atrial fibrillation; Cardioversion. [Am J Med Sci 2005;329(1):25–28.]

T

achycardia-induced cardiomyopathy (TIC) is a cardiomyopathy that occurs as a consequence of prolonged excessive heart rates. Upon normalization of heart rate, the cardiomyopathy partially or fully recovers. The earliest reported case of TIC was described in 1913 in a 23-year-old man who initially presented with atrial fibrillation and subsequently developed a dilated cardiomyopathy.1 Additional case reports of heart failure and atrial fibrillation that improved after conversion to normal sinus rhythm were also reported in the 1930s and 1940s.

From the Division of Cardiology, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina (JPS), and Beaumont Hospital, Dublin, Ireland (RGS). Correspondence: Richard G. Sheahan, MD, Consultant Cardiologist and Electrophysiologist, Beaumont Hospital, Dublin 9, Ireland (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

A 58-year-old man presented with increasing shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, increasing abdominal girth, and peripheral edema. He had to sleep upright on a recliner. Past history included mitral valvuloplasty, persistent atrial fibrillation, which was cardioverted and maintained for several years in sinus rhythm with quinidine and more recently with propafenone, and chronic obstructive pulmonary disease. On examination, the patient’s pulse was irregularly irregular, at a rate of 130 to 140 beats per minute. He had pulmonary edema, pleural effusions, marked ascites, and peripheral edema of the lower extremities extending bilaterally up to his groin. An electrocardiogram confirmed atrial fibrillation with a rapid ventricular response. An echocardiogram showed left ventricular systolic dysfunction with an ejection fraction of 30%, left atrial enlargement, and mild mitral stenosis with a valve area of 1.9 cm2. A left ventricular ejection fraction on a previous echocardiogram was estimated at 45% to 50%. A prior cardiac catheterization did not show any significant obstructive coronary disease. After treatment with diuretics, there was a dramatic improvement in his symptoms. Amiodarone treatment followed by cardioversion was recommended but the patient declined and wanted to proceed with rate control only. Because of his presentation with severe congestive heart failure in the context of deteriorating left ventricular function, an atrioventricular (AV) node ablation and VVIR pacemaker placement were undertaken.

Prevalence Tachycardia-induced cardiomyopathy has been described in atrial fibrillation,2– 4 atrial flutter,5–7 atrial tachycardias,8 –11 junctional tachycardias,10,12 AV nodal reentrant tachycardia,13 AV reentry via an accessory pathway,14 right ventricular outflow tract ventricular tachycardia,15,16 and other dysrhythmias17–19 (Table 1). It is difficult to estimate the prevalence of this disease because it is mainly described in case reports. Pathophysiology In 1962, animal models of TIC demonstrated that rapid atrial or ventricular pacing induced severe biventricular dilation and dysfunction20 (Table 2). Slower rates or decreased duration of rapid pacing resulted in less dysfunction. Hemodynamic and Structural Changes. Within 24 hours of the onset of rapid ventricular pacing, a decreased mean arterial pressure and cardiac output along with an increased pulmonary capillary wedge pressure is observed.21 Continued deterioration of cardiac function occurs for 3 to 5 weeks.22–33 Marked hemodynamic and structural changes occur in the heart, including a progressive decline in ejection fraction with increased end-diastolic and end-systolic dimensions, wall thinning, increased ventricular wall stress, and diastolic dysfunction. Deterioration of left ventricular ejection fraction and dilatation of the left ventricle are more marked in chronic ventricular tachycardia than chronic supraventricular tachycardia in a dog model.26 A report by McMahon et al33 demonstrated a 25

Tachycardia-Induced Cardiomyopathy

Table 1. Arrhythmias Associated with Tachycardia-Induced Cardiomyopathy2–19 Incessant atrial tachycardia Permanent junctional reciprocating tachycardia Atrial flutter Atrial fibrillation and flutter Junctional ectopic tachycardia AV nodal reentrant tachycardia AV reentrant tachycardia with bypass tract RV outflow tract ventricular tachycardia PVC-induced AV, Atrioventricular; PVC, premature ventricular contraction; RV, right ventricular.

nonhomogeneous response to sustained high rate pacing between the left and right ventricles. There was no change in the left ventricular mass, whereas the right ventricle demonstrated increased ventricular mass and increased myocyte cross-sectional area. The increased left ventricular dimensions result in the ventricle becoming more spherical. The initiation and progressive increase in mitral regurgitation is due to increased mitral annular area and impaired mitral leaflet coaptation.30 Cellular Mechanisms. On a cellular level, myocytes show loss of contractility, altered alignment, increased resting length, decreased beta-adrenergic density and decreased sensitivity to beta-agonists and extracellular calcium.22–25,27–29,32 Impaired action potential amplitude, diminished action potential upstroke velocity, prolongation of the myocyte action potential, and decreased calcium currents with evidence of impaired relaxation have been demonstrated.32 There is also disruption of the myocyte-basement membrane interface with decreased collagen crosslinking, decreased myocyte-basement membrane adhesion, and increased synthesis of extracellular proteoglycans with decreased myofibril synthesis.22– 25,27,28 Left atrial pacing at 240 bpm for 3 weeks was shown to cause a primary impairment in the intrinsic myocardial relaxation process independently of a decrease in restoring force.31 Atrial natriuretic peptide has also been found in right ventricular myocytes, further demonstrating the change in protein regulation.34 Other mechanisms for contractile dysfunction include energy depletion and ischemia due to shortened diastolic phase (and myocardial blood flow during Table 2. Pathophysiologic Changes from Tachycardia-Induced Cardiomyopathy19 –25 LV end-systolic dimension LV end-diastolic dimension Systemic vascular resistance Right atrial pressure Pulmonary capillary wedge pressure 11 Wall stress

1 11 11 11 11

1 1 1 1

1 Wall thinning

1 ⫽ increased; LV ⫽ left ventricular.

26

Mitral regurgitation Mitral annular dilatation Systolic dysfunction Diastolic dysfunction Spherical shape

diastole) as demonstrated by decreases in resting myocardial blood flow (during cessation of rapid pacing), decreased capillary lumen diameter, and further decreases of myocardial blood flow reserve in animals with “recovered” ventricular function at rest.23 Other causes for impaired relaxation include decreased activity of sarcoplasmic ATPase, decreased sarcoplasmic calcium release, and decreased activity of myofibrillar calcium-ATPase. Shite et al35 demonstrated a possible causative role for free radicals that can be prevented with supplementation of beta-carotene, ascorbic acid, and alpha-tocopherol in a rabbit model. Recovery. Experimental models demonstrate dramatic recovery when pacing is discontinued. The time to recovery is dependent on the rate and duration of pacing. Within 1 week after cessation of 4 weeks of right ventricular pacing at 216 beats/minute, mean ejection fraction increased from 32% to 62%. A decrease in peak systolic wall stress and circulating catecholamines were also observed.20 Left ventricular (LV) end-diastolic and end-systolic dimensions improve, although less rapidly.22–24 An increase in LV mass and wall thickness is seen during recovery. On a cellular level, the myocytes demonstrate hypertrophy and a decreased response to beta-agonists, despite decreased levels of circulating catecholamines. Clinical Reports The possibility of a diagnosis of TIC should be considered in patients who have LV dysfunction and persistently elevated heart rates, even in the presence of other causes for the cardiomyopathy. It is only retrospectively that a diagnosis of TIC is confirmed. Brignole et al2 randomized 23 patients with atrial fibrillation and flutter (with resting heart rate greater than 100 for more than 3 months) to AV node ablation and right ventricular pacemaker or right ventricular pacemaker implantation only. After 15 days, patients reported less palpitations and exertional dyspnea and an improved exercise duration. At this point, the remaining patients received AV nodal ablation. At 90 days, there were statistically significant improvements over baseline in exercise duration and New York Heart Association (NYHA) functional class. In a subgroup of patients with LV systolic dysfunction, a reversal of left ventricular dysfunction over baseline was seen. Grogan et al described nine patients with atrial fibrillation who were treated with rate or rhythm control, or both. LV ejection fraction (LVEF) increased from a range of 12% to 30% to a range of 40% to 64% during long-term follow-up of 3 to 56 months.3 The recovery of ejection fraction was not dependent on the restoration of sinus rhythm. Luchsinger et al6 described 11 patients with chronic refractory atrial flutter (with rates ⬎100 bpm) and mean LVEF of 30.9%. At a median of 7 months after ablation of the atrial flutter, LVEF had increased to 41.4% (P ⫽ 0.005), mean heart rate had decreased from 102 bpm to 79 January 2005 Volume 329 Number 1

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bpm, and NYHA functional class had improved from 2.6 to 1.6 (P ⫽ 0.002). Patients with a lower LVEF and functional class were less likely to have resolution of their cardiomyopathy. Two other reports cite atrial fibrillation secondary to thyrotoxicosis causing TIC that resolved with either ablation3 or a combination of antithyroid medication and rate control.4 The Ablate and Pace Trial was a prospective registry study of clinical outcomes and survival following ablation and pacing therapy in patients with symptomatic permanent atrial fibrillation.36 At 1 year, measures of quality of life showed significant and sustained improvement.36 Patients with an LVEF of less than 45% showed a significant improvement over baseline.36 Corey et al12 reported TIC due to incessant AV nodal reentrant tachycardia in a 49-year-old woman. Three weeks after ablation, the LVEF had increased from 39% to 58%, the increased end-diastolic and end-systolic dimensions had normalized, and the patient’s mild to moderate mitral regurgitation had resolved. Cruz et al13 reported seven patients with TIC from refractory AV reentrant tachycardia due to a concealed accessory pathway. After ablation of the accessory pathway, all patients were in NYHA class 1 and had increased their mean LVEF from 36.3% to 58.6%. Ventricular arrhythmias, including right ventricular outflow tract tachycardia, have been described as a cause of TIC. After ablation of the foci, the mean LVEF increased from 28% to 43%.15–17 Regression of TIC has also been described in cases of idiopathic ventricular tachycardia17 and in premature ventricular contraction–induced TIC.19 In the latter case, the patient was a 26-year-old woman having 25,000 to 56,000 premature ventricular contractions daily, a resting pulse of 100, and an LVEF of 43%. After ablation of multiple foci, the patient was having fewer than 2000 premature ventricular contractions daily, her LVEF improved to 58%, and her resting pulse was 60 to 70. Diagnosis A thorough search should be made for a condition responsible for systolic dysfunction, as this will often dictate treatment. In many instances, a thorough history and physical examination followed by echocardiography and possible coronary catheterization will elucidate the cause of the systolic dysfunction. Although the diagnosis of TIC can be made with certainty only in retrospect, certain clues point to potential TIC and reversibility. These include chronic or frequent cardiac arrhythmias (⬎10 –15% of the day) and heart failure with dilated chambers. Brugada et al28 have proposed the terms “pure” and “impure” TIC. In a case of pure TIC, tachycardia is the sole offending agent to a normal heart. An impure TIC superimposes a tachycardia on an already abnormal heart due to coronary artery disease, valvular heart disease, alcohol abuse, hypertension, or THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES

other forms of cardiomyopathy. Although both pure and impure TIC show variable forms of recovery, the absence of LVEF recovery does not disprove TIC but rather may represent an advanced, irreversible stage. Nevertheless, there are examples of dramatic rapid recovery in the above-mentioned case series, and while these cases may represent reporting bias, their successes speak for themselves. Management In patients with impure TIC, treatment of the underlying arrhythmia is critical. Subsequent therapies are dependent on the comorbidities. The possibility of recovery of LV function is guarded until the arrhythmia has been controlled for at least 3 months. Aggressive management of heart failure should be additionally pursued and includes the use of angiotensin-converting enzyme inhibitors, betablockers, furosemide, and spironolactone to maximally tolerated doses. Another echocardiogram should be obtained after 3 months. Holter monitoring may be required if there is any concern that the patient’s arrhythmia has recurred. Patients undergoing ablation and pacing have a high prevalence of structural heart disease and heart failure. In a meta-analysis of ablation and pacing, total 1-year mortality was estimated at 6.3%.37 This was similar to the 1.3 year total mortality seen in the Stroke and Prevention in Atrial Fibrillation Trial.38 For the majority of patients with pure TIC, treatment of the underlying arrhythmia should significantly contribute to the reversal of the left ventricular dysfunction. The exact duration of complete recovery of systolic and diastolic function remains unclear, although most patients will have recovered by 3 months. However, because the diagnosis is often made retrospectively, it is appropriate to treat all patients with aggressive heart failure medication, until recovery is confirmed by echocardiogram. Even in the event of complete recovery, the very long-term prognosis has yet to be determined. Are these patients at a higher risk for developing progressive irreversible congestive heart failure in later life? Careful follow-up of these patients is required, with the option of an annual echocardiogram. A registry of such patients needs to be developed to improve on our current understanding of patients with tachycardia-induced cardiomyopathy. Follow-Up of Our Patient The patient underwent radiofrequency ablation of his AV node and placement of a VVIR pacemaker. He was discharged on heart failure medications. At follow-up 3 months after the procedure, the patient was feeling much better. He had returned to fulltime employment. He had no further admissions for heart failure. An echocardiogram performed after this visit showed a left ventricular ejection fraction of 45% to 50%. 27

Tachycardia-Induced Cardiomyopathy

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