Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy, with an estimated prevalence in the general population of 40 to 50 cases per 100,000. Treatment of DCM can cover a wide range of interventions, from pharmacologic to surgical. The following case profiles a patient with chemotherapyinduced DCM whose treatment strategy demonstrates a stepwise approach to the medical and surgical therapy available for this patient with refractory DCM.

Case presentation

An echocardiogram was requested on a 69-year-old white female who presented with shortness of breath upon minimal activity and 2- pillow orthopnea. Her medical history included breast cancer, treated with mastectomy followed by 6 months of Adriamycin (doxorubicin hydrochloride) after she developed recurrence with metastases in the lung. Following treatment with Adriamycin, she developed a DCM with an ejection fraction in the range of 15% to 25%, and required implantation of a dual-chamber pacemaker for advanced atrioventricular (AV) nodal block. She subsequently underwent prosthetic mitral valve replacement for severe symptomatic mitral regurgitation (MR) with simultaneous placement of a tricuspid annuloplasty ring for severe tricuspid regurgitation. Coronary artery catheterization prior to valve surgery revealed no significant coronary artery disease. Intermittent atrial fibrillation (AF) prior to valve surgery became persistent postoperatively. Two years ago she underwent upgrade to biventricular pacing for cardiac resynchronization treatment (CRT). She had incomplete biventricular pacing due to AF. Percutaneous pulmonary vein ablation for AF was performed 1 year ago. This was unsuccessful, and she subsequently underwent AV node ablation for AF. Symptoms of advanced heart failure improved from New York Heart Association (NYHA) class IV to class III.

Current medications included furosemide 40 mg every other day, warfarin, Atacand (candesartan cilexetil) 75 mg daily, carvedilol 12.5 mg twice a day, and digoxin 0.125 mg daily.

Evaluation prior to echocardiogram revealed a thin female, 4 feet 11 inches tall and weighing 80 lbs. Blood pressure was 105/60 mm Hg and heart rate was 75 beats per minute. Precordial exam revealed a displaced point of maximal impulse in the 6th intercostal space midway between the midclavicular and anterior axillary line. She had a prosthetic S₁ and a normal S₂. There was no S₃ and no pedal edema.

Electrocardiogram on the ultrasound monitor showed paced biventricular rhythm and underlying AF. An echocardiogram (Figure) showed a markedly dilated left atrium and a severely dilated left ventricle (LV) with global hypokinesis and a LV ejection fraction of 30%. There was a pacemaker catheter seen in the right ventricle as well as in the coronary sinus. There was a left-to-right shunt in the middle of the interatrial septum (residual shunting post transeptal puncture during attempt for AF ablation) (Movie 1), a normally functioning mitral prosthetic valve, a tricuspid annuloplasty ring (Movie 2), and trace tricuspid regurgitation. Her pulmonary artery systolic pressure was 40 to 45 mm Hg and right atrial pressure was approximately 15 mm Hg. She underwent optimization of interventricular delay of the biventricular pacemaker. She was in the VVI pacing mode due to the presence of AF. Atrioventricular delay could not be adjusted due to the presence of AF. Adjustment of interventricular delay was performed with LV offset of -10 ms that led to improvement in aortic velocity times integral (and hence stroke volume). She derived symptomatic improvement to NYHA class II after pacemaker optimization.

Figure. Dilated left ventricle with increased end diastolic dimension (A); end systolic dimension (B); prosthetic mitral valve (C, red arrow); pacing catheter in the right ventricle (green arrow head) and in the coronary sinus (turquoise arrows, D); pacing catheter in the right ventricular apical region and a dilated left ventricle (E); and flow across the interatrial septum from left atrium to right atrium from a prior transeptal puncture during atrial fibrillation ablation (F, purple arrow).

Discussion

This case provides an example of iatrogenic heart failure presumed to be secondary to the use of a cardiotoxic drug. Several new and effective treatment modalities have become available for congestive heart failure (CHF), and this patient illustrates the effective use of several of these treatments. Adriamycin analogues are the classic cardiotoxic medications,¹ but the number of cardiotoxic drugs, in particular chemotherapeutic agents, continues to grow.² To date, however, the treatment of DCM induced by cardiotic agents remains similar to the treatment of DCM from a variety of causes. She also demonstrates some of the current surgical and device therapies available for patients with drugrefractory advanced CHF.

Pharmacologic therapy in heart failure
Pharmacologic treatments for patients with advanced heart failure are intended to address neuroendocrine activation, and reduce both preload and afterload. Standard pharmacologic therapy, therefore, consists of β-blockers, diuretics (including loop diuretics), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), or a combination of hydralazine and nitrates (especially in African Americans) and spironolactone, which acts as a mineralocorticoid inhibitor.³ In patients who remain symptomatic, mineralocorticoid inhibitors have been shown to reduce both morbidity and mortality.^4,5 Digoxin can improve symptoms and exercise capacity and prevent hospitalization in patients with CHF but does not affect mortality.⁶

Treatment of mitral regurgitation in heart failure
Mitral regurgitation may be a direct result of a dilated failing ventricle. Mitral regurgitation is significant in up to 40% of patients with CHF.⁷ Although symptomatic relief of MR is possible with diuretics, the use of afterload reducing agents such as ACE inhibitors, ARBs, and other vasodilators has not been prospectively shown to be effective. In refractory symptomatic cases, whenever possible, surgical correction via mitral valve repair using an annuloplasty ring to tighten the mitral annulus should be considered.^8,9 In patients in whom repair is not possible (ie, due to a significantly lower mitral leaflet coaptation plane), mitral valve replacement with preservation of subvalvular apparatus provides the most effective treatment,^10,11 as was done with this patient. Several investigative procedures have been tested to prevent LV modeling, restore ventricular geometry, and reduce MR. These include the Batista procedure or LV volume reduction surgery¹² (wherein a portion of the LV is removed surgically to reduce LV size and hence wall stress), use of the CorCap Cardiac Support Device (Acorn Cardiovascular, Inc, St. Paul, MN) (which covers the LV like a “sock”),¹³ an elastic ventricular restraint (Paracor HeartNet Device¹⁴ [Paracor Medical, Sunnyvale, CA]), and the coapsy device (wherein a rod is passed across the basal LV and screwed in place at the septum and lateral wall with epicardial pads).^15,16 These devices are undergoing clinical evaluation; however, the results thus far have been minimally significant in trials using these modalities.

Treatment of tricuspid regurgitation in heart failure
Tricuspid regurgitation generally does not require surgical correction in patients with heart failure unless it is felt to be related to right ventricular dilation and dysfunction or is to be performed at the time of concomitant mitral or aortic valve surgery.¹⁷ Combined mitral and tricuspid regurgitation increases the mortality from heart failure secondary to nonischemic DCM,¹⁸ and therefore surgical correction of the 2 valves is often performed simultaneously,¹⁹ as in our patient.

Treatment of atrial fibrillation in heart failure
The incidence of AF in patients with CHF is as high as 20% to 40%, and is related to stretching of the atrial walls from either increased preload due to excessive fluid, MR, or simultaneous restriction of a dysfunctional LV wall. Once AF develops, it tends to become permanent in the absence of an improvement in LV function.²⁰ Amiodarone is the most frequently used antiarrhythmic agent for both supraventricular and ventricular arrhythmias in patients with CHF. Chronotropic incompetence commonly accompanies CHF and may be exacerbated with drugs used to treat CHF. This may require pacemaker implantation, which often improves symptoms and exercise capacity.

Antiarrhythmic drugs had been the first- and second-line treatments, however, recent data have demonstrated equal efficacy of rate versus rhythm control in chronic AF. In patients with systolic heart failure who are dependent on atrial output far more than those with preserved systolic function, AF ablation is still commonly used, especially in patients with paroxysmal or persistent AF who remain symptomatic despite rate control and those who do not desire long-term anticoagulant treatment. This is performed via a transeptal puncture with ablation around the ostia of pulmonary veins²¹ or surgically via a Maze procedure.²² Our patient underwent unsuccessful percutaneous ablation of AF and was left with a residual shunt in the interatrial septum at the site of transeptal puncture. As a last resort, AV nodal ablation is performed in symptomatic patients with AF who have lack of rate control or do not achieve complete biventricular pacing due to inadequate rate control.²³

Pacemakers in heart failure
Left ventricular function and severity of CHF are strong predictors of the risk of sudden death. In patients with reduced LV ejection fraction below 35%, implantable cardioverter defibrillators (ICDs) are used prophylactically to reduce the risk of sudden death both in patients with ischemic and nonischemic dilated cardiomyopathies.^24-26 In patients with QRS width >120 ms, LV end diastolic diameter of 55 mm, and NYHA class III or IV heart failure despite maximally tolerated medical therapy, a biventricular pacemaker (which involves placement of pacing leads in the endocardium of the right ventricle and the epicardium of the LV through access obtained via the coronary sinus²⁷) is placed. Surgical implantation of the LV lead on the epicardial surface may be employed if percutaneous attempts fail.

Biventricular pacing, also known as cardiac resynchronization treatment (CRT), has been shown to improve heart failure symptoms, functional class, and exercise capacity in more than two thirds and causes reverse LV remodeling in about 50% of patients who have ischemic or nonischemic DCM.^28-32 More recent data suggest improvement in survival with CRT over and above ICD treatment.³³ As with the patient in the anecdote, pacemaker optimization may improve symptoms in patients who remain symptomatic following CRT.^34-37

References