Role of Dobutamine Stress Echocardiography in Resynchronization Therapy in a Patient With Heart Failure Secondary to Radiotherapy for Hodgkin's Disease and Ventilatory and Inotropic Dependence

A 45-year-old woman was successfully treated 18 years ago with mediastinal radiotherapy for stage IIIA Hodgkin's lymphoma. Sixteen years later, she developed heart failure (HF) and started medical therapy. Two years later, she was admitted to the hospital because of acute severe congestive HF, requiring invasive mechanical ventilation. She underwent transesophageal echocardiography, which showed severe mitral regurgitation, impaired left ventricular (LV) systolic function, worse diastolic function, and significant interventricular and intraventricular dyssynchrony. Finally, we found a significant myocardial contractile reserve by means of high dobutamine stress transesophageal echocardiography. She underwent cardiac resynchronization therapy (CRT), with immediate (after 1 day) improvement in functional class and LV ejection fraction with reduction in mitral regurgitation. Within 3 days, the patient was extubated. She went on to mobilization and was medically discharged from the hospital 84 days after admission and 7 days after CRT. The benefits of CRT continue after 4 months of follow-up. A 45-year-old woman was successfully treated 18 years ago with mediastinal radiotherapy for stage IIIA Hodgkin's lymphoma. Sixteen years later, she developed HF and started medical therapy. Two years later, she was admitted to the hospital because of acute severe congestive HF that required invasive mechanical ventilation. Despite medical treatment with a combination of high-dose dopamine, dobutamine, and diuretics, symptoms did not improve. She had numerous episodes of pulmonary edema and ventricular tachycardia. The electrocardiographic and echocardiographic characteristics of the patient are reported in the Table. Her weight was 39 kg and height 155 cm. Electrocardiographic findings showed sinus rhythm with left bundle branch block and a QRS duration of 140 ms (Figure 1). Electrocardiographic results before (top) and 4 months after (bottom) cardiac resynchronization therapy (CRT). Right cardiac catheterization was performed with a Swan-Ganz catheter, and mean pulmonary capillary wedge pressure was 28 mm Hg. Findings from 64-slice multidetector computed tomography coronary angiography demonstrated absence of coronary artery stenosis. Because of a suboptimal echocardiographic thoracic window, the patient underwent transesophageal echocardiography, which showed a light increase in LV end-diastolic (35 mm/m2) and end-systolic diameters (27 mm/m2) (Figure 2), impaired LV systolic function (ejection fraction, 35%), and severe mitral regurgitation (Figure 3). Also found was an impaired diastolic function: a pseudonormal transmitral pattern and elevated ratio between E wave mitral flow and early diastolic velocity of mitral annulus (E/Ea 16). The pressure gradient across the tricuspid valve in systole was estimated to be 45 mm Hg. By means of pulsed tissue Doppler analysis, we found a significant intraventricular dyssynchrony: the maximal difference in the 6 LV basal segments was 65 ms. Also present was a significant interventricular dyssynchrony of 45 ms. Finally, we analyzed myocardial contractile reserve by means of high-dose (40 μg/kg/min) dobutamine stress transesophageal echocardiography. At peak dobutamine stress, we found a significant increase in LV ejection fraction (from 35% to 50%, increase +30%) associated with a reduction in mitral regurgitation (from severe to mild-moderate). M-mode echocardiographic images of the left ventricle before (top) and 4 months after (bottom) cardiac resynchronization therapy (CRT). Transesophageal echocardiographic image of severe mitral regurgitation before cardiac resynchronization therapy (CRT) (top) and transthoracic echocardiographic image of mild mitral regurgitation (bottom) 4 months after CRT. A transvenous biventricular implatable cardioverter-defibrillator was implanted through a left cephalic approach. The right ventricular dual coil lead was positioned in the right ventricular apex (Medtronic Sprint Fidelis 58 cm; Medtronic, Inc, Minneapolis, MN) and right atrial lead was deployed in the appendage (Medtronic Capsurefix 52 cm). The LV lead (Medtronic Attain bipolar over the wire) was positioned in the anterolateral branch of the coronary sinus through a left subclavian approach. The leads were connected to a Medtronic In-Sync III 8040 biventricular implantable cardioverter-defibrillator positioned in a subcutaneous prefascial pocket. Following active biventricular pacing, QRS width decreased from 140 ms to 120 ms, with a rapid improvement in hemodynamic status that allowed for reduction and cessation of inotropic drug support. Twenty-four hours after device implantation, a qualitative transthoracic echocardiographic study showed an increase in ejection fraction (about 45%, mean eyeball evaluation), with a reduction in mitral regurgitation (mild-moderate). Within 3 days, ventilatory support was removed. She went on to mobilization and was discharged on medical therapy 84 days after admission to the hospital and 7 days after CRT. At 4-month follow-up, the patient was in clinically stable condition (New York Heart Association [NYHA] functional class II), began normal daily activity and mild exercise, and reprised her sedentary job. The electrocardiographic and echocardiographic characteristics of the patient after 4-month follow-up are reported in the Table. Electrocardiographic findings showed a reduction in duration of QRS complex (120 ms) (Figure 3). There was a further increase in ejection fraction (60%), with reduction in LV end-diastolic (31 mm/m2) and end-systolic diameters (21 mm/m2) (Figure 2). Mitral regurgitation was mild (Figure 1). In this case report, we showed a patient with severe, medically refractory HF after chest radiotherapy for Hodgkin's disease who was successfully weaned from both ventilation and inotropic support with the aid of CRT. CRT has been proposed as an alternative treatment in patients with severe, drug-refractory HF.1,2 A recent paper3 demonstrated that intraventricular dyssynchrony is a major predictor of response to CRT and tissue Doppler provides reproducible and noninvasive assessment of intraventricular dyssynchrony. Previous case reports and small series4,5 showed that the hemodynamic benefits of CRT can even be helpful in an acute setting, if ventricular asynchrony is a leading cause in the pathophysiology of the decompensation. A recent paper6 demonstrated that HF patients with end-stage inotrope-dependent NYHA class IV and LV dyssynchrony may favorably respond to CRT with long-term clinical benefit and improved LV function. In that respect, the novel message of this report is the use of CRT in radiation-induced cardiomyopathy. In this patient, rest and dobutamine stress transesophageal echocardiography played a major role in selection for CRT. Despite the wealth of evidence that favors use of stress echocardiography in patients with dilated cardiomyopathy,7,8 there is no clear algorithm for its use in risk stratification and therapeutic strategy. The reasons for this are not clear but probably reflect the lack of standardized protocol and measurements of LV contractile reserve. Contractile reserve is defined as the difference between values of an index of LV contractility (ie, ejection fraction,9 wall motion score index,7 force-frequency relationship10) during peak stress and its baseline values. In HF patients with reduced ejection fraction, the presence of viability play an important role in the response to therapy.11 In fact, the presence of myocardial viability predicts a good response in patients with ischemic HF cardiomyopathy who underwent myocardial revascularization therapy,12 LV dyssynchrony (left bundle branch block and QRS >120 ms) in HF patients and LV dyssynchrony (left bundle branch block and QRS .120 ms) who underwent resynchronization therapy using biventricular pacing, and in HF patients who started or increased medical therapy.13 The absence of myocardial viability is associated with a bad response to revascularization therapy in ischemic cardiomyopathy, to resynchronization therapy, and to medical therapy. HF patients with reduced systolic function without myocardial viability during stress echocardiography must often undergo heart transplant.14 Frequently, patients with invasive mechanical ventilation have a suboptimal echocardiographic thoracic window. As shown in this case report, the use of transesophageal echocardiography allowed for evaluation with pulsed tissue Doppler and dobutamine stress echocardiography. In fact, before CRT therapy, this patient underwent transesophageal echocardiography that showed the presence of significant intraventricular dyssynchrony and good myocardial contractile reserve. In this case, we studied a patient with HF late after chest radiotherapy for Hodgkin's disease. Radiotherapy has been effective in treating many patients with Hodgkin's disease. Although there are undoubtable benefits due to the resolution of the disease, however, survival after treatment is affected by radiotherapy-induced heart disease.15,16 Late clinical manifestation results from slowly evolving endothelial cell injury, leading to loss of capillaries, ischemia at the microcirculatory level, and progressive myocardial fibrosis.17 In patients with Hodgkin's lymphoma younger than 41 years at treatment, the risk of myocardial infarction and HF are increased 3- to 5-fold compared with the general population.18 Dobutamine stress echocardiography myocardial contractile reserve may play an important role in the selection of patients for CRT, and in a subset of patients with refractory HF, secondary to chest radiotherapy for Hodgkin's disease, determining ventilatory and inotropic dependence. The authors deeply appreciate Mr Felice de Rosa for his technical support.