Successful Cardiac Resynchronization Therapy in a 3-Year-Old Girl With Isolated Left Ventricular Non-Compaction and Narrow QRS Complex

Transcription

1 CASE REPORT Circ J 2009; 73: Successful Cardiac Resynchronization Therapy in a 3-Year-Old Girl With Isolated Left Ventricular Non-Compaction and Narrow QRS Complex A Case Report Kazuyoshi Saito, MD; Keijirou Ibuki, MD; Naoki Yoshimura, MD*; Keiichi Hirono, MD; Sayaka Watanabe, MD; Kazuhiro Watanabe, MD; Keiichiro Uese, MD; Satoshi Yasukouchi, MD**; Fukiko Ichida, MD; Toshio Miyawaki, MD Cardiac resynchronization therapy (CRT) is a new method of treatment for refractory heart failure. However, for children, its indication, efficacy, and long-term prognosis remain unclear. This study describes the use of CRT for a 3-year-old girl with intractable heart failure caused by isolated left ventricular non-compaction (LVNC) with narrow QRS complex. Echocardiography showed diffuse hypokinetic left ventricular (LV) wall motion (ejection fraction =29.3%) with dyssynchrony between the apex, posterior and lateral walls, where numerous prominent trabeculations existed, and severe mitral regurgitation. Biventricular resynchronization using epicardial pacing leads was performed under general anesthesia. Pacing sites for optimal synchronization in the ventricular walls where chosen using tissue Doppler imaging, and AV delay was adjusted to achieve maximal systolic blood pressure and maximal cardiac output. Over a follow-up period of 2 years, she exhibited significant and sustained improvement in LV function and clinical symptoms. BNP levels decreased from 1,960 to 82 pg/ml. QRS duration (103 ms) on ECG did not change after CRT. We conclude that pediatric CRT provides a highly useful adjunct for the treatment of heart failure, even in patients with a narrow QRS duration, and might improve the prognosis of patients with LVNC. (Circ J 2009; 73: ) Key Words: Cardiac resynchronization therapy; Children; Heart failure; Isolated left ventricular non-compaction Cardiac resynchronization therapy (CRT) has become the standard of care for the treatment of heart failure in adults with decreased ventricular function and conduction delay who remain symptomatic despite optimal medical therapy. Although there are no prospective and randomized trial data, a retrospective series show that CRT is similarly effective for managing dyssynchronyassociated heart failure in children. 1 3 The heterogeneity of anatomical and functional substrates in which CRT shows efficacy calls for further studies defining the usefulness of CRT in children. 4 Children with systolic dysfunction secondary to cardiomyopathy have mechanical dyssynchrony, unrelated to electrical dyssynchrony, and are potential candidates for CRT. 5 Left ventricular non-compaction (LVNC) is a unique form of cardiomyopathy, characterized by numerous prominent left ventricular (LV) trabeculations and deep intertrabecular recesses. 6,7 In patients with LVNC, mechanical dyssynchrony between non-compacted and compacted myocardium contribute to global LV dysfunction. 8 Tissue Doppler velocities are significantly reduced in patients with LVNC, and help identify children with LVNC who are at risk of adverse clinical outcomes, including death, and need cardiac transplantation. 9 Successful CRT in adults with isolated LVNC has been reported recently, 10 however, the efficacy of CRT for pediatric patients with LVNC has not been reported. The use of CRT in children has gained a great deal of attention, especially in Japan where there is little chance of heart transplantation. Here we report the successful use of CRT in a 3-year-old girl with intractable heart failure caused by isolated LVNC with narrow QRS complex. Case Report The patient was diagnosed with heart failure caused by isolated LVNC at 3 months of age. LVNC was diagnosed by echocardiographic criteria including: (1) presence of prominent or numerous LV trabeculations, predominantly in the distal portion (apex) of the left ventricle; (2) a 2- layered structure of the myocardium with an increased non-compacted to compacted ratio (>1.4); and (3) multiple deep intertrabecular recesses communicating with the ventricular cavity, as demonstrated by color Doppler imaging Received August 24, 2008; accepted January 21, 2009; released online April 7, 2009 Department of Pediatrics, *Department of First Surgery, University of Toyama, Toyama and **Department of Pediatric Cardiology, Nagano Prefectural Children s Hospital, Nagano, Japan Mailing address: Fukiko Ichida, MD, Department of Pediatrics, University of Toyama, 2630 Sugitani, Toyama , Japan. fukiko@med.u-toyama.ac.jp All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 2174 SAITO K et al. Figure 1. (A) Two-dimensional echocardiography of the patient demonstrating a 2-layered structure of non-compacted (N) and compacted (C) layers (N/ C >2.0), marked dilation of the left ventricle (LVDd = 48 mm, 171% of normal) and diffuse hypokinetic left ventricular wall motion (ejection fraction (EF) = 29.3%) with numerous prominent trabeculations (black arrows). (B) On M-mode echocardiogram, septal-to-posterior wall mechanical delay was 218 ms. Figure 2. Clinical course and therapy before cardiac resynchronization therapy (CRT). Despite full doses of several medications, including angiotensin-converting enzyme inhibitors, β-blocker, and pimobendan, the patient had multiple hospital admissions because of the progression of heart failure. BNP, brain natriuretic peptide. (Figure 1). 11 Despite full doses of several medications, including angiotensin-converting enzyme inhibitors (enalapril maleate, 0.4 mg kg 1 day 1, β-blocker (carvedilol, 0.5 mg kg 1 day 1, and pimobendan), she had multiple hospital admissions because of the progression of heart failure (Figure 2). At 3 years of age, she had high fever and hemoptysis, and was diagnosed with pneumonia, which worsened her heart failure and resulted in her 13 th hospitalization. Her physical activity was modified New York Heart Association class IV for children. 12 At this latest admission, she weighed 8.3 kg ( 3.3 SD), was 77.4 cm tall ( 4.3 SD), had a heart rate of 104 beats/min, a blood pressure of 98/62 mmhg, a respiration rate of 38/min, and an oxygen saturation of 95% (room air). Her face was pale and edematous, and wet rales were audible in both lung fields. Her heart sounds were a gallop rhythm, and Levine 3/6 systolic regurgitation murmur and Levine 1/6 diastolic rumbling murmur were audible. Her liver was palpable 3 4 cm below the right costal margin. A chest X-ray showed marked cardiomegaly (CTR =0.73) and pulmonary congestion (Figure 3A). An ECG showed a QRS duration of 103 ms (Figure 4). An UCG showed diffuse hypokinetic LV wall motion (ejection fraction (EF) = 29.3%) with obvious dyssynchrony between the apex, poste-

3 Successful Cardiac Resynchronization Therapy 2175 Figure 3. (A) A chest X-ray on admission, showing marked cardiomegaly (cardiac resynchronization therapy (CRT) = 0.73) and pulmonary congestion. (B) A chest X-ray after 1 year, showing improvement of cardiomegaly (CTR = 0.65) and pulmonary congestion. The left ventricular and right ventricular leads were placed epicardially. Figure 4. An electrocardiogram on admission showed QRS duration of 103 ms. HR = 100, QTc = ms. rior and lateral walls, where numerous prominent trabeculations existed, and severe mitral regurgitation. On a M-mode echocardiogram, septal-to-posterior wall mechanical delay was 218 ms (Figure 1B). There was no clinical improvement with catecholamine infusion, and CRT was considered an option. On cardiac catheterization, a simulation of CRT using intravenous electrical leads was performed, and we confirmed improvement of BP and CI by CRT. BP changed from 72/36 (49) mmhg to 89/44 (64) mmhg, and CI increased from 2.49 to 2.88 after CRT. On Tissue-Doppler imaging, septal-lateral delay improved from 52.4 ms to 14.0 ms after CRT. These results encouraged us to perform CRT in this patient. Biventricular resynchronization using epicardial pacing leads was performed surgically under general anesthesia. By using median sternotomy, we placed an atrial lead, and placed a LV lead at the lateral wall of the apex. On tissue Doppler imaging of the transesophagial echocardiography, intraventricular dyssynchrony between the interventricular septum and apex, posterior and lateral walls, was obvious. Intraventricular delay, measured as a septal to posterior wall delay, was 80.6 ms (Figure 5A, Upper panel). The pacing site of the right ventricular wall was chosen to get optimal synchronization of the ventricular walls on tissue Doppler imaging (Figure 5A, Lower panel), and AV delay was adjusted to achieve maximal systolic blood pressure and maximal cardiac output (Figure 5A). 13 Over a follow-up period of 2 years, she has exhibited significant and sustained improvement in LV function and clinical symptoms (Table). Serial echocardiographic evaluation revealed that LV dilation improved gradually and continued to improve after 2 years. BNP levels decreased from 1,960 to 82 pg/ml following initiation of CRT (Table). In contrast, QRS duration on ECG did not change after successful CRT. A chest X-ray after 1 year showed improvement of cardiomegaly (CTR =0.65) and pulmonary congestion (Figure 3B). No adverse events, such as arrhythmias, were noted in this patient. Discussion This is the first report of successful CRT for a child with severe heart failure (New York Heart Association (NYHA) IV) because of LVNC. In this patient, despite a narrow QRS duration, CRT resulted in the improvement in LV function and clinical symptoms. CRT is a rapidly evolving treatment option for patients with drug-refractory heart failure. Large clinical trials have demonstrated the sustained benefit of CRT in patients with moderate-to-severe heart failure (NYHA functional class III or IV), systolic dysfunction

4 2176 SAITO K et al. A B Figure 5. (A) Tissue Doppler imaging on transesophagial echocardiography during cardiac resynchronization therapy (CRT). Intraventricular delay measured by a septal (yellow arrow) to posterior wall delay (red arrow) was 80.6 ms (Upper panel). The pacing site of the right ventricular wall was chosen to obtain optimal synchronization of the ventricular (LV) walls on tissue Doppler imaging of transesophagial echocardiography (Lower panel), and optimal AV delay was adjusted to achieve maximal systolic blood pressure and maximal cardiac output. (B) Tissue Doppler imaging 2 years after CRT demonstrating marked improvement of intraventricular dyssynchrony. Table. Clinical and Echocardiographic Characteristics Before and After CRT After CRT Before CRT 1 year 2 years Age (years, months) 3y7m 4y7m 5y5m Modified NYHA class* IV I I Height (cm) Body weight (kg) Kaup index BNP (pg/ml) 1, LVDd (mm) (% of normal) 48 (171%) 45 (154%) 41 (133%) LVEF (%) QRS interval (ms) *Modified NYHA class for children 11. LVDd parenthesis shows % of normal value adjusted for height. CRT, cardiac resynchronization therapy; NYHA, New York Heart Association; BNP, brain natriuretic peptide; LVDd, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction. [LVEF 35%], and a widened QRS complex ( 120 ms) in adults. 14 The predominant mechanism of benefit from CRT appears to be related to the presence of LV dyssynchrony and subsequent resynchronization after CRT. The presence of baseline LV dyssynchrony might, therefore, be mandatory for a response to CRT. The duration of the QRS complex on the surface ECG has been used as a marker of LV dyssynchrony: however, recent studies demonstrated that QRS duration is only a weak marker of LV dyssynchrony. 15,16 CRT appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on tissue Doppler imaging, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complexes. 17 A study of peak systolic velocity interval by tissue Doppler revealed that LV mechanical dyssynchrony is prevalent in pediatric patients with idiopathic dilated cardiomyopathy. 18 QRS duration alone is inadequate to define dyssynchrony in pediatric cardiomyopathy, whereas the adult-derived

5 Successful Cardiac Resynchronization Therapy dyssynchrony index of >32.6 ms seems applicable to the pediatric population. 18 An International Multi Center Study, Resynchronization Therapy in Pediatric and Congenital Heart Disease Patients, revealed no relationship between baseline EF or QRS duration and EF improvement. There was a significant difference in EF before CRT, with the responders having a lower EF of 24.3±11.0% vs a 32.0± 14.2% in the non-responders (P=0.04). Only 56 out of 103 patients met the adult criteria for CRT with an EF of 35% and a QRS duration of 120 ms. 19 In our patient, no adverse events were noted during the follow-up period. Lethal arrhythmias including 3 deaths have been reported in the pediatric CRT population. 17 Also, acute adverse events such as coronary sinus lead issues, arrhythmic episodes, device pocket hematomas, and 1 each of the following: pocket infection, cerebrovascular accident, bleeding, and perforation of the myocardium requiring surgical intervention, have been reported. 19 There was an overall adverse event rate of 29% and the overall mortality was 5%. 19 Coronary sinus lead issues, which accounted for 23% of the reported complications, and were found in 18% of all transvenous pacemakers placed, were the single most common major complication. No differences in complication rates could be seen when comparing transvenous placement vs epicardial or mixed placement of devices. Conclusion We conclude that pediatric CRT provides a highly useful adjunct for the treatment of heart failure, even with narrow QRS duration, and might improve the prognosis of patients with LVNC. CRT is preferable to high-dose inotropic therapy and should be given serious consideration for the treatment of refractory heart failure prior to proceeding with heart transplantation. Further studies are needed to determine the indication, effectiveness, and the long-term benefits of this therapy in the pediatric population. References 1. Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law IH, et al. Resynchronization therapy in pediatric and congenital heart disease patients: An international multicenter study. J Am Coll Cardiol 2005; 46: Rhee EK. Cardiac resynchronization therapy in pediatrics: Emerging technologies for emerging indications. Curr Treat Options Cardiovasc Med 2005; 7: Janousek J, Tomek V, Chaloupecký VA, Reich O, Gebauer RA, Kautzner J, et al. Cardiac resynchronization therapy: A novel adjunct to the treatment and prevention of systemic right ventricular failure J Am Coll Cardiol 2004; 44: Dubin AM, Collins KK, Van Hare GF, Reddy VM, Hanisch D, Chiesa N, et al. Midterm results of resynchronization therapy in pediatrics: Do we need new guidelines? Circulation 2007; 116(Suppl): Friedberg MK, Silverman NH, Dubin AM, Rosenthal DN. Mechanical dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy: A Doppler tissue and vector velocity imaging study. J Am Soc Echocardiog 2007; 20: Ichida F, Hamamichi Y, Miyawaki T, Ono Y, Kamiya T, Akagi T, et al. Clinical features of isolated noncompaction of the ventricular myocardium: Long-term clinical course, hemodynamic properties, and genetic background. J Am Coll Cardiol 1999; 34: Iwashima S, Ishikawa T, Ohzeki T. Delayed enhancement cardiac MRI in isolated noncompaction of leftventricular myocardium in a child. Circ J 2008; 72: Lofiego C, Biagini E, Ferlito M, Pasquale F, Rocchi G, Perugini E, et al. Paradoxical contributions of non-compacted and compacted segments to global left ventricular dysfunction in isolated left ventricular noncompaction. Am J Cardiol 2006; 97: McMahon CJ, Pignatelli RH, Nagueh SF, Lee VV, Vaughn W, Valdes SO, et al. Left ventricular non-compaction cardiomyopathy in children: Characterization of clinical status using tissue Doppler-derived indices of left ventricular diastolic relaxation. Heart 2007; 93: Oginosawa Y, Nogami A, Soejima K, Aonuma K, Kubota S, Sato T, et al. Effect of cardiac resynchronization therapy in isolated ventricular noncompaction in adults: Follow-up of four cases. J Cardiovasc Electrophysiol 2008; 19: Ichida F. Left ventricular noncompaction. Circ J 2009; 73: Bruns LA, Chrisant MK, Lamour JM, Shaddy RE, Pahl E, Blume ED, et al. Carvedilol as therapy in pediatric heart failure: An initial multicenter experience. J Pediatr 2001; 138: Kiuchi K, Yoshida A, Fukuzawa K, Takano T, Kanda G, Takami K, et al. Identification of the right ventricular pacing site for cardiac resynchronization therapy (CRT) guided by electroanatomical mapping (CARTO). Circ J 2007; 71: Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005; 352: Bleeker GB, Schalij MJ, Molhoek SG, Holman ER, Verwey HF, Steendijk P, et al. Frequency of left ventricular dyssynchrony in patients with heart failure and a narrow QRS complex. Am J Cardiol 2005; 95: Achilli A, Sassara M, Ficili S, Pontillo D, Achilli P, Alessi C, et al. Long-term effectiveness of cardiac resynchronization therapy in patients with refractory heart failure and narrow QRS. J Am Coll Cardiol 2003; 42: Bleeker GB, Holman ER, Steendijk P, Boersma E, van der Wall EE, Schalij MJ, et al. Cardiac resynchronization therapy in patients with a narrow QRS complex. J Am Coll Cardiol 2006; 48: Friedberg MK, Roche SL, Balasingam M, Stephenson E, Slorach C, Fackoury C, et al. Evaluation of mechanical dyssynchrony in children with idiopathic dilated cardiomyopathy and associated clinical outcomes. Am J Cardiol 2008; 101: Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law IH, et al. Resynchronization therapy in pediatric and congenital heart disease patients: An international multicenter study. J Am Coll Cardiol 2005; 46: