International Journal of Cardiology 186 (2015) 233–235
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Takotsubo (stress) cardiomyopathy and obstructive renal stones in an infant with norovirus gastroenteritis Seigo Okada ⁎,1, Yoshihiro Azuma 1, Hidenobu Kaneyasu, Makoto Mizutani, Yuno Korenaga, Setsuaki Kittaka, Yasuo Suzuki, Yuji Ohnishi, Takashi Furuta, Shouichi Ohga Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
a r t i c l e
i n f o
Article history: Received 11 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Heart failure Norovirus Gastroenteritis Urolithiasis Renal failure
Takotsubo (stress) cardiomyopathy (TC) is characterized by transient left ventricular dysfunction in adult patients with chest pain, cardiac enzyme elevations, and electrocardiographic changes. This condition mimicking an acute coronary syndrome usually occurs in elder women after a physical or emotional stress. It is extremely rare in children as well as after infective stress [1,2]. Norovirus is a common pathogen of gastroenteritis in childhood. There is an occasional association between renal stones and gastroenteritis [3]. Rotavirus infection is the major cause of urolithiasis in viral gastroenteritis. This complication has also been reported in norovirus infection [4]. Urinary stones associated with viral gastroenteritis result in serious post-renal failure [3,4]. To our knowledge, Takotsubo-like condition has never been reported in cases of gastroenteritis with or without the complication. Here, we described a 15-month-old male who developed acute heart failure and obstructive urolithiasis associated with norovirus gastroenteritis. A 15-month-old boy with a 7-day history of vomiting, diarrhea, and low-grade fever was hospitalized. Oliguria continued after hydration. Echocardiography revealed depressed ejection fraction (EF). The patient was transferred to our intensive care unit. He was diagnosed as having congenital hydronephrosis (grade 2) at birth, but the stenotic pyeloureteral junctions were stable without calculi formation assessed
⁎ Corresponding author at: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. E-mail address: [email protected] (S. Okada). 1 S. Okada and Y. Azuma contributed equally to this paper.
http://dx.doi.org/10.1016/j.ijcard.2015.03.199 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
by repeated echographies. He suffered from Kawasaki disease at 10month-old. Normal heart was demonstrated by the follow-up studies. His growth and development were normal. There was no family history of heart or kidney disease. On admission, he presented with pallor and coldness. The puffy face, distended jugular veins, and hepatomegaly were found. Vital signs were as follows; blood pressure 121/96 mm Hg; pulse rate 140/min; respiratory rate 50/min; and body temperature of 37.9 °C. Complete blood counts showed leukocytes 13.81 × 109/L, hemoglobin 10.5 g/dL, and platelets 318.0 × 109/L. Blood chemistries revealed; urea nitrogen 79 mg/dL, creatinine 2.27 mg/dL, uric acid 14.4mg/dL, C-reactive protein 5.7 mg/dL, creatine kinase-MB 25.3 IU/L, cardiac troponin T (cTnT) 0.281 ng/mL (reference range [rr]: 0–0.014), N-terminal pro-B-type natriuretic peptide 139,038 pg/mL, adrenalin 149 pg/mL (rr: b 100), noradrenalin 165 pg/mL (rr: 100–450), dopamine 28 pg/mL (rr: b°20), sodium 133 mmol/L, potassium 5.8 mmol/L, and chloride 102 mmol/L. Venous blood gas showed pH 7.3, HCO− 3 14.0 mmol/L, base excess −14.0 mmol/L, and anion gap 20.4 mmol/L. Lactate levels were unremarkable (1.7 mmol/L, rr: 0.44– 1.78). Urinalysis showed macrohematuria and proteinuria. The antigen of norovirus, but not rotavirus or adenovirus, was detected in the feces. Echocardiography revealed severely reduced contraction of ventricles (EF 30%). The mid-to-apical segments were hypokinetic, but basal segments contracted excessively with systolic ballooning of the left ventricle (LV) and mitral regurgitation (Fig. 1AB). Electrocardiogram (ECG) showed sinus tachycardia (151/min) with flattening T-waves in lead I and ST-segment depression in V5–V6 leads. Chest radiography revealed cardiomegaly (cardiothoracic ratio 0.55) and pulmonary congestion. Abdominal ultrasonography and computed tomography showed dilated bilateral pelvises and calculi in the ureters (Fig. 2AB). These determined the diagnosis of TC and post-renal failure due to obstructive urinary stones. Milrinone, carperitide, and furosemide along with oral bicarbonate therapy led to the improvement to 65% of LVEF within 96 h. There was no serological evidence of coxsackievirus (types A2, A3, and B1–6), echovirus (types 7, 11, and 12), or adenovirus (types 2, 3, 5, and 7) infection. Urination returned with spontaneous excretion of brown sandy stones, and creatinine and uric acid levels were normalized. The stones contained urate or calcium oxalate crystals. ECG showed inverted T-waves in V1–V4 leads and ST-segment depression in V3 lead on the 4th hospital day, when angiotensin converting enzyme inhibitors were added. He was discharged from the hospital on the 18th day, because ECG was normalized and hydronephrosis returned to the previous degree.
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S. Okada et al. / International Journal of Cardiology 186 (2015) 233–235
A
B
Fig. 1. Two-dimensional echocardiogram of the patient on admission. The long axis view at the left sternal border reveals apical ballooning of LV with hypokinesis of the mid-to-apical segments (arrow heads) and normo-to-hyperkinesis of the basal segment (white arrow). A, diastolic phase; B, systolic phase.
This is the first association between transient cardiac failure and urolithiasis in viral gastroenteritis. Acute renal failure due to obstructive urolithiasis is a pediatric emergency of rotavirus or norovirus infection [3–5]. On the other hand, TC rarely occurs in pediatric population [1, 2]. The pathogenesis is involved in the excess in catecholamines,
A
B
microvascular impairment, and low estrogen levels in women [2]. The hypokinetic mid-to-apical segments in contrast to the normalexcessive motion of basal segments, and subsequent full recovery of cardiac function determined the diagnosis of cardiomyopathy in the stressed infant. Obstructive urolithiasis develops in children with gastroenteritis [3–5]. Major components of the stones were urinary acid system, especially ammonium acid urate [3,5]. Hyperuricemia associated with viral gastroenteritis arises from the tissue injury, diminished renal blood flow, mild renal dysfunction, or acidosis with massive intestinal fluid loss [5]. Urolithiasis associated with viral gastroenteritis often occurs under 3 years old, hence immature renal tubular function may contribute to hyperuricemia [3–5]. The urinary tract malformations probably predispose our infant to the stone formation [6]. In this context, prolonged dehydration in gastroenteritis and painful calculi triggered the overproduction of catecholamines followed by the cardiomyopathy. Obstructive urinary stones might contribute to the progressive renocardiac syndrome in our patient. Another concern was the elevated levels of cTnT suggesting myocarditis or myocardial infarction. TC patients reportedly showed appreciably high levels of cTnT (0.01 to 5.2 ng/mL) [2], corresponding to the levels seen in myocarditis. In addition, impaired renal function causes the accumulation of cTnT in patients with severe congestive heart failure [7]. This infant showed neither ST-segment elevation nor pericardial effusion. No circulating viruses increased progressively. These excluded the possibility of virus-associated myocarditis. Acute myocardial infarction was also implausible based on the findings of normal coronary arteries during the follow-up of Kawasaki disease, absence of typical ST-T changes or abnormal Q-waves, and the dramatic recovery of LV function in a few days without thrombolytic therapy [8]. Myocardial single-photon emission computed tomography indicated no ischemic lesions (data not shown). miRNAs may be useful to differentiate TC from myocardial infarction, but the tests have yet been validated [2]. No myocardial biopsy was performed [2], that was a limitation of our observation. TC may be underestimated or misdiagnosed in the young [1,2]. Physical and painful insults, rather than emotional stress, could be involved in this type of pediatric cardiomyopathy. It is a rare but noticeable condition in the critically ill children.
Conflict of interest Fig. 2. Abdominal computed tomography representing calculi in the ureters and dilated bilateral pelvises on admission. A: Axial section. Arrows indicate bilateral urinary stones in the ureters. B: Coronal section. Asterisks indicate markedly dilated bilateral pelvises.
This work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H26-Nanchi-013, S.O.). There were no conflicts of interests to declare.
S. Okada et al. / International Journal of Cardiology 186 (2015) 233–235
References [1] J. Finsterer, C. Stöllberger, Neurological and non-neurological triggers of Takotsubo syndrome in the pediatric population, Int. J. Cardiol. 179 (2015) 345–347. [2] L.E. Hernandez, Takotsubo cardiomyopathy: how much do we know of this syndrome in children and young adults? Cardiol. Young. 24 (2014) 580–592. [3] D. Bianchi, G. Vespasiani, P. Bove, Acute kidney injury due to bilateral ureteral obstruction in children, World. J. Nephrol. 3 (2014) 182–192. [4] A. Ashida, A. Shirasu, H. Nakakura, H. Tamai, Acute renal failure due to obstructive urate stones associated with norovirus gastroenteritis, Pediatr. Nephrol. 25 (2010) 2377–2378.
235
[5] A. Ashida, M. Fujieda, K. Ohta, H. Nakakura, H. Matsumura, T. Morita, T. Igarashi, H. Tamai, Clinical characteristics of obstructive uropathy associated with rotavirus gastroenteritis in Japan, Clin. Nephrol. 77 (2012) 49–54. [6] F. Baştuğ, R. Düşünsel, Pediatric urolithiasis: causative factors, diagnosis and medical management, Nat. Rev. Urol. 9 (2012) 138–146. [7] N. Aksoy, O. Ozer, I. Sari, M. Sucu, M. Aksoy, I. Geyikli, Contribution of renal function impairment to unexplained troponin T elevations in congestive heart failure, Ren. Fail. 31 (2009) 272–277. [8] H.D. Allen, D.J. Driscoll, R.E. Shaddy, T.F. Feltes, Moss and Adams' Heart Disease in Infants, Children and Adolescents: Including the Fetus and Young Adult, Eighth ed. Lippincott Williams & Wilkins, Philadelphia, 2013.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Takotsubo (stress) cardiomyopathy and obstructive renal stones in an infant with norovirus gastroenteritis Seigo Okada ⁎,1, Yoshihiro Azuma 1, Hidenobu Kaneyasu, Makoto Mizutani, Yuno Korenaga, Setsuaki Kittaka, Yasuo Suzuki, Yuji Ohnishi, Takashi Furuta, Shouichi Ohga Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan
a r t i c l e
i n f o
Article history: Received 11 February 2015 Accepted 17 March 2015 Available online 18 March 2015 Keywords: Heart failure Norovirus Gastroenteritis Urolithiasis Renal failure
Takotsubo (stress) cardiomyopathy (TC) is characterized by transient left ventricular dysfunction in adult patients with chest pain, cardiac enzyme elevations, and electrocardiographic changes. This condition mimicking an acute coronary syndrome usually occurs in elder women after a physical or emotional stress. It is extremely rare in children as well as after infective stress [1,2]. Norovirus is a common pathogen of gastroenteritis in childhood. There is an occasional association between renal stones and gastroenteritis [3]. Rotavirus infection is the major cause of urolithiasis in viral gastroenteritis. This complication has also been reported in norovirus infection [4]. Urinary stones associated with viral gastroenteritis result in serious post-renal failure [3,4]. To our knowledge, Takotsubo-like condition has never been reported in cases of gastroenteritis with or without the complication. Here, we described a 15-month-old male who developed acute heart failure and obstructive urolithiasis associated with norovirus gastroenteritis. A 15-month-old boy with a 7-day history of vomiting, diarrhea, and low-grade fever was hospitalized. Oliguria continued after hydration. Echocardiography revealed depressed ejection fraction (EF). The patient was transferred to our intensive care unit. He was diagnosed as having congenital hydronephrosis (grade 2) at birth, but the stenotic pyeloureteral junctions were stable without calculi formation assessed
⁎ Corresponding author at: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. E-mail address: [email protected] (S. Okada). 1 S. Okada and Y. Azuma contributed equally to this paper.
http://dx.doi.org/10.1016/j.ijcard.2015.03.199 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
by repeated echographies. He suffered from Kawasaki disease at 10month-old. Normal heart was demonstrated by the follow-up studies. His growth and development were normal. There was no family history of heart or kidney disease. On admission, he presented with pallor and coldness. The puffy face, distended jugular veins, and hepatomegaly were found. Vital signs were as follows; blood pressure 121/96 mm Hg; pulse rate 140/min; respiratory rate 50/min; and body temperature of 37.9 °C. Complete blood counts showed leukocytes 13.81 × 109/L, hemoglobin 10.5 g/dL, and platelets 318.0 × 109/L. Blood chemistries revealed; urea nitrogen 79 mg/dL, creatinine 2.27 mg/dL, uric acid 14.4mg/dL, C-reactive protein 5.7 mg/dL, creatine kinase-MB 25.3 IU/L, cardiac troponin T (cTnT) 0.281 ng/mL (reference range [rr]: 0–0.014), N-terminal pro-B-type natriuretic peptide 139,038 pg/mL, adrenalin 149 pg/mL (rr: b 100), noradrenalin 165 pg/mL (rr: 100–450), dopamine 28 pg/mL (rr: b°20), sodium 133 mmol/L, potassium 5.8 mmol/L, and chloride 102 mmol/L. Venous blood gas showed pH 7.3, HCO− 3 14.0 mmol/L, base excess −14.0 mmol/L, and anion gap 20.4 mmol/L. Lactate levels were unremarkable (1.7 mmol/L, rr: 0.44– 1.78). Urinalysis showed macrohematuria and proteinuria. The antigen of norovirus, but not rotavirus or adenovirus, was detected in the feces. Echocardiography revealed severely reduced contraction of ventricles (EF 30%). The mid-to-apical segments were hypokinetic, but basal segments contracted excessively with systolic ballooning of the left ventricle (LV) and mitral regurgitation (Fig. 1AB). Electrocardiogram (ECG) showed sinus tachycardia (151/min) with flattening T-waves in lead I and ST-segment depression in V5–V6 leads. Chest radiography revealed cardiomegaly (cardiothoracic ratio 0.55) and pulmonary congestion. Abdominal ultrasonography and computed tomography showed dilated bilateral pelvises and calculi in the ureters (Fig. 2AB). These determined the diagnosis of TC and post-renal failure due to obstructive urinary stones. Milrinone, carperitide, and furosemide along with oral bicarbonate therapy led to the improvement to 65% of LVEF within 96 h. There was no serological evidence of coxsackievirus (types A2, A3, and B1–6), echovirus (types 7, 11, and 12), or adenovirus (types 2, 3, 5, and 7) infection. Urination returned with spontaneous excretion of brown sandy stones, and creatinine and uric acid levels were normalized. The stones contained urate or calcium oxalate crystals. ECG showed inverted T-waves in V1–V4 leads and ST-segment depression in V3 lead on the 4th hospital day, when angiotensin converting enzyme inhibitors were added. He was discharged from the hospital on the 18th day, because ECG was normalized and hydronephrosis returned to the previous degree.
234
S. Okada et al. / International Journal of Cardiology 186 (2015) 233–235
A
B
Fig. 1. Two-dimensional echocardiogram of the patient on admission. The long axis view at the left sternal border reveals apical ballooning of LV with hypokinesis of the mid-to-apical segments (arrow heads) and normo-to-hyperkinesis of the basal segment (white arrow). A, diastolic phase; B, systolic phase.
This is the first association between transient cardiac failure and urolithiasis in viral gastroenteritis. Acute renal failure due to obstructive urolithiasis is a pediatric emergency of rotavirus or norovirus infection [3–5]. On the other hand, TC rarely occurs in pediatric population [1, 2]. The pathogenesis is involved in the excess in catecholamines,
A
B
microvascular impairment, and low estrogen levels in women [2]. The hypokinetic mid-to-apical segments in contrast to the normalexcessive motion of basal segments, and subsequent full recovery of cardiac function determined the diagnosis of cardiomyopathy in the stressed infant. Obstructive urolithiasis develops in children with gastroenteritis [3–5]. Major components of the stones were urinary acid system, especially ammonium acid urate [3,5]. Hyperuricemia associated with viral gastroenteritis arises from the tissue injury, diminished renal blood flow, mild renal dysfunction, or acidosis with massive intestinal fluid loss [5]. Urolithiasis associated with viral gastroenteritis often occurs under 3 years old, hence immature renal tubular function may contribute to hyperuricemia [3–5]. The urinary tract malformations probably predispose our infant to the stone formation [6]. In this context, prolonged dehydration in gastroenteritis and painful calculi triggered the overproduction of catecholamines followed by the cardiomyopathy. Obstructive urinary stones might contribute to the progressive renocardiac syndrome in our patient. Another concern was the elevated levels of cTnT suggesting myocarditis or myocardial infarction. TC patients reportedly showed appreciably high levels of cTnT (0.01 to 5.2 ng/mL) [2], corresponding to the levels seen in myocarditis. In addition, impaired renal function causes the accumulation of cTnT in patients with severe congestive heart failure [7]. This infant showed neither ST-segment elevation nor pericardial effusion. No circulating viruses increased progressively. These excluded the possibility of virus-associated myocarditis. Acute myocardial infarction was also implausible based on the findings of normal coronary arteries during the follow-up of Kawasaki disease, absence of typical ST-T changes or abnormal Q-waves, and the dramatic recovery of LV function in a few days without thrombolytic therapy [8]. Myocardial single-photon emission computed tomography indicated no ischemic lesions (data not shown). miRNAs may be useful to differentiate TC from myocardial infarction, but the tests have yet been validated [2]. No myocardial biopsy was performed [2], that was a limitation of our observation. TC may be underestimated or misdiagnosed in the young [1,2]. Physical and painful insults, rather than emotional stress, could be involved in this type of pediatric cardiomyopathy. It is a rare but noticeable condition in the critically ill children.
Conflict of interest Fig. 2. Abdominal computed tomography representing calculi in the ureters and dilated bilateral pelvises on admission. A: Axial section. Arrows indicate bilateral urinary stones in the ureters. B: Coronal section. Asterisks indicate markedly dilated bilateral pelvises.
This work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H26-Nanchi-013, S.O.). There were no conflicts of interests to declare.
S. Okada et al. / International Journal of Cardiology 186 (2015) 233–235
References [1] J. Finsterer, C. Stöllberger, Neurological and non-neurological triggers of Takotsubo syndrome in the pediatric population, Int. J. Cardiol. 179 (2015) 345–347. [2] L.E. Hernandez, Takotsubo cardiomyopathy: how much do we know of this syndrome in children and young adults? Cardiol. Young. 24 (2014) 580–592. [3] D. Bianchi, G. Vespasiani, P. Bove, Acute kidney injury due to bilateral ureteral obstruction in children, World. J. Nephrol. 3 (2014) 182–192. [4] A. Ashida, A. Shirasu, H. Nakakura, H. Tamai, Acute renal failure due to obstructive urate stones associated with norovirus gastroenteritis, Pediatr. Nephrol. 25 (2010) 2377–2378.
235
[5] A. Ashida, M. Fujieda, K. Ohta, H. Nakakura, H. Matsumura, T. Morita, T. Igarashi, H. Tamai, Clinical characteristics of obstructive uropathy associated with rotavirus gastroenteritis in Japan, Clin. Nephrol. 77 (2012) 49–54. [6] F. Baştuğ, R. Düşünsel, Pediatric urolithiasis: causative factors, diagnosis and medical management, Nat. Rev. Urol. 9 (2012) 138–146. [7] N. Aksoy, O. Ozer, I. Sari, M. Sucu, M. Aksoy, I. Geyikli, Contribution of renal function impairment to unexplained troponin T elevations in congestive heart failure, Ren. Fail. 31 (2009) 272–277. [8] H.D. Allen, D.J. Driscoll, R.E. Shaddy, T.F. Feltes, Moss and Adams' Heart Disease in Infants, Children and Adolescents: Including the Fetus and Young Adult, Eighth ed. Lippincott Williams & Wilkins, Philadelphia, 2013.
