566
Letters to the Editor
and even fewer studies focused on functional assessments with the FIM score [5]. The FIM motor scores in our cohort were 67.9 and 68.6 at the beginning (moderate dependence) and improved by 8.9 and 10.1 points reaching 76.8 and 78.7 out of 91 possible points (partial dependence). It is of note, that the initial reached functional status after cardiac surgery remains almost unchanged when assessed 1, 2, 3 and 4 years after the index operation [10]. Therefore, it is of utmost importance to admit patients, in particular older and sicker patients, immediately after cardiac surgery for intensive cardiac rehabilitation to improve functional status and functional long-term outcome, accordingly. In conclusion, patients in the TAVI group were older and sicker than SAVR patients. Despite these differences, both patient groups did benefit in the same way from a post-acute in-patient rehabilitation program as assessed by 6-Minute Walking Tests and FIM scores. References [1] Toggweiler S, Humphries KH, Lee M, et al. 5-year outcome after transcatheter aortic valve implantation. J Am Coll Cardiol 2013;61(4):413–9.
[2] Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363(17):1597–607. [3] Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364(23):2187–98. [4] Cournan M. Use of the functional independence measure for outcomes measurement in acute inpatient rehabilitation. Rehabil Nurs 2011;36(3):111–7. [5] Sansone GR, Alba A, Frengley JD. Analysis of FIM instrument scores for patients admitted to an inpatient cardiac rehabilitation program. Arch Phys Med Rehabil 2002;83(4):506–12. [6] Poole-Wilson PA. The 6-minute walk. A simple test with clinical application. Eur Heart J 2000;21(7):507–8. [7] Opasich C, De Feo S, Pinna GD, et al. Distance walked in the 6-minute test soon after cardiac surgery: toward an efficient use in the individual patient. Chest 2004;126(6):1796–801. [8] Russo N, Compostella L, Tarantini G, et al. Cardiac rehabilitation after transcatheter versus surgical prosthetic valve implantation for aortic stenosis in the elderly. Eur J Prev Cardiol 2013. [9] Williams MA, Ades PA, Hamm LF, et al. Clinical evidence for a health benefit from cardiac rehabilitation: an update. Am Heart J 2006;152(5):835–41. [10] Chaturvedi RK, Blaise M, Verdon J, et al. Cardiac surgery in octogenarians: long-term survival, functional status, living arrangements, and leisure activities. Ann Thorac Surg 2010;89(3):805–10.
http://dx.doi.org/10.1016/j.ijcard.2014.03.121 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Cardiac autonomic nervous activity in adults with coarctation of the aorta late after repair Antonia C. Moutafi a,⁎, Georgios Manis b, Christos Dellos c, Dimitrios Tousoulis d, Constantinos H. Davos a a
Cardiovascular Research Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece Department of Computer Science, University of Ioannina, Greece Department of Congenital Heart Disease, Tzanio Hospital, Piraeus, Greece d 1st Cardiology Department, University of Athens, Hippokration Hospital, Athens, Greece b c
a r t i c l e
i n f o
Article history: Received 2 February 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Coarctation Congenital heart disease Cardiac autonomic nervous activity
Patients with repaired coarctation of the aorta (CoA) present with long-term complications, despite early management, suggesting that CoA is not simply an anatomical malformation [1]. The reasons for their reduced life expectancy are unclear, and research remains limited, particularly with respect to their cardiac autonomic nervous activity (CANA). Few studies were carried out mainly in mixed cohorts of patients with congenital heart diseases (CHD), other than CoA, which indicate a CANA imbalance [2,3]. The aim of the present study was to evaluate CANA in adult patients with CoA, late after repair. We studied 18 stable patients (9 males) with previous CoA, aged 14 or older, at least 5 years after repair. Exclusion criteria included atrial fibrillation or greater than 2 ventricular ectopic beats during data acquisition and echocardiographic findings of recoarctation or aortic valve regurgitation. All patients had normal left ventricular function on echocardiography. Twenty-seven age- and sex-matched healthy controls
⁎ Corresponding author at: Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece. Tel.: + 30 2106597392; fax: + 30 2106597405. E-mail address: tania.moutafi@yahoo.com (A.C. Moutafi).
were also studied. All investigations were performed at the Cardiovascular Research Laboratory of the Academy of Athens Biomedical Research Foundation. The Foundation's Ethics Committee approved the study and all subjects, gave informed consent before their enrollment. All participants were studied under standardized conditions. They were fasted and were not allowed to smoke or drink alcohol- or caffeinecontaining beverages for 24 h before the study. They rested supine for 15 min and then underwent clinical examination, blood pressure measurement, ECG recording, a 40 min ECG and blood pressure monitoring and transthoracic echocardiography [3]. CANA was evaluated by a 40-minute ECG and SBP recordings (TaskForce monitor, CNSystems, Austria). Blood pressure was measured using a finger cuff wrapped around the index finger of the left hand. The ECG was acquired from the limb lead with the largest R wave. The readings were saved and analyzed off-line with custom designed software. The program measured RR intervals and beat-to-beat SBP. Heart rate variability (HRV) analysis was performed and time domain and frequency domain indices were calculated using our laboratory software. Assessed time domain HRV indices were: SDNN (standard deviation of all normal-to-normal RR intervals, RMSSD (square root of the mean squared differences of successive RR intervals) and pNN50 (per cent difference of successive RR intervals N50 ms). Very low (VLF, 0.0033–0.04 Hz), low (LF, 0.04–0.15 Hz) and high frequency (HF, 0.15–0.4 Hz) HRV indices were also assessed. Baroreflex sensitivity (BRS) was assessed by measuring the average amplitude of oscillations in RR interval and SBP. Power spectral analysis was performed on the RR interval and SBP data using an autoregressive algorithm. The α-index was calculated as the square root of the ratio between RR and SBP spectral power in the low frequency (0.04–0.15 Hz, αLF) and the high frequency (0.15–0.4 Hz, αHF) band in the presence of an adequate coherence (N0.5) between the RR interval and SBP as assessed by cross-spectral analysis.
Letters to the Editor
567
Table 1 Clinical, surgical, and hemodynamic characteristics of the study population.
Age, years Female Male Time after repair, years Age at first repair, years Surgical repair Stent implantation Surgical repair followed by stent implantation Bicuspid aortic valve NYHA class I II QTc (ms) SBP (mm Hg) DBP (mm Hg)
CoA patients (n = 18)
n
Controls (n = 27)
N
p value
25.22 ± 9.60 22.21 ± 9.13 28.22 ± 9.59 17.82 ± 8.10 7.40 ± 7.54 9 6 3 7
18 9 9
26.96 ± 8.85 24.89 ± 5.93 29.19 ± 11.01
27 14 13
0.54 0.4 0.8
13 5 393.17 ± 15.08 130.61 ± 19.96 70.41 ± 7.27
386.64 ± 21.8 118.67 ± 10.14 70.40 ± 9.95
0.3 0.01 0.9
Values in mean ± SD, (%).
Data were expressed as frequency for the nominal variables and as mean ± standard deviation (SD) for continuous variables. Data were analyzed by using Statview 5.0 (Abacus Concepts, SAS Institute, Cary, U.S.A.). Differences between the two subgroups were assessed by an unpaired Student's s test, or by the Mann–Whitney rank-sum for data that failed tests of normality. HRV and BRS variables not following the normal distribution were logarithmically transformed. All tests were two sided. A p value b0.05 was considered significant. Clinical, surgical, and haemodynamic data are presented in Table 1. All HRV and BRS indices were not statistically different between the two studied groups (Table 2). The present study suggests that patients with repaired CoA undergo a normalization of the noninvasively measured indicators of CANA. This is in contrast to our previous findings in patients with repaired Tetrallogy of Fallot [3], and other studies on patients with complex CHD, which showed a significant impairment of the sympatho-vagal balance,
Table 2 Baroreflex sensitivity and heart rate variability indices. BRS and HRV variables Time domain indices of HRV SDNN (ms) log SDNN RMSSD (ms) log RMSSD pNN50 (%)
CoA patients (n = 18) 84.63 ± 31.33 1.90 ± 0.15 78.56 ± 43.08 1.83 ± 0.23 0.997 ± 0.001
Power spectrum indices of HRV 936.2 ± 1519.1 VLF (ms2) log VLF 2.70 ± 0.42 2 2294.36 ± 5548.17 LF (ms ) log LF 2.98 ± 0.46 1459.96 ± 1646.66 HF (ms2) log HF 2.95 ± 0.47
Controls (n = 27) 91.75 ± 74.47 1.89 ± 0.22 85.22 ± 95.14 1.81 ± 0.29 0.997 ± 0.001
6311.88 ± 26790.87 2.75 ± 0.71 975.53 ± 1190.07 2.81 ± 0.39 1299.93 ± 1701.60 2.85 ± 0.49
Power spectrum indices of BRS α-LF (ms/mm Hg) log α-LF α-HF (ms/mm Hg) log α-HF
21.05 ± 9.84 1.27 ± 0.21 38.96 ± 19.91 1.52 ± 0.25
17.23 ± 8.92 1.19 ± 0.2 33.72 ± 30.73 1.39 ± 0.34
BRS (sequence method) BRSseq (ms/mm Hg) log BRSseq
28.55 ± 15.07 1.40 ± 0.23
24.37 ± 12.60 1.33 ± 0.22
BRS: baroreflex sensitivity; HRV: heart rate variability; SDNN: standard deviation of all RR intervals; RMSSD: square root of the mean squared differences of successive RR intervals; pNN50: percent of differences of successive RR intervals N 50 ms; VLF: very low frequency; LF: low frequency; HF: high frequency; α: alpha index, square root of the ratio between RR and SBP spectral powers in the VLF (α-VLF), LF (α-LF) and HF (α-HF) band; BRSseq: linear regression slope of RR interval vs SBP. Values are mean ± SD.
characterized by a vagal drive reduction [4,5]. Similar findings have been confirmed also by other investigators who, simultaneously, have shown that an impaired CANA short-term, in early childhood, is not the case for patients with repaired CoA [6]. This is the first study, at least to our knowledge, to declare that the CANA remains normal also in the adult life, long-term after CoA management. CoA patients after repair, present with a myocardial stability, which does not affect the baroreceptor function. All patients included in this study did not report ventricular arrhythmias or had impaired cardiac anatomy, or post-surgical myocardial scars, thus this can be a rational reason for the remained normal CANA. There is previous data showing reduced BRS and HRV indices in neonates with CoA. This was possibly due to the severe increased SBP, which may cause resetting or desensitization of the baroreceptors, to the increased arterial stiffness, particularly proximal to the coarctation, and to alterations in the central processing of the baroreflex secondary to the hemodynamic changes caused by the CoA [7]. The above study cannot answer whether an abnormal CANA maintains after repair. Another question is whether neonates can present with fully developed CANA, as there is evidence that newborns with CHD present with different CANA patterns and also retardation in the development of the autonomic centers [8]. Moreover, a recent published study which indicated reduced HRV and BRS in normotensive older children with repaired CoA attributes these results to a temporal sequence of autonomic changes, as the same investigating team had previously published no changes in CANA in children with repaired CoA. Another question raised is whether a short-5 minute recording represents the real CANA status [9]. In accordance with our findings is a recent study revealing normalization of CANA in children with repaired CoA in infancy. The investigators indicate that early repair with the beneficial effect on arterial compliance leads to the re-establishment of BRS around normal BP levels within a 5-year postoperative time [10]. In conclusion, this study is a first attempt to evaluate CANA in adult CoA patients long-term after repair. Our results show that CANA is not affected although there are previous reports from mixed cohorts of CHD patients which support the opposite. Further studies in larger cohorts of CoA patients with a longer period of observations are clearly warranted to investigate and confirm these results. HRV and BRS indices represent an indirect quantification of CANA modulation. We thank K. Karpouzi and A. Varela for their technical and nursing support. This work was supported by a grant award from the Hellenic Ministry of Development, General Secretariat of Research and Technology (V.P.; 03ED258). We have no conflicts of interest to disclose.
568
Letters to the Editor
References [1] Krieger EV, Stout K. The adult with repaired coarctation of the aorta. Heart 2010;96(20):1676–81. [2] Ohuchi H, Takasugi H, Ohashi H, et al. Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease. Circulation 2003;108:2368–76. [3] Davos CH, Davlouros PA, Wensel R, et al. Global impairment of cardiac autonomic nervous activity late after repair of tetralogy of Fallot. Circulation 2002;106(12 Suppl 1):I69–75. [4] Ohuchi H, Negishi J, Miyake A, Sakaguchi H, Miyazaki A, Yamada O. Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease. Int J Cardiol Sep 15 2011;151(3):296–302. [5] Kaltman JR, Hanna BD, Gallagher PR, et al. Heart rate variability following neonatal heart surgery for complex congenital heart disease. Pacing Clin Electrophysiol May 2006;29(5):471–8.
[6] Currie KD, Martin AA, Millar PJ, et al. Vascular and autonomic function in preschool-aged children with congenital heart disease. Congenit Heart Dis May– Jun 2012;7(3):289–97. [7] Polson JW, McCallion N, Waki H, et al. Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta. Circulation 2006;113:2844–50. [8] Kakabadze SA. The pathomorphology of the higher autonomic centers in newborn infants with congenital heart defects. Biull Eksp Biol Med 1993;116:436–9. [9] Millar PJ, Proudfoot NA, Dillenburg RF, Macdonald MJ. Reduced heart rate variability and baroreflex sensitivity in normotensive children with repaired coarctation of the aorta. Int J Cardiol Sep 20 2013;168(1):587–8. [10] Kenny D, Polson JW, Martin RP, Paton JF, Wolf AR. Normalization of autonomic function in children with coarctation of the aorta after surgical correction in infancy. Hypertension 2009;54:e21–2.
http://dx.doi.org/10.1016/j.ijcard.2014.03.120 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Too many cooks spoil the broth: The currently existing diagnostic criteria for Takotsubo syndrome Shams Y-Hassan ⁎ Karolinska Institute, Karolinska University Hospital — Huddinge, Department of Cardiology, Sweden
a r t i c l e
i n f o
Article history: Received 2 February 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Takotsubo Broken heart Neurogenic stunned myocardium Acute coronary syndrome Myocarditis
I read with great interest the recently published report by Parodi et al. [1] on takotsubo syndrome (TS). In their new revised clinical diagnostic criteria for TS, the Takotsubo Italian Network (TIN) has deleted two known exclusion criteria for TS. They have pointed out that the presence of angiographically relevant coronary artery disease should not be considered an exclusion criterion for TS when the stenotic artery does not supply the dysfunctional myocardium or when the extent of dysfunctional myocardium is wider than the territory of distribution supplied by a single stenotic coronary artery. Pheochromocytoma as an exclusion criterion has also disappeared in the new TIN criteria. This is an accurate conclusion and should be valued seriously. The TIN and all other currently existing criteria for TS are trials from the researchers to find out an approach for the diagnosis of a disease entity which has erroneously gone under different diagnoses in different medical specialties during a long time. They were probably valuable at the commencement after the introduction of the term takotsubo when TS was a newly recognized disease entity. Nevertheless, with the exponential increase in the papers reporting on the disease from different parts of the world and increasing knowledge on its clinical, laboratory, and cardiac image studies during the last years, the currently existing diagnostic criteria have created problems for the clinicians who are at the mercy of all that reported on the disease including the diagnostic criteria. Remarkably, some of the ⁎ Karolinska University Hospital, Huddinge, Department of Cardiology, S-141 86 Stockholm, Sweden. Tel.: + 46 8 58582805; fax: +46 8 58586710. E-mail address: [email protected].
used criteria are not based on any scientific evidence. Others result in exclusion of substantial numbers of patients who in fact have TS. Considerable numbers of patients may incorrectly get the diagnosis of acute myocardial infarction with the consequences of lifelong unnecessary medications with their eventual side effects. The highly underestimated incidence and prevalence of TS in some studies and in patients with ST-elevation myocardial infarction (STEMI) are the product of strict application of the currently existing diagnostic criteria for TS. This is well-demonstrated in the two recently published studies; in HORIZONSAMI [2], TS was identified in only 0.5% exclusively in women 2.1%; in another study [3], an overall prevalence of 0.9% with 3.2% prevalence in the female population was reported in patients admitted with suspected STEMI. In this manuscript, the tight spots of three of the diagnostic criteria proposed by the TIN group are critically reviewed as follows. First, “typical left ventricular wall motion abnormalities (LVWMA) with complete functional normalization within 6 weeks”: The authors define the typical LVWMA as an apical ballooning. It is well-known that the typical ballooning is seen only during the acute stage of the disease; once the acute stage has passed the LVWMA lose its ballooning appearance [4]. This implies that any delay in seeking medical care may lead to misdiagnosis of patients who actually have TS. The complete normalization in the criterion means that the patients with TS who die before or during admission days will never get the diagnosis of TS. Partial normalization is regarded as an exclusion criterion. Some patients with TS may have so severe cardiac lesions that may not be compatible with survival or may be complicated with myocardial rupture. It is reasonable to suspect that such patients who survive the acute severe stage of the disease may have partial normalization of the LVWMA. In one study [3], five out of 22 (22.7%) presenting with suspected acute STEMI, having typical features of TS and no obstructive coronary artery disease were excluded owing to this diagnostic criterion. Two out of 17 patients (11.7%) with clinical and angiographic features of TS showed late gadolinium enhancement (patchy enhancement) with non-coronary distribution. These two patients showed no significant recovery of regional LVWMA [5]. The evidence for complete normalization of the LVWMA in TS within a cut-off period of 6 weeks is lacking.
Letters to the Editor
and even fewer studies focused on functional assessments with the FIM score [5]. The FIM motor scores in our cohort were 67.9 and 68.6 at the beginning (moderate dependence) and improved by 8.9 and 10.1 points reaching 76.8 and 78.7 out of 91 possible points (partial dependence). It is of note, that the initial reached functional status after cardiac surgery remains almost unchanged when assessed 1, 2, 3 and 4 years after the index operation [10]. Therefore, it is of utmost importance to admit patients, in particular older and sicker patients, immediately after cardiac surgery for intensive cardiac rehabilitation to improve functional status and functional long-term outcome, accordingly. In conclusion, patients in the TAVI group were older and sicker than SAVR patients. Despite these differences, both patient groups did benefit in the same way from a post-acute in-patient rehabilitation program as assessed by 6-Minute Walking Tests and FIM scores. References [1] Toggweiler S, Humphries KH, Lee M, et al. 5-year outcome after transcatheter aortic valve implantation. J Am Coll Cardiol 2013;61(4):413–9.
[2] Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363(17):1597–607. [3] Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364(23):2187–98. [4] Cournan M. Use of the functional independence measure for outcomes measurement in acute inpatient rehabilitation. Rehabil Nurs 2011;36(3):111–7. [5] Sansone GR, Alba A, Frengley JD. Analysis of FIM instrument scores for patients admitted to an inpatient cardiac rehabilitation program. Arch Phys Med Rehabil 2002;83(4):506–12. [6] Poole-Wilson PA. The 6-minute walk. A simple test with clinical application. Eur Heart J 2000;21(7):507–8. [7] Opasich C, De Feo S, Pinna GD, et al. Distance walked in the 6-minute test soon after cardiac surgery: toward an efficient use in the individual patient. Chest 2004;126(6):1796–801. [8] Russo N, Compostella L, Tarantini G, et al. Cardiac rehabilitation after transcatheter versus surgical prosthetic valve implantation for aortic stenosis in the elderly. Eur J Prev Cardiol 2013. [9] Williams MA, Ades PA, Hamm LF, et al. Clinical evidence for a health benefit from cardiac rehabilitation: an update. Am Heart J 2006;152(5):835–41. [10] Chaturvedi RK, Blaise M, Verdon J, et al. Cardiac surgery in octogenarians: long-term survival, functional status, living arrangements, and leisure activities. Ann Thorac Surg 2010;89(3):805–10.
http://dx.doi.org/10.1016/j.ijcard.2014.03.121 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Cardiac autonomic nervous activity in adults with coarctation of the aorta late after repair Antonia C. Moutafi a,⁎, Georgios Manis b, Christos Dellos c, Dimitrios Tousoulis d, Constantinos H. Davos a a
Cardiovascular Research Laboratory, Biomedical Research Foundation, Academy of Athens, Athens, Greece Department of Computer Science, University of Ioannina, Greece Department of Congenital Heart Disease, Tzanio Hospital, Piraeus, Greece d 1st Cardiology Department, University of Athens, Hippokration Hospital, Athens, Greece b c
a r t i c l e
i n f o
Article history: Received 2 February 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Coarctation Congenital heart disease Cardiac autonomic nervous activity
Patients with repaired coarctation of the aorta (CoA) present with long-term complications, despite early management, suggesting that CoA is not simply an anatomical malformation [1]. The reasons for their reduced life expectancy are unclear, and research remains limited, particularly with respect to their cardiac autonomic nervous activity (CANA). Few studies were carried out mainly in mixed cohorts of patients with congenital heart diseases (CHD), other than CoA, which indicate a CANA imbalance [2,3]. The aim of the present study was to evaluate CANA in adult patients with CoA, late after repair. We studied 18 stable patients (9 males) with previous CoA, aged 14 or older, at least 5 years after repair. Exclusion criteria included atrial fibrillation or greater than 2 ventricular ectopic beats during data acquisition and echocardiographic findings of recoarctation or aortic valve regurgitation. All patients had normal left ventricular function on echocardiography. Twenty-seven age- and sex-matched healthy controls
⁎ Corresponding author at: Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, 11527 Athens, Greece. Tel.: + 30 2106597392; fax: + 30 2106597405. E-mail address: tania.moutafi@yahoo.com (A.C. Moutafi).
were also studied. All investigations were performed at the Cardiovascular Research Laboratory of the Academy of Athens Biomedical Research Foundation. The Foundation's Ethics Committee approved the study and all subjects, gave informed consent before their enrollment. All participants were studied under standardized conditions. They were fasted and were not allowed to smoke or drink alcohol- or caffeinecontaining beverages for 24 h before the study. They rested supine for 15 min and then underwent clinical examination, blood pressure measurement, ECG recording, a 40 min ECG and blood pressure monitoring and transthoracic echocardiography [3]. CANA was evaluated by a 40-minute ECG and SBP recordings (TaskForce monitor, CNSystems, Austria). Blood pressure was measured using a finger cuff wrapped around the index finger of the left hand. The ECG was acquired from the limb lead with the largest R wave. The readings were saved and analyzed off-line with custom designed software. The program measured RR intervals and beat-to-beat SBP. Heart rate variability (HRV) analysis was performed and time domain and frequency domain indices were calculated using our laboratory software. Assessed time domain HRV indices were: SDNN (standard deviation of all normal-to-normal RR intervals, RMSSD (square root of the mean squared differences of successive RR intervals) and pNN50 (per cent difference of successive RR intervals N50 ms). Very low (VLF, 0.0033–0.04 Hz), low (LF, 0.04–0.15 Hz) and high frequency (HF, 0.15–0.4 Hz) HRV indices were also assessed. Baroreflex sensitivity (BRS) was assessed by measuring the average amplitude of oscillations in RR interval and SBP. Power spectral analysis was performed on the RR interval and SBP data using an autoregressive algorithm. The α-index was calculated as the square root of the ratio between RR and SBP spectral power in the low frequency (0.04–0.15 Hz, αLF) and the high frequency (0.15–0.4 Hz, αHF) band in the presence of an adequate coherence (N0.5) between the RR interval and SBP as assessed by cross-spectral analysis.
Letters to the Editor
567
Table 1 Clinical, surgical, and hemodynamic characteristics of the study population.
Age, years Female Male Time after repair, years Age at first repair, years Surgical repair Stent implantation Surgical repair followed by stent implantation Bicuspid aortic valve NYHA class I II QTc (ms) SBP (mm Hg) DBP (mm Hg)
CoA patients (n = 18)
n
Controls (n = 27)
N
p value
25.22 ± 9.60 22.21 ± 9.13 28.22 ± 9.59 17.82 ± 8.10 7.40 ± 7.54 9 6 3 7
18 9 9
26.96 ± 8.85 24.89 ± 5.93 29.19 ± 11.01
27 14 13
0.54 0.4 0.8
13 5 393.17 ± 15.08 130.61 ± 19.96 70.41 ± 7.27
386.64 ± 21.8 118.67 ± 10.14 70.40 ± 9.95
0.3 0.01 0.9
Values in mean ± SD, (%).
Data were expressed as frequency for the nominal variables and as mean ± standard deviation (SD) for continuous variables. Data were analyzed by using Statview 5.0 (Abacus Concepts, SAS Institute, Cary, U.S.A.). Differences between the two subgroups were assessed by an unpaired Student's s test, or by the Mann–Whitney rank-sum for data that failed tests of normality. HRV and BRS variables not following the normal distribution were logarithmically transformed. All tests were two sided. A p value b0.05 was considered significant. Clinical, surgical, and haemodynamic data are presented in Table 1. All HRV and BRS indices were not statistically different between the two studied groups (Table 2). The present study suggests that patients with repaired CoA undergo a normalization of the noninvasively measured indicators of CANA. This is in contrast to our previous findings in patients with repaired Tetrallogy of Fallot [3], and other studies on patients with complex CHD, which showed a significant impairment of the sympatho-vagal balance,
Table 2 Baroreflex sensitivity and heart rate variability indices. BRS and HRV variables Time domain indices of HRV SDNN (ms) log SDNN RMSSD (ms) log RMSSD pNN50 (%)
CoA patients (n = 18) 84.63 ± 31.33 1.90 ± 0.15 78.56 ± 43.08 1.83 ± 0.23 0.997 ± 0.001
Power spectrum indices of HRV 936.2 ± 1519.1 VLF (ms2) log VLF 2.70 ± 0.42 2 2294.36 ± 5548.17 LF (ms ) log LF 2.98 ± 0.46 1459.96 ± 1646.66 HF (ms2) log HF 2.95 ± 0.47
Controls (n = 27) 91.75 ± 74.47 1.89 ± 0.22 85.22 ± 95.14 1.81 ± 0.29 0.997 ± 0.001
6311.88 ± 26790.87 2.75 ± 0.71 975.53 ± 1190.07 2.81 ± 0.39 1299.93 ± 1701.60 2.85 ± 0.49
Power spectrum indices of BRS α-LF (ms/mm Hg) log α-LF α-HF (ms/mm Hg) log α-HF
21.05 ± 9.84 1.27 ± 0.21 38.96 ± 19.91 1.52 ± 0.25
17.23 ± 8.92 1.19 ± 0.2 33.72 ± 30.73 1.39 ± 0.34
BRS (sequence method) BRSseq (ms/mm Hg) log BRSseq
28.55 ± 15.07 1.40 ± 0.23
24.37 ± 12.60 1.33 ± 0.22
BRS: baroreflex sensitivity; HRV: heart rate variability; SDNN: standard deviation of all RR intervals; RMSSD: square root of the mean squared differences of successive RR intervals; pNN50: percent of differences of successive RR intervals N 50 ms; VLF: very low frequency; LF: low frequency; HF: high frequency; α: alpha index, square root of the ratio between RR and SBP spectral powers in the VLF (α-VLF), LF (α-LF) and HF (α-HF) band; BRSseq: linear regression slope of RR interval vs SBP. Values are mean ± SD.
characterized by a vagal drive reduction [4,5]. Similar findings have been confirmed also by other investigators who, simultaneously, have shown that an impaired CANA short-term, in early childhood, is not the case for patients with repaired CoA [6]. This is the first study, at least to our knowledge, to declare that the CANA remains normal also in the adult life, long-term after CoA management. CoA patients after repair, present with a myocardial stability, which does not affect the baroreceptor function. All patients included in this study did not report ventricular arrhythmias or had impaired cardiac anatomy, or post-surgical myocardial scars, thus this can be a rational reason for the remained normal CANA. There is previous data showing reduced BRS and HRV indices in neonates with CoA. This was possibly due to the severe increased SBP, which may cause resetting or desensitization of the baroreceptors, to the increased arterial stiffness, particularly proximal to the coarctation, and to alterations in the central processing of the baroreflex secondary to the hemodynamic changes caused by the CoA [7]. The above study cannot answer whether an abnormal CANA maintains after repair. Another question is whether neonates can present with fully developed CANA, as there is evidence that newborns with CHD present with different CANA patterns and also retardation in the development of the autonomic centers [8]. Moreover, a recent published study which indicated reduced HRV and BRS in normotensive older children with repaired CoA attributes these results to a temporal sequence of autonomic changes, as the same investigating team had previously published no changes in CANA in children with repaired CoA. Another question raised is whether a short-5 minute recording represents the real CANA status [9]. In accordance with our findings is a recent study revealing normalization of CANA in children with repaired CoA in infancy. The investigators indicate that early repair with the beneficial effect on arterial compliance leads to the re-establishment of BRS around normal BP levels within a 5-year postoperative time [10]. In conclusion, this study is a first attempt to evaluate CANA in adult CoA patients long-term after repair. Our results show that CANA is not affected although there are previous reports from mixed cohorts of CHD patients which support the opposite. Further studies in larger cohorts of CoA patients with a longer period of observations are clearly warranted to investigate and confirm these results. HRV and BRS indices represent an indirect quantification of CANA modulation. We thank K. Karpouzi and A. Varela for their technical and nursing support. This work was supported by a grant award from the Hellenic Ministry of Development, General Secretariat of Research and Technology (V.P.; 03ED258). We have no conflicts of interest to disclose.
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Letters to the Editor
References [1] Krieger EV, Stout K. The adult with repaired coarctation of the aorta. Heart 2010;96(20):1676–81. [2] Ohuchi H, Takasugi H, Ohashi H, et al. Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease. Circulation 2003;108:2368–76. [3] Davos CH, Davlouros PA, Wensel R, et al. Global impairment of cardiac autonomic nervous activity late after repair of tetralogy of Fallot. Circulation 2002;106(12 Suppl 1):I69–75. [4] Ohuchi H, Negishi J, Miyake A, Sakaguchi H, Miyazaki A, Yamada O. Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease. Int J Cardiol Sep 15 2011;151(3):296–302. [5] Kaltman JR, Hanna BD, Gallagher PR, et al. Heart rate variability following neonatal heart surgery for complex congenital heart disease. Pacing Clin Electrophysiol May 2006;29(5):471–8.
[6] Currie KD, Martin AA, Millar PJ, et al. Vascular and autonomic function in preschool-aged children with congenital heart disease. Congenit Heart Dis May– Jun 2012;7(3):289–97. [7] Polson JW, McCallion N, Waki H, et al. Evidence for cardiovascular autonomic dysfunction in neonates with coarctation of the aorta. Circulation 2006;113:2844–50. [8] Kakabadze SA. The pathomorphology of the higher autonomic centers in newborn infants with congenital heart defects. Biull Eksp Biol Med 1993;116:436–9. [9] Millar PJ, Proudfoot NA, Dillenburg RF, Macdonald MJ. Reduced heart rate variability and baroreflex sensitivity in normotensive children with repaired coarctation of the aorta. Int J Cardiol Sep 20 2013;168(1):587–8. [10] Kenny D, Polson JW, Martin RP, Paton JF, Wolf AR. Normalization of autonomic function in children with coarctation of the aorta after surgical correction in infancy. Hypertension 2009;54:e21–2.
http://dx.doi.org/10.1016/j.ijcard.2014.03.120 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
Too many cooks spoil the broth: The currently existing diagnostic criteria for Takotsubo syndrome Shams Y-Hassan ⁎ Karolinska Institute, Karolinska University Hospital — Huddinge, Department of Cardiology, Sweden
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Article history: Received 2 February 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Takotsubo Broken heart Neurogenic stunned myocardium Acute coronary syndrome Myocarditis
I read with great interest the recently published report by Parodi et al. [1] on takotsubo syndrome (TS). In their new revised clinical diagnostic criteria for TS, the Takotsubo Italian Network (TIN) has deleted two known exclusion criteria for TS. They have pointed out that the presence of angiographically relevant coronary artery disease should not be considered an exclusion criterion for TS when the stenotic artery does not supply the dysfunctional myocardium or when the extent of dysfunctional myocardium is wider than the territory of distribution supplied by a single stenotic coronary artery. Pheochromocytoma as an exclusion criterion has also disappeared in the new TIN criteria. This is an accurate conclusion and should be valued seriously. The TIN and all other currently existing criteria for TS are trials from the researchers to find out an approach for the diagnosis of a disease entity which has erroneously gone under different diagnoses in different medical specialties during a long time. They were probably valuable at the commencement after the introduction of the term takotsubo when TS was a newly recognized disease entity. Nevertheless, with the exponential increase in the papers reporting on the disease from different parts of the world and increasing knowledge on its clinical, laboratory, and cardiac image studies during the last years, the currently existing diagnostic criteria have created problems for the clinicians who are at the mercy of all that reported on the disease including the diagnostic criteria. Remarkably, some of the ⁎ Karolinska University Hospital, Huddinge, Department of Cardiology, S-141 86 Stockholm, Sweden. Tel.: + 46 8 58582805; fax: +46 8 58586710. E-mail address: [email protected].
used criteria are not based on any scientific evidence. Others result in exclusion of substantial numbers of patients who in fact have TS. Considerable numbers of patients may incorrectly get the diagnosis of acute myocardial infarction with the consequences of lifelong unnecessary medications with their eventual side effects. The highly underestimated incidence and prevalence of TS in some studies and in patients with ST-elevation myocardial infarction (STEMI) are the product of strict application of the currently existing diagnostic criteria for TS. This is well-demonstrated in the two recently published studies; in HORIZONSAMI [2], TS was identified in only 0.5% exclusively in women 2.1%; in another study [3], an overall prevalence of 0.9% with 3.2% prevalence in the female population was reported in patients admitted with suspected STEMI. In this manuscript, the tight spots of three of the diagnostic criteria proposed by the TIN group are critically reviewed as follows. First, “typical left ventricular wall motion abnormalities (LVWMA) with complete functional normalization within 6 weeks”: The authors define the typical LVWMA as an apical ballooning. It is well-known that the typical ballooning is seen only during the acute stage of the disease; once the acute stage has passed the LVWMA lose its ballooning appearance [4]. This implies that any delay in seeking medical care may lead to misdiagnosis of patients who actually have TS. The complete normalization in the criterion means that the patients with TS who die before or during admission days will never get the diagnosis of TS. Partial normalization is regarded as an exclusion criterion. Some patients with TS may have so severe cardiac lesions that may not be compatible with survival or may be complicated with myocardial rupture. It is reasonable to suspect that such patients who survive the acute severe stage of the disease may have partial normalization of the LVWMA. In one study [3], five out of 22 (22.7%) presenting with suspected acute STEMI, having typical features of TS and no obstructive coronary artery disease were excluded owing to this diagnostic criterion. Two out of 17 patients (11.7%) with clinical and angiographic features of TS showed late gadolinium enhancement (patchy enhancement) with non-coronary distribution. These two patients showed no significant recovery of regional LVWMA [5]. The evidence for complete normalization of the LVWMA in TS within a cut-off period of 6 weeks is lacking.
