Author + information
- Shams Y-Hassan, MD∗ ()
- ↵∗Karolinska Institute at Karolinska University Hospital, Department of Cardiology, Huddinge, S- 141 86 Stockholm, Sweden
I read with great interest the work by Christensen et al. (1) and the editorial comment on that study by Chen et al. (2), recently published in iJACC. The investigators examined 32 patients with Takotsubo syndrome (TS) and 20 control subjects at the subacute phase and at follow-up examinations, using echocardiography, 123-metaiodobenzylguanidine (123I-MIBG) scintigraphy and, plasma catecholamine measurements. Three points deserve discussion in this well-performed study. First, 123I-MIBG scintigraphy has shown uptake defects and high washout rates during the subacute phase in TS patients. This finding is further support to the accumulated evidence for the hypothesis that the local cardiac sympathetic hyperactivation-disruption and norepinephrine seethe and spillover plays a key role in the pathogenesis of TS (3). It is not clear from the study whether the 123I-MIBG scintigraphic defects were restricted to the left ventricular wall motion abnormality regions and whether they were completely normalized during follow-up time. The principle findings of 123I-MIBG scintigraphy in TS in other studies are decreased regional uptake of 123I-MIBG in the hypokinetic/akinetic left ventricular segments and increased washout rate of 123I-MIBG.
Second, plasma catecholamine levels were examined in the study during the subacute phase and at follow-up at 105 days. The authors concluded that one of the most important finding in the study, in addition to the evidence of “myocardial sympathetic hyperactivity,” is the increased plasma epinephrine in the subacute phase of the disease and even during follow-up. From the information in the manuscript, one may conclude that plasma epinephrine was normal in control subjects during follow-up (log2 epinephrine: 4.56 pg/ml; and epinephrine: 24 pg/ml). In such a case and according to the values available in Table 2 (1), there is only mild elevation in plasma log2 epinephrine during the subacute phase (1.1-fold compared to control patients in the subacute phase and 1.3-fold compared to the control group at follow-up). Such mild elevation of plasma epinephrine may be attributed to marked elevation of plasma epinephrine in only few patients that may result in mild elevation in the whole group. In one study (4), plasma epinephrine was normal in 24 of 27 patients (89%) with TS; moderately elevated (3.8-fold the upper normal limit [UNL]) in 2 patients (7.4%); and markedly elevated (8.9-fold the UNL) in only 1 patient (3.7%). This author would be grateful if the following question were answered by the investigators: what were the normal reference values of plasma epinephrine and norepinephrine in the study? How many patients with TS had normal or nearly normal plasma epinephrine levels? What was the degree of epinephrine and norepinephrine elevations (mild, moderate, or severe)? Are the degrees of plasma catecholamine elevations in the study comparable to the striking elevations reported in the study by Wittstein et al. (see ref. 29 in Christensen et al. )?
Third, Chen et al. (2), in a reply letter, raised one important question seen in the title of the comment, which is whether the cardiac sympathetic disturbance in TS is a primary cause or a compensatory response to heart failure. In patients with chronic heart failure, there is extensive evidence for cardiac sympathetic hyperactivity, initially as a compensatory mechanism but with time continuing to cardiac sympathetic disruption with deleterious consequences (5). In addition to the 123I-MIBG scintigraphic findings in TS, there is extensive evidence, discussed elsewhere (3), supporting the hypothesis of the presence of a causal link between local cardiac sympathetic hyperactivation-disruption (triggered by emotional or physical stress factors) and TS (3). The local cardiac sympathetic hyperactivation-disruption that occurs in patients with chronic heart failure, regardless of the underlying cause, may also be a form of TS occurring in repetitive attacks or in chronic form triggered by heart failure or its severe symptoms. Cardiac sympathetic hyperactivation-disruption is most probably the primary cause of TS (3), and chronic TS with acute exacerbation may be the main cause of acute deterioration of heart failure in patients with chronic heart failure (5).
Please note: Dr. Y-Hassan has reported that he has no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Christensen T.E.,
- Bang L.E.,
- Holmvang L.,
- et al.
- Chen W.,
- Dilsizian V.
- Y-Hassan S.,
- Henareh L.
- Y-Hassan S.