Dear Mr. Eden Nonato:
We are truly grateful to yours and other reviewers’ critical comments and thoughtful
suggestions. Based on these comments and suggestions, we have made careful
modifications on the original manuscript. All changes made to the text are in red color.
In addition, we have consulted native English speakers for paper revision before the
submission this time. We hope the new manuscript will meet your magazine’s
standard. Below you will find our point-by-point responses to the reviewers’
comments/questions:
In reply to the reviewer's comments
Reviewer: Mario Iannaccone
Major Compulsory revisions
- the abstract should be reviewed. It's a case series so it is not necessary to divide into
backgroup/case presentations/conclusion. Just write an little summary of the article.
Response: Acording to the reviewer's suggestions, the abstract including
backgroup/case presentations/conclusion had been replaced by an little summary
of the article in revised manuscript.
- Generally speaking clinical relevant myocardial bridge is not easy to demonstrate.
Gold standard should be to perform coronary tomography to evaluate the coronary
artery tract length and deepness into myocardial muscle. (Alegria JR, Herrmann J,
Holmes DR Jr, Lerman A, Rihal CS. Myocardial bridging. Eur Heart J. 2005
Jun;26(12):1159-68. Epub 2005 Mar 11. Review. PubMed PMID:15764618). In the
presented cases by the angiography doesn’t seem to be significant myocardial bridge,
short tract, not complete systolic milking. Moreover another misleading point is the
pain relief with nitrate. Myocardial bridge is generally worsening by nitrate because
of the reduction in systolic pressure and coronary resistance which determine a
stronger compression “ab estrinseco” by the myocardial muscle. By my opinion it is
unclear by the showed data the myocardial bridge presence, or clinical relevance.
Moreover the coronary spasm is much more probable, unfortunately vasoactive test,
such as ergonovine/achetilcoline test were not performed. To my opinion article
should be re-wrote in order to focus to on coronary spasm. Outcome information are
really interesting, because despite is generally considered a “benign” disease one of
your cases suffered by sudden cardiac arrest.
Response: Though myocardial bridge (MB) is seen as often as 40–80% on
autopsy, the rate of angiographic bridging is ﹤ 5%, attributable to thin bridges
causing little compression. A thin or short MB is often missed [1]. In these
patients, new imaging techniques (Intravenous ultrasound (IVUS) and
multiple-slice computed tomography (MSCT)) and provocation tests may be
required to detect a bridge [2-5]. In patients with angiographically normal
coronary arteries, the use of provocation tests may reveal MB in ≤ 40% of cases
[6]. Regrettably, the present study was a retrospective study, diagnosis of MB
depends on the diameter change between systole and diastole within the bridged
coronary segment. Therefore the coronary artery tract length and deepness into
myocardial muscle were not evaluated by coronary tomography. Though a
significant “milking effect” is present when there is ≥ 70% reduction in minimal
luminal diameter, the diameter change between systole and diastole in present
study was also obvious.
Owing to intensifying systolic compression of the bridged segment, nitrates
should be avoided unless there is significant concomitant vasospasm. Indeed,
though increasing the milking effect on angiography, nitrates have been used
effectively in some patients (including case 2 in present study), which may be
associated with their capability to reduce preload and to relieve vasospasm [7].
Coronary artery spasm is not an uncommon and occurs in normal or significant
obstructive coronary artery. Coronary spasm at myocardial bridge site was more
easily to be provoked by either acetylcholine administration or physical exertion
[8]. Though coronary spasm may occur spontaneously or induced by catheter on
coronary angiography, manifestied as a reduction in luminal diameter, the MB
showed a cyclical change between systole and diastole, which was different from
that in coronary spasm. As in case 1 and 2 in present study, coronary spasm can
occur in coronary artery with or without MB.
Though MB has been regarded as to be benign clinically for a long time and most
MBs are not symptomatic, symptomatic patients who have MBs may present
with myocardial ischemia, acute coronary syndromes, coronary spasm, sudden
cardiac arrest or even sudden death. Our present study also showed that a wide
variety of clinical syndromes have been associated with MB.
-general english should be reviewed
Response: we have made careful modifications on the original manuscript.
Minor Essential Revisions
-line 31: need capital letter "we reviewed"
-line 69 writing mistake "myohemoglobin"
Response: Errors in line 31 and 69 have been corrected in the paper.
On behalf of my co-authors, we would like to express our great appreciation to
you for your comments and thoughtful suggestions.
References
[1] Möhlenkamp S et al. Update on myocardial bridging. Circulation. 2002;106:2616 –2622.
[2] Ge J et al. Comparison of intravascular ultrasound and angiography in theassessment of
myocardial bridging. Circulation. 1994;89:1725–1732.
[3] Ge J, et al. New signs characteristic of myocardial bridging demonstrated by intracoronary
ultrasound and Doppler. Eur Heart J. 1999;20:1707–1716.
[4] Zeina AR et al. Myocardial bridge: evaluation on MDCT. Am J Roentgen. 2007;188:1069
–1073.
[5] Kawawa Y et al. Detection of myocardial bridge and evaluation of its anatomical properties
by coronary multislice spiral computed tomography. Eur J Radiol. 2007;61:130 –138.
[6] Iversen S et al. Surgical treatment of myocardial bridging causing coronary artery obstruction.
Scand J Thor Cardiovasc Surg. 1992;26:107–111.
[7] Pichard AD et al. Abnormal regional myocardial flow in myocardial bridging of the left
anterior descending coronary artery. Am J Cardiol 1981;47:978-82.
[8] Xiang DC et al. Characteristics of stress tests and symptoms in patients with myocardial
bridge and coronary artery spasm. Coron Artery Dis. 2009;20:27-31.
Reviewer:Jeffrey A. Brinker
Reviewer's report:
The authors submit an interesting series of patients presenting with evidence of
ischemia and the presence of a myocardial bridge on coronary angiography without
evidence of significant atherosclerotic narrowing. Perhaps they would consider
whether attention to the following might strenthen their paper:
1. The authors note that these case reports represent "coronary artery disease with
myocardial bridge and no stenosis of coronary". I believe that these cases might better
be described as representative of 'myocardia ischemia associated with a myocardial
bridge with no significant atherosclerotic stenosis'.
Response: Acording to the reviewer's suggestions, the title of the manuscript had
been changed.
2. While most myocardial bridges evidence only systolic stenosis; some have
non-atherosclerotic diastolic stenosis as well usually of 20-40%. Did any of their
cases exhibit this?
Response: On coronary angiography, the diagnosis of myocardial bridge depends
on the diameter change between systole and diastole within the bridged coronary
segment. A significant “milking effect” is present when there is ≥ 70% reduction
in minimal luminal diameter (MLD) during systole and persistent ≥ 35% MLD
reduction during mid-to-late diastole. A thin or short MB is often missed [1].
Moreover, among patients with angiographically documented milking effect, a
fairly large percentage have concomitant atherosclerosis, it is difficult to
determine the myocardial bridges with diastolic stenosis by coronary
angiography like in present study. Intravenous ultrasound (IVUS) and
multiple-slice computed tomography (MSCT) may be improved MB detection
[2-5].
3. Ishikawa et al reference refers to atherosclerotic disease at the proximal margin of
the intramyocardia segment (e.g. bridge) of the coronary artery. The relate myocardial
infarction to this. It is true that while the bridge itself may be 'protective' of
atherosclerotic disease, the epicardial margins of bridge may favor atherosclerotic
disease and be sites of spasm which is most often the cause of acute ischemia.
Response: As the reviewer suggested, many studies have demonstrated that the
absence of atherosclerotic changes in the intramural and distal segments of
bridged vessels, whereas atherosclerotic changes are always found in the
proximal segment of the vessel [3,6], which can be attributed to biomechanical
forces at the entrance of a myocardial bridge. Moreover, coronary spasm at
myocardial bridge site was more easily to be provoked [7].
4. Prior studies have shown that since most coronary flow is diastolic, myocardial
bridging is usually not symptom producing unless the heart rate is very high. The
cases described by the authors which were presumably not associated with increased
heart rates suggest that spasm is the more likely cause as is also suggested by ST
elevation.
Response: Though myocardial bridging is seen as often as 40–80% on autopsy,
functional myocardial bridging is less commonly observed on coronary
angiography (0.5-16%). The hemodynamic impact of myocardial bridging
depends on the thickness and length of the bridge, orientation of the bridge
relative to myocardial fibers and presence of loose connective or adipose tissue
around the bridged segment. Additional pathophysiologic changes can induce
symptoms of myocardial ischemia in previously asymptomatic patients, which
included increasing left ventricular diastolic dysfunction, left ventricular
hypertrophy, coronary vasospasm and microvascular dysfunction. As the
reviewer suggested, myocardial bridging is usually not symptom producing
unless the heart rate is very high. In our study, the heart rates of case 1 and 2
were 62 and 61 bpm respectively. The ECG changes revealed that the coronary
spasm may play an important role in these patients. Indeed, coronary spasm at
myocardial bridge site was more easily to be provoked by either acetylcholine
administration or physical exertion [7]. In case 3 with faster atrial fibrillation,
the ventricular rate was 110 bpm, which increased the demand and decreased the
supply of myocardial blood flow, which intensified myocardial supply/demand
mismatch.
5. The administration of nitroglycerin either intra-coronary, intravenously, or
sublingual may bring out angiographic evidence of a bridge which was not evident
prior to administration of the drug. The authors might comment on the use of
nitroglycerin in these patients.
Response: Owing to intensifying systolic compression of the bridged segment,
nitrates should be avoided unless there is significant concomitant vasospasm.
Indeed, though increasing the milking effect on angiography, nitrates have been
used effectively in some patients (including case 2 in present study), which may
be associated with their capability to reduce preload and to relieve vasospasm [8].
The aboving comment was also included in the revised manuscript.
6. The authors might comment on therapy for patients with coronary ischemia and
only a bridge at the time of angiography.
Response: The treatment of patients with MB had beed added in the paper.
On behalf of my co-authors, we would like to express our great appreciation to
you for your comments and thoughtful suggestions.
References
[1] Möhlenkamp S et al. Update on myocardial bridging. Circulation. 2002;106:2616 –2622.
[2] Ge J et al. Comparison of intravascular ultrasound and angiography in theassessment of
myocardial bridging. Circulation. 1994;89:1725–1732.
[3] Ge J, et al. New signs characteristic of myocardial bridging demonstrated by intracoronary
ultrasound and Doppler. Eur Heart J. 1999;20:1707–1716.
[4] Zeina AR et al. Myocardial bridge: evaluation on MDCT. Am J Roentgen. 2007;188:1069
–1073.
[5] Kawawa Y et al. Detection of myocardial bridge and evaluation of its anatomical properties
by coronary multislice spiral computed tomography. Eur J Radiol. 2007;61:130 –138.
[6] Ishikawa Y et al. Anatomic properties of myocardial bridge predisposing to myocardial
infarction. Circulation. 2009; 120:376–83.
[7] Xiang DC et al. Characteristics of stress tests and symptoms in patients with myocardial
bridge and coronary artery spasm. Coron Artery Dis. 2009;20:27-31.
[8] Pichard AD et al. Abnormal regional myocardial flow in myocardial bridging of the left
anterior descending coronary artery. Am J Cardiol 1981;47:978-82.