The data presented in Welsh et al.'s paper assessing variations in
practice across the 12 countries in the ASSENT 3 PLUS trial may not be
representative of UK practice since each of the four constituent countries
of the UK have distinct health systems.
In England and Wales, both of which have national standards for the
care of STEMI patients -National Service Frameworks- and in which all 130...
The data presented in Welsh et al.'s paper assessing variations in
practice across the 12 countries in the ASSENT 3 PLUS trial may not be
representative of UK practice since each of the four constituent countries
of the UK have distinct health systems.
In England and Wales, both of which have national standards for the
care of STEMI patients -National Service Frameworks- and in which all 130
hospitals caring for heart attack patients participate in the national
audit of myocardial infarction, use of emergency ambulance services as
opposed to the requirement to contact a primary care physician first,
suggested by Welsh et al. as a reason for UK delay, was as reported by
Birkead et al. in 2002-03 67% of patients with a final diagnosis of an
acute coronary syndrome called for an emergency ambulance and 16.2%
contacted the primary care practitioner.
The Committee for the Safety of Medicines has only two entries for amiodarone extravasation injury, yet almost every consultant seems to remember a patient who has had their arm amputated following extravasation of amiodarone. Surely this is a case of the dangers of peripheral
amiodarone being exagerated? In periarrest / cardiac arrest situations amiodarone has been given as a peripheral bolus countl...
The Committee for the Safety of Medicines has only two entries for amiodarone extravasation injury, yet almost every consultant seems to remember a patient who has had their arm amputated following extravasation of amiodarone. Surely this is a case of the dangers of peripheral
amiodarone being exagerated? In periarrest / cardiac arrest situations amiodarone has been given as a peripheral bolus countless times; what proportion of cases result in extravasation injury?
Central line access has many potential complications /
contraindications (e.g. post thrombolysis). If the patient is on ITU and has a central line - great - otherwise the delay and risk involved in inexperienced juniors obtaining central access appear to me to outweigh the tiny risk of extravasation injury; providing the amiodarone is given
through a fresh antecubital fossa venflon.
This Heart article has also been featured in the BMJ and it appears to be a case of a blanket guideline being made on anecdotal evidence.
We have read the article[1] with great interest. Selection of the 23
patients is not clearly mentioned here. There is a lack of some other
information too. Once the chest pain started, after what time those
patients were selected for angioplasty? What was the percentage of lumen
narrowing or stenosis? Was the stenosis complicated or not? What was the
material used for primary angioplasty?
We have read the article[1] with great interest. Selection of the 23
patients is not clearly mentioned here. There is a lack of some other
information too. Once the chest pain started, after what time those
patients were selected for angioplasty? What was the percentage of lumen
narrowing or stenosis? Was the stenosis complicated or not? What was the
material used for primary angioplasty?
Rapid time to treatment with thrombolytic therapy is associated with
lower mortality in patients with acute myocardial infarction (MI). Study[2] suggests that physicians and health care systems should work to
minimize door-to-balloon times and that door-to-balloon time should be
considered when choosing a reperfusion strategy. Time from acute MI
symptom onset to first balloon inflation and by time from hospital arrival
to first balloon inflation (door-to-balloon time) plays an important role
in management of MI.
In a study[3] showed that, patients with AMI treated at hospitals
with high or intermediate volumes of primary angioplasty had lower
mortality with primary angioplasty than with thrombolysis, whereas
patients with AMI treated at hospitals with low angioplasty volumes had
similar mortality outcomes with primary angioplasty or thrombolysis. To
prevent restenosis or reinfarction in previously stenosed coronary vessels
drug eluting stent (paclitaxel-eluting stent) proves superior to bare
metal stent.[4] In patients with in-stent restenosis, sirolimus- or
paclitaxel-eluting stents is superior to conventional balloon angioplasty
for the prevention of recurrent restenosis. Sirolimus-eluting stents may
be superior to paclitaxel-eluting stents for treatment of this disorder.[5]
Reference:
1. Should primary angioplasty be available for all patients with an ST
elevation myocardial infarction? A de Belder. Heart 2005;91:1509-1511;
doi:10.1136/hrt.2004.059485.
2. Christopher P. Cannon; C. Michael Gibson; Costas T. Lambrew; David A.
Shoultz; Drew Levy; William J. French; Joel M. Gore; W. Douglas Weaver;
William J. Rogers; Alan J. Tiefenbrunn
Relationship of Symptom-Onset-to-Balloon Time and Door-to-Balloon Time
With Mortality in Patients Undergoing Angioplasty for Acute Myocardial
Infarction
JAMA, Jun 2000; 283: 2941 - 2947.
3. David J. Magid; B. Ned Calonge; John S. Rumsfeld; John G. Canto; Paul
D. Frederick; Nathan R. Every; Hal V. Barron; for the National Registry of
Myocardial Infarction 2 and 3 Investigators
Relation Between Hospital Primary Angioplasty Volume and Mortality for
Patients With Acute MI Treated With Primary Angioplasty vs Thrombolytic
Therapy
JAMA, Dec 2000; 284: 3131 - 3138.
4. Gregg W. Stone; Stephen G. Ellis; Louis Cannon; J. Tift Mann; Joel D.
Greenberg; Douglas Spriggs; Charles D. O'Shaughnessy; Samuel DeMaio;
Patrick Hall; Jeffrey J. Popma; Joerg Koglin; Mary E. Russell; for the
TAXUS V Investigators
Comparison of a Polymer-Based Paclitaxel-Eluting Stent With a Bare Metal
Stent in Patients With Complex Coronary Artery Disease: A Randomized
Controlled Trial
JAMA, September 14, 2005; 294: 1215 - 1223.
5. Adnan Kastrati; Julinda Mehilli; Nicolas von Beckerath; Alban Dibra;
Jörg Hausleiter; Jürgen Pache; Helmut Schühlen; Claus Schmitt; Josef
Dirschinger; Albert Schömig; for the ISAR-DESIRE Study Investigators
Sirolimus-Eluting Stent or Paclitaxel-Eluting Stent vs Balloon Angioplasty
for Prevention of Recurrences in Patients With Coronary In-Stent
Restenosis: A Randomized Controlled Trial. JAMA, January 12, 2005; 293:
165 - 171.
Dr. Huffman and colleagues [1] studied 131 post-myocardial infarction
(MI) patients (17 with major depressive disorder [MDD]) and reported that
two items from the Beck Depression Inventory (BDI) related to sadness and
loss of interest formed an effective screening tool for post-MI
depression. The sensitivity and specificity results reported by Huffman et
al. are, in fact, highly similar to those repo...
Dr. Huffman and colleagues [1] studied 131 post-myocardial infarction
(MI) patients (17 with major depressive disorder [MDD]) and reported that
two items from the Beck Depression Inventory (BDI) related to sadness and
loss of interest formed an effective screening tool for post-MI
depression. The sensitivity and specificity results reported by Huffman et
al. are, in fact, highly similar to those reported for two other existing
brief depression screens, the PHQ-2 [2], which was validated in a sample
of 580 primary care patients (41 with MDD), and a similar 2-item screen
[3], which was validated in a sample of 1,024 patients with coronary heart
disease (CHD) (224 with MDD). The validation study for the CHD screen
included a comparison to the PHQ-2 and found identical areas under the
curve (a measure of overall accuracy) of 0.84 for both instruments and
sensitivities and specificities that were very similar to those reported
by Huffman et al.when a cutoff of 1 or greater was used for each
instrument. Notably, these two screening tools and the screening tool
proposed by Huffman et al. each include slightly differently worded
versions of 2 items: an item about mood and an item about anhedonia, the
two core symptoms of a DSM-IV diagnosis of MDD.
Is it beneficial to continue to look for “new” and slightly different
versions of brief depression screening tools? The authors of a literature
synthesis of case-finding instruments for identifying depression in
primary care concluded that it is not [4]. They found 16 case-finding
instruments of 1-30 items that all had adequate performance
characteristics in primary care and found very few differences between
instruments (although there were significant differences within
instruments across studies) . In their words, “the search for a better
mousetrap has not led to an instrument with superior performance
characteristics.” Furthermore, the proliferation of new instruments with
no notable improvement in performance has the potential to create
confusion, but not better options, for clinicians and researchers.
While the search for “a better mousetrap” is not likely to add much
to the clinical care of MI patients, a simple mousetrap is clearly
desirable for use in acute cardiac care, since MI patients are generally
cared for by cardiovascular specialists whose focus is not on depression
and who often do not have the expertise to diagnose or treat this
condition. However, the question is not whether a few simple questions
can improve rates of recognition of depression in busy cardiac units.
Rather, it is whether cardiovascular specialists can and will use these
screening tools, and how they would perform in their hands under real life
conditions rather than when administered by psychiatrists as in the study
by Huffman, et al.1 In addition, research is needed that attends to
essential, but generally neglected, elements of the screening process,
such as when, where, and how often to screen patients; whether patient
characteristics, such as age, gender, and race, influence the accuracy of
depression screening in the post-MI setting; and, as noted by the authors,
whether serial screening with more than one instrument improves efficiency
and accuracy.
REFERENCES
1. Huffman JC, Smith FA, Blais MA, Beiser ME, Januzzi JL, Fricchione GL. Rapid screening for major depression in post-myocardial infarction patients: an investigation using Beck Depression Inventory II items. Heart 2006;92:1656-60.
2. Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care 2003;41:1284-92.
3. McManus D, Pipkin SS, Whooley MA. Screening for depression in patients with coronary heart disease (data from the Heart and Soul Study). Am J Cardiol 2005;96:1076-81.
4. Williams JW,Jr, Pignone M, Ramirez G, Perez Stellato C. Identifying depression in primary care: a literature synthesis of case-finding instruments. Gen Hosp Psychiatry 2002;24:225-37.
Intra-country variation versus inter-country variation in pre-hospital care management of acute MI with ST elevation is worrisome
matter. Thanks to R C Welsh et al. for wring the article. ST elevation
acute MI needs early treatment with fibrinolysis therapy as early
possible.
Study[1] shows that time management is the key of ST elevation MI.
Rapid time to treatment with thrombolytic therapy...
Intra-country variation versus inter-country variation in pre-hospital care management of acute MI with ST elevation is worrisome
matter. Thanks to R C Welsh et al. for wring the article. ST elevation
acute MI needs early treatment with fibrinolysis therapy as early
possible.
Study[1] shows that time management is the key of ST elevation MI.
Rapid time to treatment with thrombolytic therapy is associated with lower
mortality in patients with acute myocardial infarction (MI). More rapid
time to reperfusion results in lower mortality in the strategy of primary
angioplasty.
Increased mortality and delay in door-to-balloon time longer than two hours (present in nearly 50% of this cohort) suggests that physicians and
health care systems should work to minimize door-to-balloon times and that
door-to-balloon time should be considered when choosing a reperfusion
strategy. Door-to-balloon time also appears to be a valid quality-of-care
indicator.
References:
1. Christopher P. Cannon; C. Michael Gibson; Costas T. Lambrew; David A.
Shoultz; Drew Levy; William J. French; Joel M. Gore; W. Douglas Weaver;
William J. Rogers; Alan J. Tiefenbrunn
Relationship of Symptom-Onset-to-Balloon Time and Door-to-Balloon Time
With Mortality in Patients Undergoing Angioplasty for Acute Myocardial
Infarction
JAMA, Jun 2000; 283: 2941 - 2947.
At the out-set, I want to congratulate the authors of the article "The patho-physiology of myocardial reperfusion: a pathologist's perspective" (1)for an outstanding job in summarizing a complex topic in a
simplified way.
However, it was presented as if “reperfusion” is the culprit ("Reperfusion Injury”), even though, an attempt is made to clarify that the injury after reperfusion is happenin...
At the out-set, I want to congratulate the authors of the article "The patho-physiology of myocardial reperfusion: a pathologist's perspective" (1)for an outstanding job in summarizing a complex topic in a
simplified way.
However, it was presented as if “reperfusion” is the culprit ("Reperfusion Injury”), even though, an attempt is made to clarify that the injury after reperfusion is happening from previous ischemia, from present reperfusion and from ischemia that is present in the micro-
vasculature despite reperfusion. There were multiple reference articles that were quoted which again use the term" reperfusion injury" (2-4) adding to the impression that reperfusion is the "only" culprit, which in-fact, is playing a “partial” role.
From the available experimental data, we totally agree that “reperfusion associated injury” is real and proven. As agreed by authors in their article, reperfusion is only a part of this problem (while, in fact, it is the solution to the problem of coronary ischemia). It helps to have a proper terminology for this complex phenomenon so that whole gamut of the problem is reflected in the terminology rather than a part. We strongly feel that a proper terminology makes a huge difference in proper understanding, especially when a complex phenomenon is involved.
“Myocardial ischemia and reperfusion injury” (5) may be one terminology close this phenomenon than “reperfusion injury”, as it implies that the injury is happening both from ischemia and reperfusion rather than reperfusion alone.
A most appropriate terminology, we feel, is “Reperfusion Micro-vascular Ischemia (RMI)”(6) as coined by Spears et al , which signifies that the injury is caused by ischemia, reperfusion and persistent micro-vascular dysfunction despite reperfusion, rather than “reperfusion injury” alone.
References:
1. Basso C, Thiene G The pathophysiology of myocardial reperfusion: a pathologist's perspective Heart (British Cardiac Society). Nov 2006;92(11):1559-1562
2. Ambrosio G, Tritto I Reperfusion injury: experimental evidence and clinical implications American heart journal. Aug 1999;138(2 Pt 2):S69-75
3. Kloner RA Does reperfusion injury exist in humans? Journal of the American College of Cardiology. Feb 1993;21(2):537-545
4. Maxwell SR, Lip GY Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options International journal of cardiology. Jan 31 1997;58(2):95-117
6. Spears JR, Prcevski P, Xu R, Li L, Brereton G, DiCarli M, Spanta A, Crilly R, Lavine S, vander Heide R Aqueous oxygen attenuation of reperfusion microvascular ischemia in a canine model of myocardial infarction Asaio J. Nov-Dec 2003;49(6):716-720
Mulcahy's article is an interesting update on the subject of silent
myocardial ischemia.[1] He postulates that ambulatory ST segment
monitoring does not add significantly to the finding of exercise testing, because it would occur almost exclusively in patients with a positive result in the ischemia exercise test.
In a German multicentre study, we have analyzed both exercise test
and ambulat...
Mulcahy's article is an interesting update on the subject of silent
myocardial ischemia.[1] He postulates that ambulatory ST segment
monitoring does not add significantly to the finding of exercise testing, because it would occur almost exclusively in patients with a positive result in the ischemia exercise test.
In a German multicentre study, we have analyzed both exercise test
and ambulatory ST segment findings in 239 hypertensive patients. ST
segment depression was defined as 1 mm for limb or chest recordings V1 to
V6 without angina in an incremental cycle ergometry and 1 mm horizontal or
descending ST segment depression, 1 min duration, without angina pectoris,
in ambulatory ST detection. Eighteen patients had ST segment depression
only in the exercise test, 23 only in ambulatory ST detection and 28
patients had ST segment depression with both methods. The ambulatory ECG
was combined with a 24-h ambulatory blood pressure device with the
capability of additional blood pressure recording triggered by ST segment
analysis.
At the time of ST segment depression, all parameters except diastolic
blood pressure were significantly lower in the ambulatory ST detection
compared to the corresponding parameters at the time of ST segment
depression in the exercise test in the group with ST-segment depression
with both methods (systolic blood pressure: 148 + 19 vs. 188 +/- 35 mmHg;
heart rate: 93 +/- 12 vs. 120 +/- 21 beat/min.; double product: 13,714 +/-
2315 vs. 22,992 +/- 3985 mmHg/min).[2] Other groups have also reported a
substantially lower ischemic threshold in the ambulatory ST segment
detection than that measured during the exercise test.[3,4]
Furthermore, it has previously been reported that patients with
negative exercise test may have silent myocardial ischemia in the
ambulatory ST segment monitoring, a finding which was associated with
increased cardiovascular morbidity.[5,6] We therefore agree with these
groups that the two methods of detecting ischemia do not replace but
complement each other.
References
1. Mulcahy DA. The return of silent myocardial ischemia? Not really.
Heart 2005;91:1249-1250.
2. Uen S, Weisser B, Un I, Baulmann J, Vetter H, Mengden T. A
comparison of ischemic threshold as determined by exercise test and
Cardiotens monitoring in hypertensive patients. J Hypertens 2005 June,
volume 23, supplement 2, S166.
3. Benhorin J, Banai S, Moriel M, Gavish A, Keren A, Stern S, Tzivoni
D. Circadian variation in ischemic threshold and their relation to the
occurrence of ischemic episodes. Circulation 1993 Mar; 87(3):808-14.
4. Quyyumi AA, Panza JA, Diodati JG, Lakatos E, Epstein SE. Circadian
variation in ischemic threshold: a mechanism underlying the circadian
variation in ischemic events. Circulation 86 (1992) 22-24.
5. Gaetano AL, Alessandro M, Vincenzo P, Guiseppe C, Domenico C,
Filippo C, Attilio M: Ischemic-like ST-segment changes during Holter
monitoring in patients with angina pectoris and normal coronary arteries
but negative exercise testing. Am J Cardiol 79 (1997) 1-6.
6. Raby KE, Barry J, Treasure CB, Hirsowitz G, Fantasia G, Selwyn AP.
Usefulness of Holter monitoring for detecting myocardial ischemia in
patients with nondiagnostic exercise treadmill test. Am J Cardiol 72(12)
(1993) 889-893.
With interest we read the article by McMahon et al. about the application of tissue Doppler imaging (TDI) in assessing the prognosis of children with left ventricular hypertrabeculation/noncompaction (LVHT).[1]
We have, however, several questions and concerns:
There are only limited experiences in the follow-up of patients with LVHT and the prognosis is largely unknown.[2] The “undul...
With interest we read the article by McMahon et al. about the application of tissue Doppler imaging (TDI) in assessing the prognosis of children with left ventricular hypertrabeculation/noncompaction (LVHT).[1]
We have, however, several questions and concerns:
There are only limited experiences in the follow-up of patients with LVHT and the prognosis is largely unknown.[2] The “undulating phenotype” of the cardiac abnormalities is a feature of LVHT, not exclusively found in children, but also in adults.[3]
With interest we recognized that the applied diagnostic criteria are a fruitful combination of Jenni’s and our criteria. Recently we proposed to classify LVHT cases fulfilling both criteria as “definite” and fulfilling
either criterion as “probable” LVHT.[4] How was “dilated”, “hypertrophic” and “combined” phenotype defined?
It is well known that TDI parameters and measurements are influenced by the type of the echocardiographic machine.[5] Did the authors observe different results when using different machines? Were interobserver variability studies performed regarding registration of the TDI signals?
Were there any correlations between heart rate or blood pressure and the parameters measured by TDI?
We miss information about the gender of the included patients, and results of the 2-D and M-mode echocardiographic measurements, like left ventricular wall thickness or enddiastolic diameter. Why were these
parameters not included in the calculation of the Cox model? It cannot be excluded that conventional 2-D and M-mode echocardiographic parameters are predictors for prognosis of equal emphasis as TDI parameters.
According to which protocol were the follow-up investigations performed?
How to explain the discrepancy of patient recruitment starting in January 1999 and the maximal follow-up duration of 132 months? How many thromboembolic events occurred during follow-up?
How to explain the threefold increased mortality in the presented cohort compared to the 5.3% mortality/year as observed in adults?[2]
In the two patients with dysmorphic features, which genetic syndrome was diagnosed? Did these two patients also present with skeletal muscle abnormalities? At least in adults, LVHT is frequently associated with neuromuscular disorders. How many of the included 56 patients were seen by a neurologist, and in how many was a neurological disorder detected?
Interestingly, in 4 patients LVHT affected the interventricular septum.
Septal LVHT is extremely rare, thus it would be of interest to have more information about these patients.
If the authors assume that TDI is influenced by LVHT, why did they choose movement of the basal parts of the ventricle for registration, where no LVHT is located, and not the midventricular or apical parts of the left
ventricle, where LVHT is usually located? Which explanation do the authors have for their observation of decreased velocities as assessed by TDI in LVHT? Did the velocities change in patients with undulating phenotype in
accordance with improvements in left ventricular systolic function?
In conclusion, before assessing TDI parameters as useful parameters to predict outcome of patients with LVHT, information about other echocardiographic findings and extracardiac comorbidities is necessary.
References
1. McMahon CJ, Pignatelli RH, Nagueh SF, Lee VV, Vaughn W, Valdes SO, Kovalchin JP, Jefferies JL, Dreyer WJ, Denfield SW, Clunie S, Towbin JA, Eidem BW Left ventricular noncompaction cardiomyopathy in children: Characterization of clinical status using tissue Doppler-derived indices of left ventricular diastolic relaxation Heart 2006 Nov 29;ePub
2. Stöllberger C, Winkler-Dworak M, Blazek G, Finsterer J Prognosis of left ventricular hypertrabeculation/noncompaction is dependent on cardiac
and neuromuscular comorbidity Int J Cardiol 2006; in press
3. Stöllberger C, Keller H, Finsterer J Disappearance of left ventricular hypertrabeculation/noncompaction after biventricular pacing in a patient with myopathy J Card Fail 2006; in press
4. Finsterer J, Stöllberger C Definite, probable , and possible left ventricular hypertrabeculation/noncompcation Int J Cardiol 2006; in press
5. Kjaergaard J, Korinek J, Belohlavek M, Oh JK, Sogaards Hassager C Accuracy, reproducibility, and comparability of Doppler tissue imaging by two high-end ultrasound systems J Am Soc Echocardiogr 2006;19:322-8
Old medical theories, like myths, never die. In every era, long after
the initial excitement evaporates, scientific theories that have not
gathered logical strength through increasing clinical associations are
recycled to address current perceptions. Such theories, like myths, offer
a vicarious resolution of the ignorances that lies between our
insecurities and our expectations.[1,2] Wilmshurst et al....
Old medical theories, like myths, never die. In every era, long after
the initial excitement evaporates, scientific theories that have not
gathered logical strength through increasing clinical associations are
recycled to address current perceptions. Such theories, like myths, offer
a vicarious resolution of the ignorances that lies between our
insecurities and our expectations.[1,2] Wilmshurst et al. recently suggest
once again that platelets may have a role in the pathogenesis of
migraine.[3] They base this impression on the seeming efficacy of the
combination of clopidogrel and aspirin in comparison to aspirin alone in
managing attacks of migraine with aura in patients who had undergone
closure of persistent foramen ovale or atrial septal defect; this salutary
effect of combined anti-platelet regimen is believed to work through an
effect on serotonin stores.
Migraine theory and therapy is a long chain of tenuously linked
assumptions coupled to serendipity of a high order.[4] Several lines of
evidence challenge the presumed pathogenetic link between platelets,
serotonin, and migraine as well as the conclusions of the authors: (i)
Platelet hyperaggregability has been noted in a range of other medical
conditions unrelated to migraine and is found with high levels of stress.
Stress affects the vast majority of the general population but migraine
afflicts only about one-fifth of humankind. (ii) Propranolol, the gold
standard migraine prophylactic agent, enhances platelet aggregability [5].
(iii) Contrary to the general impression, evidence for migraine
prophylactic value of aspirin is poor.[6] (iv) A negative correlation
exists between migraine and antibodies to phospholipids (the membrane-
binding moiety increasing platelet aggregability), suggesting a degree of
protection against development of migraine.[7] (v) Migraine headache has
been reported in patients with thrombocytopenia.[8] (vi) Although
platelet aggregation and adhesion are commonly increased in diabetes
mellitus, it is hypogylcaemia rather than hyperglycaemia that precipitates
migraine.[9] (viii) Menstrual migraine typically improves with pregnancy[10] but estrogens increase epinephrine induced platelet aggregation.[11]
(ix) Migraine-like headache is a sequela of cocaine use, [12,13]. but
cocaine inhibits platelet aggregation and dissociates preformed platelet
aggregates [14]. (x) Amitriptyline, a first-line migraine prophylactic
agent, unambiguously stimulates brain noradrenergic as well as
serotonergic function.[15] (xi) Development of carcinoid tumour remarkably
decreased migraine frequency and intensity leading to a complete remission
with postoperative recurrence.[16] (xii) Nicotine increases platelet
aggregation [17] but is considered relatively unlikely to lead to
migraine.[18] (xiii) Nitric oxide (and endothelium-derived relaxing
factor) putatively involved in vascular headaches associated with exercise
or infection inhibits platelet aggregation and adhesion.[8,19]
Proponents of the platelet theory of migraine postulate a parallel
between the platelet and the neuron by suggesting that platelet activation
mirrors trigeminovascular system inflammation. Believing that (peripheral)
platelet function tells us anything about brain neuronal function involves
complete suspension of scientific disbelief.[15] No systemic influence,
including platelet dysfunction, can rationalize the characteristic
lateralization (unilateral, bilateral or side-shift) of migraine
headache.[21] For internists, cardiologists, and neurologists (especially
researchers into primary headaches) familiar with the useful effect of
inhibition of platelet aggregation in cardiovascular and cerebrovascular
medicine, it is indeed difficult to concede that a similar benefit might
not be available to migraine patients. Nevertheless, if migraine has to
progress from a vaguely-understood syndrome to a properly defined disease,
theories that clutter our thinking need to be addressed squarely and
discarded. The platelet theory of migraine is one such concept that might
best be passed into history.
Wilmshurst et al.[3] have also reported increased frequency and
severity of migraine with aura attacks immediately following closure of
atrial shunts, a phenomenon that has important pathophysiological
implications. Yankowsky and Kuritzky have earlier reported on aggravation
of migraine with aura into a daily pattern with clocklike precision after
closure of an atrial septal defect (ASD).[21] Importantly, there is no
suggestion of a causal link between ASD and migraine but closure of ASD
appears to be associated with appearance or worsening of migraine with
aura.[3,21] In uncomplicated ASD, correction of the septal defect would
lead to decrease in the elevated right atrial pressure and plasma atrial
natriuretic peptide levels would decrease correspondingly.[22] ANP appears
to play a role as a counterregulatory hormone in many disorders
characterized by volume expansion, including hypertension; also,
orthostatic hypotension, a characteristic feature of migraine, is
associated with lower levels of ANP, and suggests that noradrenergic
hypofunction may be involved in the pathogenesis of migraine.[23,24] A
compensatory or adaptive function has been attributed to sympathetic
hypofunction associated adrenergic receptor hypersensitivity.[25] The fact
that migraine prophylactic agents such as beta-blockers or calcium
antagonists or clonidine invariably lower elevated blood pressures or tend
to maintain normotension – while only rarely causing symptomatic
hypotension – indicates that a low blood pressure is an adaptive feature
in migraine. Nausea and vomiting is another facet of a complex vasopressin
-mediated adaptive mechanism in migraine.[26,27]
Dramatic aggravation of migraine following atrial shunt closures indicates
substantial alteration of some physiological variable with prominent
circadian variation and a critical influence on the primary
pathophysiological process in migraine.[22] In ASD, the reduced filling
pressure of the left ventricle causes a smaller than normal stroke volume
and reduced cardiac output; consequently a relatively small aorta is
commonly seen. Following closure of large atrial shunts, immediate
improvement in left ventricular stroke volume and cardiac output occurs.
Precipitation of migraine following closure of atrial septal defect [3,21]
suggests that a higher stoke volume / cardiac output might worsen or
unmask a migrainous diathesis.[22,28]
The theoretical basis for a non-neuronal non-vascular origin of
migraine has been recently elucidated.[29] A selective involvement of the
ophthalmic division of the trigeminal nerve is likely in migraine and
other primary headaches; mechanical deformation of the corneo-scleral
envelope by ocular choroidal venous congestion and rise of intraocular
pressure (IOP) has been proposed to underlie both the scintillating
scotoma as well as the headache of migraine.[29,30] In contrast to the
brain, the eye is a low-volume but far more highly vascularized organ; the
eye is anatomically less capable of accommodating any sudden increase in
stroke volume. The cardiac output increasing effect of closure of larger
atrial shunts is somewhat comparable to the immediate peripheral arterial
perfusion enhancing effect of glyceryl trinitrate (GTN) manifest by
flushing of face and throbbing headache.[31] GTN is the best available
experimental human model for migraine; it generally causes migraine
headache a few hours after consumption,[32] at which time substantial
venous pooling likely develops at the ocular choroidal venous plexus in
migraine patients due to an intrinsic regional ocular sympathetic
hypofunction. Propranolol, atenolol, metoprolol, nadolol, clonidine,
flunarizine, and verapamil lower the IOP, further supporting the nexus
between migraine, autonomic dysfunction, and intraocular pressure.[29]
Immediate aggravation of migraine attacks after closure of atrial shunts
spontaneously regresses after a few months;[21] ocular tissue creep at the
level of the corneo-scleral envelope likely dissipates the headache-
provoking effect of increased cardiac output in patients with ASD.[29]
Like trait or basal autonomic function, endogenous pain control
mechanism, and corneo-scleral distensibility, increase in cardiac output
after atrial shunt closure is likely to be a highly variable,
idiosyncratic function; these important confounding features might well
explain the results of the studies of Wilmshurst et al.[3]
References
1. Gupta VK. Migrainous stroke: are antiphospholipid antibodies
pathogenetic, a biological epiphenomenon, or an incidental laboratory
aberration? Eur Neurol 1996;36:110-111.
2. Lévi-Strauss C. Then structural study of myth; in Lévi-Strauss C
(ed): Structural Anthropology. Harmondsworth, Peregrine, 1977, pp 206-231.
3. Wilmshurst PT, Nightingale S, Walsh KP, W L Morrison WL.
Clopidogrel reduces migraine with aura after transcatheter closure of
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We injoyed very much the most interesting study by Teo et al (1). Acute coronary syndromes(ACS) and coronary risk factors; hypertension, hyperlipidemia,obesity and type 2 diabetes have become a major health problem in Asia with economic development,due to interaction of gene and
environmental factors.(2) Overswinging,that is an excessive circadian variation in blood pressure (BP) has been associated with...
We injoyed very much the most interesting study by Teo et al (1). Acute coronary syndromes(ACS) and coronary risk factors; hypertension, hyperlipidemia,obesity and type 2 diabetes have become a major health problem in Asia with economic development,due to interaction of gene and
environmental factors.(2) Overswinging,that is an excessive circadian variation in blood pressure (BP) has been associated with a large increase in cardiovascular risk,present even in absence of hypertension and
prehypertension itself.The prevalence of obesity varies between 5-7%, in the Asian urban population.The paradox is that despite low rates of obesity, the prevalence of central obesity (40-60%),prediabetes(10-15%),overswinging of BP(10-15%),type 2 diabetes(6-15%),and ACS(9-14%) are
higher, in urban areas, which are much higher among Asian immigrants to developed countries(2).The prevalence of metabolic syndrome is 5% in rural and 15%in urban south India whereas in north and western India,the prevalences appear to be slightly lower. In a cross-sectional survey, in five Indian cities,among 6940 subjects aged 25years and above, the prevalence of obesity was approximately 7% but more than half of the subjects had central obesity and one third had prehypertension,one quarter hypertension and one fifth prediabetes.About three quarters of hypertensives had central obesity in both sexes. In a subsample,(n=1633), the prevalence of metabolic syndrome comprising of central obesity, hypertension and hypertriglyceridemia and low HDL was approximately 13% and premetabolic syndrome comprising of prehypertension, prediabetes and
central obesity in 19.5%. The emerging typical South Asian, urban or immigrant has phenotype of higher percentage of body fat at a lower value of BMI,high WHR at a relatively low waist circumference and less lean body
mass compared to other ethnic groups. A similar genotype is present among Chinese and other Asians.However,in case control studies,the mean age in south Asia varies between 48 to 51 years,which is againt the finding of 61 years mean age among Asians,(3) in the study by Teo and co-workers(1,3).
In one study among 54 patients with acute coronary syndromes(ACS), 41 patients had acute myocardial infarction(AMI),5 possible MI, 4 cases unstable angina and rest 4 angina pectoris.The control subjects(n=85) were randomly selected from the population from the city of Moradabad, drawn from a similar age and sex of the subjects.Serum level of nitrite(a indicator of nitric oxide,NO) was significantly lower in patients with AMI compared to controls(mean+SD:0.36+1.42 vs 0.96+1.48uM,CI difference
0.60,0.34-1.02,P<0.03).After 4 weeks of follow up,serum nitrite level recovered showing significant increase without such changes in the control group.(0.88 vs 1.09uM;CI 0.21,0.67-1.12,P<0.05) The incidence of
lipoprotein(a) excess(>30mg/dl) and mean levels of
lipoprotein(a)(difference 6.4mg/dl,95% confidence interval 2.8-10.5,P<0.05) was significantly greater in the acute CAD group compared to control subjects.Serum levels of vitamins E,C and beta-carotine,coenzyme Q10,magnesium and potassium were significantly lower and insulin, glucose, triglycerides, and lipoprotein(a) were significantly higher
in ACS compared to their levels after 4 weeks of follow up.There was a significantly greater occurrence of acute ACS events in the second quarter of the day compared to other quarters.A circadian rhythm was also noted
for serum level of NO showing significantly lower nitrite in 6.00-12.00 AM period compared to afternoon,12.00-18.00hours period(0.27+1.12 vs 0.42+1.44 uM,P<0.04).
The differences in the nitrite levels in the two groups indicate that low levels of nitrite appears to be a risk factor of ACS.Lower levels of nitrite during acute stage of AMI and its recovery after 4 weeks of follow up indicate that transient hyperglycemia and hyperinsulinemia may also be responsible for its increase, (apart from low arginine intake and sedentary behaviour,) by inhibiting the expression of NO receptors caused by metabolic reactions evoked by ACS. Reduction in antioxidants vitamins may be due to increased oxidative stress which is common in AMI due to enhanced free radical generation which may also influence NO levels and cause endothelial dysfunction.More studies would be necessary to
demonstrate that NO deficiency is a risk factor of ACS.There is a need to compare association of protective factors; physical activity, fruit and begetable intake,n-6/n-3 ratio in the diet, moderate alcohol intakes and
stress to find out their roles in the pathogenesis of ACS among Asians and Caucasians(1-5).
In rural population of India and China,there is low plasma insulin, low glucose, triglycerides and angiotensin. There is low prevalence of central obesity and obesity is uncommon in rural areas of Asia.When these
populations migrate to urban slums or to industrialized countries, they substitute cereal based diet from ready prepared fast foods containing more linoleic acid, saturated fat, trans fatty acids, sugar, and flesh
foods and dairy products in conjunction with sedentary behaviour and increased mental stress.It seems that rapid changes in diet and lifestyle due to modest but unsustainable, economic development, without learning of
methods of prevention, result into maladaptations, that are important in the pathogenesis of acute coronary syndromes among Asians.
icn2008@mickyonline.com
REFERENCES
1.Teo M, Lalondrel S, Roughton M, Mason RG, Dubrey SW Acute coronary syndromes and their presentation in Asian and Caucasian patients in Britain Heart 2007, 93: 183-188
2.Singh RB, Suh IL, Singh VP et al. Hypertension and stroke in Asia;prevalence, control, and strategies in developing countries for prevention J Human Hyper 2000 ,14:740-763
3.Singh RB,Rastogi SS, Verma R et al. An Indian experiment with nutritional modulation in acute myocardial infarction Am J Cardiol 1992, 69: 879-885
4.Singh RB, Pella D, De Meester F What to eat and chew in acute myocardial infarction Eur Heart J 2006,27: 1628-29
5.Janus ED, Postiglion E, Singh RB, Lewis B. Coronary heart disease in Asia Circulation 1996,94: 2671-73
Dear Editor,
The data presented in Welsh et al.'s paper assessing variations in practice across the 12 countries in the ASSENT 3 PLUS trial may not be representative of UK practice since each of the four constituent countries of the UK have distinct health systems.
In England and Wales, both of which have national standards for the care of STEMI patients -National Service Frameworks- and in which all 130...
Dear Editor,
The Committee for the Safety of Medicines has only two entries for amiodarone extravasation injury, yet almost every consultant seems to remember a patient who has had their arm amputated following extravasation of amiodarone. Surely this is a case of the dangers of peripheral amiodarone being exagerated? In periarrest / cardiac arrest situations amiodarone has been given as a peripheral bolus countl...
Dear Editor,
We have read the article[1] with great interest. Selection of the 23 patients is not clearly mentioned here. There is a lack of some other information too. Once the chest pain started, after what time those patients were selected for angioplasty? What was the percentage of lumen narrowing or stenosis? Was the stenosis complicated or not? What was the material used for primary angioplasty?
Rap...
Dear Editor,
Dr. Huffman and colleagues [1] studied 131 post-myocardial infarction (MI) patients (17 with major depressive disorder [MDD]) and reported that two items from the Beck Depression Inventory (BDI) related to sadness and loss of interest formed an effective screening tool for post-MI depression. The sensitivity and specificity results reported by Huffman et al. are, in fact, highly similar to those repo...
Dear Editor,
Intra-country variation versus inter-country variation in pre-hospital care management of acute MI with ST elevation is worrisome matter. Thanks to R C Welsh et al. for wring the article. ST elevation acute MI needs early treatment with fibrinolysis therapy as early possible.
Study[1] shows that time management is the key of ST elevation MI. Rapid time to treatment with thrombolytic therapy...
Dear Editor,
At the out-set, I want to congratulate the authors of the article "The patho-physiology of myocardial reperfusion: a pathologist's perspective" (1)for an outstanding job in summarizing a complex topic in a simplified way.
However, it was presented as if “reperfusion” is the culprit ("Reperfusion Injury”), even though, an attempt is made to clarify that the injury after reperfusion is happenin...
Dear Editor,
Mulcahy's article is an interesting update on the subject of silent myocardial ischemia.[1] He postulates that ambulatory ST segment monitoring does not add significantly to the finding of exercise testing, because it would occur almost exclusively in patients with a positive result in the ischemia exercise test.
In a German multicentre study, we have analyzed both exercise test and ambulat...
Dear Editor,
With interest we read the article by McMahon et al. about the application of tissue Doppler imaging (TDI) in assessing the prognosis of children with left ventricular hypertrabeculation/noncompaction (LVHT).[1]
We have, however, several questions and concerns:
There are only limited experiences in the follow-up of patients with LVHT and the prognosis is largely unknown.[2] The “undul...
Dear Editor,
Old medical theories, like myths, never die. In every era, long after the initial excitement evaporates, scientific theories that have not gathered logical strength through increasing clinical associations are recycled to address current perceptions. Such theories, like myths, offer a vicarious resolution of the ignorances that lies between our insecurities and our expectations.[1,2] Wilmshurst et al....
Dear Editor,
We injoyed very much the most interesting study by Teo et al (1). Acute coronary syndromes(ACS) and coronary risk factors; hypertension, hyperlipidemia,obesity and type 2 diabetes have become a major health problem in Asia with economic development,due to interaction of gene and environmental factors.(2) Overswinging,that is an excessive circadian variation in blood pressure (BP) has been associated with...
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