The clinical presentation which simulates ST-segment elevation myocardial infarction(STEMI)(1) is one of the most deceptive manifestations of dissecting aortic aneurysm(DAA), deserving detailed analysis notwithstanding its infrequent(2)(3)(4) occurrence. In Zhu et al DAA was prevalent in only 0.5% of 1576 subjects with suspected STEMI(2). Conversely, Kosuge et al documented a 4%(9 patients) prevalence of ST segment elevation among 233 subjects with confirmed DAA(3). In Hirata et al ST segment elevation was prevalent in 8.2% of 159 subjects with type A aortic dissection(4). When ST segment elevation occurs as a manifestation of DAA, there is a high prevalence of involvement of the inferior leads, exemplified by 6 of the 9 patients in Kosuge et al(3)., and seven of the 13 cases in Hirata et al(4)., arguably because type A aortic dissection is more likely to compromise the ostium of the right coronary artery than the ostium of the left coronary artery(5). In view of the life-threatening nature of DAA clinicians should not rely only on clinical decision rules to raise the index of suspicion. The rationale for a more open-minded approach is that clinical decision rules such as the AAD risk score tend to emphasise typical symptoms, such as the "tearing" character of the back pain(1), almost to the total exclusion of less typical symptoms such as nonspecific back pain, the latter typically radiating from a retrosternal chest pain. For example, a literat...
The clinical presentation which simulates ST-segment elevation myocardial infarction(STEMI)(1) is one of the most deceptive manifestations of dissecting aortic aneurysm(DAA), deserving detailed analysis notwithstanding its infrequent(2)(3)(4) occurrence. In Zhu et al DAA was prevalent in only 0.5% of 1576 subjects with suspected STEMI(2). Conversely, Kosuge et al documented a 4%(9 patients) prevalence of ST segment elevation among 233 subjects with confirmed DAA(3). In Hirata et al ST segment elevation was prevalent in 8.2% of 159 subjects with type A aortic dissection(4). When ST segment elevation occurs as a manifestation of DAA, there is a high prevalence of involvement of the inferior leads, exemplified by 6 of the 9 patients in Kosuge et al(3)., and seven of the 13 cases in Hirata et al(4)., arguably because type A aortic dissection is more likely to compromise the ostium of the right coronary artery than the ostium of the left coronary artery(5). In view of the life-threatening nature of DAA clinicians should not rely only on clinical decision rules to raise the index of suspicion. The rationale for a more open-minded approach is that clinical decision rules such as the AAD risk score tend to emphasise typical symptoms, such as the "tearing" character of the back pain(1), almost to the total exclusion of less typical symptoms such as nonspecific back pain, the latter typically radiating from a retrosternal chest pain. For example, a literature search of STEMI-like DAA over the period 2000-February 2020 disclosed 4 patients(5)(6)(7)(8) in whom ST segment elevation in the inferior leads was associated with a clinical presentation which included back pain(with concurrent chest pain), and a clinically detectable murmur of aortic regurgitation, all three stigmata, namely, inferior lead ST segment elevation, back pain, and an aortic regurgitant murmur, deserving to be recognised as "red flags" for DAA in a patient with a clinical presentation which includes electrocardiographic ST segment elevation. None of these 4 patients described the back pain as being "tearing" in character. On the basis of that omission the clinicians who managed those patients initially attributed both the associated chest pain and the ST segment elevation solely to acute myocardial infarction(AMI)(5)(6)(7)(8).
The occurrence of focal neurological signs in a patient with ST segment elevation should also be recognised as a "red flag" for DAA. Over the period 2000-2020 a literature search of STEMI-like DAA disclosed 5 patients in whom inferior ST segment elevation occurred in conjunction with focal neurological symptoms comprising hemiparesis(9), right upper limb pain(10), left arm numbness(11), flaccid paraparesis(12), and paraparesis(13), respectively. One of these patients had nonspecific back pain as well(13).
In conclusion, the occurrence of ST segment elevation in one or more of the inferior leads II,III,AVF(with or without concurrent ST segment elevation in other leads) should raise the index of suspicion for DAA(3)(4), especially when such an occurrence is associated with back pain of any description, and/or clinically detectable aortic regurgitation.
I have no funding and no conflict of interest.
(1) Salmasi MY., Al Saadi N., Hartley P et al
The risk of misdiagnosis in acute thoracic aortic dissection: a review of current guidelines
Heart 2020 doi:10.1136/heartjnl-2019-316322
(2) Zhu Q-y., Tai S., Tang L et al
STEMI could be the primary presentation of acute aortic dissection
Amer J Emerg Med 2017;35:1713-1717
(3) Kosuge M., Uchida K., Imoto K et al
Frequency and implications of ST-T abnormalities on hospital admission electrocardiograms in patients with typeA aortic dissection
Am J Cardiol 2013;112L424-429
(4) Hirata K., Wake M., Kyushima M., Takahashi T et al
Electrocardiographic changes in patients with tyoe A acute aortic dissection. Incidence, patterns and underlying mechniasms in 159 cases
Journal of Cardiology 2010;56:147-153
(5)Palmiera M., Ribeiro HYU., Lira YC et al
Aortic aneurysm with complete atrioventricular block and acute coronary syndrome
BMC Research Notes 2016;9:257
(6) Hawatmeh A., Arqoub AA., Isbitan A., Shamoon F
A case of ascending aortic dissection mimicking acute myocardial infarction and complicated with pericardial tamponade
Cardiovasc Diagn Ther 2016;6:166-171
(7) Tsigkas G., Kasimis G., Theodoropoulos K et al
A successfully thrombolysed acute inferior myocardial infarction due to type A aortic dissection with lethal consequence: the importance of early cardiac echocardiography
Journal of Cardiothoracic surgery 2011;6:101
(8)Fernandez-Jimenez R., Vivas D., de Agustin HA et al
Acute aortic dissection with ongoing right coronary artery and aortic valave involvement
Int J Cardiol 2012;161:e34-e36
(9) Cook J., Aeschlimann S., Fuh A., Kohmoto T., Chang SM
Aortic dissection presenting as concomitant stroke and STEMI
J Human Hypertens 2007;21:818-821
(10) Doksoz A., Ozturk MT., Salha W., Taraktas M., Soydemir H
A case of aortic dissection complicating right subclavian artery occlussion and mimicking inferior myocardial, infarction
Emerg Case Rep 2011;8:40-42
(11) Al-Saad AA., Odunukan OW., Patton JN
Ascending aortic dissection presented as inferior myocardial infarction: a clinical and diagnostic mimicry
BMJ Case Rep 2016;doi:1136/bcr-2016-217543
(12) Tarver K., Kindier H., Lythall D
Extensive aortic dissection presenting as acute inferior myocardial infarction
Heart 2016;doi:10.1136/hrtjnl 2006.097444
(13) Abrams E., Allen A., Lahham S
Aortic dissection with subsequent hemorrhagic tamponade diagnosed with point of care ultrasound in a patient presenting with STEMI
Clin Pract Vases Emerg Med 2019;3:103-105
Release of troponin after exercise stress test in hypertrophic cardiomyopathy
Pawel Petkow Dimitrow1, Renata Rajtar-Salwa2, Tomasz Tokarek2
1 2nd Department of Cardiology, Jagiellonian University Medical College, Kraków, Poland
2 Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland
Correspondence to: Paweł Petkow Dimitrow, 2nd Department of Cardiology, Jagiellonian University Medical College, Jakubowskiego 2 Str., 30-688 Krakow, Poland, e-mail: dimitrow@mp.pl, tel. 0048 12 400 22 50
Recently Cramer et al. demonstrated very important observation on troponin level increase after exercise in patients with hypertrophic cardiomyopathy (HCM) [1]. Several concerns regarding to methodology of their study should be explained. Authors decided to perform only one measurement of troponin level at 6 hours after end of exercise. In our opinion, sampling after 6, 12, 18 and 24 hours after exercise provide more adequate profile of troponin level and allow to monitor possible post-exercise ischemia. Furthermore, data on prevalence of silent myocardial ischemia (only troponin increase) should be provided. In our study [2] painless ischemia detected by troponin measurement after normal daily physical activity was present in 25% of HCM patients. In another study [3], among HCM patients monitored by HOLTER ECG during normal daily physical activity, maximum heart rate was higher in th...
Release of troponin after exercise stress test in hypertrophic cardiomyopathy
Pawel Petkow Dimitrow1, Renata Rajtar-Salwa2, Tomasz Tokarek2
1 2nd Department of Cardiology, Jagiellonian University Medical College, Kraków, Poland
2 Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland
Correspondence to: Paweł Petkow Dimitrow, 2nd Department of Cardiology, Jagiellonian University Medical College, Jakubowskiego 2 Str., 30-688 Krakow, Poland, e-mail: dimitrow@mp.pl, tel. 0048 12 400 22 50
Recently Cramer et al. demonstrated very important observation on troponin level increase after exercise in patients with hypertrophic cardiomyopathy (HCM) [1]. Several concerns regarding to methodology of their study should be explained. Authors decided to perform only one measurement of troponin level at 6 hours after end of exercise. In our opinion, sampling after 6, 12, 18 and 24 hours after exercise provide more adequate profile of troponin level and allow to monitor possible post-exercise ischemia. Furthermore, data on prevalence of silent myocardial ischemia (only troponin increase) should be provided. In our study [2] painless ischemia detected by troponin measurement after normal daily physical activity was present in 25% of HCM patients. In another study [3], among HCM patients monitored by HOLTER ECG during normal daily physical activity, maximum heart rate was higher in the troponin positive as compared to troponin negative group (139±9 vs. 125±8 [bpm], p<0.05). Similar association was observed in current exercise study [1]. However, peak exercise left ventricular outflow tract gradient (LVOTG ) was not evaluated [1] despite previously reported association with elevated troponin level [4].
To provide more individualised and comprehensive recommendations with regard to exercise intensity in HCM some additional study should be performed with improved methodology including described above criteria.
References:
1. Cramer GE, Gommans DHF, Dieker H, et al. Exercise and myocardial injury in hypertrophic cardiomyopathy. Heart Published Online First: 30 January 2020. doi: 10.1136/heartjnl-2019-315818
2. Gębka A, Rajtar-Salwa R, Dziewierz A, Dimitrow P. Painful and painless myocardial ischemia detected by elevated level of high-sensitive troponin in patients with hypertrophic cardiomyopathy. Adv Interv Cardiol. 2018; 14: 195-198.
3. Hładij R, Rajtar-Salwa R, Petkow Dimitrow P. Associaton of elevated troponin levels with increased heart rate and higher frequency of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. Pol Arch Intern Med. 2017; 126: 445-447.
4. Rajtar-Salwa R, Gębka A, Dziewierz A, Dimitrow PP. Hypertrophic Cardiomyopathy: The Time-Synchronized Relationship between Ischemia and Left Ventricular Dysfunction Assessed by Highly Sensitive Troponin I and NT-proBNP. Dis Markers. 2019: 6487152.
ACUTE OR PRE-EXISTING CORONARY SLOW FLOW IN TAKOTSUBO CARDIOMYOPATHY: DOES IT MATTER ?
Kenan YALTA, MD a
Tulin YALTA, MD b
Muhammet GURDOGAN, MD a
aTrakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Pathology Department, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 0090505657985
In the setting of takotsubo cardiomyopathy (TTC), coronary microvascular dysfunction has been mostly considered as a causative factor (1,2). In their recently published article (1), Montone RA et al have demonstrated, for the first time, the prognostic value of coronary slow flow (CSF) phenomenon in TTC patients. Of note, as we previously discussed, on a theoretical basis, the particular prognostic value of CSF phenomenon in these patients (3), we feel now pleased to notice that this theory has been fully confirmed by a well-designed study (1). Nevertheless, we would like to make a few comments on this issue:
Firstly; temporal emergence of CSF phenomenon might possibly matter in TTC as well. Accordingly; an acutely evolving CSF pattern (due to severe adrenergic discharge (1)) as compared with a sole pre-existing one (emerging long before the index TTC as part of generalized...
ACUTE OR PRE-EXISTING CORONARY SLOW FLOW IN TAKOTSUBO CARDIOMYOPATHY: DOES IT MATTER ?
Kenan YALTA, MD a
Tulin YALTA, MD b
Muhammet GURDOGAN, MD a
aTrakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Pathology Department, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 0090505657985
In the setting of takotsubo cardiomyopathy (TTC), coronary microvascular dysfunction has been mostly considered as a causative factor (1,2). In their recently published article (1), Montone RA et al have demonstrated, for the first time, the prognostic value of coronary slow flow (CSF) phenomenon in TTC patients. Of note, as we previously discussed, on a theoretical basis, the particular prognostic value of CSF phenomenon in these patients (3), we feel now pleased to notice that this theory has been fully confirmed by a well-designed study (1). Nevertheless, we would like to make a few comments on this issue:
Firstly; temporal emergence of CSF phenomenon might possibly matter in TTC as well. Accordingly; an acutely evolving CSF pattern (due to severe adrenergic discharge (1)) as compared with a sole pre-existing one (emerging long before the index TTC as part of generalized endothelial dysfunction) might have stronger cardiovascular prognostic implications in the acute course of TTC (3). In contrast, a pre-existing CSF pattern might be associated with a poor long-term prognosis largely driven by the underlying systemic condition. In this context, CSF pattern in the settings of malignancy and neurological disease might have possibly risen as a pre-existing phenomenon in the present study (1).
Secondly; it seems quite challenging to identify whether a CSF pattern in TTC patients appears to be an acute or pre-existing phenomenon (or both) based on a single coronary angiogram (CAG) (unless making a comparison with previous CAG data). However, a sole pre-existing CSF pattern might be relatively mild and diffuse in nature as compared with a sole or superimposed acute CSF in these patients. Accordingly, did the extent and severity of CSF patterns significantly differ between those with acute cardiac complications (mostly arising due to an acute CSF) and those with exclusively long-term events on follow-up (mostly due to the systemic condition (1) associated with pre-existing CSF) ? In particular, potential prediction of an acute or exclusively pre-existing CSF pattern based on angiographic features might help establish further clinical strategies to improve prognosis (for instance; close supervision for expected acute complications or further diagnostic tests (1) for an obscure malignancy, etc.).
Lastly; vasodilator strategies in TTC patients with a CSF pattern (particularly with a predominant acute component) might be of significant benefit (4). Moreover, given the potential association of future TTC recurrences with excessive adrenergic discharge during the index event (2), TTC patients likely to have an acute CSF pattern might need well-known radical measures including sympathetic ganglion blockade, etc for TTC prevention. Accordingly, we wonder their acute and long-term management strategies in TTC patients with a CSF pattern (1).
In summary, CSF pattern might be considered as a prognostic rather than a causative factor in TTC patients (1,3). However, further categories of this phenomenon (acute vs pre-existing) along with their specific implications in these patients still remain to be established.
Conflict of Interest: None
REFERENCES:
1- Montone RA, Galiuto L, Meucci MC, et al. Coronary slow flow is associated with a worse clinical outcome in patients with Takotsubo syndrome. Heart. 2020 Jan 10. pii: heartjnl-2019-315909. doi: 10.1136/heartjnl-2019-315909. [Epub ahead of print]
2- Kawaji T, Shiomi H, Morimoto T, et al. Clinical impact of left ventricular outflow tract obstruction in takotsubo cardiomyopathy. Circ J. 2015; 79(4): 839-46.
3- Yalta K, Yilmaztepe M, Ucar F, et al. Coronary slow flow in the setting of Tako-tsubo cardiomyopathy: A causative factor? An innocent bystander? Or a prognostic sign? Int J Cardiol. 2015; 198:229-31.
4- Yalta K, Sivri N, Yalta T. Neuropeptide Y-induced coronary microvascular dysfunction: a significant contributor to the adverse outcomes in stress cardiomyopathy? Int J Cardiol. 2011; 147(2): 284.
I read with interest the super article by Chris Steadman regarding being a clinical director in the NHS. I would add to this article that a particular problem has now become grossly apparent with taking on such a role which is the amount of pension tax that many will find they have to pay in taking such a role on. Previously, leadership and management roles have often attracted a rise in pensionable salary, which was a clear incentive to take them - as per the article, they clearly result in alot of work to the individual and so should be rewarded for this. However with the pension taper which started in 2016 and a low annual allowance, this creates a major problem, with many stories of doctors taking on such roles and receiving a large tax bill as result. How big a bill this may or may not be will depend on the personal circumstances of the individual and the amount of extra pensionable salary the individual trust is offering. For example, under current rules, a £10,000 increase in pensionable pay would result in me doing such a job at a big financial loss in my first year of doing it! Unless the UK government change the pension tax rules, it has created major disincentive for doctors to take on such roles.
APICAL ANEURYSM ? OR TRANSIENT APICAL BALLOONING ? : A POTENTIAL DILEMMA IN RISK-STRATIFICATION OF HYPERTROPHIC CARDIOMYOPATHY
Kenan YALTA, MD a
Muhammet GURDOGAN, MD a
Orkide PALABIYIK, MD b
a,Trakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Department of Biophysics, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 00905056579856
Left ventricular apical aneurysm (LVAA) formation in the setting of hypertrophic cardiomyopathy (HCM) usually appears to be associated with a significant mid-ventricular obstruction, and is potentially associated with adverse cardiovascular events (1). In their recently published article (1), Ramchand J et al have suggested LVAA as a major risk marker in this setting. Though we fully agree with the authors on this point, we would like to draw attention to certain other conditions including transient LV apical ballooning that might strongly mimick LVAA leading to a potential misdiagnosis in patients with HCM:
Takotsubo cardiomyopathy (TTC) presenting with a transient apical ballooning pattern has been recently suggested to have a pure mechanical basis in certain patients with pre-existing structural heart diseas...
APICAL ANEURYSM ? OR TRANSIENT APICAL BALLOONING ? : A POTENTIAL DILEMMA IN RISK-STRATIFICATION OF HYPERTROPHIC CARDIOMYOPATHY
Kenan YALTA, MD a
Muhammet GURDOGAN, MD a
Orkide PALABIYIK, MD b
a,Trakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Department of Biophysics, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 00905056579856
Left ventricular apical aneurysm (LVAA) formation in the setting of hypertrophic cardiomyopathy (HCM) usually appears to be associated with a significant mid-ventricular obstruction, and is potentially associated with adverse cardiovascular events (1). In their recently published article (1), Ramchand J et al have suggested LVAA as a major risk marker in this setting. Though we fully agree with the authors on this point, we would like to draw attention to certain other conditions including transient LV apical ballooning that might strongly mimick LVAA leading to a potential misdiagnosis in patients with HCM:
Takotsubo cardiomyopathy (TTC) presenting with a transient apical ballooning pattern has been recently suggested to have a pure mechanical basis in certain patients with pre-existing structural heart disease including hypertensive heart disease and HCM largely attributable to acute increments in intraventricular pressure gradient leading to substantially elavated apical wall stress in these patients (2,3). Interestingly, TTC in this setting might have no preceding overt stressors (emotional, etc.) (3), and might be clinically silent generally with vague symptoms and signs along with a relatively delayed recovery pattern (hence; might potentially arise as a sole incidental finding on cardiac imaging). Nevertheless, there might still exist certain imaging clues to differentiate between true LVAA and transient apical ballooning in the setting of HCM:
Firstly; pronounced wall thinning is mostly present in true LVAA (excluding cases with severe apical hypertrophy at baseline) as opposed to transient apical ballooning that generally presents with normal or increased wall thickness.
Secondly; LVAA generally emerges due to a chronic and significant mid-ventricular gradient (1) leading to progressive structural remodeling in the apex. However, mid-ventricular gradient is relatively mild in the setting of apical ballooning that might have been induced by an abrupt, yet; transient elevation of this mild gradient to excessive levels leading to stunning in apical segments (2,3) usually without any preconditioning to such pressure elevations.
And lastly; late gadolinium enhancement (LGE) on MRI is an expected finding in LVAA (1) while it is relatively rare (and with a low-intensity pattern) in TTC (4) presenting with an apical ballooning pattern.
In summary; transient apical ballooning should also be taken into consideration in HCM patients suggestive of having a LVAA pattern on initial imaging. Therefore, a single echocardiographic examination might not suffice for decision-making for primary implantable cardiac defibrillator (ICD) therapy suggesting detailed and serial examinations along with MRI for absolute confirmation of an irreversible true LVAA in these patients.
Conflict of interest: None
REFERENCES:
1- Ramchand J, Fava AM, Chetrit M, Desai MY. Advanced imaging for risk stratification of sudden death in hypertrophic cardiomyopathy. Heart. 2020 Jan 16. pii: heartjnl-2019-315176. doi: 10.1136/heartjnl-2019-315176. [Epub ahead of print]
2- Yalta K, Yilmaztepe M, Zorkun C. Left Ventricular Dysfunction in the Setting of Takotsubo Cardiomyopathy: A Review of Clinical Patterns and Practical Implications. Card Fail Rev. 2018; 4(1): 14-20.
3- Azzarelli S, Galassi AR, Amico F, et al. Intraventricular obstruction in a patient with tako-tsubo cardiomyopathy. Int J Cardiol. 2007; 121(2): e22-4.
4- Abbas A, Sonnex E, Pereira RS, Coulden RA. Cardiac magnetic resonance assessment of takotsubo cardiomyopathy. Clin Radiol. 2016; 71(1): e110-9.
As a physician dealing with patients with confirmed or suspected Fabry disease, I've read with great interest this editorial. This is a very thought-provoking article, which introduces the process of reclassification of a prevalent variant in the GLA gene associated with the cardiac variant of Fabry disease. I would like to make only a minor correction regarding the nomenclature of the variant mentioned. As written in the article of Valtola et al, the referred variant is c.427G> A and not c.472G> A¹ (transcript NM_000169.2).
1. Valtola K, Nino-Quintero J, Hedman M, et al. Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene. Heart 2020;:heartjnl-2019-315933. doi:10.1136/heartjnl-2019-315933
In clinical practice, coronary artery aneurysms (CAAs) in the setting of Kawasaki disease (KD) mostly evolve in the earlier stages, and generally reach their maximum size by 6 weeks after disease onset (1). Importantly, they are mostly encountered in untreated cases, and are strongly associated with the disease severity (and in particular; the degree of acute necrotizing vasculitis) (1). In their recently published enlightening report (2), Brogan P have discussed long-term management of KD patients with a particular emphasis on CAAs in this setting (2). However, we would like to comment on a specific phenomenon, namely ‘late CAA’ formation that might emerge even several months to years after the index KD:
Firstly, late CAAs were previously defined as new CAAs emerging at the same location of a previously regressed CAA, and were attributed to hemodynamic and residual pathological abnormalities along the arterial wal...
In clinical practice, coronary artery aneurysms (CAAs) in the setting of Kawasaki disease (KD) mostly evolve in the earlier stages, and generally reach their maximum size by 6 weeks after disease onset (1). Importantly, they are mostly encountered in untreated cases, and are strongly associated with the disease severity (and in particular; the degree of acute necrotizing vasculitis) (1). In their recently published enlightening report (2), Brogan P have discussed long-term management of KD patients with a particular emphasis on CAAs in this setting (2). However, we would like to comment on a specific phenomenon, namely ‘late CAA’ formation that might emerge even several months to years after the index KD:
Firstly, late CAAs were previously defined as new CAAs emerging at the same location of a previously regressed CAA, and were attributed to hemodynamic and residual pathological abnormalities along the arterial wall (3). However, we hold the opinion that these aneurysms mostly arise as a ‘de novo’ phenomenon in apparently normal or mildly affected coronary segments (and hence not associated with severe necrotizing vasculitis at the onset), and might potentially be associated with dysfunctional vascular healing in the long-term (potential under-healing due to prolonged steroid use for KD or other purposes, diabetes, etc).
Secondly, as analogous to progressive aortic remodeling in connective tissue disease, an over-healing process leading to excessive vascular remodeling in the long-term (largely through genetically determined and enhanced actions of certain profibrotic substances including transforming growth factor-beta (TGF-ß) (1), ,etc.and certain enzymes including matrix metalloproteinase-9 (MMP-9)) has been previously reported in KD, and might also serve as an alternative mechanism of late CAA evolution (4-6) particularly in coronary segments with pre-existing mild vasculitis as well.
Thirdly, based on potential favorable impact of captopril on prevention of classical early CAA formation (through inhibition of MMP-9) (5), blockade of renin-angiotensin system might also be indicated indefinitely in the presence of high-risk features (persistently high levels of profibrotic mediators and MMP-9, etc.) for prevention of late CAA evolution.
Lastly, even though late CAA, reportedly appears to have a more favorable prognosis (3) (due to its smaller size and low incidence of intramural thrombus formation, etc as compared with classical CAA), close supervision of long-term changes in coronary morphology (even in the presence of normal or near-normal coronary arteries at 6 weeks) may also be indicated in high-risk patients for timely initiation of further management strategies (anticoagulation, etc.). Interestingly, since late CAAs might be associated with progressive arterial remodeling involving intima and media layers (4,6), they may possibly be more prone to specific complications including spontaneous coronary artery dissection (SCAD) in comparison to classical CAAs with substantial multi-layer necrosis.
In conclusion, late CAA formation in KD might be regarded as an under-recognized phenomenon with important implications, and might constitute a significant portion of idiopathic coronary aneurysms on routine coronary imaging regardless of confirmed KD history. However, further insights of this phenomenon still remain to be established.
Conflict of interest: None
REFERENCES:
1- Newburger JW, Takahashi M, Burns JC. Kawasaki Disease. J Am Coll Cardiol. 2016 ;67(14):1738-49.
2- Brogan P, Burns JC, Cornish J, et al. Lifetime cardiovascular management of patients with previous Kawasaki disease. Heart 2019;0:1–10. doi:10.1136/heartjnl-2019-315925
3- Tsuda E, Kamiya T, Ono Y, et al. Dilated coronary arterial lesions in the late period after Kawasaki disease. Heart. 2005; 91(2): 177-82.
4- Suzuki A, Miyagawa-Tomita S, et al. Remodeling of coronary artery lesions due to Kawasaki disease: comparison of arteriographic and immunohistochemical findings. Jpn Heart J. 2000 ;41(3):245-56.
5- Inoue N, Takai S, Jin D, et al. Effect of angiotensin-converting enzyme inhibitor on matrix metalloproteinase-9 activity in patients with Kawasaki disease. Clin Chim Acta. 2010; 411(3-4): 267-9.
6- Toyono M, Shimada S, Aoki-Okazaki M, et al. Expanding coronary aneurysm in the late phase of Kawasaki disease. Pediatr Int. 2012; 54(1): 155-8.
We thank Dr Althouse for his letter and the interests in our article and for taking time to send us his comments. We appreciate it very much.
In Figure 1, in scenario C, we incorporated the findings of “equivalence” in cases of equivalence trials. We stated in the article under the section of “Equivalence trials versus non-inferiority trials” that, in equivalence trials, the significance level is set as a two-sided p value of 0.05. We agree that, in non-inferiority trials, a one-sided p value of 0.025 is usually set as the significant level, although in some non-inferiority trials in cardiology, a significance level of one-sided p value of 0.05 was used. This is also mentioned under the same section. We have considered using a separate figure in the submission. However, we decided to submit a single figure as the separate figure incorporating only equivalence trials may be too simple and not the focus of the discussion.
In scenario E, the lower limit of the confidence intervals is below 1 and the upper limit of the confidence interval is above the non-inferior margin. Therefore, the null hypothesis that the new treatment is inferior to standard treatment cannot be rejected and the alternative hypothesis that the new treatment is non-inferior to standard treatment cannot be accepted. We agree that the interpretation is more correctly stated as “New treatment not non-inferior to standard treatment”. Alternatively, as Dr Althouse suggested “New treatment...
We thank Dr Althouse for his letter and the interests in our article and for taking time to send us his comments. We appreciate it very much.
In Figure 1, in scenario C, we incorporated the findings of “equivalence” in cases of equivalence trials. We stated in the article under the section of “Equivalence trials versus non-inferiority trials” that, in equivalence trials, the significance level is set as a two-sided p value of 0.05. We agree that, in non-inferiority trials, a one-sided p value of 0.025 is usually set as the significant level, although in some non-inferiority trials in cardiology, a significance level of one-sided p value of 0.05 was used. This is also mentioned under the same section. We have considered using a separate figure in the submission. However, we decided to submit a single figure as the separate figure incorporating only equivalence trials may be too simple and not the focus of the discussion.
In scenario E, the lower limit of the confidence intervals is below 1 and the upper limit of the confidence interval is above the non-inferior margin. Therefore, the null hypothesis that the new treatment is inferior to standard treatment cannot be rejected and the alternative hypothesis that the new treatment is non-inferior to standard treatment cannot be accepted. We agree that the interpretation is more correctly stated as “New treatment not non-inferior to standard treatment”. Alternatively, as Dr Althouse suggested “New treatment is neither inferior nor non-inferior” can be used.
I submit this comment on the recent publication by Leung et al entitled “Non-inferiority trials in cardiology: what clinicians need to know” (1) which I believe has a slight error that merits correction.
On Figure 1 in the original publication, the label says that Result E shows “New treatment inferior” but that is not a correct interpretation. The text in the footnote (“the upper bound of the 95% CI exceeds the predetermined non-inferior margin. Therefore, the new treatment is inferior to standard treatment”) is also incorrect. The data shown in Result E are not sufficient to declare a non-inferiority hypothesis met (the upper limit of the CI for relative risk is above the non-inferiority margin) but nor are they sufficient to declare the new treatment inferior (the lower limit of the CI for relative risk is below the null value). Therefore, the correct label for Result E is “New treatment neither inferior nor non-inferior.” The new treatment would only be declared inferior to the standard treatment in cases F and G (where the lower limit of the 95% CI for relative risk is above the null).
REFERENCE
1. Leung JT, Barnes SL, Lo ST, Leung DY. Non-inferiority trials in cardiology: what clinicians need to know. Heart 2019 [epub ahead of print]
Some of the risk factors for atrial fibrillation(AF) mentioned by the authors, such as hypertension, diabetes, sleep apnoea, older age, and lack of exercise, respectively(1), are also risk factors for myocardial stiffness(2)(3)(4)(5)(6). Myocardial stiffness, in turn, is a risk factor for atrial remodeling in the canine heart(7), and a parameter associated with paroxysmal AF in structurally normal human hearts(8). What is more, exercise has been shown to be capable of reversing myocardial stiffness, both in animals(9), and in human subjects(10).
In the more specific context of left atrial stiffness, obesity has emerged as a risk factor for left atrial stiffness(11)(12). Among patients with obesity, hypertension, and diabetes, respectively, a link has been hypothesised between the twin entities of left ventricular stiffness and depressed atrial compliance, on the one hand, and the development of myocardial fibrosis.(12) . The authors of the latter hypothesis proposed that obesity, hypertension and diabetes generated a systemic proinflammatory state which culminated in the emergence of the coexistence of stiff cardiomyocytes and interstitial fibrosis(12). Furthermore, in a study where the assumption was made that the existence of low voltage areas was a surrogate for left atrial fibrosis, the presence of a left atrial low voltage burden exceeding 10% was shown to be associated with significantly(p < 0.0001) higher left atrial stiffness index((LASI)(13)....
Some of the risk factors for atrial fibrillation(AF) mentioned by the authors, such as hypertension, diabetes, sleep apnoea, older age, and lack of exercise, respectively(1), are also risk factors for myocardial stiffness(2)(3)(4)(5)(6). Myocardial stiffness, in turn, is a risk factor for atrial remodeling in the canine heart(7), and a parameter associated with paroxysmal AF in structurally normal human hearts(8). What is more, exercise has been shown to be capable of reversing myocardial stiffness, both in animals(9), and in human subjects(10).
In the more specific context of left atrial stiffness, obesity has emerged as a risk factor for left atrial stiffness(11)(12). Among patients with obesity, hypertension, and diabetes, respectively, a link has been hypothesised between the twin entities of left ventricular stiffness and depressed atrial compliance, on the one hand, and the development of myocardial fibrosis.(12) . The authors of the latter hypothesis proposed that obesity, hypertension and diabetes generated a systemic proinflammatory state which culminated in the emergence of the coexistence of stiff cardiomyocytes and interstitial fibrosis(12). Furthermore, in a study where the assumption was made that the existence of low voltage areas was a surrogate for left atrial fibrosis, the presence of a left atrial low voltage burden exceeding 10% was shown to be associated with significantly(p < 0.0001) higher left atrial stiffness index((LASI)(13). The relationship between left atrial stiffness and AF is exemplified by the observation that patients with a burden of left atrial low voltage areas(LA-LVA) exceeding 10% had a significantly(p=0.0002) higher prevalence of non-paroxysmal AF than counterparts without LV-LVA(13). Furthermore, meta-analysis has confirmed that left atrial stiffness is a risk factor for recurrence of AF in patients undergoing radiofrequency catheter ablation(14). Arguably in view of these observations(12)(13(14) the hypothesis has emerged that "atrial fibrosis is a disease process that triggers the initiation and maintenance of the syndrome of AF"(15). Accordingly lifestyle modification is mandatory, not only for treatment of atrial fibrillation(1) but also , as far as is practicable, for its prevention.
I have no funding and no conflict of interest
References
(1`) Middeldorp ME., Ariyaratnam J., Lau D., Sanders P
Lifestyle modification for treatment of atrial fibrillation
Heart 2019 doi:10.1136/heartjnl-2019-315327
(2)Cvijic M., Bezy S., Petrescu A et al
Interplay of cardiac remodelling and myocardial stiffness in hypertensive heart disease: a shear wave imaging study using high-frame rate echocardiography
Eur Heart J Cardiovasc Imaging 2019;Epub ahead of print. doi:10.1093/ehjci/jez205
(3)Benech JC., Benech N., Zambrana AI et al
Diabetes increases stiffness of live cardiomyocytes measured by atomic force microscopy nanoindentation
Am J Physiol Cell Physiol 2014;307:C910-C919
(Farre N., Otero J., Falcones B et al
Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix. A multiscale study
Frontiers in Physiology doi:10.3389/phys.2018.01143
(5) Lieber SC., Aubry N., Pain J et al
Aging increases stiffness of cardiac myocytes measured by atomic force microscopy nanoindentation
Am J Physiol Heart Circ Physiol 2004;287:I1645-I1651
(6) Lalande S., Mueller PJ., Chung CS
The link between exercise and Titin passive stiffness
Exp Physiol 2017;102;1055-1066
(7) Zakeri R., Moulay G., Chai Q et al
Left atrial remodeling and atrioventricular coupling in a canine model of early heart failure with preserved ejection fraction
Circ Haert Fail 2016;9:doi:10.1161/CIRCHEARTFAILURE:115;003238
(8)Uetake S., Maruyama M., Yamamoto T et al
Left ventricular stiffness estimated by diastolic wall strain is associated with paroxysmal atrial fibrillation in structurally normal hearts
Clinical Cardiology 2016;39:728-732
(9) Slater RE., Strom JG., Granzier H
Effect of exercise on passive myocardial stiffness in mice with diastolic dysfunction
J Mol Cell Cardiol 2017;108:24-33
(10) Howden EJ., Sarma S., Lawley JS et al
Reversing the cardiac effects of sedentary aging in middle age .A randomized controlled trial
circulation 2018;137:1549-1560
(11) Mahfouz RA., Gomma A., Goda M., safwat M
Relation of left atrial stiffness to insulin resistance in obese children: Doppler strain imaging study
Echocardiography 2018;32:1157-1163
(12) Paulus WJ., Tschope C
A novel paradigm for heart failure with preserved ejection fraction
JACC 2013;62:263-271
(13)Kishima H., Mine T., Fukuhara E., Ashida K., Ishihara M
The association between left atrial stiffness and low-grade areas of left atrium in patients with atrial fibrillation
Heart and Vessels 2019;34;1830-1838
(14) de Oliveira Correia E., dos Santos Barbetta l., da Silva CMP., Mesquita ET
Left atrial stiffness A predictor of atrial fibrillation recurrence after radiofrequency catheter ablation. A systematic review and meta-analysis
Arq Bras Cardiol 2019;112:501-508
(15) gal P., Marrouche NF
Magnetic resonance imaging of atrial fibrosis : redefining atrial fibrillation to a syndrome
Eur Heart J 2017;38;14-19
The clinical presentation which simulates ST-segment elevation myocardial infarction(STEMI)(1) is one of the most deceptive manifestations of dissecting aortic aneurysm(DAA), deserving detailed analysis notwithstanding its infrequent(2)(3)(4) occurrence. In Zhu et al DAA was prevalent in only 0.5% of 1576 subjects with suspected STEMI(2). Conversely, Kosuge et al documented a 4%(9 patients) prevalence of ST segment elevation among 233 subjects with confirmed DAA(3). In Hirata et al ST segment elevation was prevalent in 8.2% of 159 subjects with type A aortic dissection(4). When ST segment elevation occurs as a manifestation of DAA, there is a high prevalence of involvement of the inferior leads, exemplified by 6 of the 9 patients in Kosuge et al(3)., and seven of the 13 cases in Hirata et al(4)., arguably because type A aortic dissection is more likely to compromise the ostium of the right coronary artery than the ostium of the left coronary artery(5). In view of the life-threatening nature of DAA clinicians should not rely only on clinical decision rules to raise the index of suspicion. The rationale for a more open-minded approach is that clinical decision rules such as the AAD risk score tend to emphasise typical symptoms, such as the "tearing" character of the back pain(1), almost to the total exclusion of less typical symptoms such as nonspecific back pain, the latter typically radiating from a retrosternal chest pain. For example, a literat...
Show MoreRelease of troponin after exercise stress test in hypertrophic cardiomyopathy
Pawel Petkow Dimitrow1, Renata Rajtar-Salwa2, Tomasz Tokarek2
1 2nd Department of Cardiology, Jagiellonian University Medical College, Kraków, Poland
2 Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland
Correspondence to: Paweł Petkow Dimitrow, 2nd Department of Cardiology, Jagiellonian University Medical College, Jakubowskiego 2 Str., 30-688 Krakow, Poland, e-mail: dimitrow@mp.pl, tel. 0048 12 400 22 50
Recently Cramer et al. demonstrated very important observation on troponin level increase after exercise in patients with hypertrophic cardiomyopathy (HCM) [1]. Several concerns regarding to methodology of their study should be explained. Authors decided to perform only one measurement of troponin level at 6 hours after end of exercise. In our opinion, sampling after 6, 12, 18 and 24 hours after exercise provide more adequate profile of troponin level and allow to monitor possible post-exercise ischemia. Furthermore, data on prevalence of silent myocardial ischemia (only troponin increase) should be provided. In our study [2] painless ischemia detected by troponin measurement after normal daily physical activity was present in 25% of HCM patients. In another study [3], among HCM patients monitored by HOLTER ECG during normal daily physical activity, maximum heart rate was higher in th...
Show MoreACUTE OR PRE-EXISTING CORONARY SLOW FLOW IN TAKOTSUBO CARDIOMYOPATHY: DOES IT MATTER ?
Kenan YALTA, MD a
Tulin YALTA, MD b
Muhammet GURDOGAN, MD a
aTrakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Pathology Department, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 0090505657985
In the setting of takotsubo cardiomyopathy (TTC), coronary microvascular dysfunction has been mostly considered as a causative factor (1,2). In their recently published article (1), Montone RA et al have demonstrated, for the first time, the prognostic value of coronary slow flow (CSF) phenomenon in TTC patients. Of note, as we previously discussed, on a theoretical basis, the particular prognostic value of CSF phenomenon in these patients (3), we feel now pleased to notice that this theory has been fully confirmed by a well-designed study (1). Nevertheless, we would like to make a few comments on this issue:
Show MoreFirstly; temporal emergence of CSF phenomenon might possibly matter in TTC as well. Accordingly; an acutely evolving CSF pattern (due to severe adrenergic discharge (1)) as compared with a sole pre-existing one (emerging long before the index TTC as part of generalized...
I read with interest the super article by Chris Steadman regarding being a clinical director in the NHS. I would add to this article that a particular problem has now become grossly apparent with taking on such a role which is the amount of pension tax that many will find they have to pay in taking such a role on. Previously, leadership and management roles have often attracted a rise in pensionable salary, which was a clear incentive to take them - as per the article, they clearly result in alot of work to the individual and so should be rewarded for this. However with the pension taper which started in 2016 and a low annual allowance, this creates a major problem, with many stories of doctors taking on such roles and receiving a large tax bill as result. How big a bill this may or may not be will depend on the personal circumstances of the individual and the amount of extra pensionable salary the individual trust is offering. For example, under current rules, a £10,000 increase in pensionable pay would result in me doing such a job at a big financial loss in my first year of doing it! Unless the UK government change the pension tax rules, it has created major disincentive for doctors to take on such roles.
APICAL ANEURYSM ? OR TRANSIENT APICAL BALLOONING ? : A POTENTIAL DILEMMA IN RISK-STRATIFICATION OF HYPERTROPHIC CARDIOMYOPATHY
Kenan YALTA, MD a
Muhammet GURDOGAN, MD a
Orkide PALABIYIK, MD b
a,Trakya University, Cardiology Department, Edirne, TURKEY
b Trakya University, Department of Biophysics, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 00905056579856
Left ventricular apical aneurysm (LVAA) formation in the setting of hypertrophic cardiomyopathy (HCM) usually appears to be associated with a significant mid-ventricular obstruction, and is potentially associated with adverse cardiovascular events (1). In their recently published article (1), Ramchand J et al have suggested LVAA as a major risk marker in this setting. Though we fully agree with the authors on this point, we would like to draw attention to certain other conditions including transient LV apical ballooning that might strongly mimick LVAA leading to a potential misdiagnosis in patients with HCM:
Show MoreTakotsubo cardiomyopathy (TTC) presenting with a transient apical ballooning pattern has been recently suggested to have a pure mechanical basis in certain patients with pre-existing structural heart diseas...
As a physician dealing with patients with confirmed or suspected Fabry disease, I've read with great interest this editorial. This is a very thought-provoking article, which introduces the process of reclassification of a prevalent variant in the GLA gene associated with the cardiac variant of Fabry disease. I would like to make only a minor correction regarding the nomenclature of the variant mentioned. As written in the article of Valtola et al, the referred variant is c.427G> A and not c.472G> A¹ (transcript NM_000169.2).
1. Valtola K, Nino-Quintero J, Hedman M, et al. Cardiomyopathy associated with the Ala143Thr variant of the α-galactosidase A gene. Heart 2020;:heartjnl-2019-315933. doi:10.1136/heartjnl-2019-315933
LATE CORONARY ANEURYSM FORMATION IN KAWASAKI DISEASE: A SUBTLE PHENOMENON WITH POTENTIAL IMPLICATIONS
Kenan YALTA, MD
Muhammet GURDOGAN, MD
Gokay TAYLAN, MD
a,Trakya University, Cardiology Department, Edirne, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 00905056579856
In clinical practice, coronary artery aneurysms (CAAs) in the setting of Kawasaki disease (KD) mostly evolve in the earlier stages, and generally reach their maximum size by 6 weeks after disease onset (1). Importantly, they are mostly encountered in untreated cases, and are strongly associated with the disease severity (and in particular; the degree of acute necrotizing vasculitis) (1). In their recently published enlightening report (2), Brogan P have discussed long-term management of KD patients with a particular emphasis on CAAs in this setting (2). However, we would like to comment on a specific phenomenon, namely ‘late CAA’ formation that might emerge even several months to years after the index KD:
Show MoreFirstly, late CAAs were previously defined as new CAAs emerging at the same location of a previously regressed CAA, and were attributed to hemodynamic and residual pathological abnormalities along the arterial wal...
We thank Dr Althouse for his letter and the interests in our article and for taking time to send us his comments. We appreciate it very much.
In Figure 1, in scenario C, we incorporated the findings of “equivalence” in cases of equivalence trials. We stated in the article under the section of “Equivalence trials versus non-inferiority trials” that, in equivalence trials, the significance level is set as a two-sided p value of 0.05. We agree that, in non-inferiority trials, a one-sided p value of 0.025 is usually set as the significant level, although in some non-inferiority trials in cardiology, a significance level of one-sided p value of 0.05 was used. This is also mentioned under the same section. We have considered using a separate figure in the submission. However, we decided to submit a single figure as the separate figure incorporating only equivalence trials may be too simple and not the focus of the discussion.
In scenario E, the lower limit of the confidence intervals is below 1 and the upper limit of the confidence interval is above the non-inferior margin. Therefore, the null hypothesis that the new treatment is inferior to standard treatment cannot be rejected and the alternative hypothesis that the new treatment is non-inferior to standard treatment cannot be accepted. We agree that the interpretation is more correctly stated as “New treatment not non-inferior to standard treatment”. Alternatively, as Dr Althouse suggested “New treatment...
Show MoreI submit this comment on the recent publication by Leung et al entitled “Non-inferiority trials in cardiology: what clinicians need to know” (1) which I believe has a slight error that merits correction.
On Figure 1 in the original publication, the label says that Result E shows “New treatment inferior” but that is not a correct interpretation. The text in the footnote (“the upper bound of the 95% CI exceeds the predetermined non-inferior margin. Therefore, the new treatment is inferior to standard treatment”) is also incorrect. The data shown in Result E are not sufficient to declare a non-inferiority hypothesis met (the upper limit of the CI for relative risk is above the non-inferiority margin) but nor are they sufficient to declare the new treatment inferior (the lower limit of the CI for relative risk is below the null value). Therefore, the correct label for Result E is “New treatment neither inferior nor non-inferior.” The new treatment would only be declared inferior to the standard treatment in cases F and G (where the lower limit of the 95% CI for relative risk is above the null).
REFERENCE
1. Leung JT, Barnes SL, Lo ST, Leung DY. Non-inferiority trials in cardiology: what clinicians need to know. Heart 2019 [epub ahead of print]
Some of the risk factors for atrial fibrillation(AF) mentioned by the authors, such as hypertension, diabetes, sleep apnoea, older age, and lack of exercise, respectively(1), are also risk factors for myocardial stiffness(2)(3)(4)(5)(6). Myocardial stiffness, in turn, is a risk factor for atrial remodeling in the canine heart(7), and a parameter associated with paroxysmal AF in structurally normal human hearts(8). What is more, exercise has been shown to be capable of reversing myocardial stiffness, both in animals(9), and in human subjects(10).
Show MoreIn the more specific context of left atrial stiffness, obesity has emerged as a risk factor for left atrial stiffness(11)(12). Among patients with obesity, hypertension, and diabetes, respectively, a link has been hypothesised between the twin entities of left ventricular stiffness and depressed atrial compliance, on the one hand, and the development of myocardial fibrosis.(12) . The authors of the latter hypothesis proposed that obesity, hypertension and diabetes generated a systemic proinflammatory state which culminated in the emergence of the coexistence of stiff cardiomyocytes and interstitial fibrosis(12). Furthermore, in a study where the assumption was made that the existence of low voltage areas was a surrogate for left atrial fibrosis, the presence of a left atrial low voltage burden exceeding 10% was shown to be associated with significantly(p < 0.0001) higher left atrial stiffness index((LASI)(13)....
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