We have read with great interest the article written by Jolicoer et al. (1) about the concordant domain analysis, a new method to interpret early phase trials and we applaud their initiative which expands the horizons in the current context of progressive diffuculties to ran studies.
Randomized controlled trials (RCT) and meta-analysis constitute the highest level of evidence and the chances to succeed are high when there is a strong financial support to launch projects as Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) with 27,564 patients, which in addition to demonstrate the hypothesis of the study, it ensures the external validity and the study of subgroups.
However, recently we are witnessing a progressively more tortuous environment to launch adequately powered RCTs due to economic restrictions, lower margin to demonstrate cost-effectivity of the new treatments and more strict legal requirements and as the authors quote, only 1 in 10 investigational agents tested in phase III trials reaches the market. Some authors have already raisen concerns about the future of research and the protagonism of new methods as adaptive studies(2) or approaches to emulate RCT (3) are foreseen in the near future.
In our opinion, the combination of pilot randomized studies with new iniciatives as the described by Jolicoer may be a promising pathway when the conditions to launch large RCTs are not possible and in fa...
We have read with great interest the article written by Jolicoer et al. (1) about the concordant domain analysis, a new method to interpret early phase trials and we applaud their initiative which expands the horizons in the current context of progressive diffuculties to ran studies.
Randomized controlled trials (RCT) and meta-analysis constitute the highest level of evidence and the chances to succeed are high when there is a strong financial support to launch projects as Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) with 27,564 patients, which in addition to demonstrate the hypothesis of the study, it ensures the external validity and the study of subgroups.
However, recently we are witnessing a progressively more tortuous environment to launch adequately powered RCTs due to economic restrictions, lower margin to demonstrate cost-effectivity of the new treatments and more strict legal requirements and as the authors quote, only 1 in 10 investigational agents tested in phase III trials reaches the market. Some authors have already raisen concerns about the future of research and the protagonism of new methods as adaptive studies(2) or approaches to emulate RCT (3) are foreseen in the near future.
In our opinion, the combination of pilot randomized studies with new iniciatives as the described by Jolicoer may be a promising pathway when the conditions to launch large RCTs are not possible and in fact, we have recently seen examples of small pilot randomized trials with clinical endpoints published in journals of very high impact factor(4). In this way, our group has recently received financial support from a large company of devices to run a pilot study with 400 patients to explore a research question that requires a large and expensive trial of 2000 patients (ANGiographic Evaluation of Left main coronary INtErvention, ANGELINE, NCT04604197).
In summary, we are assisting to relevant changes in the field of research and although RCTs and meta-analysis will be and will have to be always the first goal, new initiatives as the one that Jolicoer et al. share with us deserve our attention and are very welcome.
REFERENCES
1. Jolicoeur EM, Verheye S, Henry TD et al. A novel method to interpret early phase trials shows how the narrowing of the coronary sinus concordantly improves symptoms, functional status and quality of life in refractory angina. Heart 2021;107:41-46.
2. Rapezzi C, Maggioni AP, Ferrari R. Adapting to survive. Eur Heart J 2020;41:3981-3983.
3. Franklin JM, Patorno E, Desai RJ et al. Emulating Randomized Clinical Trials with Nonrandomized Real-World Evidence Studies: First Results from the RCT DUPLICATE Initiative. Circulation 2020.
4. Yannopoulos D, Bartos J, Raveendran G et al. Advanced reperfusion strategies for patients with out-of-hospital cardiac arrest and refractory ventricular fibrillation (ARREST): a phase 2, single centre, open-label, randomised controlled trial. Lancet 2020;396:1807-1816.
In clinical practice, timing of aortic valve intervention in asymptomatic severe aortic stenosis (ASAS) has been a challenging task particularly in the absence of overt high-risk features (low ejection fraction, etc.) (1,2). The recently published article by Bing R, et al. (1), has discussed current strategies that might help risk-stratification and management of this precarious valvular phenomenon. In this context, we fully agree with the authors that serum biomarkers including natriuretic peptides, as opposed to certain imaging modalities, generally have significant limitations (1). However, serum copeptin (the surrogate marker of arginine-vasopressine (AVP) axis) might serve as a promising guide to prognostication and clinical decision-making for aortic valve intervention in patients with ASAS (2) largely due to pathophysiological implications of AVP axis in these patients:
Firstly; copeptin elevation in patients with ASAS might help ide...
In clinical practice, timing of aortic valve intervention in asymptomatic severe aortic stenosis (ASAS) has been a challenging task particularly in the absence of overt high-risk features (low ejection fraction, etc.) (1,2). The recently published article by Bing R, et al. (1), has discussed current strategies that might help risk-stratification and management of this precarious valvular phenomenon. In this context, we fully agree with the authors that serum biomarkers including natriuretic peptides, as opposed to certain imaging modalities, generally have significant limitations (1). However, serum copeptin (the surrogate marker of arginine-vasopressine (AVP) axis) might serve as a promising guide to prognostication and clinical decision-making for aortic valve intervention in patients with ASAS (2) largely due to pathophysiological implications of AVP axis in these patients:
Firstly; copeptin elevation in patients with ASAS might help identify a subgroup with a state of subtle systemic hypoperfusion (potentially associated with the failure to increase cardiac output sufficiently under stress) that might lead to unexpected coronary ischemic events and sudden cardiac death (SCD) particularly during exercise (2). Copeptin elevation due to valvular stenosis might also suggest progressive ventricular remodeling and eventual heart failure in the long term as a consequence of enhanced AVP actions on myocardium (2). However, potential confounding factors (dehydration, infections, etc.) should also be sought before associating ASAS with copeptin elevation (2).
Secondly; augmented myocardial baroreceptor reactivity (namely Bezold-Jarish reflex) is well known to be associated with syncopal attacks and, if substantial, SCD in the setting of severe aortic stenosis largely through induction of bradyarrhythmias and peripheral vasodilatation (2). Interestingly, AVP was previously demonstrated to exert a significant stimulatory impact on baroreceptor reactivity (3,4). Therefore, substantial copeptin elevation might help identify ASAS patients who might particularly be prone to excessive Bezold-Jarish reflex (and hence; to SCD risk) on follow-up. (2).
Thirdly; AVP axis has a significant correlation with adrenergic system partly attributable to the central impact of adrenergic substances on AVP release (2). Therefore, copeptin elevation denotes a state of adrenergic hyperactivation that might account for arrhythmias in patients with ASAS, particularly in those with left ventricular hypertrophy (2).
Finally; copeptin elevation in patients with ASAS might also predict rapid progression of transaortic gradient owing to profibrotic effects of augmented AVP actions on aortic valvular tissue (2).
In summary; copeptin elevation might potentially signify a higher risk for adverse events in patients with ASAS due to the hemodynamic, autonomic and fibrogenic implications of enhanced AVP actions (2). Therefore, adjunctive evaluation of serum copeptin at regular intervals might help dynamic risk-stratification, and might further optimize the timing of aortic valve intervention in these patients (2). However, this needs to be tested in large-scale clinical studies.
Conflict of Interest: None
REFERENCES:
1- Bing R, Dweck MR. Management of asymptomatic severe aortic stenosis: check or all in?
Heart Published Online First: 04 November 2020. doi: 10.1136/heartjnl-2020-317160
2- Yalta K, Palabiyik O, Gurdogan M, Gurlertop Y. Serum copeptin might improve risk stratification and management of aortic valve stenosis: a review of pathophysiological insights and practical implications. Ther Adv Cardiovasc Dis. 2019 Jan-Dec;13:1753944719826420. doi: 10.1177/1753944719826420. PMID: 30803406; PMCID: PMC6376527.
3- Roul G, Riehl-Aleil V, Germain P, Bareiss P. Neurohormonal profile before and after beta-blockade in patients with neurocardiogenic syncope. Pacing Clin Electrophysiol. 1999; 22(7): 1020-30.
4- Mosqueda-Garcia R, Furlan R, Tank J, Fernandez-Violante R. The elusive pathophysiology of neurally mediated syncope. Circulation. 2000; 102(23): 2898-906.
We thank Güner and colleagues for their comments1 and their interest on our study.1
It is very common in the low to middle come countries to observe women with more than one pregnancy and the proposed risk stratification score (Devi’s Score) took this scenario into consideration.2 Analyses took into consideration the non-independent nature of the data structure occurring from women having more than one pregnancy and generalized estimating equations were used to produce regression models to account for the clustering occurring due to more than one pregnancy in the same patient.
Prosthetic heart valve, especially the mechanical heart valves are highly thrombogenic and are associated with complications. On univariate analysis, use of anticoagulation was found to be associated with the adverse cardiac events and since they showed high collinearity with the prosthetic heart valve, it was decided to include prosthetic heart valve in the multivariate analysis. Despite following the guidelines on managing the anticoagulation regimen during pregnancy, we experience multiple challenges in day to day practice. Monitoring and maintaining the International normalised ratio(INR) /prothrombin time within the optimal range during a dynamic hemodynamic, variability in the actual timing in switching over to heparin and the clearly evident risk of thrombo-embolic phenomena during the switch-over time till heparin takes full control are some of the real wor...
We thank Güner and colleagues for their comments1 and their interest on our study.1
It is very common in the low to middle come countries to observe women with more than one pregnancy and the proposed risk stratification score (Devi’s Score) took this scenario into consideration.2 Analyses took into consideration the non-independent nature of the data structure occurring from women having more than one pregnancy and generalized estimating equations were used to produce regression models to account for the clustering occurring due to more than one pregnancy in the same patient.
Prosthetic heart valve, especially the mechanical heart valves are highly thrombogenic and are associated with complications. On univariate analysis, use of anticoagulation was found to be associated with the adverse cardiac events and since they showed high collinearity with the prosthetic heart valve, it was decided to include prosthetic heart valve in the multivariate analysis. Despite following the guidelines on managing the anticoagulation regimen during pregnancy, we experience multiple challenges in day to day practice. Monitoring and maintaining the International normalised ratio(INR) /prothrombin time within the optimal range during a dynamic hemodynamic, variability in the actual timing in switching over to heparin and the clearly evident risk of thrombo-embolic phenomena during the switch-over time till heparin takes full control are some of the real world concerning scenarios we have observed. A detailed analysis of the outcomes of the mechanical heart valves based on the anticoagulant regimes is under manuscript preparation for submission.
The present study included women with arrythmias which were present or diagnosed prior to pregnancy, including those with atrial fibrillation, under the broad category of prior cardiovascular event and those women with new onset atrial fibrillation requiring treatment during the course of pregnancy as a part of the composite maternal cardiovascular outcome. The prior cardiovascular event was found to be a significant factor and is included in the proposed score. Chokesuwattanaskul et al3 in the metanalysis included studies reporting women with prevalent and incident cases of atrial fibrillation; the effect of which may vary on the pregnancy outcomes. They also fail to describe the exact nature of the structural heart disease included in the meta-analysis, as the reasons leasing to development of atrial fibrillation as well as it effects on the outcome may be influenced by the primary structural lesion. So, the effect of atrial fibrillation on pregnant women with RHD need to be explored further in future studies.
References
1. Güner A, Kalçık M, Güner EG, et al Challenges in the management of pregnant patients with cardiovascular diseases Heart Published Online First: 21 September 2020. doi: 10.1136/heartjnl-2020-317768.
2. Baghel J, Keepanasseril A, Pillai AA, et al. Prediction of adverse cardiac events in pregnant women with valvular rheumatic heart disease. Heart 2020; 106:1400–6.doi:10.1136/heartjnl-2020-316648.
3. Chokesuwattanaskul R, Thongprayoon C, Bathini T, O'Corragain OA, Sharma K, Prechawat S, Ungprasert P, Watthanasuntorn K, Pachariyanon P, Cheungpasitporn W. Incidence of atrial fibrillation in pregnancy and clinical significance: A meta-analysis. Adv Med Sci. 2019 Sep;64(2):415-422. doi: 10.1016/j.advms.2019.07.003.
The soul-searching analysis by Daniel McKenzie deals with the scenario where both the doctor and the patient recognise that something went wrong(1). The dynamics are different when it is only with the benefit of hindsight that it is only the professionals who realise that, all along, they have been inflicting iatrogenic harm on their patients. Even in that scenario what matters is "What will be done to prevent someone else being harmed in the future?".
The thrombolytic treatment of ST elevation myocardial infarction(STEMI) is a case in point. That treatment strategy was initiated in 1986, and it soon became the standard of care for STEMI(2). Further down the line, in September 2020, a literature review identified 138 cases(with accompanying case histories) of dissecting aortic aneurysm(DAA) characterised by STEMI-like ST segment elevation. These cases were published during the period January 2000 to March 2020(3). Arguably, there must have been, at least, the same number of cases of STEMI-like DAA in the 20 year period following the introduction of thrombolytic treatment of ST elevation myocardial infarction. At the very least, some of those cases must have been harmed by thrombolytic treatment.
Why does that matter in September 2020? It matters because thrombolysis is "back on the agenda" for some myocardial infarction patients with ST segment elevation(4). All this, without the precaution to rule out DAA either by point-of-c...
The soul-searching analysis by Daniel McKenzie deals with the scenario where both the doctor and the patient recognise that something went wrong(1). The dynamics are different when it is only with the benefit of hindsight that it is only the professionals who realise that, all along, they have been inflicting iatrogenic harm on their patients. Even in that scenario what matters is "What will be done to prevent someone else being harmed in the future?".
The thrombolytic treatment of ST elevation myocardial infarction(STEMI) is a case in point. That treatment strategy was initiated in 1986, and it soon became the standard of care for STEMI(2). Further down the line, in September 2020, a literature review identified 138 cases(with accompanying case histories) of dissecting aortic aneurysm(DAA) characterised by STEMI-like ST segment elevation. These cases were published during the period January 2000 to March 2020(3). Arguably, there must have been, at least, the same number of cases of STEMI-like DAA in the 20 year period following the introduction of thrombolytic treatment of ST elevation myocardial infarction. At the very least, some of those cases must have been harmed by thrombolytic treatment.
Why does that matter in September 2020? It matters because thrombolysis is "back on the agenda" for some myocardial infarction patients with ST segment elevation(4). All this, without the precaution to rule out DAA either by point-of-care transthoracic echocardiography(TTE) or by transoesophageal echocardiography(TOE). The former is non-invasive but suboptimally sensitive, the latter is invasive but much more sensitive.. To mitigate the suboptimal sensitivity of TTE one strategy would be to maximise the pretest probability of DAA by compiling a risk score which encompasses history of backache(which does not need to have a "rearing" quality), documentation of interarm blood pressure difference, presence of the murmur of aortic regurgitation(optimally detected by the Vivid-7 system; GE Medical, Milwauwkee, Wisconsin, USA)(5), focal neurological symptoms and signs, and mediastinal widening on chest radiography. A high pre-test probability of DAA would be sufficient to invalidate a TTE which had failed to detect stigmata of DAA.
Our patients are not aware of the dynamics that come into play when they present with chest pain and a STEMI-like electrocardiogram. They take everything on trust. It would be unconscionable for us to knowingly put them in the way of iatrogenic harm by not heeding the lessons that can be gleaned from the literature on STEMI-like DAA.
I have no funding, and no conflict of interest.
References
(1) McKenzie D
What to do when things go wrong
Heart 2020;doi.org/10.1136/heartjnl 2020.316539
(2) Van de Werf
The history of coronary reperfusion
Eur Heart J 2014;35:2510-2515
(3) Jolobe OMP
Clinical characteristics in STEMI-like aortic dissection versus STEMI-like pulmonary embolism
Archives of Vascular Medicine 2020;4:019-130
DOI:29328/journal.avm.1001013
(4) Vallabhajosyula S., Verghese D., Subramanian AV et al
Management and outcome of uncomplicated ST segment elevation myocardial infarction patients transferred after fibrinolytic treatment
Int J Cardiol IJCA-28800(Article in Press)
(5)Draper J., Subbiah S., Bailey R., Chambers J
Murmur clinic. Validation of a new model for detecting heart valve disease
Heart 2019;105;56-59
There had been controversies raging whether Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blocking Agents may be harmful, neutral or protective to the people affected by SARS-CoV-2.
The findings of this study, especially because it encompasses such huge study population will provide great relief from uncertainty and anxiety to the doctor's prescribing these class of medicines to their hypertensive patients and to the people alrady taking these medicines.
Great many sinceremost thanks to the investigators of this study!
-Arvind Joshi;
MBBS, MD; FCGP, FAMS, FICP;
Founder Convener and President:
Our Own Discussion Group (OODG);
602-C, Megh Apartments;
Ganesh Peth Lane, Dadar West, Mumbai; Maharashtra State,INDIA, PIN 400028;
Consultant Physician at:
Ruchi Clinical Laboratory/Ruchi Diagnostic Center, Sunshine CHS,
Plot 58, Sector 21, Kharghar;
Maharashtra State, INDIA, PIN 410210.
1Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinuora, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan
Address correspondence and reprint requests to: Seigo Okada, M.D., Ph.D.
Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan. Tel: 81-93-641-5111; Fax: 81-93-642-1868; E-mail: sokada0901@gmail.com; ORCID: 0000-0002-9150-1913
Dear Editor:
We read the article by Charla et al.1 with great interest. The authors conducted a phase-contrast magnetic resonance study during biphasic ventilation (BPV) in 10 patients aged 20–34 years who had Fontan circulation and 10 matched control subjects. BPV resulted in significant pulmonary blood flow and cardiac output augmentations in the Fontan group, which suggests the importance of “thoracic pump” in Fontan patients without a subpulmonary ventricle. We appreciate the authors’ efforts to assess the efficacy and feasibility of noninvasive external ventilation for Fontan patients. This is a thoughtfully conducted study, but some issues must be further discussed.
First, the authors mentioned that the study was the first to describe the impact of BPV in the Fontan population. However, we...
1Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinuora, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan
Address correspondence and reprint requests to: Seigo Okada, M.D., Ph.D.
Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan. Tel: 81-93-641-5111; Fax: 81-93-642-1868; E-mail: sokada0901@gmail.com; ORCID: 0000-0002-9150-1913
Dear Editor:
We read the article by Charla et al.1 with great interest. The authors conducted a phase-contrast magnetic resonance study during biphasic ventilation (BPV) in 10 patients aged 20–34 years who had Fontan circulation and 10 matched control subjects. BPV resulted in significant pulmonary blood flow and cardiac output augmentations in the Fontan group, which suggests the importance of “thoracic pump” in Fontan patients without a subpulmonary ventricle. We appreciate the authors’ efforts to assess the efficacy and feasibility of noninvasive external ventilation for Fontan patients. This is a thoughtfully conducted study, but some issues must be further discussed.
First, the authors mentioned that the study was the first to describe the impact of BPV in the Fontan population. However, we previously described the efficacy of BPV for failing Fontan circulation in a 16-year-old male patient with hypoplastic left heart syndrome who presented protein-losing enteropathy and plastic bronchitis (PB).2 He underwent rehabilitation using an RTX respirator (Medivent Ltd., London, UK) with the vibration mode set at −10/+10 cm H2O for 3 minutes, followed by the cough mode set at −9/+18 for 1 minute, three times for 12 minutes per session.3 The brief period of BPV increased the stroke volume without changing the heart rate. After the start of the BPV, the PB, hypoalbuminemia, and congestive symptoms all improved. No signs of recurrent circulatory failure have since been observed. As the management strategy for the complex pathophysiology of Fontan circulation is not yet established, their and our results suggest that BPV can be an effective treatment and preventive rehabilitation for failing Fontan circulation.
Second, several Fontan patients were likely to have no significant pulmonary blood flow and cardiac output augmentations during BPV.1 In the practical setting of BPV, it is important for a cuirass to fit the patient’s chest. Thereby, we wonder whether overweight or obesity is a risk factor of ineffective BPV. Do you have data regarding the relationship between body mass index and augmentation of pulmonary blood flow during BPV in your cohort? Pulmonary arterial size is an important determinant of pulmonary circulation in Fontan patients. A recent report has shown that pulmonary arterial size expressed as Nakata index is an independent predictor of functional clinical status in adult Fontan patients.4 Thus the relationship between pulmonary arterial size and augmentation of pulmonary blood flow during BPV should also be addressed.
1. Charla P, Karur GR, Yamamura K, et al. Augmentation of pulmonary blood flow and cardiac output by non-invasive external ventilation late after Fontan palliation. Heart Published Online First: 06 July 2020. doi: 10.1136/heartjnl-2020-316613
2. Okada S, Muneuchi J, Nagatomo Y, et al. Successful Treatment of Protein-Losing Enteropathy and Plastic Bronchitis by Biphasic Cuirass Ventilation in a Patient with Failing Fontan Circulation. Int Heart J 2018;59:873-6.
3. Pediheart Podcast 49: Surveillance of the Fontan Patient + Novel Ventilation Approaches for the Fontan Patient. Available from: https://podcasts.apple.com/us/podcast/pediheart-podcast-49-surveillance-... (accessed July 18, 2020).
4. Ridderbos FS, Bonenkamp BE, Meyer SL, et al. Pulmonary artery size is associated with functional clinical status in the Fontan circulation. Heart 2020;106:233-9.
We read with interest the review of non-infective endocarditis by Hurrell et al. [1] and would like to report our experience. We recently reported the case of an asymptomatic, hypertensive 36-year-old man who was found to have a mobile structure attached to the posterior mitral valve leaflet causing moderate eccentric regurgitation on routine echocardiography [2]. Extensive workup was only notable for strongly positive cardiolipin IgG and IgM antibodies and lupus anticoagulant suggesting a diagnosis of antiphospholipid antibody (APLA) syndrome. We referred the patient for surgical intervention (excision and mitral valve repair with a bovine pericardial patch) and this also allowed us to achieve a diagnosis. Histological features were typical of nonbacterial thrombotic endocarditis (NBTE) with fibrin deposits, inflammatory cells and erythrocytes and confirmed an underlying diagnosis of primary APLA syndrome.
The association of APLA syndrome with or without autoimmune disease increases prothrombotic tendency and these patients therefore have a higher likelihood of NBTE which can remain clinically silent. We therefore propose that transthoracic echocardiography should be used as a screening and surveillance tool for NBTE in all patients who are found to have primary or secondary APLA syndrome and potentially in patients with autoimmune disease and hypercoaguable states. We also emphasize consideration of a histological diagnosis when there is diagn...
We read with interest the review of non-infective endocarditis by Hurrell et al. [1] and would like to report our experience. We recently reported the case of an asymptomatic, hypertensive 36-year-old man who was found to have a mobile structure attached to the posterior mitral valve leaflet causing moderate eccentric regurgitation on routine echocardiography [2]. Extensive workup was only notable for strongly positive cardiolipin IgG and IgM antibodies and lupus anticoagulant suggesting a diagnosis of antiphospholipid antibody (APLA) syndrome. We referred the patient for surgical intervention (excision and mitral valve repair with a bovine pericardial patch) and this also allowed us to achieve a diagnosis. Histological features were typical of nonbacterial thrombotic endocarditis (NBTE) with fibrin deposits, inflammatory cells and erythrocytes and confirmed an underlying diagnosis of primary APLA syndrome.
The association of APLA syndrome with or without autoimmune disease increases prothrombotic tendency and these patients therefore have a higher likelihood of NBTE which can remain clinically silent. We therefore propose that transthoracic echocardiography should be used as a screening and surveillance tool for NBTE in all patients who are found to have primary or secondary APLA syndrome and potentially in patients with autoimmune disease and hypercoaguable states. We also emphasize consideration of a histological diagnosis when there is diagnostic uncertainty – tissue is the issue. Continued anticoagulation is particularly important in NBTE, irrespective of aetiology and even after surgical resection, because of the high incidence of associated embolic and vaso-occlusive events. In fact, the diagnosis is usually reached at post-mortem.
The benefits of regular exercise are non deniable with reduction in all cause, cardiovascular and cancer mortality (1,2,3). Endurance exercise with increase in cardiac output results in dilatation of left ventricular cavity size and eccentric hypertrophy with low normal ejection fraction that is a dilated cardiomyopathy phenocopy. The ability to distinguish true pathology from physiological remodelling remains a difficult area for cardiologists. Frequently asymptomatic athletic individuals are referred to the cardiology service with abnormal resting 12 lead ECGs. They must be appropriately investigated. The dimema for the investigating cardiologist is to determine the healthy athlete from the athlete with DCM. An erroneous diagnosis of DCM in an athlete may lead to unnecessary disqualification from sport, unnecessary pharmacotherapy and a decline in physical and psychological well being as well as implications for life insurance. Millar et al study adds vital information to the field (4). It is reassuring that the study reported that none of the athletes with a physiologically increased LV size and borderline or low resting LV ejection fraction (grey-zone participants) had replacement fibrosis of the left ventricular myocardium on cardiac MRI. In addition, the authors have reported that functional assessment of the heart by stress echocardiography can discriminate between DCM and DCM phenocopy with high sensitivity and specificity. This study will likely be a game...
The benefits of regular exercise are non deniable with reduction in all cause, cardiovascular and cancer mortality (1,2,3). Endurance exercise with increase in cardiac output results in dilatation of left ventricular cavity size and eccentric hypertrophy with low normal ejection fraction that is a dilated cardiomyopathy phenocopy. The ability to distinguish true pathology from physiological remodelling remains a difficult area for cardiologists. Frequently asymptomatic athletic individuals are referred to the cardiology service with abnormal resting 12 lead ECGs. They must be appropriately investigated. The dimema for the investigating cardiologist is to determine the healthy athlete from the athlete with DCM. An erroneous diagnosis of DCM in an athlete may lead to unnecessary disqualification from sport, unnecessary pharmacotherapy and a decline in physical and psychological well being as well as implications for life insurance. Millar et al study adds vital information to the field (4). It is reassuring that the study reported that none of the athletes with a physiologically increased LV size and borderline or low resting LV ejection fraction (grey-zone participants) had replacement fibrosis of the left ventricular myocardium on cardiac MRI. In addition, the authors have reported that functional assessment of the heart by stress echocardiography can discriminate between DCM and DCM phenocopy with high sensitivity and specificity. This study will likely be a game changer in the investigation of athletic remodelling and may reduce the requirement to ask athletic individuals to decondition and refrain from their sport.
1. Parry-Williams, G., Sharma, S. The effects of endurance exercise on the heart: panacea or poison?. Nat Rev Cardiol 17, 402–412 (2020).
2. Fiuza-Luces, C. et al. Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat. Rev. Cardiol. 15, 731–743 (2018).
3. Pedisic, Z. et al. Is running associated with a lower risk of all-cause, cardiovascular and cancer mortality, and is the more the better? A systematic review and meta-analysis. Br. J. Sports Med.
4.Millar LM, Fanton Z, Finocchiaro G, et al Differentiation between athlete’s heart and dilated cardiomyopathy in athletic individuals Heart 2020;106:1059-1065.
For the sake of completeness, the approach to narrow complex tachycardia(1), and the differential diagnosis of that disorder, should also include the entity of fascicular ventricular tachycardia, in which the duration of the QRS complex does not exceed 120 ms during ventricular tachycardia(VT)(2)(3). There are 3 subtypes, namely, left posterior fascicular VT with right bundle branch(RBBB) morphology and left axis deviation, left anterior fascicular VT with RBBB pattern and right axis deviation, and upper septal fascicular VT with a narrow QRS and normal axis configuration(2).
Talib et al evaluated 10 patients aged 14-66 with upper septal ventricular tachycardia in whom there was no structural heart disease, and in whom the QRS duration amounted to < 120 ms during VT. In 8 instances VT could be terminated by administration of verapamil. In the other 2 instances no attempt had been made to terminate the episodes of VT with that drug. In the verapamil-responsive subjects, the episodes of VT were characterised by QRS duration amounting to 75 ms, 90 ms(two patients), 93 ms, 96 ms, 105 ms, 115 ms, and 118 ms, respectively. In 4 patients precordial QRS configuration during VT was identical to QRS configuration during sinus rhythm. In the other four, QRS configuration was of the RBBB subtype during VT(3).
Narrow complex VT can also be a manifestation of coronary artery disease, but, in this context, there appears to be no involvement of the His-Purki...
For the sake of completeness, the approach to narrow complex tachycardia(1), and the differential diagnosis of that disorder, should also include the entity of fascicular ventricular tachycardia, in which the duration of the QRS complex does not exceed 120 ms during ventricular tachycardia(VT)(2)(3). There are 3 subtypes, namely, left posterior fascicular VT with right bundle branch(RBBB) morphology and left axis deviation, left anterior fascicular VT with RBBB pattern and right axis deviation, and upper septal fascicular VT with a narrow QRS and normal axis configuration(2).
Talib et al evaluated 10 patients aged 14-66 with upper septal ventricular tachycardia in whom there was no structural heart disease, and in whom the QRS duration amounted to < 120 ms during VT. In 8 instances VT could be terminated by administration of verapamil. In the other 2 instances no attempt had been made to terminate the episodes of VT with that drug. In the verapamil-responsive subjects, the episodes of VT were characterised by QRS duration amounting to 75 ms, 90 ms(two patients), 93 ms, 96 ms, 105 ms, 115 ms, and 118 ms, respectively. In 4 patients precordial QRS configuration during VT was identical to QRS configuration during sinus rhythm. In the other four, QRS configuration was of the RBBB subtype during VT(3).
Narrow complex VT can also be a manifestation of coronary artery disease, but, in this context, there appears to be no involvement of the His-Purkinje system, although the underlying mechanism has yet to be fully elucidated(4). In the latter example, a 54 year old man had a previous history of ST segment inferior myocardial infarction characterised by right coronary artery occlusion. One month later he experienced an episode of tachycardia (ventricular rate 140 beats/min) characterised by QRS duration amounting to 120 ms and atrioventricular dissociation(4).
Of all the patients with narrow complex VT the ones most likely to be confused with supraventricular tachycardia are the ones described by Talib et al, in whom QRS duration amounted to < 120 ms during VT. In some of those patients diagnostic confusion would have been compounded by the fact that QRS configuration was the same during sinus rhythm and VT. In those with RBBB during VT a potential diagnostic trap would be attribution of RBBB to rate-dependent aberrant conduction.
I have no funding and no conflict of interest
References
(1)Shah RL., Badhwar N
Approach to narrow complex tachycardia: non-invasive guide to interpretation and management
Heart 2020;106:772-783
((2)Ramprakash B., Jaishankar S., Rao H., Narasimhan C
Catheter ablation of fascicular ventricular tachycardia
Indian Journal Pacing and Electrophysiology www.ipej.org 193-201
(3)Talib AK., Nogami A., Nishiuchi S et al
Verapamil-sensitive upper septal idiopathjic left ventricular tachycardia
JACC;Clinical Electrophysiology 2015;1:369-380
(4)Sakamoto T., Fujiki A., Nakatani Y. et al
Narrow QRS ventricular tachycardia from the posterior mitral annulus without involvement of the His-Purkinje system in a patient with prior inferior myocardial infarction
Heart Vessels 2010;25;170-173
The authors (Nazir et al) of the review of CT fractional flow reserve published in Heart are to be congratulated on very well balanced and well written review of this relatively new technology (1).
We would like to raise a couple of points regarding imaging stress tests functioning as a gatekeeper to invasive coronary angiography after a stenosis is identified on CTCA. A recent survey of UK cardiologists identified imaging stress tests as the most common approach to assess the functional significance of a moderate stenosis (50-70%) on CTCA, with only 2% electing to use CT-FFR (2). The current increase in the use of CT-FFR is because it is nationally funded. Importantly, stress echocardiography is a very low cost test with a national tariff of £177, which compares favourably with the new reduced tariff for CT-FFR of £530. With time, this may be re-balance in favour of CT-FFR if the tariff drops further, particularly given the attraction of a single patient episode and with an anticipated growth of cardiac CT in line with NICE recommendations.
It is important to remind readers that the PLATFORM (3) trial compared CTCA plus CT-FFR versus the standard of care in patients with stable chest pain. The patients were divided into an invasive sub-study (n=380) and a non-invasive sub-study (n=204) and the end point of the study was reduction of invasive coronary angiography that showed no obstructive CAD. In the non-invasive sub-study there was no difference in the r...
The authors (Nazir et al) of the review of CT fractional flow reserve published in Heart are to be congratulated on very well balanced and well written review of this relatively new technology (1).
We would like to raise a couple of points regarding imaging stress tests functioning as a gatekeeper to invasive coronary angiography after a stenosis is identified on CTCA. A recent survey of UK cardiologists identified imaging stress tests as the most common approach to assess the functional significance of a moderate stenosis (50-70%) on CTCA, with only 2% electing to use CT-FFR (2). The current increase in the use of CT-FFR is because it is nationally funded. Importantly, stress echocardiography is a very low cost test with a national tariff of £177, which compares favourably with the new reduced tariff for CT-FFR of £530. With time, this may be re-balance in favour of CT-FFR if the tariff drops further, particularly given the attraction of a single patient episode and with an anticipated growth of cardiac CT in line with NICE recommendations.
It is important to remind readers that the PLATFORM (3) trial compared CTCA plus CT-FFR versus the standard of care in patients with stable chest pain. The patients were divided into an invasive sub-study (n=380) and a non-invasive sub-study (n=204) and the end point of the study was reduction of invasive coronary angiography that showed no obstructive CAD. In the non-invasive sub-study there was no difference in the rate of invasive coronary angiography between imaging stress tests and CTCA plus CT-FFR. In the invasive sub-study, CTCA plus CT-FFR reduced the rate of invasive coronary angiography as only patients found to have significant stenosis on CTCA and positive CT-FFR went on to have an invasive coronary angiogram, while in the invasive arm all patients had to undergo invasive coronary angiogram ± invasive FFR.
Finally, the ISCHAEMIA trial (4) would suggest that following CT assessment of the coronary arteries and exclusion of left main stem disease, further investigation to assess significance of coronary stenoses is not necessarily required should symptoms be controlled on optimal medical therapy.
1. Nazir MS, Mittal TK, Weir-McCall J, et al Opportunities and challenges of implementing computed tomography fractional flow reserve into clinical practice Heart Published Online First: 19 June 2020. doi: 10.1136/heartjnl-2019-315607
2. Fyyaz S, Papachristidis A, Byrne J, Alfakih K. Opinions on the expanding role of CTCA in patients with stable chest pain and beyond: a UK survey. The British Journal of Cardiology. 2018;25:107-9 doi: 10.5837/bjc.2018.019
3. Hlatky MA, De Bruyne B, Pontone G, et al. PLATFORM Investigators. Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve With Computed Tomography Angiography: PLATFORM. J Am Coll Cardiol 2015;66:2315-2323.
4. Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial Invasive or Conservative Strategy for Stable Coronary Disease. New England Journal of Medicine. 2020.
We have read with great interest the article written by Jolicoer et al. (1) about the concordant domain analysis, a new method to interpret early phase trials and we applaud their initiative which expands the horizons in the current context of progressive diffuculties to ran studies.
Show MoreRandomized controlled trials (RCT) and meta-analysis constitute the highest level of evidence and the chances to succeed are high when there is a strong financial support to launch projects as Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) with 27,564 patients, which in addition to demonstrate the hypothesis of the study, it ensures the external validity and the study of subgroups.
However, recently we are witnessing a progressively more tortuous environment to launch adequately powered RCTs due to economic restrictions, lower margin to demonstrate cost-effectivity of the new treatments and more strict legal requirements and as the authors quote, only 1 in 10 investigational agents tested in phase III trials reaches the market. Some authors have already raisen concerns about the future of research and the protagonism of new methods as adaptive studies(2) or approaches to emulate RCT (3) are foreseen in the near future.
In our opinion, the combination of pilot randomized studies with new iniciatives as the described by Jolicoer may be a promising pathway when the conditions to launch large RCTs are not possible and in fa...
Kenan YALTA, MD a
Ertan YETKIN, MD b
Gokay TAYLAN, MD a
a,TrakyaUniversity, CardiologyDepartment, Edirne, TURKEY
b Derindere Hospital, Cardiology Department, Istanbul, TURKEY
Corresponding Author: Kenan YALTA Trakya University, Cardiology Department, Edirne, TURKEY
Email- kyalta@gmail.com, akenanyalta@trakya.edu.tr Phone: 00905056579856
In clinical practice, timing of aortic valve intervention in asymptomatic severe aortic stenosis (ASAS) has been a challenging task particularly in the absence of overt high-risk features (low ejection fraction, etc.) (1,2). The recently published article by Bing R, et al. (1), has discussed current strategies that might help risk-stratification and management of this precarious valvular phenomenon. In this context, we fully agree with the authors that serum biomarkers including natriuretic peptides, as opposed to certain imaging modalities, generally have significant limitations (1). However, serum copeptin (the surrogate marker of arginine-vasopressine (AVP) axis) might serve as a promising guide to prognostication and clinical decision-making for aortic valve intervention in patients with ASAS (2) largely due to pathophysiological implications of AVP axis in these patients:
Show MoreFirstly; copeptin elevation in patients with ASAS might help ide...
Dear Editor,
We thank Güner and colleagues for their comments1 and their interest on our study.1
Show MoreIt is very common in the low to middle come countries to observe women with more than one pregnancy and the proposed risk stratification score (Devi’s Score) took this scenario into consideration.2 Analyses took into consideration the non-independent nature of the data structure occurring from women having more than one pregnancy and generalized estimating equations were used to produce regression models to account for the clustering occurring due to more than one pregnancy in the same patient.
Prosthetic heart valve, especially the mechanical heart valves are highly thrombogenic and are associated with complications. On univariate analysis, use of anticoagulation was found to be associated with the adverse cardiac events and since they showed high collinearity with the prosthetic heart valve, it was decided to include prosthetic heart valve in the multivariate analysis. Despite following the guidelines on managing the anticoagulation regimen during pregnancy, we experience multiple challenges in day to day practice. Monitoring and maintaining the International normalised ratio(INR) /prothrombin time within the optimal range during a dynamic hemodynamic, variability in the actual timing in switching over to heparin and the clearly evident risk of thrombo-embolic phenomena during the switch-over time till heparin takes full control are some of the real wor...
The soul-searching analysis by Daniel McKenzie deals with the scenario where both the doctor and the patient recognise that something went wrong(1). The dynamics are different when it is only with the benefit of hindsight that it is only the professionals who realise that, all along, they have been inflicting iatrogenic harm on their patients. Even in that scenario what matters is "What will be done to prevent someone else being harmed in the future?".
Show MoreThe thrombolytic treatment of ST elevation myocardial infarction(STEMI) is a case in point. That treatment strategy was initiated in 1986, and it soon became the standard of care for STEMI(2). Further down the line, in September 2020, a literature review identified 138 cases(with accompanying case histories) of dissecting aortic aneurysm(DAA) characterised by STEMI-like ST segment elevation. These cases were published during the period January 2000 to March 2020(3). Arguably, there must have been, at least, the same number of cases of STEMI-like DAA in the 20 year period following the introduction of thrombolytic treatment of ST elevation myocardial infarction. At the very least, some of those cases must have been harmed by thrombolytic treatment.
Why does that matter in September 2020? It matters because thrombolysis is "back on the agenda" for some myocardial infarction patients with ST segment elevation(4). All this, without the precaution to rule out DAA either by point-of-c...
There had been controversies raging whether Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blocking Agents may be harmful, neutral or protective to the people affected by SARS-CoV-2.
The findings of this study, especially because it encompasses such huge study population will provide great relief from uncertainty and anxiety to the doctor's prescribing these class of medicines to their hypertensive patients and to the people alrady taking these medicines.
Great many sinceremost thanks to the investigators of this study!
-Arvind Joshi;
MBBS, MD; FCGP, FAMS, FICP;
Founder Convener and President:
Our Own Discussion Group (OODG);
602-C, Megh Apartments;
Ganesh Peth Lane, Dadar West, Mumbai; Maharashtra State,INDIA, PIN 400028;
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Biphasic ventilation for failing Fontan physiology
Seigo Okada1, MD, PhD, Jun Muneuchi1, MD, PhD, Mamie Watanabe1, MD
1Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinuora, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan
Address correspondence and reprint requests to: Seigo Okada, M.D., Ph.D.
Department of Pediatrics, Japan Community Healthcare Organization, Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishiku, Kitakyushu, Fukuoka, 806-8501, Japan. Tel: 81-93-641-5111; Fax: 81-93-642-1868; E-mail: sokada0901@gmail.com; ORCID: 0000-0002-9150-1913
Dear Editor:
Show MoreWe read the article by Charla et al.1 with great interest. The authors conducted a phase-contrast magnetic resonance study during biphasic ventilation (BPV) in 10 patients aged 20–34 years who had Fontan circulation and 10 matched control subjects. BPV resulted in significant pulmonary blood flow and cardiac output augmentations in the Fontan group, which suggests the importance of “thoracic pump” in Fontan patients without a subpulmonary ventricle. We appreciate the authors’ efforts to assess the efficacy and feasibility of noninvasive external ventilation for Fontan patients. This is a thoughtfully conducted study, but some issues must be further discussed.
First, the authors mentioned that the study was the first to describe the impact of BPV in the Fontan population. However, we...
TO THE EDITOR:
We read with interest the review of non-infective endocarditis by Hurrell et al. [1] and would like to report our experience. We recently reported the case of an asymptomatic, hypertensive 36-year-old man who was found to have a mobile structure attached to the posterior mitral valve leaflet causing moderate eccentric regurgitation on routine echocardiography [2]. Extensive workup was only notable for strongly positive cardiolipin IgG and IgM antibodies and lupus anticoagulant suggesting a diagnosis of antiphospholipid antibody (APLA) syndrome. We referred the patient for surgical intervention (excision and mitral valve repair with a bovine pericardial patch) and this also allowed us to achieve a diagnosis. Histological features were typical of nonbacterial thrombotic endocarditis (NBTE) with fibrin deposits, inflammatory cells and erythrocytes and confirmed an underlying diagnosis of primary APLA syndrome.
Show MoreThe association of APLA syndrome with or without autoimmune disease increases prothrombotic tendency and these patients therefore have a higher likelihood of NBTE which can remain clinically silent. We therefore propose that transthoracic echocardiography should be used as a screening and surveillance tool for NBTE in all patients who are found to have primary or secondary APLA syndrome and potentially in patients with autoimmune disease and hypercoaguable states. We also emphasize consideration of a histological diagnosis when there is diagn...
The benefits of regular exercise are non deniable with reduction in all cause, cardiovascular and cancer mortality (1,2,3). Endurance exercise with increase in cardiac output results in dilatation of left ventricular cavity size and eccentric hypertrophy with low normal ejection fraction that is a dilated cardiomyopathy phenocopy. The ability to distinguish true pathology from physiological remodelling remains a difficult area for cardiologists. Frequently asymptomatic athletic individuals are referred to the cardiology service with abnormal resting 12 lead ECGs. They must be appropriately investigated. The dimema for the investigating cardiologist is to determine the healthy athlete from the athlete with DCM. An erroneous diagnosis of DCM in an athlete may lead to unnecessary disqualification from sport, unnecessary pharmacotherapy and a decline in physical and psychological well being as well as implications for life insurance. Millar et al study adds vital information to the field (4). It is reassuring that the study reported that none of the athletes with a physiologically increased LV size and borderline or low resting LV ejection fraction (grey-zone participants) had replacement fibrosis of the left ventricular myocardium on cardiac MRI. In addition, the authors have reported that functional assessment of the heart by stress echocardiography can discriminate between DCM and DCM phenocopy with high sensitivity and specificity. This study will likely be a game...
Show MoreFor the sake of completeness, the approach to narrow complex tachycardia(1), and the differential diagnosis of that disorder, should also include the entity of fascicular ventricular tachycardia, in which the duration of the QRS complex does not exceed 120 ms during ventricular tachycardia(VT)(2)(3). There are 3 subtypes, namely, left posterior fascicular VT with right bundle branch(RBBB) morphology and left axis deviation, left anterior fascicular VT with RBBB pattern and right axis deviation, and upper septal fascicular VT with a narrow QRS and normal axis configuration(2).
Show MoreTalib et al evaluated 10 patients aged 14-66 with upper septal ventricular tachycardia in whom there was no structural heart disease, and in whom the QRS duration amounted to < 120 ms during VT. In 8 instances VT could be terminated by administration of verapamil. In the other 2 instances no attempt had been made to terminate the episodes of VT with that drug. In the verapamil-responsive subjects, the episodes of VT were characterised by QRS duration amounting to 75 ms, 90 ms(two patients), 93 ms, 96 ms, 105 ms, 115 ms, and 118 ms, respectively. In 4 patients precordial QRS configuration during VT was identical to QRS configuration during sinus rhythm. In the other four, QRS configuration was of the RBBB subtype during VT(3).
Narrow complex VT can also be a manifestation of coronary artery disease, but, in this context, there appears to be no involvement of the His-Purki...
The authors (Nazir et al) of the review of CT fractional flow reserve published in Heart are to be congratulated on very well balanced and well written review of this relatively new technology (1).
We would like to raise a couple of points regarding imaging stress tests functioning as a gatekeeper to invasive coronary angiography after a stenosis is identified on CTCA. A recent survey of UK cardiologists identified imaging stress tests as the most common approach to assess the functional significance of a moderate stenosis (50-70%) on CTCA, with only 2% electing to use CT-FFR (2). The current increase in the use of CT-FFR is because it is nationally funded. Importantly, stress echocardiography is a very low cost test with a national tariff of £177, which compares favourably with the new reduced tariff for CT-FFR of £530. With time, this may be re-balance in favour of CT-FFR if the tariff drops further, particularly given the attraction of a single patient episode and with an anticipated growth of cardiac CT in line with NICE recommendations.
It is important to remind readers that the PLATFORM (3) trial compared CTCA plus CT-FFR versus the standard of care in patients with stable chest pain. The patients were divided into an invasive sub-study (n=380) and a non-invasive sub-study (n=204) and the end point of the study was reduction of invasive coronary angiography that showed no obstructive CAD. In the non-invasive sub-study there was no difference in the r...
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