852 e-Letters

  • Takotsubo Cardiomyopathy; A Tale of Two Distinct Etiologies

    To the Editor,

    In an excellent analysis published in the recent issue of the journal, “Heart” Lau et al. investigated the long-term clinic outcomes of patients with Takotsubo syndrome (TTS) in a large cohort. The results demonstrated that increasing age, male gender, diabetes mellitus, pulmonary disease and chronic kidney disease were associated with a higher risk of recurrence or death1. We wish to highlight a few points relevant to the article.

    Núñez-Gil et al reported their findings whilst categorizing patients with TTS based upon proposed etiology. Individuals with idiopathic or emotional triggers were considered as having the primary disease, whereas those with likely physical causative factors were deemed to have a secondary form of the pathology. The analysis of both groups revealed a disparity in clinical outcomes; patients with underlying physical triggers displayed higher risk of both short and long-term adverse events 2. Similar findings have also been reported in other studies 3.

    Prior published data has theorized that a history of diabetes mellitus may be relatively protective against developed of TTS possibly due to an ameliorated sympathetic response when compared to non-diabetics due to involvement related to diabetic neuropathy 4. Comparatively poorer outcomes in diabetic TTS patients as seen in this study may be possibly explained by the fact that these diabetic patients may have been overwhelmingly sicker to generate enough catecho...

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  • Modifiable risk factors for residual risk of ischaemic stroke

    The residual risk of stroke in subjects with nonvalvular atrial fibrillation(NVAF) is, in part, attributable to coexistence of nonvalvular atrial fibrillation(NVAF) and high-grade(stenosis(50% or more severity) involving the intracranial arterial circulation(1). In the latter study concomitant high-grade cerebrovascular stenosis was identified in 231 of 780 consecutive subjects of mean age 69.5 who had undergone angiographic studies at index stroke(1). Coexistence of extracranial carotid artery stenosis(CAS) and NVAF is also a risk factor for residual stroke(2). In the latter study Chang et al identified high-grade CAS(>50% severity) which was ipsilateral to the index ischemic cerebral infarct in 15 out of 25 patients presenting with stroke(2).
    Secondary prevention of stroke in NVAF patients who have the association of either high-grade stenotic intracranial cerebrovascular disease or high-grade CAS to which the index stroke can be attributed would entail coprescription of low-dose aspirin and an oral anticoagulant drug. Edoxaban would be a suitable candidate, given the fact that the 15 mg/day dose significantly mitigates the risk of stroke ( of presumably cardioembolic origin) in NVAF subjects aged 80 or more(3). That dose is even lower than the 30 mg/day dose which is associated with significantly(p < 0.001) lower risk of gastrointestinal bleeding than warfarin(4).
    Primary prevention would require strict abstinence from smoking, str...

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  • Incomplete surgical left atrial appendage closure increases thromboembolic complications in a patient with rheumatic mitral valve disease

    To the Editor,
    We have recently read with great interest the article by Kim et al entitled ‘‘Exclusion versus preservation of the left atrial appendage in rheumatic mitral valve surgery’’ [1]. We appreciate the authors for their study describing the relationship of preservation of the left atrial appendage (LAA) to the risk of adverse clinical events in patients with rheumatic mitral valve disease. On the other hand, we believe that there are several major drawbacks that need to be addressed.
    First of all, the LAA can be excluded from the systemic circula¬tion by obliterating its orifice with or without excising the body of the appendage [2]. During the two decades, mechanical occlusion of the LAA including the surgical approach has been adopted by clinicians as a potential approach for stroke prevention in selected patients with atrial fibrillation (AF) [2]. Surgical LAA ligation has been attempted with or without enabling devices. Although routine surgical LAA occlusion has been recommended by some, the evidence base for its actual benefit remains limited and conflicting. Surgical closure particularly using suture ligation can yield incomplete surgical left atrial appendage closure (iSLC) in more than one-third of the patients [2, 3]. Previously, Katz et al evaluated 50 patients who underwent surgical LAA closure in association with mitral valve surgery and similarly reported iSLC in 36% of their patients [3]. The readers may wonder whether routine p...

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  • IgG4-related constrictive pericarditis might also exhibit a variable response to corticosteroids

    The observation that transient constrictive pericarditis(CP) is associated with a significantly higher erythrocyte sedimentation rate than its counterpart, persistent pericarditis, is consistent with the hypothesis that, in the former disorder, an active inflammatory process is at play, which might be responsive to corticosteroid therapy, whereas, in the latter context, irreversiible pericardial fibrosis or even pericardial calcification might have become firmly established.
    This hypothesis can be tested in a disorder such as IgG4-related constrictive pericarditis, where corticosteroids are the only treatment modality available. In IgG4-related CP the disease spectrum includes, at one extreme,, effusive-constrictive pericarditis without pericardial calcification(1), and, at the other extreme, CP with pericardial calcification(2).In between, there may be gradations of acute inflammatory response..
    The 79-year old man with IgG4-related effusive CP reported by Yuriditsky et al had stigmata of CP identified by simultaneous left and right-sided catheterisation. He had an initially good response to corticostroids, characterised by good diuresis over the course of 10 days. However, he had a subsequent relapse, and was eventually treated by pericardiectomy(1).
    By contrast, the 29 year old woman with IgG4-related CP reported by Sekigushi et al had a consistently good response to corticosteroids. In her case, as well, there was no pericardial calcification. E...

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  • A more complete description of the deficit in knowledge

    For the sake of completeness, the evaluation of the deficit in knowledge and awareness and treatment of hypertension (1) should include an inquiry about two issues that are fundamental to the relationship between hypertension and stroke. For those issues to be addressed, the questionnaire should include the following items:-
    (i)Did you ever have your blood pressure taken in both arms?
    (ii)When you commenced antihypertensive treatment did you and your doctor agree on a "goal" blood pressure?
    The rationale for those two lines of inquiry is the following:-
    According to one meta analysis(10 cohorts; 13,317 patients) interarm blood pressure difference > 15 mm Hg is associated with a significant Cox stratified adjusted hazard ratio for subsequent stroke(hazard ratio, 2.42: 95% Confidence Interval, 1.27-4.60; p < 0.01) (2).
    Furthermore, antihypertensive medication should be titrated against the higher of the two inter arm blood pressure measurements otherwise the patient will run the risk of suboptimal drug dosing and the risk of missed diagnosis of resistant hypertension.
    A mutually agreed "goal" blood pressure should be specified from the outset otherwise there will be a risk of insidious onset of "physician inertia" which could contribute to the subsequent development of stroke.
    Younger patients have the most o gain from an ambitious "goal " blood pressure which sets the target...

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  • Next frontier is inclusion of high-grade carotid artery stenosis in the CHA2DS2 Vasc score

    A corollary to the recommendation for anticoagulant persistence is a recognition that the time is long overdue for inclusion of evaluation of the extracranial carotid artery for evidence of high grade(ie >50 occlusion) carotid artery stenosis(CAS). The following is the rationale for the latter recommendation:-
    Among patients aged > 70 high-grade CAS has a prevalence of 12% among men and 11% among women(1).
    A systematic review of 9 studies(2611 patients) reporting presumed pathophysiological stroke mechanisms in patients with nonvalvular atrial fibrillation(NVAF) disclosed that 11%-24% of patients with the association of stroke and NVAF have high-grade CAS(2).
    Some stroke patients with NVAF have high-grade CAS ipsilateral to the culprit cerebral infarct, implying an aetiological role for the CAS in the pathogenesis of the incident stroke(3).
    During the entire history of the CHA2DS2 Vasc score we have squandared the opportunity to include ultrasonography of the extracranial carotid artery in the routine work up of newly diagnosed patients with NVAF. This was a missed opportunity to identify CAS as the potential aetiological agent in the event of the occurrence of manifestations of symptomatic CAS such as amaurosis fugax, transient ischemic attack, or non disabling stroke.. Without prior knowledge of the status of the carotid arteries those manifestations might have been missed opportunities to implement strategies such as carotid arte...

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    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...

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  • Harnessing serum copeptin in asymptomatic severe aortic stenosis

    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:
    Firstly; copeptin elevation in patients with ASAS might help ide...

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  • Risk stratification using DEVI's score in pregnant women with RHD

    Dear Editor,

    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...

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  • What will be done to prevent someone else being harmed in the future

    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...

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