eLetters

72 e-Letters

published between 2018 and 2021

  • LARGER RANDOMIZED CONTROLLED TRIALS (RCT)

    Dear Editor,
    we thank you for your recent Editorial (1) that gives a balanced and useful view of the use of anti-interleukin1 agents for the treatment of recurrent pericarditis (2). As it is common, the authors conclude that “however, larger RCT data are required for further validation of the efficacy and safety of these novel medications in the treatment of recurrent pericarditis.” Here there is a technical issue, that sometimes may be not well appreciated. One of the first step in planning a RCT is to calculate the sample size. The point is that RCT that will randomize subjects to anti-IL 1 agents vs placebo will never be large, and will always include a small number of subjects, as compared to sample sizes common in other fields of cardiology, simply given the large treatment effect; for this reason is not ethical to randomize higher number of subjects. The calculated sample sizes are relatively small only due to the expected extremely high efficacy: e.g. the per protocol calculated sample sizes were 20 subjects in the AIRTRIP trial (3) and 56 in the RHAPSOSY trial (4). In practice we will never have “large” RCT on this topic, because these agents are expected to be so effective that the calculated sample sizes will be always small.

    1. Anthony C, Collier P. Anti-interleukin-1 for recurrent pericarditis; maybe a fix (but prior studies do not really mix). Heart. 2021 May 10:heartjnl-2021-319282. doi: 10.1136/heartjnl-2021-319282. Online ahead of print.

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  • Response to: “Pregnancy outcomes in women with a systemic right ventricle and transposition of the great arteries results from the ESC-EORP Registry of Pregnancy and Cardiac disease (ROPAC) by Tutarel et al.

    We read with great interest the recent results from ESC-EORP
    Registry of Pregnancy and Cardiac disease (ROPAC), concerning pregnancy.
    outcomes in women with systemic right ventricle (sRV) and transposition of the
    great arteries (TGA) by Tutarel et al. (1) In Tutarel et al. analysis HF was the
    most frequent maternal complication (9.1%). These results are concordant
    with our previous observations of 24 pregnancies of women with TGA after
    atrial switch operation and matched non-pregnant controls with TGA after atrial
    redirection. 2 In our series 2 women deteriorated from the functional NYHA
    class I to II after the first pregnancy and one woman in her fourth pregnancy
    deteriorated from class I to III. Tutarel’s results reinforce our conclusion that,
    from a cardiologist’s point of view, pregnancy after the Mustard/Senning
    operation was relatively well-tolerated and safe.
    In ROPAC study the information on tricuspid regurgitation (TR) was collected, but was
    not mandatory. Therefore Tutarel et al. concluded that dedicated studies focusing on
    sRV function and TR are warranted. Our dataset provided relevant information
    on sRV and TR. At baseline, all women had preserved or only mildly reduced
    sRV function estimated by echocardiography before pregnancy and absent or
    mild TR. There were no differences between non-pregnant matched controls
    and pregnant women in sRV function, deg...

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  • The rationale for the proposed beneficial effect of SGLT2 inhibitors in diastolic heart failure and in mitigating the risk of occurrence of atrial fibrillation

    The observation that SGLT-2 inhibitors might favourably modify the natural history of heart failure with preserved ejection fraction(HFpEF) and might also mitigate the risk of onset of atrial fibrillation(AF)(1) might have, as its rationale, the fact that both disorders are characterised by the presence of myocardial fibrosis, the latter a probable consequence of an obesity-related proinflammatory cascade which is potentially amenable to mitigation by SGLT-2 inhibitor therapy.
    Adipose tissue is a source of proinflammatory cytokines such as tumor necrosis factor-alpha(TNF-alpha), Interleukin 1(IL-1), and Interleukin 6(IL-6), all three of which are secreted in increased amounts in response to obesity(2). Accordingly the presence of myocardial fibrosis either in the atria or in the ventricles might be the end result of a proinflammatory cascade originating in adipose tissue. Atrial fibrosis has been documented in obese subjects(body mass index > 30 kg/metre squared) who do not have AF(3) and and also in subjects who have established AF(4). In the former category there are, arguably, some individuals who will subsequently develop AF.
    The relevance of SGLT-2 inhibitors to the association of myocardial fibrosis and either HFpEF or AF has emerged from the study which showed an anti-inflammatory effect of SGLT2 inhibitor therapy in the normoglycemic rabbit model of atherosclerosis. In that study the inflammatory content of atherosclerotic plaqu...

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  • Bacterial, mycobacterial, and fungal co-infection involving the pericardium or myocardium in rheumatological disordersa

    For the sake of completeness, the cardiac manifestations of rheumatological disorders documented by Sen et al(1) also ought to include bacterial as well as mycobacterial and fungal infections which invade either the pericardium or the myocardium in patients with rheumatological disorders. The following are some examples:-
    Suppurative pericarditis attributable to Staphylococcus aureus was documented by Huskisson et al in one of the patients in their series of 12 rheumatiod arthritis(RA) patients with severe , unusual and recurrent infections(2). A massive tuberculous plericardial effusion was documented in a 60 year old man with long-standing RA who was not taking any immunosuppressive medication(3).
    Staphylococcal pericarditis was reported in a 52 year old woman with systemic lupus erythematosus(SLE) who was on prednisolone(4). Tuberculous pericarditis coexisted with SLE in 3 patients who were participants in a series consisting of 72 SLE patients with coexisting active tuberculosis infection(5).
    Eosinophilic granulomatosis with polyangiitis was the underlying rheumatological disorder in a 60 year old woman who died after experiencing complications of congestive heart failure. Autopsy examination revealed invasive myocarditis secondary to Aspergillus fumigatus infection as well as multiple myocardial abscesses(6).
    Comment
    In the context of multisystem rheumatological disease the expectation is that the occurrence of pericarditis a...

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  • maximising opportunistic screening and maximising "goal" blood pressure

    The management of hypertension generates huge opportunities for opportunistic screening for atrial fibrillation(AF). To maximise that opportunity documentation of regularity of the pulse and, hence, for AF, should be routine at each visit to primary care or to secondary care. Furthermore, that should be the routine during follow up visits of patients with known hypertension. The rationale is that hypertension is a recognised risk factor for incident AF(1), and for progression of paroxysmal AF to permanent AF(2). thereby mandating a recognition that patients with known hypertension should be allocated to a high risk subgroup in whom opportunistic screening for AF should be maximised. There are opportunities for AF screening even with home blood pressure measurement. Some self blood pressure measuring devices trigger an alert when there is an irregularity in the pulse. Patients should be educated to inform their doctor when such alerts occur so that the patient can be evaluated further by electrocardiography.
    The treatment phase of hypertension addresses the challenge of atrial fibrillation by mitigating the risk of new onset development of that arrhythmia. Using data from SPRINT(Systolic Blood Pressure Intervention Trial) Soliman et al showed that intensive blood pressure lowering to a systolic blood pressure of < 120 mm Hg was associated with a 26% lower risk of developing new AF(hazard ratio, 0.74[95% Confidence Interval, 0.56-0.98]; P=0.37(3). What n...

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  • 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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