13 e-Letters

published between 2017 and 2020

  • Maintain sharp vigilance on adverse reactions of ivermectin

    To the Editor:
    We read with great interest the editorial by Dr. James J DiNicolantonio and colleagues.1 In their editorial, the authors have expressed their opinions that ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19. However, we want to highlight some concerns about the use of ivermectin for late-stage COVID-19.
    First, we do agree with the authors that ivermectin can be a potential drug for late-stage COVID-19 considering its anti-inflammatory effects. The authors stated that it is reasonable to suspect that, in doses at or modestly above the standard clinical dose, ivermectin may have important clinical potential for managing disorders associated with life-threatening respiratory distress and cytokine storm—such as advanced COVID-19.
    Second, a usual dose or modestly above the standard clinical dose of ivermectin may induce neurologic disorders, which can be fatal.2 Encephalopathy and coma are well-known side effects of ivermectin treatment in animals. But few cases of neurologic disorders after ivermectin treatment have been reported in humans.3 Neurologic disorders may include coma, ataxia, pyramidal signs, and binocular diplopia. Thus, the seriousness of the adverse reaction in humans implies that caution is warranted regarding medical prescriptions of ivermectin.
    We declare no competing interests.
    Contributors: All authors contributed to the final manuscript.

    Funding: The authors have...

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  • The Impact of Daylight Savings Time Change on the Incidence of Percutaneous Coronary Intervention for Acute Myocardial Infarction

    Five years ago, our group at the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) published an analysis exploring the impact of day light saving time (DST) changes on the state -wide volume of percutaneous coronary intervention in patients presenting with acute myocardial infarction (AMI-PCI) in the weekdays following the time change.1 Using data from our clinical registry reflecting all PCIs performed at non-Federal hospitals throughout Michigan between 1/1/2010 and 9/15/2013, we identified a significant increase in AMI-PCI on Mondays following the Spring DST change (RR = 1.24, p = 0.011), and a significant reduction in cases on Tuesdays following fall DST changes (RR = 0.79, p = 0.044), adjusting for seasonal and weekday effects, and for an overall time trend. We have now repeated the analysis using registry data for the subsequent 5 ½ years, from 9/16/2013 – 3/31/2019 using the same methodology and obtained results inconsistent with our prior publication. In our analysis of more recent data, both of the previously reported effects were substantially attenuated and are no longer statistically significant (Spring Monday after change: RR = 1.095, p = 0.207; Fall Tuesday after change: RR = 0.96, p = 0.553). Our prior publication garnered a great deal of attention in the popular media2,3, often with alarming, sensational headlines. It has also been included in meta-analysis along with other publications identifying a similar Spring time change effect4...

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  • Aortic Inflammation and Calcification in Abdominal Aortic Aneurysmal Disease

    The prospective matched-cohort study by Joshi et al., investigated inflammation in both AAA and atherosclerosis using 18-FDG PET to generate non-invasive imaging biomarkers for aneurysm expansion and destabilization[1]. Such work is of great importance as atherosclerosis and AAA often co-exist and share many of the same underlying risk factors and pathologies including vascular inflammation and calcification. However, the magnitude and distribution of these processes both locally and globally were not previously investigated and could provide novel insight into AAA progression.

    It was shown that asymptomatic aortic aneurysms had greater inflammatory activity not only in the aneurysmal region but also throughout the entire aorta when compared to the atherosclerotic cohort. This diffuse inflammation of the aorta in AAA patients is supported by our ongoing work investigating the role of the aneurysm in affecting systemic endothelial change. This is assessed by measuring the flow-mediated dilatation (FMD) of the brachial artery [2, 3]. FMD decreases with increased maximum diameter of the aneurysmal sac and reverses following surgical intervention. This suggests that the local aneurysm itself to be a nidus of stimulus for inciting global change during the aneurysm’s natural history[4].

    Furthermore, they show that aneurysms with intra-luminal thrombi (ILT) demonstrated lower 18-FDG uptake both within the thrombus and in the adjacent aortic wall. Here, the authors...

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  • Final kissing balloon inflation and proximal optimization technique should be performed in true bifurcation lesions with large side branch

    Dear editor,
    I have read with great interest the results of nordic baltic bifurcation study-4 by Kumsar et al (1), in which study clinical outcomes after treatment of lesions in large bifurcations by simple or complex stent implantation were compared. In the 6-month results of this study, compared to the provisional method, a decrease in major adverse cardiac event (MACE) was observed in the complex group, although it was not statistically significant. Again, in the comparison of the 2-year results, no difference was observed between the two groups. The fact that complex stenting is not found to be superior to simple stenting for true bifurcation lesions with such a wide side branch can be due to several reasons:
    1- All patients did not receive a final kissing balloon inflation (FKBI). It is well known that the FKBI should be performed in two-stenting techniques for full treatment of the true bifurcation lesion. In addition, why was the high rate of FKBI application required in simple stenting? It is well known that in simple stenting, POT should be used instead of FKBI unless the there is a TIMI flow <3, and / or a dissection in the side branch (2).
    2- Interestingly, no proximal optimization technique (POT) was used in any patient. In any complex two-stent technique without POT, the lesion is not considered to be truly treated (3,4). I think this is the most important limitation of the study. POT provides optimal positioning of the main vascular ste...

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  • How negative results can become positive ones

    The authors of the metanalysis "Pharmacological interventions for the prevention of contrast-induced acute kidney injury in high-risk adult patients undergoing coronary angiography: a systematic review and meta-analysis of randomised controlled trials" conclude that "several drugs are renoprotective in patients with CKD [...] the evidence is strongest for NAC".
    This conclusion is at odds with previous research and metanalyses. The same authors report 10 papers (over a total of 27) which show potentially harmful effects of NAC (OR >1). Furthermore, the paper they cite with the largest sample size (by Weisbord et al, n>2000) does not show any beneficial effect of NAC. Notwithstanding these data, the authors "recommend that NAC should be used when a high dose of contrast is anticipated". I believe the readers should be aware about the poor evidence supporting this conclusion.
    NAC is a well-tolerated substance and, clearly, its use is unlikely to represent harm for patients (even though 1/3 of the studies reported by the authors would suggest that some negative effect might exist). Therefore, the main reason for its recommendation is its anxiolytic effect on physicians, who are convinced to use a "renoprotective" drug.

  • What about aspirin use during training?

    The arguments for using pre- race aspirin for cardio protection are quite tenable and strong. But since many cardiac arrests occur in the training period, are we to advise aspirin during training period too?

  • Unanswered Questions

    In his response to my CardioBrief blog post (http://www.cardiobrief.org/2017/09/11/julio-palmaz-really-doesnt-want-yo...) Juan Granada implies that my article was neither factual, nor accurate, nor professional. However, at no point does Granada give examples backing his assertions.

    Granada neglects to mention that prior to publication of my blog post I had emailed him, offering him the opportunity to clarify or respond to the questions I raised prior to publication and to prevent any misunderstanding. Granada did not respond to my emails. In fact, after I emailed my questions to Granada I received a “cease-and-desist” letter from Julio Palmaz's attorneys. Is this his idea of "very high ethical and academic standards”?

    In his statement Granada also fails to address the differences between the listing of the study on ClinicalTrials.Org (https://clinicaltrials.gov/ct2/show/record/NCT02759406), in which the stents are described as Palmaz stents, and the Open Heart publication, in which they are described as Abbott stents. This discrepancy may, potentially, raise troubling issues, including questions about the IRB evaluation of the study and how the study was described to potential subjects during the informed consent process. Granada also offers no explanation for the discrepanc...

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  • The effect of linoleic acid on coronary heart disease may be increased coagulation rather than oxidation

    We agree with DiNicolantonio´s and O´Keefe´s hypothesis that a high intake of omega-6 vegetable oils may promote coronary heart disease (CHD).1 However, we think that the mechanism is not oxidation of LDL-cholesterol (LDL-C). It is a solidly documented but little-known fact that LDL partake in the immune system by adhering to and inactivating almost all types of microorganisms.2 As the LDL-covered microorganisms are oxidized after having been taken up by macrophages, we think that the oxidation of LDL is a secondary phenomenon. The crucial event is most likely, as explained in our papers,2,3 that complexes of LDL-covered microorganisms may aggregate, in particular in the presence of
    hyperhomocysteinemia, because homocysteine thiolactone causes aggregation and precipitation of thiolated LDL. Because of the high extra-capillary tissue pressure, aggregates of such complexes may be trapped in vasa vasorum of the major arteries and result in ischemia of the arterial wall. The reason why omega-6 oils promote CHD may be that these oils may result in increased coagulation,4 which is a well-known risk factor for CHD, even among individuals with familial hypercholesterolemia.5

    1. DiNicolantonio JJ, O’Keefe JH. Omega-6 vegetable oils as a driver of coronary heart
    disease: the oxidized linoleic acid hypothesis. Open Heart 2018;5:e000898. doi:10.1136/openhrt-2018-000898
    2. Ravnskov U, McCully KS. Vulnerable plaque formation from obstruction of...

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  • Response to CardioBrief blog post

    Clinical practice has been historically driven by evidence-based medicine. Properly sized randomized controlled trials have been the basis of accepting or rejecting research hypotheses, and clinical guidelines are developed based on data reported in such trials. Clinical research is not perfect. However, most clinical trials are conducted in a highly regulated environment and accepted for publication following a strict peer review process led by independent experts. While limitations exist in conducting and reporting clinical trials, investigators are judged at very high ethical and academic standards.

    A blog posted on September 11, 2017[1] questioned the integrity of the data and ethical conduct of the investigators of this study published in Open Heart. Due to the respect I have for the editor and this journal, I am obliged to respond on behalf of the authors.

    First, I did not receive ANY type of financial compensation as the principal investigator for this study. Second, no financial obligations or equity arrangements exist between the sponsor of the study, myself or my current Institution. Third, although all financial disclosures of all authors were properly disclosed to the journal at the time of submission, they were unfortunately not included in the final published article and therefore published subsequently as a correction[2]. Fourth, the objective of the study was to assess the 3-week healing properties of a surface-modified stent. The patient wi...

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  • The long and the short of it

    Lee et al in trying to define the accuracy of one method illustrate the huge weakness in echo vs MRI comparative data. First and foremost neither FAC or TAPSE correlated that well with RVEF ( FAC only slightly better) although statistically significant this difference is clinically of negligible importance. Secondly in assuming that MRI provides a gold standard for RVEF. As with echo there are strengths and weaknesses of MRI. On is the rather lower sensitivity to long axis abnormalities because ventricular volumes are usually defined using the short axis plane. So a reduced correlation between a purely long axis technique, a moderate correlation with a technique that has both long and short axis components and one which is defined using predominantly radial function is entirely to be expected. Long axis dysfunction is usually the first sign of ventricular deterioration with short axis hyperactivity to compensate - exactly the example cited post cardiac surgery. Finally in their conclusions they state that FAC provides a better guide to RV systolic function. This is not justified - what it does do is provide a slightly better estimate of RVEF -these two are not synonymous. So as there are no clinical correlates - prognosis, symptoms, exercise performance, hospitalisations , the comparison between the techniques tells us nothing we did not already know - all methods of defining systolic function are different - we have not answered which one is best.