Mayank Agrawal

The myocardium supplied by a chronic total occlusion is a persistently ischemic zone

Well‐developed collaterals to a myocardial segment supplied by a chronic total occlusion (CTO) and/or left ventricular dysfunction in the CTO regions in patients with chronic stable angina suggest that severe ischemia is unlikely to be present. We evaluated the presence and severity of ischemia using fractional flow reserve (FFR) of the myocardium supplied by a CTO in patients and compared the results with a non‐CTO control group.

Reversal of ischemia of donor artery myocardium after recanalization of a chronic total occlusion

Case reports have shown that an intermediate stenosis in the donor artery collateralizing the myocardium of a chronic total occlusion (CTO) can produce an ischemic fractional flow reserve (FFR) value which may revert to non‐ischemic with CTO revascularization.

Method of LDL Cholesterol Measurement Influences Classification of LDL Cholesterol Treatment Goals: Clinical Research Study

Background Low-density lipoprotein cholesterol (LDL-C) has been clearly associated with the risk of developing coronary heart disease. The best and most convenient method for determining LDL-C has come under increased scrutiny in recent years. We present comparisons of the Friedewald calculated LDL-C (C-LDL-C) and direct LDL-C (D-LDL-C) using 3 different homogenous assays. This highlights differences between the 2 methods of LDL-C measurement and how this affects the classification of samples into different LDL-C treatment goals as determined by the National Cholesterol Education Program Adult Treatment Panel III guidelines thus potentially affecting treatment strategies. Methods Lipid profiles of a total of 2208 clinic patients were retrieved from the Central Arkansas VA Healthcare System clinical laboratory database. Samples studied were of 1-week period during the 3 periods studied: 2000 (period 1), 2002 (period 2), and 2005 (period 3). Different homogenous assays for D-LDL-C measurement were used for each of the 3 periods. Results There is a fundamental disagreement between D-LDL-C and C-LDL-C, although Pearson correlation coefficients are 0.93, 0.97, and 0.98 for periods 1, 2, and 3, respectively. Using the model for period 1, when C-LDL-C is 70 mg/dL, the predicted D-LDL-C is 95 mg/dL (36% higher). The differences between C-LDL-C and predicted D-LDL-C progressively decrease at higher LDL-C cut points. In the assay used in period 3, there are 290 samples with D-LDL-C values between 100 and 130 mg/dL. Of these, only 182 samples show agreement with C-LDL-C values, whereas 90 samples with a D-LDL-C in the 100- to 130-mg/dL range are in the 70- to 100-mg/dL range using the C-LDL-C assay. Although the κ statistics suggests the LDL-C measures have relatively high levels of agreement, the significant generalized McNemar tests (P < 0.01) provide additional evidence of disagreement between C-LDL-C and D-LDL-C during all the 3 periods. Conclusions Our results highlight D-LDL-C measurements using 3 different assays during 3 different periods. In all assays, there is a substantial lack of agreement between D-LDL-C and C-LDL-C, which, in most cases, resulted in higher D-LDL-C values than C-LDL-C. This leads to clinically significant misclassification of patients LDL-C to a different LDL-C treatment goal, which would potentially result in more drug usage, thus exposing patients to more potential adverse effects and at a much greater cost with little evidence of benefit.

Use of Propranolol for Hypersexual Behavior in an Adolescent With Autism

Objective: To report a case of an adolescent with autism with clinically significant hypersexual behaviors in whom a trial of low-dose propranolol led to major clinical improvement. Case Summary: This case report describes a 13-year-old boy with a history of autism who presented to the outpatient psychiatric clinic for hypersexual behaviors that started at the onset of puberty. The behaviors affected his functioning both at school and home. A trial of low-dose propranolol, 0.3 mg/kg/d (10 mg twice a day), targeting hypersexual behavior led to remarkable clinical improvement. The behaviors remained stable on this dose of propranolol for 1 year. Discussion: Hypersexual behavior exhibited by adolescent patients with autism can be a big challenge to manage. The literature on pharmacological options to manage these behaviors in children and adolescents with autism is limited. Clinical data of propranolol use are novel. Conclusion: To our knowledge, this is the first case report of low-dose propranolol leading to clinically significant improvement in hypersexual behaviors in an adolescent with autism. Propranolol use may expand the choice of treatment option in this patient population.

Identification of provider characteristics influencing prescription of analgesics: a systematic literature review.

Pain is a comorbid and aggravating symptom that in many conditions can be perceived differently and should therefore be managed accordingly. Numerous factors, both social and cultural, are thought to influence the analgesic prescription. However, elucidation of such areas is limited. We therefore conducted a systematic literature review to test the hypothesis that variations in provider characteristics predict the prescription of pain medication.

Rebuttal: Response to letter by fan and colleagues regarding “impact on fractional flow reserve of donor artery by chronic total obstruction revascularization”

We appreciate the interest in our article by Dr Fan and colleagues regarding the first descriptive series of the effect of fractional flow reserve (FFR) change in a donor artery supplying collaterals to a chronic total occlusion (CTO) after it has been successfully revascularized [1]. In a cohort of 50 CTO patients undergoing successful PCI, this phenomenon was seen in 6 out of 14 patients (42%) with intermediate donor artery stenosis. Our data add support to previous case reports that the phenomenon of FFR reversal from [2–4] ischemic to non-ischemic may occur. We agree that the sample size in our study is relatively small but is the first series to describe the phenomenon and demonstrates that it is not unusual. From the physician and patient perspective, the major question is in patients with ischemic range FFR in donor artery with an intermediate stenosis and a CTO. Do these patients need to have revascularization in the intermediate stenosis as well as the CTO, only the intermediate donor stenosis, or only the CTO? In the DEFER trial [5], the intermediate stenosis with nonischemic FFR had a very low event rate (3%) at 5 years of follow-up. Based on this landmark trial, it seems preferable not to stent a stenosis with non-ischemic FFR. Our study demonstrates that this phenomenon may occur not infrequently if CTO recanalization is performed initially. Further, there are two studies looking at the longterm effects of CTO revascularization are under way (ClinicalTrials.gov: NCT01078051; NCT01760083), but results will not be available before 2015. Fan et al. [6] raises the question as to whether FFR in intermediate stenosis of the donor artery can worsen after CTO revascularization. Although we did not observe this result, we might speculate that if the donor artery was damaged either through the FFR wire itself or via its passage in a retrograde approach, with consequent worsening of donor artery obstruction, FFR would subsequently worsen. We recommend recanalization of a CTO when feasible in order to avoid unnecessary stenting in some cases of a donor artery.

Association of acute stent strut malapposition on long‐term outcomes

To the Editor, We read with great interest the CLI-OPCI substudy by Romagnoli et al. on the relationship between acute stent malapposition (ASM) by optical coherence tomography (OCT) and clinical outcomes [1]. The authors found that the severity of ASM, either measured as distance between strut and vessel wall or length of strut malapposition, was not related to long-term adverse events [major adverse cardiac events (MACE)] which included the combination of death, target vessel-MI (either periprocedural or long-term), and target lesion revascularization. These data add to other studies which have not shown a relationship between ASM and long-term outcomes. We have recently presented an OCT-based classification system of ASM (Table 1) based on adequacy of stent implantation and vessel anatomy [2]. We found, as in the study by Romagnoli et al, that ASM is frequent, occurring in 74.5% of all angiographically optimized stents, very similar to the current study wherein 72.3% of stents showed ASM. Of the five classes of ASM in our study, the most frequent cause of ASM was localized vessel enlargement, i.e. the stent deployment was adequate but the vessel had some degree of positive remodeling. With this ASM cause there was relatively small strut-to-wall malapposition distance and ASM vessel length. On the other hand, stent undersizing, defined as the nominal stent diameter being smaller than the proximal reference diameter and the proximal stent segment being malapposed, showed the greatest strut distance from the wall and length of strut malapposition. We have hypothesized that differences in outcome studies evaluating the relationship of ASM on long-term outcomes may be explained by different causes of ASM as reflected in our classification system. Our question to the authors is that if they limited their analysis of ASM to stent undersizing only, would there be a relationship between ASM and MACE? We understand that this analysis was not part of their original study but do believe that such an analysis would be edifying and might help to explain the heterogeneity in long-term outcomes previously reported. We thank the authors for an important contribution in understanding the significance of ASM to long-term outcomes and appreciate their consideration of our request.

Letter by Nairooz et al Regarding Article, “Improved Quality of Life After 1 Year With an Invasive Versus a Noninvasive Treatment Strategy in Claudicants: One-Year Results of the Invasive Revascularization or Not in Intermittent Claudication (IRONIC) Trial”

We read with great interest the article by Nordanstig et al.1 This randomized trial compared percutaneous and surgical revascularization with structured unsupervised exercise for claudication pain and peripheral artery disease. We commend the authors on their work. However, we believe the following issues should be clarified: 1. Comparison of percutaneous and surgical revascularization with unsupervised structured exercise program is of concern. The 2013 American Heart Association/American College of Cardiology guideline update states that the usefulness of unsupervised exercise programs is not well established as an effective initial treatment modality for intermittent claudication (class IIb), whereas supervised exercise training has a class I recommendation.2 …

WHAT ARE THE MECHANISMS OF STENT MALAPPOSITION? COMPREHENSIVE FREQUENCY DOMAIN OPTICAL COHERENCE TOMOGRAPHIC EVALUATION

Stent strut malapposition (M) is associated with adverse short-and long-term cardiac outcomes after stent deployment. Frequency domain optical coherence tomography (OCT) allows evaluation of strut-vessel interface due to its high axial resolution. We evaluated the frequency and causes of M in a ‘

Rebuttal: change in donor artery fractional flow reserve after recanalization of a chronic total occlusion-not as impressive as some might have us believe.

We appreciate the authors’ interest in our study and their agreement that the phenomenon we have described has importance in clinical management. A primary issue raised by the authors is whether the change in the fractional flow reserve (FFR) of the donor artery before and after successful percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) may be related to inherent variability of the FFR measurement at two different time points. Previous studies suggest that during a single procedure, there is high reproducibility of the FFR at different time points [1]. We suggest that changes in FFR are explained by other factors. FFR change after successful CTO PCI depends in part on the amount of viable myocardium in the area supplied by the CTO, the degree of preexisting microvascular dysfunction both in the CTO and donor artery territory, the resistance of the collateral vessels, and the donor lesion characteristics [2]. Based on differences in these factors, there might be expected differences in FFR after CTO PCI as illustrated in Fig. 1. The authors comment on the absence of any relation and claim the impact of a singular patient, but looking at the nicely plotted figure by the authors, there is again a singular patient that affects the correlation (patient with pre-procedural FFR of 0.76 and even a drop in post-procedure to 0.70 FFR. In an observational study based on small numbers, these individual outliers are an issue. Our report was not about a straight correlation, as this is not determined by FFR alone, but about the clinical caution required in assessing FFR without taking into account the role of collateral donor function. A second suggestion by the authors is that measuring donor vessel FFR after CTO PCI is a “luxury.” We cannot agree. Use of FFR for evaluation of an intermediate lesion is a class I indication in the European PCI guidelines and a class IIa recommendation in the American Fig. 1. A: CTO collateralized through a diffusely diseased donor artery with 50% angiographic stenosis. FFR is ischemic range in the donor artery. B: After successful recanalization of the CTO, there is only a slight increase in FFR because of diffuse disease in the artery with a superimposed focal narrowing. C: An identical angiographic situation exists in Panel C with an identical ischemic FFR value. D: After successful recanalization there is change in FFR to non-ischemic range because of less severe disease burden in the donor artery. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]