Tayo Addo

Myocardial Ischemia Induced by Rapid Atrial Pacing Causes Troponin T Release Detectable by a Highly Sensitive Assay : Insights From a Coronary Sinus Sampling Study

OBJECTIVES The purpose of this study was to assess whether: 1) very small increases in troponin T, measured by a new highly sensitive cardiac troponin T (hs-cTnT), may reflect ischemia without necrosis; and 2) serial changes can discriminate ischemia from other causes of cardiac troponin T (cTnT) release. BACKGROUND A new hs-cTnT assay offers greater sensitivity than current assays. METHODS Nineteen patients referred for diagnostic catheterization underwent cannulation of the coronary sinus (CS). Serial CS and peripheral plasma samples were obtained at multiple time points during and after incremental rapid atrial pacing. cTnT was quantified using both a standard and a pre-commercial highly sensitive assay. Ischemia was determined by the presence of significant coronary artery disease (CAD) and myocardial lactate release with pacing. RESULTS cTnT concentrations in CS blood increased from a median of 6.8 pg/ml prior to pacing to 15.6 pg/ml 60 min after termination of rapid atrial pacing (p < 0.0001), changes that were mirrored at 180 min in peripheral blood (5.1 to 11.8 pg/ml, p < 0.0001). Although peripheral cTnT concentrations tended to be higher at 180 min following pacing for patients with CAD and lactate elution (n = 7) when compared with those without either marker (n = 5) (25.0 pg/ml vs. 10.2 pg/ml, p = 0.10), relative (1.7-fold vs. 5.2-fold) and absolute (6.8 pg/ml vs. 8.8 pg/ml, p = 0.50) changes were not different between groups. CONCLUSIONS Brief periods of ischemia, without frank infarction, cause low-level cTnT release, and small increases are common after periods of increased myocardial work, even among patients without objective evidence of myocardial ischemia or obstructive CAD. Additional research is needed before hs-cTnT assays are widely adopted in the management of subjects with chest pain syndromes.

Continued Benefit From Paclitaxel-Eluting Compared With Bare-Metal Stent Implantation in Saphenous Vein Graft Lesions During Long-Term Follow-Up of the SOS (Stenting of Saphenous Vein Grafts) Trial

OBJECTIVES This study sought to report the long-term outcomes after drug-eluting stent (DES) implantation in saphenous vein graft (SVG) lesions in the SOS (Stenting of Saphenous Vein Grafts) trial. BACKGROUND The long-term outcomes after DES implantation in SVGs are poorly studied. Apart from the SOS trial, the only other randomized trial comparing DES with bare-metal stents (BMS) in SVGs reported higher mortality in the DES group at 32 months. METHODS In the SOS trial, 80 patients with 112 lesions in 88 SVGs were randomized to a BMS or paclitaxel-eluting stent (PES) and demonstrated improved short-term angiographic and clinical outcomes with PES. Extended clinical follow-up was subsequently obtained. RESULTS Mean age was 67 ± 9 years, and all patients were men. The indications for stenting included acute coronary syndrome in 60% and stable angina in 31% of patients. The mean SVG age was 12 ± 6 years. The baseline characteristics of the patients in the 2 study groups were similar. Procedural success was achieved in 77 patients (96%). During a median follow-up of 35 months, compared with patients randomized to BMS, those receiving PES had a lower incidence of myocardial infarction (hazard ratio [HR]: 0.32, p = 0.01), target lesion revascularization (HR: 0.20, p = 0.004), target vessel revascularization (HR: 0.41, p = 0.03), and target vessel failure (HR: 0.34, p = 0.001) as well as a trend toward less definite or probable stent thrombosis (HR: 0.15, p = 0.08). All-cause mortality (HR: 2.04, p = 0.19) and cardiac mortality (HR: 0.62, p = 0.51) did not differ between groups. CONCLUSIONS During long-term follow-up, use of PES was associated with significantly better clinical outcomes than BMS in SVG lesions. (Stenting of Saphenous Vein Grafts Trial [SOS]; NCT00247208).

Renal Production, Uptake, and Handling of Circulating αKlotho

αKlotho is a multifunctional protein highly expressed in the kidney. Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance. The role of the kidney in circulating αKlotho production and handling is incompletely understood, however. Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans. In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding. Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal to the apical side of the proximal tubule via transcytosis. Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasing αKlotho into the circulation and clearing αKlotho from the blood into the urinary lumen.

Pilot Trial of Cryoplasty or Conventional Balloon Post-Dilation of Nitinol Stents for Revascularization of Peripheral Arterial Segments: The COBRA Trial

OBJECTIVES The purpose of this study is to compare post-dilation strategies of nitinol self-expanding stents implanted in the superficial femoral artery of diabetic patients with peripheral arterial disease. BACKGROUND Endovascular treatment of superficial femoral artery disease with nitinol self-expanding stents is associated with high rates of in-stent restenosis in patients with diabetes mellitus. METHODS We conducted a prospective, multicenter, randomized, controlled clinical trial of diabetic patients to investigate whether post-dilation of superficial femoral artery nitinol self-expanding stents using a cryoplasty balloon reduces restenosis compared to a conventional balloon. Inclusion criteria included diabetes mellitus, symptomatic peripheral arterial disease, and superficial femoral artery lesions requiring implantation of stents>5 mm in diameter and >60 mm in length. Primary endpoint was binary restenosis at 12 months, defined as ≥2.5-fold increase in peak systolic velocity by duplex ultrasonography. RESULTS Seventy-four patients, with 90 stented superficial femoral artery lesions, were randomly assigned to post-dilation using cryoplasty (n=45 lesions) or conventional balloons (n=45 lesions). Mean lesion length was 148±98 mm, mean stented length was 190±116 mm, mean stent diameter was 6.1±0.4 mm, and 50% of the lesions were total occlusions. Post-dilation balloon diameters were 5.23±0.51 mm versus 5.51±0.72 mm in the cryoplasty and conventional balloon angioplasty groups, respectively (p=0.02). At 12 months, binary restenosis was significantly lower in the cryoplasty group (29.3% vs. 55.8%, p=0.01; odds ratio: 0.36, 95% confidence interval: 0.15 to 0.89). CONCLUSIONS Among diabetic patients undergoing implantation of nitinol self-expanding stents in the superficial femoral artery, post-dilation with cryoplasty balloon reduced binary restenosis compared to conventional balloon angioplasty. (Study Comparing Two Methods of Expanding Stents Placed in Legs of Diabetics With Peripheral Vascular Disease [COBRA]; NCT00827853).

Contemporary use of embolic protection devices in saphenous vein graft interventions: Insights from the stenting of saphenous vein grafts trial

Background: We sought to evaluate the contemporary use of embolic protection devices (EPDs) in saphenous vein graft (SVG) interventions. Methods: We examined EPD use in the stenting of saphenous vein grafts (SOS) trial, in which 80 patients with 112 lesions in 88 SVGs were randomized to a bare metal stent (39 patients, 43 grafts, and 55 lesions) or paclitaxel‐eluting stent (41 patients, 45 grafts, and 57 lesions). Results: An EPD was used in 60 of 112 lesions (54%). A Filterwire (Boston Scientific) was used in 70% of EPD‐treated lesions, Spider (ev3, Plymouth, Minnesota) in 12%, Proxis (St. Jude, Minneapolis, Minnesota) in 12%, and Guardwire (Medtronic, Santa Rosa, California) in 7%. Of the remaining 52 lesions, an EPD was not utilized in 13 lesions (25%) because the lesion was near the distal anastomosis, in 14 lesions (27%) because of an ostial location, in one lesion (2%) because of small SVG size, in two in‐stent restenosis lesions (4%) because of low distal embolization risk, and in 22 lesions (42%) because of operators preference even though use of an EPD was feasible. Procedural success was achieved in 77 patients (96%); in one patient a Filterwire was entrapped requiring emergency coronary bypass graft surgery and two patients had acute stent thrombosis. Conclusion: In spite of their proven efficacy, EPDs were utilized in approximately half of SVG interventions in the SOS trial. Availability of a proximal protection device could allow protection of ∼25% of unprotected lesions, yet operator discretion appears to be the major determinant of EPD use.

Systems-Based Improvement in Door-to-Balloon Times at a Large Urban Teaching Hospital A Follow-Up Study From Parkland Health and Hospital System

Background—Timely reperfusion in ST-segment elevation myocardial infarction (STEMI) patients improves clinical outcomes. Implementing strategies to target institutional-specific delays are crucial for improved patient care. Methods and Results—Using a novel strategy to analyze specific components of door-to-balloon time (DBT) at our institution, we previously identified several specific interval delays in our prior STEMI protocol. We then implemented 4 strategies to reduce DBT: (1) emergency department physician activation of the STEMI protocol; (2) “single call” broadcast paging of the STEMI team by the page operator; (3) immediate feedback to the emergency and cardiology departments with joint monthly quality improvement meetings; and (4) transfer of the off-hours STEMI patient directly to the laboratory on activation by an in-hospital team. After implementation of the new protocol, we examined each component time interval from the first 59 consecutive STEMI patients treated with the new protocol between March 2007 and June 2008 and compared time intervals with the previous 184 STEMI patients. Compared with the previous 184 STEMI patients, the median DBT of the subsequent 59 STEMI patients significantly improved from 125 to 86 minutes (P<0.0001). This improvement was largely driven by a decrease in the interval from the initial 12-lead ECG to activation of the on-call catheterization team (from 40 to 11 minutes, P<0.0001). Conclusions—After examining specific component delays in our institution’s DBT, we were able to successfully use quality improvement strategies to focus on specific sources of delay in our institution. This dramatically improved our median DBT toward the goal of achieving a guideline-recommended <90 minutes for all patients.

Prevalence and outcomes of intermediate saphenous vein graft lesions: Findings from the stenting of saphenous vein grafts randomized-controlled trial

BACKGROUND We sought to examine the prevalence and progression rate of intermediate saphenous vein graft (SVG) lesions in the Stenting Of Saphenous vein grafts (SOS) trial. METHODS The baseline and follow-up angiograms of 80 patients participating in the SOS trial were analyzed to determine the prevalence of intermediate (30-60% angiographic diameter stenosis) SVG lesions and their progression rate. RESULTS At least one intermediate SVG lesion was present in 31 of 143 (22%) SVGs in 27 of 80 (34%) patients. Most intermediate lesions were present in the SOS stented SVGs (20 grafts in 19 patients). During a median follow-up of 35 months, angiographic follow-up was available for 28 grafts in 25 patients. Progression (defined as percent diameter stenosis ≥ 70% but <100% at follow-up angiography) was seen in 11 of 28 SVGs (39%) in 11 of 25 patients (44%). Progression rate at 12, 24 and 36 months was 28% and 47% and 84%, respectively. Seven of 11 patients (64%) with intermediate SVG lesion progression presented with an acute coronary syndrome and 8 (73%) underwent PCI. Four of the 28 grafts with intermediate lesions at baseline were 100% occluded at follow-up; all of those SVGs had received a stent in another location in the SVG as part of the SOS trial. CONCLUSIONS Intermediate SVG lesions are common in patients undergoing SVG stenting, have high rates of progression and frequently present with an acute coronary syndrome. Further study of pharmacologic and mechanical treatments to prevent progression of these lesions is needed.

Clinical outcomes following predilation with a novel 1.25-mm diameter angioplasty catheter†

Objective: An unmet need is represented in angioplasty catheters that permit the predilation stage of treating complex coronary anatomy oftentimes not amenable to conventional device therapies. Background: Lesion preparation with balloon angioplasty prior to stent placement remains the most common method of percutaneous coronary revascularization. Methods: Clinical and angiographic outcomes were evaluated following a treatment strategy of coronary artery disease that included predilation with a low‐profile, 1.25‐mm angioplasty catheter prior to stent placement. The study primary end point of procedural success was defined as successful device delivery and lesion treatment, including the absence of clinically significant perforation, arrhythmia, flow‐limiting dissection, or reduction in baseline Thrombolysis In Myocardial Infarction (TIMI) grade with final achievement of TIMI 3 flow. Results: Among 51 patients (54 lesions), predilation using a 1.25 mm angioplasty catheter was associated with procedural and device‐related success rates of 100%. In‐hospital target lesion failure occurred in one patient (2.0%) related to postprocedural myocardial infarction. Patient and angiographic characteristics included diabetes, 43.1%; lesion length ≥20 mm, 20.4%; bifurcation lesion, 31.5%; lesion classification B2/C, 74.1%; and baseline TIMI 0/1 flow, 13.0%. No subsequent in‐hospital adverse events occurred. Conclusions: Percutaneous coronary revascularization involving a predilation strategy with a low profile, 1.25‐mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective initial treatment for complex coronary anatomy.

Optical coherence tomography findings after chronic total occlusion interventions: Insights from the “AngiographiC evaluation of the everolimus-eluting stent in chronic Total occlusions” (ACE-CTO) study (NCT01012869)

BACKGROUND There is limited information on optical coherence tomography (OCT) findings after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs). OCT allows high resolution imaging that can enhance understanding of the vascular response after stenting of chronically occluded vessels. METHODS The Angiographic Evaluation of the Everolimus-Eluting Stent in Chronic Total Occlusions (ACE-CTO) study collected angiographic and clinical outcomes from 100 patients undergoing CTO PCI with the everolimus-eluting stent (EES). OCT was performed 8-months post stenting in 62 patients. Every third frame was analyzed throughout the course of the stented arterial segment. Lumen contours were semi-automatically traced and stent struts were manually delineated, with automatic measurement of the strut to lumen distance. Struts on the luminal side of the lumen contour were classified as malapposed if the distance to the lumen contour exceeded 0.108mm. RESULTS A total of 44,450 struts in 6047 frames were analyzed, of which 4113 9.3%, 95% confidence intervals [CI] 9.0% to 9.5%) were malapposed and 1230 (2.8%, 95% CI 2.6% to 2.9%) were uncovered. Fifty-five of 62 patients (88.7%, 95% CI 78.5% to 98.4%) had at least one malapposed stent strut and 50 patients (80.7%, 95% CI 69.2% to 88.6%) had at least one uncovered stent strut. Mean strut-intimal thickness of the apposed and malapposed struts was 0.126±0.140mm and -0.491±0.440mm, respectively. CONCLUSION High rates of stent strut malapposition and incomplete stent strut coverage were observed after CTO PCI using EES, highlighting unique challenges associated with stent implantation in CTOs.

Association between low ankle-brachial index and accelerometer-derived sedentary and exercise time in the asymptomatic general population:

Sedentary behavior is an adverse health risk factor that is independent of physical activity. The relationship between sedentary behavior, exercise activity and the ankle-brachial index (ABI) is not well understood. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004. Accelerometer data were used to quantify exercise and sedentary time for each participant. A low ABI was defined as a value <1.0 (including borderline values). Multi-variable adjusted logistic regression analyses were performed with sedentary and exercise times as independent variables, adjusting for important confounders. There were 1443 asymptomatic participants (mean age 61 years, 49% female, 55% current/prior smokers) with mean daily sedentary and exercise times of 454±144 and 18±20 minutes, respectively. Of the participants, 23% had an ABI <1.0 (8.7% with ABI <0.9). Sedentary time was positively associated with a low ABI (odds ratio [OR] 1.22 per 1 standard deviation [SD], [95% confidence interval (CI), 1.03–1.43]; p=0.02) while exercise time was inversely associated with a low ABI (OR 0.71 per 1 SD, [95% CI, 0.57–0.89]; p=0.003). Sedentary time is associated with low ABI values in the asymptomatic population. This association appears to be independent of exercise time and warrants further investigation.