Joel P. Giblett

Direct stenting is an independent predictor of improved survival in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction

Aims: Randomised trials have shown that direct stenting (DS) is associated with improved markers of reperfusion during primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI). However, data evaluating its impact on long-term clinical outcomes are lacking. We set out to evaluate the effect of DS on mortality in a contemporary population of patients undergoing PPCI for STEMI. Methods: Consecutive patients undergoing PPCI for STEMI at two high-volume UK heart attack centres between September 2008– December 2010 (n=1562) were included in the analysis. Local databases were analysed for patient demographics, as well as details on PPCI strategy, including use of DS versus predilatation (PD) followed by stenting, manual thrombus aspiration (MT) and glycoprotein IIb/IIIa inhibitors (GPIs). National databases were interrogated for in-hospital, 30-day and one-year mortality. To determine the impact of PPCI strategy on one-year survival, multivariate logistic analysis was performed. Results: Altogether 489 patients underwent DS (31.3%) and 1073 (68.7%) received PD prior to stenting. Patients receiving DS had reduced mortality at 30 days (2.04 versus 4.66%, p=0.01) and one year (3.27 versus 8.48%, p=0.0001). After multivariate adjustment, PD remained an independent predictor of one-year mortality (odds ratio 2.42, 95% confidence interval 1.08–5.45, p=0.032) along with age, cardiogenic shock, number of diseased vessels, and left main or proximal left anterior descending artery intervention. However, neither GPI use nor MT improved survival in either univariate or multivariate analyses. Conclusions: In a contemporary, unselected population of patients undergoing PPCI for STEMI, DS – when compared with stenting after PD – is independently predictive of improved 30-day and one-year survival.

Cardioprotection for percutaneous coronary intervention — Reperfusion quality as well as quantity

Ischaemia-reperfusion (IR) injury is an important cause of myocardial damage during percutaneous coronary intervention (PCI). There are few therapies in widespread clinical use which impact on IR injury and it remains an important and underutilized target for treatment in acute myocardial infarction. This review will examine the translational scientific evidence for ischaemic conditioning and pharmacological agents including conditioning mimetics such as cyclosporine, anti-inflammatory agents, and those which modify myocardial glucose metabolism. We will address the reasons why many trials have failed to demonstrate clinical benefit and emphasize the need to deliver the right therapy to the right patient, at the right time to achieve successful translation of cardioprotection from bench-to-bedside. We critique trial design and offer advice for future translational trials in the field to ensure that effective treatments can be demonstrated clinically to improve patient outcomes during PCI.

Implantation of bioresorbable vascular scaffolds following acute coronary syndrome is associated with reduced early neointimal growth and strut coverage.

AIMS Registry data have suggested higher than anticipated rates of scaffold thrombosis following bioresorbable vascular scaffold (BVS) implantation. We examined early neointimal growth and strut coverage in BVS to ascertain whether this was affected by clinical presentation. METHODS AND RESULTS Patients undergoing optical coherence tomography (OCT)-guided BVS implantation, either for stable angina (SA) or acute coronary syndrome (ACS), were recruited to this observational study. Repeat OCT was performed at follow-up (median 74 days), and scaffolds analysed at 1 mm longitudinal intervals for scaffold/flow area, scaffold apposition, neointimal growth and strut coverage. Twenty-nine BVS were included in the analysis (62% implanted following ACS). There were no differences in baseline patient/lesion characteristics. All BVS achieved >90% predicted scaffold area with only 1.64% of struts classified as incompletely apposed, compared with 0.47% at follow-up (p=0.006). Reductions in mean scaffold (-4.0%, p=0.01) and flow (-8.4%, p<0.001) areas were observed at follow-up, with larger reductions in mean flow area in stable patients (-14.5±14.2 vs. -4.9±7.9%, p=0.03). ACS patients had reduced neointimal growth (0.51±0.18 vs. 0.87±0.37 mm2, p=0.002), and increased percentage of uncovered struts (2.68±1.67 vs. 1.43±0.87%, p=0.015). CONCLUSIONS Early neointimal growth and strut coverage are reduced following ACS in patients receiving BVS. These results may, in part, explain the high rates of ST in registry data.

Glucagon-Like Peptide-1: A Promising Agent for Cardioprotection During Myocardial Ischemia

Summary Glucagon-like peptide-1-(7-36) amide (GLP-1) is a human incretin hormone responsible for the release of insulin in response to food. Pre-clinical and human physiological studies have demonstrated cardioprotection from ischemia-reperfusion injury. It can reduce infarct size, ischemic left ventricular dysfunction, and myocardial stunning. GLP-1 receptor agonists have also been shown to reduce infarct size in myocardial infarction. The mechanism through which this protection occurs is uncertain but may include hijacking the subcellular pathways of ischemic preconditioning, modulation of myocardial metabolism, and hemodynamic effects including peripheral, pulmonary, and coronary vasodilatation. This review will assess the evidence for each of these mechanisms in turn. Challenges remain in successfully translating cardioprotective interventions from bench-to-bedside. The window of cardioprotection is short and timing of cardioprotection in the appropriate clinical setting is critically important. We will emphasize the need for high-quality, well-designed research to evaluate GLP-1 as a cardioprotective agent for use in real-world practice.

Remote Ischemic Conditioning in Elective PCI

This review examines the rationale for using remote ischemic conditioning (RIC) in elective percutaneous coronary intervention (PCI) to prevent procedure-related ischemia–reperfusion injury and justifies the importance of periprocedural biomarker elevation following elective PCI as a valid target for RIC. We review the evidence for the use of RIC as a treatment in this setting and document the salutary rules that must be followed to successfully translate RIC for clinical benefit.

Letter in response to glucagon-like peptide-1 mediates cardioprotection by remote ischaemic conditioning

We read with interest the study by Basalay et al 1 recently published in Cardiovascular Research investigating the mechanism of remote ischaemic conditioning (RIc) signalling. Whilst the results are intriguing, a number of unresolved issues remain when considering RIc in humans. First, the authors state that Glucagon-like Peptide 1 (GLP-1) had a protective effect against ischaemia-reperfusion injury in humans. It is noteworthy that the cardioprotective effect of GLP-1 in humans is …

Letter by Giblett and Hoole Regarding Article, “Remote Ischemic Postconditioning During Percutaneous Coronary Interventions: Remote Ischemic Postconditioning-Percutaneous Coronary Intervention Randomized Trial”

We read with interest the article written by Lavi et al.1 However, we are concerned that there seem to be several limitations in their methodological design that may have led to the failure of their remote postconditioning trial to show benefit in elective percutaneous coronary intervention. The first is that by the time the threshold for conditioning was met, the window …

Optical Coherence Tomography Guided Percutaneous Coronary Intervention

Optical coherence tomography (OCT) is an increasingly available intracoronary imaging modality that provides high-resolution imaging of coronary arteries. Its fundamental reliance on the emission and reflection of light enables rapid data acquisition without compromise of image resolution. As such, OCT can inform operators planning percutaneous coronary intervention (PCI) by accurately defining luminal geometry and detailing plaque composition. Following PCI, OCT imaging delivers a thorough assessment of the treated arterial segment and can identify specific features not always visible on alternate imaging modalities, including stent edge-related dissection, plaque tissue prolapse, incomplete stent apposition and the presence of intra-coronary thrombus. Clinical trials highlight that procedural strategy is frequently altered based on OCT findings, while concerns over final stent dimensions have been mitigated through use of a sizing protocol based on external elastic lamina dimensions in the reference arterial segment. Randomised trials are now warranted to definitively ascertain whether OCT-guidance improves clinical outcomes when utilised during PCI.

Early disarticulation of a bioresorbable vascular scaffold: an underreported consequence of repeat imaging

A 54 year-old male presented with a non ST-elevation myocardial infarction. Coronary angiography revealed significant stenoses in the proximal left anterior descending (LAD) and circumflex arteries. The LAD lesion had only mild calcification and was not tortuous. It was 1:1 (balloon:vessel) pre-dilated and a 3.5 9 18 mm absorb bioresorbable vascular scaffold (BVS, Abbott Vascular, USA) was deployed at 14 atmospheres and optimized with a 4.0 9 12 mm non-compliant balloon to 10 atmospheres. Post-deployment optical coherence tomography (OCT, Dragonfly C7XR, St. Jude Medical, USA) showed a wellexpanded and apposed scaffold with no evidence of scaffold strut fracture (Fig. 1a and Supplementary Video). The patient was discharged with the intention of staged PCI to the circumflex. Following successful FFR-guided PCI to the circumflex 58 days later, OCT reimaging of the LAD demonstrated disarticulation of a distal portion of the BVS (Fig. 1b and Supplementary Video). The distal portion of the BVS was 4.1 mm distal to the main body of the scaffold. We hypothesize that scaffold strut fracture occurred during implantation or optimization of the BVS, but with non-displaced struts, this was invisible on initial OCT. During follow-up imaging, it is possible that the bulky OCT device may have caused the already fractured distal portion to displace downstream. Whilst BVS have a number of potential advantages, the struts are bulky and may be more vulnerable to fracture than metallic stents. Identification of fracture or migration is challenging, as BVS struts are not easily identifiable on coronary angiography or intravascular ultrasound (IVUS). Most studies mandating serial imaging of BVS used IVUS, whilst those using OCT, such as absorb cohort B, have only assessed simple lesion subsets [1]. This type V fracture (i.e. a fracture with transection of the scaffold and a gap) occurred in a vessel despite the absence of predisposing lesion characteristics [2]. Our images highlight the need for serial OCT studies to assess the performance of these devices in ‘real-world’ practice, and suggest that operators should exert great care when optimizing or later re-instrumenting BVS.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies

Background We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Methods and Results Ten subjects with single‐vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low‐pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia‐induced diastolic dysfunction was seen 1 minute after RP (end‐diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end‐diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15‐minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end‐diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15‐minutes recovery (end‐diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load‐independent indices of systolic function at 15 minutes after RP (end‐systolic elastance and ventriculo‐arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). Conclusions RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve.