Liam M. McCormick

Remote Ischemic Preconditioning Improves Outcome at 6 Years After Elective Percutaneous Coronary Intervention The CRISP Stent Trial Long-term Follow-up

Background—Postprocedural myocardial infarction (type 4a) has been shown to be an adverse prognostic indicator after elective percutaneous coronary intervention (PCI). The Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study demonstrated that remote ischemic preconditioning reduced procedural symptoms, ECG ST-segment deviation, and cardiac troponin I release after elective PCI and reduced the major adverse cardiac and cerebral event (MACCE) rate at 6 months. We were interested to confirm if this early benefit in MACCE rate in the remote ischemic preconditioning group was sustained long-term. Methods and Results—Patients were telephoned by researchers blinded to the randomization details. MACCE, defined as all-cause mortality, nonfatal myocardial infarction, transient ischemic attack or stroke, and heart failure requiring hospital admission, were adjudicated by case note and national database review. One hundred ninety-two (89.3%) of the 225 patients with elective PCI randomized in the original study were available for long-term follow-up (mean time to event or last follow-up: 1579.7±603.6 days). There were a total of 59 (30.7%) MACCEs. Patients with an MACCE had a higher mean cardiac troponin I after PCI (±SD): 2.07±6.99 versus 0.91±2.07 ng/mL (P=0.05). The MACCE rate at 6 years remained lower in the remote ischemic preconditioning group (hazard ratio, 0.58; 95% confidence interval, 0.35–0.97; P=0.039; absolute risk reduction=0.13 and number needed to treat=8 to prevent the MACCE at 6 years). Conclusions—Remote ischemic preconditioning reduces the incidence of postprocedural cardiac troponin I after elective PCI and confers an MACCE-free survival benefit at both short- and long-term follow-up. Clinical Trial Registration—URL: http://www.ukcrn.org.uk. Unique identifier: UKCRN 4074

Chronic Dipeptidyl Peptidase-4 Inhibition With Sitagliptin Is Associated With Sustained Protection Against Ischemic Left Ventricular Dysfunction in a Pilot Study of Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease

Background—The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7–36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease. Methods and Results—A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7–36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, −2.27±0.65 versus −1.98±0.58 s−1; P=0.001), whereas no effect was seen in nonischemic segments (−2.19±0.48 versus −2.18±0.54 s−1; P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan. Conclusions—The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning. Clinical Trial Registration—URL: http://www.isrctn.org. Unique identifier ISRCTN61646154.

Expansion and malapposition characteristics after bioresorbable vascular scaffold implantation

This study sought to investigate the postdeployment expansion and malapposition characteristics of the bioresorbable vascular scaffold (BVS) in real‐world practice.

Pre-treatment with glucagon-like Peptide-1 protects against ischemic left ventricular dysfunction and stunning without a detected difference in myocardial substrate utilization.

OBJECTIVES This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention. BACKGROUND GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear. METHODS Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients. RESULTS BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups. CONCLUSIONS Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).

Optimising cardioprotection during myocardial ischaemia: targeting potential intracellular pathways with glucagon-like peptide-1

Coronary heart disease and type-2 diabetes are both major global health burdens associated with an increased risk of myocardial infarction (MI). Following MI, ischaemia-reperfusion injury (IRI) remains a significant contributor to myocardial injury at the cellular level. Research has focussed on identifying a strategy or intervention to minimise IRI to optimise reperfusion therapy, with the aim of delivering a superior clinical outcome. The incretin hormone glucagon-like peptide-1, already an established basis for the treatment of type-2 diabetes, also has the potential to protect against IRI. We explain the physiology and cellular processes involved in IRI, and the intracellular pathways activated by GLP-1, which could intercept IRI and deliver cardioprotection. The review also examines the current preclinical and clinical evidence for GLP-1 in cardioprotection and future directions for research as we look for an effective adjunctive treatment to minimise IRI.

Serial assessment of the index of microcirculatory resistance during primary percutaneous coronary intervention comparing manual aspiration catheter thrombectomy with balloon angioplasty (IMPACT study): a randomised controlled pilot study

Objective Utilising a novel study design, we evaluated serial measurements of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) to assess the impact of device therapy on microvascular function, and determine what proportion of microvascular injury is related to the PPCI procedure, and what is an inevitable consequence of STEMI. Design 41 patients undergoing PPCI for STEMI were randomised to balloon angioplasty (BA, n=20) or manual thrombectomy (MT, n=21) prior to stenting. Serial IMR measurements, corrected for collaterals, were recorded at baseline and at each stage of the procedure. Microvascular obstruction (MVO) and infarct size at 24 h and 3 months were measured by troponin and cardiac MRI (CMR). Results IMR did not change significantly following PPCI, but patients with lower IMR values (<32, n=30) at baseline had a significant increase in IMR following PPCI (baseline: 21.2±7.9 vs post-stent: 33.0±23.7, p=0.01) attributable to prestent IRA instrumentation (baseline: 21.7±8.0 vs post-BA or MT: 36.9±25.9, p=0.006). Post-stent IMR correlated with early MVO on CMR (p=0.01). There was no significant difference in post-stent IMR, presence of early MVO or final infarct size between patients with BA and patients treated with MT. Conclusions Patients with STEMI and less microcirculatory dysfunction may be susceptible to acute iatrogenic microcirculatory injury from prestent coronary devices. MT did not appear to be superior to BA in maintaining microcirculatory integrity when the guide wire partially restores IRA flow during PPCI. Trial registration number ISRCTN31767278.

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.

Initial SYNTAX Score Predicts Major Adverse Cardiac Events After Primary Percutaneous Coronary Intervention

We assessed whether interventional complexity in patients presenting with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) predicted long-term outcome. Consecutive patients undergoing PPCI for STEMI underwent SYNTAX scoring, based on angiographic images obtained at coronary intervention. Patients were classified as SYNTAX score (SS) ≤22 (low, L), 23 to 32 [intermediate (IM)], and ≥33 (high, H). The median SS for the cohort was 19 [Interquartile range (IQR), 11.0-25.5] with median tertile scores of L 14 (IQR 9.0-18.5, n = 437), IM 26 (IQR 24.0-28.5, n = 170), and H 36 (IQR 34.5-40.5, n = 67). Two-year freedom from major adverse cardiac events (MACE) was L 88.1%, IM 78.8%, and H 68.7% (P < .001). Multivariate analysis confirmed that increasing SS tertile was an independent predictor of MACE [IM hazard ratio (HR) 1.61, confidence interval (CI) 1.05-2.47; P = .03, H HR 1.99, CI 1.16-3.41; P = .01]. The SS, when applied to patients undergoing PPCI for STEMI, provides prognostic information.

A contemporary re-evaluation of culprit lesion severity in patients presenting with STEMI

Background: Historical data report fatal myocardial infarction occurring when mildly-stenotic coronary plaques rupture; however, recent data suggest haemodynamically-significant coronary stenoses with fractional flow reserve (FFR) ≤ 0.8 and vessels with high plaque burden and minimum luminal area (MLA) < 4 mm2 by intravascular ultrasound (IVUS) may be prognostically important. Therefore, we sought to re-evaluate culprit stenosis severity in patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: Patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI with adjunctive thrombectomy between October 2008 and February 2010 (n = 336/572; 59%) underwent quantitative coronary angiography (QCA) after thrombus aspiration to determine vessel reference area (RA), MLA and percentage area stenosis (AS). To validate findings, QCA and FFR were measured in 50 patients with stable angina and an angiographically-intermediate lesion. Results: STEMI patients had anatomically-severe underlying culprit disease similar to that of the stable cohort (AS: 91.6 ± 9.5% versus 90.1 ± 8.1%; P = 0.11). Additionally, anatomically-severe lesions defined by QCA were more likely to be functionally-significant by FFR and vice-versa (P = 0.02 and 0.002 respectively). Conclusion: These contemporary data suggest that STEMI culprit lesions, defined by luminal stenosis after thrombus aspiration, are angiographically significant, with similar stenosis severity to stable, ischaemia-inducing lesions.

Left bundle branch block with acute thrombotic occlusion is associated with increased myocardial jeopardy score and poor clinical outcomes in primary percutaneous coronary intervention activations

Objective To assess the utility of left bundle branch block (LBBB) as an activation criterion for primary percutaneous coronary intervention (PPCI). Design Retrospective observational cohort study. Setting Single UK heart attack centre. Patients Consecutive patients referred for PPCI September 2008–December 2011 (n=2192). Interventions Demographic and outcome data were obtained by review of case notes, angiograms and interrogation of local/national databases. Main outcome measures Angiographic culprit lesion assessment defined appropriate and inappropriate activations. Patients outcomes were assessed by Major adverse cardiac events (MACE), defined as a composite of mortality and unplanned revascularisation at 1-year. Results LBBB-activation occurred in 120 patients (5.5%), of whom 21 (17.5%) had acute coronary occlusion angiographically, and were adjudicated appropriately. Compared with appropriate activations for ST segment elevation, appropriate LBBB-activations were older (71.0±9.6 vs 64.2±12.4 years, p=0.01) and more likely to be in cardiogenic shock (19.0% vs 4.3%, p<0.01). Extent of disease quantified by the SYNTAX score did not differ (median 21.5, IQR 11.0–27.0 vs 19, 11.0–25.5, p=0.66), but amount of myocardium at-risk was higher in appropriate LBBB-activations (culprit jeopardy score median 4, IQR 2–6 vs 2, 2–4, p=0.02). Final diagnoses for LBBB-activations were acute coronary syndrome (39.2%), non-acute coronary syndrome cardiac chest pain (33.3%) and non-cardiac chest pain (27.5%). In appropriate LBBB-activations 1-year mortality and MACE were higher (23.8% vs 6.6%, p=0.002 and 28.6% vs 10.5%, p=0.007, respectively). Conclusions Our data suggests that despite its poor specificity for identifying acute coronary occlusion, LBBB should at the present time remain an activation criterion for PPCI and such patients should continue to be transferred to heart attack centres for assessment and treatment.