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Late, repetitive or chronic remote ischaemic conditioning (CRIC) is a potential cardioprotective strategy against adverse remodelling following ST-segment elevation myocardial infarction (STEMI). In the randomised Daily Remote Ischaemic Conditioning Following Acute Myocardial Infarction (DREAM) trial, CRIC following primary percutaneous coronary intervention (P-PCI) did not improve global left ventricular (LV) systolic function. A post-hoc analysis was performed to determine whether CRIC improved regional strain. All 73 patients completing the original trial were studied (38 receiving 4 weeks' daily CRIC, 35 controls receiving sham conditioning). Patients underwent cardiovascular magnetic resonance at baseline (5-7 days post-STEMI) and after 4 months, with assessment of LV systolic function, infarct size and strain (longitudinal/circumferential, in infarct-related and remote territories). At both timepoints, there were no significant between-group differences in global indices (LV ejection fraction, infarct size, longitudinal/circumferential strain). However, regional analysis revealed a significant improvement in longitudinal strain in the infarcted segments of the CRIC group (from - 16.2 ± 5.2 at baseline to - 18.7 ± 6.3 at follow up, p = 0.0006) but not in corresponding segments of the control group (from - 15.5 ± 4.0 to - 15.2 ± 4.7, p = 0.81; for change: - 2.5 ± 3.6 versus + 0.3 ± 5.6, respectively, p = 0.027). In remote territories, there was a lower increment in subendocardial circumferential strain in the CRIC group than in controls (- 1.2 ± 4.4 versus - 2.5 ± 4.0, p = 0.038). In summary, CRIC following P-PCI for STEMI is associated with improved longitudinal strain in infarct-related segments, and an attenuated increase in circumferential strain in remote segments. Further work is needed to establish whether these changes may translate into a reduced incidence of adverse remodelling and clinical events. Clinical Trial Registration: http://clinicaltrials.gov/show/NCT01664611 .

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BACKGROUND: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically. METHODS: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI). Patients were recruited from four UK hospitals and randomised to receive either 4 weeks of daily rIC or sham conditioning using the autoRIC Device (CellAegis) starting on day 3 post P-PCI. The primary endpoint was the improvement in LVEF over 4 months assessed by cardiac MRI (CMR). Seventy-three patients (38 cases, 35 controls) completed the study. RESULTS: The treatment and control groups were well matched at baseline including for mean LVEF (42.8% vs 44.3% respectively, p=0.952). There was no difference in the improvement in LVEF over 4 months between the treatment and control groups (4.8%±7.8% vs 4.6%±5.9% respectively, p=0.924). No differences were seen in the secondary outcome measures including changes in infarct size and left ventricular end-diastolic and systolic volumes, major adverse cardiac and cerebral event, mean Kansas City Cardiomyopathy Questionnaire score and change in N-terminal pro-brain natriuretic peptide levels. CONCLUSIONS: Daily rIC starting on day 3 and continued for 4 weeks following successful P-PCI for STEMI did not improve LVEF as assessed by CMR after 4 months when compared with a matched control group. TRIAL REGISTRATION NUMBER: NCT0166461.

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Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year-old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study.

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Primary percutaneous coronary intervention (PPCI) is superior to thrombolysis in STEMI (ST segment elevation myocardial infarction) patients. Data on late stent thrombosis (ST) have raised concerns regarding the use of drug-eluting stents during PPCI. We report the first 3-year clinical evaluation of the zotarolimus-eluting stent (ZES) in patients undergoing PPCI for STEMI, a single-center, prospective cohort study of consecutive patients admitted with STEMI. All underwent PPCI within 12 hours of symptoms; each received one or more ZES in one or more target lesions. All patients received aspirin 300 mg, clopidogrel 600 mg, abciximab, and unfractionated heparin. A total of 102 STEMI patients (76 male, mean 62 years) received 162 ZES (mean 1.6 stents/patient). Median call-to-balloon time was 123 (102-152) minutes. Thirty-day combined major adverse cardiovascular event (MACE) rate was 3.9% (n = 4). Subacute ST occurred in 2 patients (1.96%). Combined MACE rates at 12 months and 3 years were 7.8% (n = 8) and 13.7% (n = 14). Late ST occurred in 1 patient (1%) with no occurrence of very late ST. This is the first 3-year report of the use of the ZES in an unselected, consecutive PPCI population. Overall 3-year incidence of MACE and target lesion revascularization (5.9%) was low, and was comparable to that seen with sirolimus- and paclitaxel-eluting stents in randomized controlled trials. At 3 years there was no occurrence of very late ST.

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Over the past decade, the advent of drug-eluting stents (DES) has revolutionised the field of interventional cardiology by having a major impact on patient care through their efficacy in reducing the need for repeat revascularisation. A number of stents capable of delivering an anti-proliferative agent designed to prevent neointimal hyperplasia, the principal mechanism of restenosis after stenting, have been evaluated; four of these devices are currently approved by the U.S. Food and Drug Administration (FDA). Bare metal stent (BMS) and first-generation DES, such as sirolimus-eluting (SES-Cypher(®)) and paclitaxel-eluting stents (PES-Taxus(®)), have further improved results of percutaneous coronary intervention (PCI) by improving early results and reducing the risk of restenosis. However, there is currently debate on the safety of these first-generation DES, given the potential for late stent thrombosis (LST), especially after discontinuation of dual anti-platelet therapy. Second-generation DES, such as zotarolimus-eluting (ZES-Endeavor(®)) and everolimus-eluting stents (EES-Xience V(®)), are become available in the USA and/or Europe. Recently, long-term results comparing DES with BMS in patients with ST-segment-elevation MI (STEMI) have raised some questions about the long-term risks of the drug-eluting devices. It may be useful to pause, reflect for a moment, and consider some recent pertinent results regarding their wider use. This systematic review tries to provide a concise and critical appraisal of the data available to compare first and second generation stents especially to assess risk of stent thrombosis (ST) with second-generation DES.

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OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic despite drug-eluting stents (DES), especially in diabetic patients and in those with small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both thrombosis and proliferation. The aim of the present studies was to examine the absorption and elution characteristics of eptifibatide on polymer-coated stents and investigated their effect on SMC proliferation, platelet deposition and platelet aggregation in vitro. METHODS AND RESULTS: Polymer-mixed eptifibatide and H3-labeled eptifibatide were loaded onto bare metal stents. A maximum of 111 mcg of eptifibatide was loaded onto 3.0 x 18 mm stents. Drug elution characteristics were tested in a PBS perfusion circuit. Elution profile consisted of an early rapid phase (24% +/- 0.03 loss over 1 hour) followed by a sustained release with 44% +/- 2.30 still present on the stent after 30 days. Eluted eptifibatide significantly inhibited adenosine diphosphate (ADP)-induced platelet aggregation by 95% +/- 0.70 (p < 0.01). Efficacy of stents eluting eptifibatide for antiplatelet effect was determined by measuring deposition of 111indium-labeled platelets on stents. Platelet deposition was significantly reduced by 48% +/- 6 in comparison to controls (p = 0.0065). Finally, drug-loaded stents were placed in SMC culture and showed a distinct zone of cell growth inhibition within 1 mm2 (88 +/- 22 vs. 208 +/- 23 SMCs in control), and within 2 mm2 of stent (131 +/- 32 vs. 191 +/- 23 SMCs in control) (both p < 0.01). CONCLUSIONS: Eptifibatide can be successfully loaded onto stents. It elutes in a predictable manner, significantly inhibiting platelet deposition, aggregation and SMC proliferation in vitro. These studies pave the way to developing stent-based delivery of a potent antiplatelet agent, which additionally may inhibit SMC activity.

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