Standard Primary Percutaneous Coronary Intervention Research Articles

Effect of remote ischaemic conditioning on left ventricular function in ST-segment elevation myocardial infarction patients: The CONDI-2 echocardiographic sub-study.

Remote ischaemic conditioning (RIC) applied to the arm by inflation and deflation of a pneumatic cuff has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). However, the effect of RIC on left ventricular ejection fraction (LVEF) following infarct healing remains unknown. To investigate whether RIC applied in the ambulance before PPCI can improve left ventricular (LV) function in STEMI patients 3 months following infarction. Echocardiography was performed in a total of 694 patients from the CONDI-2 study a median of 112 days (IQR 63) after the initial admission. LVEF and LV end-diastolic and end-systolic volumes were calculated using the modified Simpsons biplane method of disks. LV global longitudinal strain (GLS) was estimated using 2-dimensional cine-loops with a frame rate > 55 frames/second, measured in the three standard apical views. There was no difference in the measured echocardiographic parameters in the RIC group as compared to the control group, including LV EF, LV GLS, tricuspid annular plane systolic excursion or left ventricular volumes. In the control group, 32% had an ejection fraction < 50% compared to 37% in the RIC group (p = 0.129). In this largest to date randomized imaging study of RIC, RIC as an adjunct to PPCI was not associated with a change in echocardiographic measures of cardiac function compared to standard PPCI alone.

Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD).

BackgroundIntramyocardial edema and hemorrhage are key pathological mechanisms in the development of reperfusion‐related microvascular damage in ST‐segment–elevation myocardial infarction. These processes may be facilitated by abrupt restoration of intracoronary pressure and flow triggered by primary percutaneous coronary intervention. We investigated whether pressure‐controlled reperfusion via gradual reopening of the infarct‐related artery may limit microvascular injury in patients undergoing primary percutaneous coronary intervention.Methods and ResultsA total of 83 patients with ST‐segment–elevation myocardial infarction were assessed for eligibility and 53 who did not meet inclusion criteria were excluded. The remaining 30 patients with totally occluded infarct‐related artery were randomized to the pressure‐controlled reperfusion with delayed stenting (PCRDS) group (n=15) or standard primary percutaneous coronary intervention with immediate stenting (IS) group (n=15) (intention‐to‐treat population). Data from 5 patients in each arm were unsuitable to be included in the final analysis. Finally, 20 patients undergoing primary percutaneous coronary intervention who were randomly assigned to either IS (n=10) or PCRDS (n=10) were included. In the PCRDS arm, a 1.5‐mm balloon was used to achieve initial reperfusion with thrombolysis in myocardial infarction grade 3 flow and, subsequently, to control distal intracoronary pressure over a 30‐minute monitoring period (MP) until stenting was performed. In both study groups, continuous assessment of coronary hemodynamics with intracoronary pressure and Doppler flow velocity was performed, with a final measurement of zero flow pressure (primary end point of the study) at the end of a 60‐minute MP. There were no complications associated with IS or PCRDS. PCRDS effectively led to lower distal intracoronary pressures than IS over 30 minutes after reperfusion (71.2±9.37 mm Hg versus 90.13±12.09 mm Hg, P=0.001). Significant differences were noted between study arms in the microcirculatory response over MP. Microvascular perfusion progressively deteriorated in the IS group and at the end of MP, and hyperemic microvascular resistance was significantly higher in the IS arm as compared with the PCDRS arm (2.83±0.56 mm Hg.s.cm−1 versus 1.83±0.53 mm Hg.s.cm−1, P=0.001). The primary end point (zero flow pressure) was significantly lower in the PCRDS group than in the IS group (41.46±17.85 mm Hg versus 76.87±21.34 mm Hg, P=0.001). In the whole study group (n=20), reperfusion pressures measured at predefined stages in the early reperfusion period showed robust associations with zero flow pressure values measured at the end of the 1‐hour MP (immediately after reperfusion: r=0.782, P<0.001; at the 10th minute: r=0.796, P<0.001; and at the 20th minute: r=0.702, P=0.001) and peak creatine kinase MB level (immediately after reperfusion: r=0.653, P=0.002; at the 10th minute: r=0.597, P=0.007; and at the 20th minute: r=0.538, P=0.017). Enzymatic myocardial infarction size was lower in the PCRDS group than in the IS group with peak troponin T (5395±2991 ng/mL versus 8874±1927 ng/mL, P=0.006) and creatine kinase MB (163.6±93.4 IU/L versus 542.2±227.4 IU/L, P<0.001).ConclusionsIn patients with ST‐segment–elevation myocardial infarction, pressure‐controlled reperfusion of the culprit vessel by means of gradual reopening of the occluded infarct‐related artery (PCRDS) led to better‐preserved coronary microvascular integrity and smaller myocardial infarction size, without an increase in procedural complications, compared with IS.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02732080.

БЕССОБЫТИЙНАЯ ВЫЖИВАЕМОСТЬ ПАЦИЕНТОВ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА С ПРИМЕНЕНИЕМ КОМБИНИРОВАННОГО ДИСТАНТНОГО ИШЕМИЧЕСКОГО КОНДИЦИОНИРОВАНИЯ В ТЕЧЕНИЕ 36 МЕСЯЦЕВ

Background. Reperfusion injury occurs after revascularization of the coronary artery in patients with myocardial infarction (MI) significantly contributing to the development of chronic heart failure. This article describes the results of studying the effectiveness of one of the promising cardioprotection strategies aimed at limiting reperfusion injury. Materials and methods. Patients with acute anterior MI with ST elevation (STEMI) (n = 87) were included in an open-label prospective randomized controlled trial. Intervention group (IG) patients underwent primary percutaneous coronary intervention (PPCI) and remote ischemic preconditioning in combination with delayed postconditioning (RIPerPostC) (n = 43). Control group patients (CG) underwent only standard PPCI (n = 44). Event-free survival was estimated by Kaplan-Meier curves. Results. A comparative analysis of the frequency of the composite endpoint (re-hospitalizations for the underlying disease, repeated MI and death from cardiac causes) by the 36th month of follow-up had shown that the proportion of patients who reached the endpoint was significantly higher in the CG: 45.5% vs 20.9% in the IG (p = 0.015). According to the results of the log-rank test, there are statistically significant differences in the event-free survival of the analyzed groups (LR = 1.99, p = 0.047). The Kaplan-Meier curves of the CG and IG during the first 12 months after AMI did not differ visually in height and slope, which indicated the absence of intergroup differences in the cumulative functions of event-free survival during the indicated observation period. After 12 months, there was a discrepancy between the Kaplan-Meier curves due to the fact that the survival rate continued to decrease rapidly only in the CG. According to the survival function, in 25% of CG patients, adverse events occurred within the first 13 months after AMI. Taking into account censored observations, the cumulative proportion of patients without major clinical events 36 months after AMI in the IG was 74% versus 38% in the CG. Conclusion. In patients with STEMI the DIPerPostC method in combination with PPCI has a positive effect on patient survival over 36 months in comparison with isolated PPCI. The highest number of adverse events occurred during the period from 12 to 36 months of observation in the CG.

Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI.

The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P=0.24), and ventricular fibrillation occurred in 5 and 3 patients (P=0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6days after enrollment. No stent thrombosis was observed in the control group (P=0.50). Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.

MR findings of microvascular perfusion in infarcted and remote myocardium early after successful primary PCI.

ObjectivesThe aim of the study was to evaluate CMR myocardial first-pass perfusion in the injured region as well as the non-infarcted area in ST-elevation myocardial infarction (STEMI) patients few days after successful primary percutaneous coronary intervention (PCI).Materials and methods220 patients with first time STEMI successfully treated with PCI (with or without postconditioning) were recruited from the Postconditioning in STEMI study. Contrast enhanced CMR was performed at a 1.5 T scanner 2 (1–5) days after PCI. On myocardial first-pass perfusion imaging signal intensity (SI) was measured in the injured area and in the remote myocardium and maximum contrast enhancement index (MCE) was calculated. MCE = (peak SI after contrast—SI at baseline) / SI at baseline x 100.ResultsThere were no significant differences in first-pass perfusion between patients treated with standard PCI and patients treated with additional postconditioning. The injured myocardium showed a significantly lower MCE compared to remote myocardium (94 ± 55 vs. 113 ± 49; p < 0.001). When patients were divided into four quartiles of MCE in the injured myocardium (MCE injured myocardium), patients with low MCE injured myocardium had: significantly lower ejection fraction (EF) than patients with high MCE injured myocardium, larger infarct size and area at risk, smaller myocardial salvage and more frequent occurrence of microvascular obstruction on late gadolinium enhancement. MCE in the remote myocardium revealed that patients with larger infarction also had significantly decreased MCE in the non-infarcted, remote area.ConclusionCMR first-pass perfusion can be impaired in both injured and remote myocardium in STEMI patients treated with primary PCI. These findings indicate that CMR first-pass perfusion may be a feasible method to evaluate myocardial injury after STEMI in addition to conventional CMR parameters.

Effect of Selective Thrombus Aspiration on Serum Lipoprotein-Associated Phospholipase A2 in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention with High Thrombus Burden.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a potential therapeutic target in acute coronary syndromes. Although recent evidence does not support the routine use of manual thrombus aspiration (TA) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the use of TA is associated with a significant improvement in myocardial reperfusion, especially in patients with high thrombus burden (HTB). We hypothesized that TA would reduce the serum Lp-PLA2 levels in STEMI patients undergoing PPCI with HTB. Our study cohort included 320 consecutive STEMI patients undergoing PPCI with HTB who were randomly assigned to receive either TA before PPCI (TA group, n = 160) or PPCI alone (standard PPCI group, n = 160). The baseline characteristics of study participants were well-matched. After 30 ± 2 days, serum Lp-PLA2 levels decreased by 53.9% in the TA group (152.9 ± 58.1 ng/mL) and decreased by 31.2% in the standard PPCI group (84.2 ± 86.6 ng/mL, p < 0.001). The TA group had a significantly lower prevalence of balloon predilatation, number of stents used, total stent length and corrected thrombolysis in myocardial infarction frame count, and a higher percentage of myocardial blush grade ≥ 2 compared with the standard PPCI group (all p < 0.001). No significant difference between the groups was observed in 30 ± 2 days for major adverse cardiovascular and cerebrovascular events (p = 0.702). After 30 ± 2 days of treatment, TA may significantly reduce serum levels of Lp-PLA2 in STEMI patients undergoing PPCI with HTB.

Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis

BackgroundDespite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI.MethodsDatabase searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events.ResultsForty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects.ConclusionsThe intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen.

Effect of preinfarction angina on primary percutaneous coronary intervention outcomes

Background: Preinfarction angina has been recognized as a surrogate for preconditioning episodes. This study was designed to evaluate the cardiovascular effects of preinfarction anginal episodes among acute myocardial infarction (AMI) patients undergoing primary percutaneous coronary intervention (PCI). Materials and Methods: Of 520 patients who had undergone primary PCI, 393 patients were finally included in a prospective cohort study. Standard primary PCI procedure according to the latest guidelines was performed. The patients were divided into three groups based on previous symptoms as follows: asymptomatic (Group A), chronic stable angina (Group B) and unstable angina (Group C). Results: A total of 393 patients were evaluated. 185 (47.1%) patients were described as asymptomatic, 48 (12.2%) had stable angina and 160 (40.7%) were categorized as unstable angina. There was no significant difference among the study groups regarding pre- and post-PCI thrombolysis in myocardial infarction flow grade (P = 0.81). Median of peak post-PCI creatine-kinase-muscle/brain level of Group A (asymptomatic) was 250.5 (115.5–389), and it was significantly higher than Group C (176 [60.00–313.50]) (P = 0.03). Q wave formation was observed in 142 (88.75%), 31 (64.5%), and 96 (52.0%) patients of Group A, B, and C patients, respectively, which was significantly higher in asymptomatic patients (P = 0.002). There was no significant difference among the three groups regarding in-hospital and 6-month mortality (P = 0.36, 0.06, respectively). The composite endpoint of 6-month mortality, acute coronary events, cerebrovascular accidents, and target vessel revascularization was not significantly different between the three groups (P = 0.11). Conclusion: Preinfarction angina among AMI patients undergoing primary PCI seems to have a limited beneficial effect on infarct size, and this benefit was not translated to any clinical benefit.

Microcatheter-Facilitated Primary Angioplasty in ST-Segment Elevation Myocardial Infarction

BackgroundDirect stenting is the best method for achieving reperfusion in primary percutaneous coronary intervention (PPCI). We hypothesized that the use of a microcatheter (MC) during PPCI when Thrombolysis in Myocardial Infarction (TIMI) flow ≤ 1 after wire crossing would allow visualization of the downstream artery with an optimal TIMI 3 flow at the end of the procedure. MethodsIn this pilot study, PPCI patients with TIMI flow ≤ 1 after wire crossing formed the MC group (n = 60); the MC was positioned in the distal part of the culprit artery and a small amount of contrast was injected through it to determine stent size and length to treat the culprit lesion. The MC group was compared with previous consecutive patients treated using standard PPCI (n = 94; similar characteristics except for the rate of previous percutaneous coronary intervention). ResultsIn the MC group, downstream arteries were visualized in 98% of cases and direct stenting was achieved in 72% vs 31% (P < 0.0001). Final TIMI 3 flow was similar in both groups (97%). There was less manual thrombectomy (20% vs 63%; P < 0.001) and bailout glycoprotein IIb/IIIa inhibitor use (6.7% vs 29.8%; P < 0.002). The incidence of major adverse events (death, shock, severe arrhythmia) and left ventricular ejection fraction were similar. The peak cardiac enzymes level was significantly lower in the MC group. ConclusionsThe MC strategy appears feasible and safe. It could allow exploring new strategies on the basis of more systematic direct stenting and prepared reperfusion by injecting drugs through the MC before reperfusion.

Thrombus aspiration versus standard technique in patients with ST-elevation myocardial infarction

Objective The aim of this study was to assess the efficacy of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI). Background The idea of an occluding thrombus as an etiology for ST-elevation myocardial infarction (STEMI) and its dissolution as a treatment had been around since the 1950s. Patients and methods The study included 70 patients with STEMI undergoing PPCI within 12 h from symptoms. These patients were divided equally into two groups (35 patients each): TA group and standard PPCI (SP) group. Primary endpoints were ST-segment resolution 90 min after procedure and thrombolysis in myocardial infarction flow and myocardial blush grade at the end of procedure. Secondary endpoint was in-hospital major adverse cardiovascular effects. Results ST-segment resolution more than 70%, that is, complete reperfusion, was seen in 42.9% of patients in the TA group in comparison with 8.6% in the SP group (P < 0.005). Myocardial blush grade more than or equal to 2 was seen in 91.4% in TA group in comparison with 54.3% in SP group (P < 0.005). We reported death of three patients in the SP group; however, this did not reach statistical significance (P = 0.120). Conclusion TA has significantly improved the reperfusion in patients with STEMI and significantly decreased the incidence of no reflow. Thus, we recommend TA as a routine procedure in PPCI.

Combined analysis of the safety of intra-coronary drug delivery during primary percutaneous coronary intervention for acute myocardial infarction: A study of three clinical trials.

BackgroundThe local injection of novel cardioprotective study drugs prior to percutaneous coronary intervention could cause embolisation of thrombus, resulting in increased reperfusion injury and subsequent infarct size. The aim of this study was to assess the safety of the delivery of an intracoronary therapy delivered during primary percutaneous coronary intervention for acute myocardial infarction prior to the re-establishment of thrombolysis in myocardial infarction III flow.MethodsOne hundred sixty-seven patients with acute myocardial infarction successfully reperfused through primary percutaneous coronary intervention and undergoing Cardiac MRI within the first week after reperfusion were studied. Patients either underwent the delivery of an intracoronary agent (IMP or placebo) prior to balloon dilatation (n = 80) or standard primary percutaneous coronary intervention procedure (n = 117).ResultsBaseline characteristics were similar between the two groups. There were a similar number of successful procedures (IC IMP 75 (93.8%) vs. No IMP 114, (97.4%), p = 0.374), rates of no-reflow (IC IMP 1 (1.3%) vs. No IMP 2 (1.7%), p = 0.99) and levels of ST segment resolution (88.5% IC IMP vs. No IC IMP 87.0%, p = 0.669) between the two groups. Similar levels of microvascular obstruction were seen between the two groups with a trend to reduced infarct size, and improved ejection fractions in the IMP group. Lower MACE rates were seen in the IMP group.ConclusionThe local intracoronary infusion of potential cardioprotective agents prior to the restoration of TIMI flow in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction appears to be safe and does not increase microvascular damage. This route should be considered when testing novel cardioprotective agents.

The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention

BackgroundMicrovascular obstruction (MVO) predicts short- and longer-term outcomes following primary percutaneous coronary intervention (PPCI) treatment of ST-elevation myocardial infarction (STEMI). The evidence base supporting the role of adenosine and sodium nitroprusside (SNP), the most evaluated adjunctive therapies aimed at attenuating MVO and infarct size, remains weak as the trials involved have had variable end points and used differing drug doses and modes of delivery.ObjectiveTo determine whether intracoronary administration of adenosine or SNP following thrombus aspiration reduces infarct size and/or MVO measured by cardiac magnetic resonance (CMR) imaging in patients undergoing PPCI within 6 hours of onset of STEMI.DesignMulticentre, prospective, parallel, randomised controlled and open-label trial with blinded end point analysis.SettingFour high-volume UK PPCI centres.ParticipantsPatients with STEMI undergoing PPCI with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0/1 in the infarct-related artery and no significant bystander coronary artery disease on angiography.InterventionsParticipants were anticoagulated with bivalirudin and allocated by an automated 24-hour telephone randomisation service to one of three groups: (1) standard PPCI (control), (2) PPCI with adjunctive adenosine 1–2 mg or (3) PPCI with adjunctive SNP 250 µg. The study drugs were delivered intracoronary immediately following thrombus aspiration and again following successful stenting.Main outcome measuresThe primary outcome was infarct size (% total left ventricular end-diastolic mass; %LVM) measured by CMR imaging undertaken 48–96 hours post PPCI. Secondary outcome measures included MVO (hypoenhancement within the infarct core) on CMR imaging, electrocardiographic and angiographic markers of microvascular perfusion and major adverse cardiac events (MACEs) during a median of 6 months’ follow-up. The study aimed to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in infarct size).ResultsThe trial completed recruitment in April 2014 having randomised 247 patients (standard PPCI group,n = 86; PPCI + adenosine group,n = 82; PPCI + SNP group,n = 79). In total, 79% of participants were male and the mean ± standard deviation age of participants was 59.3 ± 12.3 years. CMR imaging was completed in 197 (80%) patients (standard PPCI,n = 65; PPCI + adenosine,n = 63; PPCI + SNP,n = 69) for the primary outcome. There was no significant difference in infarct size [%LVM, median, interquartile range (IQR)] between the adenosine group (10.1, 4.7–16.2), the SNP group (10.0, 4.2–15.8) and the control group (8.3, 1.9–14.0) (p = 0.062 andp = 0.160 vs. control, respectively). MVO (%LVM, median, IQR) was similar across the groups [1.0, 0.0–3.7 (p = 0.205) and 0.6, 0.0–2.4 (p = 0.244) for adenosine and SNP, respectively, vs. 0.3, 0.0–2.8 for the control]. Using per-protocol analysis, infarct size (%LVM) was increased in adenosine-treated patients compared with control patients (12.0 vs. 8.3;p = 0.031). Increased left ventricular volume and reduced left ventricular ejection fraction were also observed in the adenosine arm. There was a significant increase in MACEs in patients undergoing adenosine-facilitated PPCI compared with control patients, driven by heart failure, at 30 days [hazard ratio (HR) 5.39, 95% confidence interval (CI) 1.18 to 24.60;p = 0.04] and 6 months (HR 6.53, 95% CI 1.46 to 29.2;p = 0.01) post randomisation.ConclusionsHigh-dose intracoronary adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR imaging. Furthermore, adenosine may adversely affect mid-term clinical outcome and should not be used during PPCI to prevent reperfusion injury.Trial registrationClinicalTrials.gov NCT01747174 and EudraCT 2010–023211–34.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Strategies to attenuate micro-vascular obstruction during P-PCI: the randomized reperfusion facilitated by local adjunctive therapy in ST-elevation myocardial infarction trial.

BackgroundMicrovascular obstruction (MVO) following primary percutaneous coronary intervention (PPCI) treatment of ST-segment elevation myocardial infarction (STEMI) contributes to infarct expansion, left ventricular (LV) remodelling, and worse clinical outcomes. The REFLO-STEMI trial tested whether intra-coronary (IC) high-dose adenosine or sodium nitroprusside (SNP) reduce infarct size and/or MVO determined by cardiac magnetic resonance (CMR).Methods and resultsREFLO-STEMI, a prospective, open-label, multi-centre trial with blinded endpoints, randomized (1:1:1) 247 STEMI patients with single vessel disease presenting within 6 h of symptom onset to IC adenosine (2–3 mg total) or SNP (500 μg total) immediately following thrombectomy and again following stenting, or to standard PPCI. The primary endpoint was infarct size % LV mass (%LVM) on CMR undertaken 24–96 h after PPCI (n = 197). Clinical follow-up was to 6 months. There was no significant difference in infarct size (%LVM, median, interquartile range, IQR) between adenosine (10.1, 4.7–16.2), SNP (10.0, 4.2–15.8), and control (8.3, 1.9–14.0), P = 0.062 and P = 0.160, respectively, vs. control. MVO (% LVM, median, IQR) was similar across groups (1.0, 0.0–3.7, P = 0.205 and 0.6, 0.0–2.4, P = 0.244 for adenosine and SNP, respectively, vs. control 0.3, 0.0–2.8). On per-protocol analysis, infarct size (%LV mass, 12.0 vs. 8.3, P = 0.031), major adverse cardiac events (hazard ratio, HR, 5.39 [1.18–24.60], P = 0.04) at 30 days and 6 months (HR 6.53 [1.46–29.2], P = 0.01) were increased and ejection fraction reduced (42.5 ± 7.2% vs. 45.7 ± 8.0%, P = 0.027) in adenosine-treated patients compared with control.ConclusionsHigh-dose IC adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR. Furthermore, adenosine may adversely affect mid-term clinical outcome.Clinical Trial registrationClinicalTrials.gov Identifier: NCT01747174; https://clinicaltrials.gov/ct2/show/NCT01747174

Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.

Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI. We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408. Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups. In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population. Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Cardiology update 2016

In the latter half of 2016, the important trials were ATMOSPHERE, INOVATE-HF, and IMPEDANCE-HF. The inclusion of angiotensin receptor–neprilysin inhibitor (valsartan/sacubitril) and sinoatrial node modulator (ivabradine) in the guidelines was a significant change. HOPE-3 was a major trial in 2016 expanding the dimension of statin use. ixCELL-DCM trial evaluated stem cells in dilated cardiomyopathy. Mobile-health and medication event monitoring system technology showed increasing use of technology in both prevention and treatment in cardiology. RIDDLE-non-ST-segment elevation myocardial infarction (NSTEMI) studied the immediate versus delayed intervention in NSTEMI. In STEMI, DANAMI 3-DEFER trial evaluated the concept of immediate stent implantation or deferred stent implantation 48 h after the index procedure with standard primary percutaneous coronary intervention. EARLY-BAMI tested intravenous metoprolol in acute STEMI with the use of magnetic resonance imaging. The utility of “Chest Pain Choice” tool demonstrated shared decision-making between physician and patients in the context of chest pain. Risk factors profile and demographic and angiographic features of aorto-ostial atherosclerotic coronary artery disease are evaluated extensively. Transcatheter aortic valve replacement results in comparison to surgery and its association with volume, and in-hospital outcomes are also analyzed. The VANISH trial addressed a very critical issue in post-MI ICMP. Factors associated with erosion related to Amplatzer septal occluder in atrial septal defect closure are described in detail.

Postconditioning Reduces Enzymatic Infarct Size and Improves Microvascular Reperfusion in Patients with ST-Segment Elevation Myocardial Infarction

Objectives: Postconditioning has been reported to reduce infarct size in ST-segment myocardial infarction (STEMI). However, recently, few other studies did not show any effect of postconditioning and suggested that it may be even harmful. We sought to assess whether postconditioning could reduce infarct size and improve myocardial reperfusion in early presenters with STEMI. Methods: 72 STEMI patients treated with primary percutaneous coronary intervention (PCI) were randomly assigned to either the postconditioning (n = 35) or the standard PCI group (control group; n = 37). Blood samples were obtained for creatine kinase (CK) and its MB isoform (CK-MB) within 36 h. The angiographic (myocardial blush grade, MBG) and electrocardiographic (ST-segment resolution, STR) data were evaluated and compared between groups. Results: The areas under the curve of CK and CK-MB release were significantly reduced in the postconditioning group compared with the control group (38,612.91 ± 25,028.42 vs. 60,547.30 ± 25,264.63 for CK and 5,498.23 ± 3,787.91 vs. 7,443.12 ± 3,561.13 for CK-MB, p < 0.0001). MBG was significantly better in the postconditioning group than in the control group (MBG 3: 82.3 vs. 47.1%, p = 0.0023). In the postconditioning group, STR >70% was more often observed (97.1 vs. 64.1%, p = 0.0007). Conclusions: In patients with STEMI, postconditioning could significantly reduce enzymatic infarct size and improve myocardial reperfusion.

Angiographic and Clinical Impact of Successful Manual Thrombus Aspiration in Diabetic Patients Undergoing Primary PCI.

Background. Diabetes mellitus is associated with worse angiographic and clinical outcomes after percutaneous coronary intervention (PCI). Aim. To investigate the impact of manual thrombus aspiration on in-stent restenosis (ISR) and clinical outcome in patients treated by bare-metal stent (BMS) implantation for ST-segment elevation myocardial infarction (STEMI). Methods. 100 diabetic patients were prospectively enrolled. They were randomly assigned to undergo either standard primary PCI (group A, 50 patients) or PCI with thrombus aspiration using Export catheter (group B, 50 patients). The primary endpoint was the rate of eight-month ISR. The secondary endpoint included follow-up for major adverse cardiac events (MACE). Results. Mean age of the study cohort was 59.86 ± 8.3 years, with 64 (64%) being males. Baseline characteristics did not differ between both groups. Eight-month angiogram showed that group B patients had significantly less late lumen loss (0.17 ± 0.35 versus 0.60 ± 0.42 mm, P < 0.001), with lower incidence of ISR (4% versus 16.6%, P < 0.001). There was a trend towards lower rate of MACE in the same group of patients. Conclusion. In diabetic patients undergoing primary PCI, manual thrombus aspiration (compared with standard PCI) was associated with better ISR rate after BMS implantation.

The impact of successful manual thrombus aspiration on in-stent restenosis after primary PCI

This study sought to investigate the impact of successful manual thrombus aspiration on angiographic in-stent restenosis and clinical outcome in patients treated by bare metal stent implantation for ST-segment elevation acute myocardial infarction. There are very limited data on the impact of manual thrombus aspiration on the occurrence of in-stent restenosis after bare metal stent implantation. This was a prospective, randomized, single-center study. Patients (N=60) presenting within 12 h of ST-segment elevation acute myocardial infarction symptom onset were randomized to primary percutaneous coronary intervention (PCI) with (N=30) or without (N=30) upfront manual thrombus aspiration using the Export aspiration catheter. All patients underwent control coronary angiography after 6 months. Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. Patients who underwent successful manual thrombus aspiration had significantly higher minimal lumen diameter after 6 months (2.25±0.90 vs. 1.63±0.76, P=0.005), significantly lower percentage diameter stenosis (28.81 vs. 45.03%, P=0.017), and significantly lower late lumen loss (0.73±0.84 vs. 1.18±0.79, P=0.035). There was a trend for lower rate of major adverse cardiocerebrovascular events such as death, myocardial reinfarction, stroke, and target lesion revascularization in the same group of patients (16.67 vs. 26.67%, P=0.347). Successful upfront manual thrombus aspiration during primary PCI showed beneficial effects on the reduction of in-stent restenosis after bare metal stent implantation compared with standard PCI.

Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial

BackgroundPostconditioning (PC) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI), nevertheless clinical experience is limited. We aimed to explore the cardioprotective effect of PC using cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients treated by PPCI. MethodsA total of 78 patients with first STEMI (aged 59±12years) referred for PPCI, were stratified for STEMI location and randomly assigned to conventional PPCI or PPCI with PC. All patients, with occluded infarct related artery and no collateral circulation, received abciximab intravenously before PPCI. After reperfusion by effective direct stenting, control subjects underwent no further intervention, while in treated patients PC was performed within 1min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Primary end-point was infarct size (IS) reduction, expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10days after index PPCI. ResultsAll baseline characteristics but diabetes (p=0.06) were balanced between groups. Postconditioning patients trended toward a larger IS compared to those treated by standard PPCI (20±12% vs 14±10%, p=0.054). After exclusion of diabetics, PC group still showed a trend to larger IS (p=0.116). Major adverse events seem to be more frequent in PC group irrespective to diabetic status (p=0.053 and p=0.080, respectively). ConclusionsThis prospective, randomized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab. (Clinical Trial Registration-unique identifier: NCT01004289).

Additive benefit of glycoprotein IIb/IIIa inhibition and adjunctive thrombus aspiration during primary coronary intervention: Results of the Initial Thrombosuction and Tirofiban Infusion (ITTI) trial

BackgroundThrombus aspiration has been shown to provide significant benefits during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The aim of the current study was to evaluate the additional benefit of tirofiban to thrombus aspiration during primary PCI in myocardial reperfusion. Methods100 STEMI patients were randomized according to a 2×2 factorial design into 1 of the 4 groups: standard PCI, PCI with initial thrombus aspiration (IT), PCI with tirofiban infusion (TI), and PCI with both treatments (IT+TI). ResultsThe myocardial blush grade (MBG) 3 was achieved in 30.4%, 45.8%, 56% and 78.6% in the 4 groups respectively. More frequent MBG 3 (p=0.015) and complete (>70%) ST-segment resolution (STR, 67.9% vs. 41.7%, p=0.058) were observed in IT±TI group compared with IT group. If actuarial analysis was done after reassigning the 2 TI patients who crossed over to IT+TI, the difference between IT+TI and IT groups became more significant (MBG 3 rates: 76.7% vs. 45.8%, p=0.009; complete STR rates: 70% vs. 41.7%, p=0.036). Infusion of tirofiban resulted in improved MBG and STR (p=0.003 and 0.037, respectively). Thrombus aspiration resulted in improved MBG only (p=0.048) but not in STR. 6-month MACE (death, reinfarction, target lesion revascularization and stroke) was similar among groups (p=0.725). ConclusionsTirofiban may augment thrombus aspiration therapy on myocardial reperfusion in primary PCI. The benefit of thrombus aspiration treatment without tirofiban might be less significant, especially on resolution of ST-segment elevation.