Project description: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.
Project description:BackgroundThe appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared with the administration in the Cathlab.MethodsWe conducted a "before-after" observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pretreated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pretreatment protocol.ResultsA total of 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pretreated compared with no pretreated population showed better basal reperfusion, expressed as basal Thrombolysis in Myocardial Infarction (TIMI)-flow (p for trend p < 0.001). Pretreated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.32-0.67, p < 0.001) and higher frequency of TIMI 2-3 (33.3% vs. 19.3% OR: 2.0, 95% CI: 1.38-2.00, p < 0.001) and TIMI 3 (14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92-2.65), p = 0.094). Pretreated compared with no pretreated population showed reduced infarct size expressed as Troponin Peak (20,286 (8726-75,027) versus 48,676 (17,229-113,900), p = 0.001), and higher left ventricular ejection fraction at discharge (53% (44-59) vs. 50% (44-56), p = 0.027). In-hospital BARC ≥ 2 bleeding were similar (2.1% vs. 2.0%, p = 0.929, in pretreated versus no pretreated population, respectively).ConclusionThis study provides support for an early pretreatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.
Project description:ObjectiveTo compare the efficacy of pharmacoinvasive strategy versus primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). Primary PCI is the preferred treatment for STEMI, but it is not a feasible option for many. A pharmacoinvasive strategy might be a practical solution in the Indian context, although few empirical data exist to guide this approach.MethodsThis is a prospective, observational, multicentre pilot study. Two hundred consecutive patients with STEMI aged 18-75 years, presenting within 12 h of onset of symptoms and requiring a reperfusion strategy, were studied from five primary PCI capable centres in South India. Patients who opted for pharmacoinvasive strategy (n=45) formed group A. Group B consisted of patients treated with primary PCI (n=155). One patient was lost to follow-up at 1 year. The primary end point was a composite of death, cardiogenic shock, reinfarction, repeat revascularisation of a culprit artery and congestive heart failure at 30 days.ResultsThe primary end point occurred in 11.1% in group A and in 3.9% in group B, p=0.07 (RR=2.87; 95% CI 0.92 to 8.97). The infarct-related artery patency at angiogram was 82.2% in group A and 22.6% in group B (p<0.001). PCI was performed in 73.3% in group A versus 100% in group B (p<0.001), and a thrombus was present in 26.7% in group A versus 63.2% in group B (p<0.001). Failed fibrinolysis occurred in 12.1% in group A. There was no difference in bleeding risk, 2.2% in group A versus 0.6% in group B, (p=0.4).ConclusionsThis pilot study shows that a pharmacoinvasive strategy can be implemented in patients not selected for primary PCI in India and hints at the possibility of similar outcomes. Larger studies are required to confirm these findings.Trial registration numberTRIAL IS REGISTERED WITH CLINICAL TRIAL REGISTRY OF INDIA, CTRI NUMBER: REF/2011/07/002556.
Project description:Lon is a widely distributed AAA+ (ATPases associated with diverse cellular activities) protease known for degrading poorly folded and damaged proteins and is often classified as a weak protein unfoldase. Here, using a Lon-degron pair from Mesoplasma florum (MfLon and MfssrA, respectively), we perform ensemble and single-molecule experiments to elucidate the molecular mechanisms underpinning MfLon function. Notably, we find that MfLon unfolds and degrades stably folded substrates and that translocation of these unfolded polypeptides occurs with a ∼6-amino-acid step size. Moreover, the time required to hydrolyze one ATP corresponds to the dwell time between steps, indicating that one step occurs per ATP-hydrolysis-fueled "power stroke." Comparison of MfLon to related AAA+ enzymes now provides strong evidence that HCLR-clade enzymes function using a shared power-stroke mechanism and, surprisingly, that MfLon is more processive than ClpXP and ClpAP. We propose that ample unfoldase strength and substantial processivity are features that contribute to the Lon family's evolutionary success.
Project description:AimsThis subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome.MethodsPatients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis.ResultsMajor/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024).ConclusionAfter PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
Project description:BackgroundTraining in complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) has frequently been reserved for established operators (consultants/attending) with trainees (fellows-in-training or FIT) being often discouraged from carrying out such procedures as a primary operator due to their high-risk nature. Whether the outcomes of these cases differ if the primary operator is a supervised FIT compared with a consultant is unknown.MethodsUsing multicentre PCI data from three cardiac centres in South Wales, UK (2018-2022), we identified 2295 CHIP-PCI cases with a UK-BCIS CHIP Score of 3 or more. These were then divided by primary operator status (supervised FIT vs consultant); the primary outcome was in-hospital major adverse cardiac events (IH-MACCE). Multivariate logistic models were developed to adjust for differences in baseline and procedural characteristics.ResultsThe primary operator in 838 (36%) of the PCIs was a supervised FIT. Baseline and procedural characteristics had lower complexity in CHIP-PCI cases carried out by supervised FIT vs consultant. In a multivariate-adjusted model, supervised FIT procedures were associated with lower odds of concurrent valve disease (OR 0.45, 95% CI: 0.29 to 0.69), dual access (OR 0.58, 95% CI: 0.41 to 0.83), cutting/scoring balloons (OR 0.59, 95% CI: 0.44 to 0.79) and rotational atherectomy (OR 0.60, 95% CI: 0.42 to 0.87). After adjusting for all variables, however, there was no difference in the primary outcome (OR 0.72, 95% 0.34 to 1.51) or any secondary outcomes. Sensitivity analyses restricted to patients with higher CHIP Scores (4+ and 5+) showed comparable IH-MACCE.ConclusionsTraining FIT as primary operators in CHIP-PCI appears to be feasible and safe and can be delivered within the standard training programme. The comparable outcomes are likely driven by the two-operator 'buddy' effect that a FIT supervised by a consultant benefits from.
Project description:BackgroundDuring primary percutaneous coronary intervention (PCI), manual thrombectomy may reduce distal embolization and thus improve microvascular perfusion. Small trials have suggested that thrombectomy improves surrogate and clinical outcomes, but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI to a strategy of routine upfront manual thrombectomy versus PCI alone. The primary outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association (NYHA) class IV heart failure within 180 days. The key safety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomy group versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in the thrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P=0.86). The rates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone; hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P=0.34) and the primary outcome plus stent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio, 1.00; 95% CI, 0.89 to 1.14; P=0.95) were also similar. Stroke within 30 days occurred in 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%) in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P=0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy, as compared with PCI alone, did not reduce the risk of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heart failure within 180 days but was associated with an increased rate of stroke within 30 days. (Funded by Medtronic and the Canadian Institutes of Health Research; TOTAL ClinicalTrials.gov number, NCT01149044.).
Project description:BackgroundComplete revascularization may improve outcomes compared with an infarct-related artery (IRA)-only strategy in patients being treated with primary percutaneous coronary intervention (PPCI) who have multivessel disease presenting with ST-segment elevation myocardial infarction (STEMI). However, there is concern that non-IRA PCI may cause additional non-IRA myocardial infarction (MI).ObjectivesThis study sought to determine whether in-hospital complete revascularization was associated with increased total infarct size compared with an IRA-only strategy.MethodsThis multicenter prospective, randomized, open-label, blinded endpoint clinical trial evaluated STEMI patients with multivessel disease having PPCI within 12 h of symptom onset. Patients were randomized to either IRA-only PCI or complete in-hospital revascularization. Contrast-enhanced cardiovascular magnetic resonance (CMR) was performed following PPCI (median day 3) and stress CMR at 9 months. The pre-specified primary endpoint was infarct size on pre-discharge CMR. The study had 80% power to detect a 4% difference in infarct size with 100 patients per group.ResultsOf the 296 patients in the main trial, 205 participated in the CMR substudy, and 203 patients (98 complete revascularization and 105 IRA-only) completed the pre-discharge CMR. The groups were well-matched. Total infarct size (median, interquartile range) was similar to IRA-only revascularization: 13.5% (6.2% to 21.9%) versus complete revascularization, 12.6% (7.2% to 22.6%) of left ventricular mass, p = 0.57 (95% confidence interval for difference in geometric means 0.82 to 1.41). The complete revascularization group had an increase in non-IRA MI on the pre-discharge CMR (22 of 98 vs. 11 of 105, p = 0.02). There was no difference in total infarct size or ischemic burden between treatment groups at follow-up CMR.ConclusionsMultivessel PCI in the setting of STEMI leads to a small increase in CMR-detected non-IRA MI, but total infarct size was not significantly different from an IRA-only revascularization strategy. (Complete Versus Lesion-Only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605).
Project description:Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-elevation myocardial infarction (STEMI). Clinical practice guidelines recommend performing pPCI <120 minutes after the diagnosis of STEMI. Nevertheless, in a real world model this treatment is not always the fastest option. This is mostly due to the transfer delays when patients arrive to non-PCI capable hubs. These delays can decrease the benefits of the PPCI. Regional networks have been created to speed up these times and administer reperfusion therapy as early as possible. The pharmacoinvasive strategy (PIs) consists of the administration of fibrinolytic drugs in the non-pPCI setting followed by the immediate transfer of the patient to a pPCI center. Purpose To compare the efficacy and safety of pharmacoinvasive strategy compared with referral for primary PCI in patients with STEMI presenting to non PCI hubs. Methods A retrospective analysis of the PHASE-MX study (ClinicalTrials.gov Identifier: NCT03974581) including patients with STEMI whom initially presented to non-PCI hospitals and underwent either systemic fibrinolysis followed by pharmaco-invasive strategy or were transfer to perform primary PCIc according to the decision made by the doctor in the non-PCI center, the ease of referring the patient and the proximity of the PCI center. The primary composite endpoint included the occurrence of cardiovascular death, cardiogenic shock, recurrent MI or congestive heart failure at 30 days of follow-up. Results A total of 448 patients were included, of whom 273 (60.9%) underwent PIs and 175 (39.0%) were transfered for pPCI. Mean age was 58+-10 years, and most patients (86.8%) were male. No statistically significant differences in risk factors and other clinically meaningful variables were found. There was a 40% reduction in the risk of the primary composite endpoint (HR 0.60 for PIs: 95% CI:0.36-0.99; p = 0.048) for those undergoing PIs compared with pPCI, (Figure 1). Conclusion The pPCI main limitation is the impossibility to use it in the entire population due to its limited geographic availability and the delays involved in the transfer of patients from non-pPCI centers to reference hospitals. Through the PIs patients who arrive at non-PCI hospitals with STEMI and receive thrombolysis and then are redirect to PCI center there was a 40% reduction in the risk of a major endpoint occurring.
Project description:BackgroundAlthough there are studies examining each one separately, there are no data in the literature comparing the magnitudes of the iatrogenic, percutaneous coronary intervention (PCI)-induced, microvascular dysfunction (Type-4 CMD) and coronary microvascular dysfunction (CMD) in the setting of ischaemia in non-obstructed coronary arteries (INOCA) (Type-1 CMD).ObjectivesWe aimed to compare the characteristics of Type-1 and Type-4 CMD subtypes using coronary haemodynamic (resistance and flow-related parameters), thermodynamic (wave energy-related parameters) and hyperemic ECG changes.MethodsCoronary flow reserve (CFR) value of <2.5 was defined as CMD in both groups. Wire-based multimodal perfusion markers were comparatively analysed in 35 patients (21 INOCA/CMD and 14 CCS/PCI) enrolled in NCT05471739 study.ResultsBoth groups had comparably blunted CFR values per definition (2.03±0.22 vs 2.11±0.37; p: 0.518) and similar hyperemic ST shift in intracoronary ECG (0.16±0.09 vs 0.18±0.07 mV; p: 0.537). While the Type-1 CMD was characterised with impaired hyperemic blood flow acceleration (46.52+12.83 vs 68.20+28.63 cm/s; p: 0.017) and attenuated diastolic microvascular decompression wave magnitudes (p=0.042) with higher hyperemic microvascular resistance (p<0.001), Type-4 CMD had blunted CFR mainly due to higher baseline flow velocity due to post-occlusive reactive hyperemia (33.6±13.7 vs 22.24±5.3 cm/s; p=0.003).ConclusionsThe perturbations in the microvascular milieu seen in CMD in INOCA setting (Type-1 CMD) seem to be more prominent than that of seen following elective PCI (Type-4 CMD), although resulting reversible ischaemia is equally severe in the downstream myocardium.