Tissue characterisation by cardiovascular magnetic resonance in ST-segment elevation myocardial infarction

Acute ST-segment elevation myocardial infarction (STEMI) and its associated co-morbidities are among the leading causes of death and disability worldwide. We used multi-parametric mapping by cardiovascular magnetic resonance (CMR) to provide insights into the pathological processes underlying the ischaemic insult and LV remodelling. In Chapter 4 we showed that T1 mapping could quantify the AAR as well as T2 mapping. Secondly, the presence of a hypo-intense core on T1 or T2 maps performed equally well to detect intramyocardial haemorrhage (IMH). Lastly, we showed that post-contrast T1 maps could accurately delineate acute MI size. In chapter 5, we found that 6 standard deviations (SD) was the most accurate semi-automatic method both for acute and chronic MI size quantification using paired CMR scans. However, all 4 of the promising semi-automated techniques assessed (5-SD, 6SD, full width half maximum and Otsu) were equally precise. In chapter 6, we showed that the majority of patients with IMH had residual iron at follow-up and the latter was associated with adverse LV remodelling. Adverse LV remodelling itself was associated with delayed resolution of oedema in the MI zone. The remote extracellular volume fraction (ECV) was higher in the STEMI patients within the first week, when compared to controls, but only remained elevated in those patients who developed adverse LV remodelling. In Chapter 7, we obtained the minimal detectable changes for percentage change in LV end-diastolic volume (%ΔLVEDV – 12%) and %Δ in LV end-systolic volume (%ΔLVESV – 13%) in paired acute and follow-up STEMI patients. Combining %ΔLVEDV and %ΔLVESV revealed 4 patterns of LV remodelling. In conclusion, T1, T2 and T2* CMR mapping complement each other, and provide valuable insights into the pathophysiology of STEMI and adverse LV remodelling. These parameters could be used to risk-stratify, assess response to treatment and for prognostication in reperfused STEMI patients

Benefits and harms of extending the duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stents: a meta-analysis

Background. The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is unclear. Methods. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating risk of adverse events in participants receiving different durations of DAPT following insertion of drug-eluting stents. Results. Five trials were included, but only four had data suitable for meta-analysis ( participants). No significant increase in the composite endpoint of death and nonfatal myocardial infarction was observed with earlier cessation of DAPT in any instance when compared to longer durations of DAPT (RR 0.64 95% CI 0.25–1.63 for 3 versus 12 months, RR 1.09 95% CI 0.84–1.41 for 6 versus 12 months and, RR 0.64 95% CI 0.35–1.16 for 12 versus 24 months). Pooled results showed a significantly lower risk of major bleeding (RR 0.48 95% CI 0.25–0.93) and total bleeding (RR 0.30 95% CI 0.16–0.54) for shorter compared to longer duration of DAPT. Subgroup analysis based on age, prior diabetes, and prior ACS failed to show any group where longer durations were consistently better than shorter ones. Conclusions. There are no cardiovascular or mortality benefits associated with extended duration of DAPT, but the risk of major bleeding was significantly lower with shorter lengths of therapy

Mapping Myocardial Salvage Index by Extracellular Volume Fraction Are We There Yet?

In ST-segment–elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI), the myocardial salvage index (MSI) provides a more sensitive measure for assessing the efficacy of novel cardioprotective therapies, than an absolute reduction in myocardial infarct (MI) size. Knowledge of the MI size and the size of the area at risk (AAR) are prerequisites for measuring the MSI, and both may be obtained by cardiovascular magnetic resonance (CMR) in reperfused STEMI patients, with the MSI shown to predict clinical outcomes after PPCI.1 CMR is considered the gold standard imaging modality for quantifying MI size, and it can also delineate the edema-based AAR, with T2- and T1-mapping CMR emerging as the most robust techniques,2 although no consensus has yet been reached

Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?

Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction