Abstract The relentlessly beating heart has the greatest oxygen consumption of any organ in the body at rest reflecting its huge metabolic turnover and energetic demands. The vast majority of its ...energy is produced and cycled in form of ATP which stems mainly from oxidative phosphorylation occurring at the respiratory chain in the mitochondria. Apart from energy production, the respiratory chain is also the main source of reactive oxygen species and plays a pivotal role in the regulation of oxidative stress. Dysfunction of the respiratory chain is therefore found in most common heart conditions. The pathophysiology of mitochondrial respiratory chain dysfunction in hereditary cardiac mitochondrial disease, the ageing heart, in LV hypertrophy and heart failure, and in ischaemia–reperfusion injury is reviewed. We introduce the practising clinician to the complex physiology of the respiratory chain, highlight its impact on common cardiac disorders and review translational pharmacological and non-pharmacological treatment strategies.
Takotsubo syndrome mimics acute myocardial infarction (MI) at presentation.
To explore differences in ECG time-course that could further help distinguish the two conditions.
Serial ECG's (day 0–4) of ...27 acute takotsubo and 37 MI patients, all presenting with anterior ST-elevation, were analysed for detailed morphology and timing of de/re-polarisation. All underwent cardiac magnetic resonance.
The presenting ECG (day 0) showed significantly fewer total abnormal leads (p = .001), comparable number of ST-elevation leads but lesser total magnitude of ST-elevation (p = .003), smaller sum of positive T wave amplitude (p = .006) and lesser number of pathological Q waves (p = .005) in takotsubo vs the MI group. After day 0, takotsubo patients developed more widespread T wave inversion (p = .001, day 3) and/or deeper T waves compared to MI, (sum of the T-wave amplitude slope of change between days 0–3: −43.1 ± 9.6 vs − 16.6 ± 5.4 mm, p = .02). Although there was no difference in mean QTc between the groups on any day, between days 0–3 there was a progressive increase in QTc in takotsubo vs a decrease in MI (34.1 ± 12.2 vs −29.5 ± 9.3 ms, slope of change p < .001). There was significantly more myocardial oedema (native T1 mapping) in takotsubo vs MI (p = .02), which resulted in increased left ventricular mass index in takostubo (p = .04).
The differences in presenting (day 0) ECG between takotsubo and MI are significant but subtle, reinforcing the importance of acute cardiac catheterisation for accurate diagnosis. During the next 3 days there is progressive increase in the depth and spread of T-waves and QTc duration in takotsubo vs MI - these may aid the diagnostic confidence in patients with bystander non-obstructive coronary disease.
•Presenting ECG in Takotsubo has fewer total abnormal leads, lesser magnitude of ST-elevation/pathological Q waves than MI.•The 4-day evolution of Takotsubo ECG compared to MI is characterised by much more widespread and deeper T wave inversion.•The mean QTc progressively increases in takotsubo whilst in MI decreases.
Abstract Objectives To compare 3T T1 mapping to conventional T2 -weighted (T2 W) imaging for delineating myocardial oedema one week after ST-elevation myocardial infarction (STEMI), and to explore ...the confounding effects of microvascular obstruction (MVO) on each technique. Methods T2 W spectral attenuated inversion recovery and native T1 mapping were applied in 10 healthy volunteers and 62 STEMI patients, and late gadolinium enhancement was included for infarct localisation at 1 week and at 6 months post-STEMI. Segmental T1 values and T2 W signal intensity ratios were calculated; oedema volumes and salvage indices were determined in patients using image thresholding—a receiver operator characteristic (ROC) derived T1 threshold, and a 2SD T2 W threshold; and the results were compared between patients with/without MVO ( n = 35/27). Results Native T1 mapping delineated oedema with significantly better discriminatory power than T2 W—as indicated by ROC analysis (area-under-the-curve, AUC = 0.89 versus 0.83, p = 0.009; and sensitivity/specificity = 83/83% versus 73/73%). The optimal ROC threshold derived for T1 mapping was 1241 ms, which gave significantly larger oedema volumes than 2SD T2 W ( p = 0.006); with this threshold, patients with and without MVO showed similar oedema volumes, but patients with MVO had significantly poorer salvage indices ( p < 0.05) than those without. Neither method was significantly affected by MVO, the volume of which was seen to increase exponentially with infarct size. Conclusions Native T1 mapping at 3T can delineate oedema one week post-STEMI, showing larger oedema volumes and better discriminatory power than T2 W imaging, and it is suitable for quantitative thresholding. Both techniques are robust against MVO-related magnetic susceptibility.
Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute ...event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial.
The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING, ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26).
ClinicalTrials.gov: NCT01388504 and Current Controlled Trials: ISRCTN57596739.
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