Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

Background: The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. Methods: This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. Results: 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1–1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01–1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62–0.93], P = 0.009). Conclusions: Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors

Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Ischaemic conditioning and reperfusion injury

The 30-year anniversary of the discovery of 'ischaemic preconditioning' is in 2016. This endogenous phenomenon can paradoxically protect the heart from acute myocardial infarction by subjecting it to one or more brief cycles of ischaemia and reperfusion. Apart from complete reperfusion, this method is the most powerful intervention known for reducing infarct size. The concept of ischaemic preconditioning has evolved into 'ischaemic conditioning', a term that encompasses a number of related endogenous cardioprotective strategies, applied either directly to the heart (ischaemic preconditioning or postconditioning) or from afar, for example a limb (remote ischaemic preconditioning, perconditioning, or postconditioning). Investigations of signalling pathways underlying ischaemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. Over the past 3 decades, a number of ischaemic and pharmacological cardioprotection strategies, discovered in experimental studies, have been examined in the clinical setting of acute myocardial infarction and CABG surgery. The results from many of the studies have been disappointing, and no effective cardioprotective therapy is currently used in clinical practice. Several large, multicentre, randomized, controlled clinical trials on cardioprotection have highlighted the challenges of translating ischaemic conditioning and pharmacological cardioprotection strategies into patient benefit. However, a number of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischaemic heart disease

If not now, when? Enhancing cardiologists’ psychological well-being as a COVID-19 gain

COVID-19 has highlighted potential shortcomings in our approach to psychological health that had perhaps become the accepted status quo within cardiology. Importantly, the pandemic may offer a unique opportunity to redress them. During 2020, physicians have had to question their ability to deliver optimal care with scarce resources, limited knowledge, concerns about personal safety and, by extension, the safety of one’s family. For some, these challenges may have a lasting psychological impact. Encouragingly, many staff have acknowledged the potential effect of these pressures on their mental health, making short-term adaptations and promoting staff camaraderie. However, achieving long-lasting changes in our approach to supporting those affected could create a positive legacy to this pandemic

Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial.

BACKGROUND: Novel cardioprotective strategies are required to improve clinical outcomes in high risk patients undergoing coronary artery bypass graft (CABG) ± valve surgery. Remote ischemic preconditioning (RIC), in which brief episodes of non-lethal ischemia and reperfusion are applied to the arm or leg, has been demonstrated to reduce perioperative myocardial injury following CABG ± valve surgery. Whether RIC can improve clinical outcomes in this setting is unknown and is investigated in the effect of remote ischemic preconditioning on clinical outcomes (ERICCA) trial in patients undergoing CABG surgery. (ClinicalTrials.gov Identifier: NCT01247545). METHODS: The ERICCA trial is a multicentre randomized double-blinded controlled clinical trial which will recruit 1,610 high-risk patients (Additive Euroscore ≥ 5) undergoing CABG ± valve surgery using blood cardioplegia via 27 tertiary centres over 2 years. The primary combined endpoint will be cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1 year. Secondary endpoints will include peri-operative myocardial and acute kidney injury, intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes of quality of life and exercise tolerance. Patients will be randomized to receive after induction of anesthesia either RIC (4 cycles of 5 min inflation to 200 mmHg and 5 min deflation of a blood pressure cuff placed on the upper arm) or sham RIC (4 cycles of simulated inflations and deflations of the blood pressure cuff). IMPLICATIONS: The findings from the ERICCA trial have the potential to demonstrate that RIC, a simple, non-invasive and virtually cost-free intervention, can improve clinical outcomes in higher-risk patients undergoing CABG ± valve surgery