Editorial articles

The renin–angiotensin system (RAS) has been at the forefront of research aimed at mitigating the infectivity and mortality associated with the coronavirus disease 2019 (COVID-19) pandemic. This stems from the observation that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, utilises angiotensin-converting enzyme 2 (ACE2) as its receptor to invade host cells. Since emergence of COVID-19, conflicting guidance has been published on the use of medications that may increase ACE2 levels. Specifically, initial reports suggested that ACE inhibitors and angiotensin II type 1 receptor blockers (ARBs) may result in increased virulence of COVID-19 due to elevated ACE2. Thus, discontinuation of these RAS blockers was advised. However, the data on ACE2 expression with use of RAS blockers in humans without COVID-19 are not clear, and for humans with COVID-19 are not yet available. Moreover, discontinuation of these medications may be deleterious in some patients for whom they are prescribed to treat heart failure, hypertension and ischaemic heart disease. For this reason, professional organisations, including the American College of Cardiology, American Heart Association, Heart Failure Society of America and the European Society of Cardiology, have issued statements advising against discontinuation of any RAS-related treatments in patients during the COVID-19 crisis.

The benefit of percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) is undisputed. Clinical trials like DANAMI-2 (DANish Acute Myocardial Infarction 2),^1-3 PRAGUE-2 (Primary Angioplasty in AMI Patients from General Community Hospitals Transported to PTCA Units vs Emergency Thrombolysis),^4,5 STAT (Stenting Versus Thrombolysis in Acute Myocardial Infarction),⁶ AIR PAMI (Air Primary Angioplasty in Myocardial Infarction),⁷ Stent Versus Thrombolysis for Occluded Coronary Arteries in Patients With Acute Myocardial Infarction (STOPAMI)-1,⁸ and STOPAMI-2⁹ have demonstrated better outcomes with primary PCI over fibrinolysis. Other clinical trials^10-14 have demonstrated superiority of PCI over sole medical therapy for non-ST elevation myocardial infarction (NSTEMI) and unstable angina.

In contrast, there is ambiguity surrounding the benefit of elective PCI in stable coronary disease. The available evidence suggests no prognostic advantage over optimum medical therapy but deeper data scrutiny indicates that this remains uncertain. COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation),¹⁵ BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes),¹⁶ and ISCHEMIA (Initial Invasive or Conservative Strategy for Stable Coronary Disease)¹⁷ are the main trials that examined this issue, all concluding against the prognostic usefulness of elective PCI. We argue that those studies contained inherent flaws that impacted on their results, thereby rendering their final conclusions unreliable. We suggest an alternative design for a new trial so the question can be answered decisively, once and for all.

The utility of computed tomography (CT) coronary angiography (CTCA) is underpinned by its excellent sensitivity and negative-predictive value for coronary artery disease (CAD), although it lacks specificity. Invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR), are gold-standard investigations for coronary artery disease, however, they are resource intensive and associated with a small risk of serious complications. FFR-CT has been shown to have comparable performance to FFR measurements and has the potential to reduce unnecessary ICAs. The aim of this study is to briefly review FFR-CT, as an investigational modality for stable angina, and to share ‘real-world’ UK data, in consecutive patients, following the initial adoption of FFR-CT in our district general hospital in 2016.

A retrospective analysis was performed of a previously published consecutive series of 157 patients referred for CTCA by our group in a single, non-interventional, district general hospital. Our multi-disciplinary team (MDT) recorded the likely definitive outcome following CTCA, namely intervention or optimised medical management. FFR-CT analysis was performed on 24 consecutive patients where the MDT recommendation was for ICA. The CTCA + MDT findings, FFR-CT and ICA ± FFR were correlated along with the definitive outcome.

In comparing CTCA + MDT, FFR-CT and definitive outcome, in terms of whether a percutaneous coronary intervention was performed, FFR-CT was significantly correlated with definitive outcome (r=0.471, p=0.036) as opposed to CTCA + MDT (r=0.378, p=0.07). In five cases (21%, 5/24), FFR-CT could have altered the management plan by reclassification of coronary stenosis. FFR-CT of 60 coronary artery vessels (83%, 60/72) (mean FFR-CT ratio 0.82 ± 0.10) compared well with FFR performed on 18 coronary vessels (mean 0.80 ± 0.11) (r=0.758, p=0.0013).

In conclusion, FFR-CT potentially adds value to MDT outcome of CTCA, increasing the specificity and predictive accuracy of CTCA. FFR-CT may be best utilised to investigate CTCAs where there is potentially prognostically significant moderate disease or severe disease to maximise cost-effectiveness. These data could be used by other NHS trusts to best incorporate FFR-CT into their diagnostic pathways for the investigation of stable chest pain.

“Alone we can do so little, together we can do so much.” Helen Keller

The links between kidney disease and cardiovascular disease have been reported as far back as 1827 with Richard Bright describing the changes in the left ventricle associated with kidney disease, and subsequently, Frederick Akbar Mahomed reporting increased arterial stiffness in patients with Bright’s disease.¹ Over the last two to three decades it has become increasingly apparent that kidney disease is the most important predictor of outcomes in all cardiology diseases and that cardiovascular disease is the leading cause of death in patients with chronic kidney disease.² In 2008, a systematic approach to the bi-directional interactions of heart and kidney diseases, or cardiorenal syndromes (table 1), was proposed.³ Cardiorenal syndromes can be broadly defined as disorders of the heart and kidney whereby acute or chronic dysfunction in one organ can induce acute or chronic dysfunction in the other.⁴ This was followed by increasing efforts to develop strategies to manage patients with combined heart and kidney dysfunction, as demonstrated by an increasing number of publications on cardiorenal syndromes.⁵

In 2015 one of my patients in the Fourier PCSK9 inhibitor trial asked me if I would like to attend his ‘bespoke’ total knee replacement operation. I said yes and witnessed an amazing procedure.

When the extent of the coronavirus threat became clear, it was an obvious imperative to close down elective catheter lab work for all cases except for patients at the highest level of clinical urgency. The effect of this action is illustrated by the national survey reported by Adlan and colleagues.¹

Above and beyond the immediate, unarguable imperative to limit elective work, a range of other equally immediate challenges relating to patient care were apparent, and generated strong but divergent opinion within the interventional cardiology community. Firstly, the optimal treatment plan for patients presenting with ST-elevation myocardial infarction (STEMI)… should primary percutaneous coronary intervention (PCI) remain the default strategy, or should it now be to adopt thrombolysis as a default, as recommended by hastily constructed care pathways in other countries which were affected by COVID-19 earlier than the UK? Secondly, what level of personal protective equipment (PPE) should cardiologists and cath lab staff wear for the cases who did make it to the lab? Finally, how should patients admitted to hospital with severe symptomatic aortic stenosis be treated?

The current President of the United States once stated that “the kidney has a very special place in the heart”; despite the questionable anatomical reference, the truth is that the kidneys and heart are intertwined, affected by common pathophysiological processes and sharing many of the same disease-causing risk factors. Ronco and colleagues have previously classified the complex array of inter-related derangements that simultaneously involve both organs, and this serves as a useful starting point in understanding their important physiological and pathophysiological inter-dependence.¹

Cardiac surgery for adults became widely available around 50 years ago, due mainly to the introduction of relatively safe cardiopulmonary bypass. Initially, mortality rates were quite high, even for relatively young and fit patients, and, therefore, patients and carers focused on this outcome measure. Moreover, it was easy to define and record. Local and national registries developed into databases that allowed comparison of mortality rates and were then further refined with risk modelling.

As the odds of survival after cardiac surgery improved, sicker and older patients were offered cardiac surgery, including octogenarians and extending to nonagenarians.

Clearly, surviving cardiac surgery is very important – but is survival the top priority for the 92-year old after bypass surgery who becomes unable to live independently again and who’s quality of life is insufferable? Should quality of life be the main factor driving therapeutic decisions for the frail and elderly?

The use of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape for a number of tumour types over the past decade. Targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; ipilimumab), programmed cell death protein 1 (PD1; nivolumab, pembrolizumab), and programmed death-ligand 1 (PD-L1; atezolizumab, avelumab, or durvalumab), as monotherapy or in combination, activates the immune system to recognise and target cancer cells via a T-cell-mediated immune response and can lead to improved survival in the metastatic setting in a number of malignancies, as well as improved recurrence-free survival when utilised in multi-modality radical treatment paradigms in melanoma and non-small cell lung cancer (NSCLC).^1,2 The systemic activation of T-cells can also lead to auto-immune toxicity, affecting any body system; most commonly skin, gastrointestinal, liver and endocrine toxicities.³

When I first arrived at Whitby Group Practice (WGP) in the middle 80s, my surgery was next to Whitby Hospital Outpatients, where Anthony Bacon conducted his cardiology clinic. Dr Bacon’s article on aortic stenosis was in our previous issue.¹ In this issue, Tariq Enezate and colleagues add to our knowledge of managing this condition.²