In terms of clinical practice guidelines, new or updated guidelines were released in four areas relevant to current clinical practice at ESC 2022: cardio-oncology, pulmonary hypertension, cardiovascular assessment of patients undergoing non-cardiac surgery, and ventricular arrhythmias and sudden cardiac death. 

The cardio-oncology guidelines have been published for the first time and emphasise the integration of knowledge across cardiology, oncology and haematology with specific emphasis on minimising unnecessary cancer therapy interruptions and cancer therapy-related cardiovascular toxicity across the entire spectrum of cancer care.¹

In terms of the updated pulmonary hypertension (PH) guidelines, key messages to note are that the definition of PH has been updated to a mean pulmonary artery pressure > 20 mmHg (from 25 mmHg) with a peripheral vascular resistance (PVR) of > 2 WU and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, although the efficacy of pulmonary hypertension therapies at the lower limits of this range is unproven.²

In terms of ventricular arrhythmias and the prevention of sudden cardiac death, when considering ICD therapy benefit, competing risk factors for non-arrhythmic death and the patient’s wishes and quality of life need to be taken into account.³

From the point of view of guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery, it is important to note that clinical examination, patient-reported functional capacity and non-invasive tests represent the cornerstone of pre-operative cardiac assessment, and invasive assessment is not always required.⁴

Left ventricular dysfunction

Several ground-breaking trials, published simultaneously in the New England Journal of Medicine, were presented at ESC. REVIVED-BCIS2 was a study on percutaneous revascularisation for ischaemic left ventricular dysfunction.⁵ It was academia-led and independent from industry funding. The hypothesis of this study was that revascularisation in combination with optimal medical therapy, compared to optimal medical therapy alone, leads to improved event-free survival in patients with severe ischaemic left ventricular dysfunction and evidence of myocardial viability. Of note, there is evidence that in the same setting, albeit without formal viability assessment, that surgical revascularisation improves long-term survival on the basis of the results of the STITCH trial.⁶

To be included, patients needed to have a left ventricular ejection fraction of less than 35% and have demonstrated evidence of viability in at least four myocardial segments that were amenable to percutaneous revascularisation. Patients also required reasonably extensive evidence of coronary artery disease and this was assessed by a special scoring system, the BCIS Jeopardy score, which is not in routine use outside of the UK. It was a trial of chronic coronary syndrome, so patients with a recent acute coronary syndrome or current unstable presentation were excluded. 

The overarching result was that there is no difference between PCI and optimal medical therapy in terms of the primary outcome of death from any cause or hospitalisation for heart failure (HF). Specifically, the relative risk was 0.99 (95% CI 0.78-1.27) for patients treated with PCI. Of note, there was a difference in the numbers of spontaneous myocardial infarction (MI) with 18 in the PCI arm versus 33 in the medical therapy arm. Ultimately, when interpreting the results of the trial, it is important to take the inclusion criteria into account and not generalise the results of this study, taking note in particular that patients with angina were not well represented. Overall, the results of this trial do re-emphasise that the niche for PCI in stable ischaemic coronary artery disease is symptom control, rather than providing a mortality benefit. It would be interesting to determine if the results of the STICH trial still held up if it were run in the present day with excellent medical therapy for HF, in particular the availability of sacubitril-valsartan and SGLT-2 inhibitors.

DOACs vs warfarin in RHD

INVICTUS was a non-inferiority trial which aimed to compare the use of the DOAC (direct oral anticoagulant), rivaroxaban versus vitamin K antagonists in the treatment of rheumatic heart disease in Africa, Asia and Latin America.⁷ The presence of a metallic valve or likelihood of implantation of a metallic valve in the next six months was an exclusion criterion. The primary endpoint was a composite of stroke, systemic embolism, MI or death from vascular or unknown causes. In terms of the Kaplan-Meier curves, we can clearly see a divergence between rivaroxaban and vitamin K antagonists at 54 months, in favour of vitamin K antagonists in a statistically significant manner, although numerically there were more bleeding events in the vitamin K antagonist group compared to the rivaroxaban group. However, this difference in bleeding outcomes was not statistically significant. Thus, vitamin K antagonists remain the anticoagulant of choice in the setting of rheumatic valvular heart disease.

Outcomes in patients post high-risk PCI 

The Post-PCI trial attempted to answer the question of whether routine care or systematic postprocedural functional testing led to differing outcomes for patients post high-risk PCI.⁸ Patients required at least one high-risk anatomical feature such as a bifurcation or left main lesion for inclusion in the study, or one high-risk clinical feature, eg. diabetes or chronic kidney disease. A total of 1,706 patients were included. Functional testing included nuclear, exercise ECG or exercise stress test. The primary endpoint was a composite of death from any cause, MI or hospitalisation from unstable angina at two years. The key result was that no difference was seen between the functional testing group versus standard of care, with the primary endpoint occurring in 5.5% of the functional testing group compared to 6.0 % of the standard care group. Looking at the individual components of the primary endpoint, there was a numerical but not statistically significant difference in terms of all cause death and MI (with higher event rates in the functional testing arm) and there does not appear to be a clear mechanistic explanation underlying them. Overall, we can conclude that there is no additional benefit to routine functional testing over standard care post-PCI.

Dapagliflozin in heart failure

DELIVER looked at dapagliflozin in HF with mildly reduced or preserved ejection fraction.⁹ This was a double blind randomised controlled trial and patients were only eligible for randomisation if they had a left ventricular ejection fraction of > 40%, had elevated natriuretic peptides and evidence of structural heart disease. The primary outcome was defined as a composite of either an unplanned hospitalisation for HF, an urgent visit for HF or cardiovascular death. A significant difference was seen in the dapagliflozin arm compared to the placebo arm, corresponding to a hazard ratio of 0.82 (0.73-0.92), p < 0.001 for dapagliflozin. Adverse events appeared well balanced between the groups. Here, we can conclude that dapagliflozin is one of the few medications that is safe and effective in the difficult-to-treat cohort of patients with mildly reduced or preserved HF. It will be interesting to see further research outlining the differential effect of dapagliflozin as ejection fraction increases, particular in terms of whether a benefit remains in those patients with an EF of > 60%.

Polypill treatment 

The SECURE trial looked at the efficacy of a polypill-based strategy, containing aspirin, ramipril and atorvastatin, as compared to usual care, with respect to major cardiovascular outcomes in older patients with recent MI.¹⁰ Eligible patients needed to have had a type one MI in the past six months and have a significant risk factor profile as dictated by age > 75 or > 65 with diabetes, mild or moderate kidney dysfunction, previous MI or coronary revascularisation or previous stroke. The hazard ratio for the polypill compared to usual care was 0.76 (95% CI, 0.60-0.96), p = 0.02 for superiority in terms of a primary endpoint of death from cardiovascular causes, non-fatal type one MI, non-fatal ischaemic stroke or urgent revascularisation. Even without consideration of urgent revascularisation, there was a significant difference between groups. While use of a polypill is reasonably common in Ireland, this is not the case in other European countries, and it will be interesting to see if there is an increased uptake internationally on the basis of this trial. Furthermore, the currently available polypill has the weakness that it does not come in a formulation that includes a high-intensity statin (eg. atorvastatin 80mg), and it would be interesting to assess the additional difference in outcomes as a consequence of including this higher dose. Overall though, we can conclude that use of a polypill is a relatively simple strategy to improve patient outcomes in this higher-risk cohort, and should be implemented where possible.

Acetazolamide in HF treatment

The ADVOR trial was designed to assess the benefit of acetazolamide in acute decompensated HF with volume overload.¹¹ The aim of the study was to assess if the addition of acetazolamide to standard IV loop diuretic therapy would improve the incidence of successful decongestion. It was a multicentre, parallel-group, double-blind, randomised, placebo-controlled trial in adult patients with AHDF, clinical signs of volume overload and elevated natriuretic peptide levels. The primary endpoint was successful decongestion – absence of signs of volume overload within three days after randomisation without an indication for escalation of decongestive therapy. Patients needed to be on a stable dose of oral diuretics for at least one month prior to randomisation. Of note, treatment with other medication which acted on the proximal tubule, including SGLT2 inhibitors, was an exclusion criterion. In summary, the risk ratio for successful decongestion within three days after randomisation was 1.46 (95% CI, 1.17-1.82) for acetazolamide vs placebo, with successful decongestion at discharge also being higher (78.8% of acetazolamide vs 62.5% of placebo, RR 1.27, 95% CI 1.13-1.43). In the longer term, there was no significant difference between death from any cause or rehospitalisation for HF during follow-up. Overall, we can report that acetazolamide seems to be helpful in terms of improving decongestion, but at present does not translate into a difference in hard clinical endpoints.

In summary, in the spheres of percutaneous coronary intervention in ischaemic heart disease, HF with reduced ejection fraction and anticoagulation for rheumatic heart, significant new information at ESC 2022 has been made available, which will guide our assessment and management of these challenging cases.

References

1. Lyon AR, Lopez-Fernandez T, Couch LS et al. 2022 ESC Guidelines on cardio-oncology. Eur Heart J. 2022. doi: 10.1093/eurheartj/ehac244
2. Humbert M, Kovacs G, Hoeper MM et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43:3618-3731. doi: 10.1093/eurheartj/ehac237
3. Zeppenfeld K, Tfelt-Hansen J, de Riva M et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43:3997-4126. doi: 10.1093/eurheartj/ehac262
4. Halvorsen S, Mehilli J, Cassese S et al. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J. 2022;43:3826-3924
5. Perera D, Clayton T, O’Kane PD et al. Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction. N Engl J Med. 2022;387:1351-1360. doi: 10.1056/NEJMoa2206606
6. Velazquez EJ, Lee KL, Deja MA et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364:1607-1616. doi: 10.1056/NEJMoa1100356
7. Connolly SJ, Karthikeyan G, Ntsekhe M et al. Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation. N Engl J Med. 2022;387:978-988. doi: 10.1056/NEJMoa2209051
8. Park DW, Kang DY, Ahn JM et al. Routine Functional Testing or Standard Care in High-Risk Patients after PCI. N Engl J Med. 2022;387:905-915
9. Solomon SD, McMurray JJV, Claggett B et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387:1089-1098. doi: 10.1056/NEJMoa2206286
10. Castellano JM, Pocock SJ, Bhatt DL et al. Polypill Strategy in Secondary Cardiovascular Prevention. N Engl J Med. 2022;387:967-977. doi: 10.1056/NEJMoa2208275
11. Mullens W, Dauw J, Martens P et al. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022;387:1185-1195