ESC Congress 2020 - The Digital Experience Day 1
With public gatherings banned in the Netherlands due to the COVID-19 pandemic, the 2020 edition of the European Society of Cardiology Congress, originally due to take place in Amsterdam, was staged online from 29 August to 1 September. BCS members in attendance share their experience of the first day of this new format.
Dr Noor Sharrack, Cardiology SpR
Professor Barbara Casadei nicely opened the conference in her inaugural lecture with a stark reminder of the importance of unity and collaboration in the era of COVID-19. She reminded us of the great research being undertaken by our colleagues across the globe and the toll this pandemic has taken on our patients. The first day presented the results of 2 important trial results, EMPEROR-Reduced and EXPLORER-HCM both of which have been published in the NEJM.
Milton Packer presented the results of EMPEROR-Reduced recently published in the NEJM. 3730 patients were randomised to either empaglifozin 10mg (n=1863) or placebo (1867). All patients were receiving optimal medical treatment for heart failure. All 3 endpoints were reached with statistical significance. The primary outcome of cardiovascular death, or HF hospitalisation for empaglifozin vs placebo was 19.4% vs. 24.7% (hazard ratio 0.75, CI 0.65-10.86, P<0.001. Second endpoint was total heart failure hospitalisations and the third was slope of decline in glomerular filtration rate over time.
Compared to DAPA-HF, this study enrolled patients with lower ejection fractions and worsening renal function. 70% of patients enrolled had an ejection fraction <30%.
The 25% decrease in the risk of the composite of cardiovascular death and heart failure hospitalisations was identical to that seen in DAPA-HF. Empaglifozin also slowed down the decline of renal disease.
In the EXPLORER-HCM global phase 3 trial, 251 patients with symptomatic obstructive HCM were randomised to once-daily mavacamten (5 mg initially with a two-step dose titration) or placebo for 30 weeks. Mavacamten is a selective allosteric inhibitor of cardiac myosin ATPase designed to target fundamental abnormalities associated with HCM.
The primary endpoint was the treatment effect of mavacamten at week 30 relative to placebo on both symptoms and cardiac function, defined as achieving 1) ≥1.5 mL/kg/min improvement in peak oxygen consumption (peak VO2) and ≥1 New York Heart Association (NYHA) class reduction or 2) ≥3.0 mL/kg/min improvement in peak VO2 and no worsening of NYHA class.
EXPLORER-HCM demonstrated the efficacy of mavacamten in obstructive HCM. Primary and all secondary endpoints were met with high statistical significance. At week 30, 45 (36.6%) patients on mavacamten met the primary endpoint vs. 22 (17.2%) patients on placebo (p=0.0005).
Mavacamtem demonstrated clinically important effects on post-exercise LVOT gradients. Nearly 75% of patients saw a reduction below guideline-defined thresholds for invasive septal reduction therapy (SRT) and 56% showed complete relief of obstruction. Mavecemten was well tolerated with a safety profile comparable to placebo.
Image Guided Care in Heart Failure - Meet the Experts
Professor James Thomas from Northwestern University in Chicago presented an interesting case of cardiac sarcoidosis. He recalled the heterogeneity of presentation in this condition; heart block, A/V arrhythmias, HFrEF, HpPEF, sudden cardiac death. A number of imaging modalities helped clinch the diagnosis; echo, cardiac MRI and FDG-PET. ECHO can show non-specific findings, such as regional wall motion abnormalities in a non coronary artery distribution, reduced ejection fraction, diastolic dysfunction, and secondary pulmonary affects from pulmonary sarcoid such as RVH and RV dysfunction.
In acute cardiac sarcoidosis with inflammation of the heart, CMR can show oedema, early Gd enhancement and increased intensity on T2 weighted imaging. Later stages show fibrosis in a non-coronary artery distribution, Gd enhancement in the mid wall and epicardial regions.
He reminded us of FDG-PET scanning as one of the most specific tests in diagnosing sarcoidosis and helped monitor the treatment of sarcoidosis with steroids.
Phillipe Meyer, from Belgium, presented another interesting case of a patient with diastolic dysfunction with was ultimately diagnosed with cardiac amyloidosis.
In this case a variety of imaging modalities were used; echo, CMR, DPD scanning and PET-CT. Echo can show LVH, reduced longitudinal strain, apical sparing and diastolic dysfunction. CMR shows sub-endocardial enhancement of gadolinium suggestive of amyloid infiltration. He highlighted the importance of DPD bone scanning in this condition (particularly in TTR amyloid), and a haematological workup. His feeling was that if there was a negative haematological work-up, biopsy is not needed. However, if there was a positive haematology panel, biopsy would be indicated. He also illustrated PET-CT as a research method used in his centre in the diagnosis of amyloidosis to avoid biopsy.
He concluded by reminding clinicians that cardiac amyloidosis should be suspected in any patient with HfPEF and increased wall thickness. The diagnosis requires a multi-imaging approach and myocardial biopsies are rarely needed. An accurate and rapid diagnosis is crucial because specific therapies are available for AL and ATTR amyloidosis. The mid-term prognosis is poor, especially for AL amyloidosis.
Multimodality Cardiac Imaging in Clinical Practice - Essential Update
Professor James Moon from Barts and UCL talked about multimodality imaging in patients with left ventricular hypertrophy. LVH measurement is often very variable depending on who and how it is measured (with differences up to 1cm). He highlighted the new era of Artificial Intelligence, and how this will help streamline measurements of LVH.
He also talked about the under-diagnosis of TTR amyloid in the population and especially in certain groups of patients. For example, 1/8 TAVI patients have TTR amyloid. He mentioned TPD scanning as an important test. CMR in AL amyloid is crucial; LVH, LGE, T1 and ECV mapping.
This was an excellent day were two clinical trials published in the NEJM were presented. The digital experience worked very well. One was able to re-watch lectures at a later time if they had missed them and nobody struggled to find a seat! Looking forward to the next 3 days.
Dr Rajiv Sankaranarayanan, Consultant Heart Failure Cardiologist
Day 1 of the #ESCCongress2020 witnessed the presentation of results from the EMPEROR-Reduced trial. In this RCT of 3730 pts with NYHA II-IV (primarily NYHA II-III) in HFrEF (with and without diabetes), Empagliflozin on top of optimal medical therapy.
⬇️ Primary outcome of composite CV death/HF hospitalization: HR 0.75(0.65-0.86) after 16 months f/u regardless of diabetes
⬇️ Secondary outcome of HF hospitalisations HR 0.70 (95%CI 0.58-0.85;p<0.001) -delayed annual decrease in eGFR (secondary endpoint)- 50% reduction in renal events
⬆️ Genital infections
There were subtle differences in the EMPEROR-Reduced population in comparison to DAPA-HF
Baseline characteristics in EMPEROR-Reduced
⬆️ Severe HF (Mean EF ≤30%)
⬆️ NTpro-BNP levels (1887 vs 1428 ph/ml)
⬆️ Number of patients on ARNI (18.3 vs 10.5%)
⬇️ Renal function at baseline
⬆️ Patients on ARNI
✔️ Similar CV death / HF hospitalisations
✔️ ⬆️ Significant Renal benefit
✔️ No statistically significant CV death benefit
This is the 1st evidence of a class effect of SGLT2I in #HFrEF, establishing the role of this class as a component of quadruple therapy (beta-blocker, ACE/ARNI, MRA and SGLT2I). There is a need for head to head comparison trials of SGLT2I for unravelling of the lack of reduction in cardiovascular deaths.
Dr Koehler (Germany) spoke regarding the role of biomarker guided remote patient monitoring in reducing the NNT for all cause death from 28 to 21 and would also save 150 hours of effort per year per 100 eligible patients. He also elucidated the role of artificial intelligence in iOS along the number of patients per telemedical centre
Several new Mechanical Circulatory Support Devices were presented including the pulsatile Total Artificial Heart which is designed to mimic native heart function, Carmat (pulsatile device with bovine pericardial membrane- so patients may not require anticoagulation as blood contacting surfaces are biological) and BiVACOR TAH (continuous flow TAH with rotary pump and expected durability of 10 years due to magnetic levitation and lack of contacting surfaces).
Tomorrow we look forward to results from several exciting trials including PARALLAX (role of ARNI on quality of life in HFpEF6 and DAPA-CKD (efficacy of Dapagliflozin in moderate to severe CKD).
Dr Stephanie Connaire, Cardiology SpR
Reflection on Day 1 in HEART FAILURE
Day 1 of the ESC Congress 2020 opened with Professor David Playford from University of Notre Dame presenting on Diastolic Dysfunction and Mortality in 436, 360 Men and Women: the National Echo Database Australia (NEDA). This study used ASE/EACVI classification from the 2016 guidelines and NEDA data to describe guideline- classified diastolic dysfunction in this large nationwide cohort and examine the pattern of mortality of each of the main diastolic parameters.
- ASE/EACVI guidelines identify increased mortality risk in diastolic dysfunction in both patients with preserved and impaired LVEF, but with a high proportion of “indeterminate” classification.
- Individual parameters of diastolic dysfunction were found to have specific pivot points of increased mortality- ~90 cm/s for E wave velocity, ~9cm/s for septal e’ velocity, ~ 9 for E:e’ ratio and ~32ml/m2 for indexed LA volume.
- LVEF and age have important influences on diastolic function, but sex does not.
- These observations may be relevant to future diastolic dysfunction function guidelines.
Professor Burkert Pieske and Professor Franck Ruschitzka then debated the topic of whether classification by ejection fraction should be maintained. Professor Burkert argued the pros and Professor Ruschitzka the cons.
- Ejection fraction is universally accepted, and everyone knows how to apply and interpret it.
- It is relatively easy to use.
- Current heart failure guidelines clearly recommend the use of ejection fraction.
- Ejection fraction enables us to differentiate different phenotypes: HFrEF, HFmrEF HFpEF.
- It has been a key parameter in current influential clinical trials including PARADIGM and DAPA-HF.
- Heart failure is a syndrome of many different disease- ejection fraction is an oversimplification.
- It’s imprecise and arbitrary.
- What is a normal ejection fraction? There is some debate on what is actually classified as normal.
In the concluding discussion, both speakers agreed that ejection fraction should be complimented by additional measures such as strain. Interestingly, they also agreed that ejection fraction should not be the main determinant of improvement when following up patients as this should be guided by the clinical picture. It was also agreed that immunology and genetics will likely pave the way in the near future.
Professor Andrew Coats presented “The Management of Comorbidities in Heart Failure”. Three frequent and important co-morbidities were highlighted- sleep apnoea, atrial fibrillation and secondary mitral regurgitation.
- Sleep apnoea is commonly treated with CPAP. However, there are two types which must be distinguished- obstructive and central sleep apnoea. The SERVE-HF study in 2015 showed that the use of positive pressure ventilation in patients with HFrEF and central sleep apnoea actually caused an excess cardiovascular mortality.
- In the BB-META-HF trial, all of the major RCTs of beta blockers in HFrEF were analysed and it was found that the benefit of beta blockers was restricted to heart failure patients in sinus rhythm. In atrial fibrillation, beta blockers were not shown to have any impact on mortality or hospitalisations. The CASTLE-AF trial, however, showed that catheter ablation improved outcomes for patients with AF and heart failure compared to conventional drug use.
- Drug treatments can reduce the severity of functional MR therefore we should optimise drug treatment first. But there have been two important trials looking at MitraClip- COAPT and MITRA-FR. These trials had very different results with the MITRA-FR trial showing no benefit whereas the COAPT trial showed 37% reduction in 12 months mortality and hospitalisation rate. Hopefully the results of the RESHAPE-HF-2 trial should be available within the next few years to clarify any benefit of MitraClip in secondary MR.
We also heard Professor John McMurray discuss heart failure treatments: where we stand today and what’s around the corner?
Where we stand today:
- In 2020 we now have five pillars of HFrEF therapy, also known as the “five alive”. This includes ACEi/ARB, beta blockers, MRAs, neprolysin inhibition and SGLT-2 inhibitors. They have additive and incremental benefits.
- A key question recently has been whether dapagliflozin taken alongside sacubitril/valsartan is effective and safe. Analysis of the subgroup of patients in the DAPA-HF trial who were talking sacubitril/valsartan showed that these patients had the same relative risk reduction (25%) in the primary composite end point as those patients not taking sacubitril/valsartan. The drugs were also found to be well tolerated when taken together.
- Another topic for debate is what order do we commence these “five alive” drugs and at what dose? Professor McMurray suggested considering symptoms of congestion, blood pressure, potassium level and renal function in guiding these.
What’s around the corner?
- The EMPEROR-reduced trial looking at the use of empagliflozin in patients with HFrEF with the primary endpoints of cardiovascular death and heart failure hospitalisation. The results of this are being presented at the ESC Congress this year.
- GALACTIC-HF trial using a novel treatment known as a cardiac-specific myosin activator (omecamtiv mecarbil). The drug improves LV systolic function by prolonging the duration of systole. The treatment has already been tested in a phase II “proof of concept” study with promising results showing a reduction in heart rate, NT-proBNP and LV end-systolic volume. The study also reported an improvement in stroke volume and LVEF.
One year after the results of the DAPA-HF trial were presented at the ESC Congress, it was interesting to hear what has happened since then. Professor John McMurray led us through a number of papers that have been published since and their key findings.
There has been additional analysis of a number of subgroups within the trial, such as the effect of Dapagliflozin according to age. Further analysis of this showed that the hazard ratio is consistently <1 right across the spectrum of age with no significant interaction between age and the benefit of Dapagliflozin.