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Patients with HFPEF are more restricted in their daily activities and difficult to diagnose, lack of effective therapeutic drugs, emperor-preserved studies, or breakout treatment limitations.
In recent years, the prevalence of heart failure (referred to as heart failure) in China has continued to increase, and it is expected to reach 8.9 million. Epidemiological surveys have shown that heart failure is characterized by high prevalence, high mortal disability rate, high rate of re-hospitalization, and high medical costs. However, the heart failure with a high proportion of ejection fraction retention type heart failure (hfpef), which is difficult to diagnose and lacks effective therapeutic drugs, how to deal with clinical treatment in the face of difficult hfpef patients?
The annual Great Wall Cardiology Conference (the "Great Wall Conference") was officially held in Beijing on October 27, and many experts gathered online to discuss the progress in the cardiovascular field. At the Heart Failure Forum on October 29th, professor Zhang Jian of Fuwai Hospital of Chinese Academy of Medical Sciences and Professor Huang Jun of the First Affiliated Hospital of Nanjing Medical University gathered together to talk about cutting-edge information related to the diagnosis and treatment of heart failure, including Professor Xu Dingli of Southern Hospital of Southern Medical University, Professor Zhang Yuhui of Fuwai Hospital of Chinese Academy of Medical Sciences, Professor Jin Wei of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, and Professor Du Xin of Beijing Anzhen Hospital affiliated to Capital Medical University.
HFPEF, HFREF is very different,
How can diagnosis and treatment options be improved?
Professor Xu Dingli pointed out in his speech that the latest "2021 European College of Cardiology (ESC) Guidelines for the Diagnosis and Treatment of Acute/Chronic Heart Failure" mainly divides heart failure based on left heart ejection fraction (lvef) into reduced ejection fraction type heart failure (hfref, lvef≤40%), mildly reduced ejection fraction type heart failure (hfmref, lvef 41% to 49%) and ejection fraction reserved heart failure (hfpef, lvef≥50%); in addition, for baseline lvef≤40%, The second measurement increased lvef from baseline by ≥10 and lvef > 40% of heart failure defined as hfimpef-improved heart failure.
In the past 30 years, hfpef has increased from 41% to 56% (p<0.001) in patients with heart failure. Patients with hfpef were similarly or worse in daily activity restriction compared to those with reduced or improved lvef, and mortality was similar to that of hfref.
From a pathophysiological point of view, patients with hfref usually have left ventricular systolic dysfunction, and decreased ventricular pumping due to weakened myocardial contractility leads to systemic hypoperfusion. Patients with hfref have myocardial ganglia tandem hyperplasia, myocardial cell growth, centrifugal hypertrophy. Its pathogenesis is dominated by neuroendocrine mechanisms.
Patients with hfpef are mostly characterized by damage to left ventricular filling, which may be that the stiff myocardium cannot be normally dilated so that ventricular filling is reduced, and the patient's myocardial nodes are parallel proliferation, and the myocardial cells are thickened and hypertrophic. Its pathogenesis is more complex than that of hfref patients, involving a variety of pathophysiological mechanisms including systemic inflammation, myocardial ischemia, tissue fibrosis, energy abnormalities, abnormal cell signaling, myocyte mastrophy, and secondary to multiple organ dysfunction.
Figure 1 hfpef is a clinical syndrome involving multiple pathophysiological mechanisms and multiple organs
Due to the lack of specific indicators of hfpef, its diagnosis is far more difficult than hfref. Esc suggests a combination of symptoms ± signs, 50% of lvef ≥, elevated natriuretic peptide levels, and the presence of structurally-related heart disease (left ventricular hypertrophy and/or left atrial enlargement) or diastolic dysfunction, but its sensitivity is only 60% and the specificity is about 75%. HFPEF score and HFA-PEFF score, as well as diagnostic criteria that combine the patient's symptoms, signs, and adjunctive tests, improve the accuracy of hfpef diagnosis.
In terms of treatment, several drugs for hfref treatment have reached their primary endpoint in clinical trials, however, for hfpef, there has been no drug with clear clinical benefit previously confirmed by clinical studies. The 2021 ESC Guidelines for the Diagnosis and Treatment of Acute/Chronic Heart Failure also point out that current treatment of hpfef is limited to its comorbidities, and there are no treatment options to improve heart failure outcomes.
On the day of the release of the 2021 ESC heart failure guidelines, a blockbuster study was unveiled at esc conference, the emperor-preserved study, which added a sodium-glucose synergistic transporter-2 inhibitor (sglt-2i) to standard drug therapy – which significantly reduced the risk of cardiovascular death/hospitalization for heart failure in 40% of patients with lvef > heart failure.
emperor-preserved: 21% reduction in relative risk of primary composite endpoints in the empagliflozin group
Professor Zhang Yuhui interpreted the superior-preserved study at the conference. The emperor-preserved study was a phase III clinical trial conducted in 5988 lvef>40% of patients with heart failure, ≥ 18 years of age, Nyha ii-iv grade, with or without type 2 diabetes mellitus (T2d), to explore the efficacy and safety of empagliflozin 10 mg qd compared with placebo in patients with hfpef.
The primary endpoint of the study was the time until the first time a determined cardiovascular death or hospitalization for heart failure occurred. Results showed that empagliflozin significantly reduced the relative risk of primary composite endpoints of cardiovascular death or hospitalization due to heart failure by 21% compared with placebo (hr: 0.79; 95% ci, 0.69-0.90; p<0.001). A pre-set subgroup analysis of the study suggested that the benefit of empagliflozin to the primary endpoint was consistent across genders, in different baseline lvef subgroups, and was not affected by baseline drug use.
Fig. 2 Empagliflozin significantly reduces the relative risk of primary composite endpoint by 21%
In the confirmatory secondary endpoint, the empagliflozin group had a 27% reduction in the relative risk of hospitalization for first and recurrent heart failure (hr: 0.73; 95% ci, 0.61 to 0.88; p<0.001).
Figure 3 In the confirmatory secondary endpoint, the relative risk of first-time and recurrent hospitalizations due to heart failure in the Empagliflozin group was reduced by 27%
In addition, the study suggests that empagliflozin can protect the kidneys by significantly delaying the decline in renal function. The estimated decrease in glomerular filtration rate (egfr) in the empagliflozin group was half that of the placebo group, with a difference in egfr slope of 1.36 ml/min/1.73 m/year (95% ci, 1.06 to 1.66; p<0.001).
Figure 4 Patients in the empagliflozin group had half the rate of egfr decline compared with those in the placebo group
Emperor-preserved is the first clinical study in the history of heart failure treatment to benefit patients with hfpef by reducing the risk of cardiovascular death or hospitalization for heart failure, and the first clinically significant study to benefit consistently across all pre-set subgroup analyses, confirming that empagliflozin may be the first and currently the only therapy to improve the heart-kidney outcome of all types of heart failure patients, regardless of ejection fraction, and that this result may change clinical practice.
The future can be expected: the emperor-preserved results may change clinical practice
After the wonderful speeches of the two experts, the online experts had an in-depth discussion on the diagnosis and treatment of hpfif and the study of embroider-preserved.
Experts point out that hfpef has a variety of etiology and pathogenesis, and the treatment strategies for heart failure due to different etiologies are different, so it is particularly important to diagnose the patient's etiology. However, the causes of heart failure are diverse, and the current detection methods are complex, and the efficacy of drug therapy is not ideal, today's heart failure treatment concept should consider exploring the "method of co-treatment of all lvef type heart failure", on the one hand, the use of loop diuretics to improve symptoms, on the other hand, the use of sglt-2i, the current emperor-preserved and emperor-reduced studies suggest that empagliflozin can improve the clinical outcomes of patients with various types of lvef.
During the discussion, some experts asked: Due to the short decline in the use of empagliflin in the early stage of empagliflam, what experiences are shared in the clinical use of empagliflozin in patients with low egfr?
Experts pointed out that according to the results of the emperor-preserved study, the short-term decline in egfr occurred in the early stage of empagliflozin treatment and gradually recovered, and in the long run, empagliflozin delayed the decline of egfr, which is consistent with the results of previous studies. It is also based on the available evidence of benefit of sglt-2i for renal outcomes, the emperor-preserved study included patients with egfr ≥ 20 ml/min/1.73 m, the lowest standard of egfr of all heart failure studies. Clinically, sglt-2i can further realize the benefits of the kidneys on the basis of improving renal function with drugs in the renin-angiotensin-aldosterone system.
Experts suggest that for patients with heart failure with low egfr, renal function can be monitored at the beginning of sglt-2i treatment, and if the egfr decrease does not exceed 20%, the treatment is basically safe.
Based on the "epoch-making" and "landmark" results of the emperor-preserved study, the experts present believe that empagliflozin will appear in the major consensus and guideline treatment recommendations in the future, or will change the clinical practice of heart failure treatment, and look forward to more follow-up studies to further explore the mechanism of empagliflozin in the treatment of heart failure, further bringing the gospel to the majority of patients.
This article is only used to provide scientific information to healthcare professionals and does not represent the position of the Platform
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