Currently, the therapeutically relevant classification of HF remains based on LVEF. All guidelines use the terminology of HFpEF and HFrEF, but differ in the terminology used in patients with EFs between 40 and 49% . HFpEF is a heterogeneous syndrome with various clinical presentations. Compared with patients with LVEF > 50%, those with LVEF 40–50% exhibit a higher prevalence of coronary heart disease and may have similar characteristics to those with LVEF < 40% . Patients with HFmrEF may show similar responses to treatment as those with LVEF < 40% . A post-hoc analysis of the TOPCAT trial suggested that mineralocorticoid receptor antagonists reduce morbidity and mortality in elderly patients with HF with a homogenous treatment effect in HFpEF [4, 5]. The PARADIGM-HF trial demonstrated that angiotensin receptor-neprilysin inhibitors (ARNis) improved survival in patients with HFrEF, but failed to reduce the incidence of the primary endpoint in patients with HFpEF. However, subgroup analysis suggested that the effect of ARNis on the primary endpoints was significant in patients with HFpEF with lower LVEF . Therefore, the 2021 ESC Universal Definition and Classification of HF proposed HFmrEF as the category for patients with an LVEF between 40 and 49% . Further classification into HFmrEF has potential utility as well as challenges due to its ambiguity, uncertainty, and dynamic trajectory. Patients with HF stratified according to different categories of LVEF present diverse phenotypes of demography, clinical presentation, etiology, and outcomes. Patients with HFmrEF possess similar features as those with HFrEF, including age, sex, and ischemic etiology , but have better outcomes, as opposed to higher rates of mortality and HF readmissions seen in patients with HFrEF . The ‘gray zone’ of LVEF between 40 and 50% requires further characterization. STEMI is an important cause of HF, and the state of LV function after STEMI is an important indicator of prognosis. GLS derived from 2D-STE can detect LV systolic dysfunction at an earlier stage than LVEF and is associated with a worse outcome [19, 20]. MCE can be used for CMD and provides important information for prognosis. Therefore, we evaluated LV function and coronary microcirculation in patients with mildly reduced LVEF after STEMI using 2D-STE and MCE.
A total of 119 patients with STEMI were enrolled in this study, 26.9% with HFmrEF and 14.3% with HFrEF. The median BNP levels in the HFmrEF and HFrEF groups were 290 (170–901) pg/mL and 625 (167–1534) pg/mL, respectively. A total of 58.8% of the patients had an LVEF ≥ 50%. The normal value for GLS depends on the definition of the measurement position in the myocardium, vendor, and version of the analysis software, resulting in considerable heterogeneity in the published literature. The 2015 ASE guidelines recommend that a peak GLS in the range of -20% can be expected in a healthy person . In our study, although 58.8% of patients had a normal LVEF (≥ 50%), most patients had impaired GLS. Only 5.9% of patients had a GLS above − 20.0%, 88.2% patients had a GLS below -18.0%, and the median GLS of all patients was − 11.9 ± 3.8%. This means that GLS can detect LV systolic dysfunction earlier than LVEF. Doeblin et al. observed that patients with HFmrEF differed from healthy individuals and shared similarities with patients with HFrEF in cardiac magnetic resonance parameters of fibrosis and inflammation . By means of STI, we found that the GLS in patients with HFmrEF was − 9.9 ± 2.5%, which was more comparable to that in patients with HFrEF (− 8.0 ± 2.3%, P = 0.052), but significantly lower than that in the normal group (− 13.8 ± 3.5%, P < 0.001). Additionally, WMSI in the HFmrEF group also resembled that in the HFrEF group (1.76 ± 0.30 vs. 1.81 ± 0.43, P = 0.618) and was significantly poorer than that in the normal group (1.33 ± 0.25, P < 0.001). These results reveal significant adverse remodeling beyond systolic functional impairment and WM in patients with HFmrEF, comparable to the changes seen in patients with HFrEF, but different from those in patients with LVEF > 50%. And these distinctions were not affected by the medicine treatment. Therefore, patients with HFmrEF after STEMI require greater attention.
Despite successful opening of the culprit epicardial vessel, adverse LV remodeling, HF, and even death still occur. CMD, as a possible reason, has attracted more attention in recent years . Studies have shown that the prevalence of CMD is 60–89% in successfully treated STEMI [12, 22]. We detected 119 patients with STEMI by MCE and identified 66.7% of patients with CMD. This result was consistent with previous literature. Furthermore, we found no significant difference in MPI between patients with HFmrEF and patients HFrEF (1.24 ± 0.33 vs 1.18 ± 0.19, P = 0.486), which were both poorer than that in normal group (1.08 ± 0.14, P = 0.005). This result reveals that the coronary microcirculation status in patients with HFmrEF is comparable to that in patients with HFrEF, but poorer than that in patients with LVEF > 50%. The presence of CMD after STEMI predicts adverse prognoses such as rehospitalization, HF, and mortality [23, 24]. It is also a powerful predictor of LV adverse remodeling . The presence and extent of CMD after primary PCI in STEMI are strongly associated with major adverse cardiovascular events within 1 year . The occurrence of CMD in patients with HFmrEF after STEMI requires greater attention, and its effect on long-term prognosis requires further study. It was unexpected that the MPI in the HFrEF group was higher than that in the normal group, but no statistical difference was observed between the two groups. This may be due to the small sample size, and thus, further research is required.
HFmrEF is a new concept. Actually, it is still a controversial topic whether HFmrEF pertinently addresses a distinct category or merely a transition zone between HFpEF and HFrEF. Whereas it’s been well accepted that HFrEF and HFpEF differed in terms of the underlying aetiologies, demographics clinical feather, and morbidities. Conversely, it’s still not clear when comes to the HFmrEF patients, despite the evolving knowledge and recognition in HFmrEF.We described the UCG phenotypic characteristics of patients with HFmrEF. According to our knowledge, it’s the first time to view HFmrEF in the sight of LV systolic function and microcirculation. The significance of our finding is the GLS and MPI of HFmrEF patients were similar to thse of the HFrEF ones but not the normal ones, i.e. it’s plausible to construe HFmrEF as sort of HFrEF at least in one sense. Since HFmrEF is pretty new and evolving, controversy haunts doctors about whether HFmrEF should be considered a distinct category or a transition zone. Our encouraging finding provides the evidence to help give an end to this controversial topic.
Patients with HFrEF suffer functional, structural, cellular, and interstitial changes that are known as left ventricular remodeling. The treatments targeting remodeling are a mainstay of HFrEF therapy. Conversely, these treatments failed to benefit the patients with HFpEF. However, it’s intriguing that no solid conclusion could be reached for the HFmrEF ones given the dearth of understanding of HFmrEF. We demonstrated that HFmrEF is more analogous to the HFrEF but the normal one. That hinted at the plausible value of positive treatments. Further, our available data suggested a possible benefit from treatment against remodeling.
In our study, the time of symptom-to-flow restoration in the HFrEF group [144 (5.3–264.0) h] was significantly longer than that in the normal group [4.9 (2.5–10.8) h] and HFmrEF group [5.0 (3.0–24.4) h]. Indeed, patients with HFrEF had worse clinical symptoms, critical conditions, and delayed PCI combined to develop worse cardiac function in this group. Therefore, delayed PCI resulted in patients with HFrEF experiencing even worse LV systolic dysfunction and CMD. Nevertheless, patients with HFmrEF showed similar LV systolic function and coronary microcirculation perfusion to those with HFrEF, and these results further confirmed that patients with HFmrEF might have a poor prognosis. However, our study only involved patients with STEMI who underwent either emergency PCI, selective PCI (including post-thrombolysis), or patients who did not receive any revascularization (thrombolysis or PCI). Meanwhile, the study is relatively small and includes only 119 patients. It’s the limit of this study. However, we demonstrated the difference among the groups in spite of the small size. In the future, further studies with larger sample sizes are required. Meanwhile the lack of clinical outcome and follow-up data is the limitation of our article. Whether echocardiographic parameters will recover during follow-up and whether GLS will improve earlier than LVEF? More study about the prognosis and echocardiographic parameters outcome need to be done in the future.
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