Comprehensive stress echocardiography uncovers the heterogenity of phenotypes in non-ischemic heart failure with abnormal ejection fraction

Abstract Background Heart failure (HF) with abnormal left ventricular (LV) ejection fraction (EF) manifests in multiple phenotypes, each presenting distinct and potentially actionable therapeutic targets. This study aimed to assess the potential of the ABCDE+ stress echocardiography (SE) protocol in uncovering different phenotypes of non-ischemic HF. Methods With a retrospective analysis of prospectively acquired data, we identified 265 patients (mean age: 65.7±12.6 years; 154 males, 59.9%) with non-ischemic HF with EF<50% (mean =41.4±7.5) enrolled by 23 certified laboratories between 2021 and 2023. Ischemic origin was excluded based on data of angiography and medical history. ABCDE-SE was evaluated with exercise (n=98, 37.0%), dobutamine (n=50, 18.9%), or vasodilators (n=117, 44.1%). The protocol consisted of several steps: A assessed regional wall motion abnormality (RWMA); B evaluated number of B-lines; C measured left ventricular contractile reserve; Step D with coronary flow velocity reserve (CFVR) in the left anterior descending artery (LAD) was completed in 102 patients (38.5%); step E assessed heart rate reserve. Additionally, step F (evaluated in 188 patients at rest and 107 at peak stress) noted the presence of rest or stress-induced moderate-to-severe secondary mitral regurgitation. The SE response was graded on a scale from 0 (all steps normal) to 5 (all ABCDE+ steps abnormal). Results The mean ABCDE score was 1.5±1.2, ranging from 0 (n=59, 22.3%) to 5 (n=2, 0.8%) (see distribution of scores in Figure 1A). Abnormal results were observed in 21 subjects (7.9%) for A, 86 (32.5 %) for B, 147 (55.5%) for C, 42/102 (41.2%) for D, and 101 (38.1%) for E steps. Step F was abnormal in 22/188 (11.8%) at rest and in 16/107 (14.9%) at peak stress. The predominant "solitary phenotypes" (only one step abnormal) were impaired LV contractile function phenotype (step C in 47, 51.1%) followed by chronotropic insufficiency (step E in 17, 18.5%) and congestive phenotype (step B in 17, 18.5%) (see Figure 1B). The most frequent combined phenotype was BCE – congestive phenotype with impaired ventricular and heart rate reserves (28 [62.2%]). Notably, 38 patients (14.3%) demonstrated improved regional contractility, while 27 patients (10.2%) showed new regional wall motion abnormality (see Table). Conclusion Non-ischemic HF patients with abnormal EF exhibit a broad spectrum of phenotypes. Impaired left ventricular contractility, interstitial congestion, and chronotropic insufficiency are the most frequent abnormalities detected by ABCDE-SE. Up to one-quarter of such patients demonstrate normal SE results. This comprehensive approach paves the way for personalized, SE-guided therapy.