Prognostic value of reverse remodelling criteria in heart failure with reduced or mid‐range ejection fraction

Abstract

Aims Reverse remodelling (RR) is the recovery from left ventricular (LV) dilatation and dysfunction. Many arbitrary criteria for RR have been proposed. We searched the criteria with the strongest prognostic yield for the hard endpoint of cardiovascular death. Methods and resultsWe performed a systematic literature search of diagnostic criteria for RR. We evaluated their prognostic significance in a cohort of 927 patients with LV ejection fraction (LVEF) < 50% undergoing two echocardiograms within 12 ± 2 months. These patients were followed for a median of 2.8 years (interquartile interval 1.3-4.9) after the second echocardiogram, recording 123 cardiovascular deaths. Two prognostic models were defined. Model 1 included age, LVEF, N-terminal pro-B-type natriuretic peptide, ischaemic aetiology, cardiac resynchronization therapy, estimated glomerular filtration rate, New York Heart Association, and LV end-systolic volume (LVESV) index, and Model 2 the validated Cardiac and Comorbid Conditions Heart Failure score. We identified 25 criteria for RR, the most used being LVESV reduction ≥15% (12 studies out of 42). In the whole cohort, two criteria proved particularly effective in risk reclassification over Model 1 and Model 2. These criteria were (i) LVEF increase >10 U and (ii) LVEF increase ≥1 category [severe (LVEF ≤ 30%), moderate (LVEF 31-40%), mild LV dysfunction (LVEF 41-55%), and normal LV function (LVEF ≥ 56%)]. The same two criteria yielded independent prognostic significance and improved risk reclassification even in patients with more severe systolic dysfunction, namely, those with LVEF < 40% or LVEF ≤ 35%. Furthermore, LVEF increase >10 U and LVEF increase ≥1 category displayed a greater prognostic value than LVESV reduction ≥15%, both in the whole cohort and in the subgroups with LVEF < 40% or LVEF ≤ 35%. For example, LVEF increase >10 U independently predicted cardiovascular death over Model 1 and LVESV reduction ≥15% (hazard ratio 0.40, 95% confidence interval 0.18-0.90, P = 0.026), while LVESV reduction ≥15% did not independently predict cardiovascular death (P = 0.112). Conclusions Left ventricular ejection fraction increase >10 U and LVEF increase ≥1 category are stronger predictors of cardiovascular death than the most commonly used criterion for RR, namely, LVESV reduction ≥15%.

Cardiac remodelling – Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

“…The definition of RR has not been standardized 17 . A dedicated search for diagnostic criteria of RR identified as many as 25 criteria from 42 studies (online supplementary Table ), 18 some of them quite elaborate and difficulty applicable in everyday clinical practice. All these criteria considered changes in LV diameters or volumes, LVEF or fractional shortening (FS), either alone or in combination, and with the use of arbitrarily defined cut‐offs, and just one criterion considered changes in LV mass over time.…”

“…All these criteria considered changes in LV diameters or volumes, LVEF or fractional shortening (FS), either alone or in combination, and with the use of arbitrarily defined cut‐offs, and just one criterion considered changes in LV mass over time. The most frequently used criterion was LV end‐systolic volume (LVESV) reduction ≥15% (12 studies out of 42) 18 …”

“…When applying all the RR criteria on a same cohort of HF outpatients with baseline LVEF <50%, as many as 52% of patients had RR when using the criterion ‘final LVEF >35%’ (although 43% of patients had a baseline LVEF >35%), and just 2% with an elaborate criterion (LVEDD decrease >5 mm to a final LVEDD <55 mm AND FS increase >5% to a final FS >25% AND LV mass decrease >10%). Thirty‐one percent of patients were categorized as having RR when using the most common criterion for RR (LVESV reduction ≥15%) 18 …”

“…The most frequently used criterion was LV end-systolic volume (LVESV) reduction ≥15% (12 studies out of 42). 18 Adverse remodelling was first described as the progression of the left ventricle with large transmural infarctions towards HF. 16 A more progressive deterioration of LV geometry and function can be encountered in patients with HF, although progresses in drug and device therapy are making such deterioration increasingly .…”

Mass Customized Outlook for Regenerative Heart Failure Care

“…Indeed, left ventricular size is a marker of organ remodeling with a window in disease progression when the failing heart has not passed the point of no return, and is most amenable for therapy [ 64 , 65 ]. Accordingly, reversal of left ventricular enlargement serves as a surrogate of therapeutic success [ 66 , 67 , 68 ]. While initially described with cardiopoietic cell therapy in ischemic heart disease and pinpointed at the molecular level on the basis of documented reverse remodeling of the cardiac proteome [ 63 ], a left-ventricular-size-dependent outcome was also documented in non-ischemic heart failure treated with distinct cell types [ 69 ].…”