Dysregulated myocardial water balance and adverse outcomes in heart failure with preserved ejection fraction: insights from the NETDiamond cohort CMR substudy
F Vasques-Novoa, A Razaghizad, A Sharma, J Mancio, C Ferreira, E Hillier, P Marques, J Almeida, F Frioes, M G Friedrich, N Bettencourt, R Roncon-Albuquerque Jr, A F Leite-Moreira, J P FerreiraAbstract
Background
Myocardial edema may impair relaxation, increase diastolic stiffness, and compromise perfusion, yet its presence and clinical relevance in heart failure with preserved ejection fraction (HFpEF) remain poorly defined.
Aim
To compare myocardial free water and interstitial expansion in HFpEF versus controls, and to assess the prognostic value of T2 mapping compared with native T1 mapping and extracellular volume (ECV).
Methods
HFpEF patients (n=30), a cardiovascular comorbidity matched control group (n=10), and healthy controls (n=50) underwent 3T cardiac magnetic resonance with native T1 and T2 and ECV mapping in basal and mid left ventricular short axis slices. Mapping was analysed by two independent observers. HFpEF patients were followed for a median of 4.3 years. The primary endpoint was cardiovascular death or HF progression (HF hospitalisation, acute HF episodes, or diuretic intensification). Time-to-first events were analysed with Cox proportional hazards models; recurrent events were analysed with negative binomial regression, adjusting for age, sex, BNP, and creatinine.
Results
HFpEF patients were elderly (mean age 77 years) and predominantly female (60%). Compared with comorbidity matched controls, HFpEF had higher BNP (164.6 [76.7 to 284.1] vs 21.7 [11.2 to 34.8] pg/mL, p<0.001), larger left atrial volume index (39.3 [34.1 to 50.0] vs 23.8 [23.1 to 25.0] mL/m², p<0.001), and higher estimated pulmonary artery systolic pressure (40 [28 to 45] vs 23.5 [23 to 26.5] mmHg, p<0.001). On CMR, native T1 was higher in HFpEF than both control groups, and ECV was higher in HFpEF than comorbidity matched controls. T2 was higher in HFpEF, while T2 did not differ between healthy and comorbidity matched controls. In multivariable analyses, higher T2 remained independently associated with the primary endpoint and with recurrent events; ECV remained independently associated only in time-to-first event analysis, and native T1 was not independently associated.
Conclusion(s)
HFpEF is characterised by increased myocardial T2 consistent with higher myocardial water content, and T2 mapping provided the most robust prognostic information among CMR tissue markers. Routine inclusion of T2 mapping in HFpEF CMR protocols may improve phenotyping and risk stratification, and myocardial edema may represent an underrecognised mechanism and a tractable therapeutic and trial target.