Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection Fraction

Abstract

N early half of all heart failure patients present with normal or near normal systolic left ventricular (LV) function. 1 This condition has been labeled heart failure with preserved ejection fraction (HFpEF).2 The pathophysiology underlying HFpEF is complex and still incompletely understood. Expansion of the extracellular volume (ECV) due to accumulation of extracellular matrix in the interstitial myocardial space is thought to be one of the main pathophysiologic mechanisms underlying LV stiffening in HFpEF.3,4 Despite the central role of ECV in this condition, data on its prognostic relevance are limited. 5 The gold standard for ECV quantification relies on the histological analysis of endomyocardial biopsies retrieved from the LV. This method, however, is invasive and carries significant risks. Our group previously showed that myocardial postcontrast T1 time by cardiac magnetic resonance (CMR) imaging is significantly associated with prognosis and correlates with ECV by histology.5 However, more recently, CMR T1 mapping, using the modified Look-Locker inversion recovery (MOLLI) sequence, has been proposed as the more robust technique, independent of potential confounders such as renal function, heart rate, or time of acquisition.6-10 However, the diagnostic and prognostic power of ECV as measured by the MOLLI technique in HFpEF is unknown.

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…Coronary microvascular dysfunction is exceptionally common in HFpEF and, when present, is associated with a two‐fold increase in the prevalence of AF . Cardiac magnetic resonance imaging (MRI) reveals meaningful myocardial fibrosis (in the LA and LV) in both patients with HFpEF and those with AF . Fibrosis is indicative of an underlying atrial and ventricular myopathy and may precede the clinical identification of AF or HFpEF …”

The Prognostic Role of T1 Mapping Sequences: Can T1 Mapping Parameters Have a Role in Risk Stratification?

“…It has been suggested that myocardial fibrosis can be reversed, and cells and enzymes regulating collagen could be potential therapeutic targets [20]. However a more recent prospective study showed that MOLLI-ECV in HFpEF accurately reflected histological ECV and correlated with markers of disease severity; ECV≥ 28.9% (median) was associated with shorter event-free survival (log-rank, p=0.028), but not after adjustment for important clinical and invasive hemodynamic parameters (Table 2) [21]. The problems to be solved are that conventional echo-based diastolic functional parameters such as E/e' were not included in the multivariate analysis and many patients were excluded due to previous pacemaker/implantable cardioverter-defibrillator (ICD) implantation, estimated glomerular filtration rate (eGFR)<30 mL/min, claustrophobia, immobility and premature discontinuation of CMR scanning.…”

Persistent atrial fibrillation in heart failure with preserved ejection fraction: Prognostic relevance and association with clinical, imaging and invasive haemodynamic parameters

“…While the relative importance of the atrial booster pump function remains controversial, 23 the negative influence of irregular heart rate on cardiac output has previously been described. 26,27 It enhances left ventricular stiffness, which causes atrial enlargement due to increased atrial afterload. Furthermore, the extent of atrial enlargement was independently associated with persistent AF.…”

“…Extracellular volume expansion plays a key role in the pathogenesis and prognosis of HFpEF. 26,27 It enhances left ventricular stiffness, which causes atrial enlargement due to increased atrial afterload. Values are given as mean ± SD or median and interquartile range or total numbers and per cent.…”