Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies

Abstract

Most patients survive acute myocardial infarction (MI). Yet this encouraging development has certain drawbacks: heart failure (HF) prevalence is increasing and patients affected tend to have more comorbidities worsening economic strain on healthcare systems and impeding effective medical management. The heart's pathological changes in structure and/or function, termed myocardial remodelling, significantly impact on patient outcomes. Risk factors like diabetes, chronic obstructive pulmonary disease, female sex, and others distinctly shape disease progression on the 'road to HF'. Despite the availability of HF drugs that interact with general pathways involved in myocardial remodelling, targeted drugs remain absent, and patient risk stratification is poor. Hence, in this review, we highlight the pathophysiological basis, current diagnostic methods and available treatments for cardiac remodelling following MI. We further aim to provide a roadmap for developing improved risk stratification and novel medical and interventional therapies.

Keywords: Fibrosis; Heart failure; Myocardial Infarction; Remodelling.

Graphical Abstract

After a cardiac injury, comorbidites and various pathophysiologic mechanisms contribute to left ventricular remodelling and heart failure. Strategies to improve patient care beyond currently available treatment algorithms should include novel diagnostics, improved and treatment specific patient selection as well as novel therapies.

Figure 1

(A) Pathophysiology of left ventricular remodelling post-myocardial infarction. Schematic display of mechanical (left) and non-mechanical (right) pathophysiology leading to adverse left ventricular remodelling. Left: Persistent increase of afterload, and subsequently preload, promotes mechanical stretching of the tissue and activation of pro-hypertrophic pathways leading to pathological myocyte growth and the development of remodelling. Right: Derangements in energy metabolism leading to suboptimal energy production (metabolic remodelling) as well as activation of the renin–angiotensin–aldosterone system and sympathetic nervous system via natriuretic peptides, activation of pro-inflammatory pathways and changes in the extracellular matrix leading to myocardial fibrosis. These expand left ventricular remodelling post-myocardial infarction. (B) Histological changes in the heart following myocardial infarction. Following acute myocardial infarction, pressure and volume overload lead to increased wall stress and declining left ventricular function. An orchestrated process involving myocardial infiltration of different immune cells leads to scar tissue formation and progressive cardiomyocyte death. Chronic inflammation and other stimuli fuel the expansion of the extracellular matrix and promote chronic remodelling.

Figure 2

(A) Detection and severity assessment of left ventricular remodelling by transthoracic echocardiography. (a) Quantification of left ventricular function showing severely reduced left ventricular ejection fraction, enlarged volume, and an apical aneurysm. (b) Assessment of myocardial deformation using two-dimensional strain imaging (same patient). The bulls-eye plot of segmental longitudinal strain is a composition of individual two-dimensional acquisitions and displays dyskinetic segments in blue. (c) Three-dimensional strain imaging provides simultaneous assessment of strain throughout the cardiac cycle in all myocardial regions, summarized in a volumetric display and a bulls-eye plot, with dyskinesia displayed in blue. (B) Post-infarct myocardial tissue characterization by cardiac magnetic resonance imaging. Short-axis views of inferior subacute myocardial infarction acquired using a 1.5 T system. (a) Mid-systolic frame of a cine sequence after administration of contrast agent; dark area indicates microvascular obstruction (see red arrow). (b) T2-weighted image sequence where bright area represents peri-infarction oedema (red arrow); grey area sub-endocardially indicates the presence of microvascular obstruction. (c) Late gadolinium enhancement acquisition following administration of gadolinium-based contrast agent; bright areas (red arrow) represent tissue necrosis/scar formation with an encapsulated dark area indicating microvascular obstruction. (d) Modified Look–Locker inversion recovery T1-map following administration of contrast media with bright green/red areas corresponding to scar and dark blue areas indicating microvascular obstruction.

Figure 3

Novel molecular imaging techniques. Schematic display of molecular imaging-guided, targeted therapy in left ventricular remodelling. Potential imaging targets are listed in the grey circle in the centre. Imaging visualizes the presence or absence of up-regulated pathways in the myocardium (global, regional) and interactions with other organs (top). Imaging signal strength predicts individual adverse outcomes and progressive myocardial remodelling (left). High personal risk triggers dedicated therapeutic intervention to attenuate target mechanisms and reduce risk (right). Repeat imaging may be used to monitor success.

Figure 4

Therapies for left ventricular remodelling and healing. Overview of currently available and possible future treatments for left ventricular healing and remodelling following myocardial infarction.

Figure 5

Trials to evaluate left ventricular remodelling attenuation post-myocardial infarction. Markedly improved total mortality in patients at risk for heart failure after myocardial infarction in the last 30 years as reflected by declining mortality rates in trials of renin–angiotensin–aldosterone system inhibitors (modified from Pfeffer M, presented at ACC 2021). SAVE, AIRE, and TRACE showed significantly reduced mortality resulting from angiotensin-converting enzyme inhibitors vs. placebo; VALIANT demonstrated equivalence of angiotensin-converting enzyme inhibition and the angiotensin II receptor blocker valsartan; in PARADISE-MI sacubitril/valsartan was not superior to the angiotensin-converting enzyme inhibitor ramipril.