Ischaemic Myocardial Fibrosis Is the Villain of Sudden Coronary Death

Gaetano Thiene

Disclosures

Eur Heart J. 2022;43(47):4931-4932. 

Graphical Abstract

Sudden death in a 43 years-old man with archipelago-like spots of myocardial fibrosis (A) and "zig-zag" electric impulse transmission (B). (A, B) From Thiene G, Rizzo S, Basso C. Pathology of sudden death, cardiac arrhythymias, and conduction system. In: Maximilian Buja L, Butany J (Eds.), Cardiovascular Pathology. Chapter 11. Academy Press, January 2022, 447–534. ISBN: 9780128222249, modified.

Chronic ischaemic heart disease is by far the main cause of sudden cardiac death (SCD).[1,2] A recurrent episode of myocardial ischaemia, due to coronary atherosclerotic plaque instability (thrombosis, intraplaque haemorrhage, fibrous cap rupture, erosion) is the popular interpretation for SCD in this setting.[3–6]

The findings of the investigation, published in this issue of the Journal,[7] question this belief and shift the attention to the myocardial fibrosis (MF) as a cause of electrical instability, triggering ventricular fibrillation and cardiac arrest.

An impressive number of 600 patients, who died suddenly with obstructive coronary artery disease, underwent autopsy within the Fingesture project in Northern Finland, with a detailed microscopic study of the culprit coronary plaque and myocardium. In Finland all victims of SCD undergo post-mortem by law: the highest rate in Western Countries. The mean age at death was 64.0 ± 11.2 years, which means that SCD in the young (<40 years old) was excluded. The fatal outcome occurred at rest or during/soon after mild exercise in 77% of subjects.

Unexpectedly the findings revealed that the majority of cases (52%) showed stable culprit plaques and that MF with cardiac hypertrophy was the life-threatening arrhythmic substrate. MF was present in 93% of the victims, in the form not only of a large post-infarct scar but also of scattered fibrotic spots, the ideal substrate for 'zig-zag' electrical impulse propagation, facilitating a re-entry mechanism for onset of fatal arrhythmias (see Graphical Abstract). Myocardial hypertrophy was present in 78% of patients.

Plaque destabilization causing acute myocardial ischaemia was responsible for SCD in the remaining 48% of patients.

There are some limitations. When evaluating the coronary tree, only the culprit plaque was examined under the microscope. Inflammation and calcification, as well as healing of previous fibrous cap rupture, were not reported. Moreover, the various types of MF were not documented.

Importantly, a potential cause of acute ischaemia responsible for SCD in the absence of plaque disruption is coronary artery spasm. Lack of information on symptoms (angina) and electrocardiography recording does not allow determination of how many patients without plaque disruption had an acute ischaemic episode before SD. In our practice within the Registry of the Veneto Region (Italy),[8] we had the chance to record transient myocardial ischaemia with Holter monitoring on the eve of the arrhythmic cardiac arrest, suggesting coronary artery vasospasm as the fatal mechanism with reflow.[9]

Despite these limitations, the results of the study by Holmstrom et al.[7] have important implications. In chronic ischaemic heart disease, the source of fatal arrhythmias may reside in the fibrotic myocardium, without recurrence of an acute ischaemic episode.

To my mind, the type of MF plays a pivotal role. The quality rather than quantity of post-infarction scarring accounts for the arrhythmic threat. As wisely affirmed by the authors: 'Interaction between pre-existing anatomic substrate and acute ischemia … is probably more relevant than plaque complications alone in the development of life-threatening arrhythmias and SCD'.[7]

The risk assessment is not necessarily the amount of myocardial loss calculated by the residual left ventricular ejection fraction (LVEF) through 2D echocardiogram. This consideration questions the dogma of less than 35% LVEF for the need of an implantable cardioverter defibrillator (ICD), which means that even scarce fibrotic healing may trigger ventricular tachycardia-fibrillation leading to SCD.

MF as a predictor of SCD in patients with chronic ischaemic heart disease has been the topic of a recent retrospective investigation using cardiac magnetic resonance.[10] The findings suggest that myocardial fibrosis was more strongly associated with ventricular arrhythmias and SCD than left ventricular ejection fraction. A prospective randomized clinical trial should be implemented to test such preliminary findings.

In conclusion, the message deriving from the results of the investigation by Holmström and co-authors[7] is novel. It strongly suggests that post ischaemic MF associated with cardiac hypertrophy might be the main killer in adult-elderly patients with chronic coronary artery disease. Is cardiac hypertrophy the consequence of arterial hypertension or a compensatory phenomenon for the loss of myocardium following infarct? Cardiac hypertrophy is less likely than fibrosis to be an arrhythmic substrate.

Cardiovascular medicine nowadays owns non invasive instrumental facilities[10,11] to cope with diagnosis, risk stratification, and therapy, as well as prevention of SCD with the implant of an ICD, the miraculous tool which resuscitates the patient from most arrhythmic cardiac arrests. Would patients with chronic ischaemic heart disease and ventricular fibrillation have died if an ICD had been implanted? We should seriously take advantage of the results of this commendable study.[7] Once more, 'mors ubi gaudet succurrere vitae'(death here rejoices to rescue life), as written in the entrance of the Anatomic Theatre of Fabrici d'Acquapendente at the University of Padua.

The time has come for screening in cardiovascular medicine as in oncology. Is post-infarction screening by cardiac magnetic resonance feasible?[10] Is it cost-effective? The jury is out to decide.

processing....