Visually assessed myocardial fibrosis plus quantified GZF tied to sudden death, arrhythmic events

Myocardial fibrosis on visual assessment (MFVA) and quantified “gray zone” of myocardial fibrosis using the 3SD method (GZF3SD) more strongly predicts sudden cardiac death (SCD) and ventricular arrhythmia (VA) than reduced left ventricular ejection fraction (LVEF) in patients with coronary artery disease (CAD), according to a study.

“On this basis, we propose that arrhythmic risk stratification in CAD patients should focus on MFVA and then on quantifying GZF3SD mass, rather than on LVEF,” the researchers said. “Whether or not this decision pathway translates to benefit from implantable cardioverter-defibrillator (ICD) therapy requires a randomized controlled trial.”

This retrospective study of 979 CAD patients (mean age, 65.8±12.3 years) assessed the presence of MFVA and GZF mass in relation to SCD and the composite, arrhythmic endpoint of SCD or VAs.

Of the patients, 29 (2.96 percent) experienced SCD and 80 (8.17 percent) met the arrhythmic endpoint over a median 5.82 years (interquartile range, 4.1–7.3 years). MVFA in the whole cohort showed a robust association with SCD (hazard ratio [HR], 10.1, 95 percent confidence interval [CI], 1.42–1,278.9) and the arrhythmic endpoint (HR, 28.0, 95 percent CI, 4.07–3,525.4). [J Am Coll Cardiol 2021;77:29-41]

Competing risks analyses revealed weaker associations between LVED <35 percent and SCD (subdistribution [s]HR, 2.99, 95 percent CI, 1.42–6.31) and the arrhythmic endpoint (sHR, 4.71, 95 percent CI, 2.97–7.47).

In competing risk analyses of the MVFA subcohort (n=832), GZF3SD >5.0 g strongly correlated with SCD (sHR, 10.8, 95 percent CI, 3.74–30.9) and the arrhythmic endpoint (sHR, 7.40, 95 percent CI, 4.29–12.8). Associations were weaker between LVEF <35 percent and SCD (sHR, 2.62, 95 percent CI, 1.24–5.52) and the arrhythmic endpoint (sHR, 4.14, 95 percent CI, 2.61–6.57).

“We may ask whether GZF mass adds to the predictive value of CMR beyond MFVA. In this respect, early electrophysiological studies suggested that GZF provides a substrate for VAs,” the researchers said. [J Cardiovasc Electrophysiol 2005;16:465-471]

“Subsequently, several small studies, mainly comprising CAD patients undergoing ICD therapy, have supported a link between GZF and VAs,” they added. [Circ Cardiovasc Imaging 2009;2:183-190; Heart 2011;97:1951-1956; Int J Cardiol 2014;177:392-399; J Am Coll Cardiol Img 2018;11:561-572; Heart Rhythm 2015;12:802-808]

In addition, findings of the current study emerged in the context that primary prevention ICDs are prescribed based on LVEF <35 percent or <30 percent, consistent with the inclusion criteria of the primary prevention ICD trials. [N Engl J Med 2002;346:877-883; N Engl J Med 2005;352:225-237]

“Although these trials confirmed a role for LVEF in patient selection, they did not validate LVEF as a risk predictor in broad populations of CAD patients,” the researchers said. “Moreover, they do not inform on SCD risk in patients with an LVEF >35 percent.”

The current study was limited by its retrospective design. It was based on referrals to a tertiary cardiovascular magnetic resonance centre, so findings could not be generalized to primary care or the general population. In addition, CMR variables were not compared with the panoply of variables that have previously been proposed for arrhythmic risk stratification.