Unexplained Heart Enlargement May Be Causing Sudden Deaths in Obesity

Obesity cardiomyopathy (OCM) was identified as a distinct pathology associated with sudden cardiac death (SCD) based on records from a national referral center in the U.K.

Autopsies showed that out of more than 6,400 SCDs, 53 people who died with obesity had cardiomegaly without a medical history suggesting a usual etiology of heart disease. Mean age at death was 42 years, and 64% were men.

Their pathology was dubbed OCM — characterized by right ventricular (RV) hypertrophy and symmetrical left ventricular (LV) hypertrophy in the absence of myocyte disarray or infiltrative disease, with fibrosis seen in only a minority of cases — by Joseph Westaby, PhD, and colleagues of St. George’s University of London.

“The cause of OCM associated with SCD is not fully understood,” the authors wrote in JACC: Advances. “Only a small proportion of cases had fibrosis on microscopy suggesting that SCD in OCM may be mediated through increased ventricular mass.”

Their criteria for OCM related to SCD were cardiomegaly (hearts weighing >550 g in men and >450 g in women) in individuals with a body mass index (BMI) >30 with no history of hypertension or diabetes and no coronary or valve disease at autopsy.

Ultimately, the OCM cohort had hearts weighing an average 598 g versus 400 g for matched obese controls with normal-size hearts (P<0.001) and was more severely obese (BMI 42 vs 35, P<0.001). Affected men died younger than female peers (40 vs 45 years, P=0.036).

“This raises the question of whether or not screening echocardiograms or MRIs should be recommended in younger patients at a certain BMI to identify those with OCM. If so, a practical definition or cutoff for OCM using left ventricular mass would be needed,” said Timothy Fitzgibbons, MD, PhD, of the University of Massachusetts Chan School of Medicine in Worcester, in an accompanying editorial.

“This study has important implications considering the global burden of obesity and the socioeconomic consequences of the loss of these young productive members of society,” Fitzgibbons added.

Fitzgibbons also pointed to the global rise in obesity in children, with obese children likely to become obese adults who are at greater risk of cardiovascular disease and diabetes. One estimate has one in five adults having obesity by the year 2025, he said.

“Public health initiatives to address obesity may be one potential target to decrease SCD risk,” Westaby and colleagues suggested, though they acknowledged that “the relevance of OCM to the general population with obesity is uncertain.”

“The number of cases identified in this study is likely to be an underrepresentation of the incidence of this condition as some cases may be mislabeled as hypertensive heart disease at initial autopsy, despite the absence of a history of hypertension,” they wrote.

The retrospective case-control autopsy study was conducted at a national referral center for SCD. Of 6,457 SCD cases, 53 cases of OCM were identified and matched to 106 controls with obesity and 106 normal-weight controls.

There were increases in RV and LV wall thickness in OCM cases compared with both controls, whereas RV epicardial fat was increased in decedents with OCM compared with normal-weight controls only. LV fibrosis was identified in 13% of OCM cases.

Prior to SCD, 87% of OCM decedents had been asymptomatic. Death occurred at rest or during sleep in 91% of cases.

Westaby’s group acknowledged the possibility of referral bias, since the study center typically sees more complex cases. They also could not exclude the existence of some undetected electrical or genetic abnormalities that would explain someone’s sudden death.

“[OCM’s] relevance and basis as a marker of risk for SCD now requires assessment in population studies,” they wrote.