Did Jesus die of a 'broken heart'?

Could these biblical texts be interpreted as the historical evidence that Jesus of Nazareth died of heart rupture or ‘a broken heart’ causing pericardial tamponade (punctured by the soldier’s spear)? During the last decade, a strange syndrome of extensive reversible cardiac dysfunction precipitated by acute emotional or physical stress has been increasingly recognized. The syndrome has various names, including stress-induced cardiomyopathy (SIC), takotsubo cardiomyopathy (named after a Japanese octopus-trapping pot), transient left-ventricular apical-ballooning syndrome, and brokenheart syndrome. In some patients, SIC may lead literally to heart rupture (and death) due to intensive local cell necrosis. It is, therefore, plausible to propose that SIC should be one additional diagnosis on the list over the possible causes of death during crucifixion. Stress-induced cardiomyopathy is an unusual form of regional myocardial dysfunction that may affect both the left and right ventricle. It typically occurs in the absence of obstructive coronary artery stenosis although it has been reported that SIC may coexist with significant coronary artery disease. For reasons as yet unknown, SIC most commonly affects post-menopausal women and the epidemiology remains largely unknown. The mechanisms behind SIC are poorly understood. Excessive sympathetic stimulation of the myocardium due to ‘catecholamine storm’ has been proposed. Several lines of evidence support the hypothesis that catecholamine toxicity may be the key noxious stimulus. Wittstein et al. have reported that patients with SIC triggered by emotional stress have raised plasma concentrations of catecholamines that are several times higher than those of patients with acute heart failure (Killip III) after myocardial infarction and that SIC may be directly induced by the dobutamine stress protocol. These observations are supported by results from animal experiments. Although some researchers suggest that neurological insults and phaeochromocytoma should be excluded before diagnosing SIC, the cases reported in the literature show that SIC can be triggered by almost any insult that elicits a sudden activation of the sympathetic system. An increasing number of publications about SIC have appeared in PubMed over the last few years. This publishing ‘proliferation’ is a testimony to the increasing interest in this cryptic syndrome, as more and more clinicians diagnose SIC in everyday practice. An attempt at systematic review will reveal a shortage of studies addressing the molecular mechanisms involved in SIC. Only a few published studies have addressed such mechanisms. In this context, the study by Nef et al. presented in this issue of the European Journal of Heart Failure is unique as it provides novel insights at the cellular level. The authors obtained samples of affected left ventricular myocardium from 16 patients with SIC during the acute phase. These samples were then compared with samples taken from the same patients during the recovery phase. The authors investigated the difference in gene expression and protein levels in pro-survival signalling systems during these two phases. They focused on the PI3K/AKT pathway based on results from their previous work, which showed increased gene expression of several components in the PI3K/AKT system during the recovery phase of SIC. Indeed, by applying standard molecular biology assays for gene and protein analysis, they have confirmed and partly extended their previous observations. The results show that several components of the PI3K/AKT signalling pathway and its down-stream targets, mTOR (the mammalian target of rapamycin), GSK3 (glycogen synthase kinase 3), and elF4E (the eukaryotic initiation factor 4E), are up-regulated during the recovery phase. The authors postulate that activation of the PI3K/AKT signalling pathway may provide the explanation for the absence of extensive myocardial damage and for the rapid recovery observed in SIC.