Coronary microvascular dysfunction leads to cardiac dysfunction and development of transient apical ballooning (1079.27)

Transient apical ballooning also known as Takotsubo cardiomyopathy, is a particular acute coronary syndrome and is characterized by transient systolic ballooning of the apex in the absence of significant epicardial coronary disease. The exact mechanism of transient apical ballooning is still unknown, but it is speculated that impaired microvascular metabolic dilation produces the pathology. Previously we found that metabolic dilation (increase in coronary flow in response to augmented cardiac work) was compromised in mice null for Kv1.5 channels (Kv1.5 ‐/‐ ) compared to wild type mice (WT). Because compromised flow during metabolic stress (what we observed in the Kv1.5 ‐/‐ mice) is thought to be an initiating factor for apcial ballooning, we hypothesized that Kv1.5 ‐/‐ mice, with impaired coronary metabolic dilation, develop apical ballooning when subjected to a chronic metabolic challenge. Transaortic constriction (TAC) was performed to chronically increase afterload in Kv1.5 ‐/‐ and WT male mice. Measurements of cardiac function were made 7 days after TAC, then at day 10 the constriction was released (de‐banding). Cardiac function was measured up to 6 weeks after de‐banding using high frequency ultrasound. More than 50 % of Kv1.5 ‐/‐ mice developed apical ballooning 7 days after TAC. M‐mode echocardiography was performed at the apex and at the base of the heart to identify ballooning. The apex was significantly dilated compared to the base in Kv1.5 ‐/‐ mice. During systole the base contracted, but the apex dilated. One week after de‐banding, apical ballooning was absent and 6 weeks later ejection fraction approximated that before TAC. Based on these data, we conclude that impaired coupling of myocardial blood flow to cardiac work, a condition known as coronary microvascular dysfunction, causes apical ballooning during heightened cardiac work.