Angina due to coronary artery spasm (variant angina): diagnosis and intervention strategies.

INTRODUCTION: Since Prinzmetal first described a 'variant' form of angina pectoris, with predominantly resting episodes of pain and cyclic severity variations, it has gradually become apparent that this clinical presentation is caused by episodes of coronary artery spasm (CAS) involving focal or diffuse changes in large and/or small coronary arteries in the presence or absence of 'fixed' coronary artery stenoses. However, most clinicians have only limited understanding of this group of disorders. AREAS COVERED: We examine the clinical presentation of CAS, associated pathologies outside the coronary vasculature, impediments to making the diagnosis, provocative diagnostic tests, available and emerging treatments, and the current understanding of pathogenesis. EXPERT OPINION: CAS is often debilitating and substantially under-diagnosed and occur mainly in women. Many patients presenting with CAS crises have non-diagnostic ECGs and normal serum troponin concentrations, but CAS can be suspected on the basis of history and association with migraine, Raynaud's phenomenon and Kounis syndrome. Definitive diagnosis requires provocative testing at coronary angiography. Treatment still centers around the use of calcium antagonists, but with greater understanding of pathogenesis, new management options are emerging.

Incidence and clinical/laboratory correlates of early hypotension in takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is a form of acute myocardial inflammation, often triggered by catecholamine release surges, which accounts for approximately 10% of 'myocardial infarctions' in female patients above the age of 50. Its associated substantial risk of in-hospital mortality is mainly driven by the development of hypotension and shock. While hypotension is induced largely by factors other than low cardiac output, its precise cause is unknown, and clinical parameters associated with hypotension have not been identified previously. We therefore sought to identify the incidence and clinical/laboratory correlates of early hypotension in TTS. METHODS AND RESULTS: We analysed the in-hospital data of patients recruited to the South Australian TTS Registry. Associations between the development of hypotension, patient demographics, severity of the acute TTS attack, and key biochemical markers were sought. One hundred thirteen out of 319 patients (35%) were hypotensive (median systolic blood pressure 80 mmHg) during their index hospitalization. Development of hypotension preceded all in-hospital deaths (n = 8). On univariate analyses, patients who developed hypotension had lower left ventricular ejection fraction (P = 0.009), and higher plasma N-terminal pro brain natriuretic peptide and troponin-T concentrations (P = 0.046 and 0.008, respectively), all markers of severity of the TTS attack; hypotension also occurred less commonly in male than in female patients (P = 0.014). On multivariate linear regression analysis, female sex and lower left ventricular ejection fraction were independent correlates of the development of hypotension (P = 0.009 and 0.010, respectively). CONCLUSIONS: Early development of hypotension is very common in TTS, and its presence is associated with a substantial risk of in-hospital mortality. Hypotension is a marker of severe TTS attacks and occurs more commonly in female TTS patients.

Takotsubo Syndrome: Finally Emerging From the Shadows?

It is now 30 years since Japanese investigators first described Takotsubo Syndrome (TTS) as a disorder occurring mainly in ageing women, ascribing it to the impact of multivessel coronary artery spasm. During the intervening period, it has become clear that TTS involves relatively transient vascular injury, followed by prolonged myocardial inflammatory and eventually fibrotic changes. Hence symptomatic recovery is generally slow, currently an under-recognised issue. It appears that TTS is induced by aberrant post-ß2-adrenoceptor signalling in the setting of "surge" release of catecholamines. Resultant activation of nitric oxide synthases and increased inflammatory vascular permeation lead to prolonged myocardial infiltration with macrophages and associated oedema formation. Initially, the diagnosis of TTS was made via exclusion of relevant coronary artery stenoses, plus the presence of regional left ventricular hypokinesis. However, detection of extensive myocardial oedema on cardiac MRI imaging offers a specific basis for diagnosis. No adequate methods are yet available for definitive diagnosis of TTS at hospital presentation. Other major challenges remaining in this area include understanding of the recently demonstrated association between TTS and antecedent cancer, the development of effective treatments to reduce risk of short-term (generally due to shock) and long-term mortality, and also to accelerate symptomatic recovery.