Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

We employed physiogenomic analyses to investigate the relationship between myalgia and selected polymorphisms in serotonergic genes, based on their involvement with pain perception and transduction of nociceptive stimuli. We screened 195 hypercholesterolemic, statin-treated patients, all of whom received either atorvastatin, simvastatin, or pravastatin. Patients were classified as having no myalgia, probable myalgia, or definite myalgia, and assigned a myalgia score of 0, 0.5, or 1, respectively. Fourteen single nucleotide polymorphisms (SNPs) were selected from candidates within the 5-HT receptor gene families [5a-hydroxytryptamine receptor genes (HTR) 1D, 2A, 2C, 3A, 3B, 5A, 6, 7] and the serotonin transporter gene (SLC6A4). SNPs in the HTR3B and HTR7 genes, rs2276307 and rs1935349, respectively, were significantly associated with the myalgia score. Individual differences in pain perception and nociception related to specific serotonergic gene variants may affect the development of myalgia in statin-treated patients.

Background: Takotsubo cardiomyopathy is a syndrome of transient left ventricular dysfunction following acute emotional or physical stress without obstructive coronary artery disease. The leading hypothesis for the etiology is stress-induced catecholamine surge. Hypothesis: People taking outpatient β-adrenergic receptor antagonist therapy have less-severe presentation and clinical course of Takotsubo cardiomyopathy. Methods: We identified patients diagnosed with Takotsubo cardiomyopathy from October 2005 to January 2011 by analyzing our cardiac-catheterization database. Clinical records and angiograms were reviewed by 2 experienced observers independently to confirm the diagnosis. We collected clinical, demographic, laboratory, and angiographic data for the identified patients. We then compared the severity of myocardial dysfunction or damage (cardiac enzymes, left ventricular end diastolic pressure, and left ventricular ejection fraction) between patients taking outpatient β-adrenergic antagonist therapy upon admission vs those who were not. Arrival and peak values for cardiac enzymes were analyzed when available. Analysis of parameters related to the severity of myocardial dysfunction or damage was conducted using the Mann-Whitney U test. Means for age were compared using the Student t test. Statistical significance was set at P< 0.05 (2-tailed). Results: Out of 64 patients identified, 16 (25%) were on one of 3 β-adrenergic antagonists on presentation: metoprolol succinate, metoprolol tartrate, or atenolol, with mean doses of 75 mg daily, 52.5 mg twice daily, and 37.5 mg daily, respectively. Patients on β-blockers were older (mean age 73.1 years vs 66 years; P < 0.05). There was no statistically significant difference in levels of cardiac enzymes, left ventricular end diastolic pressure, or left ventricular ejection fraction between the 2 groups. Conclusions: Prior therapy with low-dose β-adrenergic antagonists does not affect the severity of presentation and clinical course of Takotsubo cardiomyopathy as measured by common markers of myocardial dysfunction.

The diagnosis of stress cardiomyopathy is often made during coronary angiography. At this point hemodynamic parameters should be assessed; a right heart catheterization with measurement of cardiac output by Fick and thermodilution methods is helpful. Patients with acute neurologic pathology who develop left ventricular dysfunction (neurogenic stunned myocardium) may not be candidates for coronary angiography and in such cases real-time myocardial contrast echocardiography or nuclear perfusion scan can be used to exclude obstructive coronary disease. Hypotension and shock can be due to low output state or left ventricular outflow tract obstruction. Low output state can be managed with diuretics and vasopressor support. Refractory shock and/or severe mitral regurgitation may require an intra-aortic balloon pump for temporary support. In patients with intraventricular gradient intravenous beta-blockers have been used safely. Hemodynamically unstable patients should be managed in a critical care unit and stable patients should be monitored on a telemetry unit as arrhythmias may occur. An echocardiogram should be performed to look for intraventricular gradient, mitral regurgitation, or left ventricular thrombus. If left ventricular thrombus is seen or suspected anticoagulation with warfarin or low molecular weight heparin is generally advised until recovery of myocardial function and resolution of thrombus occurs. In patients with subarachnoid hemorrhage the use of vasopressors to reduce cerebral vasospasm may worsen left ventricular outflow tract gradient. In hemodynamically stable patients, a beta-blocker or combined alpha/beta blocker should be initiated. Myocardial function generally recovers within days to weeks with supportive treatment in most patients. The use of a standard heart failure regimen including an angiotensin-converting enzyme inhibitor or aldosterone receptor antagonist, beta-blocker titrated to maximal dose, diuretics, and aspirin is common until complete recovery of myocardial function occurs. Chronic therapy with a beta-blocker may be advisable. The underlying diagnosis that precipitated stress cardiomyopathy such as critical illness, neurologic injury, or medication exposure should be identified and treated.

Takotsubo cardiomyopathy is a phenomenon of transient acute left ventricular dysfunction without obstructive coronary disease seen predominantly in postmenopausal women in the setting of acute emotional or physical stress. Neurocardiogenic injury from acute neurologic events such as intracranial bleeding can precipitate transient left ventricular dysfunction (termed ‘neurogenic stunned myocardium’) that may be indistinguishable from takotsubo cardiomyopathy. There is controversy about the diagnosis of takotsubo cardiomyopathy in the setting of acute neurologic disorders. We describe a case of a 67-year-old female who initially presented with takotsubo cardiomyopathy due to an acute gastrointestinal illness and 4 years later developed a recurrence in the setting of an ischemic cerebrovascular accident that was associated with more prominent EKG changes and much higher cardiac biomarker release but similar degree of left ventricular dysfunction. This case suggests that susceptibility to this disorder is likely due to patient-specific factors rather than etiology, and acute neurologic disorders should be included as precipitants of takotsubo cardiomyopathy. We also theorize that there may be patients with milder forms of stress-related cardiac injury who do not develop left ventricular dysfunction, being similar to the wide range of cardiac manifestations in patients with acute neurologic disorders. We review published literature on neurologic precipitants of takotsubo cardiomyopathy.