Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials.

AIM: To evaluate the safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab according to diabetes mellitus status. METHODS: Safety data from 14 trials (8-104-week durations) were analysed by treatment (alirocumab or placebo/ezetimibe control) and diabetes status (yes/no, defined by medical history). Adverse event data were assessed using descriptive statistics and Cox models. RESULTS: Of the 5234 trial participants, 1554 (29.7%) had diabetes. Overall, treatment-emergent adverse events were similar in the alirocumab and control groups, except for more frequent local injection site reactions with alirocumab. Fewer people with diabetes experienced local injection site reactions [alirocumab, 3.5%, control, 2.9%; hazard ratio 1.24 (95% CI 0.68-2.25)] than those without diabetes [alirocumab, 7.5%; control, 4.9%; hazard ratio 1.51 (95% CI 1.13-2.01)]. Those with diabetes reported a greater number of serious adverse events (alirocumab, 19.4%; control, 19.7%) than those without diabetes (alirocumab, 14.5%; control, 13.5%). In people with diabetes, major adverse cardiac events occurred in 2.7% of alirocumab-treated people [control, 3.3%; hazard ratio 0.74 (95% CI 0.41-1.35)]; in those without diabetes, 1.8% of alirocumab-treated people had major adverse cardiac events [control, 1.7%; hazard ratio 0.95 (95% CI 0.56-1.62)]. Overall, no increase in HbA1c or fasting plasma glucose vs control treatment groups was observed, regardless of diabetes status. CONCLUSION: This pooled analysis across 14 trials demonstrated similar safety for alirocumab vs control treatment, irrespective of diabetes status, except for more frequent local injection site reactions with alirocumab. People with diabetes reported fewer local injection site reactions than those without diabetes.

Pulmonary embolism from in situ right atrial thrombus after coronary artery bypass surgery.

Pulmonary embolism after cardiac surgery is attributed to embolization from thrombus within the deep venous system. We report two cases of pulmonary embolism after coronary artery bypass surgery in which transesophageal echocardiography detected in situ right atrial thrombus. The right atrium should be screened for thrombus in patients who have pulmonary embolism after cardiac surgery.

Risk of catheter-related emboli in patients with atherosclerotic debris in the thoracic aorta.

The aim of this study was to evaluate the risk of performing cardiac catheterization or intraaortic balloon pump placement in patients with transesophageal echocardiographically detected atherosclerotic aortic debris. Cardiac catheterization was performed in 70 patients with atherosclerotic aortic debris (in 11 via the brachial approach and in 59 via the femoral approach) and in 71 control patients. An embolic event occurred in 10 (17%) of 59 patients with atherosclerotic aortic debris after femoral catheterization compared to 2 (3%) of 71 control patients without atherosclerotic aortic debris (p = 0.01). None of the 11 patients with atherosclerotic aortic debris who underwent brachial catheterization had an embolic event. An intraaortic balloon pump was placed in 10 patients with atherosclerotic aortic debris and in 12 control patients. An embolic event related to placement of the intraaortic balloon pump occurred in 5 (50%) of 10 patients with atherosclerotic aortic debris; no control patient had an embolic event (p = 0.02). Patients with mobile atherosclerotic aortic debris were at the highest risk for catheter-related embolism. The strongest clinical predictors of atherosclerotic aortic debris were advanced age and peripheral vascular disease. Transesophageal echocardiographic recognition of atherosclerotic aortic debris identifies patients at high risk of stroke or peripheral embolism after cardiac catheterization or intraaortic balloon pump placement. If the aortic debris is mobile, the risk is particularly high. When atherosclerotic aortic debris is detected, especially if the debris is mobile, substituting brachial for femoral catheterization and avoiding placement of an intraaortic balloon pump may reduce the risk of embolism.

Spontaneous arterial embolization after thrombolytic therapy for acute myocardial infarction: the role of transesophageal echocardiography.

Arterial embolization from thrombolytic therapy for acute myocardial infarction is rare. We report two cases of spontaneous arterial embolization following the use of tissue plasminogen activator for acute myocardial infarction. Transesophageal echocardiography was able to identify the source of embolism as mobile atherosclerotic debris within the thoracic aorta. This information was of value in the management of these patients, in that femoral catheterization which could have precipitated further embolization was avoided.

The role of echocardiography in blunt chest trauma: a transthoracic and transesophageal echocardiographic study.

Previous studies assessing the value of transthoracic echocardiography (TTE) in blunt chest trauma are limited because patients with severe chest wall injury often have suboptimal echocardiographic findings. Transesophageal echocardiography (TEE) can provide high quality images when the transthoracic image quality is poor. To provide complete echocardiographic assessment of cardiac structure and function we prospectively performed TTE in 105 patients with severe blunt chest trauma and TEE in 20 of the 105 patients (19%) whose TTE examination results were suboptimal. Myocardial contusion was diagnosed in 31 patients (30%), 22 by TTE and nine by TEE. Cardiac complications developed in 8 of 31 patients (26%) with myocardial contusion compared with 2 of 74 patients (3%) with normal echocardiographic findings (p = 0.001). Cardiac complications required treatment in only four patients. Echocardiography was of value in detecting severe right ventricular dysfunction as the cause of hypotension in two patients with suspected cardiac tamponade. Four patients with myocardial contusion died compared with two patients with normal echocardiographic findings (p = NS). No death was related to the cardiac status. In addition, TEE detected aortic injury in five patients, four with focal intimal tears and one with an aortic transection. We conclude that myocardial contusion is common following blunt chest trauma, rarely requires treatment, and is associated with a favorable prognosis. Only patients who develop cardiac complications benefit from echocardiography. Transesophageal echocardiography is of value when the TTE examination results are suboptimal and when aortic injury is suspected.

Severe right ventricular contusion mimicking cardiac tamponade: the value of transesophageal echocardiography in blunt chest trauma.

Clinically, severe right ventricular contusion may mimic cardiac tamponade. We report two cases of suspected cardiac tamponade after blunt chest trauma in which the diagnosis of severe right ventricular contusion was made only by transesophageal echocardiography, avoiding unnecessary and hazardous pericardiocentesis. These cases illustrate the value of transesophageal echocardiography in diagnosing blunt chest trauma.

The role of transesophageal echocardiography in the acute onset of paraplegia.

BACKGROUND AND PURPOSE: Acute paraplegia must be investigated promptly to exclude reversible causes. In this report we illustrate the usefulness of transesophageal echocardiography in identifying the vascular etiologies of acute paraplegia. CASE DESCRIPTIONS: Two patients presented with acute paraplegia, one spontaneously and the other after removal of an intra-aortic balloon pump catheter. Through the use of transesophageal echocardiography, we excluded aortic dissection and identified protruding atherosclerotic plaques in the descending thoracic aorta of each patient. Embolization of atheromatous material from the thoracic aorta was considered the most likely etiology of paraplegia in both cases. CONCLUSIONS: Embolization from atherosclerotic plaques in the thoracic aorta may be an underestimated cause of acute paraplegia. Transesophageal echocardiography provides a safe, rapid, and reliable tool for investigating a vascular etiology of acute paraplegia.

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis. Clinical and surgical implications.

BACKGROUND: Secondary involvement of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet (subaortic structures) can occur in patients with aortic valve endocarditis. The secondary involvement of these structures occurs as a result of direct extension of the infection from the aortic valve or as a result of an infected aortic regurgitant jet striking the ventricular surfaces of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet. The abscess of mitral-aortic intervalvular fibrosa can expand to form an aneurysm. Subsequently, this mitral-aortic intervalvular fibrosa aneurysm can develop a perforation and communicate with the left atrium, resulting in the systolic regurgitation of blood from the left ventricular outflow tract into the left atrium. Secondary infection can also occur on the ventricular surface of the anterior mitral leaflet and result in the formation of an aneurysm or perforation of anterior mitral leaflet. METHODS AND RESULTS: This study examines the utility of transesophageal echocardiography in the detection of these subaortic complications in 55 consecutive patients with aortic valve endocarditis. A total of 24 patients (44%) had involvement of subaortic structures, including four with an abscess in the mitral-aortic intervalvular fibrosa, four with mitral-aortic intervalvular fibrosa aneurysm, seven with perforation of the mitral-aortic intervalvular fibrosa with communication into the left atrium, two with an aneurysm of the anterior mitral leaflet, and seven with perforation of the anterior mitral leaflet. The transesophageal echocardiographic findings were confirmed at surgery in 20 patients and at necropsy in two. By comparison, transthoracic echocardiography visualized these lesions in five of 24 patients (21%), including none of four with mitral-aortic intervalvular fibrosa abscesses, two of four with mitral-aortic intervalvular fibrosa aneurysms, one of seven with mitral-aortic intervalvular fibrosa perforations, one of two with anterior mitral leaflet aneurysms, and one of seven anterior mitral leaflet perforations. Eccentric mitral regurgitation-type systolic jets were noted in eight additional patients by transthoracic color flow imaging, and this finding suggested the possibility of these unusual subaortic complications. If these patients are included, then transthoracic echocardiography suggested the presence of these subaortic complications in 13 of 24 patients (54%). CONCLUSIONS: The results indicate that 1) involvement of the subaortic structures in patients with aortic valve endocarditis may be more common than previously recognized, 2) patients with aortic valve endocarditis and eccentric jets of mitral regurgitation on transthoracic echocardiography should undergo further evaluation by transesophageal echocardiography to exclude these unusual complications, 3) precise recognition of these complications is of value in the optimal medical and surgical management of these patients, and 4) these complications may be responsible for unexplained congestive heart failure and hemodynamic deterioration in some patients with aortic valve endocarditis.

Single-plane transesophageal echocardiography for assessing function of mechanical or bioprosthetic valves in the aortic valve position.

To assess the value and limitations of single-plane transesophageal echocardiography in the evaluation of prosthetic aortic valve function, 89 patients (69 mechanical and 20 bioprosthetic aortic valves) were studied by combined transthoracic and transesophageal 2-dimensional and color flow Doppler echocardiography. In the assessment of aortic regurgitation, the transthoracic and transesophageal echocardiographic findings were concordant in 71 of 89 patients (80%). In 8 patients, the degree of aortic regurgitation was underestimated by the transthoracic approach; in each case the quality of the transthoracic echocardiogram was poor. In 10 patients, transesophageal echocardiography failed to detect trivial aortic regurgitation due to acoustic shadowing of the left ventricular outflow tract from a mechanical valve in the mitral valve position. Transesophageal echocardiography was superior to transthoracic echocardiography in diagnosing perivalvular abscess, subaortic perforation, valvular dehiscence, torn or thickened bioprosthetic aortic valve cusps, and in clearly distinguishing perivalvular from valvular aortic regurgitation. Transesophageal echocardiography correctly diagnosed bioprosthetic valve obstruction in 1 patient, but failed to diagnose mechanical valve obstruction in another. In conclusion, transesophageal echocardiography offers no advantage over the transthoracic approach in the detection and quantification of prosthetic aortic regurgitation unless the transthoracic image quality is poor. Transesophageal echocardiography is limited in detecting mechanical valve obstruction and in detecting aortic regurgitation in the presence of a mechanical prosthesis in the mitral valve position. However, it is superior to transthoracic echocardiography in identifying perivalvular pathology, differentiating perivalvular from valvular regurgitation and in defining the anatomic abnormality responsible for the prosthetic valve dysfunction. Combined transthoracic and transesophageal examination provides complete anatomic and hemodynamic assessment of prosthetic aortic valve function.

Diagnosis of superior vena caval obstruction by transesophageal echocardiography.

Superior vena caval (SVC) syndrome may be caused by extravascular compression or intravascular obstruction. Knowing the mechanism of SVC syndrome enables the physician to choose appropriate treatment. Transesophageal echocardiography (TEE) is a safe bedside procedure that is excellent for evaluating the SVC and its surrounding structures. We report the valuable role of TEE in demonstrating the mechanism of SVC syndrome.