The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Comprehensive echocardiographic diagnosis of right heart enlargement in association with partial anomalous pulmonary venous drainage in three adult women.

Partial anomalous pulmonary venous drainage is a rare congenital anomaly which can lead to right heart enlargement. It may present in isolation or more commonly in association with other congenital cardiac anomalies. We present three different cases of partial anomalous pulmonary venous drainage in adults. The importance of identifying partial anomalous venous drainage as the cause of otherwise unexplained right heart enlargement is illustrated by these cases.

Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction. BACKGROUND: Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability. METHODS: Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [+/- SD] 29 +/- 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 micrograms/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography. RESULTS: After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 +/- 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 +/- 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch. CONCLUSIONS: In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.

Risk factors for lacunar stroke: a case-control transesophageal echocardiographic study.

To reassess the independent risk factors for lacunar stroke and to clarify the role of potential embolic sources, we conducted a case-control study using transesophageal echocardiography and duplex ultrasonography. Among 62 consecutive patients with their first lacunar stroke and 202 normal controls, we found that hypertension (p < 0.001), smoking (p = 0.001), and aortic arch atheroma (p = 0.006) were independently associated with an increased risk of lacunar stroke. Whether proximal aortic arch atheroma is mechanistically associated with lacunar stroke or merely coexistent is uncertain.

Evidence that patent foramen ovale is not a risk factor for cerebral ischemia in the elderly.

Patent foramen ovale (PFO) may be a risk factor for ischemic stroke in young patients. The aim of this study was to assess the importance of PFO in subjects with a wider age range using patient-control methodology. Transesophageal contrast echocardiography and carotid imaging were performed in 220 consecutive patients with cerebral ischemia (mean age 66 +/- 13 years) and in 202 community-based control subjects (mean age 64 +/- 11 years). Of patients with stroke, 35 (16%) had PFO compared with 31 control subjects (15%) (p = 0.98). Analysis of PFO prevalence by age did not show a significant difference between patients and controls subjects in the age groups < 50 years (27% vs 11%; p = 0.33), 50 to 69 years (17% vs 15%; p = 0.78), and > or = 70 years (12% vs 17%; p = 0.43). However, the group aged < 50 years was relatively small (26 cases, 19 controls). No significant difference in PFO prevalence was detected between patients with cryptogenic stroke (20%), noncryptogenic stroke (14%), and control subjects (15%). These results suggest that PFO is not a risk factor for cerebral ischemia in subjects aged > 50 years, which would have major implications for the investigation and management of stroke patients in this age group. Longitudinal studies are now required to assess the incidence of stroke in symptom-free patients with PFO.

Atrial fibrillation with left atrial spontaneous contrast detected by transesophageal echocardiography is a potent risk factor for stroke.

Nonrheumatic atrial fibrillation (AF) frequently coexists with other risk factors for cerebral ischemia. This study was originally designed to determine which combinations of clinical and echocardiographic abnormalities were most closely associated with the risk of cerebral ischemic events. Patients with cerebral ischemic events (n = 214) and community-based control subjects (n = 201) underwent transesophageal echocardiography and carotid artery imaging. Adjusted odds ratios (ORs) were determined using multiple logistic regression analysis. Independent risk factors for cerebral ischemia included diabetes, carotid stenosis, aortic sclerosis, left ventricular dysfunction, left ventricular hypertrophy, left atrial (LA) spontaneous contrast, and proximal aortic atheroma. Nonrheumatic AF in combination with LA spontaneous contrast and LA enlargement showed a strong association with cerebral ischemic events (OR 33.7 [95% confidence interval 4.53 to 251]). In subjects with sinus rhythm or nonrheumatic AF, LA enlargement was not associated with an increased risk of cerebral ischemic events in the absence of LA spontaneous contrast. However, only 2 patients and 1 control subject had nonrheumatic AF without LA spontaneous contrast or LA enlargement. Therefore, study of a larger number of subjects is required to address the issue of whether nonrheumatic AF itself carries increased risk. The combination of nonrheumatic AF with LA spontaneous contrast is a potent risk factor for cerebral ischemia. Ascertaining the risk factor in nonrheumatic AF requires adequate examination for underlying cardiac, aortic, and carotid vascular disease. Transesophageal echocardiography may contribute to this assessment.

Left ventricular false aneurysm complicating mitral valve repair.

Left ventricular false aneurysm is a rare complication of mitral valve replacement or myocardial infarction. A case of left ventricular false aneurysm complicating mitral valve repair is presented. The patient was clinically asymptomatic, and the diagnosis was made on postoperative transesophageal echocardiography. The patient subsequently underwent successful mitral valve replacement and false aneurysm repair.

Precise evaluation of a complex coronary arteriovenous fistula: the utility of transesophageal color Doppler.

The transesophageal color flow Doppler appearance of coronary artery fistulas have not been described previously. We present a patient with a fistulous connection between the right coronary artery and the right atrium with an additional connection to the coronary sinus. The fistulous connection to the coronary sinus, confirmed at operation, was only diagnosed with transesophageal color flow Doppler and missed on both transthoracic echocardiography and cardiac catheterization. In addition, intraoperative transesophageal echocardiography was extremely useful in confirming closure of both these fistulas, thus confirming a successful operative result.

Doppler echocardiographic quantitation of volumetric flow rate.

Doppler echocardiographic determination of cardiac output has been well validated in clinical and experimental settings. Doppler measurement of volumetric flow rate remains useful in clinical practice in a wide variety of settings, especially when serial or comparative determinations are required. As improved echocardiographic equipment enhances image resolution and includes more sophisticated on-line analysis packages, the feasibility of expediently quantitating flow with Doppler echocardiography will be facilitated.

Clinical implications of the morphological features of central pulmonary artery thromboemboli shown by transoesophageal echocardiography.

OBJECTIVES: To illustrate the use of transoesophageal echocardiography in the detection of the morphological features of central pulmonary artery thromboemboli and their clinical implications. DESIGN: Review of five cases of central pulmonary artery thromboemboli detected by transoesophageal echocardiography. SETTING: University teaching hospital. PATIENTS: Five patients (three men and two women) admitted under general medical units. RESULTS: Central pulmonary artery thromboemboli were detected by the use of transoesophageal echocardiography in all the patients presented. Presentations were acute, subacute, or chronic. The morphological features of the thromboemboli on transoesophageal echocardiography were used to correlate with the time course of the illness, and to guide treatment. Two patients received thrombolytic treatment, one patient was treated with anticoagulation alone, and two patients had inferior vena caval filters implanted. CONCLUSIONS: Transoesophageal echocardiography is an alternative diagnostic tool in the detection of central pulmonary artery thromboemboli. Morphological features of central pulmonary thromboemboli on echocardiography can provide useful information that may help to guide treatment.

Proximal aortic atheroma. An independent risk factor for cerebral ischemia.

BACKGROUND AND PURPOSE: Transesophageal echocardiography frequently demonstrates aortic atheroma in patients with cerebral and peripheral emboli. The aim of this study was to determine whether atheroma in the ascending aorta and arch is an independent risk factor for cerebral ischemia. METHODS: We studied 215 consecutive patients with a first stroke or transient ischemic attack and 202 community-based control subjects using transesophageal echocardiography to detect aortic atheroma and potential cardiac sources for embolism. Information about other stroke risk factors was obtained from a structured interview, and the presence of carotid vascular disease was assessed by means of duplex ultrasonography or digital subtraction angiography. Multiple logistic regression analysis was used to determine adjusted odds ratios for each risk factor. RESULTS: Atheroma in the ascending aorta and aortic arch was a significant risk factor for cerebral ischemia, independent of other well-established risk factors including high-grade carotid stenosis. The odds ratio for simple atheroma was 2.3 (95% confidence interval, 1.2 to 4.2) and for complex atheroma 7.1 (2.7 to 18.4). CONCLUSIONS: Ascending aortic and arch atheroma detected by transesophageal echocardiography is an important new independent risk factor for cerebral ischemia. Further characterization of the embolic potential of atheroma with different echocardiographic appearances and development of optimal management strategies are now needed.

Multiple cardiac papillary fibroelastomas and rheumatic heart disease.

A case of severe rheumatic mitral stenosis was found to have multiple echodense masses attached to the ventricular surface of the mitral valve and papillary muscle at preoperative 2-dimensional echocardiography. Subsequent surgery involved mitral valve replacement and excision of the masses. Complete excision was confirmed by intraoperative transoesophageal echocardiography. Histologic examination of the surgical specimens showed typical papillary fibroelastomas. This is the first case report of multiple papillary fibroelastomas in association with rheumatic valvular disease demonstrated by 2-dimensional echocardiography.

Transoesophageal echocardiography in the investigation of stroke: experience in 135 patients with cerebral ischaemic events.

BACKGROUND: The importance of cardiogenic embolism as a cause of cerebral ischaemic events may be underestimated if potential cardiac sources of embolism remain undetected. Transoesophageal echocardiography (TOE) is more sensitive in detecting such abnormalities than earlier methods and may result in more frequent recognition of cardiogenic embolism. AIMS: To establish in an unselected stroke population the prevalence of potential cardiac sources of embolism detectable on TOE and their relationship to atrial fibrillation and carotid stenosis. METHODS: One hundred and thirty-five consecutive patients with cerebral ischaemic events were studied using transthoracic and monoplane transoesophageal contrast echocardiography and carotid Duplex imaging or cerebral angiography. RESULTS: Thirty patients (22%) had atrial fibrillation. In 43 patients (32%), no cardiac source of embolism was identified; in eight echocardiography was normal. At least one potential cardiac source of embolism was identified in 92 patients (68%) with multiple findings in 41; these patients were older (70 +/- 9 years vs 61 +/- 14 years; p = 0.0001), more frequently in atrial fibrillation (28/92 vs 2/43; p = 0.0017) and more frequently had cortical or large subcortical stroke (71/92 vs 23/43; p = 0.005). Carotid stenoses were detected in 55% of patients, not significantly different in those with and without cardiac abnormalities. CONCLUSION: When bias in selection of patients is avoided, TOE detects a potential cardiac source of embolism in most patients with cerebral ischaemia, particularly those older and in atrial fibrillation. Multiple cardiac abnormalities and coexistent carotid disease are common. The implication of these findings for prevention of stroke awaits age-matched controlled studies.

Development and validation of echocardiographic methods for estimating left ventricular mass in rats.

1. The aim of this study was to develop non-invasive echocardiographic methods of measuring left ventricular mass (LVM) in rats, and to determine their usefulness in detecting left ventricular hypertrophy. 2. After initial studies to identify the optimum transducer and to ascertain the resolution limits of echocardiography, the repeatability of LVM estimates was studied. The average difference between two independent estimates in 86 male rats (average LVM = 674.7 mg) was 5.4 mg, and the standard deviation of the difference was 107.6 mg. 3. To determine agreement between direct and indirect methods, LVM was measured in 38 male rats by echocardiography and compared with direct measurement of the left ventricular weight at sacrifice. The mean difference between the two methods was 9.14 +/- 56.6 mg. The limits of agreement were from -122.4 to +104.1 mg. 4. Echocardiography was then used to measure LVM in eight male spontaneously hypertensive rats and eight male normotensive Donryu rats at 9 weeks of age. The mean LVM of SHR was 768.2 mg +/- 152.6, which was significantly (2P less than 0.001) greater than the LVM of DRY (435.4 mg +/- 32.2). 5. We conclude that echocardiography provides a non-invasive, repeatable and relatively accurate estimate of LVM in rats. The method is a potentially useful tool for studying the development or regression of cardiac hypertrophy in longitudinal experiments.

Assessment of coronary artery disease by dobutamine stress echocardiography (DSE).

BACKGROUND: Dobutamine stress echocardiography (DSE) is a new non-invasive imaging modality which combines two-dimensional echocardiography with cardiovascular stress induced by dobutamine infusion. Its use in patients with suspected or documented coronary artery disease (CAD) is currently under extensive investigation. AIMS: To illustrate the clinical utility, safety and diagnostic value of DSE. METHODS: One hundred and thirty-seven consecutive patients referred for DSE were studied. Eighty-four patients also underwent coronary angiography. RESULTS: Eleven patients (8%) did not undergo DSE because of poor image quality. Of the remaining 126 patients, 110 (87%) achieved their target heart rate or reached a pre-determined end point during DSE. Eight patients (6%) developed non-cardiac side effects during DSE, none of which required premature termination of the procedure. Cardiac arrhythmias were documented in 15 patients (12%) but only one required intervention. In 84 patients who underwent coronary angiography, DSE showed a sensitivity and specificity of 88% and 83%, respectively, in detecting the presence of, and 75% and 75%, respectively, in localising significant CAD. In 35 patients who underwent DSE after uncomplicated myocardial infarction, the positive and negative predictive values for cardiac events following infarction in a six-month followup period were 74% and 62%, respectively. CONCLUSIONS: DSE is a well tolerated, safe and useful test in detecting and localising significant CAD. It can also provide useful post-infarctional prognostic information.

Cardiac metastases from malignant melanoma.

BACKGROUND: Cardiac metastases are uncommon, with the exception of malignant melanoma. More cases of cardiac involvement are being diagnosed in association with the rising incidence and increasing survival of patients with melanoma. Surgical intervention may be an effective palliative measure and should be considered for selected patients who present with this problem. METHODS: In this article, the authors present clinical, laboratory, and imaging data from two patients with malignant melanoma who presented with cardiac metastases. A discussion of these patients is accompanied by a review of the current literature on this topic. RESULTS: Two females with known metastatic malignant melanoma presented with nonspecific pulmonary symptoms and were found to have intracardiac metastases involving the right heart. One patient underwent successful surgical removal of a large tumor mass, which resulted in relief of symptoms and prevention of imminent death from cardiac complications. Together with the literature review, these cases demonstrate the important clinical features of cardiac metastases from melanoma and define the best means of diagnosis as well as the potential benefits of surgical intervention. CONCLUSIONS: Cardiac involvement by malignant melanoma is now diagnosed with increasing frequency. A diagnosis can be made with relative ease, but clinical suspicion must precede it. Surgery may be useful to palliate symptoms and prevent death from cardiac complications.