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.

Thiazolidinediones and congestive heart failure--exacerbation or new onset of left ventricular dysfunction?

BACKGROUND: Patients with diabetes mellitus have a high incidence of coronary heart disease and congestive heart failure (CHF). Thiazolidinediones (TZD) are a new class of pharmacological agents for the treatment of Type 2 diabetes mellitus, which have many beneficial cardiovascular effects. Peripheral oedema and weight gain have been reported in 4.8% of subjects on TZDs alone, with a higher incidence noted in those receiving combination insulin therapy (up to 15%), but there is limited data on the occurrence of CHF. METHODS AND RESULTS: In this paper, we report on six cases of TZD-induced fluid retention with symptoms and signs of peripheral oedema and/or CHF that occurred in subjects attending our diabetic clinic. The predominant finding in all cases was of diastolic dysfunction. All subjects were obese and hypertensive, with 5/6 having the additional risk factor of LVH, 5/6 subjects had microvascular complications, whilst 3/6 were also on insulin therapy. CONCLUSION: We suggest that obese, hypertensive diabetics may benefit from echocardiographic screening prior to commencement of TZDs, as these agents may exacerbate underlying undiagnosed left ventricular diastolic dysfunction.

Lacunar stroke: transoesophageal echocardiographic factors influencing long-term prognosis.

OBJECTIVE: Since little is known concerning factors which may influence long-term prognosis of patients presenting with lacunar stroke, we conducted a longitudinal study of this stroke subtype. Variables likely to affect outcome were assessed at baseline, including those from transoesophageal echocardiographic studies. METHODS: Consecutive patients presenting with first-ever lacunar stroke underwent diagnostic workup that included brain CT or MRI, carotid duplex, and transthoracic and transoesophageal echocardiography. An assessment of patients was planned at entry (baseline), and thereafter every 12 months (clinic visit or telephone call), drop-out, or endpoint. The primary endpoint was nonfatal or fatal stroke. Secondary endpoint was death due to any cause. RESULTS: Among 60 consecutive lacunar patients with the mean follow-up period of 3.9 years, 12 patients (20%) had stroke recurrence. The mean annual rate for stroke was 5.2%, and for death 2.8%. For multivariate Cox proportional hazards analysis, the following three variables with the values of p < 0.1 after univariate testing were chosen: age (p = 0.095); aortic atheroma (p = 0.066); and any source of embolism from heart (p = 0.007). Any source of embolism from heart was the only factor which significantly enhanced the risk of stroke recurrence (p = 0.015). Using Kaplan-Meier life table analysis, the curves of percent free of recurrent stroke were significantly different (log rank test p = 0.002). CONCLUSIONS: Until the mechanism of lacunar stroke is better understood, it is reasonable to suggest that its investigation and prevention should be directed at all potential causes of future strokes including cardioembolism.

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.

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.

The intraoperative assessment of ascending aortic atheroma: epiaortic imaging is superior to both transesophageal echocardiography and direct palpation.

OBJECTIVES: To determine the optimal method for detecting ascending aortic atheroma intraoperatively by comparing manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging); and to assess risk factors for severe aortic atheroma. DESIGN: A longitudinal prospective study. Assessment of the atheroma by manual palpation was blinded to the results of the ultrasound images. SETTING: The study was performed in a single university tertiary referral hospital. PARTICIPANTS: One hundred consecutive patients undergoing coronary bypass or valve surgery were studied after their written, informed consent. INTERVENTIONS: Potential risk factors were evaluated by both a patient questionnaire and examination of prior hospital records. The ascending aorta was assessed by the following methods: manual palpation by the operating surgeon, intraoperative transesophageal echocardiography, and epiaortic ultrasound (linear and phased-array imaging) performed by an echocardiologist. For analysis, the ascending aorta was divided into three equal segments: proximal, mid, and distal, corresponding to regions of different operative manipulations. MEASUREMENTS AND MAIN RESULTS: Age older than 70 years and hypertension were significant risk factors for severe ascending aortic atheroma with adjusted odds ratios of 3.3 (95% CI, 1.2 to 9.3) and 3.9 (95% CI, 1.3 to 12.0), respectively. There was no significant difference in atheroma detection between the two ultrasonic epiaortic probes in any segment; however, epiaortic probes were superior to manual palpation in all segments and also superior to transesophageal echocardiography in the mid and distal segments of the ascending aorta. CONCLUSIONS: Age older than 70 years and hypertension are significant risk factors for severe ascending aortic atheroma. Intraoperative detection of ascending aortic atheroma is best achieved by epiaortic ultrasound with either a linear or phased array transducer. Transesophageal echocardiography is an insensitive technique for evaluation of mid and distal ascending aortic atheroma and, therefore, of little value in guiding surgical manipulations such as cross-clamping.

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.

Validation of an echocardiographic assessment of cardiac function following moderate size myocardial infarction in the rat.

1. The present study determined whether two dimensional guided M-mode echocardiography could assess left ventricular (LV) geometry and function following a moderate size myocardial infarction in the rat. 2. Myocardial infarction (MI) was induced by left coronary artery ligation and rats were studied 4 weeks later. Infarct rats showed increased LV internal diastolic diameter (7.33 +/- 0.8 vs 5.91 +/- 0.6 mm; P < 0.001), LV systolic diameter (3.73 +/- 1.2 vs 1.87 +/- 0.6 mm; P < 0.001) and thickening of the noninfarcted posterior wall compared with sham operated rats (1.81 +/- 0.2 vs 1.47 +/- 0.3; P < 0.001; n = 10/group; mean +/- s.d.). Systolic function was impaired in infarct rats who showed reduced fractional shortening (50 +/- 12 vs 68 +/- 9%; P < 0.001) and fractional area change (41 +/- 14 vs 78 +/- 5%; P < 0.001). Infarct size measured echocardiographically was comparable to that measured by quantitative histological examination (29 +/- 10 vs 28 +/- 5%; NS). 3. The present study indicates that postinfarction remodelling leading to LV cavity dilation, hypertrophy of surviving myocardium and impaired systolic function is apparent 4 weeks following moderate size MI in the rat. 4. Transthoracic echocardiography is a noninvasive technique that may be used to assess serially the efficacy of therapeutic interventions designed to prevent remodelling in moderate size MI in the rat.

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.

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.

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.

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.

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.

Evaluation of mitral valve repair by intraoperative transoesophageal echocardiography.

BACKGROUND: Mitral valve repair is the procedure of choice in the surgical management of mitral regurgitation. Intraoperative confirmation of successful repair is essential to the effectiveness of this procedure. AIMS: The aims of this study were: (a) to compare intraoperative transoesophageal echocardiography (TOE) with the surgeon's assessment of valve competence; (b) to assess the impact of routine intraoperative imaging on the hospital echocardiography laboratory. METHODS: Eighty-six consecutive patients undergoing mitral valve repair formed the study population. Valve competence following repair was assessed intraoperatively by: TOE; saline insufflation of the flaccid left ventricle; and evaluation of the pulmonary capillary wedge pressure for the presence of a significant V wave. RESULTS: TOE demonstrated successful valve repair (< or = 1 + residual regurgitation) in 75 patients (87%) and detected significant residual regurgitation (> or = 3+) in seven (8.2%). The mechanism of regurgitation was also clearly shown. Of these seven patients, four underwent immediate valve replacement, two had successful revision of the initial repair and one required valve replacement one week later. In all seven patients the valve repair had been assessed as successful by saline testing and only one had a post-repair V wave 10 mmHg above the mean pulmonary capillary wedge pressure. In 30 non-selected patients the imaging equipment was required in theatre for 43 +/- 18 minutes. CONCLUSIONS: TOE is currently the most sensitive method for detection and quantitation of residual mitral regurgitation following valve repair. Evaluation can be performed within a similar time to that required for one complete transthoracic study and can usually be performed with minimal disruption to the hospital echocardiography laboratory.

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.