Looking for optimal antithrombotic strategy after transcatheter left atrial appendage occlusion: a real-world comparison of different antiplatelet regimens.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an effective procedure for the prevention of thromboembolic events in non-valvular atrial fibrillation (AF) patients with contraindications to oral anticoagulation. After the procedure, different antithrombotic regimens have been used, in order to prevent device-related thrombus and trying to minimize bleedings. The search for the optimal antithrombotic strategy is still ongoing. We sought to assess efficacy and safety of different antiplatelet therapy (APT) regimens. METHODS: We enrolled non-randomized consecutive patients who underwent LAAO at the University Hospital of Parma between 2010 and 2021. Three study groups were identified according to post-procedural APT: long (>1, ≤12 months)-dual APT (DAPT), short (≤ 1 month)-DAPT, lifelong single APT (SAPT). The choice of the APT was left to multidisciplinary team evaluation. The incidence of the primary outcome, a composite of any ischemic or hemorrhagic event, was assessed at follow-up. RESULTS: We enrolled a total of 130 patients. Technical success was achieved in 123 (94.6%) patients. After LAAO, 39 [31.7%] patients were discharged on short-DAPT, 35 [28.5%] on long-DAPT and 49 [39.8%] on SAPT. After a median follow-up of 32 months, short-DAPT group had a significantly lower occurrence of the primary outcome (3 [7.7%] vs. 7 [20.0%] in long-DAPT vs. 14 [28.6%] in SAPT, p = 0.049], mainly driven by a lower occurrence of the bleeding endpoint (0 vs. 4 [11.4%] in long-DAPT vs. 9 [18.4%] in SAPT, p = 0.020). Finally, comparison of the Kaplan-Meier curves showed that short-DAPT group had a higher primary endpoint-free survival [p = 0.015] compared to the other groups. CONCLUSION: Post-procedural short-DAPT strategy was associated with better outcomes, mainly driven by reduction of major bleedings.

Molecular study of human herpesvirus 6 and 8 involvement in coronary atherosclerosis and coronary instability.

Several lines of evidence suggest the involvement of infectious agents in the pathogenesis of atherosclerosis. Furthermore, a correlation between infection-driven inflammatory burden and acute manifestation of coronary artery disease has been hypothesized. The aim of this work was to assess whether human herpesvirus (HHV)-6 and HHV-8, two DNA viruses with a distinct tropism for endothelium and lymphocytes, may be associated with coronary instability. An age- and gender-matched cross-sectional study was undertaken in 70 patients with testing of plasma HHV-6 and HHV-8 DNA load in different cardiovascular clinical settings: 29 patients with acute myocardial infarction, 21 patients with stable coronary artery disease, and 20 patients without coronary and carotid artery atherosclerosis subjected to cardiac valve replacement. In all patients, HHV-6 and HHV-8 plasma DNA was tested by using highly sensitive, calibrated quantitative real-time PCR assays which employ a synthetic DNA calibrator to adjust for DNA extraction and amplification efficiency. HHV-8 viremia was undetectable in all three groups. HHV-6 viremia was detected in a substantial fraction of the samples examined (18.6%) without significant differences among the three groups (ST segment elevation myocardial infarction: 17.2%; stable coronary artery disease: 14.3%; patients without coronary and carotid artery atherosclerosis: 25%). Furthermore, no significant differences in plasma HHV-6 load were observed amongst the three groups of patients. These findings indicate that coronary instability is not associated specifically with active HHV-6 or HHV-8 infection. However, an unusually high rate of active HHV-6 infection was documented among patients without atherosclerosis admitted to hospital with cardiac disease.

Adenosine-induced severe bronchospasm in a patient without pulmonary disease.

Adenosine is widely used for the treatment of supraventricular tachycardias for its efficacy and excellent safety, but it has been reported to precipitate severe bronchospasm in patients with pulmonary disease. The drug is therefore contraindicated in asthmatic subjects and should be used with caution in patients with chronic obstructive pulmonary disease. Nevertheless, true bronchospasm is rare and should be distinguished from the much more common occurrence of dyspnea, only as a symptom and without respiratory compromise, which is benign and transient. We describe the occurrence of severe bronchospasm following adenosine administration for a supraventricular tachycardia in a young male without any history of pulmonary disease. To our knowledge, this is the first time such complication is reported in a subject without lung disease. The patient arrived at the emergency department for palpitations with a regular wide QRS tachycardia with a left bundle-branch block morphology. Sinus carotid massage was unsuccessful, and 2 intravenous adenosine boluses were given without effect. A further 12-mg bolus cardioverted the patient, who became increasingly dyspneic and hypoxic, with diffuse bronchospasm. An urgent chest radiograph had normal results. He was treated with oxygen and inhaled and intravenous steroids, but dyspnea and bronchospasm resolved only after intravenous aminophylline. The arrhythmia recurred and was finally terminated by intravenous flecainide. Although dyspnea after adenosine administration is usually a transient, benign phenomenon, physicians should be alert to the presence of objective signs of respiratory distress, which should prompt immediate treatment, even in subjects without previous history of pulmonary disease.

Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. METHODS: Sixty patients with NVAF underwent LAAO (75.4 ±â€Š9 years); mean CHA2DS2-VASc was 4.4 ±â€Š1.7, mean HAS-BLED 3.2 ±â€Š0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. RESULTS: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ±â€Š1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. CONCLUSION: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding.

A surprise behind the dark.

Standard ultrasound has a poor accuracy in the detection of carotid plaque surface irregularities and ulcers, which are features of vulnerable lesions. Sonographic contrast agents can improve vessel wall lumen definition, thus potentially overcoming this limitation. Recent studies also suggest that contrast ultrasound can be used to study intraplaque neovascularizaion, a potential marker of high-risk lesions. This case represents a striking example of the added value of contrast ultrasound to improve diagnostic accuracy of vascular studies, particularly in the detection of plaque surface irregularities and plaque neovascularization.

Contrast-enhanced ultrasound imaging of periadventitial vasa vasorum in human carotid arteries.

AIMS: Arterial vasa vasorum (VV) are known to be involved in the atherosclerotic process. The aim of the present study was to explore whether ultrasound imaging with contrast agent is able to visualize adventitial VV in human carotid atherosclerosis. METHODS AND RESULTS: We studied with standard ultrasound 25 patients with carotid stenosis >50% (ATS group) and 15 patients without carotid artery plaques and an intima-media thickness (IMT) <1.0 mm (CTRL group). All patients underwent contrast ultrasound to evaluate periadventitial VV and B-flow imaging (BFI) modality was used to improve and measure periadventitial flow signal. On contrast-enhanced images, a fast microbubble flow and a homogeneous and linear periadventitial contrast signal using BFI were detectable in the adventitial area in all patients of both groups. Periadventitial signal thickness by BFI was higher in patients with atherosclerosis than in the control group (mean +/- SD: CTRL 0.80+/-0.06 mm; ATS 1.10+/-0.11 mm; P<0.001). Moreover, considering the whole study population, the adventitial signal thickness significantly correlated with IMT values (r=0.88, r(2)=0.77; P<0.0001). CONCLUSION: Periadventitial contrast signal was detected in all patients and BFI thickness was higher in patient with carotid atherosclerosis and correlated with IMT.

Inflammation as a possible link between coronary and carotid plaque instability.

BACKGROUND: Multiple complex stenoses, plaque fissures, and widespread coronary inflammation are common in acute coronary syndromes. A systemic cause of atherosclerotic plaque instability is also suggested by studies of ischemic cerebrovascular disease. We investigated the association between coronary and carotid plaque instability and the potential common causal role of inflammation. METHODS AND RESULTS: The ultrasound characteristics of carotid plaques were evaluated retrospectively in patients scheduled for coronary bypass surgery, 181 with unstable and 92 with stable angina, and prospectively in a similar group of patients, 67 with unstable and 25 with stable angina, in whom serum C-reactive protein levels were also measured. The prevalence of carotid plaques was similar in the retrospective and prospective studies and >64% in both unstable and stable coronary patients. The prevalence of complex, presumably unstable carotid plaques was 23.2% in unstable versus 3.2% in stable patients (P<0.001) in the retrospective study and 41.8% versus 8.0% (P=0.002) in the prospective study. C-reactive protein levels were higher in patients with complex (7.55 mg/L) than in those with simple (3.94 mg/L; P<0.05) plaques or without plaques (2.45 mg/L; P<0.05). On multivariate analysis, unstable angina and C-reactive protein levels >3 mg/L were independently associated with complex carotid plaques (OR, 6.09; 95% CI, 1.01 to 33.72; P=0.039, and OR, 5.80; 95% CI, 1.55 to 21.69; P=0.009, respectively). CONCLUSIONS: In unstable angina, plaque instability may not be confined to coronary arteries, and inflammation may be the common link with carotid plaque instability. These observations may have relevant implications for understanding the mechanisms of acute widespread atherothrombotic plaque inflammation.

Carotid plaque inflammation in a patient with unstable angina.

Coronary instability has been associated with multifocal plaque activation in the coronary circulation and in remote vascular districts, suggesting a systemic cause of instability, possibly inflammation. Magnetic resonance imaging offers a great potential for the detection of plaque inflammation. We describe the case of a 73-year-old female admitted for unstable angina, elevated levels of C-reactive protein and three-vessel disease, in whom carotid ultrasound examination revealed an atherosclerotic plaque of the left proximal internal carotid artery with an irregular profile and a heterogeneous echographic texture, determining a 50% stenosis. Magnetic resonance imaging of the plaque before and after contrast enhancement by gadolinium-DTPA showed the following signs of inflammation: an increased vessel wall thickness, an increased triple inversion recovery-fast spin-echo signal intensity indicative of tissue edema, and a homogeneous plaque contrast enhancement indicative of an increased capillary permeability and neovasculature. As the carotid stenosis was < 70% and did not give rise to any symptom, the patient was submitted to coronary bypass surgery without concomitant carotid endarterectomy. Two days later she developed an ischemic stroke with right brachiocrural hemiplegia. In the present case report, the simultaneous presence of coronary instability and a carotid plaque with magnetic resonance features suggestive of inflammation, which was probably responsible for the stroke complicating cardiac surgery, may indicate a multifocal plaque instability.

Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques.

Proliferation of the adventitial vasa vasorum (VV) is inherently linked with early atherosclerotic plaque development and vulnerability. Recently, direct visualization of arterial VV and intraplaque neovascularization has emerged as a new surrogate marker for the early detection of atherosclerotic disease. This clinical review focuses on contrast-enhanced ultrasound (CEUS) as a noninvasive application for identifying and quantifying carotid and coronary artery VV and intraplaque neovascularization. These novel approaches could potentially impact the clinician's ability to identify individuals with premature cardiovascular disease who are at high risk. Once clinically validated, the uses of CEUS may provide a method to noninvasively monitor therapeutic interventions. In the future, the therapeutic use of CEUS may include ultrasound-directed, site-specific therapies using microbubbles as vehicles for drug and gene delivery systems. The combined applications for diagnosis and therapy provide unique opportunities for clinicians to image and direct therapy for individuals with vulnerable lesions.

Magnetic resonance imaging of carotid plaque inflammation in acute coronary syndromes: a sign of multisite plaque activation.

Widespread plaque inflammation has been demonstrated in acute coronary syndromes (ACS). We evaluated signs of plaque inflammation in carotid arteries of patients with ACS by contrast-enhanced magnetic resonance imaging (MRI). Carotid MRI was performed in 13 patients with ACS and in 9 controls having at least 1 carotid plaque with a stenosis > or =40%. MRI criteria of plaque inflammation were: increased T2 signal >50% of the plaque areas (tissue oedema) and/or enhancement after gadolinium injection (neo-vascularization). MRI signs of inflammation were found in 95% and in 33% of patients with ACS and controls, respectively (p<0.001). Carotid artery MRI may serve as a window to the entire cardiovascular system, to identify "vulnerable" patients.

Contrast-enhanced ultrasound imaging of intraplaque neovascularization in carotid arteries: correlation with histology and plaque echogenicity.

OBJECTIVES: This study was designed to evaluate contrast-enhanced ultrasound imaging of carotid atherosclerosis as a clinical tool to study intraplaque neovascularization. BACKGROUND: Plaque neovascularization is associated with plaque vulnerability and symptomatic disease; therefore, imaging of neovascularization in carotid atherosclerosis may represent a useful tool for clinical risk stratification and monitoring the efficacy of antiatherosclerotic therapies. METHODS: Thirty-two patients with 52 carotid plaques were studied by standard and contrast-enhanced ultrasound imaging. In 17 of these patients who underwent endarterectomy, the surgical specimen was available for histological determination of microvessel density by CD31/CD34 double staining. Plaque echogenicity and degree of stenosis at standard ultrasound imaging were evaluated for each lesion. Contrast-agent enhancement within the plaque was categorized as absent/peripheral (grade 1) and extensive/internal (grade 2). RESULTS: In the surgical subgroup, plaques with higher contrast-agent enhancement showed a greater neovascularization at histology (grade 2 vs. grade 1 contrast-agent enhancement: median vasa vasorum density: 3.24/mm(2) vs. 1.82/mm(2), respectively, p = 0.005). In the whole series of 52 lesions, echolucent plaques showed a higher degree of contrast-agent enhancement (p < 0.001). Stenosis degree was not associated with neovascularization at histology or with the grade of contrast-agent enhancement. CONCLUSIONS: Carotid plaque contrast-agent enhancement with sonographic agents correlates with histological density of neovessels and is associated with plaque echolucency, a well-accepted marker of high risk lesions, but it is unrelated to the degree of stenosis. Contrast-enhanced carotid ultrasound imaging may provide valuable information for plaque risk stratification and for assessing the response to antiatherosclerotic therapies, beyond that provided by standard ultrasound imaging.

Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes.

Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-alpha expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6-7.3) mg/l vs. CSA 1.8 (0.6-3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6-5.5) pg/ml vs. CSA 1.7 (1.4-4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.

Reduction of mitral valve regurgitation caused by acute papillary muscle ischemia.

BACKGROUND: A 67-year-old man was admitted to a coronary care unit for non-ST-segment elevation myocardial infarction with complicating acute heart failure. Severe mitral regurgitation was detected by echocardiography at presentation. Repeat echocardiography carried out during another ischemic episode revealed a marked reduction in the patient's mitral regurgitation that was related to decreased apical traction of the valve leaflets. INVESTIGATIONS: Physical examination, electrocardiography, laboratory tests, coronary angiography, chest radiography, echocardiography. DIAGNOSIS: Mitral regurgitation associated with acute coronary syndrome. MANAGEMENT: Early revascularization by percutaneous coronary intervention, supported by pharmacological therapy to decrease left ventricular filling pressure.

Myocardial infarction complicating the initial phase of an ovarian stimulation protocol.

Two previous reports have reported myocardial infarction during ovarian hyperstimulation syndrome, a complication of controlled ovarian stimulation characterized by ascites, pleural effusion, hemoconcentration and an increased thromboembolic risk, but no association with the initial phase (before treatment with human chorionic gonadotropin) of a normal ovarian stimulation protocol for infertility has ever been described. We report the first case, to our knowledge, of acute myocardial infarction occurring during the initial phase of an otherwise uncomplicated ovarian stimulation protocol. A young woman with infertility associated to polycystic ovary syndrome was treated with leuprolide acetate and recombinant follicle stimulating hormone to induce ovarian stimulation for in vitro fertilization and embryo transfer. After 12 days the patient presented a non-ST elevation myocardial infarction, which was treated with aspirin, clopidogrel, enoxaparin, intravenous nitrates and beta blockers. Cardiac catheterization showed angiographically normal coronary arteries. Echocardiography showed a circumscribed akinesis of the inferior apical segment of the left ventricle and right ventricular apex, which was confirmed by cardiac magnetic resonance. A screening for thrombophilic diathesis was negative. The patient was discharged and remained asymptomatic at 1 and 3 months follow up. Further ovarian stimulations were excluded and a trial of oocyte retrieval on spontaneous cycle was planned. Myocardial infarction can complicate ovarian stimulation protocols for infertility even in their early phase without any sign of ovarian hyperstimulation syndrome.