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1.
J Clin Med ; 13(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276138

ABSTRACT

BACKGROUND: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data. METHODS: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level. RESULTS: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%). CONCLUSIONS: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

2.
Eur Heart J ; 44(34): 3250-3260, 2023 09 07.
Article in English | MEDLINE | ID: mdl-36747318

ABSTRACT

AIMS: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). METHODS AND RESULTS: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. CONCLUSION: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.


Subject(s)
Heart Defects, Congenital , Hospitalization , Humans , Risk Factors , Heart Defects, Congenital/complications , Heart Defects, Congenital/epidemiology , Risk Assessment , Proportional Hazards Models
3.
J Clin Med ; 11(10)2022 May 10.
Article in English | MEDLINE | ID: mdl-35628825

ABSTRACT

BACKGROUND: The extent of aortic replacement for aneurysms of the distal ascending aorta remains controversial and opinions vary between standard cross-clamp resection and open hemiarch anastomosis in circulatory arrest and selective cerebral perfusion. As the deleterious effects of extended circulatory arrest are well-known, borderline indication for distal ascending aorta aneurysm repair must be outweighed against the potential risk of complications related to the open anastomosis. In the present study, we describe our own approach consisting of "transversal arch clamping" for exhaustive resection of aneurysms of the distal ascending aorta without open anastomosis and we present the postoperative outcomes. METHODS: Between May 2017 and December 2019, 35 patients with aneurysm of the ascending aorta (20 male, 15 female) underwent replacement with repair of the lesser curvature without circulatory arrest. Pre-operative, intraoperative, and postoperative clinical outcomes were retrospectively withdrawn from our institutional database and analyzed. RESULTS: Maximal diameter of distal ascending aorta was 47.5 mm. Patient median age was 66 years (IQR 14) (range 42-86). Preoperative logistic median EuroSCORE II was 17% (IQR 11.3). Median duration of cardiopulmonary bypass and cardiac arrest were 137 (IQR 64) and 93 (IQR 59) min, respectively. In-hospital and 30-day mortality were 0%. There were no cases with acute low output syndrome, surgical re-exploration for bleeding, kidney injury requiring dialysis, or wound infection. Disabling stroke was observed in one patient (2.9%). There was one case of major ventricular arrhythmia (2.9%). CONCLUSIONS: Our institutional experience suggests that this novel technique is safe and feasible. It facilitates complete resection of the aortic ascending aneurysm avoiding circulatory arrest, antegrade cerebral perfusion, additional peripheral cannulation, and all related complications.

4.
J Clin Med ; 11(7)2022 Apr 05.
Article in English | MEDLINE | ID: mdl-35407633

ABSTRACT

Background: Amiodarone has a profound adverse toxicity profile. Large population-based analyses quantifying the risk of thyroid dysfunction (TD) in adults with and without congenital heart disease (ACHD) are lacking. Methods: All adults registered with a major German health insurer (≈9.2 million members) with amiodarone prescriptions were analyzed. Occurrence of amiodarone-associated TD was assessed. Results: Overall, 48,891 non-ACHD (37% female; median 73 years) and 886 ACHD (34% female; median 66 years) received amiodarone. Over 184,787 patient-years, 10,875 cases of TD occurred. The 10-year risk for TD was 38% in non-ACHD (35% ACHD). Within ACHD, compared to amiodarone-naïve patients, the hazard ratio (HR) for TD was 3.9 at 4 years after any amiodarone exposure. TD was associated with female gender (HR 1.42, p < 0.001) and younger age (HR 0.97 per 10 years, p = 0.009). Patients with congenital heart disease were not at increased risk (HR 0.98, p = 0.80). Diagnosis of complex congenital heart disease, however, was a predictor for TD (HR 1.56, p = 0.02). Amiodarone was continued in 47% of non-ACHD (38% ACHD), and 2.3% of non-ACHD (3.5% ACHD) underwent thyroid surgery/radiotherapy. Conclusions: Amiodarone-associated TD is common and comparable in non-ACHD and ACHD. While female gender and younger age are predictors for TD, congenital heart disease is not necessarily associated with an elevated risk.

5.
Eur Heart J ; 42(41): 4252-4260, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34638134

ABSTRACT

AIMS: The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD). METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, ∼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001). CONCLUSIONS: This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.


Subject(s)
Heart Defects, Congenital , Pregnancy Complications, Cardiovascular , Cesarean Section , Female , Heart Defects, Congenital/complications , Heart Defects, Congenital/epidemiology , Humans , Pregnancy , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Outcome/epidemiology , Retrospective Studies
6.
Eur Heart J ; 42(41): 4241-4248, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34269382

ABSTRACT

AIMS: The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population. METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up. CONCLUSION: Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.


Subject(s)
Cardiology , Heart Defects, Congenital , Adult , Delivery of Health Care , Female , Heart Defects, Congenital/therapy , Humans , Male , Morbidity , Proportional Hazards Models
7.
Heart ; 107(13): 1069-1076, 2021 Jun 11.
Article in English | MEDLINE | ID: mdl-33109710

ABSTRACT

OBJECTIVES: Data on the clinical outcome of patients with congenital heart disease (CHD) affected by severe viral pneumonia are limited. We analysed morbidity and mortality of viral pneumonia and evaluated the association between medical conditions, medication, vaccination and outcome specifically in patients with CHD requiring hospitalisation for viral pneumonia. METHODS: Based on data from one of Germany's largest health insurers, all cases of viral pneumonia requiring hospital admission (2005-2018) were studied. Mortality, and composites of death, transplantation, mechanical circulatory support, ventilation or extracorporeal lung support served as endpoints. RESULTS: Overall, 26 262 viral pneumonia cases occurred in 24 980 patients. Of these, 1180 cases occurred in patients with CHD. Compared with patients without CHD, mortality rate was elevated in patients with CHD. As a group, patients with CHD aged 20-59 years even exceeded mortality rates in patients without CHD aged >60 years. No mortality was observed in patients with CHD with simple defects <60 years of age without associated cardiovascular risk factors. On multivariable logistic regression analysis, age, CHD complexity, chromosomal anomalies, cardiac medication, use of immunosuppressants and absence of vaccination for influenza emerged as risk factors of adverse outcome. CONCLUSIONS: We present timely data on morbidity and mortality of severe viral pneumonia requiring hospital admission in patients with CHD. Need for mechanical ventilation and risk of death in CHD increase early in life, reaching a level equivalent to non-CHD individuals >60 years of age. Our data suggest that except for patients with isolated simple defects, patients with CHD should be considered higher-risk individuals when faced with severe viral pneumonia.

9.
Int J Cardiol ; 273: 56-62, 2018 Dec 15.
Article in English | MEDLINE | ID: mdl-30104033

ABSTRACT

OBJECTIVES: To analyze the timing of appearance of conduction abnormalities (CAs) after transcatheter aortic valve implantation (TAVI), to identify predictors of delayed CAs requiring pacemaker (PM) implantation and to provide guidance regarding the duration of telemetry monitoring. BACKGROUND: How long patients remain at risk of development of CAs requiring PM implantation after TAVI and for how long they should be monitored remains unclear but is crucial when considering early discharge. METHODS: Development of CAs was studied in 701 consecutive patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7 days in a single center. After excluding valve-in-valve procedures and patients with previous PM, 606 patients remained for analysis. Predictors of CAs requiring PM and the time of onset of CAs were analyzed. RESULTS: Of 606 patients 76 (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48 h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs within the first 48 h after TAVI. CONCLUSION: After TAVI using a new-generation balloon-expandable valve, delayed development of CAs requiring PM implantation is not uncommon, even after 5 days. More importantly, 23.5% of patients eventually requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this study. These results question the safety of early discharge and support ECG monitoring for a longer time period. The most optimal way to monitor these patients is yet to be determined.


Subject(s)
Electrocardiography, Ambulatory/trends , Heart Valve Prosthesis/trends , Pacemaker, Artificial/trends , Transcatheter Aortic Valve Replacement/trends , Aged , Aged, 80 and over , Electrocardiography/mortality , Electrocardiography/trends , Electrocardiography, Ambulatory/mortality , Female , Hospital Mortality/trends , Humans , Male , Telemetry/methods , Telemetry/mortality , Telemetry/trends , Time Factors , Transcatheter Aortic Valve Replacement/mortality , Treatment Outcome
10.
Int J Cardiol ; 269: 91-96, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-29980366

ABSTRACT

BACKGROUND: In patients with repaired Tetralogy of Fallot (ToF), implantable cardioverter defibrillators (ICD) are considered reasonable in selected adults with multiple risk factors for sudden cardiac death. PATIENTS AND METHODS: We performed a retrospective cohort study of all 174 patients with repaired ToF who are followed at the University Hospital of Muenster. We analyzed data according to the risk score previously proposed by Khairy and coworkers and patient outcome. We analyzed data separately for patients without previous sustained ventricular tachycardia (VT) (risk stratification group, n = 157) and patients with VT/secondary prevention ICD (n = 17). RESULTS: In the risk stratification group, a mean of 4 ±â€¯1 risk score parameters were available. All six risk parameters were known in 10%, five in 14%. Risk score increased with availability of parameters. 15 patients with secondary prevention ICD had a mean risk score of 6.3 ±â€¯2.2 (range 2-10). 11 patients of the risk stratification group with primary prevention ICD had a mean risk score 5.8 ±â€¯2.4 (range 3-8). During follow-up of up to 14 years, five patients died (3%): at age 58, two at 69 and two at 76 years. CONCLUSION: In the majority of patients risk score variables were incomplete, severely limiting its applicability because the true score cannot be calculated. Risk scores were not different between patients with secondary prevention ICD and patients with ICD for primary prevention based on current guidelines. Standardization of follow-up and prospective evaluation of these standards in large prospective patient cohorts is desirable to improve risk stratification in patients with ToF.


Subject(s)
Death, Sudden, Cardiac/prevention & control , Primary Prevention/methods , Secondary Prevention/methods , Tetralogy of Fallot/surgery , Adolescent , Adult , Aged , Child , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Primary Prevention/trends , Prospective Studies , Retrospective Studies , Risk Assessment/methods , Secondary Prevention/trends , Tetralogy of Fallot/diagnosis , Tetralogy of Fallot/mortality , Treatment Outcome , Young Adult
11.
Rev Esp Cardiol (Engl Ed) ; 71(10): 838-846, 2018 Oct.
Article in English, Spanish | MEDLINE | ID: mdl-29859895

ABSTRACT

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. Early surgical repair has dramatically improved the outcome of this condition. However, despite the success of contemporary approaches with early complete repair, these are far from being curative and late complications are frequent. The most common complication is right ventricle outflow tract (RVOT) dysfunction, affecting most patients in the form of pulmonary regurgitation, pulmonary stenosis, or both, and can lead to development of symptoms of exercise intolerance, arrhythmias, and sudden cardiac death. Optimal timing of restoration of RVOT functionality in asymptomatic patients with RVOT dysfunction after TOF repair is still a matter of debate. Percutaneous pulmonary valve implantation, introduced almost 2 decades ago, has become a major game-changer in the treatment of RVOT dysfunction. In this article we review the pathophysiology, the current indications, and treatment options for RVOT dysfunction in patients after TOF repair with a focus on the role of percutaneous pulmonary valve implantation in the therapeutic approach to these patients.


Subject(s)
Heart Valve Prosthesis , Pulmonary Valve/surgery , Tetralogy of Fallot , Time-to-Treatment/trends , Ventricular Function, Right/physiology , Ventricular Outflow Obstruction/surgery , Humans , Reoperation , Tetralogy of Fallot/complications , Tetralogy of Fallot/physiopathology , Tetralogy of Fallot/surgery , Ventricular Outflow Obstruction/etiology , Ventricular Outflow Obstruction/physiopathology
13.
JACC Cardiovasc Interv ; 9(8): 805-813, 2016 Apr 25.
Article in English | MEDLINE | ID: mdl-27017367

ABSTRACT

OBJECTIVES: The aim of this study was to analyze the pacemaker implantation rate (PMIR) with the new balloon-expandable Edwards SAPIEN 3 valve (S3) and the factors associated with it. BACKGROUND: The introduction of the S3 for transcatheter aortic valve replacement (TAVR) has led to a reduction in paravalvular regurgitation. There are, however, concerns that the new design may increase the PMIR. METHODS: The first 206 patients treated with the S3 were compared with 371 preceding patients treated with SAPIEN XT valves. Patients who previously underwent pacemaker or implantable cardioverter defibrillator implantation or transapical and valve-in-valve procedures were excluded from the analysis. All patients were monitored for at least 7 days. Previous and new conduction abnormalities were documented, and prosthesis implantation height was assessed for the S3. RESULTS: There were no significant differences in baseline characteristics between groups. The PMIR was, however, significantly higher for the S3 (19.1% vs. 12.2%; p = 0.046). The mean implantation height was significantly lower in patients requiring PMI (67%/33% vs. 72%/28% aortic/ventricular stent extension, p = 0.032). On multivariate regression analysis, implantation height was the only independent predictor of PMI (odds ratio: 0.94 [95% confidence interval: 0.90 to 0.99]; p = 0.009). It increased from 68%/32% to 75%/25% when comparing the first with the second half of S3 implantations (p < 0.0001). This change was associated with a significant decrease in PMIR from 25.9% to 12.3% (p = 0.028), no longer different from the XT valve (12.2%). CONCLUSIONS: The PMIR after TAVR is higher with the S3 than with the XT and is independently associated with the implantation height. This increase in the PMIR may be avoided by intending an aortic stent extension >70%.


Subject(s)
Aortic Valve Insufficiency/prevention & control , Aortic Valve Stenosis/therapy , Aortic Valve , Arrhythmias, Cardiac/therapy , Cardiac Catheterization/instrumentation , Cardiac Pacing, Artificial , Heart Valve Prosthesis Implantation/instrumentation , Heart Valve Prosthesis , Pacemaker, Artificial , Aged , Aged, 80 and over , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Aortic Valve Insufficiency/etiology , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/physiopathology , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Chi-Square Distribution , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Humans , Logistic Models , Male , Multivariate Analysis , Odds Ratio , Prosthesis Design , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
14.
Echocardiography ; 32(4): 660-70, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25109241

ABSTRACT

AIMS AND OBJECTIVES: New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. METHODS: Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. RESULTS: One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. CONCLUSION: The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures.


Subject(s)
Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/surgery , Catheter Ablation/methods , Echocardiography/methods , Endosonography/methods , Surgery, Computer-Assisted/methods , Cardiology/education , Education , Female , Humans , Male , Radiology/education , Treatment Outcome
17.
Pulm Med ; 2013: 768064, 2013.
Article in English | MEDLINE | ID: mdl-23691310

ABSTRACT

Coronary artery disease (CAD) and obstructive sleep apnea (OSA) are both complex and significant clinical problems. The pathophysiological mechanisms that link OSA with CAD are complex and can influence the broad spectrum of conditions caused by CAD, from subclinical atherosclerosis to myocardial infarction. OSA remains a significant clinical problem among patients with CAD, and evidence suggesting its role as a risk factor for CAD is growing. Furthermore, increasing data support that CAD prognosis may be influenced by OSA and its treatment by continuous positive airway pressure (CPAP) therapy. However, stronger evidence is needed to definitely answer these questions. This paper focuses on the relationship between OSA and CAD from the pathophysiological effects of OSA in CAD, to the clinical implications of OSA and its treatment in CAD patients.

18.
JACC Cardiovasc Imaging ; 2(8): 997-1005, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19679288

ABSTRACT

OBJECTIVES: We used human umbilical cord segments as an ex vivo model to investigate the possible clinical diagnostic and therapeutic applications of microbubbles (MBs). BACKGROUND: Microbubbles are commonly used in clinical practice as ultrasound contrast agents. Several studies have addressed the in vivo applications of MBs for specific targeting of vascular dysfunction or sonoporation in animal models, but to date no human tissue model has been established. METHODS: Primary venular endothelial cell monolayers were targeted with MBs conjugated to an antibody against a highly expressed endothelial marker (tetraspanin CD9), and binding was assessed under increasing flow rates (0.5 to 5 dynes/cm(2)). Furthermore, CD9-coupled MB endothelial targeting was measured under flow conditions by contrast-enhanced ultrasound analysis in an ex vivo human macrovascular model (umbilical cord vein), and the same tissue model was used for the detection of inflamed vasculature with anti-intercellular adhesion molecule (ICAM)-1-coated MBs. Finally, plasmids encoding fluorescent proteins were sonoporated into umbilical cord vessels. RESULTS: Specific endothelial targeting in the in vitro and ex vivo models described previously was achieved by the use of MBs covered with an anti-CD9. Furthermore, we managed to induce inflammation in umbilical cord veins and detect it with real-time echography imaging using anti-ICAM-1-coupled MBs. Moreover, expression and correct localization of green fluorescent protein and green fluorescent protein-tagged ICAM-1 were assessed in this human ex vivo model without causing vascular damage. CONCLUSIONS: In the absence of clinical trials to test the benefits and possible applications of ultrasound contrast agents for molecular imaging and therapy, we have developed a novel ex vivo human model using umbilical cords that is valid for the detection of inflammation and for exogenous expression of proteins by sonoporation.


Subject(s)
Contrast Media , Endothelium, Vascular/diagnostic imaging , Immunoconjugates , Inflammation/diagnostic imaging , Microbubbles , Transfection/methods , Ultrasonic Therapy , Ultrasonics , Umbilical Cord/diagnostic imaging , Antigens, CD/immunology , Biomarkers/metabolism , Cell Survival , Cells, Cultured , Contrast Media/metabolism , Contrast Media/therapeutic use , Endothelium, Vascular/immunology , Endothelium, Vascular/metabolism , Humans , Immunoconjugates/metabolism , Immunoconjugates/therapeutic use , Inflammation/immunology , Inflammation/metabolism , Inflammation Mediators/immunology , Intercellular Adhesion Molecule-1/immunology , Membrane Glycoproteins/immunology , Tetraspanin 29 , Tumor Necrosis Factor-alpha/metabolism , Ultrasonography , Umbilical Cord/immunology , Umbilical Cord/metabolism
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