Aortic root diameter is associated with HLA-B27: identifying the patient with ankylosing spondylitis at risk for aortic valve regurgitation.

To assess the association between the aortic root diameter in HLA-B27 positive (+) and HLA-B27 negative (-) ankylosing spondylitis (AS) patients from the CARDAS cohort. The CARDAS study is a cross-sectional study in AS patients between 50 and 75 years who were recruited from a large rheumatology outpatient clinic. Patients underwent cardiovascular screening including echocardiography, with 2D, spectral, and color flow Doppler measurements. The aortic root was measured at sinuses of Valsalva during diastole. The aortic root diameter was adjusted for body surface area (BSA) (aortic root index, cm/m2). 193 Consecutive AS patients were included of whom 158 (82%) were HLA-B27 positive. The aortic root index was significantly higher in HLA-B27 + patients compared to HLA-B27- patients, respectively, 1.76 cm ± 0.21 vs. 1.64 cm ± 0.14, p < 0.001. No difference was seen in the prevalence of aortic valve regurgitation (AVR), p = 0.8. Regression analysis showed a significant association between HLA-B27 and aortic root index corrected for age, sex and cardiovascular risk factors (ß 0.091, 95% CI 0.015-0.168, p = 0.02). Especially, male HLA-B27 + patients had a significantly increased aortic root index compared to male HLA-B27- AS patients, respectively, 1.76 cm (1.63-1.88) and 1.59 cm (1.53-1.68), p < 0.001. We found an increased aortic root index in elderly HLA-B27 + AS patients compared to HLA-B27- AS patients, especially in male patients. No difference was seen in the prevalence of AVR. However, as AVR can be progressive, echocardiographic monitoring in elderly male HLA-B27 + AS might be considered.

Prediction of prognosis in patients with left ventricular dysfunction using three-dimensional strain echocardiography and cardiac magnetic resonance imaging.

BACKGROUND: We evaluated three-dimensional speckle tracking echocardiography (3DSTE) strain and cardiac magnetic resonance (CMR) with delayed contrast enhancement (DCE) for the prediction of cardiac events in left ventricular (LV) dysfunction. METHODS: CMR and 3DSTE in 75 patients with ischaemic and 38 with non-ischaemic LV dysfunction were analysed and temporally correlated to cardiac events during 41 ± 9 months of follow-up. RESULTS: Cardiac events occurred in 44 patients, more in patients with ischaemic LV dysfunction. LV ejection fraction (LVEF), global circumferential and global area strain were reduced more in patients with more cardiac events, whereas 3DSTE LV end-systolic volumes and 3DSTE LV masses were larger. However, the area under the curve using receiver-operating characteristic analysis showed modest sensitivity and specificity for all evaluated parameters. Additionally, DCE did not differ significantly between the two groups. Univariate analysis showed ischaemic aetiology of LV dysfunction, LVEF and LV mass by CMR to be predictors of cardiac events with an increased relative risk of 2.4, 1.6 and 1.5, respectively. By multivariate analysis, only myocardial ischaemia and LVEF ≤ 39% were independent predictors of events (p = 0.004 and 0.005, respectively). Subgroup analysis in ischaemic and non-ischaemic patients showed only 3DSTE LV mass in ischaemic patients to have a significant association (p = 0.033) but without an increased relative risk. CONCLUSION: LVEF calculated by 3DSTE or CMR were both good predictors of cardiac events in patients with LV dysfunction. A reduced LVEF ≤ 39% was associated with a 1.6-fold higher probability of a cardiac event. 3DSTE strain measurements and DCE-CMR did not add to the prognostic value of LVEF.

Sonothrombolysis in the ambulance for ST-elevation myocardial infarction: rationale and protocol.

BACKGROUND: Treatment of ST-elevation myocardial infarction (STEMI) has improved over the years. Current challenges in the management of STEMI are achievement of early reperfusion and the prevention of microvascular injury. Sonothrombolysis has emerged as a potential treatment for acute myocardial infarction, both for epicardial recanalisation as well as improving microvascular perfusion. This study aims to determine safety and feasibility of sonothrombolysis application in STEMI patients in the ambulance. METHODS: Ten patients with STEMI will be included and treated with sonothrombolysis in the ambulance during transfer to the PCI centre. Safety will be assessed by the occurrence of ventricular arrhythmias and shock during sonothrombolysis intervention. Feasibility will be assessed by the extent of protocol completion and myocardial visibility. Efficacy will be determined by angiographic patency rate, ST-elevation resolution, infarct size and left ventricular volumes, and function measured with cardiovascular magnetic resonance imaging, and contrast and strain echocardiography. A comparison will be made with matched controls using an existing STEMI database. DISCUSSION: Sonothrombolysis is a novel technique for the treatment of cardiovascular thromboembolic disease. The first clinical trials on its use for STEMI have demonstrated promising results. This study will be the first to examine the feasibility of in-ambulance sonothrombolysis for STEMI. TRIAL REGISTRATION: EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

Infective endocarditis in the Netherlands: current epidemiological profile and mortality : An analysis based on partial ESC EORP collected data.

INTRODUCTION: Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized. AIM: The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE. METHODS: This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018. RESULTS: A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F­fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days. CONCLUSION: We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias.

Appropriate use criteria for echocardiography in the Netherlands.

INTRODUCTION: Appropriate use criteria (AUC) for echocardiography based on clinical scenarios were previously published by an American Task Force. We determined whether members of the Dutch Working Group on Echocardiography (WGE) would rate these scenarios in a similar way. METHODS: All 32 members of the WGE were invited to judge clinical scenarios independently using a blanked version of the previously published American version of AUC for echocardiography. During a face-to-face meeting, consensus about the final rating was reached by open discussion for each indication. For reasons of simplicity, the scores were reduced from a 9-point scale to a 3-point scale (indicating an appropriate, uncertain or inappropriate echo indication, respectively). RESULTS: Nine cardiologist members of the WGE reported their judgment on the echo cases (n = 153). Seventy-one indications were rated as appropriate, 35 were rated as uncertain, and 47 were rated as inappropriate. In 5% of the cases the rating was opposite to that in the original (appropriate compared with inappropriate and vice versa), whereas in 20% judgements differed by 1 level of appropriateness. After the consensus meeting, the appropriateness of 7 (5%) cases was judged differently compared with the original paper. CONCLUSIONS: Echocardiography was rated appropriate when it is applied for an initial diagnosis, a change in clinical status or a change in patient management. However, in about 5% of the listed clinical scenarios, members of the Dutch WGE rated the AUC for echocardiography differently as compared with their American counterparts. Further research is warranted to analyse this decreased external validity.

Evaluation of extracorporeal shock wave therapy for refractory angina pectoris with quantitative analysis using cardiac magnetic resonance imaging: a short communication.

AIMS: There is a continuing search for new treatment options in patients who suffer from refractory angina pectoris to improve quality of life. Several studies have recently demonstrated promising results by stimulating angiogenesis using extracorporeal shockwave therapy in these patients. The purpose of this study is to quantitatively analyse the effect of extracorporeal shockwave therapy on myocardial perfusion in patients with refractory angina pectoris. METHODS: We included 15 patients with NYHA class 3-4 of whom 8 patients underwent baseline and follow-up cardiac magnetic resonance imaging (CMR). All patients received 9 shockwave treatments of their ischaemic zone over a period of 3 months. RESULTS: Quantitative analysis of myocardial perfusion using CMR revealed no significant improvement of myocardial perfusion after treatment (0.80 ± 0.22 vs 0.76 ± 0.31; p = 0.42). However, the total group of 15 patients did experience a significant improvement in NYHA class (p = 0.034) and reduction of nitroglycerin use (p = 0.012). CONCLUSION: Although treatment with extracorporeal shockwave was associated with an improvement in NYHA class, we could not observe an improvement in myocardial ischaemic zone and perfusion with CMR. To unravel the exact mechanisms of shockwave treatment, more in vitro and animal studies as well as larger (placebo-controlled) studies are required.

Three-dimensional speckle tracking echocardiography and cardiac magnetic resonance for left ventricular chamber quantification and identification of myocardial transmural scar.

BACKGROUND: We compared three-dimensional speckle tracking echocardiography (3DSTE) and its strain to cardiac magnetic resonance (CMR) with delayed contrast enhancement for left ventricular (LV) chamber quantification and transmurality of myocardial scar. Furthermore, we examined the ability of 3DSTE strain to differentiate between ischaemic and non-ischaemic LV dysfunction. METHODS: In 80 consecutive patients with ischaemic and 40 patients with non-ischaemic LV dysfunction, the correlations between LV volumes and ejection fraction were measured using 3DSTE and CMR. Global and regional 3DSTE strains and total or percentage enhanced LV mass were evaluated. RESULTS: LV end-diastolic and end-systolic volumes and ejection fraction correlated well between 3DSTE and CMR (r: 0.83, 0.88 and 0.89, respectively). However, 3DSTE significantly underestimated volumes. Correlation for LV mass was modest (r = 0.59). All 3DSTE regional strain values except for radial strain were lower in segments with versus segments without transmural enhancement. However, strain parameters could not identify the transmurality of scar. No significant difference between ischaemic and non-ischaemic LV dysfunction was observed in either global or regional 3DSTE strain except for twist, which was lower in the non-ischaemic group (4.9 ± 3.3 vs. 6.4 ± 3.2°, p = 0.03). CONCLUSION: 3DSTE LV volumes are underestimated compared with CMR, while LV ejection fraction revealed excellent accuracy. Functional impairment by 3DSTE strain does not correlate well with scar localisation or extent by CMR. 3DSTE strain could not differentiate between ischaemic and non-ischaemic LV dysfunction. Future studies will need to clarify if 3DSTE strain and CMR delayed contrast enhancement can provide incremental value to the prediction of future cardiovascular events.

Acute myocardial infarction does not affect functional characteristics of adipose-derived stem cells in rats, but reduces the number of stem cells in adipose tissue.

In most pre-clinical animal studies investigating stem cell therapy in acute myocardial infarction (AMI), the administered stem cells are isolated from healthy donors. In clinical practice, however, patients who suffer from AMI will receive autologous cells, for example using adipose-derived stem cells (ASC). During AMI, inflammation is induced and we hypothesized that this might affect characteristics of ASC. To investigate this, ASC were isolated from rat adipose tissue 1 day (1D group, n = 5) or 7 days (7D group, n = 6) post-AMI, and were compared with ASC from healthy control rats (Control group, n = 6) and sham-operated rats (Sham 1D group, n = 5). We found that significantly fewer ASC were present 1 day post-AMI in the stromal vascular fraction (SVF), determined by a colony-forming-unit assay (p < 0.001 vs. Control and 7D). These data were confirmed by flow cytometry, showing fewer CD90-positive cells in SVF of the 1D group. When cultured, no differences were found in proliferation rate and cell size between the groups in the first three passages. Also, no difference in the differentiation capacity of ASC was found. In conclusion, it was shown that significantly fewer stem cells were present in the SVF 1 day post-AMI; however, the stem cells that were present showed no functional differences.

Intravital microscopy of localized stem cell delivery using microbubbles and acoustic radiation force.

The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study, we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (<5 bubbles/cell) do not respond to ultrasound application (1 MHz, peak negative acoustical pressure P_ = 200 kPa, 10% duty cycle). However, stem cells which are fully saturated with targeted microbubbles (>30 bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 and 177 µm/s for P- = 200 and 450 kPa, respectively. This technique therefore offers potential for enhanced and well-controlled stem cell delivery for improved cardiac repair after a myocardial infarction.

Atypical aortic coarctation as a cause of a cardiomyopathy.

Atypical locations for aortic coarctation have been previously described. However, to our knowledge, no case has been described of a rapidly progressive dilated cardiomyopathy caused by an atypical coarctation, with a rapid normalisation of ventricular function after treatment.

Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications.

Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium.

Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study.

BACKGROUND AND AIMS: To investigate associations between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and myocardial structure and function after 8 years of follow-up in older Dutch subjects. METHODS: We included 256 subjects of the Hoorn Study, a population-based cohort. They underwent a standardized 2-dimensional echocardiogram at baseline between 2000 and 2001, and again between 2007 and 2009. We studied the association of 25(OH)D quartiles with echocardiographic measures of the left ventricular mass index (LVMI), left ventricular systolic function and markers of diastolic function using linear regression analyses. RESULTS: At baseline, subjects had a mean age of 67.4 ± 5.2 years and 41.4% had prior cardiovascular disease (CVD). Low serum 25(OH)D levels were only associated with higher LVMI at 8-year follow-up in subjects without prior CVD and in subjects with low kidney function (median estimated glomerular filtration rate ≤77.5 ml/min/1.73m(2)). The associations attenuated after adjustments for parathyroid hormone (PTH), which was associated with higher LVMI (g/m(2.7)) in subjects with low kidney function (regression coefficient highest quartile 6.3, 95% CI: 0.2, 12.5). CONCLUSION: This study showed no strong associations of 25(OH)D with myocardial structure and function. However, PTH - a possible modifiable mediator in the relation between 25(OH)D and myocardial structure - was positively associated with LVMI in subjects with low kidney function.

Impact of Time of Surgery on the Outcome after Surgical Stabilization of Rib Fractures in Severely Injured Patients with Severe Chest Trauma-A Matched-Pairs Analysis of the German Trauma Registry.

Purpose: In severely injured patients with multiple rib fractures, the beneficial effect of surgical stabilization is still unknown. The existing literature shows divergent results, and the indication and especially the right timing of an operation are the subject of a broad discussion. The aim of this study was to determine the influence of the time point of surgical stabilization of rib fractures (SSRF) on the outcome in a multicenter database with special regard to the duration of ventilation, intensive care, and overall hospital stay. Methods: Data from the TraumaRegister DGU collected between 2010 and 2019 were used to evaluate patients above 16 years of age with severe rib fractures [Abbreviated Injury Score (AIS) ≥ 3] who received an SSRF in a matched-pairs analysis. In this matched-pairs analysis, we compared the effects of an early SSRF within 48 h after initial trauma vs. late SSRF 3-10 days after trauma. Results: After the selection process, we were able to find 142 matched pairs for further evaluation. Early SSRF was associated with a significantly shorter length of stay in the intensive care unit (16.2 days vs. 12.7 days, p = 0.020), and the overall hospital stay (28.5 days vs. 23.4 days, p = 0.005) was significantly longer in the group with late SSRF. Concerning the days on mechanical ventilation, we were able to demonstrate a trend for an approximately 1.5 day shorter ventilation time for patients after early SSRF, although this difference was not statistically significant (p = 0.226). Conclusions: We were able to determine the significant beneficial effects of early SSRF resulting in a shorter intensive care unit stay and a shorter length of stay in hospital and additionally a trend to a shorter time on mechanical ventilation.

Therapeutic application of ultrasound: contrast-enhanced thrombolysis in acute ST-elevation myocardial infarction; the Sonolysis study.

Contrast enhancement by microbubble infusion has proven its applicability in the field of diagnostic ultrasound. Recent studies also indicate a therapeutic effect of the combined use of ultrasound and microbubbles. Results from animal studies demonstrate that diagnostic ultrasound in combination with intravenous microbubbles can dissolve thrombi. So far, this effect has never been tested in patients with an acute ST-elevation myocardial infarction (STEMI). We recently launched a pilot study in acute STEMI patients to assess safety, feasibility and efficacy of the treatment in this patient group with transthoracic three-dimensional diagnostic ultrasound and intravenous microbubbles immediately after prehospital thrombolysis, but prior to primary percutaneous coronary intervention.

Survival among patients with severe high cervical spine injuries - a TraumaRegister DGU® database study.

BACKGROUND: Trauma is a significant cause of death and impairment. The Abbreviated Injury Scale (AIS) differentiates the severity of trauma and is the basis for different trauma scores and prediction models. While the majority of patients do not survive injuries which are coded with an AIS 6, there are several patients with a severe high cervical spinal cord injury that could be discharged from hospital despite the prognosis of trauma scores. We estimate that the trauma scores and prediction models miscalculate these injuries. For this reason, we evaluated these findings in a larger control group. METHODS: In a retrospective, multi-centre study, we used the data recorded in the TraumaRegister DGU® (TR-DGU) to select patients with a severe cervical spinal cord injury and an AIS of 3 to 6 between 2002 to 2015. We compared the estimated mortality rate according to the Revised Injury Severity Classification II (RISC II) score against the actual mortality rate for this group. RESULTS: Six hundred and twelve patients (0.6%) sustained a severe cervical spinal cord injury with an AIS of 6. The mean age was 57.8 ± 21.8 years and 441 (72.3%) were male. 580 (98.6%) suffered a blunt trauma, 301 patients were injured in a car accident and 29 through attempted suicide. Out of the 612 patients, 391 (63.9%) died from their injury and 170 during the first 24 h. The group had a predicted mortality rate of 81.4%, but we observed an actual mortality rate of 63.9%. CONCLUSIONS: An AIS of 6 with a complete cord syndrome above C3 as documented in the TR-DGU is survivable if patients get to the hospital alive, at which point they show a survival rate of more than 35%. Compared to the mortality prognosis based on the RISC II score, they survived much more often than expected.

Impact of high altitude on echocardiographically determined cardiac morphology and function in patients with coronary artery disease and healthy controls.

AIMS: To evaluate the impact of high altitude on cardiac morphology and function in patients with coronary artery disease (CAD) and healthy controls. METHODS AND RESULTS: Eight patients with a history of acute myocardial infarction [53 +/- 8 years, left ventricular (LV) ejection fraction 54 +/- 6%] and a low risk score were compared with seven healthy controls (41 +/- 16 years) during the Dutch Heart Expedition 2007 at the Aconcagua (6960 m) in Argentina. An exercise test and echocardiography were performed at sea level and at base camp (4200 m). In the apical four-chamber view, right ventricular (RV) diameter, tricuspid annular plane systolic excursion (TAPSE), early transmitral inflow peak velocity (E), atrial transmitral inflow peak velocity (A), and peak tissue velocity during early diastole (E') were obtained. Changes in global LV function and wall motion score index (WMSI) were used as markers of ischaemia. There were no significant differences in individual global LV function and WMSI at high altitude compared with sea level in both groups. A significant increase in RV diameter was observed in the patient group at 4200 m compared with sea level and a trend towards the same result in the control group. A decrease in TAPSE was observed. Measurements of the E' showed a significant decrease in the LV septum and lateral wall at high altitude compared with sea level in both groups. CONCLUSION: Symptoms and echocardiographic signs of myocardial ischaemia were absent in low-risk patients with a history of CAD during and after exercise up to an altitude of 4200 m. Patients and healthy controls showed comparable changes at high altitude compared with sea level with an increase in RV diameter, a decrease in TAPSE, and decreased E' as early signs of pulmonary hypertension and LV diastolic dysfunction. As these alterations are most likely physiological adaptation to high altitude, the results seem to affirm current guidelines. The safety of expanding previous recommendations to patients with low-risk CAD to an altitude ascent of 4200 m requires confirmation in a larger study with appropriately defined clinical endpoints.

Vitamin D deficiency and myocardial structure and function in older men and women: the Hoorn study.

BACKGROUND: Vitamin D deficiency is frequently observed in heart failure patients and it has been shown that vitamin D exerts various effects on the heart that may be relevant for the pathogenesis of myocardial diseases. AIMS: We aimed to elucidate the largely unknown association of 25-hydroxyvitamin D [25(OH)D] serum levels with echocardiographic measures of left ventricular (LV) structure and function. MATERIAL/SUBJECTS AND METHODS: We measured 25(OH)D serum levels and performed standardized LV echocardiograms in 614 persons from a population-based cohort of older men and women. Echocardiographic data were used to calculate LV mass and geometry and for classification of systolic and diastolic dysfunction. To consider the seasonal variations of 25(OH)D levels we categorized our study participants according to season-specific 25(OH)D quartiles. RESULTS: LV systolic function, mass and geometry were not significantly associated with 25(OH)D serum levels. In binary logistic regression analyses, the prevalence of LV diastolic dysfunction was significantly higher in the first season-specific 25(OH)D quartile when compared to the fourth quartile [odds ratio 2.32 (95% CI: 1.42-3.80); p=0.001] but significance was lost after adjustments for age [odds ratio 1.51 (0.89-2.57); p=0.123] and established risk factors for heart failure [odds ratio 1.47 (0.84-2.59); p=0.178]. CONCLUSIONS: Serum levels of 25(OH)D are not significantly associated with LV structure and function but a non-significant trend towards increased risk of diastolic dysfunction in persons with vitamin D deficiency warrants further studies.

Safety and feasibility of real time adenosine myocardial contrast echocardiography with emphasis on induction of arrhythmias: a study in healthy volunteers and patients with stable coronary artery disease.

INTRODUCTION: Some studies reported an increased incidence of premature ventricular complexes (PVCs) during triggered myocardial contrast echocardiography (MCE) using high-intensity ultrasound destruction. Whether PVCs are also induced by real time MCE using low emission power, is unknown. The aim of the study was to assess the occurrence of arrhythmias during real time adenosine MCE in healthy volunteers and patients with stable coronary artery disease (CAD). METHODS: Fifty healthy volunteers and 26 patients with stable CAD underwent real time MCE using Sonovue and power pulse inversion (ATL 5000) at rest and during adenosine stress. The occurrence of premature atrial complexes (PAC) and PVCs was analyzed before and during MCE using ECG-tracings from videotapes. RESULTS: In healthy subjects, the occurrence of PVCs at baseline (0.04 +/- 0.23 PVCs/min) was similar at rest (0.04 +/- 0.23 PVCs/min, P = NS), and adenosine stress (0.03 +/- 0.14, P = NS). In CAD patients, the occurrence of PVCs at baseline was 0.30 +/- 0.76 PVC/min, compared to 0.29 +/- 0.74 at rest (P = NS), and 0.34 +/- 0.74 during adenosine stress (P = NS). The number of subjects demonstrating PVCs did not increase during MCE. The occurrence of PACs during MCE was not increased compared to baseline. CONCLUSION: Real time MCE using low emission power does not increase the occurrence of premature complexes in healthy volunteers or CAD patients.

Clinical application of three-dimensional echocardiography: past, present and future.

Significant advances in three-dimensional echocardiography have made this modality a powerful diagnostic tool in the cardiology clinic. It can provide accurate and reliable measurements of chamber size and function, including the quantification of left ventricular mechanical dyssynchrony to guide patient selection for cardiac resynchron-isation therapy. Furthermore, three-dimensional echocardiography offers novel views and comprehensive anatomic definition of valvular and congenital abnormalities, improving diagnosis and preoperative planning. In addition, it is extremely useful in monitoring the effectiveness of surgical or percutaneous transcatheter interventions. As its efficacy for more and more clinical applications is demonstrated, it is clear that three-dimensional echocardiography has become part of the routine clinical diagnostic armamentarium. In this article, we describe the development of three-dimensional echocardiography over the last decades, review the scientific evidence for its current clinical use and discuss potential future applications. (Neth Heart J 2009;17:18-24.).

Ultrasound and microbubble-targeted delivery of therapeutic compounds: ICIN Report Project 49: Drug and gene delivery through ultrasound and microbubbles.

The molecular understanding of diseases has been accelerated in recent years, producing many new potential therapeutic targets. A noninvasive delivery system that can target specific anatomical sites would be a great boost for many therapies, particularly those based on manipulation of gene expression. The use of microbubbles controlled by ultrasound as a method for delivery of drugs or genes to specific tissues is promising. It has been shown by our group and others that ultrasound increases cell membrane permeability and enhances uptake of drugs and genes. One of the important mechanisms is that microbubbles act to focus ultrasound energy by lowering the threshold for ultrasound bioeffects. Therefore, clear understanding of the bioeffects and mechanisms underlying the membrane permeability in the presence of microbubbles and ultrasound is of paramount importance. (Neth Heart J 2009;17:82-6.).