Randomised comparison of a balloon-expandable and self-expandable valve with quantitative assessment of aortic regurgitation using magnetic resonance imaging.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a safe and effective treatment for inoperable, intermediate- or high-risk patients with severe symptomatic aortic stenosis and has been associated with excellent clinical outcomes. A clinically relevant remaining problem is aortic regurgitation (AR) post-TAVI, which is associated with increased mortality. Therefore, we conducted a prospective randomised trial to assess the safety and efficacy of a first-generation self-expandable valve (SEV; CoreValve) and a third-generation balloon-expandable valve (BEV; Sapien 3) with respect to clinical outcomes and AR as determined quantitatively by magnetic resonance imaging (MRI). METHODS: The ELECT study was an investigator-initiated, single-centre trial involving patients with severe symptomatic aortic stenosis and with a clinical indication for transfemoral TAVI. Fifty-six patients were randomly assigned to the BEV or SEV group. RESULTS: AR determined quantitatively by MRI was lower in the BEV than in the SEV group [regurgitant fraction: 1.1% (0-8.0) vs 8.7% (3.0-14.8) for SEV; p = 0.01]. Secondary endpoints according to the criteria of the Second Valve Academic Research Consortium (VARC-2) showed BEV to have better early safety [0 (0%) vs 8 (30%); p = 0.002] at 30 days and a lower risk of stroke [0 (0%) vs 5 (21%); p = 0.01], major adverse cardiac and cerebrovascular events [0 (0%) vs 10 (38%); p < 0.001] or death [0 (0%) vs 5 (19%); p = 0.02] in the 1st year compared with SEV. CONCLUSIONS: The use of the latest generation of BEV was associated with less AR as quantitatively assessed by MRI. Although the use of MRI to quantify AR is not feasible in daily clinical practice, it should be considered as a surrogate endpoint for clinical outcomes in comparative studies of valves for TAVI. ClinicalTrials.gov number NCT01982032.

Validation of aortic valve 4D flow analysis and myocardial deformation by cardiovascular magnetic resonance in patients after the arterial switch operation.

BACKGROUND: Aortic regurgitation (AR) and subclinical left ventricular (LV) dysfunction expressed by myocardial deformation imaging are common in patients with transposition of the great arteries after the arterial switch operation (ASO). Echocardiographic evaluation is often hampered by reduced acoustic window settings. Cardiovascular magnetic resonance (CMR) imaging provides a robust alternative as it allows for comprehensive assessment of degree of AR and LV function. The purpose of this study is to validate CMR based 4-dimensional flow quantification (4D flow) for degree of AR and feature tracking strain measurements for LV deformation assessment in ASO patients. METHODS: A total of 81 ASO patients (median 20.6 years, IQR 13.5-28.4) underwent CMR for 4D and 2D flow analysis. CMR global longitudinal strain (GLS) feature tracking was compared to echocardiographic (echo) speckle tracking. Agreements between and within tests were expressed as intra-class correlation coefficients (ICC). RESULTS: Eleven ASO patients (13.6%) showed AR > 5% by 4D flow, with good correlation to 2D flow assessment (ICC = 0.85). 4D flow stroke volume of the aortic valve demonstrated good agreement to 2D stroke volume over the mitral valve (internal validation, ICC = 0.85) and multi-slice planimetric LV stroke volume (external validation, ICC = 0.95). 2D flow stroke volume showed slightly less, though still good agreement with 4D flow (ICC = 0.78) and planimetric LV stroke volume (ICC = 0.87). GLS by CMR was normal (- 18.8 ± 4.4%) and demonstrated good agreement with GLS and segmental analysis by echocardiographic speckle tracking (GLS = - 17.3 ± 3.1%, ICC of 0.80). CONCLUSIONS: Aortic 4D flow and CMR feature tracking GLS analysis demonstrate good to excellent agreement with 2D flow assessment and echocardiographic speckle tracking, respectively, and can therefore reliably be used for an integrated and comprehensive CMR analysis of aortic valve competence and LV deformation analysis in ASO patients.

Effect of body mass index on clinical outcome and all-cause mortality in patients undergoing transcatheter aortic valve implantation.

OBJECTIVES: To assess the effect of body mass index (BMI) on outcome among patients with severe aortic stenosis (AS) admitted for transcatheter aortic valve implantation (TAVI). BACKGROUND: Being overweight or obese is associated with improved outcome following certain medical treatments, suggesting the existence of a BMI paradox. However, the relationship between BMI and mortality after TAVI remains controversial. METHODS: Patients were classified according to World Health Organisation criteria such as normal weight, overweight, or obesity according to their BMI (18.5 to 24.9 kg/m2, 25.0 to 29.9 kg/m2, and ≥30.0 kg/m2, respectively). RESULTS: A total of 549 consecutive patients (age: 80.2 ± 7.5 years; logistic European system for cardiac operative risk evaluation [EuroSCORE]: 17.3 ± 9.9%) who underwent TAVI for AS were included. Of these patients, 43% (n = 237) had normal weight, 36% (n = 200) were overweight, and 20% (n = 112) were obese. There were no differences in peri-operative bleeding or vascular complication rates between the groups. All-cause mortality after 30 days, and 1 year, were higher in normal weight patients compared with overweight and obese patients (7% vs. 5 and 4%, p = 0.383, and 19% vs. 9 and 10%, p = 0.006, respectively). After adjustment for several confounding factors, overweight was associated with a decreased 30-day and 1­year all-cause mortality outcome (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.47-0.99, and HR 0.65; 95% CI 0.45-0.94, respectively). CONCLUSIONS: Despite the well-documented adverse effects of increased body weight on health, being overweight is associated with improved survival following TAVI when compared with normal weight.

No psychological distress in sportsmen aged 45 years and older after cardiovascular screening, including cardiac CT: The Measuring Athlete's Risk of Cardiovascular events (MARC) study.

BACKGROUND: Psychological distress caused by cardiovascular pre-participation screening (PPS) may be a reason not to implement a PPS program. We assessed the psychological impact of PPS, including cardiac computed tomography (CT), in 318 asymptomatic sportsmen aged ≥45 years. METHODS: Coronary artery disease (CAD) was defined as a coronary artery calcium score ≥100 Agatson units and/or ≥50% luminal stenosis on contrast-enhanced cardiac CT. Psychological impact was measured with the Impact of Event Scale (IES) (seven items) on a six-point scale (grade 0-5). A sum score ≥19 indicates clinically relevant psychological distress. A Likert scale was used to assess overall experiences and impact on sports and lifestyle. RESULTS: A total of 275 participants (86.5% response rate, 95% CI 83-90%) with a mean age of 54.5 ± 6.4 years completed the questionnaires, 48 (17.5%, 95% CI 13-22%) of whom had CAD. The median IES score was 1 (IQR 0-2, [0-23]). IES was slightly higher in those with CAD (mean rank 175 vs. 130, p < 0.001). One participant (with CAD) experienced clinically relevant psychological distress (IES = 23). Participants reported numerous benefits, including feeling safer exercising (58.6%, 95% CI 53-65%) and positive lifestyle changes, especially in those with CAD (17.2 vs. 52.1%, p < 0.001). The majority were satisfied with their participation (93.8%, 95% CI 91-97%). CONCLUSION: Cardiovascular PPS, including cardiac CT, causes no relevant psychological distress in older sportsmen. Psychological distress should not be a reason to forego screening in sportsmen.

Rationale and design of the Measuring Athlete's Risk of Cardiovascular events (MARC) study : The role of coronary CT in the cardiovascular evaluation of middle-aged sportsmen.

BACKGROUND: More than 90 % of exercise-related cardiac arrests occur in men, predominantly those aged 45 years and older with coronary artery disease (CAD) as the main cause. The current sports medical evaluation (SME) of middle-aged recreational athletes consists of a medical history, physical examination, and resting and exercise electrocardiography. Coronary CT (CCT) provides a minimally invasive low radiation dose opportunity to image the coronary arteries. We present the study protocol of the Measuring Athlete's Risk of Cardiovascular events (MARC) study. MARC aims to assess the additional value of CCT to a routine SME in asymptomatic sportsmen ≥45 years without known CAD. DESIGN: MARC is a prospective study of 300 asymptomatic sportsmen ≥45 years who will undergo CCT if the SME does not reveal any cardiac abnormalities. The prevalence and determinants of CAD (coronary artery calcium score ≥100 Agatston Units (AU) or ≥50 % luminal stenosis) will be reported. The number needed to screen to prevent the occurrence of one cardiovascular event in the next 5 years, conditional to adequate treatment, will be estimated. DISCUSSION: We aim to determine the prevalence and severity of CAD and the additional value of CCT in asymptomatic middle-aged (≥45 years) sportsmen whose routine SME revealed no cardiac abnormalities.

Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events.

The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10(-5)) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.

Continuous-flow left ventricular assist device support in patients with advanced heart failure: points of interest for the daily management.

Today, continuous-flow left ventricular assist devices (cf-LVADs) are implanted more often in patients with end-stage heart failure. Because of greater durability they can be implanted for an extended period of time. As a result of increased numbers of patients on cf-LVAD support, healthcare professionals should be aware of the potential complications inherent to this therapy. Both bleeding and thrombosis may occur, and also complications related either to the device itself or to the ensuing altered haemodynamics, valvular pathology, and rhythm disturbances such as ventricular tachycardias and fibrillation. Accurate clinical evaluation, together with an electrocardiogram and, if necessary, combined with an echocardiogram, is obligatory in these situations. This review summarizes common complications complemented by a few clinical cases.

The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo.

Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended.

Rationale and design of the CAREFUL study : The yield of CARdiogenetic scrEening in First degree relatives of sudden cardiac and UnexpLained death victims <45 years.

Background. Sudden cardiac death (SCD) in the young (1-45 years) is a strong risk factor for the presence of inherited cardiac diseases in surviving first-degree relatives. Postmortem investigation of the victim and cardiogenetic evaluation of the first-degree relatives is indicated to detect inherited cardiac diseases and treat relatives at an early stage to prevent SCD. In the Netherlands, postmortem investigation is often not performed and relatives of SCD and sudden unexplained death (SUD) victims are rarely evaluated for inherited cardiac diseases.Methods. A prospective population-based follow-up study carried out in two intervention regions and two control regions. In the intervention regions a comprehensive intervention (stimulate autopsy and storage of victims DNA and the referral of first-degree relatives for cardiogenetic evaluation) is applied in a 'top down' and 'bottom up' mode. In each region, young sudden death victims are registered and for all cases performance of autopsy and evaluation of relatives in a cardiogenetics outpatient clinic will be determined.Expected results. The study will provide information on the incidence of sudden death in the young and the proportion of diagnosed inherited cardiac diseases. Moreover, the additional value of the introduction of two different preventive strategies directed at early detection of inherited cardiac diseases in first-degree relatives to usual care will be evaluated. Conclusion. The CAREFUL study will help to set a new standard of care in the evaluation of young sudden death victims and their relatives to identify the presence of inherited cardiac diseases, in order to prevent sudden death. (Neth Heart J 2010;18:286-90.).

Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells.

Patients suffering from heart failure as a result of myocardial infarction are in need of heart transplantation. Unfortunately the number of donor hearts is very low and therefore new therapies are subject of investigation. Cell transplantation therapy upon myocardial infarction is a very promising strategy to replace the dead myocardium with viable cardiomyocytes, smooth muscle cells and endothelial cells, thereby reducing scarring and improving cardiac performance. Despite promising results, resulting in reduced infarct size and improved cardiac function on short term, only a few cells survive the ischemic milieu and are retained in the heart, thereby minimizing long-term effects. Although new capillaries and cardiomyocytes are formed around the infarcted area, only a small percentage of the transplanted cells can be detected months after myocardial infarction. This suggests the stimulation of an endogenous regenerative capacity of the heart upon cell transplantation, resulting from release of growth factor, cytokine and other paracrine molecules by the progenitor cells--the so-called paracrine hypothesis. Here, we focus on a relative new component of paracrine signalling, i.e. exosomes. We are interested in the release and function of exosomes derived from cardiac progenitor cells and studied their effects on the migratory capacity of endothelial cells.

Simultaneous aortic and coronary assessment in abdominal aortic aneurysm patients by thoraco-abdominal 64-detector-row CT angiography: estimate of the impact on preoperative management: a pilot study.

OBJECTIVES: To estimate the influence of information on the coronary arteries obtained from routine thoraco-abdominal CT angiography (CTA) on pre-operative clinical management in abdominal aortic aneurysm (AAA) patients. METHODS: Twenty-eight AAA patients underwent pre-operative thoraco-abdominal electrocardiography (ECG)-gated 64-detector-row CTA to evaluate aortic pulsatility for prosthesis size matching. Retrospectively, the coronaries were reconstructed from the same data set and scored on a per segment basis for stenosis (0%, 50%) and grading confidence (poor, adequate or high). An experienced cardiologist was presented information on patient characteristics obtained from patient records and CTA findings. Suggested changes in European Society of Cardiology guidelines based patient management based on CTA information were scored. RESULTS: On CTA, 17 patients (61%) had significant coronary disease (>50% stenosis) including left main (n=4), single (n=7) and multiple (n=6) vessel disease. Grading confidence was adequate or high in 86% of proximal and middle segments. Based on CTA findings, patient management would have been changed in 4 out of the 28 patients (14%; 95% CI 1-27%) by adding coronary angiography (n=4). In five patients who underwent coronary artery bypass grafting previously, CT did not change management but confirmed graft patency. CONCLUSIONS: Information on coronary pathology and coronary bypass graft patency can be readily obtained from thoraco-abdominal CTA and may alter pre-operative patient management, as shown in 14% of AAA patients in our study.

Matrix metalloproteinases 2 and 3 gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention: Is there still room for determining genetic variation of MMPs for assessment of an increased risk of restenosis?

OBJECTIVE: Mixed results have been reported of matrix metalloproteinases (MMP) and their association with restenosis after percutaneous coronary intervention (PCI). The current study examines whether multiple single nucleotide polymorphisms (SNPs), covering the full genomic region of MMP2 and MMP3, were associated with restenosis in the GENDER study population. METHODS AND RESULTS: The GENetic DEterminants of Restenosis (GENDER) study enrolled 3104 consecutive patients after successful PCI. The primary endpoint was clinical restenosis, defined as target vessel revascularization (TVR), occurring in 9.8% of the patients. From the Hapmap database, 19 polymorphisms of MMP2 and 11 of MMP3 were selected. Furthermore, in a subpopulation, a genome-wide association analysis (GWA) was performed. No significant association was found with any of the investigated SNPs, including the previously reported 5A/6A polymorphism (rs3025058), with regard to TVR using single SNP analysis or haplotype analysis. CONCLUSION: We found no significant association of MMP2 or MMP3 with TVR with this SNP-broad gene approach. Although we did not test all the known polymorphisms of these genes, using tagging analyses we examined those SNPs covering all known haplotypes of MMP2 and MMP3 to conclude that these genes do not correlate with a genetic risk of coronary restenosis after successful PCI.

Left ventricular assist device: a functional comparison with heart transplantation.

BACKGROUND: A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. OBJECTIVES: In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. METHODS: We compared peak VO(2) of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. RESULTS: After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO(2) was 20.0+/-4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0+/-3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570+/-307 pmol/l to 31+/-25 pmol/l and creatinine levels decreased from 191+/-82 mumol/l to 82+/-25 mumol/l, indicating significant unloading of the ventricles and haemodynamic recovery. CONCLUSION: With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.).

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity.

Vascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype. (Neth Heart J 2007;15:100-8.).

Intracoronary abciximab.

Here we report the potential benefits of the use of intracoronary abciximab during percutaneous coronary intervention for an acute myocardial infarction.

Heart transplantation in the Netherlands: quo vadis?

Heart transplantation is limited by the lack of donor organs. Twenty years after the start of the Dutch transplant programmes in Rotterdam and Utrecht the situation has even worsened, despite efforts to increase the donor pool. The Dutch situation seems to be worse than in other surrounding countries, and several factors that may influence donor organ availability and organ utilisation are discussed. The indications and contraindications for heart transplantation are presented, which are rather restrictive in order to select optimal recipients for the scarce donor hearts. Detailed data on donor hearts, rejected for transplantation, are shown to give some insight into the difficult process of dealing with marginal donor organs. It is concluded that with the current low numbers of acceptable quality donor hearts, there is no lack of capacity in the two transplanting centres nor is the waiting list limiting the number of transplants. The influence of our current legal system on organ donation, which requires (prior) permission from donor and relatives, is probably limited. The most important determinants of donor organ availability are: 1. The potential donor pool, consisting of brain dead victims of (traffic) accidents and CVAs and 2. Lack of consent to a request for donation. The potential donor pool is remarkably small in the Netherlands, due to relatively low numbers of (traffic) accidents, with an almost equal number of CVA-related brain dead patients compared with neighbouring countries. Lack of consent can only be pushed back by improved public awareness of the importance of donation and improved skills of professionals in asking permission in case there is no previous consent.

[The polypill: optimal strategy for reduction of cardiovascular disease]. / De 'polypil': de beste strategie tegen hart- en vaatziekten.

Treating all persons above 55 years of age with a polypill for primary and secondary cardiovascular-disease prevention may reduce cardiovascular events by more than 80%. This strategy is expected to be cost-effective and the associated risk of side effects is estimated to be low.

Progress in noninvasive coronary artery imaging using multislice CT.

Conventional coronary angiography (CAG) has been the reference standard for the assessment of coronary artery disease since its introduction in 1958. However, several studies have shown that diagnostic CAG has an average morbidity of 2% and a mortality of approximately 0.1%. In the last decade, progress in medical imaging has opened the way to noninvasive assessment of the coronary arteries at lower cost and risk. Of the different modalities, multislice CT (MSCT) has made the biggest step forward. At the 2005 European Congress of Radiology (ECR), experiences with the latest developments in noninvasive coronary artery imaging were reported. This report summarises the advances in the use of MSCT in coronary stenosis detection, emergency decision-making, plaque imaging, and the analysis of cardiac function and late enhancement. Also, attention is paid to new strategies to reduce MSCT-related radiation exposure.