Safety and efficacy of stenting for aortic arch hypoplasia in patients with coarctation of the aorta

Netherlands Heart Journal - Despite a successful repair procedure for coarctation of the aorta (CoA), up to two-thirds of patients remain hypertensive. CoA is often seen in combination...     

Peripartum cardiomyopathy: the need for a national database

Peripartum cardiomyopathy (PPCM) is a rare and life-threatening disease that affects young women in the last month of pregnancy or within 5 months of delivery. It is a form of dilated cardiomyopathy with left-sided systolic dysfunction. The incidence rate in the Western world is estimated to be 1:3000. Symptoms of PPCM vary greatly and may be obscured by common physiological aspects of pregnancy. Therefore, the incidence rate might be higher. Echocardiography or MRI can confirm or rule out PPCM. Unfortunately, there is no specific risk factor profile available. The clinical course varies from complete recovery to deterioration of cardiac function. Patients with PPCM, especially those whose ventricular function has not returned to normal, are advised against further pregnancy. Recently, more disease-specific therapeutic strategies have been developed with promising results for prolactin blockade by bromocriptine. Increasing awareness for PPCM among general practitioners, gynaecologists and cardiologists may help to diagnose patients efficiently in order to start adequate treatment. A national registry is warranted to identify risk factor profiles and to optimise treatment strategies.     

Percutaneous renal denervation for the treatment of resistant essential hypertension; the first Dutch experience

Background

In a subpopulation of patients with essential hypertension, therapeutic targets are not met, despite the use of multiple types of medication. In this paper we describe our first experience with a novel percutaneous treatment modality using renal artery radiofrequency (RF) ablation.

Methods

Patients who were resistant to at least three types of antihypertensive medical therapy (office systolic blood pressure?≥?160 mmHg; n?=?9) or who did not tolerate medication (n?=?2) were selected. Between July and November 2010, a total of 11 patients received percutaneous RF treatment. Patients were followed up for 1 month after treatment. Urine and blood samples were taken to evaluate the effects on renal function and neurohumeral factors.

Results

No periprocedural complications or adverse events during follow-up were noted. A reduction of mean office blood pressure was seen from 203/109?±?32/19 mmHg at baseline to 178/97?±?28/21 mmHg at 1 month follow-up (mean difference 25?±?12 mmHg, p?<?0.01). Also, we noted a significant decrease in aldosterone level (391?±?210 pmol/L versus 250?±?142 pmol/L; p?=?0.03), while there was no decrease in plasma renin activity (190?±?134 fmol/L/s versus 195?±?163 fmol/L/s; p?=?0.43). No change in renal function was noted.

Conclusion

Catheter-based renal denervation seems an attractive novel minimally invasive treatment option in patients with resistant hypertension, with a low risk of serious adverse events.     

MiR-155 inhibits cell migration of human cardiomyocyte progenitor cells (hCMPCs) via targeting of MMP-16

Undesired cell migration after targeted cell transplantation potentially limits beneficial effects for cardiac regeneration. MicroRNAs are known to be involved in several cellular processes, including cell migration. Here, we attempt to reduce human cardiomyocyte progenitor cell (hCMPC) migration via increasing microRNA‐155 (miR‐155) levels, and investigate the underlying mechanism. Human cardiomyocyte progenitor cells (hCMPCs) were transfected with pre‐miR‐155, anti‐miR‐155 or control‐miR (ctrl‐miR), followed by scratch‐ and transwell‐ assays. These functional assays displayed that miR‐155 over‐expression efficiently inhibited cell migration by 38 ± 3.6% and 59 ± 3.7% respectively. Conditioned medium from miR‐155 transfected cells was collected and zymography analysis showed a significant decrease in MMP‐2 and MMP‐9 activities. The predicted 3′‐UTR of MMP‐16, an activator of MMP‐2 and ‐9, was cloned into the pMIR‐REPORT vector and luciferase assays were performed. Introduction of miR‐155 significantly reduced luciferase activity which could be abolished by cotransfection with anti‐miR‐155 or target site mutagenesis. By using MMP‐16 siRNA to reduce MMP‐16 levels or by using an MMP‐16 blocking antibody, hCMPC migration could be blocked as well. By directly targeting MMP‐16, miR‐155 efficiently inhibits cell migration via a reduction in MMP‐2 and ‐9 activities. Our study shows that miR‐155 might be used to improve local retention of hCMPCs after intramyocardial delivery.     

From concept to product in cardiology

As academic physicians and researchers, we are expected to try to valorise basic concepts and turn them into useful products. Despite the general call from the public for these initiatives and an encouraging stimulation package from the Ministry of Economic Affairs there are counterbalancing forces that are keeping researchers from going along the arduous path of claiming intellectual property (IP), filing for a patent, and seeking funding for the initial translation steps from idea to product.     

Search for haplotype interactions that influence susceptibility to type 1 diabetes, through use of unphased genotype data

Type 1 diabetes is a T-cell-mediated chronic disease characterized by the autoimmune destruction of pancreatic insulin-producing beta cells and complete insulin deficiency. It is the result of a complex interrelation of genetic and environmental factors, most of which have yet to be identified. Simultaneous identification of these genetic factors, through use of unphased genotype data, has received increasing attention in the past few years. Several approaches have been described, such as the modified transmission/disequilibrium test procedure, the conditional extended transmission/disequilibrium test, and the stepwise logistic-regression procedure. These approaches are limited either by being restricted to family data or by ignoring so-called "haplotype interactions" between alleles. To overcome this limit, the present study provides a general method to identify, on the basis of unphased genotype data, the haplotype blocks that interact to define the risk for a complex disease. The principle underpinning the proposal is minimal entropy. The performance of our procedure is illustrated for both simulated and real data. In particular, for a set of Dutch type 1 diabetes data, our procedure suggests some novel evidence of the interactions between and within haplotype blocks that are across chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 15, 16, 17, 19, and 21. The results demonstrate that, by considering interactions between potential disease haplotype blocks, we may succeed in identifying disease-predisposing genetic variants that might otherwise have remained undetected.     

Driving restrictions for Dutch patients with an implantable cardioverter defibrillator

Background

Dutch patients with an implantable cardioverter defibrillator (ICD) are restricted from driving for two months after implantation or shocks. This requires significant lifestyle adjustments and is one of the primary concerns of ICD patients. Previous studies indicated that compliance with the driving restrictions is poor, but insight in socio-demographic, clinical and psychological factors associated with compliance is limited. Hence, this study aimed to explore compliance with the driving restrictions and associated factors in a large sample of Dutch ICD patients.

Method

Dutch ICD patients (N = 313) completed an elaborative set of questionnaires at time of implantation and at four months after implantation, assessing socio-demographic, psychological and driving-related characteristics. Clinical data were collected from the patients’ medical records.

Results

A substantial subgroup (28%) of the patient sample (median age 64 (interquartile range = 55–71), 81% male) reported to have been noncompliant with the driving restrictions. Univariate analysis indicated that noncompliant patients more often considered refusing the ICD due to the restrictions, compared to compliant patients (19% versus 10%, p = 0.02). Multivariate analysis showed that the feeling of understanding the reason behind the driving restrictions was associated with better compliance (odds ratio = 2.16, 95% confidence interval 1.02–4.56, p = 0.04). No other socio-demographic, clinical, psychological or driving-related factors were associated with compliance.

Conclusion

A large number of ICD patients does not comply with the driving restrictions after implantation. This study emphasised the importance of the patient’s feeling of understanding the reason behind the restrictions.