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1.
Eur Heart J Cardiovasc Imaging ; 25(6): 764-770, 2024 May 31.
Article En | MEDLINE | ID: mdl-38412329

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.


Ventricular Fibrillation , Humans , Female , Ventricular Fibrillation/diagnostic imaging , Male , Retrospective Studies , Middle Aged , Adult , Magnetic Resonance Imaging, Cine/methods , Mitral Valve/diagnostic imaging , Cohort Studies , Mitral Valve Prolapse/diagnostic imaging , Mitral Valve Prolapse/complications , Prevalence , Risk Assessment
2.
Neth Heart J ; 31(2): 52-60, 2023 Feb.
Article En | MEDLINE | ID: mdl-35976610

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

3.
Cardiovasc Diabetol ; 20(1): 220, 2021 11 09.
Article En | MEDLINE | ID: mdl-34753497

BACKGROUND: Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. METHODS: Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. RESULTS: 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. CONCLUSION: Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.


Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/mortality , Inflammation/mortality , Aged , Biomarkers/blood , Blood Glucose/metabolism , C-Reactive Protein/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cause of Death , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Female , Glycated Hemoglobin/metabolism , Heart Disease Risk Factors , Humans , Incidence , Inflammation/blood , Inflammation/diagnosis , Inflammation Mediators/blood , Lipids/blood , Male , Middle Aged , Netherlands , Prognosis , Prospective Studies , Risk Assessment , Time Factors
4.
Neth Heart J ; 29(10): 479-485, 2021 Oct.
Article En | MEDLINE | ID: mdl-34114176

Cardiac rehabilitation (CR) has evolved as an important part of the treatment of patients with cardiovascular disease. However, to date, its full potential is fairly underutilised. This review discusses new developments in CR aimed at improving participation rates and long-term effectiveness in the general cardiac population. It consecutively highlights new or challenging target groups, new delivery modes and new care pathways for CR programmes. These new or challenging target groups include patients with atrial fibrillation, obesity and cardiovascular disease, chronic coronary syndromes, (advanced) chronic heart failure with or without intracardiac devices, women and frail elderly patients. Also, the current evidence regarding cardiac telerehabilitation and loyalty programmes is discussed as new delivery modes for CR. Finally, this paper discusses novel care pathways with the integration of CR in residual risk management and transmural care pathways. These new developments can help to make optimal use of the benefits of CR. Therefore we should seize the opportunities to reshape current CR programmes, broaden their applicability and incorporate them into or combine them with other cardiovascular care programmes/pathways.

5.
Neth Heart J ; 29(2): 105-110, 2021 Feb.
Article En | MEDLINE | ID: mdl-32940869

BACKGROUND: According to the current guidelines of the European Society of Cardiology, patients with left-sided infective endocarditis are treated with intravenous antibiotics for 4-6 weeks, leading to extensive hospital stay and high costs. Recently, the Partial Oral Treatment of Endocarditis (POET) trial suggested that partial oral treatment is effective and safe in selected patients. Here, we investigated if such patients are seen in our daily clinical practice. METHODS: We enrolled 119 adult patients diagnosed with left-sided infective endocarditis in a retrospective, observational study. We identified those that would be eligible for switching to partial oral antibiotic treatment as defined in the POET trial (e.g. stable clinical condition without signs of infection). Secondary objectives were to provide insight into the time until each patient was eligible for partial oral treatment, and to determine parameters of longer hospital stay and/or need for extended intravenous antibiotic treatment. RESULTS: Applying the POET selection criteria, the condition of 38 patients (32%) was stable enough to switch them to partial oral treatment, of which 18 (47.3%), 8 (21.1%), 9 (23.7%) and 3 patients (7.9%) were eligible for switching after 10, 14, 21 days or 28 days of intravenous treatment, respectively. CONCLUSION: One-third of patients who presented with left-sided endocarditis in routine clinical practice were possible candidates for switching to partial oral treatment. This could have major implications for both the patient's quality of life and healthcare costs. These results offer an interesting perspective for implementation of such a strategy, which should be accompanied by a prospective cost-effectiveness analysis.

6.
Neth Heart J ; 29(5): 288-294, 2021 May.
Article En | MEDLINE | ID: mdl-33201485

BACKGROUND: The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established. AIM: The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice. METHODS: Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment. DISCUSSION: Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.

7.
Neth Heart J ; 28(7-8): 387-390, 2020 Jul.
Article En | MEDLINE | ID: mdl-32676982

The ongoing coronavirus disease 2019 (COVID-19) crisis is having a large impact on acute and chronic cardiac care. Due to public health measures and the reorganisation of outpatient cardiac care, traditional centre-based cardiac rehabilitation is currently almost impossible. In addition, public health measures are having a potentially negative impact on lifestyle behaviour and general well-being. Therefore, the Working Group of Cardiovascular Prevention and Rehabilitation of the Dutch Society of Cardiology has formulated practical recommendations for the provision of cardiac rehabilitation during the COVID-19 pandemic, by using telerehabilitation programmes without face-to-face contact based on current guidelines supplemented with new insights and experiences.

8.
Neth Heart J ; 28(2): 89-95, 2020 Feb.
Article En | MEDLINE | ID: mdl-31953775

AIM: To determine the feasibility and potential benefit of a full cardiac magnetic resonance (CMR) work-up for assessing the location of scarred myocardium and the region of latest contraction (LCR) in patients with ischaemic cardiomyopathy (ICM) undergoing cardiac resynchronisation therapy (CRT). METHODS: In 30 patients, scar identification and contraction timing analysis was retrospectively performed on CMR images. Fluoroscopic left ventricular (LV) lead positions were scored with respect to scar location, and when placed outside scar, with respect to the LCR. The association between the lead position with respect to scar, the LCR and echocardiographic LV end-systolic volume (LVESV) reduction was subsequently evaluated. RESULTS: The CMR work-up was feasible in all but one patient, in whom image quality was poor. Scar and contraction timing data were succesfully displayed on 36-segment cardiac bullseye plots. Patients with leads placed outside scar had larger LVESV reduction (-21 ± 21%, n = 19) compared to patients with leads within scar (1 ± 25%, n = 11), yet total scar burden was higher in the latter group. There was a trend towards larger LVESV reduction in patients with leads in the scar-free LCR, compared to leads situated in scar-free segments but not in the LCR (-34 ± 14% vs -15 ± 21%, p = 0.06). CONCLUSIONS: The degree of reverse remodelling was larger in patients with leads situated in a scar-free LCR. In patients with leads situated within scar there was a neutral effect on reverse remodelling, which can be caused both by higher scar burden or lead position. These findings demonstrate the feasibility of a CMR work-up and potential benefit in ICM patients undergoing CRT.

9.
Neth Heart J ; 27(11): 559-564, 2019 Nov.
Article En | MEDLINE | ID: mdl-31359321

INTRODUCTION: Rheumatic mitral stenosis continues to be prevalent in developing countries, notably in endemic areas. Over the last few decades, percutaneous balloon mitral valvuloplasty (PBMV) has been established as a lower-cost alternative treatment for mitral stenosis (MS) in low-to-middle-income countries. PBMV has also been suggested to be an effective and safe alternative treatment modality. This study aims to analyse the survival of rheumatic MS patients treated with PBMV compared with those treated with mitral valve surgery (MVS). METHODS: This study was a national, single-centre, longitudinal study using a survival analysis method in 329 consecutive patients suffering from rheumatic heart disease with severe MS who underwent PBMV compared with 142 consecutive patients with similar characteristics who underwent MVS between January 2011 and December 2016. Survival analysis and event-free duration were determined over a median follow-up of 24 months in the PBMV group and 27 months in the MVS group. RESULTS: The results showed that of the 329 consecutive patients in the PBMV group, 61 patients (18.5) had an event (6 patients died and 55 patients were hospitalised), and of the 142 consecutive patients in the MVS group, 19 patients (13.4%) had an event (5 patients died, and 14 patients were hospitalised). The hazard ratio was 0.631 (95% confidence interval, 0.376-1.058; P = 0.081). Longer short-term survival was found in the MVS group but was not statistically significant. Event-free survival was significantly longer in the MVS group (P = 0.002), by 5 months. CONCLUSIONS: In this study, the efficacy and safety of PBMV was reconfirmed, as PBMV proved to be non-inferior to MVS in survival prognosis, but sustained event-free duration was significantly better in the MVS group than in the PBMV group.

10.
Neth Heart J ; 26(11): 552-561, 2018 Nov.
Article En | MEDLINE | ID: mdl-30276525

BACKGROUND: In patients with mild to moderate functional tricuspid regurgitation (TR) and absence of right ventricular dysfunction or tricuspid annulus (TA) dilatation, there is currently no indication for concomitant tricuspid valve (TV) repair during elective mitral valve (MV) surgery. However, long-term results are conflicting. Here, we sought to determine the clinical outcome of this cohort, the rate of TR progression after MV surgery and the role of MV aetiology. METHODS: Patients for elective MV surgery without concomitant TV repair were retrospectively analysed with longitudinal echocardiographic and clinical follow-up, focusing on TR progression and MV aetiology. Linear regression analysis was performed for change in TR at follow-up, using pre-determined variables and confounders. RESULTS: In total 204 patients without TV repair were analysed. Development of more than moderate TR after a median of 3.1 [1.6-4.6] years was rarely seen: only in 2 out of 161 patients (1.2%) with known TR grade at follow-up. Overall, median preoperative and late postoperative TR grade were equal (p = 0.116). Subanalysis showed no significant difference in MV aetiology subgroups. Preoperative TR grade and male gender were inversely correlated to change in TR. Mortality was not influenced by the 1­year postoperative TR severity. CONCLUSION: Our data showed that in a study population of patients with mild to moderate TR undergoing MV surgery without concomitant TV repair, significant late TR was rarely seen. Based on our study, it is safe to waive concomitant TV repair in this specific patient cohort.

11.
Neth Heart J ; 26(11): 521-532, 2018 Nov.
Article En | MEDLINE | ID: mdl-30141030

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients. Progression to overt heart failure carries a strikingly poor prognosis with a 2-year mortality rate of 60%. Early detection of left ventricular damage by periodic monitoring and prompt initiation of heart failure treatment is key in improving cardiovascular prognosis. To meet the growing demand for a specialised interdisciplinary approach for the prevention and management of cardiovascular complications induced by cancer treatment, a new discipline termed cardio-oncology has evolved. However, an uniform, multidisciplinary approach is currently lacking in the Netherlands. This overview provides an introduction and comprehensive summary of this emerging discipline and offers a practical strategy for the outpatient management of this specific patient population.

12.
Cardiovasc Ultrasound ; 16(1): 6, 2018 Mar 27.
Article En | MEDLINE | ID: mdl-29580287

BACKGROUND: Stress echocardiography (SE) has recently regained momentum as an important diagnostic tool for the assessment of both ischemic and non-ischemic heart disease. Performing SE during physical exercise is challenging due to a suboptimal patient position and vigorous movements of the patient's chest. This hampers a stable ultrasound position and reduces the diagnostic performance of SE. A stable ultrasound probe position would facilitate producing high quality images during continuous measurements. With Probefix (Usono, Eindhoven, The Netherlands), a newly developed tool to fixate the ultrasound probe to the patient's chest, stabilization of the probe during physical exercise is possible. IMPLEMENTATION AND RESULTS: The technique of SE with the Probefix and its' feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound probe to the patient's chest, using two chest straps and a fixation device. The ultrasound probe position and angle may be altered with a relative high degree of freedom. We tested the Probefix for continuous echocardiographic imaging in 12 study subjects during supine and upright ergometer stress tests. One patient was unable to perform exercise and in two study subjects good quality images were not achieved. In the other patients (82%) a stable probe position was obtained, with subsequent good quality echocardiographic images during SE. CONCLUSION: We have demonstrated the feasibility of the Probefix support during ergometer tests in supine and upright positions and conclude that this external fixator may facilitate continuous monitoring of cardiac function in a group of patients.


Echocardiography, Stress/instrumentation , Exercise Test/instrumentation , Heart Valve Diseases/diagnostic imaging , Adult , Aged , Aged, 80 and over , Echocardiography, Stress/methods , Echocardiography, Stress/standards , Exercise Test/methods , Exercise Test/standards , Feasibility Studies , Female , Healthy Volunteers , Humans , Male , Middle Aged , Pilot Projects , Young Adult
13.
Int J Cardiovasc Imaging ; 34(8): 1193-1204, 2018 Aug.
Article En | MEDLINE | ID: mdl-29524077

The purpose of this study was to evaluate mitral regurgitation (MR) severity in patients undergoing transcatheter aortic valve replacement (TAVR) by standardized assessment of two-dimensional (2D) transthoracic echocardiography (TTE) and 1-year echocardiographic and clinical outcomes. Pre- and post-procedural TTE's of patients undergoing TAVR between 2008 and 2014 were analyzed. MR was graded according to current guidelines with a systematic and integrated approach. Longitudinal echocardiographic and clinical results were analyzed. Regression analysis was performed for change in MR grade at follow-up, using pre-determined variables and confounders. Pre- and post-procedural TTE were available in 213 subjects. Significant MR was seen in 22% at baseline and 15% at follow-up; MR grade ≥ 3 in < 10%. Severity did not change in 61%, and decreased in 20% of the patients. Overall, the prevalence of MR grades pre- and post TAVR was not significantly different, nor influenced by MR etiology or TAVR prosthesis type. However, higher MR grades and pacemaker absence at baseline, were independently correlated to more improvement of MR after TAVR. Regarding clinical outcomes, NYHA class improved in two-thirds of the patients, irrespective of the baseline MR grade. Overall survival was not significantly different amongst MR grades post-TAVR. MR grading using an systematic 2D echocardiographic approach in patients undergoing TAVR is feasible in clinical practice. Our data revealed a relatively frequent prevalence of significant MR (although grade ≥ 3 was scarce), overall no change in the MR grade at 1 year follow-up, improvement of functional NYHA class, and no significant differences in long-term survival amongst the post-TAVR MR grades.


Aortic Valve Stenosis/surgery , Mitral Valve Insufficiency/diagnostic imaging , Transcatheter Aortic Valve Replacement , Adult , Aged , Aged, 80 and over , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/diagnostic imaging , Echocardiography , Female , Humans , Male , Middle Aged , Mitral Valve Insufficiency/complications , Retrospective Studies
14.
Basic Res Cardiol ; 112(4): 46, 2017 07.
Article En | MEDLINE | ID: mdl-28624975

In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min. ECG, and left (LV) and right ventricular (RV) monophasic action potentials durations (MAPD) were recorded; activation time (AT) and activation recovery interval (ARI) were determined from ten distinct LV electrograms; interventricular mechanical delay (IVMD) and time-to-peak strain (TTP) of the LV septal and lateral wall (ΔTTP: lateral wall minus septal wall) were obtained echocardiographically. Dofetilide (25 µg/kg/5 min) was infused to study TdP inducibility. In baseline AAVB, in comparison to SR, RVA bradypacing acutely increased QT interval, LV, and RVMAPD. Echocardiographic IVMD and ΔTTP were initially increased, which was partially corrected after 3 weeks of RVA pacing (IVMD: 22 ± 13 vs. 42 ± 11 vs. 31 ± 6 ms; ΔTTP: -2 ± 47 vs. -114 ± 38 vs. -36 ± 22 ms). QT interval (362 ± 23 vs. 373 ± 29 ms), LVMAPD (245 ± 18 vs. 253 ± 22 ms), RVMAPD (226 ± 26 vs. 238 ± 31 ms), and mean LV-ARI (268 ± 5 vs. 267 ± 6 ms) were not significantly changed after 3 weeks of RVA pacing. During AAVB, dofetilide increased mean LV-ARI (381 ± 11 ms) with largest increases in the later activated basal areas (slope AT-ARI: +0.96). In contrast with acute RVA pacing, 3 week pacing increased TdP inducibility (0/13 vs. 11/21) and mean LV-ARI (484 ± 18 ms), while the slope of AT-ARI responded differently on dofetilide (-2.37), with larger APD increases in the early region. The latter was supported at the molecular level: reduced RNA expressions of three repolarization-related ion channel genes in early (KCNQ1, KCNH2, and KCNJ2) versus two in late regions (KNCQ1 and KCNJ2). In conclusion, bradycardic RVA pacing acutely induced LV intra- and interventricular mechanical dyssynchrony, which was partially reversed after 3 weeks of pacing (remodeling). The latter occurred without apparent baseline electrical effects. However, dofetilide clearly unmasked (region-specific) arrhythmic consequences of remodeling.


Arrhythmias, Cardiac/physiopathology , Bradycardia/physiopathology , Cardiac Pacing, Artificial/adverse effects , Heart Ventricles/physiopathology , Ventricular Remodeling/physiology , Animals , Dogs , Torsades de Pointes
15.
Maturitas ; 105: 37-45, 2017 Nov.
Article En | MEDLINE | ID: mdl-28583397

The number of cancer survivors has tremendously increased over the past decades as a result of aging of the population and improvements in early cancer detection and treatment. Ongoing successes in cancer treatment are expected to result in a further increase in the number of long-term survivors. However, cancer treatment can have detrimental cardiovascular side-effects that impact morbidity and mortality, reducing quality of life in cancer survivors. The spectrum of radiotherapy- and chemotherapy-induced cardiovascular disease is broad, varying from subclinical valvular dysfunction to overt congestive heart failure, and such effects may not be apparent for more than twenty years after the initial cancer treatment. Awareness of these long-term side-effects is of crucial value in the management of these patients, in order to reduce the impact of cardiovascular morbidity and mortality. This review provides a comprehensive overview of the long-term cardiovascular complications of cancer treatments (radiotherapy and chemotherapy) in adult cancer survivors.


Cancer Survivors , Cardiovascular Diseases/etiology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Humans , Neoplasms/drug therapy , Neoplasms/radiotherapy
16.
Acta Physiol (Oxf) ; 220(3): 382-393, 2017 07.
Article En | MEDLINE | ID: mdl-28168814

AIM: Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. METHODS: Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF-kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed. RESULTS: Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure (MAP). CONCLUSION: Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 (AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five-drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney.


Cardio-Renal Syndrome/drug therapy , Cyclic N-Oxides/therapeutic use , Losartan/therapeutic use , Metoprolol/therapeutic use , Molsidomine/therapeutic use , Pyrrolidines/therapeutic use , Thiocarbamates/therapeutic use , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Coronary Vessels , Cyclic N-Oxides/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Therapy, Combination , Fibrosis , Heart/drug effects , Kidney/drug effects , Kidney Function Tests , Ligation , Losartan/pharmacology , Male , Metoprolol/pharmacology , Molsidomine/pharmacology , NF-kappa B/antagonists & inhibitors , Nephrectomy , Nitric Oxide Donors/pharmacology , Nitric Oxide Donors/therapeutic use , Pyrrolidines/pharmacology , Rats, Inbred Lew , Spin Labels , Sympatholytics/pharmacology , Sympatholytics/therapeutic use , Thiocarbamates/pharmacology
17.
Neth Heart J ; 24(12): 740-747, 2016 Dec.
Article En | MEDLINE | ID: mdl-27580740

PURPOSE: With the increased use of genetic testing for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), this disease is being increasingly recognised among elderly patients. However, elderly ARVD/C patients were underrepresented in prior cohorts. We aimed to describe the phenotypical characteristics and outcomes among ARVD/C patients surviving ≥50 years. METHODS: We assessed detailed phenotypical data of 29 patients who (1) presented at ≥50 years of age; and (2) fulfilled 2010 Task Force Criteria (TFC) for ARVD/C by last follow-up. Primary outcome was the occurrence of a major ventricular arrhythmia (sudden cardiac death, resuscitated sudden cardiac arrest or sustained ventricular tachycardia). RESULTS: The majority (55 %) of elderly ARVD/C subjects were male, with a mean age of 59.0 ± 5.8 years at presentation. Study participants fulfilled a median of six (IQR 5-8) TFC criteria by last follow-up, of which arrhythmia criteria were most frequent (97 %), followed by structural criteria (83 %), depolarisation criteria (72 %) and repolarisation criteria (69 %). By last follow-up, 15 (52 %) patients had experienced major ventricular arrhythmias. Most patients (n = 12) presented with this arrhythmia, while three experienced the event during 5.4 ± 3.2 years of follow-up. Compared with patients without an arrhythmic event, patients with major arrhythmias were more likely to be proband (p < 0.001) and male (p = 0.042). Likewise, survival free from sustained ventricular arrhythmia was lower among probands and males. CONCLUSION: Phenotypic characteristics of elderly ARVD/C patients are characterised by depolarisation abnormalities and structural cardiac changes. Ventricular arrhythmias in this elderly cohort are associated with male gender and proband status.

18.
Int J Cardiol ; 221: 1061-6, 2016 Oct 15.
Article En | MEDLINE | ID: mdl-27448533

Delays in patients suspected of acute coronary syndrome (ACS) should be kept as short as possible to reduce complications and mortality. In this review we discuss the substantial pre-hospital delays of ST-elevated myocardial infarction (STEMI) patients as well as non-STEMI patients. The pre-hospital delays include patient, doctor and emergency medical transport (EMT) delay. Patient delay is among the longest in the pre-hospital chain of ACS patients. Interventions as mass media campaigns or individual education programs have not yet shown much improvement. Patients with chest pain most often contact the general practitioner (GP) instead of the recommended EMT, increasing delays as well. To decrease the delays by referring all patients promptly and without restriction to the emergency department (ED) is not feasible. Up to 80% of the patients with chest pain do not have a cardiac diagnosis and thus referral of all these patients would result in overcrowding of the ED. Triage is therefore crucial. Triage of patients with chest pain is therefore imperative and there is a great need of (validated) triage tools.


Delayed Diagnosis/prevention & control , Emergency Medical Services , Non-ST Elevated Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/therapy , Triage/organization & administration , Emergency Medical Services/methods , Emergency Medical Services/standards , Humans
20.
Neth Heart J ; 24(4): 237-43, 2016 Apr.
Article En | MEDLINE | ID: mdl-26905581

Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes.

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