Els Vandecasteele

Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices

IntroductionPeripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients.MethodsThis was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010).ResultsSix PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II®, Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation.ConclusionsIn PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant.

Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing primary PCI: results from the Belgian STEMI registry

AIMS The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI). Here, we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI. METHODS AND RESULTS In-hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%] male patients) consecutive pPCI-treated STEMI patients, included in the prospective, observational Belgian STEMI registry (January 2007 to February 2011). A multivariable logistic regression model, including TIMI risk score variables and gender, evaluated differences in in-hospital mortality between men and women. The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration. Mortality rates for TIMI scores in women and men were compared. Female patients were older, had more comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1% in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, p<0.001). When adjusting for TIMI risk score variables, mortality remained higher in women (OR 1.47, 95% CI: 1.15-1.87, p=0.002). The TIMI risk score provided a good predictive discrimination and calibration in women as well as in men (c-statistic=0.84 [95% CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873-0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI scores was better in men (p=0.02 for TIMI score x gender interaction). CONCLUSIONS In the Belgian STEMI registry, pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables. The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men. The database was registered with clinicaltrials.gov (NCT00727623).

Antimicrobial prophylaxis in liver transplant patients – a multicenter survey endorsed by the European Liver and Intestine Transplant Association

Perioperative infections remain an important problem for patients undergoing liver transplantation (LT). For prevention of these infections, perioperative prophylaxis has become the standard procedure. Yet, either guidelines or data on current practice are lacking. The aim of the study was to gain insight into prophylactic antimicrobial strategies used in Europe. A survey questionnaire was sent out to all LT centers that are member of the European Liver and Intestine Transplant Association. In the survey questionnaire, we asked for details on the prophylactic antimicrobial regimen used in LT recipients. The response rate was 48%. Antibiotic prophylaxis for elective LT was provided by a first‐line betalactam antibiotic or co‐trimoxazole in 25%. Seventy‐three per cent of those centers surveyed gave an extended spectrum, and one center used a 6‐month rotation strategy. Antifungal prophylaxis was administered in 35% of centers in all LT recipients, in 53% of centers in patients at risk, and in 12% of centers not at all. Cytomegalovirus prophylaxis was never administered in 10%. In 12% of the centers surveyed, all the patients received cytomegalovirus prophylaxis, and another 78% of the centers gave it only to risk groups. In Europe, there is a considerable variation in the different antibiotic, antifungal and cytomegalovirus prophylactic strategies used for LT. These findings underscore the need for randomized controlled trials to determine the optimal prophylactic antimicrobial regimen.

The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review

INTRODUCTION Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by fibroproliferative vasculopathy, immunological abnormalities and progressive fibrosis of multiple organs including the skin. In this study, all English speaking articles concerning the role of endothelial cells (ECs) in SSc vasculopathy and representing biomarkers are systematically reviewed and categorized according to endothelial cell (EC) (dys)function in SSc. METHODS A sensitive search on behalf of the EULAR study group on microcirculation in Rheumatic Diseases was developed in Pubmed, The Cochrane Library and Web of Science to identify articles on SSc vasculopathy and the role of ECs using the following Mesh terms: (systemic sclerosis OR scleroderma) AND pathogenesis AND (endothelial cells OR marker). All selected papers were read and discussed by two independent reviewers. The selection process was based on title, abstract and full text level. Additionally, both reviewers further searched the reference lists of the articles selected for reading on full text level for supplementary papers. These additional articles went through the same selection process. RESULTS In total 193 resulting articles were selected and the identified biomarkers were categorized according to description of EC (dys)function in SSc. The most representing and reliable biomarkers described by the selected articles were adhesion molecules for EC activation, anti-endothelial cell antibodies for EC apoptosis, vascular endothelial growth factor (VEGF), its receptor VEGFR-2 and endostatin for disturbed angiogenesis, endothelial progenitors cells for defective vasculogenesis, endothelin-1 for disturbed vascular tone control, Von Willebrand factor for coagulopathy and interleukin (IL)-33 for EC-immune system communication. Emerging, relatively new discovered biomarkers described in the selected articles, are VEGF165b, IL-17A and the adipocytokines. Finally, myofibroblasts involved in tissue fibrosis in SSc can derive from ECs or epithelial cells through a process known as endothelial-to-mesenchymal transition. CONCLUSION This systematic review emphasizes the growing evidence that SSc is primarily a vascular disease where EC dysfunction is present and prominent in different aspects of cell survival (activation and apoptosis), angiogenesis and vasculogenesis and where disturbed interactions between ECs and various other cells contribute to SSc vasculopathy.

Severe infection, sepsis and acute kidney injury

Abstract Both severe infection and acute kidney injury (AKI) have a high, and rising incidence in critically ill patients admitted to the intensive care unit (ICU), and are associated with increased in-hospital mortality. Septic AKI patients are more severely ill compared to non-septic AKI patients and have worse outcome. Severe infection is a major cause of AKI in ICU patients, while conversely, AKI patients are at increased risk for infection. The dogma from the past relates the development of AKI in sepsis patients to decreased renal blood flow. However, current data suggest that there is no impairment of renal blood flow in patients with sepsis. The pathogenesis of AKI in sepsis is probably related to cyto-toxic effects of inflammation, and impaired microcirculation. In addition, hyperglycaemia, and antimicrobial agent-induced drug nephrotoxicity may contribute to the development of AKI. On the other hand, AKI patients are at greater risk for infection as a result of volume overload, dialysis catheter insertion and secondary manipulation, inflammation of the kidneys leading to ‘organ cross talk’, and impaired host immunity.

Stabilization of Microcirculation in Patients with Early Systemic Sclerosis with Diffuse Skin Involvement following Rituximab Treatment: An Open-label Study

To the Editor: Systemic sclerosis (SSc) is a multisystemic autoimmune disease characterized by fibrosis of the skin and internal organs, generalized microvasculopathy, and antibody response against various cellular antigens. Severe organ involvement occurs early in the course of diffuse cutaneous SSc (dcSSc) and has a bad prognosis1. Survival of the first years of the disease is associated with improved outcome. Therapies that may help the patient overcome this early period seem warranted2. Rituximab (RTX) has been reported as optional therapy in SSc3,4,5. Our group reported stabilization of internal organ involvement during a 2-year followup in an open pilot study of a 2–treatment course (months 0 and 6) of RTX in patients with early dcSSc6,7. In our pilot studies, modified Rodnan skin score (mRSS) decreased significantly after RTX course. The percent of decrease in the open pilot studies was corroborated by a similar decrease in the percentage of collagen score in blindly assessed histopathological skin analyses. Because SSc is characterized by a pronounced microangiopathy over time … Address correspondence to Dr. V. Smith, Department of Rheumatology, Ghent University Hospital, Faculty of Medicine and Health Sciences, Department of Internal Medicine, Ghent University, De Pintelaan 185, B – 9000 Ghent, Belgium. E-mail: vanessa.smith{at}ugent.be

Screening for pulmonary arterial hypertension in an unselected prospective systemic sclerosis cohort

Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. The DETECT screening algorithm is recommended in a high-risk SSc subgroup. This study aims to compare prospectively the positive predictive value of screening using the DETECT algorithm and the 2009 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines, and to compare their cost-effectiveness in an unselected, day-to-day SSc population. Post hoc, screening according to the 2015 ESC/ERS guidelines using echocardiographic parameters alone (“2015 echo screening”) or combined with the DETECT algorithm (“2015 combined screening”) in high-risk subjects was analysed. 195 consecutive SSc patients included in the Ghent University Hospital SSc cohort were screened using different algorithms. The referral rate for right heart catheterisation was 32% (63 out of 195 patients) (46/4/13/34/40 patients using the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). Right heart catheterisation was performed in 53 patients (84%) (36 (78%)/four (100%)/13 (100%)/28 (82%)/32 (80%) patients recommended by the DETECT algorithm/2009 guidelines/both/2015 echo screening/2015 combined screening). PAH was diagnosed in three patients (incidence 1.5%·year–1, 95% CI 0.5–4.4), in whom all algorithms recommended a right heart catheterisation. The positive predictive value was 6% (95% CI 2–17%; three out of 49 patients) for the DETECT algorithm, 18% (95% CI 6–41%; three out of 17 patients) for the 2009 guidelines, 23% (95% CI 8–50%; three out of 13 patients) for both, 11% (95% CI 4–27%; three out of 28 patients) for the 2015 echo screening and 9% (95% CI 3–24%; three out of 32 patients) for the 2015 combined screening. The cost was EUR224/80/90/112 per patient using the DETECT algorithm/2009 guidelines/2015 echo screening/2015 combined screening. Echocardiography may remain a candidate first step for PAH screening in SSc. Echocardiography remains a candidate first step in screening for PAH in an unselected systemic sclerosis population http://ow.ly/nuoh3096nRh

Two years follow-up of an open-label pilot study of treatment with rituximab in patients with early diffuse cutaneous systemic sclerosis

Abstract Objectives: Following results in open-label studies of rituximab in patients with systemic sclerosis, a Belgian three-centre initiative was launched to explore safety and efficacy of rituximab in early, diffuse cutaneous systemic sclerosis (dcSSc). Methods: Open-label study of 17 patients with early dcSSc, treated with two courses of rituximab, at month 0 and 6. Clinical examination, lung function testing, echocardiography, disease activity score (DAS) and functional status were performed at baseline and over 24 months of follow-up. Results: Modified Rodnan skin score (MRSS) changed significantly over time, with a mean of 25.5 (standard deviation [SD] 6.0) at baseline to 12.6 (SD 5.1) at month 24 (Mixed Model Analysis [MMA] p < 0.0001), which is a decrease of 51% at month 24 vs. baseline. DAS showed significant decrease over the total study period, with a score of 4.1 (SD 1.7) at baseline to 1.5 (SD 1.8) at month 24 (MMA p < 0.0001). Additionally, this was significant at all time points vs. baseline, both for MRSS and DAS. Internal organ status remained clinically stable throughout the study period. No statistically significant differences compared to baseline were found at the follow-up time points. Seven serious adverse events took place, all except for one, considered unrelated to study medication. Conclusions: This is the first multicentre Belgian collaboration investigating potential efficacy of rituximab in early dcSSc. Rituximab appears to be safe and tolerable and it may have beneficial effects on skin involvement, on overall disease activity and on stabilization of internal organ status in early dcSSc.

The heart and pulmonary arterial hypertension in systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials.

Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma

We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.