Clinical translation of the assets of biomedical engineering - a retrospective analysis with looks to the future.

Introduction: Biomedical-engineering (BME) plays a major role in modern medicine. Many BME-based assets have been brought to clinical translation in the twentieth century, but translation currently stagnates. Here, we compare the impact of past and present scientific, economic and societal climates on the translation of BME-based assets, in order to provide the BME-community with incentives to address current stagnation.Areas covered: In the twentieth century, W.J. Kolff brought kidney dialysis, the total artificial heart, artificial vision and limbs to clinical application. This success raises the question whether Kolff and other past giants of clinical translation had special mind-sets, or whether their problem selection, their training, or governmental and regulatory control played roles. Retrospective analysis divides the impact of BME-based assets to clinical application into three periods: 1900-1970: rapid translation from bench-to-bedside, 1970-1990: new diseases and increased governmental control, and the current translational crisis from 1990 onward.Expert opinion: Academic and societal changes can be discerned that are concurrent with BME's translational success: mono-disciplinary versus multi-disciplinary training, academic reward systems based on individual achievements versus team achievements with strong leadership, increased governmental and regulatory control, and industrial involvement. From this, recommendations can be derived for accelerating clinical translation of BME-assets.

Effect of cardiac resynchronization therapy on endothelium-dependent vasodilatation in the cutaneous microvasculature.

AIMS: Cardiac resynchronization therapy (CRT) improves hemodynamic parameters, exercise capacity, symptoms, functional status, and prognosis among patients with chronic heart failure (CHF). The role of the vascular endothelium in these improvements is largely unknown. In this study, we aimed to investigate whether the endothelium-dependent reactivity of the peripheral microcirculation improves in CHF patients during the first 2 months of CRT. METHODS: We used local heating and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to measure endothelial function and smooth muscle function in the cutaneous microvasculature of 11 CHF patients before and 2 months after CRT. RESULTS: We found that the perfusion response in the skin to local heating was increased 2 months post-CRT compared with baseline, both in terms of maximum perfusion (baseline: 113 [90-137] vs 2-months post-CRT: 137 [98-175], P=0.037) and area under curve (baseline: 1,601 [935-2,268] vs 2-months CRT: 2,205 [1,654-2,757], P=0.047). Also, the perfusion response to iontophoresis of ACh was improved (Emax: 23.9 [20.6-26.2]vs at 2-months CRT: 31.2 [29.3-33.4], P=0.005). No difference was found between the responses to SNP before and after CRT. CONCLUSION: These results show that CRT improves endothelium-dependent vasodilatory capacity in the peripheral microcirculation within 2 months of therapy. The improvement in functional capacity that is seen in patients treated with CRT may, therefore, be in part mediated by an improvement of endothelium-dependent vasodilatory capacity.

Health status in patients treated with cardiac resynchronization therapy: modulating effects of personality.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising treatment in chronic heart failure (CHF). However, a subgroup of patients still report impaired health status, cardiac symptoms, and feelings of disability following CRT. The aims of this study were to examine (1) whether CHF patients treated with CRT improved in patient-centered outcomes and functional capacity, and (2) whether personality traits exert a stable effect on these outcomes over two months. METHODS: Analyses are based on 31 patients (65% male; mean age 70 +/- 8) with CHF treated with CRT. Two weeks before and two months after CRT, patients completed the Type-D Scale (negative affectivity, i.e., tendency to experience negative emotions, and social inhibition, i.e., tendency to inhibit self-expression), the Minnesota Living with Heart Failure Questionnaire (disease-specific health status), and the Health Complaints Scale (cardiac symptoms and perceived disability), and performed the six-minute walking test (functional capacity). RESULTS: There was an improvement in disease-specific health status (P< 0.001), cardiac symptoms (P = 0.001), perceived disability (P< 0.001), and functional capacity (P = 0.007) in all patients over two months. However, high negative affectivity patients reported significantly lower disease-specific health status (P = 0.046), and more cardiac symptoms (P = 0.035), and perceived disability (P = 0.015) as compared to low negative affectivity patients. There was no significant main effect for negative affectivity on functional capacity. High negative affectivity patients still reported lower disease-specific health status (P = 0.06) and significantly more perceived disability (P = 0.04) when adjusting for left ventricular ejection fraction, gender, and age. The effects of negative affectivity on patient-centered outcomes, as measured by Cohen's effect size index, were moderate to large. CONCLUSIONS: Patient-centered outcomes improved over a two-month period in patients treated with CRT, but negative affectivity exerted a stable, negative effect on health status, cardiac symptoms, and perceived disability. Personality traits should be taken into account when evaluating effects of CRT.

Type-D personality but not depression predicts severity of anxiety in heart failure patients at 1-year follow-up.

BACKGROUND: Chronic heart failure (CHF) is a debilitating condition associated with poor outcome, including increased anxiety. However, anxiety and its determinants have not yet been studied systematically in CHF. We examined whether type-D personality and depressive symptoms would predict clinically significant anxiety at 1-year follow-up. METHODS: Consecutive patients with systolic CHF (n=149; 79% men; mean age 66+/-8.6) completed the type-D Scale (DS14), the Beck Depression Inventory, and the Anxiety Sensitivity Index at baseline. A clinical interview (Hamilton Anxiety Rating Scale) was used to assess clinically significant anxiety at 1-year follow-up. RESULTS: At 12 months follow-up, 26% (9/35) of type-D patients had clinically significant anxiety versus only 6% (7/114) of the non type-Ds (p=0.001). In univariable analyses, type-D personality (OR=5.3; p=0.002) and anxiety sensitivity (OR=4.5; p=0.009), but not depressive symptoms (p=0.27) predicted clinically significant anxiety. Type-D remained an independent predictor of anxiety at 1 year (OR=5.7; p=0.01), controlling for depressive symptoms, anxiety sensitivity, socio-demographic and clinical variables. Adding type-D in a hierarchical logistic regression model, comprising standard and psychological risk factors, enhanced the level of prediction of clinically significant anxiety substantially (-2LL=75.16 chi(2)=26.46; p=0.009). CONCLUSIONS: Type-D personality, but not depressive symptoms predicted 1-year clinically significant anxiety. The type-D scale could be used to identify CHF patients at high risk of anxiety, as these patients may be at an increased risk of adverse prognosis and impaired quality of life.