BackgroundTakotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology.ObjectivesThis study analyzed altered cardiac hemodynamics during TTS to... Show moreBackgroundTakotsubo syndrome (TTS) is a reversible form of heart failure with incompletely understood pathophysiology.ObjectivesThis study analyzed altered cardiac hemodynamics during TTS to elucidate underlying disease mechanisms.MethodsLeft ventricular (LV) pressure–volume loops were recorded in 24 consecutive patients with TTS and a control population of 20 participants without cardiovascular diseases.ResultsTTS was associated with impaired LV contractility (end-systolic elastance 1.74 mm Hg/mL vs 2.35 mm Hg/mL [P = 0.024]; maximal rate of change in systolic pressure over time 1,533 mm Hg/s vs 1,763 mm Hg/s [P = 0.031]; end-systolic volume at a pressure of 150 mm Hg, 77.3 mL vs 46.4 mL [P = 0.002]); and a shortened systolic period (286 ms vs 343 ms [P < 0.001]). In response, the pressure–volume diagram was shifted rightward with significantly increased LV end-diastolic (P = 0.031) and end-systolic (P < 0.001) volumes, which preserved LV stroke volume (P = 0.370) despite a lower LV ejection fraction (P < 0.001). Diastolic function was characterized by prolonged active relaxation (relaxation constant 69.5 ms vs 45.9 ms [P < 0.001]; minimal rate of change in diastolic pressure –1,457 mm Hg/s vs –2,192 mm Hg/s [P < 0.001]), whereas diastolic stiffness (1/compliance) was not affected during TTS (end-diastolic volume at a pressure of 15 mm Hg, 96.7 mL vs 109.0 mL [P = 0.942]). Mechanical efficiency was significantly reduced in TTS (P < 0.001) considering reduced stroke work (P = 0.001), increased potential energy (P = 0.036), and a similar total pressure–volume area compared with that of control subjects (P = 0.357).ConclusionsTTS is characterized by reduced cardiac contractility, a shortened systolic period, inefficient energetics, and prolonged active relaxation but unaltered diastolic passive stiffness. These findings may suggest decreased phosphorylation of myofilament proteins, which represents a potential therapeutic target in TTS. (Optimized Characterization of Takotsubo Syndrome by Obtaining Pressure Volume Loops [OCTOPUS]; NCT03726528) Show less
Berboth, L.; Zirngast, B.; Manninger, M.; Steendijk, P.; Tschope, C.; Scherr, D.; ... ; Alogna, A. 2022
Lower body negative pressure (LBNP) is a tool to study compensatory mechanisms to central hypovolemia for decades. However, the underlying hemodynamic mechanisms were mostly assessed noninvasively... Show moreLower body negative pressure (LBNP) is a tool to study compensatory mechanisms to central hypovolemia for decades. However, the underlying hemodynamic mechanisms were mostly assessed noninvasively and remain unclear. We hypothesized that incremental LBNP reduces diastolic filling and thereby affects left ventricular (LV) diastolic suction (DS). Here, we investigated the impact of graded LBNP at three different levels of seal as well as during b-adrenergic stimulation by invasive pressure-volume (PV) analysis. Eight Landrace pigs were instrumented closed-chest for PV assessment. LBNP was applied at three consecutive locations: I) cranial, 10 cm below xiphoid process; II) medial, half-way between cranial and caudal; III) caudal, at the iliac spine. Level III was repeated under dobutamine infusion. At each level, baseline measurements were followed by application of incremental LBNP of -15, -30, and -45 mmHg. LBNP induced varying degrees of preload-dependent hemodynamic changes, with cranial LBNP inducing more pronounced effects than caudal. According to the Frank???Starling mechanism, graded LBNP progressively reduced LV stroke volume (LV SV) following a decrease in LV end-diastolic volume. Negative intraventricular minimal pressures were observed during dobutamine-infusion as well as higher levels of LBNP. Of note, incremental LV negative pressures were accompanied by increasing DS volumes, derived by extrapolating the volume at zero transmural pressure, the so-called equilibrium volume (V0), related to LV SV. In conclusion, graded preload reduction via LBNP shifts the PV loop to smaller volumes and end-systolic volume below V0, which induces negative LV pressures and increases LV suction. Accordingly, NEW & NOTEWORTHY This study examined the effects of incremental lower body negative pressure (LBNP) from -15 to -45 mmHg on hemodynamic regulation using invasive pressure-volume assessment in closed-chest pigs. Graded preload reduction via LBNP induces negative left ventricular (LV) pressures while increasing LV suction and thus allowing the ventricle to eject below the equilibrium volume at the end of systole. Accordingly, LBNP-induced central hypovolemia is associated with increased diastolic suction. Show less
Blankenstein, F.M. van; O’Sullivan, J.F.; Saab, N.; Steendijk, P. 2021
BackgroundTeaching is an important professional skill for physicians and providing feedback is an important part of teaching. Medical students can practice their feedback skills by giving each... Show moreBackgroundTeaching is an important professional skill for physicians and providing feedback is an important part of teaching. Medical students can practice their feedback skills by giving each other peer feedback. Therefore, we developed a peer feedback training in which students observed a peer that modelled the use of good feedback principles. Students then elaborated on the modelled feedback principles through peer discussion. This combination of peer modelling and discussing the modelled feedback principles was expected to enhance emulation of the feedback principles compared to (1) only peer modelling and (2) discussing the feedback principles without previous modelling.MethodsIn a quasi-experimental study design, 141 medical students were assigned randomly to three training conditions: peer modelling plus discussion (MD), non-peer modelled example (NM) or peer modelling without discussion (M). Before and after the training, they commented on papers written by peers. These comments served as a pre- and a post-measure of peer feedback. The comments were coded into different functions and aspects of the peer feedback. Non-parametrical Kruskall-Wallis tests were used to check for pre- and post-measure between-group differences in the functions and aspects.ResultsBefore the training, there were no significant between-group differences in feedback functions and aspects. After the training, the MD-condition gave significantly more positive peer feedback than the NM-condition. However, no other functions or aspects were significantly different between the three conditions, mainly because the within-group interquartile ranges were large.ConclusionsThe large interquartile ranges suggest that students differed substantially in the effort placed into giving peer feedback. Therefore, additional incentives may be needed to motivate students to give good feedback. Teachers could emphasise the utility value of peer feedback as an important professional skill and the importance of academic altruism and professional accountability in the peer feedback process. Such incentives may convince more students to put more effort into giving peer feedback. Show less
Blankenstein, F.M. van; O'Sullivan, J.F.; Saab, N.; Steendijk, P. 2021
Background Teaching is an important professional skill for physicians and providing feedback is an important part of teaching. Medical students can practice their feedback skills by giving each... Show moreBackground Teaching is an important professional skill for physicians and providing feedback is an important part of teaching. Medical students can practice their feedback skills by giving each other peer feedback. Therefore, we developed a peer feedback training in which students observed a peer that modelled the use of good feedback principles. Students then elaborated on the modelled feedback principles through peer discussion. This combination of peer modelling and discussing the modelled feedback principles was expected to enhance emulation of the feedback principles compared to (1) only peer modelling and (2) discussing the feedback principles without previous modelling. Methods In a quasi-experimental study design, 141 medical students were assigned randomly to three training conditions: peer modelling plus discussion (MD), non-peer modelled example (NM) or peer modelling without discussion (M). Before and after the training, they commented on papers written by peers. These comments served as a pre- and a post-measure of peer feedback. The comments were coded into different functions and aspects of the peer feedback. Non-parametrical Kruskall-Wallis tests were used to check for pre- and post-measure between-group differences in the functions and aspects. Results Before the training, there were no significant between-group differences in feedback functions and aspects. After the training, the MD-condition gave significantly more positive peer feedback than the NM-condition. However, no other functions or aspects were significantly different between the three conditions, mainly because the within-group interquartile ranges were large. Conclusions The large interquartile ranges suggest that students differed substantially in the effort placed into giving peer feedback. Therefore, additional incentives may be needed to motivate students to give good feedback. Teachers could emphasise the utility value of peer feedback as an important professional skill and the importance of academic altruism and professional accountability in the peer feedback process. Such incentives may convince more students to put more effort into giving peer feedback. Show less
Aims Failure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by... Show moreAims Failure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by the ratio of RV end-systolic to PA elastances (Ees/Ea). Using pressure-volume loop (PV-L) technique we aimed to identify an Ees/Ea cut-off predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to heart failure with reduced ejection fraction (HFREF).Methods and results This post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography and a baseline PV-L and RV catheter measurement. A subgroup of patients (n = 50) without a pre-implanted cardiac device underwent magnetic resonance imaging at baseline. The analysis revealed that 0.68 is an optimal Ees/Ea cut-off (area under the curve: 0.697, P < 0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea >= 0.68 vs. <0.68, log-rank 8.9, P = 0.003). In patients with PH (n = 76, 68%) multivariate Cox regression demonstrated the independent prognostic value of RV-Ees/Ea in PH patients (hazard ratio 0.2, P < 0.038). Patients without PH (n = 36, 32%) and those with PH but RV-Ees/Ea >= 0.68 showed comparable RV-Ees/Ea ratios (0.88 vs. 0.9, P = 0.39), RV size/function, and survival. In contrast, secondary PH with RV-PA coupling ratio Ees/Ea < 0.68 corresponded extremely close to cut-off values that define RV dilatation/remodelling (RV end-diastolic volume >160 mL, RV-mass/volume-ratio <= 0.37 g/mL) and dysfunction (right ventricular ejection fraction <38%, tricuspid annular plane systolic excursion <16 mm, fractional area change <42%, and stroke-volume/end-systolic volume ratio <0.59) and is associated with a dramatically increased short and medium-term all-cause mortality. Independent predictors of prognostically unfavourable RV-PA coupling (Ees/Ea < 0.68) in secondary PH were a pre-existent dilated RV [end-diastolic volume >171 mL, odds ratio (OR) 0.96, P = 0.021], high pulsatile load (PA compliance <2.3 mL/mmHg, OR 8.6, P = 0.003), and advanced systolic left heart failure (left ventricular ejection fraction <30%, OR 1.23, P = 0.028).Conclusions The RV-PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodelling, and left ventricular dysfunction. Prognostically favourable coupling (RV-Ees/Ea >= 0.68) in PH was associated with preserved RV size/function and mid-term survival, comparable with HFREF without PH. Show less
Background Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial... Show moreBackground Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia (TEA) was previously shown to reduce right and left ventricular systolic function and effective pulmonary arterial elastance. At conditions of constant paced heart rate, cardiac output and systemic hemodynamics were unchanged. In this study, we further investigated the effect of cardiac sympathicolysis during physical stress and increased oxygen demand.Methods In a cross-over design, 12 patients scheduled to undergo thoracic surgery performed dynamic ergometric exercise tests with and without TEA. Hemodynamics were monitored and biventricular function was measured by transthoracic two-dimensional and M-mode echocardiography, pulsed wave Doppler and tissue Doppler imaging.Results TEA attenuated systolic RV function (TV SMODIFIER LETTER PRIME: - 21%, P < 0.001) and LV function (MV SMODIFIER LETTER PRIME: - 14%, P = 0.025), but biventricular diastolic function was not affected. HR (- 11%, P < 0.001), SVI (- 15%, P = 0.006), CI (- 21%, P < 0.001) and MAP (- 12%, P < 0.001) were decreased during TEA, but SVR was not affected. Exercise resulted in significant augmentation of systolic and diastolic biventricular function. During exercise HR, SVI, CI and MAP increased (respectively, + 86%, + 19%, + 124% and + 17%, all P < 0.001), whereas SVR decreased (- 49%, P < 0.001). No significant interactions between exercise and TEA were found, except for RPP (P = 0.024) and MV E DT (P = 0.035).Conclusion Cardiac sympathetic blockade by TEA reduced LV and RV systolic function but did not significantly blunt exercise-induced increases in LV and RV function. These data indicate that additional mechanisms besides those controlled by the cardiac sympathetic nervous system are involved in the regulation of cardiac function during dynamic exercise. Show less
Versteeg, M.; Bressers, G.; Wijnen-Meijer, M.; Ommering, B.W.C.; Beaufort, A.J. de; Steendijk, P. 2021
PhenomenonAs a component of self-regulated learning, metacognition is gaining attention in the medical education research community. Metacognition, simply put, is thinking about one's thinking.... Show morePhenomenonAs a component of self-regulated learning, metacognition is gaining attention in the medical education research community. Metacognition, simply put, is thinking about one's thinking. Having a metacognitive habit of mind is essential for healthcare professionals. This study identified the metacognitive competencies of medical students as they completed a conceptual learning task, and provided insight into students' perceptions of self-regulated learning in their curriculum. Approach: Eleven third-year medical students from a Dutch University were purposively sampled to participate in this qualitative study. The study design included a think-aloud assignment followed by a semi-structured interview. During the assignment, participants were instructed to think aloud while solving questions about medical physiological concepts such as blood flow, pressure, and resistance. Think-aloud data were collected through audiotaping and used to identify participants' metacognitive competencies. The assignment also served as a prompt for an interview in which participants were questioned about metacognitive knowledge, monitoring, experiences, and perceptions of self-regulated learning in their curriculum. All data were transcribed verbatim and analyzed iteratively using a template analysis. Findings: Students differed in their use of metacognitive skills, with an overall focus on monitoring and, to a lesser extent, on planning and evaluation. Additionally, differences were found in students' metacognitive knowledge and metacognitive experiences. There was apparent use of inefficient, superficial predictive cues. Regarding perceptions of self-regulated learning skills, some students felt no need to develop such skills as they perceived medical education as an exercise in memorizing facts. Others emphasized the need for more insight into their actual level of knowledge and competence. Insights: Pre-clinical medical students require explicit teaching of metacognitive skills to facilitate self-regulated learning. Educators should aim to integrate metacognition in the everyday discourse of the classroom to foster an environment in which students discuss their own learning.Supplemental data for this article is available online at . Show less
Aims The aim of this study was to validate the tricuspid annular plane systolic excursion/systolic pulmonary artery (PA) pressure (TAPSE/PASP) ratio with the invasive pressure-volume (PV) loop... Show moreAims The aim of this study was to validate the tricuspid annular plane systolic excursion/systolic pulmonary artery (PA) pressure (TAPSE/PASP) ratio with the invasive pressure-volume (PV) loop-derived end-systolic right ventricular (RV) elastance/PA elastance (Ees/Ea) ratio in patients with heart failure with reduced ejection fraction (HFREF) and secondary pulmonary hypertension (PH).Methods and results The relationship of TAPSE and TAPSE/PASP with RV-PV loop (single-beat)-derived contractility Ees, afterload Ea, and Ees/Ea was assessed in 110 patients with HFREF with and without secondary PH. The results were compared with other surrogate parameters such as the fractional area change/PASP ratio. The association of the surrogates with all-cause mortality was evaluated. In patients with PH (n=74, 67%), TAPSE significantly correlated with Ees (r = 0.356), inverse with Ea (r = -0.514) but was most closely associated with Ees/Ea (r = 0.77). Placing TAPSE in a ratio with PASP slightly reduced the relationship to Ees/Ea (r = 0.71) but was more closely related to the parameters of PA vascular Load, diastolic RV function, and RV energetics. The area under the curve of TAPSE/PASP and TAPSE for discriminating overall survival in receiver operating characteristic analysis was not different (P = 0.78. Prognostic relevant cut-offs were 17mm for TAPSE and 0.38 mmimmHg for TAPSE/PASP. Both parameters in multivariate cox regression remained independently prognostically relevant.Conclusion TAPSE is an easily and reliably obtainable and valid surrogate parameter for RV-PA coupling in PH due to HFREF. Putting TAPSE into a ratio with PASP did not further improve the coupling information or prognostic assessment. Show less
Versteeg, M.; Hafkemeijer, A.; Beaufort, A.J. de; Steendijk, P. 2020
Obtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in... Show moreObtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in the brain. Therefore, misconceptions must be cognitively inhibited in order to select the scientific knowledge. There is, however, lack of substantial neuroscientific evidence supporting this hypothesis. In this study, we sought for this evidence by investigating medical students who solved a cardiovascular conceptual problem in a magnetic resonance imaging scanner. Brain activation was compared between understanders who had the scientific knowledge, and misunderstanders who held a misconception. No significant activation was found in brain areas related to cognitive inhibition in understanders compared with misunderstanders. Therefore, we could not confirm the idea that cognitive inhibition is involved in overcoming a misconception. Instead, we found that the putamen was significantly activated in misunderstanders compared with understanders, suggesting a role for episodic memory in learners holding a misconception. Show less
Versteeg, M.; Hafkemeijer, A.; Beaufort, A.J. de; Steendijk, P. 2020
Obtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in... Show moreObtaining adequate understanding of scientific concepts is considered challenging due to learners' misconceptions about natural phenomena. Misconceptions may coexist with scientific knowledge in the brain. Therefore, misconceptions must be cognitively inhibited in order to select the scientific knowledge. There is, however, lack of substantial neuroscientific evidence supporting this hypothesis. In this study, we sought for this evidence by investigating medical students who solved a cardiovascular conceptual problem in a magnetic resonance imaging scanner. Brain activation was compared between understanders who had the scientific knowledge, and misunderstanders who held a misconception. No significant activation was found in brain areas related to cognitive inhibition in understanders compared with misunderstanders. Therefore, we could not confirm the idea that cognitive inhibition is involved in overcoming a misconception. Instead, we found that the putamen was significantly activated in misunderstanders compared with understanders, suggesting a role for episodic memory in learners holding a misconception. Show less
Timmer, M.C.J.; Steendijk, P.; Arend, S.M.; Versteeg, M. 2020
IntroductionPoor knowledge retention is a persistent problem among medical students. This challenging issue may be addressed by optimizing frequently used instructional designs, such as lectures.... Show moreIntroductionPoor knowledge retention is a persistent problem among medical students. This challenging issue may be addressed by optimizing frequently used instructional designs, such as lectures. Guided by neuroscientific literature, we designed a spaced learning lecture in which the educator repeats the to-be-learned information using short temporal intervals. We investigated if this modified instructional design could enhance students' retention.Materials and MethodsSecond-year medical students (n = 148) were randomly allocated to either the spaced lecture or the traditional lecture. The spaced lecture consisted of three 15-min instructional periods, separated by 5-min intervals. A short summary of the preceding information was provided after each interval. The traditional lecture encompassed the same information including the summary in the massed format, thus without the intervals. All students performed a baseline knowledge test 2 weeks prior to the lectures and students' knowledge retention was assessed 8 days after the lectures.ResultsThe average score on the retention test (alpha = 0.74) was not significantly different between the spaced lecture group (33.8% 13.6%) and the traditional lecture group (31.8% +/- 12.9%) after controlling for students' baseline-test performance (F(1,104) = 0.566, p = 0.458). Students' narrative comments showed that the spaced lecture format was well-received and subjectively benefitted their attention-span and cognitive engagement.Discussion and Conclusion We were unable to show increased knowledge retention after the spaced lecture compared with the traditional lecture. Based on these findings, we provide recommendations for further research. Ultimately, we aim for optimized spaced learning designs to facilitate learning in the medical curriculum and to help educate health professionals with a solid knowledge base. Show less
Versteeg, M.; Loon, M.H. van; Wijnen-Meijer, M.; Steendijk, P. 2020
BackgroundIn medical physiology, educators and students face a serious challenge termed misconceptions. Misconceptions are incorrect ideas that do not match current scientific views. Accordingly,... Show moreBackgroundIn medical physiology, educators and students face a serious challenge termed misconceptions. Misconceptions are incorrect ideas that do not match current scientific views. Accordingly, they have shown to hamper teaching and learning of physiological concepts. Conceptual Change Theory forms the basis of new teaching and learning practices that may alleviate misconceptions and facilitate critical thinking skills that are essential in becoming knowledgeable, self-regulated health professionals. In this study, we examined if such an intervention named refutation texts, could enhance medical students' cognition and metacognition.MethodsFirst-year medical students (N=161) performed a pre-test and post-test on cardiovascular physiology concepts, including a self-perceived confidence rating. In between, students read either a standard text with an explanation of the correct answer, or a refutation text which additionally refuted related misconceptions.ResultsIn both groups, average performance scores (refutation: +22.5%, standard: +22.8%) and overall confidence ratings (refutation: Delta 0.42 out of 5, standard: Delta 0.35 out of 5) increased significantly (all p<.001), but a significant effect of the specific refutation element was not found. Initially incorrect answers were corrected less frequently in cases of high confidence (35.8%) than low confidence (61.4%).ConclusionsOur results showed that refutation texts significantly increased students' knowledge, however, the refutation element did not have a significant additional effect. Furthermore, high confidence in incorrect answers negatively affected the likelihood of correction. These findings provide implications for teaching practices on concept learning, by showing that educators should take into account the key role of metacognition, and the nature of misconceptions. Show less
Reil, J.C.; Reil, G.H.; Kovacs, A.; Sequeira, V.; Waddingham, M.T.; Lodi, M.; ... ; Hamdani, N. 2020
Key pointsThe Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload... Show moreKey pointsThe Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload. As a result of the missing preload stretch in our model, the Anrep effect differs from the slow force response and has a different mechanism. The Anrep effect demonstrated two different phases. First, the sudden increased afterload was momentary equilibrated by the enhanced LV contractility as a result of higher power strokes of strongly-bound myosin cross-bridges. Second, the slightly delayed recovery of SV is perhaps dependent on Ca2+/calmodulin-dependent protein kinase II activation caused by oxidation and myofilament phosphorylation (cardiac myosin-binding protein-C, myosin light chain 2), maximizing the recruitment of available strongly-bound myosin cross-bridges. Short-lived oxidative stress might present a new facet of subcellular signalling with respect to cardiovascular regulation. Relevance for human physiology was demonstrated by echocardiography disclosing the Anrep effect in humans during handgrip exercise. The present study investigated whether oxidative stress and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity are involved in triggering the Anrep effect. LV pressure-volume (PV) analyses of isolated, preload controlled working hearts were performed at two afterload levels (60 and 100 mmHg) in C57BL/6N wild-type (WT) and CaMKII-double knockout mice (DKOCaMKII). In snap-frozen WT hearts, force-pCa relationship, H(2)O(2)generation, CaMKII oxidation and phosphorylation of myofilament and Ca(2+)handling proteins were assessed. Acutely raised afterload showed significantly increased wall stress, H(2)O(2)generation and LV contractility in the PV diagram with an initial decrease and recovery of stroke volume, whereas end-diastolic pressure and volume, as well as heart rate, remained constant. Afterload induced increase in LV contractility was blunted in DKOCaMKII-hearts. Force development of single WT cardiomyocytes was greater with elevated afterload at submaximal Ca(2+)concentration and associated with increases in CaMKII oxidation and phosphorylation of cardiac-myosin binding protein-C, myosin light chain and Ca(2+)handling proteins. CaMKII activity is involved in the regulation of the Anrep effect and associates with stimulation of oxidative stress, presumably starting a cascade of CaMKII oxidation with downstream phosphorylation of myofilament and Ca(2+)handling proteins. These mechanisms improve LV inotropy and preserve stroke volume within few seconds. Show less
Aims Restrictive mitral annuloplasty (RMA) can provide a durable solution for functional mitral regurgitation (MR), but might result in obstruction to antegrade mitral flow. Aim of this study was... Show moreAims Restrictive mitral annuloplasty (RMA) can provide a durable solution for functional mitral regurgitation (MR), but might result in obstruction to antegrade mitral flow. Aim of this study was to assess the magnitude of change in mitral valve area (MVA) during exercise after RMA, to relate the change in MVA to left ventricular (LV) geometry and function, and to assess its haemodynamic and clinical impact.Methods and results Bicycle exercise echocardiography was performed in 32 patients after RMA. Echocardiographic data at rest and am !sults during exercise were compared with preoperative echocardiographic data. Clinical endpoints were collected following the study visit. MVA increased during exercise in 25 patients (1.6 +/- 0.4 cm(2) to 2.0 +/- 0.6 cm(2), P < 0.001), whereas MVA decreased in 7 patients (1.8 +/- 0.5 cm(2) to 1.5 +/- 0.4 cm(2), P = 0.020). Patients with an increased MVA showed a significant reduction in LV volumes at rest compared to preoperatively, and an increase in stroke volume and cardiac output (CO) during exercise. In patients with decreased MVA, LV reverse remodelling was absent and myocardial flow reserve limited. Patients with decreased exercise MVA had a higher increase in mean pulmonary artery pressure (PAP) with respect to CO and worse survival 36 months after the study visit (69 +/- 19% vs. 92 +/- 5%, P= 0.005).Conclusions Both increased and decreased MVA were observed during exercise echocardiography after RMA for functional MR. Change in MVA was related to the extent of LV geometrical and functional changes. A decreased MVA during exercise was associated with a higher increase in mean PAP with respect to CO, and worse survival. Show less
Versteeg, M.; Hendriks, R.A.; Thomas, A.; Ommering, B.W.C.; Steendijk, P. 2020
Objectives To investigate the definitions and applications of 'spaced learning' and to propose future directions for advancing its study and practice in health professions education. Method The... Show moreObjectives To investigate the definitions and applications of 'spaced learning' and to propose future directions for advancing its study and practice in health professions education. Method The authors searched five online databases for articles published on spaced learning in health professions education prior to February 2018. Two researchers independently screened articles for eligibility with set inclusion criteria. They extracted and analysed key data using both quantitative and qualitative methods. Results Of the 2972 records retrieved, 120 articles were included in the review. More than 90% of these articles were published in the last 10 years. The definition of spaced learning varied widely and was often not theoretically grounded. Spaced learning was applied in distinct contexts, including online learning, simulation training and classroom settings. There was a large variety of spacing formats, ranging from dispersion of information or practice on a single day, to intervals lasting several months. Generally, spaced learning was implemented in practice or testing phases and rarely during teaching. Conclusions Spaced learning is infrequently and poorly defined in the health professions education literature. We propose a comprehensive definition of spaced learning and emphasise that detailed descriptions of spacing formats are needed in future research to facilitate the operationalisation of spaced learning research and practice in health professions education. Show less
Abawi, D.; Faragli, A.; Schwarzl, M.; Manninger, M.; Zweiker, D.; Kresoja, K.P.; ... ; Alogna, A. 2019
Background Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill... Show moreBackground Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min(- 1) is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min(- 1) under various inotropic states. Methods We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 +/- 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 degrees C, 38.0 degrees C and 40.5 degrees C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min(- 1) against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dt(max)). Results CPO showed the best correlation with LV SW min(- 1) (r(2) = 0.89; p < 0.05) while LV EF did not correlate at all (r(2) = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min(- 1) (LVP(max)r(2) = 0.47, RPP r(2) = 0.67; and TP r(2) = 0.54). LV dP/dt(max) correlated worst with LV SW min(- 1) (r(2) = 0.28). Conclusion CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU. Show less
BackgroundHypercholesterolemia is a major risk factor for ischemic heart disease including acute myocardial infarction. However, long-term effects of hypercholesterolemia in a rodent myocardial... Show moreBackgroundHypercholesterolemia is a major risk factor for ischemic heart disease including acute myocardial infarction. However, long-term effects of hypercholesterolemia in a rodent myocardial ischemia-reperfusion injury model are unknown. Therefore, the effects of diet-induced hypercholesterolemia on cardiac function and remodeling were investigated up to eight weeks after myocardial ischemia-reperfusion (MI-R) injury which was induced in either normocholesterolemic (NC-MI) or hypercholesterolemic (HC-MI) APOE*3-Leiden mice.MethodsLeft ventricular (LV) dimensions were serially assessed using parasternal long-axis echocardiography followed by LV pressure-volume measurements. Subsequently, infarct size and the inflammatory response were analyzed by histology and fluorescence-activated cell sorting (FACS) analysis.ResultsIntrinsic LV function eight weeks after MI-R was significantly impaired in HC-MI compared to NC-MI mice as assessed by end-systolic pressure, dP/dt(MAX), and -dP/dt(MIN). Paradoxically, infarct size was significantly decreased in HC-MI compared to NC-MI mice, accompanied by an increased wall thickness. Hypercholesterolemia caused a pre-ischemic peripheral monocytosis, in particular of Ly-6C(hi) monocytes whereas accumulation of macrophages in the ischemic-reperfused myocardium of HC-MI mice was decreased.ConclusionDiet-induced hypercholesterolemia caused impaired LV function eight weeks after MI-R injury despite a reduced post-ischemic infarct size. This was preceded by a pre-ischemic peripheral monocytosis, while there was a suppressed accumulation of inflammatory cells in the ischemic-reperfused myocardium after eight weeks. This experimental model using hypercholesterolemic APOE*3-Leiden mice exposed to MI-R seems suitable to study novel cardioprotective therapies in a more clinically relevant animal model. Show less
Alderliesten, T.; Bel, F. van; Aa, N.E. van der; Steendijk, P.; Haastert, I.C. van; Vries, L.S. de; ... ; Lemmers, P. 2019
Objective To assess whether high and low levels of cerebral oxygenation (regional cerebral oxygenation [rScO(2)]) in infants born at <32 weeks of gestation were associated with adverse long-term... Show moreObjective To assess whether high and low levels of cerebral oxygenation (regional cerebral oxygenation [rScO(2)]) in infants born at <32 weeks of gestation were associated with adverse long-term outcome.Study design Observational cohort study including preterm infants born at <32 weeks of gestation at the Wilhelmina Children's Hospital, The Netherlands, between April 2006 and April 2013. The rScO(2) was continuously monitored for 72 hours after birth using near-infrared spectroscopy. Outcome was assessed at 15 and 24 months of corrected age by certified investigators. An unfavorable composite outcome was defined as an outcome score below -1 SD or death. Various rScO(2) thresholds were explored.Results In total, 734 infants were eligible for analysis, 60 of whom died. Associations with an unfavorable cognitive outcome in multivariable analysis were comparable for time spent with a rScO(2) below 55% and -1.5 SD (according to published reference values), with an OR of 1.4 (CI 1.1-1.7) for 20% of time below either threshold. Results at 15 months were comparable with results at 24 months. Results were not statistically significant for thresholds defining high values of rScO(2). The composite motor outcome was not significantly related to either low or high values or rScO(2).Conclusions Low, but not high, rScO(2) was associated with an unfavorable cognitive outcome. This suggests the use of a threshold of rScO(2) <55% for future clinical studies when using adult near-infrared sensors (rScO(2) <65% for neonatal sensors, approximately). Show less
Versteeg, M.; Blankenstein, F.M. van; Putter, H.; Steendijk, P. 2019
