Sheep can be used as animal model of regional myocardial remodeling and controllable work

Background: Pacing the right heart has been shown to induce reversible conduction delay and subse­quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. Methods: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven­tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. Results: DDD pacing acutely induced a left bundle branch block (LBBB) — like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (–30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (–31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (–69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (–27% and -25%, respectively, p < 0.05). Conclusions: This study presents the development a new sheep model with an asymmetrically remod­eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling

Fontan failure associated with a restrictive systemic ventricle

publisher: Elsevier articletitle: Fontan failure associated with a restrictive systemic ventricle journaltitle: The Journal of Thoracic and Cardiovascular Surgery articlelink: http://dx.doi.org/10.1016/j.jtcvs.2017.02.016 content_type: article copyright: © 2017 by The American Association for Thoracic Surgerystatus: publishe

Validating the Concept of Mechanical Circulatory Support with a Rotary Blood Pump in the Inferior Vena Cava in an Ovine Fontan Model

Right-sided mechanical support of the Fontan circulation by existing devices has been compounded by the cross-sectional design of vena cava anastomosis to both pulmonary arteries. Our purpose was to investigate whether increasing inferior vena cava (IVC) flow with a rotary blood pump in the IVC only in an ovine animal model of Fontan would lead to acceptable superior vena cava (SVC) pressure. To achieve this, a Fontan circulation was established in four female sheep by anastomosing the SVC to the main pulmonary artery (MPA) and by interposing a Dacron graft between the IVC and the MPA. A rotary blood pump was then introduced in the graft, and the effect of incremental flows was observed at increasing flow regimen. Additionally, to stimulate increased pulmonary resistance, the experience was repeated in each animal with the placement of a restrictive band on the MPA distally to the SVC and Dacron graft anastomosis. Circulatory support of IVC flow alone increased the systemic cardiac output significantly, both with and without banding, indicating the feasibility of mechanical support of the Fontan circulation by increasing the flow only in the inferior vena cava. The increase in SVC pressure remained within acceptable limits, indicating the potential effectiveness of this mode of support. The findings suggest that increasing the flow only in the inferior vena cava is a feasible method for mechanical support of the Fontan circulation, potentially leading to an increase in cardiac output with acceptable increases in superior vena cava pressure

Creation of the Fontan circulation in sheep: a survival model

OBJECTIVES: Patients with a single ventricle survive thanks to the Fontan palliation. Nevertheless, there is a growing number of Fontan patients with progressive heart failure. To validate therapeutic options in these patients, we developed a chronic Fontan large animal model. METHODS: A Fontan circulation was surgically created in 15 sheep. The superior vena cava was anastomosed end-to-side to the pulmonary artery. The inferior vena cava was connected to the pulmonary artery by an ePTFE conduit, and the inferior vena cava-right atrium junction was ligated. RESULTS: Total cavopulmonary connection was successfully performed in all 15 animals. After creation of the Fontan circulation, central venous pressure increased from 4 [interquartile range (IQR) 3-6] mmHg to 16 (IQR 14-17) mmHg, mean arterial blood pressure decreased from 68 (IQR 54-75) mmHg to 52 (IQR 50-61) mmHg and cardiac output decreased from 5.1 (IQR 4.6-6.8) l/min to 1.7 (IQR 1.3-2.7) l/min. Five animals were electively sacrificed after a follow-up period of 21 weeks. CONCLUSIONS: These results demonstrate that it is feasible to create a chronic animal model with unsupported Fontan circulation. This animal model not only opens perspectives to investigate the pathophysiology of the failing Fontan circulation, but also provides the possibility to study therapeutic options such as the effect of mechanical circulatory support in the failing Fontan physiology.status: publishe

Exercise capacity in left ventricular assist device patients with full and partial support

In the present work, we investigated the exercise capacities of patients with partial flow left ventricular assist devices and its evolution over time. We then compared the exercise capacities of these patients with those of full support ventricular assist device patients.status: publishe

Assembly and testing of a wireless, battery powered epicardial accelerometer for contractility sensing

This work presents the assembly, biocompatible packaging and validation of a three-axis digital accelerometer to record the vibrations generated by the heart during its contraction. The device, designed to be stitched on the outer cardiac wall, is intended to provide information about heart contractility during acute and chronic in-vivo tests and could be used to monitor cardiac functionality in ischaemic patients. A dedicated system was developed (Fig.1) featuring a commercially available miniature three-axis accelerometer (BMA-280 Bosh Sensortec), a microcontroller with an integrated 433MHz wireless transceiver (CC430F5137, Texas Instruments) for data collection and transmission and a 64GBit flash memory (AT45db641e, Adesto) for data logging. The device is specifically designed for very low power consumption and is powered by a 3.3V coin cell battery with a capacity of 40mAh (cr1220, Panasonic). A tailored packaging technique was designed and implemented to minimize the immune response of the host organism while protecting the electronics from the aggressive body fluids. Two successive coatings were applied: a thin parylene-C layer was deposited by chemical vapour deposition and medical PDMS (NUSIL MED-6015) was moulded around the sensor. Three lobes in the PDMS package allow for stitching of the sensor on the cardiac muscle (Fig.2, Fig.3). The final device is 7mm thick and has a diameter of 24mm. The device was initially tested in-vitro for current leakage and water diffusion. Later, in-vivo performance was evaluated recording acceleration signals from different locations on the heart of a sheep during an acute test (Fig.4). Finally, the long term effects of the packaging strategy were investigated during a chronic experiment. Three sensors were implanted on different locations on the heart of a sheep and left in place for two months. At explantation, the sensors were nicely encapsulated in scar tissue making them adherent to the myocardium. No leakage of fluids in the sensors was observedstatus: publishe

Sheep can be used as animal model of regional myocardial remodelling and controllable work

A-V-sequential pacing has been shown to induce reversible conduction delay and subsequent asymmetric remodelling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore aim of this study focusses at developing a more feasible and easy-to-use animal model in sheep.status: Published onlin

A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data

OBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date. METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures. RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 ± 14.4 years, DPH diameter 24.4 ± 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 ± 0.6 years, the primary efficacy end points mean peak gradient (16.1 ± 12.1 mmHg) and regurgitation (mean 0.25 ± 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 ± 10.4 years, diameter 24.1 ± 4.2 mm, follow-up 5.1 ± 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 ± 2.1%, CH 84.4 ± 3.2%, P = 0.029 and BJV 82.7 ± 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 ± 6.6%, CH 39.9 ± 4.4%, n.s., BJV 47.5 ± 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH.Trial registration clinicaltrials.gov identifier: NCT02035540.status: publishe

Long-term outcomes of atrioventricular septal defect and single ventricle: A multicenter study.

The study objective was to analyze survival and incidence of Fontan completion of patients with single-ventricle and concomitant unbalanced atrioventricular septal defect. Data from 4 Dutch and 3 Belgian institutional databases were retrospectively collected. A total of 151 patients with single-ventricle atrioventricular septal defect were selected; 36 patients underwent an atrioventricular valve procedure (valve surgery group). End points were survival, incidence of Fontan completion, and freedom from atrioventricular valve reoperation. Median follow-up was 13.4 years. Cumulative survival was 71.2%, 70%, and 68.5% at 10, 15, and 20 years, respectively. An atrioventricular valve procedure was not a risk factor for mortality. Patients with moderate-severe or severe atrioventricular valve regurgitation at echocardiographic follow-up had a significantly worse 15-year survival (58.3%) compared with patients with no or mild regurgitation (89.2%) and patients with moderate regurgitation (88.6%) (P = .033). Cumulative incidence of Fontan completion was 56.5%, 71%, and 77.6% at 5, 10, and 15 years, respectively. An atrioventricular valve procedure was not associated with the incidence of Fontan completion. In the valve surgery group, freedom from atrioventricular valve reoperation was 85.7% at 1 year and 52.6% at 5 years. The long-term survival and incidence of Fontan completion in our study were better than previously described for patients with single-ventricle atrioventricular septal defect. A concomitant atrioventricular valve procedure did not increase the mortality rate or decrease the incidence of Fontan completion, whereas patients with moderate-severe or severe valve regurgitation at follow-up had a worse survival. Therefore, in patients with single-ventricle atrioventricular septal defect when atrioventricular valve regurgitation exceeds a moderate degree, the atrioventricular valve should be repaired

Prevalence of Insomnia and Sleep Habits during the First and Second Wave of COVID-19 in Belgium

Belgium has one of the highest numbers of COVID-19 cases per 1 million inhabitants. The pandemic has led to significant societal changes with repercussions on sleep and on mental health. We aimed to investigate the effect of the first and the second wave of COVID-19 on the sleep of the Belgian populationWe launched two online questionnaires, one during the first lockdown (7240 respondents) and one during the second (3240 respondents), to test differences in self-reported clinical insomnia (as measured by the Insomnia Severity Index) and sleep habits during the two lockdowns in comparison with the pre-COVID period. The number of persons with clinical insomnia rose during the first lockdown (19.22%) and further during the second (28.91%) in comparison with pre-lockdown (7.04–7.66%). Bed and rise times were delayed and there was an increased time in bed and sleep onset latency. There was further a decrease in total sleep time and in sleep efficiency during both confinements. The prevalence of clinical insomnia quadrupled during the second wave in comparison with the pre-lockdown situation. Sleep habits were most altered in the younger population, indicating a greater risk for this group to develop a sleep-wake rhythm disorder