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This study aimed to explore the potential impact of the angular position of the outflow graft on thromboembolic events and aortic valve regurgitation in people with a left ventricular assist device (LVAD). We analyzed contrast computed tomography (CT) data of patients with LVAD implantation between 2016 and 2021. Three-dimensional reconstructions of the outflow graft and aortic arch were performed to calculate the horizontal (azimuth) angle and vertical (polar) angle, as well as the relative distance between the outflow graft, aortic valve, and brachiocephalic artery. Among 59 patients (median age 57, 68% male), a vertical angle ≥107° correlated significantly with increased cerebrovascular accidents (hazard ratio [HR]: 5.8, 95% confidence interval [CI]: 1.3-26.3, p = 0.022) and gastrointestinal bleeding (HR: 3.4, 95% CI: 1.0-11.2, p = 0.049) during a median 25 month follow-up. No significant differences were found between the vertical angle and aortic valve regurgitation or survival. The horizontal angle and relative distance did not show differences regarding clinical adverse events. This study emphasizes the importance of the LVAD outflow graft angular position to prevent life-threatening thromboembolic events. This study suggests the need for prospective research to further validate these findings.
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OBJECTIVES: Myocardial recovery in children supported by a durable left ventricular assist device is a rare, but highly desirable outcome because it could potentially eliminate the need for a cardiac transplant and the lifelong need for immunosuppressant therapy and the risk of complications. However, experience with this specific outcome is extremely limited. METHODS: All patients < 19 years old supported by a durable left ventricular assist device from the European Registry for Patients with Mechanical Circulatory Support database were included. Participating centres were approached for additional follow-up data after explantation. Associated factors for explantation due to myocardial recovery were explored using Cox proportional hazard models. RESULTS: The incidence of recovery in children supported by a durable left ventricular assist device was 11.7% (52/445; median duration of support, 122.0 days). Multivariable analyses showed body surface area (hazard ratio 0.229; confidence interval 0.093-0.565; P = 0.001) and a primary diagnosis of myocarditis (hazard ratio 4.597; confidence interval 2.545-8.303; P < 0.001) to be associated with recovery. Left ventricular end-diastolic diameter in children with myocarditis was not associated with recovery. Follow-up after recovery was obtained for 46 patients (88.5%). Sustained myocardial recovery was reported in 33/46 (71.7%) at the end of the follow-up period (28/33; >2 year). Transplants were performed in 6/46 (11.4%) (in 5 after a ventricular assist device was reimplanted). Death occurred in 7/46 (15.2%). CONCLUSIONS: Myocardial recovery occurs in a substantial portion of paediatric patients supported with durable left ventricular assist devices, and sustainable recovery is seen in around three-quarters of them. Even children with severely dilated ventricles due to myocarditis can show recovery. Clinicians should be attentive to (developing) myocardial recovery. These results can be used to develop internationally approved paediatric weaning guidelines.
Subject(s)
Heart Failure , Heart Transplantation , Heart-Assist Devices , Myocarditis , Humans , Child , Young Adult , Adult , Heart-Assist Devices/adverse effects , Myocarditis/surgery , Myocardium , Diastole , Heart Failure/surgery , Treatment OutcomeABSTRACT
BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.
Subject(s)
Acetaminophen , Morphine , Humans , Morphine/therapeutic use , Morphine/administration & dosage , Acetaminophen/therapeutic use , Acetaminophen/administration & dosage , Male , Female , Infant , Double-Blind Method , Pain, Postoperative/drug therapy , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Belgium , Netherlands , Infant, Newborn , Administration, Intravenous , Cardiac Surgical Procedures/methods , Child, Preschool , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Intensive Care Units, Pediatric/organization & administration , Intensive Care Units, Pediatric/statistics & numerical data , Pain Measurement/methodsABSTRACT
OBJECTIVES: Congenital supravalvular aortic stenosis (SVAS) is a rare form of congenital outflow tract obstruction and long-term outcomes are scarcely reported. This study aims to provide an overview of outcomes after surgical repair for congenital SVAS. METHODS: A systematic review of published literature was conducted, including observational studies reporting long-term clinical outcome (>2 years) after SVAS repair in children or adults considering >20 patients. Early risks, late event rates and time-to-event data were pooled and entered into a microsimulation model to estimate 30-year outcomes. Life expectancy was compared to the age-, sex- and origin-matched general population. RESULTS: Twenty-three publications were included, encompassing a total of 1472 patients (13 125 patient-years; pooled mean follow-up: 9.0 (6.2) years; median follow-up: 6.3 years). Pooled mean age at surgical repair was 4.7 (5.8) years and the most commonly used surgical technique was the single-patch repair (43.6%). Pooled early mortality was 4.2% (95% confidence interval: 3.2-5.5%) and late mortality was 0.61% (95% CI: 0.45-0.83) per patient-year. Based on microsimulation, over a 30-year time horizon, it was estimated that an average patient with SVAS repair (mean age: 4.7 years) had an observed life expectancy that was 90.7% (95% credible interval: 90.0-91.6%) of expected life expectancy in the matched general population. The microsimulation-based 30-year risk of myocardial infarction was 8.1% (95% credible interval: 7.3-9.9%) and reintervention 31.3% (95% credible interval: 29.6-33.4%), of which 27.2% (95% credible interval: 25.8-29.1) due to repair dysfunction. CONCLUSIONS: After surgical repair for SVAS, 30-year survival is lower than the matched-general-population survival and the lifetime risk of reintervention is considerable. Therefore, lifelong monitoring of the cardiovascular system and in particular residual stenosis and coronary obstruction is recommended.
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Aortic Stenosis, Supravalvular , Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Child , Adult , Humans , Child, Preschool , Aortic Stenosis, Supravalvular/surgery , Heart Valve Prosthesis Implantation/adverse effects , Reoperation , Constriction, Pathologic/etiology , Treatment OutcomeABSTRACT
OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.
Subject(s)
Heart Septal Defects, Atrial , Hypertension , Humans , Male , Adult , Middle Aged , Adolescent , Female , Follow-Up Studies , Quality of Life , Treatment Outcome , Stroke Volume , Ventricular Function, Right , Heart Septal Defects, Atrial/diagnosis , Heart Septal Defects, Atrial/surgery , Arrhythmias, Cardiac/etiology , Hypertension/complications , Cardiac Catheterization/adverse effectsABSTRACT
AIMS: This retrospective study investigated the association between anatomical variations in the aortic arch branching and adverse events, including the risk of cerebrovascular accidents (CVAs), in patients with a left ventricular assist device (LVAD). METHODS: Medical charts were reviewed for all patients with HeartMate 3 LVAD support at our center from 2016 to 2021. Computed tomography scans were evaluated to categorize the variations in the aortic arch branching based on seven different types, as described in the literature. RESULTS: In total, 101 patients were included: 86 (85.1%) with a normal branching pattern and 15 (14.9%) with an anatomical variation. The following variations were observed: eight (7.9%) with a bovine arch and seven (6.9%) with a left vertebral arch. The median age was 57âyears, 77.2% were men, and the median follow-up was 25âmonths. No difference was found in the rate of early (< 30âdays) re-exploration due to bleeding after LVAD implantation. The rate of CVA and mortality did not differ significantly between patients with a normal arch or an anatomical variation during follow-up, with hazard ratios of 1.47 [95% confidence interval (CI): 0.48-4.48; Pâ=â0.495] and 0.69 (95% CI: 0.24-1.98; Pâ=â0.489), respectively. CONCLUSION: This preliminary study showed no differences in early and long-term adverse events, including CVA, when comparing patients with a variation in the aortic arch branching to patients with a normal aortic arch. However, knowledge of the variations in aortic arch branching could be meaningful during cardiac surgery for potential differences in surgical events in the perioperative period.
Subject(s)
Heart-Assist Devices , Stroke , Male , Humans , Middle Aged , Female , Retrospective Studies , Aorta, Thoracic/diagnostic imaging , Heart-Assist Devices/adverse effects , Tomography, X-Ray Computed , Stroke/epidemiology , Stroke/etiologyABSTRACT
Background: Scientific research regarding male-female differences in ascending aortic surgery is scarce. The objective of this study was to identify male-female differences in presentation, treatment and peri-operative outcome in elective ascending aortic surgery. Methods: Elective ascending aortic surgery procedures that took place in the Netherlands between 01/01/2013-31/12/2017 were identified from the Netherlands Heart Registration. Male-female differences in presentation, treatment characteristics, and in-hospital mortality and morbidity were explored. Results: The study population consisted of 887 females (31%) and 1,972 males (69%). Females were older (median age 67 versus 62 years, P<0.001), more often had chronic lung disease (12.3% versus 9.1%, P=0.011), New York Heart Association (NYHA) class III-IV (21.5% versus 15.5%, P=0.003), and less often a history of percutaneous coronary intervention (PCI) (3.2% versus 5.0%, P=0.033). Isolated supracoronary aortic replacement was performed in 47.7% of females versus 30.6% of males (P<0.001), and ascending aorta with root replacement in 40.6% of females versus 56.7% of males (P<0.001). Females more often underwent concomitant interventions of the aortic arch (33.1% versus 20.2%, P<0.001) and the mitral valve (8.2% versus 5.2%, P=0.002), and less often concomitant coronary artery bypass grafting (CABG) (14.4% versus 19.1%, P=0.002). Overall, in-hospital mortality was significantly higher in females (5.1% versus 2.7%, P=0.003). In multivariable regression analysis, being female was an independent risk factor for in-hospital mortality [odds ratio (OR) 1.55, 95% confidence interval (CI): 1.02-2.37]. Conclusions: This nation-wide cohort shows clear differences between females and males in patient presentation, procedural characteristics, in-hospital outcomes, and risk factors for in-hospital mortality in elective ascending aortic surgery. Further exploration of these differences, and of modifiable within-male and within-female risk factors, may offer great opportunities in improving treatment and thereby outcomes for both males and females.
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OBJECTIVES: To support clinical decision-making in children with aortic valve disease, by compiling the available evidence on outcome after paediatric aortic valve repair (AVr). METHODS: A systematic review of literature reporting clinical outcome after paediatric AVr (mean age at surgery <18 years) published between 1 January 1990 and 23 December 2021 was conducted. Early event risks, late event rates and time-to-event data were pooled. A microsimulation model was employed to simulate the lives of individual children, infants and neonates following AVr. RESULTS: Forty-one publications were included, encompassing 2 623 patients with 17 217 patient-years of follow-up (median follow-up: 7.3 years; range: 1.0-14.4 years). Pooled mean age during repair for aortic stenosis in children (<18 years), infants (<1 year) or neonates (<30 days) was 5.2 ± 3.9 years, 35 ± 137 days and 11 ± 6 days, respectively. Pooled early mortality after stenosis repair in children, infants and neonates, respectively, was 3.5% (95% confidence interval: 1.9-6.5%), 7.4% (4.2-13.0%) and 10.7% (6.8-16.9%). Pooled late reintervention rate after stenosis repair in children, infants and neonates, respectively, was 3.31%/year (1.66-6.63%/year), 6.84%/year (3.95-11.83%/year) and 6.32%/year (3.04-13.15%/year); endocarditis 0.07%/year (0.03-0.21%/year), 0.23%/year (0.07-0.71%/year) and 0.49%/year (0.18-1.29%/year); and valve thrombosis 0.05%/year (0.01-0.26%/year), 0.15%/year (0.04-0.53%/year) and 0.19%/year (0.05-0.77%/year). Microsimulation-based mean life expectancy in the first 20 years for children, infants and neonates with aortic stenosis, respectively, was 18.4 years (95% credible interval: 18.1-18.7 years; relative survival compared to the matched general population: 92.2%), 16.8 years (16.5-17.0 years; relative survival: 84.2%) and 15.9 years (14.8-17.0 years; relative survival: 80.1%). Microsimulation-based 20-year risk of reintervention in children, infants and neonates, respectively, was 75.2% (72.9-77.2%), 53.8% (51.9-55.7%) and 50.8% (47.0-57.6%). CONCLUSIONS: Long-term outcomes after paediatric AVr for stenosis are satisfactory and dependent on age at surgery. Despite a high hazard of reintervention for valve dysfunction and slightly impaired survival relative to the general population, AVr is associated with low valve-related event occurrences and should be considered in children with aortic valve disease.
Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Infant, Newborn , Humans , Child , Infant , Adolescent , Aortic Valve/surgery , Constriction, Pathologic , Treatment Outcome , Retrospective Studies , ReoperationABSTRACT
BACKGROUND: Low-level vagus nerve stimulation through the tragus (tLLVNS) is increasingly acknowledged as a therapeutic strategy to prevent and treat atrial fibrillation. However, a lack in understanding of the exact antiarrhythmic properties of tLLVNS has hampered clinical implementation. OBJECTIVES: In this study, the authors aimed to study the effects of tLLVNS on atrial electrophysiology by performing intraoperative epicardial mapping during acute and chronic tLLVNS. METHODS: Epicardial mapping of the superior right atrium was performed before and after arterial graft harvesting in patients undergoing coronary artery bypass grafting without a history of atrial fibrillation. The time needed for arterial graft harvesting was used to perform chronic tLLVNS. Electrophysiological properties were compared before and during chronic tLLVNS. RESULTS: A total of 10 patients (median age 74 years [IQR: 69-78 years]) underwent tLLVNS for a duration of 56 minutes (IQR: 43-73 minutes). During acute and chronic tLLVNS, a shift of the sinoatrial node exit site toward a more cranial direction was observed in 5 (50%) patients. Unipolar potential voltage increased significantly during acute and chronic tLLVNS (3.9 mV [IQR: 3.1-4.8 mV] vs 4.7 mV [IQR: 4.0-5.3 mV] vs 5.2 mV [IQR: 4.8-7.0 mV]; P = 0.027, P = 0.02, respectively). Total activation time, slope of unipolar potentials, amount of fractionation, low-voltage areas and conduction velocity did not differ significantly between baseline measurements and tLLVNS. Two patients showed consistent "improvement" of all electrophysiological properties during tLLVNS, while 1 patient appeared to have no beneficial effect. CONCLUSIONS: We demonstrated that tLLVNS resulted in a significant increase in unipolar potential voltage. In addition, we observed the following in selective patients: 1) reduction in total activation time; 2) steeper slope of unipolar potentials; 3) decrease in the amount of fractionation; and 4) change in sinoatrial node exit sites.
Subject(s)
Atrial Fibrillation , Vagus Nerve Stimulation , Humans , Aged , Atrial Fibrillation/therapy , Heart Atria , Coronary Artery Bypass , Cardiac ElectrophysiologyABSTRACT
OBJECTIVES: A small percentage of paediatric patients supported with a ventricular assist device (VAD) can have their device explanted following myocardial recovery. The goal of this systematic review is to summarize the current literature on the clinical course in these children after weaning. METHODS: A systematic literature search was performed on 27 May 2022 using Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar to include all literature on paediatric patients supported by a durable VAD during the last decade. Overlapping study cohorts and registry-based studies were filtered out. RESULTS: Thirty-seven articles were included. Eighteen of them reported on the incidence of recovery in cohort studies, with an overall incidence rate of 8.7% (81/928). Twenty-two of the included articles reported on clinical outcomes after VAD explantation (83 patients). The aetiologies varied widely and were not limited to diseases with a natural transient course like myocarditis. Most of the patients in the included studies (70; 84.3%) were supported by a Berlin Heart EXCOR, and in 66.3% (55/83), only the left ventricle had to be supported. The longest follow-up period was 19.1 years, and multiple studies reported on long-term myocardial recovery. Fewer than half of the reported deaths had a cardiac cause. CONCLUSIONS: Myocardial recovery during VAD support is dependent on various contributing components. The interactions among patient-, device-, time- and hospital-related factors are complex and not yet fully understood. Long-term recovery after VAD support is achievable, even after a long duration of VAD support, and even in patients with aetiologies different from myocarditis or post-cardiotomy heart failure. More research is needed on this favourable outcome after VAD support.
Subject(s)
Heart Failure , Heart-Assist Devices , Myocarditis , Child , Humans , Heart-Assist Devices/adverse effects , Myocarditis/complications , Treatment Outcome , Heart Failure/surgery , Heart Failure/etiology , Heart , Retrospective StudiesABSTRACT
AIMS: To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes. METHODS AND RESULTS: A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR. CONCLUSION: Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Humans , Child , Adolescent , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/methods , Retrospective Studies , Prospective Studies , Treatment OutcomeABSTRACT
OBJECTIVES: In complex double outlet right ventricle (DORV) patients, the optimal surgical approach may be difficult to assess based on conventional 2-dimensional (2D) ultrasound (US) and computed tomography (CT) imaging. The aim of this study is to assess the added value of 3-dimensional (3D) printed and 3D virtual reality (3D-VR) models of the heart used for surgical planning in DORV patients, supplementary to the gold standard 2D imaging modalities. METHODS: Five patients with different DORV subtypes and high-quality CT scans were selected retrospectively. 3D prints and 3D-VR models were created. Twelve congenital cardiac surgeons and paediatric cardiologists, from 3 different hospitals, were shown 2D-CT first, after which they assessed the 3D print and 3D-VR models in random order. After each imaging method, a questionnaire was filled in on the visibility of essential structures and the surgical plan. RESULTS: Spatial relationships were generally better visualized using 3D methods (3D printing/3D-VR) than in 2D. The feasibility of ventricular septum defect patch closure could be determined best using 3D-VR reconstructions (3D-VR 92%, 3D print 66% and US/CT 46%, P < 0.01). The percentage of proposed surgical plans corresponding to the performed surgical approach was 66% for plans based on US/CT, 78% for plans based on 3D printing and 80% for plans based on 3D-VR visualization. CONCLUSIONS: This study shows that both 3D printing and 3D-VR have additional value for cardiac surgeons and cardiologists over 2D imaging, because of better visualization of spatial relationships. As a result, the proposed surgical plans based on the 3D visualizations matched the actual performed surgery to a greater extent.
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OBJECTIVE: Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF). METHODS: We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment-including blood sampling and speckle tracking echocardiography-occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples. RESULTS: We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p < 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p < 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population. CONCLUSIONS: The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL5129.
Subject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Pulmonary Valve Insufficiency , Pulmonary Valve , Tetralogy of Fallot , Humans , Tetralogy of Fallot/genetics , Tetralogy of Fallot/surgery , Tetralogy of Fallot/complications , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Pulmonary Valve Insufficiency/diagnostic imaging , Pulmonary Valve Insufficiency/etiology , Pulmonary Valve Insufficiency/surgery , Heart Valve Prosthesis Implantation/adverse effects , Ventricular Function, Right/physiology , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Ventricular Function , BiomarkersABSTRACT
Living myocardial slices (LMS) are beating sections of intact human myocardium that maintain 3D microarchitecture and multicellularity, thereby overcoming most limitations of conventional myocardial cell cultures. We introduce a novel method to produce LMS from human atria and apply pacing modalities to bridge the gap between in-vitro and in-vivo atrial arrhythmia studies. Human atrial biopsies from 15 patients undergoing cardiac surgery were dissected to tissue blocks of ~ 1 cm2 and cut to 300 µm thin LMS with a precision-cutting vibratome. LMS were placed in a biomimetic cultivation chamber, filled with standard cell culture medium, under diastolic preload (1 mN) and continuous electrical stimulation (1000 ms cycle length (CL)), resulting in 68 beating LMS. Atrial LMS refractory period was determined at 192 ± 26 ms. Fixed rate pacing with a CL of 333 ms was applied as atrial tachyarrhythmia (AT) model. This novel state-of-the-art platform for AT research can be used to investigate arrhythmia mechanisms and test novel therapies.
Subject(s)
Atrial Fibrillation , Humans , Biomimetics , Research Design , Myocardium , Myocytes, CardiacABSTRACT
In this study, we aim to elucidate the clinical impact and long-term course of tricuspid regurgitation (TR), taking into account its dynamic nature, after biatrial orthotopic heart transplant (OHT). All consecutive adult patients undergoing biatrial OHT (1984-2017) with an available follow-up echocardiogram were included. Mixed-models were used to model the evolution of TR. The mixed-model was inserted into a Cox model in order to address the association of the dynamic TR with mortality. In total, 572 patients were included (median age: 50 years, males: 74.9%). Approximately 32% of patients had moderate-to-severe TR immediately after surgery. However, this declined to 11% on 5 years and 9% on 10 years after surgery, adjusted for survival bias. Pre-implant mechanical support was associated with less TR during follow-up, whereas concurrent LV dysfunction was significantly associated with more TR during follow-up. Survival at 1, 5, 10, 20 years was 97% ± 1%, 88% ± 1%, 66% ± 2% and 23% ± 2%, respectively. The presence of moderate-to-severe TR during follow-up was associated with higher mortality (HR: 1.07, 95% CI (1.02-1.12), p = 0.006). The course of TR was positively correlated with the course of creatinine (R = 0.45). TR during follow-up is significantly associated with higher mortality and worse renal function. Nevertheless, probability of TR is the highest immediately after OHT and decreases thereafter. Therefore, it may be reasonable to refrain from surgical intervention for TR during earlier phase after OHT.
Subject(s)
Heart Transplantation , Tricuspid Valve Insufficiency , Ventricular Dysfunction, Left , Male , Adult , Humans , Middle Aged , Tricuspid Valve Insufficiency/diagnostic imaging , Echocardiography , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Sex does have an effect on disease perception and outcomes after cardiac surgery. OBJECTIVES: The aim of this study was to quantify the differences in cardiovascular risk profiles within an age-matched cohort and assess the long-term survival differences in males and females who underwent surgical aortic valve replacement (SAVR) with or without concomitant coronary artery bypass surgery. METHODS: All-comers patients who underwent SAVR with or without coronary artery bypass surgery were included. Characteristics, clinical features and survival up to 30 years were compared between female and male patients. Propensity matching and age matching using propensity scores were used to compare both groups. RESULTS: During the total study period between 1987 and 2017, there were 3462 patients {mean age 66.8 [standard deviation (SD): 11.1] years, 37.1% female} who underwent SAVR with or without coronary artery bypass surgery at our institution. In general, female patients were older than male patients (69.1 (SD : 10.3) versus 65.5 (SD : 11.3), respectively). In the age-matched cohort, female patients were less likely to have multiple comorbidities and undergo concomitant coronary artery bypass surgery. Twenty-year survival following the index procedure was higher in age-matched female patients (27.1%) compared to male patients (24.4%) in the overall cohort (P = 0.018). CONCLUSIONS: Substantial sex differences in cardiovascular risk profile exist. However, when SAVR with or without coronary artery bypass surgery is performed, extended long-term mortality is comparable between males and females. More research regarding sex-dimorphic mechanisms of aortic stenosis and coronary atherosclerosis would promote more awareness in terms of sex-specific risk factors after cardiac surgery and contribute to more guided personalized surgery in the future.
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PURPOSE: Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients. METHODS: Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters. RESULTS: Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively). CONCLUSION: The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.
ABSTRACT
Mechanical device malfunction remains a known issue in left ventricular assist devices (LVADs). We investigated the incidence of mechanical device malfunction in the HeartMate II and HeartMate 3 LVADs. We conducted a retrospective study of all HeartMate II and HeartMate 3 LVADs implanted in our center. We evaluated major malfunction, potential major malfunction, minor malfunction, and need of device exchange. In total, 163 patients received an LVAD; in 63 (39%) a HeartMate II, and in 100 (61%) a HeartMate 3, median support time of respectively 24.6 months (interquartile range [IQR]: 32.4) and 21.1 months [IQR: 27.2]. Mechanical device malfunction, consisting of both major and potential major malfunction, occurred significantly less in the HeartMate 3 patients with a hazard ratio (HR) of 0.37 (95% confidence interval [CI]: 0.15-0.87, p = 0.022). Major malfunction alone occurred significantly less in HeartMate 3 patients with a HR of 0.18 (95% CI: 0.05-0.66, p = 0.009). HeartMate 3 patients had a significantly decreased hazard of a pump or outflow graft exchange (HR 0.13, 95% CI: 0.08-0.81, p = 0.008). System controller defects occurred significantly less in HM 3 patients ( p = 0.007), but battery-clips defects occurred significantly more in HM 3 patients ( p = 0.039). Major device malfunction including pump or outflow graft exchange occurred significantly less in HeartMate 3 compared to HeartMate II, while minor malfunctions were similar. Periodical assessment of the technical integrity of the device remains necessary during long-term LVAD support.
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Heart Failure , Heart-Assist Devices , Humans , Heart Failure/surgery , Retrospective Studies , Heart-Assist Devices/adverse effects , IncidenceABSTRACT
BACKGROUND: Since 1998, there has been a national programme for paediatric heart transplantations (HT) in the Netherlands. In this study, we investigated waiting list mortality, survival post-HT, the incidence of common complications, and the patients' functional status during follow-up. METHODS: All children listed for HT from 1998 until October 2020 were included. Follow-up lasted until 1 January 2021. Data were collected from the patient charts. Survival, post-operative complications as well as the functional status (Karnofsky/Lansky scale) at the end of follow-up were measured. RESULTS: In total, 87 patients were listed for HT, of whom 19 (22%) died while on the waiting list. Four patients were removed from the waiting list and 64 (74%) underwent transplantation. Median recipient age at HT was 12.0 (IQR 7.2-14.4) years old; 55% were female. One-, 5, and 10-year survival post-HT was 97%, 95%, and 88%, respectively. Common transplant-related complications were rejections (50%), Epstein-Barr virus infections (31%), cytomegalovirus infections (25%), post-transplant lymphoproliferative disease (13%), and cardiac allograft vasculopathy (13%). The median functional score (Karnofsky/Lansky scale) was 100 (IQR 90-100). CONCLUSION: Children who undergo HT have an excellent survival rate up to 10 years post-HT. Even though complications post-HT are common, the functional status of most patients is excellent. Waiting list mortality is high, demonstrating that donor availability for this vulnerable patient group remains a major limitation for further improvement of outcome.