Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

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 Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis.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.

Paediatric aortic valve replacement: a meta-analysis and microsimulation study.

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.

Incidental findings on routine preoperative noncontrast chest computed tomography and chest radiography prior to cardiac surgery in the multicenter randomized controlled CRICKET study.

OBJECTIVE: To describe the prevalence and consequences of incidental findings when implementing routine noncontrast CT prior to cardiac surgery. METHODS: In the multicenter randomized controlled CRICKET study, 862 adult patients scheduled for cardiac surgery were randomized 1:1 to undergo standard of care (SoC), which included a chest-radiograph, or an additional preoperative noncontrast chest CT-scan (SoC+CT). In this subanalysis, all incidental findings detected on the chest radiograph and CT-scan were analyzed. The influence of smoking status on incidental findings was also evaluated, adjusting for sex, age, and group allocation. RESULTS: Incidental findings were observed in 11.4% (n = 49) of patients in the SoC+CT group and in 3.7% (n = 16) of patients in the SoC-group (p < 0.001). The largest difference was observed in findings requiring follow-up (SoC+CT 7.7% (n = 33) vs SoC 2.3% (n = 10), p < 0.001). Clinically relevant findings changing the surgical approach or requiring specific treatment were observed in 10 patients (1.2%, SoC+CT: 1.6% SoC: 0.7%), including lung cancer in 0.5% of patients (n = 4) and aortic dilatation requiring replacement in 0.2% of patients (n = 2). Incidental findings were more frequent in patients who stopped smoking (OR 1.91, 1.03-3.63) or who actively smoked (OR 3.91, 1.85-8.23). CONCLUSIONS: Routine CT-screening increases the rate of incidental findings, mainly by identifying more pulmonary findings requiring follow-up. Incidental findings are more prevalent in patients with a history of smoking, and preoperative CT might increase the yield of identifying lung cancer in these patients. Incidental findings, but not specifically the use of routine CT, are associated with delay of surgery. KEY POINTS: • Clinically relevant incidental findings are identified more often after a routine preoperative CT-scan, when compared to a standard of care workup, with some findings changing patient management. • Patients with a history of smoking have a higher rate of incidental findings and a lung cancer rate comparable to that of lung cancer screening trials. • We observed no clear delay in the time to surgery when adding routine CT screening.

18F-FDG/PET-CT imaging findings after sternotomy.

BACKGROUND: The clinical diagnosis of deep sternal wound infection (DSWI) is supported by imaging findings including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). To avoid misinterpretation due to normal post-surgery inflammation we assessed normal imaging findings in non-infected patients after sternotomy. METHODS: This is a prospective cohort study including non-infectious patients with sternotomy. All patients underwent 18F-FDG-PET/CT at either 5 weeks (group 1), 12 weeks (group 2) or 52 weeks (group 3) post-surgery. 18F-FDG uptake was scored visually in five categories and assessed quantitatively. RESULTS: A total of 44 patients were included. Sternal mean SUVmax was 7.34 (± 1.86), 5.22 (± 2.55) and 3.20 (± 1.80) in group 1, 2 and 3, respectively (p < 0.01). Sternal mean SUVmean was 3.84 (± 1.00), 2.69 (± 1.32) and 1.71 (± 0.98) in group 1, 2 and 3 (p < 0.01). All patients in group 1 had elevated uptake whereas group 2 and 3 showed 2/15 (13%) and 11/20 (55%) patients respectively with no elevated uptake. Group 3 still showed an elevated uptake pattern in in 9/20 (45%) and in 3/9 (33%) with a high-grade diffuse uptake pattern. CONCLUSION: This study shows significant lower sternal 18F-FDG at 55 weeks compared to 5 weeks post-sternotomy however elevated uptake patterns may persist.

Acute Biomechanical Effects of Empagliflozin on Living Isolated Human Heart Failure Myocardium.

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.

The Dutch national paediatric heart transplantation programme: outcomes during a 23-year period.

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.

Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

OBJECTIVES: To evaluate if routine screening for aortic calcification using unenhanced CT lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (SoC). METHODS: In this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from September 2014 to October 2019 were randomized 1:1 into two groups: SoC alone, including chest radiography, vs. SoC plus preoperative noncontrast CT. The primary endpoint was in-hospital perioperative stroke. Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium. The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect. RESULTS: A total of 862 patients were evaluated (SoC-group: 433 patients (66 ± 11 years; 74.1% male) vs. SoC + CT-group: 429 patients (66 ± 10 years; 69.9% male)). The perioperative stroke rate (SoC + CT: 2.1%, 9/429 vs. SoC: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (SoC + CT: 4.0% (17/429) vs. SoC: 2.8% (12/433, p = 0.35) did not differ between groups. In-hospital mortality and postoperative delirium were comparable between groups. In the SoC + CT group, aortic calcification was observed on CT in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379). CONCLUSIONS: Preoperative noncontrast CT in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care. Aortic calcification is a frequent finding on the CT scan in these patients but results in major surgical alterations to prevent stroke in only few patients. KEY POINTS: • Aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery. • Routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care. • No effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.

Optimal temperature management in aortic arch surgery: A systematic review and network meta-analysis.

OBJECTIVES: New temperature management concepts of moderate and mild hypothermic circulatory arrest during aortic arch surgery have gained weight over profound cooling. Comparisons of all temperature levels have rarely been performed. We performed direct and indirect comparisons of deep hypothermic circulatory arrest (DHCA) (≤20°C), moderate hypothermic circulatory arrest (MHCA) (20.1-25°C), and mild hypothermic circulatory arrest (mild HCA) (≥25.1°C) in a network meta-analysis. METHODS: The literature was systematically searched for all papers published through February 2022 reporting on clinical outcomes after aortic arch surgery utilizing DHCA, MHCA and mild HCA. The primary outcome was operative mortality. The secondary outcomes were postoperative stroke and acute kidney failure (AKI). RESULTS: A total of 34 studies were included, with a total of 12,370 patients. DHCA was associated with significantly higher postoperative incidence of stroke when compared with MHCA (odds ratio [OR], 1.46, 95% confidence interval [CI], 1.19-1.78) and mild HCA: (OR, 1.50, 95% CI, 1.14-1.98). Furthermore, DHCA and MHCA were associated with higher operative mortality when compared with mild HCA (OR 1.71, 95% CI, 1.23-2.39 and OR 1.50, 95% CI, 1.12-2.00, respectively). Separate analysis of randomized and propensity score matched studies showed sustained increased risk of stroke with DHCA in contrast to MHCA and mild HCA (OR, 1.61, 95% CI, 1.18-2.20, p value = .0029 and OR, 1.74, 95% CI, 1.09-2.77, p value = .019). CONCLUSIONS: In the included studies, the moderate to mild hypothermia strategies were associated with decreased operative mortality and the risk of postoperative stroke. Large-scale prospective studies are warranted to further explore appropriate temperature management for the treatment of aortic arch pathologies.

Vagus Nerve Stimulation and Atrial Fibrillation: Revealing the Paradox.

BACKGROUND AND OBJECTIVE: The cardiac autonomic nervous system (CANS) plays an important role in the pathophysiology of atrial fibrillation (AF). Cardiovascular disease can cause an imbalance within the CANS, which may contribute to the initiation and maintenance of AF. Increased understanding of neuromodulation of the CANS has resulted in novel emerging therapies to treat cardiac arrhythmias by targeting different circuits of the CANS. Regarding AF, neuromodulation therapies targeting the vagus nerve have yielded promising outcomes. However, targeting the vagus nerve can be both pro-arrhythmogenic and anti-arrhythmogenic. Currently, these opposing effects of vagus nerve stimulation (VNS) have not been clearly described. The aim of this review is therefore to discuss both pro-arrhythmogenic and anti-arrhythmogenic effects of VNS and recent advances in clinical practice and to provide future perspectives for VNS to treat AF. MATERIALS AND METHODS: A comprehensive review of current literature on VNS and its pro-arrhythmogenic and anti-arrhythmogenic effects on atrial tissue was performed. Both experimental and clinical studies are reviewed and discussed separately. RESULTS: VNS exhibits both pro-arrhythmogenic and anti-arrhythmogenic effects. The anatomical site and stimulation settings during VNS play a crucial role in determining its effect on cardiac electrophysiology. Since the last decade, there is accumulating evidence from experimental studies and randomized clinical studies that low-level VNS (LLVNS), below the bradycardia threshold, is an effective treatment for AF. CONCLUSION: LLVNS is a promising novel therapeutic modality to treat AF and further research will further elucidate the underlying anti-arrhythmogenic mechanisms, optimal stimulation settings, and site to apply LLVNS.

Atrial electrophysiological characteristics of aging.

INTRODUCTION: Advancing age is a known risk factor for developing atrial fibrillation (AF), yet it is unknown which electrophysiological changes contribute to this increased susceptibility. The goal of this study is to investigate conduction disturbances and unipolar voltages (UV) related to aging. METHODS: We included 216 patients (182 male, age: 36-83 years) without a history of AF undergoing elective coronary artery bypass surgery. Five seconds of sinus rhythm were recorded intraoperatively at the right atrium (RA), Bachmann's bundle (BB), the left atrium and the pulmonary vein area (PVA). Conduction delay (CD), -block (CB), -velocity (CV), length of longest CB lines and UV were assessed in all regions. RESULTS: With aging, increasing conduction disturbances were found, particularly at RA and BB (RA: longest CB line rs = .158, p = .021; BB: CB prevalence rs = .206, p = .003; CV rs = -.239, p < .0005). Prevalence of low UV areas (UV <5th percentile) increased with aging at the BB and PVA (BB: rs = .237, p < .0005 and PVA: rs = .228, p = .001). CONCLUSIONS: Aging is accompanied by an increase in conduction disturbances during sinus rhythm and a higher prevalence of low UV areas, particularly at BB and in the RA. These electrophysiological alterations could in part explain the increasing susceptibility to AF development associated with aging.

Right ventricular phenotype, function, and failure: a journey from evolution to clinics.

The right ventricle has long been perceived as the "low pressure bystander" of the left ventricle. Although the structure consists of, at first glance, the same cardiomyocytes as the left ventricle, it is in fact derived from a different set of precursor cells and has a complex three-dimensional anatomy and a very distinct contraction pattern. Mechanisms of right ventricular failure, its detection and follow-up, and more specific different responses to pressure versus volume overload are still incompletely understood. In order to fully comprehend right ventricular form and function, evolutionary biological entities that have led to the specifics of right ventricular physiology and morphology need to be addressed. Processes responsible for cardiac formation are based on very ancient cardiac lineages and within the first few weeks of fetal life, the human heart seems to repeat cardiac evolution. Furthermore, it appears that most cardiogenic signal pathways (if not all) act in combination with tissue-specific transcriptional cofactors to exert inductive responses reflecting an important expansion of ancestral regulatory genes throughout evolution and eventually cardiac complexity. Such molecular entities result in specific biomechanics of the RV that differs from that of the left ventricle. It is clear that sole descriptions of right ventricular contraction patterns (and LV contraction patterns for that matter) are futile and need to be addressed into a bigger multilayer three-dimensional picture. Therefore, we aim to present a complete picture from evolution, formation, and clinical presentation of right ventricular (mal)adaptation and failure on a molecular, cellular, biomechanical, and (patho)anatomical basis.

Sinus rhythm voltage fingerprinting in patients with mitral valve disease using a high-density epicardial mapping approach.

AIMS: Unipolar voltage (UV) mapping is increasingly used for guiding ablative therapy of atrial fibrillation (AF) as unipolar electrograms (U-EGMs) are independent of electrode orientation and atrial wavefront direction. This study was aimed at constructing individual, high-resolution sinus rhythm (SR) UV fingerprints to identify low-voltage areas and study the effect of AF episodes in patients with mitral valve disease (MVD). METHODS AND RESULTS: Intra-operative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium, Bachmann's bundle (BB), and pulmonary vein area was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). In all patients, there were considerable regional variations in voltages. UVs at BB were lower in patients with PAF compared with those without [no AF: 4.94 (3.56-5.98) mV, PAF: 3.30 (2.25-4.57) mV, P = 0.006]. A larger number of low-voltage potentials were recorded at BB in the PAF group [no AF: 2.13 (0.52-7.68) %, PAF: 12.86 (3.18-23.59) %, P = 0.001]. In addition, areas with low-voltage potentials were present in all patients, yet we did not find any predilection sites for low-voltage potentials to occur. CONCLUSION: Even in SR, advanced atrial remodelling in MVD patients shows marked inter-individual and regional variation. Low UVs are even present during SR in patients without a history of AF indicating that low UVs should carefully be used as target sites for ablative therapy.

Identification of local atrial conduction heterogeneities using high-density conduction velocity estimation.

AIMS: Accurate determination of intra-atrial conduction velocity (CV) is essential to identify arrhythmogenic areas. The most optimal, commonly used, estimation methodology to measure conduction heterogeneity, including finite differences (FiD), polynomial surface fitting (PSF), and a novel technique using discrete velocity vectors (DVV), has not been determined. We aim (i) to identify the most suitable methodology to unravel local areas of conduction heterogeneities using high-density CV estimation techniques, (ii) to quantify intra-atrial differences in CV, and (iii) to localize areas of CV slowing associated with paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: Intra-operative epicardial mapping (>5000 sites, interelectrode distances 2 mm) of the right and left atrium and Bachmann's bundle (BB) was performed during sinus rhythm (SR) in 412 patients with or without PAF. The median atrial CV estimated using the DVV, PSF, and FiD techniques was 90.0 (62.4-116.8), 92.0 (70.6-123.2), and 89.4 (62.5-126.5) cm/s, respectively. The largest difference in CV estimates was found between PSF and DVV which was caused by smaller CV magnitudes detected only by the DVV technique. Using DVV, a lower CV at BB was found in PAF patients compared with those without atrial fibrillation (AF) [79.1 (72.2-91.2) vs. 88.3 (79.3-97.2) cm/s; P < 0.001]. CONCLUSIONS: Areas of local conduction heterogeneities were most accurately identified using the DVV technique, whereas PSF and FiD techniques smoothen wavefront propagation thereby masking local areas of conduction slowing. Comparing patients with and without AF, slower wavefront propagation during SR was found at BB in PAF patients, indicating structural remodelling.

Safety and feasibility of hemodynamic pulmonary artery pressure monitoring using the CardioMEMS device in LVAD management.

BACKGROUND: There is a clinical need for additional remote tools to improve left ventricular assist device (LVAD) patient management. The aim of this pilot concept study was to assess the safety and feasibility of optimizing patient management with add-on remote hemodynamic monitoring using the CardioMEMS in LVAD patients during different treatment stages. METHODS: Ten consecutive patients accepted and clinically ready for (semi-) elective HeartMate 3 LVAD surgery were included. All patients received a CardioMEMS to optimize filling pressure before surgery. Patients were categorized into those with normal mean pulmonary artery pressure (mPAP) (≤25 mmHg, n = 4) or elevated mPAP (>25 mmHg, n = 6), and compared to a historical cohort (n = 20). Endpoints were CardioMEMS device safety and a combined endpoint of all-cause mortality, acute kidney injury, renal replacement therapy and/or right ventricular failure at 1-year follow-up. Additionally, we investigated hospital-free survival and improvement in quality of life (QoL) and exercise tolerance. RESULTS: No safety issues or signal interferences were observed. The combined endpoint occurred in 60% of historical controls, 0% in normal and 83% in elevated mPAP group. Post-discharge, the hospital-free survival was significantly better, and the QoL improved more in the normal compared to the elevated mPAP group. CONCLUSION: Remote hemodynamic monitoring in LVAD patients is safe and feasible with the CardioMEMS, which could be used to identify patients at elevated risk of complications as well as optimize patient management remotely during the out-patient phase with less frequent hospitalizations. Larger pivotal studies are warranted to test the hypothesis generated from this concept study.

Uncertainties and challenges in surgical and transcatheter tricuspid valve therapy: a state-of-the-art expert review.

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study.

BACKGROUND: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. METHODS: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. RESULTS: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28-627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0 .013). CONCLUSIONS: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.

Surgically implanted aortic valve bioprostheses deform after implantation: insights from computed tomography.

OBJECTIVE: Little is known about the prevalence and degree of deformation of surgically implanted aortic biological valve prostheses (bio-sAVRs). We assessed bio-sAVR deformation using multidetector-row computed tomography (MDCT). METHODS: Three imaging databases were searched for patients with MDCT performed after bio-sAVR implantation. Minimal and maximal valve ring diameters were obtained in systole and/or diastole, depending on the acquired cardiac phase(s). The eccentricity index (EI) was calculated as a measure of deformation as (1 - (minimal diameter/maximal diameter)) × 100%. EI of < 5% was considered none or trivial deformation, 5-10% mild deformation, and > 10% non-circular. Indications for MDCT and implanted valve type were retrieved. RESULTS: One hundred fifty-two scans of bio-sAVRs were included. One hundred seventeen measurements were performed in systole and 35 in diastole. None or trivial deformation (EI < 5%) was seen in 67/152 (44%) of patients. Mild deformation (EI 5-10%) was seen in 59/152 (39%) and non-circularity was found in 26/152 (17%) of cases. Overall, median EI was 5.5% (IQR 3.4-7.8). In 77 patients, both systolic and diastolic measurements were performed from the same scan. For these scans, the median EI was 6.5% (IQR 3.4-10.2) in systole and 5.1% (IQR3.1-7.6) in diastole, with a significant difference between both groups (p = 0.006). CONCLUSIONS: Surgically implanted aortic biological valve prostheses show mild deformation in 39% of cases and were considered non-circular in 17% of studied valves. KEY POINTS: • Deformation of surgically implanted aortic valve bioprostheses (bio-sAVRs) can be adequately assessed using MDCT. • Bio-sAVRs show at least mild deformation (eccentricity index > 5%) in 56% of studied cases and were considered non-circular (eccentricity index > 10%) in 17% of studied valves. • The higher deformity rate found in bio-sAVRs with (suspected) valve pathology could suggest that geometric deformity may play a role in leaflet malformation and thrombus formation similar to that of transcatheter heart valves.

Classification of sinus rhythm single potential morphology in patients with mitral valve disease.

AIMS: The morphology of unipolar single potentials (SPs) contains information on intra-atrial conduction disorders and possibly the substrate underlying atrial fibrillation (AF). This study examined the impact of AF episodes on features of SP morphology during sinus rhythm (SR) in patients with mitral valve disease. METHODS AND RESULTS: Intraoperative epicardial mapping (interelectrode distance 2 mm) of the right and left atrium (RA, LA), Bachmann's bundle (BB), and pulmonary vein area (PVA) was performed in 67 patients (27 male, 67 ± 11 years) with or without a history of paroxysmal AF (PAF). Unipolar SPs were classified according to their differences in relative R- and S-wave amplitude ratios. A clear predominance of S-waves was observed at BB and the RA in both the no AF and PAF groups (BB 88.8% vs. 85.9%, RA 92.1% vs. 85.1%, respectively). Potential voltages at the RA, BB, and PVA were significantly lower in the PAF group (P < 0.001 for each) and were mainly determined by the size of the S-waves amplitudes. The largest difference in S-wave amplitudes was found at BB; the S-wave amplitude was lower in the PAF group [4.08 (2.45-6.13) mV vs. 2.94 (1.40-4.75) mV; P < 0.001]. In addition, conduction velocity (CV) at BB was lower as well [0.97 (0.70-1.21) m/s vs. 0.89 (0.62-1.16) m/s, P < 0.001]. CONCLUSION: Though excitation of the atria during SR is heterogeneously disrupted, a history of AF is characterized by decreased SP amplitudes at BB due to loss of S-wave amplitudes and decreased CV. This suggests that SP morphology could provide additional information on wavefront propagation.

Emerging electromagnetic interferences between implantable cardioverter-defibrillators and left ventricular assist devices.

AIMS: To investigate the prevalence of electromagnetic interference (EMI) between left ventricular assist devices (LVADs) and implantable cardioverter-defibrillators (ICDs)/pacemakers (PMs). METHODS AND RESULTS: A retrospective single-centre study was conducted, including all patients undergoing HeartMate II (HMII) and HeartMate 3 (HM3) LVAD implantation (n = 106). Electromagnetic interference was determined by the inability to interrogate the ICD/PM. Overall, 85 (mean age 59 ± 8, 79% male) patients had an ICD/PM at the time of LVAD implantation; 46 patients with HMII and 40 patients with HM3. Among the 85 LVAD patients with an ICD's/PM's, 11 patients (13%) experienced EMI; 6 patients (15%) with an HMII and 5 patients (11%) with an HM3 (P = 0.59). Electromagnetic interference from the HMII LVADs was only present in patients with a St Jude/Abbott device; 6 of the 23 St Jude/Abbott devices. However, in the HM3 patients, EMI was mainly present in patients with Biotronik devices: 4 of the 18 with only one (1/25) patient with a Medtronic device. While initial interrogation of these devices was not successful, none of the 11 cases experienced pacing inhibition or inappropriate shocks. CONCLUSION: In summary, the prevalence of EMI between ICDs in the older and newer type of LVAD's remains rather high. While HMII patients experienced EMI with a St Jude/Abbott device (which was already known), HM3 LVAD patients experience EMI mainly with Biotronik devices. Prospective follow-up, preferably in large registries, is warranted to investigate the overall prevalence and impact of EMI in LVAD patients.

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91-123) for neonatal, 99% (95% CI: 85-115) for infant, and 77% (95% CI: 67-89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116-177) for neonatal, 111% (95% CI: 89-137) for infant, and 120% (95% CI: 97-149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.