Early results from the prospective ESPOIR Trial have indicated excellent results for pulmonary valve replacement using decellularized pulmonary homografts (DPH).
A 5-year analysis of ESPOIR Trial ...patients was performed to provide an insight into the midterm DPH performance. ESPOIR Trial and Registry patients were matched with cryopreserved homografts (CH) patients considering patient age, type of heart defect and previous procedures to present the overall experience with DPH.
A total of 121 patients (59 female) were prospectively enrolled (8/2014-12/2016), median age 16.5 years (interquartile range 11.2-29.8), and median DPH diameter 24 mm. One death (73 year-old) occurred during a median follow-up of 5.9 years (5.4-6.4), in addition to 2 perioperative deaths resulting in an overall mortality rate of 2.5%. One case of endocarditis in 637 patient-years was noticed, resulting in an incidence of 0.15% per patient-year. At 5 years, the mean peak gradient was 19.9 mmHg (9.9), mean regurgitation 0.9 (0.6, grade 0-3) and freedom from explantation/any reintervention 97.5% (1.5). The combined DPH cohort, n = 319, comprising both Trial and Registry data, showed significantly better freedom from explantation for DPH 95.5% (standard deviation 1.7) than CH 83.0% (2.8) (P < 0.001) and less structural valve degeneration at 10 years when matched to 319 CH patients DPH 65.5% (standard deviation 4.4) and CH 47.3% (3.7), P = 0.11.
The 5-year data of the prospective ESPOIR Trial show excellent performance for DPH and low rates of adverse events. ESPOIR Registry data up to 15 years, including a matched comparison with CH, demonstrated statistically significant better freedom from explantation.
Background
Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) ...in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation.
Methods
Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years.
Results
In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (
P
< 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27–3.29;
P
= 0.003), pre-existing TR (OR 4.30; 95% CI 2.51–7.38;
P
< 0.001), female sex (OR 1.68; 95% CI 1.16–2.43;
P
= 0.006), single RV lead (OR 1.67; 95% CI 1.09–2.56;
P
= 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42–3.05;
P
< 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07–3.67;
P
= 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04–1.84;
P
= 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02–1.77;
P
= 0.034), heart failure (HR 1.75; 95% CI 1.31–2.33;
P
< 0.001), kidney disease (HR 1.62; 95% CI 1.25–2.11;
P
< 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17–3.71;
P
< 0.001).
Conclusions
Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival.
Graphic abstract
Abstract
OBJECTIVES
We reviewed our institutional experience with outflow graft stenosis (OGS) in 3 contemporary left ventricular assist devices (LVAD).
METHODS
Data from 347 consecutive adult ...recipients of LVAD Medtronic HVAD (n = 184, 53.0%), Abbott HeartMate II (n = 62, 17.9%) and Abbott HeartMate 3 (n = 101, 29.1%) implanted between March 2006 and October 2019 were analysed retrospectively. Primary study end points were the incidence of OGS necessitating treatment and survival on LVAD support.
RESULTS
During the study period, 17 patients (4.9%) developed OGS requiring treatment with a probability of 0.6% at 1 year, 1.9% at 2 years, 3.8% at 3 years, 4.7% at 4 years and 5.9% at 5 years of LVAD support. Notably, in 13.8% of patients, a compression-related narrowing of the outflow graft with a probability of 1.5% at 6 months, 1.8% 1 year, 6.0% at 2 years, 12.3% at 3 years, 15.4% at 4 years and 16.6% at 5 years of LVAD support with no difference between devices (P = 0.26) was observed. There was a trend towards increased risk of mortality with OGS (hazard ratio 2.21, 95% confidence interval 0.87–5.51; P = 0.09). OGS preferentially occurred in segments of the outflow graft covered by a protective coating.
CONCLUSIONS
OGS is a rare but potentially lethal complication during LVAD support. Modifications of pump design and implant techniques may be needed because OGS preferentially occurs within covered portions of the outflow graft. Systematic screening may be warranted.
The durability of contemporary implantable left ventricular assist devices (LVAD) enables their use for long-term support.
Malignant cells ensure telomere maintenance by the alternative lengthening of telomeres (ALT) in the absence of telomerase activity (TA). The retrotransposons “long interspersed nuclear element-1” ...(LINE-1, L1) are expressed in malignant cells and are primarily known to contribute to complex karyotypes. Here we demonstrate that LINE-1 ribonucleoprotein particles (L1-RNPs) expression is significantly higher in ALT+- versus in TA+-human glioma. Analyzing a role of L1-RNP in ALT, we show that L1-RNPs bind to telomeric repeat containing RNA (TERRA), which is critical for telomere stabilization and which is overexpressed in ALT+ cells. In turn, L1-RNP knockdown (KD) abrogated the nuclear retention of TERRA, resulted in increased telomeric DNA damage, decreased cell growth and reduced expression of ALT characteristics such as c-circles and PML-bodies. L1-RNP KD also decreased the expression of Shelterin- and the ALT-regulating protein Topoisomerase IIIα (TopoIIIα) indicating a more general role of L1-RNPs in supporting telomeric integrity in ALT. Our findings suggest an impact of L1-RNP on telomere stability in ALT+ dependent tumor cells. As L1-RNPs are rarely expressed in normal adult human tissue those elements might serve as a novel target for tumor ablative therapy.
Objective Extracorporeal circulation is considered the gold standard in the treatment of hypothermic cardiocirculatory arrest; however, few centers use extracorporeal membrane oxygenation instead of ...standard extracorporeal circulation for this indication. The aim of this study was to evaluate whether extracorporeal membrane oxygenation-assisted resuscitation improves survival in patients with hypothermic cardiac arrest. Methods A consecutive series of 59 patients with accidental hypothermia in cardiocirculatory arrest between 1987 and 2006 were included. Thirty-four patients (57.6%) were resuscitated by standard extracorporeal circulation, and 25 patients (42.4%) were resuscitated by extracorporeal membrane oxygenation. Accidental hypothermia was caused by avalanche in 22 patients (37.3%), drowning in 22 patients (37.3%), exposure to cold in 8 patients (13.5%), and falling into a crevasse in 7 patients (11.9%). Multivariate logistic regression analysis was used to compare extracorporeal membrane oxygenation with extracorporeal circulation resuscitation, with adjustment for relevant parameters. Results Restoration of spontaneous circulation was achieved in 32 patients (54.2%). A total of 12 patients (20.3%) survived hypothermia. In the extracorporeal circulation group, 64% of the nonsurviving patients who underwent restoration of spontaneous circulation died of severe pulmonary edema, but none died in the extracorporeal membrane oxygenation group. In multivariate analysis, extracorporeal membrane oxygenation-assisted resuscitation showed a 6.6-fold higher chance for survival (relative risk: 6.6, 95% confidence interval: 1.2–49.3, P = .042). Asphyxia-related hypothermia (avalanche or drowning) was the most predictive adverse factor for survival (relative risk: 0.09, 95% confidence interval: 0.01–0.60, P = .013). Potassium and pH failed to show statistical significance in the multivariate analysis. Conclusions Extracorporeal rewarming with an extracorporeal membrane oxygenation system allows prolonged cardiorespiratory support after initial resuscitation. Our data indicate that prolonged extracorporeal membrane oxygenation support reduces the risk of intractable cardiorespiratory failure commonly observed after rewarming.
The use of polytetrafluoroethylene (PTFE) material as a protective cover for left ventricular assist device (LVAD) outflow grafts (OG) is a common practice. However, it has descriptively been linked ...to the development of blood flow obstruction (BFO).
Patient data from 194 consecutive HVAD (Medtronic Inc; Medtronic, Minneapolis, MN) recipients implanted between March 2006 and January 2021 were retrospectively analyzed. PTFE covers were used in 102 patients. Study outcomes included the incidence of BFO and survival on LVAD support.
Thirty-seven patients (19.1%) developed BFO during the study period. On a multivariable Cox regression analysis, PTFE use was an independent predictor for the development of BFO (HR 2.15, 95% CI 1.03-4.48, p = .04). BFO comprised of 2 types of device malfunction: eleven patients (5.7%) developed outflow graft stenosis (OGS), and 31 patients (16.0%) developed pump thrombosis (PT). There was a significantly higher cumulative incidence of OGS in patients with PTFE cover than in those without (Gray's test, p =.03). However, the observed higher cumulative incidence of PT in PTFE patients was non-significant (Gray's test, p =.06). In a multivariable Cox regression model, the effect of PTFE use on survival was non-significant (HR 0.95, 95% CI 0.60-1.48, p =.81), while the development of BFO was independently associated with increased mortality (HR 3.43, 95% CI 1.94-6.06, p < .0001).
The use of PTFE OG cover in LVAD patients is associated with an increased cumulative probability of development of BFO, the latter adversely impacting survival and is therefore, harmful.
Abstract
OBJECTIVES
Options for paediatric aortic valve replacement (AVR) are limited if valve repair is not feasible. Results of paediatric Ross procedures are inferior to adult Ross results, and ...mechanical AVR imposes constant anticoagulation with the inherent risks.
METHODS
The study design was a prospective, multicentre follow-up of all paediatric patients receiving decellularized aortic homografts (DAHs) for AVR in 8 European centres.
RESULTS
A total of 106 children (77 boys) were operated (mean age 10.1 ± 4.8 years, DAH diameter 20.5 ± 3.8 mm). A total of 60 (57%) had undergone previous surgical interventions: 34 with 1, 15 with 2 and 11 with ≥3. There was one early death in a 12-year-old girl, who underwent her fourth aortic valve operation, due to intracerebral haemorrhage on extracorporeal membrane oxygenation after coronary reimplantation problems following 3-sinus reconstruction 1 year earlier. One 2-year-old patient died due to sepsis 2 months postoperatively with no evidence for endocarditis. In addition, a single pacemaker implantation was necessary and a 2.5-year-old girl underwent successful HTx due to chronic myocardial failure despite an intact DAH. After a mean follow-up of 3.30 ± 2.45 years, primary efficacy end points mean peak gradient (18.1 ± 20.9 mmHg) and regurgitation (mean 0.61 ± 0.63, grade 0–3) were very good. Freedom from death/explantation/endocarditis/bleeding/stroke at 5 years was 97.8 ± 1.6/85.0 ± 7.4/100/100/100% respectively. Calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.9 years), lower than in Ross patients (9.4 years) and in the same range as mechanical AVR (12.8 years).
CONCLUSIONS
Even though the overall number of paediatric DAH patients and the follow-up time span are still limited, our data suggest that DAHs may present a promising additional option for paediatric AVR.
Angiographic studies have shown that external stenting reduces disease progression in saphenous vein grafts (SVG) for coronary artery bypass grafting (CABG). However, reports of clinical outcomes of ...external SVG stenting are limited.
We conducted a retrospective analysis using a prospectively maintained national registry to evaluate clinical outcomes in patients undergoing either isolated CABG or combined (CABG + valve) procedures with use of an external SVG stent between December 2015 and December 2019. Median follow-up was 36.2 months (IQR: 24.4-41.6 months). The primary endpoint was ischemia-driven target vessel revascularization at 1 year. Secondary endpoints included all-cause death, non-fatal myocardial infarction (MI), stroke, and the composite of death, non-fatal MI or stroke at 1 year. Kaplan-Meier rates of survival, freedom from the composite of death, non-fatal MI or stroke and freedom from repeat revascularization were calculated at 3 years.
The study population included 74 patients (isolated CABG, N.=61; combined procedure, N.=13). Mean age was 65.5±9.2 years, and 81% were male. External stenting of one SVG was performed in 63 patients (85%) and external stenting of 2 SVG in 11 patients (15%). External stenting was most frequently performed on an SVG to the right coronary artery (N.=45 patients; 53%). Ischemia-driven target-vessel revascularization occurred in 0% at 1 year. All-cause death, MI, stroke, and the composite of death, MI, or stroke at 1 year occurred in 2.7% (2/74), 0% (0/74), 1.4% (1/74), and 4.1% (3/74), respectively. At 3 years, the rates of survival, freedom from the composite of death, non-fatal MI or stroke, and freedom from repeat revascularization were 89.7% (95% CI: 78.0-95.3), 88.3% (95% CI: 76.5-94.4), and 94.8% (95% CI: 84.6-98.3), respectively.
Clinical outcomes with external SVG stenting are excellent without ischemia-driven target-vessel revascularization at 1 year, and low rates of repeat revascularization at 3 years. Further follow-up will show whether external stenting reduces SVG failure with a benefit on long-term clinical outcomes.
Thoracic aortic aneurysm (TAA) is an age-related and life-threatening vascular disease. Telomere shortening is a predictor of age-related diseases, and its progression is associated with premature ...vascular disease. The aim of the present work was to investigate the impacts of chronic hypoxia and telomeric DNA damage on cellular homeostasis and vascular degeneration of TAA. We analyzed healthy and aortic aneurysm specimens (215 samples) for telomere length (TL), chronic DNA damage, and resulting changes in cellular homeostasis, focusing on senescence and apoptosis. Compared with healthy thoracic aorta (HTA), patients with tricuspid aortic valve (TAV) showed telomere shortening with increasing TAA size, in contrast to genetically predisposed bicuspid aortic valve (BAV). In addition, TL was associated with chronic hypoxia and telomeric DNA damage and with the induction of senescence-associated secretory phenotype (SASP). TAA-TAV specimens showed a significant difference in SASP-marker expression of IL-6, NF-κB, mTOR, and cell-cycle regulators (γH2AX, Rb, p53, p21), compared to HTA and TAA-BAV. Furthermore, we observed an increase in CD163
macrophages and a correlation between hypoxic DNA damage and the number of aortic telocytes. We conclude that chronic hypoxia is associated with telomeric DNA damage and the induction of SASP in a diseased aortic wall, promising a new therapeutic target.
Nosocomial infections are a common complication in clinical practice with major impact on surgical success and patient outcome. The probability of nosocomial infections is rapidly increasing during ...hospitalization. Therefore, we investigated the impact of a prolonged pre-operative hospital stay on the development of post-operative infection. Within this prospective observational study, 200 patients scheduled for elective cardiac surgery were enrolled. Patients were followed during hospital admission and screened for the development of nosocomial infection. Logistic regression analysis was used to assess the impact of a prolonged pre-operative hospital stay on the development of infection. A total of 195 patients were suitable for the final analysis. We found a strong and direct association of the duration of pre-operative hospital stay and the number of patients developing infection (+23.5%; p = 0.006). Additionally, the length of patients' pre-operative hospital stay was independently associated with the development of post-operative nosocomial infection, with an adjusted OR per day of 1.38 (95%CI: 1.02-1.86; p = 0.036). A prolonged pre-operative hospital stay was significantly associated with the development of nosocomial infection after cardiac surgery. Those findings need to be considered in future clinical patient management in order to prevent unnecessary antibiotic use and potential harm to patients.
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