OBJECTIVES—Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of ...atherosclerosis.
METHODS AND RESULTS—In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.61.1.–2.3, P=0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm, P<0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies.
CONCLUSION—Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations.
Successful therapy of heart failure with preserved ejection fraction (HFpEF) remains a major unmet clinical need. Device-based treatment approaches include the interatrial shunt device (IASD), ...conventional assist devices pumping blood from the left ventricle (LV-VAD) or the left atrium (LA-VAD) towards the aorta, and a valveless pulsatile assist device with a single cannula operating in co-pulsation with the native heart (CoPulse). Hemodynamics of two HFpEF subgroups during rest and exercise condition were translated into a lumped parameter model of the cardiovascular system. The numerical model was applied to assess the hemodynamic effect of each of the four device-based therapies. All four therapy options show a reduction in left atrial pressure during rest and exercise and in both subgroups (> 20%). IASDs concomitantly reduce cardiac output (CO) and shift the hemodynamic overload towards the pulmonary circulation. All three mechanical assist devices increase CO while reducing sympathetic activity. LV-VADs reduce end-systolic volume, indicating a high risk for suction events. The heterogeneity of the HFpEF population requires an individualized therapy approach based on the underlying hemodynamics. Whereas phenotypes with preserved CO may benefit most from an IASD device, HFpEF patients with reduced CO may be candidates for mechanical assist devices.
This study sought to assess the long-term outcome of active surveillance in these patients.
The optimal timing of mitral valve surgery in asymptomatic primary mitral regurgitation (MR) remains ...controversial.
Between 1997 and 2015, 280 consecutive patients with severe asymptomatic primary MR were enrolled in our heart valve clinic follow-up program. They were prospectively followed up every 6 months clinical and echocardiographical examinations until surgical criteria were reached. Event-free survival and overall survival as compared with the age- and gender-matched general population were assessed.
During a median potential follow-up of 93.4 (quartiles 55.3 to 152.9) months, 161 patients developed an indication for surgery and 13 patients died. Event-free survival rates were 78.0% (95% confidence interval CI: 73.2% to 83.2%) at 2 years, 52.2% (95% CI: 46.3% to 59.0%) at 6 years, 35.5% (95% CI: 29.3% to 43.1%) at 10 years, and 18.7% (95% CI: 12.3% to 28.5%) at 15 years. Overall survival rate was 99.6% (95% CI: 98.9% to 100%) at 2 years, 94.6% (95% CI: 91.7% to 97.6%) at 6 years, 85.6% (95% CI: 80.3% to 91.2%) at 10 years, and 74.5% (95% CI: 66.6% to 83.4%) at 15 years. Overall survival of patients managed according to an active surveillance strategy was comparable with the expected cumulative survival and early survival rates were even better in the study population (standardized mortality ratio: 0.667; 95% CI: 0.463 to 0.963; p = 0.013).
Patients with severe asymptomatic primary MR may remain free of indications for surgery for extensive periods of time. In such patients, active surveillance performed in experienced centers is associated with a favorable prognosis, resulting in timely referral to surgery, excellent long-term survival, and good surgical outcomes.
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Asymptomatic Severe Aortic Stenosis in the Elderly Zilberszac, Robert, MD; Gabriel, Harald, MD; Schemper, Michael, PhD ...
JACC. Cardiovascular imaging,
2017, January 2017, 2017-01-00, 20170101, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives This study sought to assess the natural history and optimal timing of surgery in elderly patients with severe asymptomatic aortic stenosis (AS). Background AS is increasingly ...diagnosed in an aging population, and large numbers of elderly patients are undergoing aortic valve procedures. However, the average age of patients represented in most natural history studies on AS is between 60 and 70 years. Methods A total of 103 consecutive patients >70 years of age (51 female; mean age 77 ± 5 years) with asymptomatic severe AS (peak aortic jet velocity AV-Vel 4.7 ± 0.6 m/s) were prospectively followed. Results During follow-up, 91 events occurred, including an indication for aortic valve replacement in 82 patients and cardiac deaths in 9, respectively. Event-free survival was 73%, 43%, 23%, and 16% at 1, 2, 3, and 4 years, respectively. Physical mobility was impaired in 29% of the patients, and symptom onset was severe (New York Heart Association functional class ≥III) in 43% of those who developed symptoms. Patients with AV-Vel ≥5.0 m/s had event-free survival rates of 21% and 6% at 2 and 4 years, respectively, compared with 57% and 23% for patients with AV-Vel <5.0 m/s (p < 0.001). Seventy-one patients underwent aortic valve replacement, and post-operative survival was 89% and 77% after 1 and 3 years, respectively. Conclusions In elderly patients with severe but asymptomatic AS, mild symptoms may be difficult to detect, particularly when mobility is impaired and severe symptom onset is common, warranting close clinical follow-up. Furthermore, a very high event rate can be expected, and cardiac deaths are not infrequent. Thus, elective aortic valve procedures may be considered in selected elderly patients at low procedural risk.
Treatment of aortic-valve disease in young patients still poses challenges. The Ross procedure offers several potential advantages that may translate to improved long-term outcomes.
This study ...reports long-term outcomes after the Ross procedure.
Adult patients who were included in the Ross Registry between 1988 and 2018 were analyzed. Endpoints were overall survival, reintervention, and major adverse events at maximum follow-up. Multivariable regression analyses were performed to identify risk factors for survival and the need of Ross-related reintervention.
There were 2,444 adult patients with a mean age of 44.1 ± 11.7 years identified. Early mortality was 1.0%. Estimated survival after 25 years was 75.8% and did not statistically differ from the general population (p = 0.189). The risk for autograft reintervention was 0.69% per patient-year and 0.62% per patient-year for right-ventricular outflow tract (RVOT) reintervention. Larger aortic annulus diameter (hazard ratio HR: 1.12/mm; 95% confidence interval CI: 1.05 to 1.19/mm; p < 0.001) and pre-operative presence of pure aortic insufficiency (HR: 1.74; 95% CI: 1.13 to 2.68; p = 0.01) were independent predictors for autograft reintervention, whereas the use of a biological valve (HR: 8.09; 95% CI: 5.01 to 13.08; p < 0.001) and patient age (HR: 0.97 per year; 95% CI: 0.96 to 0.99; p = 0.001) were independent predictors for RVOT reintervention. Major bleeding, valve thrombosis, permanent stroke, and endocarditis occurred with an incidence of 0.15% per patient-year, 0.07% per patient-year, 0.13%, and 0.36% per patient-year, respectively.
The Ross procedure provides excellent survival over a follow-up period of up to 25 years. The rates of reintervention, anticoagulation-related morbidity, and endocarditis were very low. This procedure should therefore be considered as a very suitable treatment option in young patients suffering from aortic-valve disease. (Long-Term Follow-up After the Autograft Aortic Valve Procedure Ross Operation; NCT00708409)
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The aim of this study was to evaluate mortality and neurological outcomes of cardioembolic cerebral stroke in infective endocarditis (IE) patients requiring cardiac surgery.
A consecutive series of ...214 patients undergoing cardiac surgery for IE was followed up for 20 years. In 65 patients (mean age, 52 years), IE was complicated by computed tomography- or magnetic resonance imaging-verified stroke (n=61) or transient ischemic attack (n=4). Perioperative (30-day) and long-term mortality was assessed with regression models adjusting for age. Complete neurological recovery of IE survivors was defined by a modified Rankin score of < or = 1 and a Barthel index of 20 points.
Fifty of 61 stroke patients (81.9%) survived surgery. In comparison with nonstroke patients, the age-adjusted perioperative mortality risk was 1.70-fold (95% CI, 0.73 to 3.96, P=0.22) higher and long-term mortality risk was 1.23-fold (95% CI, 0.72 to 2.11, P=0.45) higher in stroke patients. Patients with complicated stroke (meningitis, hemorrhage, or brain abscess) showed a higher perioperative mortality rate (38.9% vs 8.5%, P=0.007) but no higher neurological complication rate than patients with uncomplicated ischemic stroke. Complete neurological recovery was achieved in 35 IE survivors (70%, 95% CI, 55% to 82%). However, in the case of middle cerebral artery stroke, recovery was only 50% and was significantly lower compared with non-middle cerebral artery stroke (P=0.012).
Uncomplicated IE-related stroke showed a favorable prognosis with regard to both long-term survival and neurological recovery. The formidable risk of secondary cerebral hemorrhage due to cardiac surgery seems to be much lower than previously thought.
Abstract
Left ventricular assist devices can reverse pulmonary hypertension in cardiac transplant candidates with heart failure with a reduced ejection fraction. Whether a similar approach is ...applicable in restrictive cardiomyopathy is uncertain. We report the successful implantation of a Medtronic HVAD left ventricular assist device in a bridge-to-candidacy concept in 2 paediatric patients with restrictive cardiomyopathy.
Pulmonary hypertension (PH) is frequent in patients with restrictive cardiomyopathy and a contraindication for a cardiac transplant due to the risk of post-transplant failure of the unconditioned right ventricle 1.
Driveline infections (DLI) are common adverse events in left ventricular assist devices (LVADs), leading to severe complications and readmissions. The study aims to characterize risk factors for DLI ...readmission 2 years postimplant. This single‐center study included 183 LVAD patients (43 HeartMate II HMII, 29 HeartMate 3 HM3, 111 HVAD) following hospital discharge between 2013 and 2017. Demographics, clinical parameters, and outcomes were retrospectively analyzed and 12.6% of patients were readmitted for DLI, 14.8% experienced DLI but were treated in the outpatient setting, and 72.7% had no DLI. Mean C‐reactive protein (CRP), leukocytes and fibrinogen were higher in patients with DLI readmission (P < .02) than in outpatient DLI and patients without DLI, as early as 60 days before readmission. Freedom from DLI readmission was comparable for HMII and HVAD (98% vs. 87%; HR, 4.52; 95% CI, 0.58‐35.02; P = .15) but significantly lower for HM3 (72%; HR, 10.82; 95% CI, 1.26‐92.68; P = .03). DLI (HR, 1.001; 95% CI, 0.999‐1.002; P = .16) or device type had no effect on mortality. DLI readmission remains a serious problem following LVAD implantation, where CRP, leukocytes, and fibrinogen might serve as risk factors already 60 days before. HM3 patients had a higher risk for DLI readmissions compared to HVAD or HMII, possibly because of device‐specific driveline differences.
Graphical presentation of the methods, results and implications of this study.
Abstract
OBJECTIVES
Although post-cardiotomy extracorporeal life support (PC-ECLS) is a potentially life-saving resource for patients with cardiopulmonary failure after cardiac surgery, adverse ...outcomes have been reported even in successfully weaned patients. The goal of this study was to assess outcome in patients weaned from PC-ECLS.
METHODS
Of 573 consecutive patients who received PC-ECLS at a single centre between 2000 and 2019, 478 patients were included in a retrospective analysis. Successful weaning was defined as survival >24 h after extracorporeal life support (ECLS) explantation. Mortality of patients on ECLS, as well as in-hospital mortality of weaned patients, was assessed. A binary logistic regression model with backward elimination was used to identify predictors for in-hospital mortality after successful ECLS explantation.
RESULTS
Of 478 included patients, 120 patients (25.1%) died on ECLS or within 24 h after ECLS explantation. A total of 358 patients were successfully separated from ECLS and survived for >24 h (n = 352 weaned, n = 3 transitioned to durable left ventricular assist device and n = 3 transitioned to a heart transplant). A total of 35.5% of patients who were successfully weaned from ECLS did not survive until hospital discharge. In-hospital deaths of the whole cohort were 51.7% (247/478 patients). For patients who survived to discharge (231/478 patients, 48.3%), survival was 87% after 1 year and 68.9% after 5 years.
CONCLUSIONS
In-hospital mortality of patients requiring PC-ECLS is high even in case of successful weaning. Longer ECLS duration, older age, female gender and low preoperative glomerular filtration rate were risk factors for in-hospital mortality after ECLS weaning. Survival of patients discharged after PC-ECLS was encouraging.
Along with the rising complexity of procedures and the increasing age and morbidity of the patient population, the utilization of temporary extracorporeal life support (ECLS) after cardiac surgery (post-cardiotomy ECLS (PC-ECLS) is steadily increasing 1–4.
The demand for decellularized xenogeneic tissues used in reconstructive heart surgery has increased over the last decades. Complete decellularization of longer and tubular aortic sections suitable ...for clinical application has not been achieved so far. The present study aims at analyzing the effect of pressure application on decellularization efficacy of porcine aortas using a device specifically designed for this purpose. Fresh porcine descending aortas of 8 cm length were decellularized using detergents. To increase decellularization efficacy, detergent treatment was combined with pressure application and different treatment schemes. Quantification of penetration depth as well as histological staining, scanning electron microscopy, and tensile strength tests were used to evaluate tissue structure. In general, application of pressure to aortic tissue does neither increase the decellularization success nor the penetration depth of detergents. However, it is of importance from which side of the aorta the pressure is applied. Application of intermittent pressure from the adventitial side does significantly increase the decellularization degree at the intimal side (compared to the reference group), but had no influence on the penetration depth of SDC/SDS at both sides. Although the present setup does not significantly improve the decellularization success of aortas, it is interesting that the application of pressure from the adventitial side leads to improved decellularization of the intimal side. As no adverse effects on tissue structure nor on mechanical properties were observed, optimization of the present protocol may potentially lead to complete decellularization of larger aortic segments.
Graphical Abstract
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