Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

The Clinical Impact of the Extension of Acute Type A Aortic Surgery on Long-Term Outcomes: Should We Tend to Be Conservative?

Background and Objectives: Despite advances in surgical techniques, industry adjuncts, and cerebral perfusion techniques, the in-hospital mortality rate of type A acute dissection (TAAD) remains at 15-30%. This study aimed to investigate the influence of different extents of aortic resection on survival and quality of life (QoL) after long-term follow-up. Materials and Methods: A retrospective observational trial was performed, including 165 patients operated upon for TAAD. Patients were divided into two groups according to the extent of their aortic repair: the first group comprised patients who had ascending aorta replacement and the second included patients who had hemiarch or total arch replacement. The groups were compared with regard to their baseline characteristics, operative characteristics, survival, complications, and QoL during nine years of follow-up. Results: The mean follow-up time was 75.6 months (1-108 months). The mean survival in the ascending aorta repair group was 89.651 (81.242-98.061) months and was 54.801 (40.053-69.548) months in the hemiarch and arch group; the difference between the groups was significant (log-rank p < 0.001). The rate of new postoperative neurological deficits was statistically higher in the hemiarch and arch group (17.5% vs. 8.4%, p = 0.045), the most common being stroke, and was also more frequent in the hemiarch and arch group than in the ascending aorta group (with statistical significance (15.7% vs. 6.5%)). The mean SF-12 physical score from the QoL questionnaire was higher in the ascending aorta replacement group than in the hemiarch and arch group (50.1 ± 7.3 vs. 44.0 ± 11.9, p = 0.017). Additionally, the mean SF-12 mental score was higher in the ascending aorta replacement group (52.3 ± 7.3 vs. 47.1 ± 12.8, p = 0.032). Conclusions: A more aggressive approach involving aortic arch repair means a lower survival rate and lesser quality of life after long-term follow-up in comparison with the replacement of the ascending aorta. If clinically applicable, a more defensive strategy may be considered.

Pulmonary Artery Hypertension as A Risk Factor for Long-Term Survival after Heart Transplantation.

BACKGROUND: Heart failure is the most frequent cause of pulmonary artery hypertension (PAH) and its severity may predict the development of heart failure (HF) and is known to be a prognostic factor of poor outcome after heart transplant (HTx). The aim of this study was to investigate the impact of preoperative PAH related to left-sided HF on long-term survival after HTx and to identify the hemodynamic parameters of PAH that predict survival after HTx. METHODS: A prospective observational trial was performed, and it included 44 patients subjected to heart transplantation. Patients were divided into two groups: The first one with the preoperative diagnosis of PAH and the second one without the PAH diagnosed prior to the HTx. The two groups were compared for baseline characteristics, operative characteristics, survival, and hemodynamic parameters obtained by right heart catheterization. Survival was analyzed using Kaplan Meyer analysis, and Cox regression analysis was performed to determine independent predictors of survival. RESULTS: The median follow-up time was 637.4 days (1-2028 days). The median survival within the group of patients with preoperative PAH was 1144 days (95% CI 662.884-1625.116) and 1918.920 days (95% CI 1594.577-2243.263) within the group of patients without PAH (P = .023), HR 0.279 (95% [CI]: 0.086-0.910; P = .034. The 30-day mortality in patients within PAH group was significantly higher, six versus two patients in the non PAH group (χ2 = 5.103, P < .05), while the long-term outcome after this period did not differ between the groups. Patients with preoperative PAH had significantly higher values of MPAP, PCWP, TPG and PVRI, while CO and CI did not differ between the two groups. Mean PVRI was 359.1 ± 97.3 dyn·s·cm-5 in the group with preoperative PAH and 232.2 ± 22.75 dyn·s·cm-5 in the group without PAH, P < .001. TPG values were 11.95 ± 5.08 mmHg in the PAH group while patients without PAH had mean values of 5.16 ± 1.97 mmHg, P < .001. Cox regression analysis was done for the aforementioned parameters. Hazard ratio for worse survival after HTx for elevated values of PVRI was 1.006 (95% [CI]: 1.001-1.012; P = .018) TPG had a hazard ratio of 1.172 (95% [CI]: 1.032-1.233; P = .015). CONCLUSION: Pulmonary artery hypertension is an independent risk factor for higher 30-day mortality after HTx, while it does not affect the long-term outcome. Hemodynamic parameters obtained by right heart catheterization in heart transplant candidates could predict postoperative outcome. PVRI and TPG have been identified as independent predictors of higher 30-day postoperative mortality.

Surgical Challenges of Heart Mate 3 Pump Implantation in Aneurysmally Changed Heart Ventricles.

We presented surgical treatment of three patients indicated for implantation of a permanent mechanical circulatory support device and with the associated left ventricular aneurysms. In order to evade the left ventricular rupture, adverse thromboembolic events and provide safe implantation of the inflow cannula, LVAD HM3 implantation together with the reconstruction of the left ventricular aneurysmal wall was performed in two patients. Regarding the third patient, LVAD implantation upon the reconstruction of the left ventricular wall was abandoned because there was no safe location for placement of the inflow cannula.

The Challenges to Abdominal and Cardiac Surgeons: Emergency Splenectomy after LVAD Implantation-A Case Report.

The paper presents collaboration of an abdominal surgeon and heart team in deciding upon surgical management of a patient with the implanted left ventricular assist device, who has undergone emergency abdominal operation for spleen rupture. The paper focuses on the significance of prompt diagnostics, clinical challenges of hemodynamic and anticoagulant treatment, abdominal organ exposure along the placed left ventricular assist device driveline, identification of vascular structures in conditions of continuous blood flow, and reconstruction of the surgical wound in the driveline projection.

A novel composite smeared finite element for mechanics (CSFEM): Some applications.

BACKGROUND: Mechanical forces at the micro-scale level have been recognized as an important factor determining various biological functions. The study of cell or tissue mechanics is critical to understand problems in physiology and disease development. OBJECTIVE: The complexity of computational models and efforts made for their development in the past required significant robustness and different approaches in the modeling process. METHOD: For the purpose of modeling process simplifications, the smeared mechanics concept was introduced by M. Kojic as a general concept for modeling the deformation of composite continua. A composite smeared finite element for mechanics (CSFEM) was formulated which consists of the supporting medium and immersed subdomains of deformable continua with mutual interactions. Interaction is modeled using 1D contact elements (for both tangential and normal directions), where the interaction takes into account appropriate material parameters as well as the contact areas. RESULTS: In this paper we have presented verification examples with applications of the CSFEMs that include the pancreatic tumor tissue, nano-indentation model and tumor growth model. CONCLUSION: We have described CSFEM and contact elements between compartments that can interact. Accuracy and applicability are determined on two verification and tumor growth examples.

Impact of Right Heart Failure on Clinical Outcome of Left Ventricular Assist Devices (LVAD) Implantation: Single Center Experience.

The aim of this study was to examine the incidence and significance of right heart failure (RHF) in the early and late phase of left ventricular assist device (LVAD) implantation with the identification of predictive factors for the development of RHF. This was a prospective observational analytical cohort study. The study included 92 patients who underwent LVAD implantation and for whom all necessary clinical data from the follow-up period were available, as well as unambiguous conclusions by the heart team regarding pathologies, adverse events, and complications. Of the total number of patients, 43.5% died. The median overall survival of patients after LVAD implantation was 22 months. In the entire study population, survival rates were 88.04% at one month, 80.43% at six months, 70.65% at one year, and 61.96% at two years. Preoperative RHF was present in 24 patients, 12 of whom died and 12 survived LVAD implantation. Only two survivors developed early RHF (ERHF) and two late RHF (LRHF). The most significant predictors of ERHF development are brain natriuretic peptide (BNP), pre-surgery RHF, FAC < 20%, prior renal insufficiency, and total duration of ICU stay (HR: 1.002, 0.901, 0.858, 23.554, and 1.005, respectively). RHF following LVAD implantation is an unwanted complication with a negative impact on treatment outcome. The increased risk of fatal outcome in patients with ERHF and LRHF after LVAD implantation results in a need to identify patients at risk of RHF, in order to administer the available preventive and therapeutic methods.

Morphogenetic dispositions for variability in acute kidney injury after cardiac surgery: Pilot study.

Background: The aim of our study was to evaluate the degree of genetic homozygosity in cardiac surgical patients with postoperative acute kidney injury (AKI), compared to the subgroup without postoperative AKI, as well as to evaluate antropomorpho-genetic variability in cardiac surgical patients with regard to the presence and severity degree of AKI. Materials and methods: The prospective cohort study included an analysis of 138 eligible coronary artery disease (CAD) surgical patients that were screened consecutively. The tested group was divided into three subgroups according to RIFLE criteria: Subgroup NoAKI (N = 91), risk (N = 31), and injury (N = 16). All individuals were evaluated for the presence of 19 observable recessive human traits (ORHT) as a marker of chromosomal homozygosity and variability. Results: Comparing subgroups NoAKI and risk, four ORHTs were significantly more frequent in the risk subgroup. Comparing subgroups NoAKI and injury, nine ORHTs were significantly more frequent in the injury subgroup; while comparing the injury subgroup and risk, five ORHTs were significantly more frequent in injury than in the risk subgroup. Results also showed a significant increase in the mean value of ORHTs for the injury subgroup compared to NoAKI subgroup (p = 0.039). Variability decreased proportionally to the increase in the severity of AKI (V NoAKI = 32.81%, V Risk = 30.92%, and V Injury = 28.62%). Conclusion: Our findings pointed to the higher degree of recessive homozygosity and decreased variability in AKI patients vs. NoAKI individuals, thus presumably facilitating the development and severity degree expression of AKI in patients after cardiac surgery.

Oxidative Stress in Patients before and after On-Pump and Off-Pump Coronary Artery Bypass Grafting: Relationship with Syntax Score.

OBJECTIVE: Coronary artery bypass grafting (CABG) represents the significant source of increased oxidative stress (OS). We aimed to follow the OS status parameters (i.e., ischemia-modified albumin (IMA), malondialdehyde (MDA), superoxide anion, prooxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), and superoxide-dismutase (SOD)) change through the predefined study times in two different surgical procedures, i.e., cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting (OPCAB). Additionally, we aimed to investigate those OS status parameters in specific study times according to SYNTAX score (SS), an established angiographic score for evaluating the extensity and severity of coronary artery disease. Patients and Methods. A total of 107 patients that were planned to undergo CABG were included (i.e., 47 patients in OPCAB and 60 patients in CPB group). Blood samples were taken at 6 time intervals: before surgery (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after termination of the operation (t6). RESULTS: IMA levels were higher in CPB than that in OPCAB baseline and rose in CPB group in t2 point. TOS decreased in both study groups, compared to baseline values, but without statistical significance. Superoxide anion and PAB significantly increased in t3-t6 study times, in both groups. MDA significantly increased only in CPB group in t5 and t6 interval. MDA was significantly higher in CPB group compared to OPCAB in t6 study point. CPB patients had significantly lower TAS compared to OPCAB patients at the beginning and in t2 and t3 study points. They also had significantly lower SOD activities compared to OPCAB, baseline, and in several study points. Moreover, TAS, SOD, and TAS/TOS ratio were significantly lower, whereas PAB and TOS/TAS were significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of high SS. CONCLUSION: CPB patients were in more severe ischemia baseline than OPCAB group and IMA rose in CPB patients immediately after the surgery end, but not later. Also, the antioxidant status was significantly lower, whereas the prooxidant status was significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of CAD (as determined with SS), showing that SOD and IMA had very good discriminatory capability towards higher SS status.

Genetic and Environmental Dispositions for Cardiovascular Variability: A Pilot Study.

BACKGROUND: The aim of our study was to evaluate the degree of genetic homozygosity in the group of patients with coronary artery disease (CAD), as well as to evaluate morphogenetic variability in CAD patients regarding the presence of investigated risk factors (RF) compared to a control sample of individuals. Additionally, we aimed to evaluate the distribution of ABO blood type frequencies between tested samples of individuals. METHODS: This study analyzed individual phenotype and morphogenetic variability of 17 homozygously-recessive characteristics (HRC), by using HRC test in a sample of 148 individuals in CAD patients group and 156 individuals in the control group. The following RF were analyzed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. RESULTS: The mean value of HRC in CAD patients is significantly higher, while variability decreases compared to the control sample (CAD patients: 4.24 ± 1.59, control sample: 3.75 ± 1.69; VCAD-patients = 37.50%, VC = 45.07%). There is a significant difference in individual variations of 17 HRC between control sample and CAD patients (χ² = 169.144; p < 0.01), which points out to different variability for tested genes. Mean values of HRC significantly differed in CAD patients in regard to the number of RF present. A blood type (OR = 1.75) is significant predictor for CAD, while O blood type (OR = 0.43) was significantly associated with controls. CONCLUSION: There is a higher degree of recessive homozygosity in CAD patients versus individuals in the control sample, and the presence of significant variations in the degree of recessive homozygosity as the number of tested RF increases.

Assessment of cortical bone fracture resistance curves by fusing artificial neural networks and linear regression.

Bone injures (BI) represents one of the major health problems, together with cancer and cardiovascular diseases. Assessment of the risks associated with BI is nontrivial since fragility of human cortical bone is varying with age. Due to restrictions for performing experiments on humans, only a limited number of fracture resistance curves (R-curves) for particular ages have been reported in the literature. This study proposes a novel decision support system for the assessment of bone fracture resistance by fusing various artificial intelligence algorithms. The aim was to estimate the R-curve slope, toughness threshold and stress intensity factor using the two input parameters commonly available during a routine clinical examination: patients age and crack length. Using the data from the literature, the evolutionary assembled Artificial Neural Network was developed and used for the derivation of Linear regression (LR) models of R-curves for arbitrary age. Finally, by using the patient (age)-specific LR models and diagnosed crack size one could estimate the risk of bone fracture under given physiological conditions. Compared to the literature, we demonstrated improved performances for estimating nonlinear changes of R-curve slope (R2 = 0.82 vs. R2 = 0.76) and Toughness threshold with ageing (R2 = 0.73 vs. R2 = 0.66).

The Gender Impact on Morphogenetic Variability in Coronary Artery Disease: A Preliminary Study.

We analyzed morphogenetic variability and degree of genetic homozygosity in male and female individuals with coronary artery disease (CAD) versus unaffected controls. We have tested 235 CAD patients; 109 were diagnosed also with diabetes mellitus (DM) and 126 with hypertension (HTN). We additionally evaluated 152 healthy individuals without manifested CAD. For the evaluation of the degree of recessive homozygosity, we have performed the homozygously recessive characteristics (HRC) test and tested 19 HRCs. In controls, the frequency of HRC for males was 2.88 ± 1.89, while for females, it was 3.65 ± 1.60. In the CAD group, the frequency of HRC for males was 4.21 ± 1.47, while for females, it was 4.73 ± 1.60. There is significant difference in HRC frequencies between controls and CAD separately for males (p < 0.001) and females (p < 0.001). The same applies between controls and CAD with DM (males: p < 0.001 and females: p = 0.004), and controls and CAD with HTN (males: p < 0.001 and females: p < 0.001). There is no significant difference in HRC frequencies between the group of CAD with DM and the group of CAD with HTN (males: p = 0.952 and females: p = 0.529). Our findings point to the increased degree of recessive homozygosity and decreased variability in both genders of CAD patients versus controls, indicating the potential genetic predisposition for CAD.