Mechanical Circulatory Support During Surgical Revascularization for Ischemic Cardiomyopathy.

BACKGROUND: This study aimed to describe the use of perioperative mechanical circulatory support (MCS) and its impact on outcomes in patients with ischemic cardiomyopathy who were undergoing surgical revascularization. METHODS: Patients with an ejection fraction <35% who underwent isolated coronary artery bypass grafting (CABG) from 2015 to 2021 were identified (N = 378). Patients were divided into no MCS, preoperative MCS, and postoperative MCS groups on the basis of timing of MCS initiation, which included intraaortic balloon pump, extracorporeal membrane oxygenation, or Impella device (Abiomed) use. The primary outcome of interest was operative mortality. RESULTS: The median Society of Thoracic Surgeons Predicted Risk of Mortality was 2.4%. Sixty-six percent (n = 246) of patients had a previous myocardial infarction, and 61.8% of these patients were within 21 days of CABG. Twenty-one patients (5.6%) presented in cardiogenic shock. The preoperative MCS cohort consisted of 31 patients (8.2%) who underwent CABG a median of 2 days after MCS initiation. Thirty (7.9%) patients required postoperative MCS. Independent risk factors for requiring postoperative MCS included the preoperative ejection fraction (odds ratio, 0.93; P = .01 and the presence of preoperative MCS (odds ratio, 3.06; P = .02). Overall, operative mortality was 3.4%, and 3-year survival was 87.0%. Operative mortality in patients who did and did not receive preoperative MCS was 7.7% and 2.9% (P = .12) with no difference in long-term survival (P = .80), whereas patients requiring postoperative MCS had significantly increased operative (16.7%) and late mortality (63%; P <.01). CONCLUSIONS: CABG can be performed safely in patients with ischemic cardiomyopathy with selective use of perioperative MCS. Despite advanced disease severity, patients requiring preoperative MCS demonstrate acceptable short- and long-term survival. Patients requiring postoperative MCS have increased postoperative morbidity and mortality.

Aortic insufficiency following balloon aortic valvuloplasty does not impact long-term autograft durability after the Ross procedure.

OBJECTIVE: Preoperative aortic insufficiency (AI) is associated with inferior autograft durability after the Ross procedure. However, many patients with aortic stenosis (AS) undergo balloon aortic valvuloplasty (BAV) early and present with longstanding AI before Ross. We studied how BAV and subsequent valvular pathology impacts autograft durability. METHODS: Patients undergoing the Ross operation from 1993 to 2020 were identified. Those who underwent BAV before Ross were compared with patients who did not undergo BAV and underwent Ross for predominant AI (AI group) or AS (AS group). Those who underwent previous open surgical aortic valve intervention were excluded. Primary outcome of interest was autograft failure, defined as a composite of autograft reintervention or severe insufficiency. RESULTS: A total of 198 patients were included. Seventy-nine (39.9%) underwent BAV and subsequently underwent the Ross for predominant AI (45.6%) or AS (54.4%). Of patients who did not undergo BAV, 66 (33.3%) presented with predominant AI and 53 (26.8%) with AS. Freedom from autograft failure at 15 years was 90%, 92%, and 62% in BAV, AS, and AI groups, respectively. The AI group was at significantly increased risk of long-term autograft failure (hazard ratio, 5.6; P = .01), whereas the AS and BAV groups had similar, low risk (hazard ratio, 1.1; P = .91). Autograft durability was similar among patients who received BAV and presented with AS or AI before the Ross (P = .84). CONCLUSIONS: BAV before the Ross procedure is common in patients with AS. These patients have excellent long-term autograft durability regardless of preoperative valvular pathology and should strongly be considered for the Ross operation.

Long-term autograft dilation and durability after the Ross procedure are similar in infants, children, and adolescents with primary aortic stenosis.

BACKGROUND: Autograft durability and remodeling are thought to be superior in younger pediatric patients after the Ross operation. We sought to delineate the fate of autografts across the pediatric age spectrum in patients with primary aortic stenosis (AS). METHODS: We retrospectively reviewed patients age ≤18 years with primary AS who underwent the Ross operation between 1993 and 2020. Patients were categorized by age. The primary endpoint was autograft dimensional change, and secondary endpoints were severe neo-aortic insufficiency (AI) and autograft reintervention. RESULTS: A total of 119 patients underwent the Ross operation, including 37 (31.1%) in group I (age <18 months), 24 (20.2%) in group II (age 18 months-8 years), and 58 (48.7%) in group III (age 8-18 years). All groups exhibited similar annular growth rates within the first 5 postoperative years, followed by a collective decrease in annulus growth rates from year 5 to year 10. Group III experienced rapid sinus dilation in the first 5 years, followed by stabilization of the sinus z-score from year 5 to year 10, whereas groups I and II demonstrated stable sinus z-scores over 10 years. There were 4 early deaths (3.4%) and 2 late deaths (1.7%) at a median follow-up of 8.1 years (range, 0.01-26.3 years). At 15 years, the incidences of severe neo-AI (0.0 ± 0.0% vs 0.0 ± 0.0% vs 3.9 ± 3.9%; P = .52) and autograft reintervention (8.4 ± 6.0% vs 0.0 ± 0.0% vs 2.4 ± 2.4%; P = .47) were similar in the 3 groups. CONCLUSIONS: Age at the time of Ross operation for primary AS does not influence long-term autograft remodeling or durability. Other physiologic or technical factors are likely greater determinants of autograft fate.

Reintervention after valve-sparing aortic root replacement: A comprehensive analysis of 781 David V procedures.

OBJECTIVE: Studies of reintervention after valve-sparing aortic root replacement (VSRR) are limited by sample size and failure to evaluate all types of reinterventions, including distal aorta and transcatheter interventions. In this report, reintervention after VSRR using a large patient cohort was comprehensively analyzed. METHODS: In a series involving 2 academic aortic centers, 781 consecutive patients from 2005 to 2020 undergoing David V VSRR for aortic aneurysm (91%) or dissection (9%) were included. Median age was 50 years, and 23% had a bicuspid aortic valve (AV). Median follow-up was 7.0 years. Open or transcatheter reintervention on the AV, proximal, or distal thoracic aorta was identified. Cumulative incidence was calculated, and subdistribution hazard models identified factors associated with reintervention. Time-dependent incidence of reintervention was plotted using risk-hazard functions. RESULTS: Sixty-eight reinterventions (57 open, 11 transcatheter) were performed. Reinterventions were divided by indication into degenerative AV (n = 26, including 1 transcatheter aortic valve replacement), endocarditis (n = 11), proximal aorta (n = 8), and distal aorta (n = 23, including 10 thoracic endovascular aortic repairs). Risk of reintervention for endocarditis peaked 1 to 3 years after VSRR, whereas other indications had stable, low rates of occurrence throughout the follow-up period. The cumulative incidence of reintervention was 12.5% whereas the cumulative incidence of AV reintervention was 7.0% at 10 years and was associated with residual postoperative aortic insufficiency. In-hospital mortality after reintervention was 3%. CONCLUSIONS: Reintervention rates after VSRR are relatively low in long-term follow-up and can be performed with acceptable operative risk. The majority of reinterventions are performed for indications other than AV degeneration, with the timing of reintervention varying by the specific clinical indication.

Increasing waiting times for status 2 patients in new United Network for Organ Sharing allocation system: Impact on waitlist and posttransplant outcomes.

OBJECTIVE: Since the heart transplant allocation policy change in 2018, there has been an increase in temporary mechanical circulatory support for Status 2 patients. We sought to examine the temporal pattern of waitlist and posttransplant outcomes for Status 2 patients. METHODS: Adult patients in the United Network for Organ Sharing registry who were listed as Status 2 from January 2019 to June 2022 were included. Temporal trends in waitlist time, waitlist events, and posttransplant outcomes were assessed. Probability of transplant or death after being listed was compared over time. Multivariable regression was performed to identify risk factors for mortality after transplant. RESULTS: A total of 6310 patients were included. From 2019 to 2022, the number of Status 2 patients listed increased from 4.2 to 5.9 per day. Microaxial ventricular assist devices at Status 2 listing increased over time (P < .001). During the study period, median waitlist time (18 days vs 23 days, P < .001) as well as Status 2 days (8 days vs 12 days, P < .001) increased. Waitlist mortality remained stable (5.5%); however, probability of transplant within 90 days of Status 2 listing progressively declined (P < .001). Finally, longer waitlist duration was independently associated with 30-day posttransplant mortality (odds ratio, 1.01; 95% confidence interval, 1.00-1.01, P = .02). CONCLUSIONS: Since the allocation policy change there has been a steady rise in the number of patients listed for Status 2. This has led to increasing waitlist times and lower probability of transplantation for Status 2 patients, which may have negative consequences for posttransplant outcomes.

Influence of preoperative aortic regurgitation on long-term autograft durability and dilatation in children and adolescents undergoing the Ross procedure.

OBJECTIVE: Primary aortic insufficiency (AI) is a risk factor for autograft reintervention in adults undergoing the Ross procedure. We sought to examine the influence of preoperative AI on autograft durability in children and adolescents. METHODS: From 1993 to 2020, 125 consecutive patients between ages 1 and 18 underwent a Ross procedure. The autograft was implanted using a full-root technique in 123 (98.4%) and included in a polyethelene terephthalate graft in 2 (1.6%). Patients with aortic stenosis (aortic stenosis group) (n = 85) were retrospectively compared with those with AI or mixed disease (AI group) (n = 40). Median length of follow-up was 8.2 years (interquartile range, 3.3-15.4 years). The primary end point was the incidence of severe AI or autograft reintervention. Secondary end points included changes in autograft dimensions analyzed using mixed-effect models. RESULTS: The incidence of severe AI or autograft reintervention was 39.0% ± 13.0% in the AI group and 8.8% ± 4.4% in the aortic stenosis group at 15 years (P = .02). Annulus z scores increased in both aortic stenosis and AI groups over time (P < .001). However, the annulus dilated at a faster rate in the AI group (absolute difference, 3.8 ± 2.0 vs 2.5 ± 1.7; P = .03). Sinus of Valsalva z scores increased in both groups as well (P < .001), but at similar rates over time (P = .11). CONCLUSIONS: Children and adolescents with AI undergoing the Ross procedure have higher rates of autograft failure. Patients with preoperative AI have more pronounced dilatation at the annulus. Akin to adults, a surgical aortic annulus stabilization technique that modulates growth is needed in children.

Noncoding mutations cause super-enhancer retargeting resulting in protein synthesis dysregulation during B cell lymphoma progression.

Whole-genome sequencing of longitudinal tumor pairs representing transformation of follicular lymphoma to high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma) identified coding and noncoding genomic alterations acquired during lymphoma progression. Many of these transformation-associated alterations recurrently and focally occur at topologically associating domain resident regulatory DNA elements, including H3K4me3 promoter marks located within H3K27ac super-enhancer clusters in B cell non-Hodgkin lymphoma. One region found to undergo recurrent alteration upon transformation overlaps a super-enhancer affecting the expression of the PAX5/ZCCHC7 gene pair. ZCCHC7 encodes a subunit of the Trf4/5-Air1/2-Mtr4 polyadenylation-like complex and demonstrated copy number gain, chromosomal translocation and enhancer retargeting-mediated transcriptional upregulation upon lymphoma transformation. Consequently, lymphoma cells demonstrate nucleolar dysregulation via altered noncoding 5.8S ribosomal RNA processing. We find that a noncoding mutation acquired during lymphoma progression affects noncoding rRNA processing, thereby rewiring protein synthesis leading to oncogenic changes in the lymphoma proteome.

Valved Conduits for Right Ventricular Outflow Tract Reconstruction: A Review of Current Technologies and Future Directions.

The need for right ventricular outflow tract reconstruction is common and growing in congenital heart surgery given expanding indications for the repair of congenital as well as acquired heart disease. Various valved conduit options currently exist including homografts, xenograft pulmonary valved conduits (Contegra™), and porcine valved conduits. The major limitation for all conduits is implant durability, which requires reoperation. Currently, cryopreserved homografts are often used given their superiority shown in long-term data. Significant limitations remain in the cost and availability of the graft, particularly for smaller sizes. Contegra conduits are available in a variety of sizes. Nonetheless, the data regarding long-term durability are less robust and studies comparing durability with homografts have been conflicting. Additionally, there is concern for increased rates of late endocarditis in this conduit. Porcine valved conduits offer a reliable option but are limited by structural valve degeneration associated with all types of bioprosthetic heart valve replacements. New developments in the field of tissue engineering have produced promising bio-restorative valved conduits that may overcome many of the limitations of previous conduit technologies. These remain in the early stages of clinical testing. This review summarizes the clinical data surrounding the conduits used most commonly in clinical practice today and explores emerging technologies that may bring us closer to developing the ideal conduit.

Valve-sparing aortic root replacement versus composite valve graft with bioprosthesis in patients under age 50.

BACKGROUND: Although the unique risks of implanting a prosthetic valve after aortic valve (AV) surgery in young patients are well established, studies of aortic root replacement (ARR) are lacking. We investigated long-term outcomes after valve-sparing root replacement (VSRR) versus the use of a composite valve graft with bioprosthesis (b-CVG) in patients age <50 years. METHODS: A total of 543 patients age <50 years underwent VSRR (n = 335) or b-CVG (n = 208) between 2004 and 2021 from 2 aortic centers, excluding those with dissection or endocarditis. Endpoints included mortality over time, reoperative aortic valve replacement (AVR), and development of greater than moderate aortic insufficiency (AI) or aortic stenosis (AS). Fine and Gray competing risk regression was used to compare the risk of reintervention. Propensity score matching (PSM) balanced patient comorbidities, and landmark analysis isolated outcomes beginning 4 years postoperatively. RESULTS: Compared with VSRR, b-CVG was associated with lower 12-year survival (88.6% vs 92.9%; P = .036) and a higher rate of AV reintervention (37.6% vs 12.0%; P = .018). After PSM, survival was similar in the 2 arms (93.4% for b-CVG vs 93.0% for VSRR; P = .72). However, both Fine and Gray multivariable risk regression and PSM showed that b-CVG was independently associated with AV reintervention at >4 years postoperatively (Fine and Gray: subdistribution hazard ratio, 4.3 [95% confidence interval, 1.8-10.2; P = .001]; PSM: 35.7% for b-CVG versus 14.3% for VSRR; P = .024]). PSM rates of greater than moderate AI/AS at 10 years were more than 2-fold greater in the b-CVG arm compared with the VSRR arm (37.1% vs 15.9%; P = .571). CONCLUSIONS: b-CVG in young patients is associated with early valvular degeneration, with increasing rates of reoperative AVR occurring even within 10 years. In contrast, VSRR is durable with excellent survival. In eligible young patients, every effort should be made to retain the native AV.

Modeling the dispersion of traffic-derived black carbon emissions into hilly terrain.

This study examines hilly terrain's effect on black carbon (BC) dispersion. The apportionment of distinct sources obtained by a two-component mixing model (Aethalometer: AE-33) using improved radiative transfer equations showed the dominance of traffic-derived black carbon (BCFF) emissions in the study region. The AERMOD was used to model BC emissions from moving traffic as a line source and parking lot as area source using observational and WRF-processed meteorology for the winter (January to March 2020). The model results showed that the BC levels substantially vary with local meteorological conditions, traffic volume, and composition. The hilly terrain obstructs the winds and develops a negative pressure loading to a vacuum on the other side of the hills, which promotes the accumulation of emissions, causing high BC concentrations. The pockets of higher concentration were seen at the locations where steep slopes were associated with low winds (<1 m s-1) and hill fogs. The AERMOD model, after statistical evaluation against the observational datasets, has been applied to study the reduction in BCFF concentrations due to the implementation of Indian emission norms as mitigation measures, i.e., BS-IV (equivalent to Euro 4) and BS-VI (equivalent to Euro 6). It was found that the BCFF concentrations for BS-IV and BS-VI reduced by 35% and 75%, respectively. The model was also used to study the contribution of the different vehicular categories to BC concentration.

Operative mortality after Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1 to 3 procedures: Deficiencies and opportunities for quality improvement.

OBJECTIVES: We examined cases of operative mortality at a single quaternary academic center for patients undergoing relatively lower-risk (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1-3) procedures, as a means of identifying systemic weaknesses and opportunities for quality improvement. METHODS: A retrospective review of all operative mortality events for patients who underwent a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1, 2, or 3 index procedure (2009-2020) at our institution was performed. After a detailed chart review was performed by 2 independent faculty for each case, factors and system deficiencies that contributed to mortality were identified. RESULTS: A total of 42 mortalities were identified. A total of 37 patients (88%) had at least 1 Society of Thoracic Surgeons-designated risk factor, including prior cardiac operations (48%), extracardiac malformations (43%), and preoperative ventilation (33%). Eight patients (19%) had non-Society of Thoracic Surgeons-designated preoperative patient-level variables considered as at potential risk, including severe ventricular dysfunction, pulmonary hypertension, lung hypoplasia, and undiagnosed severe coronary abnormalities. Four patients (10%) had no identified preoperative risk factors. After detailed chart review, 5 broad categories were identified: patient-related factors (n = 33; 78%), postoperative infection (n = 13; 31%), postoperative residual lesions (n = 7; 17%), Fontan physiology failure (n = 4; 10%), and unexplained left ventricular failure after tetralogy of Fallot repair (n = 3; 7%). A total of 74% of patients had at least 1 preoperative, intraoperative, or postoperative system deficiency. A total of 50% of surgeries were urgent or emergency. CONCLUSIONS: Operative mortality after Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Mortality Category 1 to 3 procedures is related to the presence of multifactorial risk patterns (Society of Thoracic Surgeons and non-Society of Thoracic Surgeons-designated patient-level risk factors and variables, broad risk categories, system deficiencies, emergency surgery). A multidisciplinary approach to care, with early recognition and treatment of modifiable additional burdens, could reduce this risk.

Activation of Mas and pGCA receptor pathways protects renal epithelial cell damage against oxidative-stress-induced injury.

Over-activation of the renin-angiotensin-aldosterone system (RAAS) is a leading cause of cardio-renal complications. Oxidative stress is one of the major contributing factors in the over-activation of RAAS. Angiotensin-converting enzyme2/Angiotensin1-7/MasR and natriuretic peptide/particulate guanylyl cyclase receptor-A pathways play a key role in cardiorenal disease protection. Even though individual activation of these pathways possesses cardiorenal protective effects. However, the dual activation of these pathways under stress conditions and the underlying mechanism has not been explored. The study aimed to investigate whether activation of these pathways by dual-acting peptide (DAP) shows a protective effect in-vitro in oxidative stress-induced renal epithelial cells. Oxidative stress was induced in renal epithelial NRK-52E cells with H2O2. Co-treatment with Ang 1-7, BNP, and DAP was given for 30 min. AT1, MasR, and pGCA expression were measured by RT-PCR. The markers of oxidative stress and apoptosis were measured by confocal microscopy and FACS analysis. A significant increase in AT1, renin, α-SMA, and NFk-ß expression and a significant decrease in MasR and pGCA expression was observed in H2O2-induced cells. DAP improved H2O2-induced pathological changes in NRK-52E cells. The effect of DAP was superior to that of Ang1-7 and BNP alone. Interestingly, MasR and pGCA inhibitors could block the effect of DAP in H2O2-induced cells. DAP shows superior anti-RAAS activity, and it is effective against H2O2-induced oxidative stress, apoptosis, fibrosis, and inflammation compared to Ang1-7 and BNP alone. The protective effect is mediated by the dual activation of MasR and pGCA.

A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy.

Inhibiting the formation of a tight junction between two malaria parasite proteins, apical membrane antigen 1 and rhoptry neck protein 2, crucial for red blood cell invasion, prevents progression of the disease. In this work, we have used a unique approach to design a chimeric peptide, prepared by fusion of the best features of two peptide inhibitors, that has displayed parasite growth inhibition ex vivo with nanomolar IC50 , which is 100 times better than any of its parent peptides. Furthermore, to gain structural insights, we computationally modelled the hybrid peptide on its receptor.

Diabetes workshops for providers improve glucose control in coronary artery bypass grafting patients.

OBJECTIVES: Postoperative hyperglycemia occurs in up to 80% of cardiac surgery patients and is associated with poor outcomes. We sought to determine if case-based diabetes workshops for providers would improve postoperative glycemic control and outcomes in patients undergoing coronary artery bypass grafting  (CABG). METHODS: Healthcare providers taking care of patients in the cardiothoracic step-down unit underwent 30-min weekly case-based diabetes workshops over 6 months. Workshops focused on initiation of insulin treatment, titration of insulin dosing, and transitioning from insulin drips to subcutaneous insulin. Isolated-CABG patients were recorded during 29-month periods before (Jan 2013-June 2015) and after training (Jan 2016-June 2018). Glycemic control and outcomes were compared between groups balanced for preoperative risk factors using inverse probability treatment weights. RESULTS: A total of 938 and 1032 patients were included in pre- and posttraining groups, respectively. Compared to the pretraining period, the posttraining period had a lower median of mean patient day glucose levels (151 vs. 144 mg/dl, p < .001) and percentage of patient days with a glucose level >250 mg/dl (20% vs. 14%, p < .001). The percentage of patient days with mean glucose values in the target range (80-180 mg/dl) increased from 71% to 77% (p < .001). The incidence of hypoglycemic events did not significantly change after training (p = .15). The incidence of sepsis was significantly lower in the posttraining period (1.7% vs. 0.2%, p < .001). CONCLUSIONS: Weekly diabetes workshops for healthcare providers were associated with improved glycemic control and reduced postoperative sepsis among isolated CABG patients.