Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2 deficient (Npr2+/-) mice using high frequency ultrasound.

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance (e.g., ~2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models). For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low density lipoprotein receptor deficient background (Npr2+/-;Ldlr-/-; 32 male, 18 female) were imaged at 4- and 8-weeks of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including: i) abnormal trans-aortic flow patterns on color Doppler (recirculation and regurgitation); ii) peak systolic flow velocities distal to the aortic valves reaching or surpassing ~1250 mm/s by pulsed wave Doppler; and iii) putative fusion of cusps along commissures and abnormal movement elucidated by 2D imaging with ultra-high temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type 0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost-effective and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.

Long-term outcomes following valve-sparing root replacement with concomitant mitral repair.

OBJECTIVES: To examine the late outcomes of valve-sparing root replacement and concomitant mitral valve repair in patients who have been followed prospectively for more than 2 decades. METHODS: From 1992 to 2020, 54 consecutive patients (mean age, 47 ± 16 years; 80% men) underwent valve-sparing root replacement (45 reimplantation and 9 remodeling) with concomitant repair of the mitral valve. Patients were followed prospectively for a median of 9 years (IQR, 3-14 years). RESULTS: No patient experienced perioperative death or stroke. There were 3 late deaths and the 15-year overall survival was 96.0% (95% CI, 74.8%-99.4%), similar to the age- and sex-matched population. Over the follow-up period, 6 patients had reoperation of the aortic valve and 3 on the mitral valve. Of those, 2 had reoperation on both aortic and mitral valves for a total of 7 reoperations in this cohort. The cumulative proportion of reoperation at 10 years of either or both valves were as follows: aortic valve 11.4% (95% CI, 3.9%-33.3%), mitral valve 4.2% (95% CI, 0.6%-28.4%), and both valves 11.4% (95% CI, 3.9%-33.3%). The estimated probability of developing moderate/severe aortic insufficiency at 15 years was 18.5% (95% CI, 9.0%-34.2%). On final echocardiographic follow-up, none of the patients had developed moderate/severe mitral regurgitation. CONCLUSIONS: In this single-center series of concomitant valve-sparing root replacement and mitral valve repair, we observed excellent clinical outcomes with a low risk of death or valve-related complications. Continued surveillance of late valve function is necessary.

Axillary vs Femoral Arterial Cannulation in Acute Type A Dissection: International Multicenter Data.

BACKGROUND: Cannulation strategy in acute type A dissection (ATAD) varies widely without known gold standards. This study compared ATAD outcomes of axillary vs femoral artery cannulation in a large cohort from the International Registry of Acute Aortic Dissection (IRAD). METHODS: The study retrospectively reviewed 2145 patients from the IRAD Interventional Cohort (1996-2021) who underwent ATAD repair with axillary or femoral cannulation (axillary group: n = 1106 [52%]; femoral group: n = 1039 [48%]). End points included the following: early mortality; neurologic, respiratory, and renal complications; malperfusion; and tamponade. All outcomes are presented as axillary with respect to femoral. RESULTS: The proportion of patients younger than 70 years in both groups was similar (n = 1577 [74%]), as were bicuspid aortic valve, Marfan syndrome, and previous dissection. Patients with femoral cannulation had slightly more aortic insufficiency (408 [55%] vs 429 [60%]; P = .058) and coronary involvement (48 [8%] vs 70 [13%]; P = .022]. Patients with axillary cannulation underwent more total aortic arch (156 [15%] vs 106 [11%]; P = .02) and valve-sparing root replacements (220 [22%] vs 112 [12%]; P < .001). More patients with femoral cannulation underwent commissural resuspension (269 [30.9%] vs 324 [35.3%]; P = .05). Valve replacement rates were not different. The mean duration of cardiopulmonary bypass was longer in the femoral group (190 [149-237] minutes vs 196 [159-247] minutes; P = .037). In-hospital mortality was similar between the axillary (n = 165 [15%]) and femoral (n = 149 [14%]) groups (P = .7). Furthermore, there were no differences in stroke, visceral ischemia, tamponade, respiratory insufficiency, coma, or spinal cord ischemia. CONCLUSIONS: Axillary cannulation is associated with a more stable ATAD presentation, but it is a more extensive intervention compared with femoral cannulation. Both procedures have equivalent early mortality, stroke, tamponade, and malperfusion outcomes after statistical adjustment.

Hemiarch versus extended arch repair for acute type A dissection: Results from a multicenter national registry.

OBJECTIVE: We compared perioperative outcomes of patients with acute type A aortic dissection undergoing hemiarch (HA) versus extended arch (EA) repair with or without descending aortic intervention. METHODS: Nine hundred twenty-nine patients underwent acute type A aortic dissection repair (2002-2021, 9 centers) including open distal repair (HA) with or without additional EA repair. EA with intervention on the descending aorta (EAD) included elephant trunk, antegrade thoracic endovascular aortic replacement, or uncovered dissection stent. EA with no descending intervention (EAND), included unstented suture-only methods. Primary outcomes were in-hospital mortality, permanent neurologic deficit, computed tomography malperfusion resolution, and a composite. Multivariable logistic regression was also performed. RESULTS: Mean age was 66 ± 18 years, 30% (278 out of 929) were women, and HA was performed more frequently (75% [n = 695]) than EA (25% [n = 234]). EAD techniques included: dissection stent (39 out of 234 [17%]), thoracic endovascular aortic replacement (18 out of 234 [7.7%]), and elephant trunk (87 out of 234 [37%]). In-hospital mortality (EA: n = 49 [21%] and HA: n = 129 [19%]; P = .42), and neurological deficit (EA: n = 43 [18%] and HA: n = 121 [17%]; P = .74) were similar. EA was not independently associated with death (EA vs HA odds ratio, 1.09; 95% CI, 0.77-1.54; P = .63) or neurologic deficit (EA vs HA odds ratio, 0.85; 95% CI, 0.47-1.55; P = .59). Composite adverse events differed significantly (EA vs HA odds ratio, 1.47; 95% CI, 1.16-1.87; P = .001). Malperfusion resolved more frequently after EAD (EAD: n = 32 [80%], EAND: n = 18 [56%], HA: n = 71 [50%]; P = .004), although multivariable analysis was not significant (EAD vs HA odds ratio, 2.17; 95% CI, 0.83-5.66; P = .10). CONCLUSIONS: Extended arch interventions pose similar perioperative mortality and neurologic risks as Hemiarch. Descending aortic reinforcement may promote malperfusion restoration. Extended techniques should be approached with caution in acute dissection due to increased risk of adverse events.

The Call for the "Interventional/Hybrid" Aortic Surgeon: Open, Endovascular, and Hybrid Therapies of the Aortic Arch.

Aortic arch pathology is relatively rare but potentially highly fatal and associated with considerable comorbidity. Operative mortality and complication rates have improved over time but remain high. In response, aortic arch surgery is one of the most rapidly evolving areas of cardiac surgery in terms of surgical volume and improved outcomes. Moreover, there has been a surge in novel devices and techniques, many of which have been developed by or codeveloped with vascular surgeons and interventional radiologists. Nevertheless, the extent of arch surgery, the choice of nadir temperature, cannulation, and perfusion strategies, and the use of open, endovascular, or hybrid options vary according to country, centre, and surgeon. In this review article, we provide a technical overview of the surgical, total endovascular, and hybrid repair options for aortic arch pathology through historical developments and contemporary results. We highlight key information for surgeons, cardiologists, and trainees to understand the management of patients with aortic arch pathology. We conclude by discussing training paradigms, the role of aortic teams, and gaps in knowledge, arguing for the need for wire skills for the future "interventional aortic surgeon" and increased research into techniques and novel devices to continue improving outcomes for aortic arch surgery.

Considerations & challenges of mitral valve repair in females: diagnosis, pathology, and intervention.

PURPOSE OF REVIEW: Disparities in mitral valve (MV) repair outcomes exist between men and women. This review highlights sex-specific differences in MV disease aetiology, diagnosis, as well as timing and type of intervention. RECENT FINDINGS: Females present with more complicated disease: anterior or bileaflet prolapse, leaflet dysplasia/thickening, mitral annular calcification, and mixed mitral lesions. The absence of indexed echocardiographic mitral regurgitation (MR) severity parameters contributes to delayed intervention in women, resulting in more severe symptom burden at time of surgery. The sequelae of chronic MR also necessitate concomitant procedures (e.g. tricuspid repair, arrhythmia surgery) at the time of mitral surgery. Complex MV pathology, greater patient acuity, and more complicated procedures collectively pose challenges to successful MV repair and postoperative recovery. As a consequence, women receive disproportionately more MV replacement than men. In-hospital mortality after MV repair is also greater in women than men. Long-term outcomes of MV repair are comparable after risk-adjustment for preoperative status; however, women experience a greater incidence of postoperative heart failure. SUMMARY: To address the inequity in MV repair outcomes between sexes, indexed diagnostic measurements, diligent surveillance of asymptomatic MR, increased recruitment of women in large clinical trials, and mandatory reporting of sex-based subgroup analyses are recommended.

Reconstruction Technique Options for Achieving Total Arterial Revascularization and Multiple Arterial Grafting.

Ischemic heart disease is the leading cause of morbidity and mortality worldwide and may require coronary revascularization when more severe or symptomatic. Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure and can be performed with different bypass conduits and anastomotic techniques. Saphenous vein grafts (SVGs) are the most frequently used conduits for CABG, in addition to the left internal thoracic artery. Outcomes with a single internal thoracic artery and SVGs are favorable, and the long-term patency of SVGs may be improved through novel harvesting techniques, preservation methods, and optimal medical therapy. However, increasing evidence points towards the superiority of arterial grafts, especially in the form of multiple arterial grafting (MAG). Nevertheless, the uptake of MAG remains limited and variable, both as a result of technical complexity and a scarcity of conclusive randomized controlled trial evidence. Here, we present an overview of CABG techniques, harvesting methods, and anastomosis types to achieve total arterial revascularization and adopt MAG. We further narratively summarize the available evidence for MAG versus single arterial grafting to date and highlight remaining gaps and questions that require further study to elucidate the role of MAG in CABG.

Sex differences in D-dimer and critical illness in patients with COVID-19: A systematic review and meta-analysis.

Background: Observed sex differences in COVID-19 outcomes suggest that men are more likely to experience critical illness and mortality. Thrombosis is common in severe COVID-19, and D-dimer is a significant marker for COVID-19 severity and mortality. It is unclear whether D-dimer levels differ between men and women, and the effect of D-dimer levels on disease outcomes remains under investigation. Objectives: We aimed to evaluate the sex difference in the D-dimer level among hospitalized patients with COVID-19 and the effect of sex and D-dimer level on disease outcomes. Methods: We meta-analyzed articles reporting D-dimer levels in men and women hospitalized for COVID-19, until October 2021, using random effects. Primary outcomes were mortality, critical illness, and thrombotic complications. Results: In total, 11,682 patients from 10 studies were analyzed (N = 5606 men (55.7%), N = 5176 women (44.3%)). Men had significantly higher odds of experiencing mortality (odds ratios (OR) = 1.41, 95% CI: [1.25, 1.59], P ≤ .001, I2 = 0%) and critical illness (OR = 1.76, 95% CI: [1.43, 2.18], P ≤ .001, I2 = 61%). The mean D-dimer level was not significantly different between men and women (MD = 0.08, 95% CI: [-0.23, 0.40], P = .61, I2 = 52%). In the subgroup analysis, men had significantly higher odds of experiencing critical illness compared with women in both the "higher" (P = .006) and "lower" (P = .001) D-dimer subgroups. Conclusion: Men have significantly increased odds of experiencing poor COVID-19 outcomes compared with women. No sex difference was found in the D-dimer level between men and women with COVID-19. The diversity in D-dimer reporting impacts data interpretation and requires further attention.

Improved Outcomes of Reimplantation vs Remodeling in Marfan Syndrome: A Propensity-Matched Study.

BACKGROUND: Valve-sparing root replacement (VSRR) has excellent outcomes when performed in experienced centers in well-selected patients. It is suggested that reimplantation of the aortic valve may have better durability than remodeling in patients with Marfan syndrome (MFS), although long-term comparative data are limited. METHODS: Between 1988 and 2018, 194 patients with MFS underwent VSRR at our institution. From these, we derived a propensity-matched cohort of 68 patients (44 who underwent reimplantation and 24 who had remodeling). Early outcomes included death and perioperative complications. Late outcomes were survival, probability of aortic insufficiency, and reintervention up to 20 years of follow-up. Median follow-up was 17.8 years (interquartile range, 12.0-20.6 years) for the entire matched cohort. RESULTS: Baseline variables were similar between reimplantation and remodeling patients after matching: age (39 ± 12 vs 40 ± 13 years, P = .75) and male sex (28 [64%] vs 15 [63%], P = 1.0). Similar 20-year survival was observed after reimplantation compared with remodeling (82% vs 72%, P = .20), whereas the probability of developing greater than mild aortic insufficiency at 20 years was increased after remodeling (5.8% vs 13%, P = .013). More patients underwent reoperation on the aortic valve after a remodeling procedure than after reimplantation of the aortic valve (18% vs 0%, P = .018). CONCLUSIONS: VSRR provides excellent long-term survival and freedom from valve-related complications outcomes in patients with MFS. Reimplantation of the aortic valve was associated with a lower risk of aortic valve reoperation and aortic insufficiency than the remodeling procedure after 2 decades of follow-up.

Multiple arterial coronary bypass grafting is associated with better survival compared with second-generation drug-eluting stents in patients with stable multivessel coronary artery disease.

OBJECTIVE: We sought to compare the long-term outcomes of multiarterial graft (MAG) coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) to treat stable multivessel coronary artery disease. METHODS: This study was a multicenter population-based retrospective analysis of all residents of Ontario, Canada, from January 1, 2011, to December 31, 2019. We identified 3600 cases of elective primary isolated CABG with MAG and 2187 cases of PCI with second-generation DES. RESULTS: After the application of propensity score-weighting using overlap weights, MAG was associated with better survival over 5 years compared with DES (96.8% vs 94.5%; hazard ratio [HR], 0.56; 95% CI, 0.37-0.85). MAG was also associated with better secondary outcomes including a composite of death, myocardial infarction, and stroke (94.3% vs 88.5%; HR, 0.49; 95% CI, 0.36-0.65). The rate of death, stroke, myocardial infarction, and repeat revascularization (91.2% vs 70.7%; HR, 0.24; 95% CI, 0.20-0.30), and the individual end points of myocardial infarction (1.4% vs 6.9%; HR, 0.22; 95% CI, 0.13-0.35), and repeat revascularization (4.1% vs 24.2%; HR, 0.14; 95% CI, 0.10-0.18) were lower with MAG. PCI with second-generation DES was associated with a lower rate of stroke up to 5 years (0.6% vs 1.8%; HR, 3.97; 95% CI, 1.45-10.88). CONCLUSIONS: CABG with MAG was associated with better survival and fewer major cardiac adverse events compared with second-generation DES and might be considered the treatment of choice for patients with stable multivessel coronary artery disease. Further randomized controlled trials are needed to confirm this hypothesis.

Hybrid arch frozen elephant trunk repair for acute type A aortic dissection: Extra-anatomic subclavian reconstruction.

Acute type A aortic dissection is a life-threatening condition that confers significant early perioperative risk but is also associated with late aortic disease progression and the need for reintervention. Recent efforts to improve patient outcomes have focused on improving quality of care and extending treatment in the aortic root and arch to reduce late aortic events. The hybrid arch frozen elephant trunk technique facilitates a more aggressive distal aortic repair that may help mitigate the early and late deleterious effects of persistent false lumen perfusion. However, in the acute and emergency settings, management of the left subclavian artery remains a challenge. We present a step-by-step instructional guide on performing an emergency hybrid arch frozen elephant trunk procedure with emphasis on management of the difficult left subclavian artery. Our case report demonstrates a transthoracic aortoaxillary extra-anatomic bypass of the left axillary artery. We discuss the most important considerations when managing the left subclavian artery in an acute type A aortic dissection. Finally, we detail the benefits and limitations of the transthoracic aortoaxillary extra-anatomic technique and discuss other approaches to left subclavian artery reconstruction.

Left ventricular assist device implantation via lateral thoracotomy: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist device (LVAD) implantation via lateral thoracotomy can offer similar effectiveness to conventional approaches with less perioperative adverse events. We performed a systematic review and meta-analysis to determine the potential benefits of lateral thoracotomy (LT) for LVAD implantation compared to median sternotomy. METHODS: We searched MEDLINE and Embase databases for studies comparing continuous-flow LVAD implantation using LT with conventional sternotomy. Main outcomes were perioperative mortality and complications. RESULTS: Twenty-five observational studies enrolling 3072 patients were included with a median follow-up of 10 months. Perioperative mortality (30 day or in-hospital) was 7% (LT) and 14% (sternotomy); however, mortality differences were no longer statistically significant in matched/adjusted studies (RR:0.86; 95%CI:0.52-1.44; p = 0.58). LT was associated with decreased need for blood product transfusions (mean difference[MD]: -4.7; 95%CI: -7.2 to -2.3 units; p < 0.001), reoperation for bleeding (RR:0.34; 95%CI:0.22-0.54; p < 0.001), postoperative RVAD implantation (RR:0.53; 95%CI:0.36-0.77; p < 0.001), days requiring inotropes (MD: -1.1; 95%CI: -2.1 to -0.03 inotrope days; p = 0.04), ICU (MD: -3.3; 95%CI: -6.0 to -0.7 ICU days; p = 0.01), and hospital length of stay (MD: -5.1; 95%CI: -10.1 to -0.1 hospital days; p = 0.04) in matched/adjusted studies. Overall mortality during follow-up was significantly lower for LT in unmatched/unadjusted studies but not statistically significantly lower in matched/adjusted studies (Hazard Ratio:0.82; 95%CI:0.59-1.14; p = 0.24). CONCLUSION: LVAD implantation via LT was associated with significantly decreased need for blood products, reoperation for bleeding, and postoperative RVAD implantation. Furthermore, days on inotropic support were also lower, likely contributing to the shorter length of stay. These findings support greater use of a LT approach for carefully selected patients.

The use of objective assessments in the evaluation of technical skills in cardiothoracic surgery: a systematic review.

OBJECTIVES: With reductions in training time and intraoperative exposure, there is a need for objective assessments to measure trainee progression. This systematic review focuses on the evaluation of trainee technical skill performance using objective assessments in cardiothoracic surgery and its incorporation into training curricula. METHODS: Databases (EBSCOHOST, Scopus and Web of Science) and reference lists of relevant articles for studies that incorporated objective assessment of technical skills of trainees/residents in cardiothoracic surgery were included. Data extraction included task performed; assessment setting and tool used; number/level of assessors; study outcome and whether the assessments were incorporated into training curricula. The methodological rigour of the studies was scored using the Medical Education Research Study Quality Instrument (MERSQI). RESULTS: Fifty-four studies were included for quantitative synthesis. Six were randomized-controlled trials. Cardiac surgery was the most common speciality utilizing objective assessment methods with coronary anastomosis the most frequently tested task. Likert-based assessment tools were most commonly used (61%). Eighty-five per cent of studies were simulation-based with the rest being intraoperative. Expert surgeons were primarily used for objective assessments (78%) with 46% using blinding. Thirty (56%) studies explored objective changes in technical performance with 97% demonstrating improvement. The other studies were primarily validating assessment tools. Thirty-nine per cent of studies had established these assessment tools into training curricula. The mean ± standard deviation MERSQI score for all studies was 13.6 ± 1.5 demonstrating high validity. CONCLUSIONS: Despite validated technical skill assessment tools being available and demonstrating trainee improvement, their regular adoption into training curricula is lacking. There is a need to incorporate these assessments to increase the efficiency and transparency of training programmes for cardiothoracic surgeons.

Dealing With the Epidemic of Endocarditis in People Who Inject Drugs.

North America is facing an opioid epidemic and growing illicit drug supply, contributing to growing numbers of injection drug use-related infective endocarditis (IDU-IE). Patients with IDU-IE have high early and late mortality. Patients with IDU-IE more commonly present with right-side IE compared with those with non-IDU IE, and a majority are a result of Streptococcus aureus. Although most patients can be successfully managed with intravenous antibiotic treatment, surgery is often required in part owing to high relapse rates, potential treatment biases, and more aggressive pathophysiology in some. Multidisciplinary management as endocarditis teams, including not only cardiologists and cardiac surgeons, but also infectious disease specialists, drug addiction experts, social workers, neurologists, and neurosurgeons, is essential to best manage substance use disorder and facilitate safe discharge to home and society. Structural and population-level interventions, such as harm-reduction programs, are necessary to reduce IDU-IE relapse rates in the community and other IDU-related health concerns, such as overdoses. In this review, we describe the pathophysiologic, clinical, surgical, social, and ethical characteristics of IDU-IE and their management. We present the most recent clinical guidelines for this condition and discuss existing gaps in knowledge to guide future research, practice changes, and policy interventions.