Ethnicity Is Associated With Differing Presentation and Outcomes of Patients Undergoing Aortic Valve Replacement for Calcific Aortic Stenosis in Aotearoa New Zealand.

AIM: Surgical aortic valve replacement (SAVR) has been the gold standard for treatment of severe symptomatic aortic stenosis (AS) for decades. We examined whether ethnic differences exist in the presentation and outcomes of patients undergoing aortic valve replacement (AVR) for AS in New Zealand. METHODS: Patients of New Zealand European, Maori, and Pacific Island ethnicities undergoing SAVR with or without other procedures in New Zealand public hospitals from 2017 to 2019 were included. Major postoperative outcomes were compared between ethnic groups, with 30-day mortality being the primary outcome. RESULTS: A total of 1,175 patients were included: 1,085 European, 50 Maori, and 40 Pacific. The mean age was 71.1±9.4 years, and men accounted for more than half of all patients (69.9%). Maori (64.7±9.4 years) and Pacific (65.4±10.1 years) patients were younger when undergoing SAVR compared with European patients (71.7±9.2; analysis of variance p<0.001). Maori and Pacific patients had a higher prevalence of diabetes, poorer renal function, and worse left ventricular function; 30-day mortality was higher in Maori and Pacific compared with European patients (6% and 10% vs 2.4%, respectively; Fisher's exact test p=0.011), with odds ratio of 3.06 (95% confidence interval [CI] 0.88-10.66) for Maori patients after adjustment for EuroSCORE II and odds ratio of 5.23 (95% CI 1.79-16.07) for Pacific patients. CONCLUSIONS: There are significant differences in presentation and outcomes of patients undergoing AVR in New Zealand. Maori and Pacific patients undergo SAVR at a younger age, have more preoperative comorbidities, and have higher rates of 30-day mortality than European patients.

Epithelial Sodium Channel δ Subunit Is Expressed in Human Arteries and Has Potential Association With Hypertension.

BACKGROUND: Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension. METHODS: Human internal mammary artery (IMA) and aorta were obtained from cardiovascular patients undergoing coronary artery bypass graft surgery. Expression of the ENaC subunit was analyzed by polymerase chain reaction, Western blot, and immunohistochemistry. ENaC function was observed by patch-clamp electrophysiology in endothelial cells isolated from IMA. Levels of ENaC subunit expression levels were compared between arteries from normotensive, uncontrolled hypertensive, and controlled hypertensive patients. RESULTS: For the first time, expression of α, ß, γ, and δ was detected at mRNA and protein levels in human IMA and aorta. Single-channel patch-clamp recordings identified both αßγ- and δßγ-like channel conductance in primary endothelial cells isolated and cultured from IMA. Reduced expression of the δ subunit was observed in controlled hypertensive IMA, whereas reduced expression of γ-ENaC was observed in controlled hypertensive aorta. CONCLUSIONS: These data suggest that functional ENaC channels are expressed in human arteries and their expression levels are associated with hypertension.

Combination of Cardiac Progenitor Cells From the Right Atrium and Left Ventricle Exhibits Synergistic Paracrine Effects In Vitro.

Cardiovascular diseases, such as ischemic heart disease, remain the most common cause of death worldwide. Regenerative medicine with stem cell therapy is a promising tool for cardiac repair. Combination of different cell types has been shown to improve the therapeutic potential, which is thought to be due to synergistic or complimentary reparative effects. We investigated if the combination of cardiac progenitor cells (CPCs) of right atrial appendage (RAA) and left ventricle (LV) that are isolated from the same patient exert synergistic or complimentary paracrine effects for apoptotic cell death and angiogenesis in an in vitro model. Flow cytometry analysis showed that both RAA and LV CPCs expressed the mesenchymal cell markers CD90 and CD105, and were predominantly negative for the hematopoietic cell marker, CD34. Analysis of conditioned media (CM) collected from the CPCs cultured either alone or in combination in serum-deprived hypoxic conditions to simulate ischemia showed marked increase in the level of pro-survival hepatocyte growth factor and pro-angiogenic vascular endothelial growth factor-A in the combined RAA and LV CPC group. Next, to determine the therapeutic potential of CM, AC16 human ventricular cardiomyocytes and human umbilical vein endothelial cells (HUVECs) were treated with CM. Results showed a significant reduction in hypoxia-induced apoptosis of human cardiomyocytes treated with CM collected from combined RAA and LV CPC group. Similarly, matrigel assay showed a significantly increased tube length formed by HUVECs when treated with CM from combined RAA and LV CPC group. Our study provided evidence that the combination of RAA CPCs and LV CPCs may have superior therapeutic effects due to synergistic paracrine effects for cardiac repair. Therefore, in vivo studies are warranted to determine if a combination of different stem cell types have greater therapeutic potential than single-cell therapies.

Comparison of Heart Team vs Interventional Cardiologist Recommendations for the Treatment of Patients With Multivessel Coronary Artery Disease.

Importance: Although the heart team approach is recommended in revascularization guidelines, the frequency with which heart team decisions differ from those of the original treating interventional cardiologist is unknown. Objective: To examine the difference in decisions between the heart team and the original treating interventional cardiologist for the treatment of patients with multivessel coronary artery disease. Design, Setting, and Participants: In this cross-sectional study, 245 consecutive patients with multivessel coronary artery disease were recruited from 1 high-volume tertiary care referral center (185 patients were enrolled through a screening process, and 60 patients were retrospectively enrolled from the center's database). A total of 237 patients were included in the final virtual heart team analysis. Treatment decisions (which comprised coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy) were made by the original treating interventional cardiologists between March 15, 2012, and October 20, 2014. These decisions were then compared with pooled-majority treatment decisions made by 8 blinded heart teams using structured online case presentations between October 1, 2017, and October 15, 2018. The randomized members of the heart teams comprised experts from 3 domains, with each team containing 1 noninvasive cardiologist, 1 interventional cardiologist, and 1 cardiovascular surgeon. Cases in which all 3 of the heart team members disagreed and cases in which procedural discordance occurred (eg, 2 members chose coronary artery bypass grafting and 1 member chose percutaneous coronary intervention) were discussed in a face-to-face heart team review in October 2018 to obtain pooled-majority decisions. Data were analyzed from May 6, 2019, to April 22, 2020. Main Outcomes and Measures: The Cohen κ coefficient between the treatment recommendation from the heart team and the treatment recommendation from the original treating interventional cardiologist. Results: Among 234 of 237 patients (98.7%) in the analysis for whom complete data were available, the mean (SD) age was 67.8 (10.9) years; 176 patients (75.2%) were male, and 191 patients (81.4%) had stenosis in 3 epicardial coronary vessels. A total of 71 differences (30.3%; 95% CI, 24.5%-36.7%) in treatment decisions between the heart team and the original treating interventional cardiologist occurred, with a Cohen κ of 0.478 (95% CI, 0.336-0.540; P = .006). The heart team decision was more frequently unanimous when it was concordant with the decision of the original treating interventional cardiologist (109 of 163 cases [66.9%]) compared with when it was discordant (28 of 71 cases [39.4%]; P < .001). When the heart team agreed with the original treatment decision, there was more agreement between the heart team interventional cardiologist and the original treating interventional cardiologist (138 of 163 cases [84.7%]) compared with when the heart team disagreed with the original treatment decision (14 of 71 cases [19.7%]); P < .001). Those with an original treatment of coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy, 32 of 148 patients [22.3%], 32 of 71 patients [45.1%], and 6 of 15 patients [40.0%], respectively, received a different treatment recommendation from the heart team than the original treating interventional cardiologist; the difference across the 3 groups was statistically significant (P = .002). Conclusions and Relevance: The heart team's recommended treatment for patients with multivessel coronary artery disease differed from that of the original treating interventional cardiologist in up to 30% of cases. This subset of cases was associated with a lower frequency of unanimous decisions within the heart team and less concordance between the interventional cardiologists; discordance was more frequent when percutaneous coronary intervention or medication therapy were considered. Further research is needed to evaluate whether heart team decisions are associated with improvements in outcomes and, if so, how to identify patients for whom the heart team approach would be beneficial.

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.

Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study.

BACKGROUND: Cardiac surgery patients are at high risk for postoperative bleeding. Intravenous (IV) tranexamic acid (TxA) is a commonly used antifibrinolytic drug, but is associated with postoperative seizures. We conducted this pilot randomized controlled trial (RCT) to determine the feasibility of a larger trial that will be designed to investigate the impact of TxA administration route, intrapericardial (IP) vs IV, on postoperative bleeding and seizures. METHODS: In this single-center, double-blinded, pilot RCT we enrolled adult patients undergoing nonemergent on-pump cardiac operations through a median sternotomy. Participants were randomized to IP or IV TxA groups. The primary outcomes were cumulative chest tube drainage, transfusion requirements, and incidence of postoperative seizures. RESULTS: A total of 97 participants were randomized to the intervention and control groups. Baseline characteristics were similar in both groups. Most participants underwent a CABG and/or aortic valve replacement. There was no statistical difference. The IP TxA group was found to have a tendency for less chest tube drainage in comparison to the IV TxA group, 500.5 (370.0-700.0) and 540.0 (420.0-700.0) mL, respectively, which was not statistically significant (P = 0.2854). Fewer participants in the IP TxA group with cardiac tamponade and/or required a reoperation for bleeding and fewer packed red blood cell transfusions. None of the IP TxA group developed seizure vs one from the IV TxA group. CONCLUSION: This is the first known pilot RCT to investigate the role of TxA route of administration in open cardiac surgery. Intrapericardial TxA shows promising results with decreased bleeding, transfusion requirements, reoperations, and postoperative seizures. A larger RCT is needed to confirm these results and lead to a change in practice.

The Ross procedure versus prosthetic and homograft aortic valve replacement: a systematic review and meta-analysis.

OBJECTIVES: Young adults undergoing aortic valve replacement (AVR) have decreased life expectancy compared to matched controls. The Ross procedure aims to improve valve lifespan while avoiding anticoagulation. We prepared a systematic review and meta-analysis to assess the Ross procedure compared to conventional AVR. METHODS: We searched MEDLINE, EMBASE and Cochrane CENTRAL for studies evaluating the Ross procedure versus any conventional AVR in adult patients. We performed screening, full-text assessment, risk of bias evaluation and data collection independently and in duplicate. We evaluated the risk of bias with the ROBINS-I and Cochrane tools and quality of evidence with the GRADE framework. We pooled data using the random- and fixed-effects models. RESULTS: Thirteen observational studies and 2 randomized controlled trials (RCTs) were identified (n = 5346). No observational study was rated as having low risk of bias. The Ross procedure was associated with decreased late mortality in observational and RCT data [mean length of follow-up 2.6 years, relative risk (RR) 0.56, 95% confidence interval (CI) 0.38-0.84, I2 = 58%, very low quality]. The RCT estimate of effect was similar (mean length of follow-up 8.8 years, RR 0.33, 95% CI 0.11-0.96, I2 = 66%, very low quality). No difference was observed in mortality <30 days after surgery. All-site reintervention was similar between groups in cohorts and significantly reduced by the Ross procedure in RCTs (RR 1.41, 95% CI 0.89-2.24, I2 = 55%, very low quality and RR 0.41, 95% CI 0.22-0.78, I2 = 68%, high quality, respectively). CONCLUSIONS: Observational data, with residual confounding, and RCT data suggest a late survival benefit with the Ross procedure with no increased risk of reintervention when compared to conventional AVR. Considering the quality of available evidence and limited follow-up, additional high-quality randomized studies are required to strengthen these findings. Systematic review PROSPERO registration: CRD42016052512.

Management of Lower Extremity Ischaemia During Type A Dissection Repair.

INTRODUCTION: Type A aortic dissection can present with malperfusion syndrome. Lower limb ischaemia may resolve with repair of the dissection; however, the long duration of repair and/or persistent ischaemia may leave tissue at risk of necrosis with potential for substantial morbidity. REPORT: Here, the case of a 67 year old man who presented with a Type A aortic dissection with malperfusion of the lower extremities is described. The Vascular Surgery and Cardiac Surgery divisions were consulted simultaneously. A decision was made to perform bilateral superficial femoral artery cannulation with perfusion initially via the right axillary artery prior to sternotomy, then via the cardiopulmonary bypass circuit. At completion of the arch replacement, lower extremity inflow was reassessed with formal repair of the femoral arteries. Post-operatively, the patient had complete return of motor-sensory function, despite densely ischaemic symptoms at presentation several hours previously. DISCUSSION: Cannulation of the superficial femoral arteries serves as a means to limit limb ischaemia intra-operatively and potentially improve outcomes in the setting of Type A aortic dissection with lower extremity malperfusion.

Hemodynamic outcomes of the Ross procedure versus other aortic valve replacement: a systematic review and meta-analysis.

INTRODUCTION: Life expectancy in young adults undergoing mechanical or bioprosthetic aortic valve replacement (AVR) may be reduced by up to 20 years compared to age matched controls. The Ross procedure is a durable, anticoagulation-sparing alternative. We performed a systematic review and meta-analysis to compare the valve hemodynamics of the Ross procedure versus other AVR. EVIDENCE ACQUISITION: We searched Cochrane CENTRAL, MEDLINE and EMBASE from inception to February 2017 for randomized controlled trials (RCTs) and observational studies (n≥10 Ross). Independently and in duplicate, we performed title and abstract screening, full-text eligibility assessment, and data collection. We evaluated the risk of bias with the Cochrane and CLARITY tools, and the quality of evidence with the GRADE framework. EVIDENCE SYNTHESIS: We identified 2 RCTs and 13 observational studies that met eligibility criteria (N.=1412). In observational studies, the Ross procedure was associated with a lower mean aortic gradient at discharge (MD -9 mmHg, 95% CI: -13 to -5, P<0.0001, I2=97%) and latest follow-up (MD -5 mmHg, 95% CI: -7 to -3, P<0.0001, I2=92%). There was no significant difference in the incidence of severe aortic regurgitation at latest follow-up (RR 1.3, 95% CI: 0.3 to 5.8, P=0.70, I2=30%). In RCTs, the Ross procedure was associated with a lower mean gradient at latest follow-up (MD -15 mmHg, 95% CI: -32 to 2, P=0.08, I2=99%). The mean pulmonic gradient for the Ross procedure was 18.0 mmHg (95% CI: 16 to 20, P<0.0001) at latest follow-up. The evidence for all outcomes from observational studies was deemed to be of very low quality, while the evidence from RCTs was downgraded for imprecision and moderately serious risk of bias. CONCLUSIONS: Compared to conventional AVR, the Ross procedure was associated with better aortic valve hemodynamics. Future studies should evaluate the impact of the Ross procedure on exercise capacity and quality of life.

Mini-thoracotomy vs. conventional sternotomy mitral valve surgery: a systematic review and meta-analysis.

INTRODUCTION: Minimal access mitral valve surgery (mini-MVS) approaches are becoming increasingly common. They are thought to be associated with less perioperative bleeding and postoperative pain, resulting in shorter hospital length-of-stay (LOS) and faster return to daily activities. However, there are concerns that this approach may have inferior surgical results - with resultant increases in morbidity and mortality - when compared to conventional mitral valve surgery. To address this gap in the literature, we undertook a systematic review and meta-analysis, comparing right thoracotomy mini-MVS (MT-MVS) to conventional mitral valve surgery using a median sternotomy (sternotomy-MVS) approach. EVIDENCE ACQUISITION: We searched the Cochrane Library, MEDLINE, PubMed, EMBASE and Clinicaltrials.gov for randomized trials comparing MT-MVS to sternotomy-MVS in adults. Outcomes of interest were mortality, stroke, hospital length of stay, bleeding, cardiopulmonary bypass (CPB) and cross-clamp times. Studies reporting reoperation data were excluded. References were screened independently and in duplicate, and studies deemed to be potentially relevant were evaluated for inclusion by full-text review. Risk of bias was assessed using the Cochrane tool. Extracted outcome data were pooled for meta-analysis using RevMAN 5.3. The overall quality of evidence for each outcome was evaluated using the GRADE framework. EVIDENCE SYNTHESIS: Three trials including 280 patients met eligibility criteria. Studies were considered to be at high risk of bias due to lack of blinding and small number of patients. Pooled results showed no significant difference in mortality (RR 0.50, 95% CI [0.05 to 5.39], low quality) or stroke (RR 0.50, 95% CI [0.05 to 5.39], low quality). Technique-related outcomes were also similar: cardiopulmonary bypass (CPB) time (MD 17.72 minutes, 95% CI [-7.22 to 42.67), very low quality), cross-clamp time (MD 5.31 minutes, 95% CI [-14.35 to 24.96), very low quality), and bleeding (MD -148.95 mL, 95% CI [-491.02 to 193.12), low quality). Length of stay was significantly shorter in the mini-MVS group (MD -1.89 days, 95% CI [-3.57 to -0.22], P=0.03, low quality). CONCLUSIONS: MT-MVS does not result in increased morbidity and mortality or procedural duration, and may decrease hospital LOS. Our preliminary results suggest that MT-MVS is a safe and potentially beneficial approach to the surgical management of mitral valve disease. However, current evidence is of low quality and larger, more methodologically rigorous randomized trials are required.

Short and medium term outcomes of surgery for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: We report one surgeon's experience of corrective surgery for hypertrophic obstructive cardiomyopathy (HOCM) over a 10-year span and comment on factors that influence longer term outcomes. Septal myectomy (SM) and adjunctive procedures, including shortening of the aorta, a novel technique in HOCM patients, are described. METHODS: Perioperative data were obtained by retrospective review of institutional surgical databases between 2001 and 2011. Review of most recent echocardiogram and clinical status by telephone interview was performed. RESULTS: A total of 211 patients underwent SM for HOCM. There was a bimodal age distribution related to sex; mean age for males and females was 46 ± 13 and 54 ± 14 years, respectively (p < 0.001). Functional New York Heart Association (NYHA) class improved significantly after surgery; 79% were in class III-IV preoperatively and 84% were in class I-II at follow-up (p < 0.001). Sixty percent had angina of Canadian Cardiovascular Society (CCS) grade III-IV preoperatively and 89% were in CCS I-II at follow-up (p < 0.001). There were significant improvements in resting left ventricular outflow tract gradient (64 ± 36 to 5 ± 5 mm Hg, p < 0.001), right ventricular systolic pressure (36 ± 7.3 to 32 ± 8 mm Hg, p < 0.001), left atrial size (4.6 ± 0.7 to 4.3 ± 0.6 cm, p < 0.001), and grade of mitral regurgitation (moderate to severe mitral regurgitation 28% to 3.5%, p < 0.001). In-hospital mortality was 0.5%, 1 year survival 98.6%, and 5-year survival 98.1%. Predictors of worse clinical outcomes were preoperative NYHA and CCS class III-IV (p < 0.001, p = 0.05), new onset atrial fibrillation (p < 0.001), and female sex (p = 0.03). CONCLUSIONS: Septal myectomy in patients with obstructive HOCM offers excellent symptom relief and minimal operative risk.

Transcatheter aortic valve implantation and left ventricular assist device: a word of caution.

Aortic valve disease in the setting of a left ventricular assist device presents unique challenges. We present the case of a patient who underwent transcatheter aortic valve implantation to replace a stenotic aortic valve to facilitate left ventricular assist device explantation. Thirty-three days later, the porcine pericardial valve cusps were fused and a thick pseudomembrane had occluded the left ventricular outflow tract, forcing the explant to be aborted.

Expanding retrograde saphenous vein graft aneurysm treated with endovascular coiling.

Saphenous vein graft aneurysm is a potentially fatal complication of coronary artery bypass grafting and usually requires surgery. This report describes endovascular coiling of a saphenous vein graft aneurysm that developed after redo coronary artery bypass grafting. The aneurysm occurred in a proximally occluded saphenous vein graft after revascularization of the same target vessel. The procedure required a retrograde approach through a patent left internal mammary and left anterior descending artery to reach and successfully thrombose the aneurysm.