Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Impact of ischemia on left atrial remodeling and dysfunction in swine models of mitral regurgitation.

Left atrial (LA) dysfunction is one of the predictive factors of worse outcomes after mitral valve surgery for mitral regurgitation (MR). We aimed to investigate the effect of MR etiology on progression of LA remodeling in swine MR models. MR was induced in 14 Yorkshire pigs using catheter-based procedures. Seven pigs underwent simultaneous occlusions of the left circumflex artery and the diagonal branch, which resulted in ischemic mitral regurgitation (IMR group). The other seven pigs underwent chordal severing to induce leaflet prolapse simulating degenerative mitral regurgitation (DMR group). Changes in LA volume and function were assessed at baseline, 1 mo, and 3 mo using echocardiography and hemodynamic evaluations. Histopathological assessments were conducted to evaluate LA hypertrophy and fibrosis. At 3 mo, quantitative MR severity was comparable and severe in both groups. Despite the similar degree of MR, minimum LA volume index increased significantly more in the IMR group (IMR: 11.9 ± 6.4 to 73.2 ± 6.4 mL/m2, DMR: 10.7 ± 6.4 to 29.5 ± 6.4 mL/m2, Pinteraction = 0.004). Meanwhile, increase in maximum LA volume index was similar between the groups, resulting in lower LA emptying function in the IMR group (IMR: 60.1 ± 3.1 to 29.4 ± 3.1%; DMR: 62.4 ± 3.1 to 58.2 ± 3.1%, Pinteraction = 0.0003). LA reservoir strain assessed by echocardiography was also significantly lower in the IMR group. Histological analyses revealed increased LA cellular hypertrophy and fibrosis in the IMR group. In conclusion, ischemic MR is associated with aggressive remodeling and reduced emptying function compared with the MR due to leaflet prolapse. Earlier intervention might be necessary for ischemic MR to prevent LA remodeling.NEW & NOTEWORTHY We show different LA structural and functional remodeling patterns between ischemic MR and MR due to leaflet prolapse. Severe ischemic MR was accompanied by extensive LA remodeling, which may be associated with poor clinical outcomes. Our data suggest that detailed structural and functional LA remodeling assessment is important for managing IMR and to determine the presence of LA ischemia.

Right anterior minithoracotomy for redo aortic valve replacement after coronary artery bypass grafting with bilateral internal thoracic artery: A case report.

A 63-year-old male, with a history of coronary artery bypass grafting using bilateral internal thoracic artery (ITA) grafts, underwent surgical aortic valve replacement (AVR). Avoiding the graft injury, we selected the right anterior minithoracotomy approach under cardiac arrest with systemic hyperkalemia with remaining bilateral ITA grafts open. Deep hypothermia was induced to obtain more reliable myocardial protection. We believe this strategy can be considered as a therapeutic option in patients requiring AVR but unsuitable for transcatheter AVR.

Alport syndrome: A case study of chronic type A aortic dissection.

A 39-year-old woman with a history of Alport syndrome was admitted to our hospital for heart failure due to severe aortic regurgitation. Computed tomography revealed a chronic type A aortic dissection that required valve-sparing aortic root replacement. The pathological examination demonstrated that elastic fibers in the tunica media of the aortic wall are torn and severely disorganized. Immunostaining showed fragmented alpha 5 chains, indicating Alport syndrome. These findings imply Alport syndrome may have connective tissue vulnerability, rendering patients susceptible to the development of aortic disease at a young age.

Impact of tricuspid annuloplasty on postoperative changes in the right ventricular systolic and diastolic function: A retrospective cohort study.

OBJECTIVES: To elucidate the impact of regulation of tricuspid regurgitation (TR) using tricuspid annuloplasty on postoperative changes in right ventricular (RV) systolic and diastolic functions. METHODS: We enrolled 69 patients who underwent aortic or mitral valve surgery between July 2016 to March 2018 without recurrence. Patients with concomitant coronary artery bypass grafting or a history of previous cardiovascular surgery were excluded, remaining 45 patients enrolled. Patients were divided into two groups according to concomitant tricuspid annuloplasty (T: n = 12 vs non-T: n = 33). RV global longitudinal strain (RVGLS), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), and early tricuspid inflow velocity/early diastolic tricuspid annular velocity ratio (tricuspid E/e') were assessed as functional indices at preoperative, postoperative and 1-year follow-up periods. RESULTS: RVFAC deteriorated postoperatively but recovered at follow-up in group T, whereas that in group non-T showed gradual deterioration overtime. RVGLS and TAPSE showed similar temporary deterioration and recovery between groups. Tricuspid E in group T increased postoperatively and showed significant difference, which was kept until follow-up period. Tricuspid e' decreased postoperatively, and recovered slightly in both groups. As a result, postoperative RV diastolic function (tricuspid E/e') showed significant difference between groups. This difference was maintained until follow-up. CONCLUSIONS: RV systolic function deteriorated postoperatively, but there was a tendency to improve at follow-up regardless of tricuspid annuloplasty. RV diastolic function may potentially be impaired when TR was regulated by tricuspid annuloplasty.

Multiple Spontaneous Iliac and Femoral Arteriovenous Fistulas.

An arteriovenous fistula (AVF) in a limb involves an abnormal connection between a limb artery and vein. It can be due to trauma or iatrogenic injury. Traumatic AVFs can be caused by penetrating or gunshot injuries to the limb, whereas iatrogenic causes include catheter intervention to the groins or open surgery of the inguinal space. By contrast, the occurrence of multiple spontaneous AVFs is rare. We report a case of endovascular therapy for multiple spontaneous AVFs between the iliac artery and the vein, common femoral artery and the vein, superficial artery and the saphenous vein, and deep femoral artery and the vein.

Popliteal Artery Pseudoaneurysm Caused by Osteochondroma.

A 16-year-old boy developed pulsating pain and dysesthesia in his right knee. Computed tomography showed a large aneurysm in the right upper popliteal artery and a spiked bone tumor arising from the right distal femoral shaft. Pseudoaneurysm due to osteochondroma was suspected, and the patient underwent emergency surgery. A 2-mm pinhole was detected in the arterial wall behind the tumor. After resection of the tumor, the damaged arterial wall was removed, and the defect was repaired using a saphenous vein patch. We suggest that patch repair is preferable to direct closure or end-to-end anastomosis to prevent recurrent pseudoaneurysm at a later time, even if the defect is small.

Endovascular Treatment for Proximal Anastomotic Pseudoaneurysm after Total Arch Replacement in Behcet's Disease.

A 17-year-old patient underwent total arch replacement for aortic arch aneurysm due to vascular Behcet's disease (BD). Follow-up computed tomography, performed 6 months after the operation, demonstrated pseudoaneurysm formation at the proximal anastomotic site. We performed endovascular treatment and used a short stent graft that was originally designed for abdominal aortic aneurysm. To avoid the occlusion of the coronary or brachiocephalic artery (BCA) due to stent graft migration, we used right ventricular rapid pacing and BCA ballooning. Thus, we believe that endovascular treatment can be used for anastomotic complications in the ascending aorta after open surgery for connective tissue disorders including BD.

Inhibition of endothelial to mesenchymal transition in a large animal preclinical arterio-venous fistula model leads to improved remodeling and reduced stenosis.

AIMS: Vein grafts are used for many indications, including bypass graft surgery and arterio-venous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia and adverse remodeling. Recently, endothelial to mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts. We aimed to evaluate the clinical potential of inhibiting EndMT, and developed the first dedicated preclinical model to study the efficacy of local EndMT inhibition immediately prior to AVF creation. METHODS AND RESULTS: We first undertook pilot studies to optimize the creation of a femoral AVF in pigs and verify that EndMT contributes to neointimal formation. We then developed a method to achieve local in vivo SMAD3 knockdown by dwelling a lentiviral construct containing SMAD3 shRNA in the femoral vein prior to AVF creation. Next, in Phase 1, 6 pigs were randomized to SMAD3 knockdown or control lentivirus to evaluate the effectiveness of SMAD3 knockdown and EndMT inhibition 8 days after AVF creation. In Phase 2, 16 pigs were randomized to SMAD3 knockdown or control lentivirus and were evaluated to assess longer-term effects on AVF diameter, patency and related measures at 30 days after AVF creation.In Phase 1, compared to controls, SMAD3 knockdown achieved a 75% reduction in the proportion of CD31+ endothelial cells co-expressing SMAD3 (p<0.001), and also a significant reduction in the extent of EndMT (p<0.05). In Phase 2, compared to controls, SMAD3 knockdown was associated with an increase in the minimum diameter of the venous limb of the AVF (1.56±1.66 versus 4.26±1.71mm, p<0.01) and a reduced degree of stenosis (p<0.01). Consistent with this, neointimal thickness was reduced in the SMAD3 knockdown group (0.88±0.51 versus 0.45±0.19mm, p<0.05). Furthermore, endothelial integrity (the proportion of luminal cells expressing endothelial markers) was improved in the SMAD3 knockdown group (p<0.05). CONCLUSIONS: EndMT inhibition in a preclinical AVF model by local SMAD3 knockdown using gene therapy led to reduced neointimal hyperplasia, increased endothelialization and a reduction in the degree of AVF stenosis. This provides important proof-of-concept to pursue this approach as a clinical strategy to improve the patency of AVFs and other vein grafts.

Body temperature as a predictor of mortality in COVID-19.

It remains uncertain if body temperature (BT) is a useful prognostic indicator in coronavirus disease 2019 (COVID-19). We investigated the relationship between BT and mortality in COVID-19 patients. We used a de-identified database that prospectively collected information from patients screened for COVID-19 at the Mount Sinai facilities from February 28, 2020 to July 28, 2021. All patients diagnosed with COVID-19 that had BT data were included. BT at initial presentation, maximum BT during hospitalization, comorbidity, and vaccination status data were extracted. Mortality rate was assessed as a primary outcome. Among 24,293 cases, patients with initial BT below 36 °C had higher mortality than those with BT of 36-37 °C (p < 0.001, odds ratio 2.82). Initial BT > 38 °C was associated with high mortality with an incremental trend at higher BT. In 10,503 in-patient cases, a positive association was observed between mortality and maximum BT except in patients with BT < 36 °C. Multiple logistic regression analyses including the comorbidities revealed that maximum BT was an independent predictor of mortality. While vaccination did not change the distribution of maximum BT, mortality was decreased in vaccinated patients. Our retrospective cohort study suggests that high maximum BT is an independent predictor of higher mortality in COVID-19 patients.

Intimal tear closure by false lumen stent graft placement for postdissection thoracoabdominal aortic aneurysm.

We report a false lumen (FL) stent graft technique to close the intimal tears at the visceral segment for a postdissection thoracoabdominal aneurysm after initial thoracic endovascular aortic repair. Following endovascular abdominal aortic repair, a stent graft was deployed in the FL, overlapping the main bodies from both previous repairs just after a bare metal stent was implanted in the FL proximal to the target lesion to prevent overdilation. A reentry tear at the iliac level was intentionally preserved to protect spinal cord perfusion and develop a collateral network and will be closed in the future staged procedure.

Rapid-Deployment Aortic Valve Replacement: Patient Selection and Special Considerations.

Sutureless or rapid deployment valves in the setting of aortic valve replacement (AVR) is an emerging surgical technique using the transcatheter valve technology, which may lead to reduction in cross-clamp time and potentially better hemodynamics compared to a stented bioprosthetic valve. The absence of subannular pledgets results to excellent hemodynamic performance with reduced turbulent flow and larger effective orifice area. However, complications from both surgical and transcatheter AVR may still occur and impact survival. The incidence of paravalvular leakage and permanent pacemaker implantation are not low. Although technical modifications can improve these outcomes, there is a learning curve effect. Therefore, technical and anatomical considerations as well as better patient selection are paramount for better outcomes. In this review, we discuss the use of sutureless or rapid deployment valves in setting of (1) complex procedures, (2) minimally invasive AVR, and (3) small aortic annulus. The advantage of sutureless or rapid deployment valves in terms of mortality remains to be clarified; therefore, it is necessary to accumulate long-term outcomes in an appropriate patient cohort.

Selection of Vascular Closure Devices in Transcatheter Aortic Valve Replacement: Systematic Review and Network Meta-Analysis.

Various vascular closure devices (VCDs) are commonly used for percutaneous transcatheter aortic valve replacement (TAVR). However, superiority and safety profile among them remain unclear. We compared periprocedural complications among various VCDs in patients undergoing TAVR. PubMed and EMBASE were searched through January 2022 to identify clinical studies comparing any 2 VCDs of Prostar, Proglide and MANTA in patients who underwent TAVR. Studies using surgical cut-down or alternative access other than transfemoral approach were excluded. We analyzed the odds ratios (ORs) of vascular complications (VC), bleeding, acute kidney injury and all-cause mortality using a network meta-analysis. All outcomes were defined by Valve Academic Research Consortium 2 criteria. Two randomized controlled trials and 15 observational studies were identified, yielding a total of 11,344 patients including Prostar (n = 4499), Proglide (n = 5705), or MANTA group (n = 1140). The rates of major VC and life-threatening and major bleeding were significantly lower in Proglide compared to Prostar (OR [95 % CI] = 0.54 [0.32-0.89], 0.68 [0.52-0.90], and 0.49 [0.26-0.95], respectively). There was no significant difference in major VC and bleeding between Proglide and MANTA groups. Proglide was associated with a lower rate of acute kidney injury (0.56 [0.34-0.92]) and red blood cell transfusion (0.39 [0.16-0.98]) compared to Prostar. There was no significant difference in additional interventions and 30-day overall mortality among three groups. In this network meta-analysis of VCD in patients undergoing TAVR, MANTA and Proglide had comparable outcomes while Proglide appears superior to Prostar in terms of major VC and bleeding.

Cardioprotective effect of Interleukin-11 against warm ischemia-reperfusion injury in a rat heart donor model.

Shortage of donor organs for heart transplantation is a worldwide problem. Donation after circulatory death (DCD) has been proposed to expand the donor pool. However, in contrast to the donation after brain death that undergoes immediate cold preservation, warm ischemia and subsequent reperfusion injury are inevitable in DCD. It has been reported that interleukin-11 (IL-11) mitigates ischemia-reperfusion injury in rodent models of myocardial infarction and donation after brain death heart transplantation. We hypothesized that IL-11 also offers benefit to warm ischemia in an experimental model of cardiac transplantation that resembles DCD. The hearts of naïve male Sprague Dawley rats (n = 15/group) were procured, subjected to 25-min warm ischemia, and reperfused for 60 min using Langendorff apparatus. IL-11 or saline was administered intravenously before the procurement, added to maintenance buffer, and infused via perfusion during reperfusion. IL-11 group exhibited significantly better cardiac function post-reperfusion. Severely damaged mitochondria was found in the electron microscopic analysis of control hearts whereas the mitochondrial structure was better preserved in the IL-11 treated hearts. Immunoblot analysis using neonatal rat cardiomyocytes revealed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation at Ser727 after IL-11 treatment, suggesting its role in mitochondrial protection. Consistent with expected activation of mitochondrial respiration by mitochondrial STAT3, immunohistochemical staining demonstrated a higher mitochondrial cytochrome c oxidase subunit 2 expression. In summary, IL-11 protects the heart from warm ischemia reperfusion injury by alleviating mitochondrial injury and could be a viable therapeutic option for DCD heart transplantation.

Vascular access for transcatheter aortic valve replacement: A network meta-analysis.

BACKGROUND: The choice of an alternative access for transcatheter aortic valve replacement (TAVR) remains controversial when transfemoral (TF) access is not feasible. METHODS: We conducted a network meta-analysis to compare the outcomes of TAVR via various peripheral vascular accesses. MEDLINE and EMBASE were searched through July 2022 to identify studies that investigated outcomes in patients who underwent TAVR via TF, trans-subclavian (Tsc), transcarotid (TC), or transcaval (Tcav) access. A network meta-analysis was conducted via random-effects model. Outcomes of interest were major or life-threatening bleeding, stroke, major vascular complication, and 30-day mortality. RESULTS: No randomized trial was identified. Our analysis included 33 observational studies that enrolled a total of 43,455 patients who underwent TAVR via TF (n = 36,202), Tsc (n = 3869), TC (n = 3066), or Tcav (n = 318) access. The risk of major or life-threatening bleeding was higher via Tsc compared with TF [odds ratio (OR); 95 % confidence interval (CI) =1.51 (1.03-2.23), p = 0.034]. The risk of stroke was higher via Tsc compared with TF and Tcav [OR (95 % CI) =2.00 (1.14-3.52), p = 0.018, OR (95 % CI) =2.43 (1.03-5.74), p = 0.044, respectively]. The risk of major vascular complications was lower via TC compared with Tsc, and Tcav and higher with Tcav compared with TF and Tsc. 30-day mortality was higher via Tsc compared with TF. Tsc was associated with higher risk of major or life-threatening bleeding compared with TF, and higher risk of stroke compared to TF and Tcav. Tcav had the highest risk of major vascular complications. CONCLUSION: In patients who underwent TF, Tsc, TC, or Tcav TAVR, Tsc had a higher rate of stroke compared to TF and Tcav, and major or life-threatening bleeding compared to TF. The rate of major vascular complications in Tcav was the highest among the four approaches.

Negative Impact of Acute Reloading after Mechanical Left Ventricular Unloading.

Mechanical LV unloading for acute myocardial infarction (MI) is a promising supportive therapy to reperfusion. However, no data is available on exit strategy. We evaluated hemodynamic and cellular effects of reloading after Impella-mediated LV unloading in Yorkshire pigs. First, we conducted an acute study in normal heart to observe effects of unloading and reloading independent of MI-induced ischemic effects. We then completed an MI study to investigate optimal exit strategy on one-week infarct size, no-reflow area, and LV function with different reloading speeds. Initial studies showed that acute reloading causes an immediate rise in end-diastolic wall stress followed by a significant increase in cardiomyocyte apoptosis. The MI study did not result in any statistically significant findings; however, numerically smaller average infarct size and no-reflow area in the gradual reloading group prompt further examination of reloading approach as an important clinically relevant consideration.

Late open conversion after endovascular treatment for the coarctation of aorta in adult due to restenosis with thrombus.

A 22-year-old man was referred to our hospital for rib notching found on a radiograph and hypertension. Computed tomography revealed coarctation of the descending aortic isthmus. Because he refused open surgery, endovascular treatment was performed. The 2-year follow-up computed tomography scan showed infolding of the stent graft and thrombus formation. He had presented with intermittent claudication; therefore, graft interposition was performed. Endovascular surgery plays an important role in the treatment of coarctation of the aorta. However, insufficient dilatation can lead to restenosis accompanied by thrombus formation, and excess ballooning can cause aortic wall injury. Careful performance of the procedure and close postoperative follow-up are essential.

Cardiac Gene Delivery in Large Animal Models: Antegrade Techniques.

Percutaneous antegrade coronary injection is among the least invasive cardiac selective gene delivery methods. However, the transduction efficiency of a simple bolus antegrade injection is quite low. In order to improve transduction efficiency in antegrade intracoronary delivery, several additional approaches have been proposed.In this chapter, we will describe the important elements associated with intracoronary delivery methods and present protocols for three different catheter-based antegrade gene delivery techniques in a preclinical large animal model. This is the second edition of this chapter, and it includes modifications we have made over the past several years that further enhance transduction efficacy.

Device-Based Approaches Targeting Cardioprotection in Myocardial Infarction: The Expanding Armamentarium of Innovative Strategies.

Coronary reperfusion therapy has played a pivotal role for reducing mortality and heart failure after acute myocardial infarction. Although several adjunctive approaches have been studied for reducing infarct size further, both ischemia-reperfusion injury and microvascular obstruction are still major contributors to both early and late clinical events after acute myocardial infarction. The progress in the field of cardioprotection has found several promising proof-of-concept preclinical studies. However, translation from bench to bedside has not been very successful. This comprehensive review discusses the importance of infarct size as a driver of clinical outcomes post-acute myocardial infarction and summarizes recent novel device-based approaches for infarct size reduction. Device-based interventions including mechanical cardiac unloading, myocardial cooling, coronary sinus interventions, supersaturated oxygen therapy, and vagal stimulation are discussed. Many of these approaches can modify ischemic myocardial biology before reperfusion and offer unique opportunities to target ischemia-reperfusion injury.