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1.
Cardiovasc Revasc Med ; 59: 9-13, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37550124

ABSTRACT

BACKGROUND/PURPOSE: The cusp overlap technique has standardized implantation for self-expanding valves with the goal of achieving more consistent implantation depths and lowering permanent pacemaker (PPM) implantation rates. We retrospectively compared short-term outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with a self-expanding valve implanted using the cusp overlap technique vs. the traditional coplanar technique in a large tertiary referral center. METHODS: We conducted a retrospective study among PPM-naïve patients who underwent TAVR using the CoreValve Evolut PRO/PRO+. We compared in-hospital PPM rates in patients who underwent TAVR using the cusp overlap technique vs. the coplanar technique. Additional outcomes included in-hospital all-cause mortality, stroke, major vascular complications, annular rupture, and >mild paravalvular leak. Furthermore, we compared outcomes over time to see whether there was evidence of a learning curve. RESULTS: Of the 528 patients included, 270 underwent TAVR using the coplanar technique and 258 underwent TAVR using the cusp overlap technique. The rate of new PPM implantation did not differ between cohorts (17.0 % vs. 16.7 %; p = 0.910). Additionally, rates of in-hospital all-cause mortality (0.0 % vs. 0.4 %; p = 0.328), stroke (3.7 % vs. 1.6 %; p = 0.124), major vascular complications (0.7 % vs. 1.2 %; p = 0.617), annular rupture (0.4 % vs. 0.0 %; p = 0.328) and >mild paravalvular leak (0.0 % vs. 0.4 %; p = 0.444) were similar. Our secondary analysis did not identify any evidence of a learning curve. CONCLUSIONS: The cusp overlap technique may not yield a reduction in PPM rates when compared with the coplanar technique. Other confounders should be explored to further minimize in-hospital PPM rates.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Pacemaker, Artificial , Stroke , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Retrospective Studies , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Treatment Outcome , Risk Factors , Prosthesis Design
2.
Eur Heart J Case Rep ; 7(5): ytad218, 2023 May.
Article in English | MEDLINE | ID: mdl-37181467

ABSTRACT

Background: Aspergillus endocarditis is a rare cause of infective endocarditis and requires high index of suspicion for diagnosis. Case summary: We describe a case of a 50-year-old man with history of metastatic thymoma on immunosuppression (gemcitabine and capecitabine) who presented with progressive dyspnoea. Echocardiography and computed tomography (CT) of chest showed filling defect in the pulmonary artery. The initial differential diagnosis was of pulmonary embolism and metastatic disease. The mass was subsequently excised, which revealed a diagnosis of Aspergillus endocarditis of the pulmonary valve. Unfortunately, he passed away despite medical treatment with antifungal therapy after surgery. Discussion: Aspergillus endocarditis should be suspected in immunosuppressed hosts with negative blood cultures and large vegetations on echocardiography. Diagnosis is made by tissue histology but may be difficult or delayed. Optimal treatment involves aggressive surgical debridement and prolonged antifungal therapy; prognosis is poor with high mortality.

3.
J Am Coll Cardiol ; 81(21): 2115-2127, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37225366

ABSTRACT

Mechanical prosthetic heart valves, though more durable than bioprostheses, are more thrombogenic and require lifelong anticoagulation. Mechanical valve dysfunction can be caused by 4 main phenomena: 1) thrombosis; 2) fibrotic pannus ingrowth; 3) degeneration; and 4) endocarditis. Mechanical valve thrombosis (MVT) is a known complication with clinical presentation ranging from incidental imaging finding to cardiogenic shock. Thus, a high index of suspicion and expedited evaluation are essential. Multimodality imaging, including echocardiography, cine-fluoroscopy, and computed tomography, is commonly used to diagnose MVT and follow treatment response. Although surgery is oftentimes required for obstructive MVT, other guideline-recommended therapies include parenteral anticoagulation and thrombolysis. Transcatheter manipulation of stuck mechanical valve leaflet is another treatment option for those with contraindications to thrombolytic therapy or prohibitive surgical risk or as a bridge to surgery. The optimal strategy depends on degree of valve obstruction and the patient's comorbidities and hemodynamic status on presentation.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Thrombosis , Humans , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/therapy , Heart Valve Prosthesis/adverse effects , Anticoagulants/therapeutic use , Heart Valves
4.
Am J Cardiol ; 193: 1-18, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36857839

ABSTRACT

Since the first transcatheter delivery of an aortic valve prosthesis was performed by Cribier et al in 2002, the picture of aortic stenosis (AS) therapeutics has changed dramatically. Initiated from an indication of inoperable to high surgical risk, extending to intermediate and low risk, transcatheter aortic valve replacement (TAVR) is now an approved treatment for patients with severe, symptomatic AS across all the risk categories. The current evidence supports TAVR as a frontline therapy for treating severe AS. The crucial question remains concerning the subset of patients who still are not ideal candidates for TAVR because of certain inherent anatomic, nonmodifiable, and procedure-specific factors. Therefore, in this study, we focus on these scenarios and reasons for referring selected patients for surgical aortic valve replacement in 2023.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Risk Factors , Treatment Outcome , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/etiology , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis/adverse effects
5.
Catheter Cardiovasc Interv ; 100(3): 404-412, 2022 09.
Article in English | MEDLINE | ID: mdl-35723247

ABSTRACT

OBJECTIVES: Evaluate transcatheter heart valve (THV) geometry according to left ventricular outflow tract (LVOT) calcium degree and its impact on hemodynamics and outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with a contemporary self-expanding THV. BACKGROUND: LVOT calcium remains challenging for contemporary THVs. LVOT calcium location and degree may affect THV deployment and impact flow patterns and shear stress, accelerating THV degeneration. METHODS: EPROMPT (CoreValve Evolut Pro Prospective Registry; NCT03423459) is a prospective, investigator-initiated, multicenter registry of patients undergoing TAVR using CoreValve Evolut PRO/PRO + THVs. A total of 107 patients were enrolled in EPROMPT's computed tomography (CT) cohort between January 2018 and October 2021. These patients underwent follow-up CT scan 30 days post-TAVR. We analyzed THV geometry and its interaction with the aortic root following deployment using 30-day post-TAVR CT in patients with none/mild versus moderate/severe LVOT calcium. RESULTS: Thirty-day THV inflows were less eccentric in the short axis in patients with none/mild versus moderate/severe LVOT calcium (1.16 ± 0.09 vs. 1.21 ± 0.12; p = 0.007). THV became more circular and was similar between both cohorts at the THV waist (1.08 ± 0.06 vs. 1.09 ± 0.11; p = 0.551), leaflet tips (1.03 ± 0.04 vs. 1.05 ± 0.09; p = 0.299), and THV outflow (1.04 ± 2.2 vs. 1.03 ± 2.7; p = 0.143). Thirty-day > mild paravalvular leak was low in both cohorts (1.5% vs. 2.4%; p = 0.724); mean gradients were similar (7.7 ± 3.6 vs. 7.7 ± 3.4 mmHg; p = 0.955). CONCLUSIONS: Despite inflow deformities observed in patients with moderate/severe LVOT calcium, Evolut PRO/PRO + conforms to elliptical aortic annuli, maintaining circularity and proper function at the leaflets and outflow, even in patients with moderate/severe LVOT calcium.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/etiology , Aortic Valve Stenosis/surgery , Calcium , Humans , Prosthesis Design , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome
6.
Cardiovasc Revasc Med ; 42: 109-113, 2022 09.
Article in English | MEDLINE | ID: mdl-35361569

ABSTRACT

BACKGROUND/PURPOSE: Coronary artery bypass graft (CABG) in the presence of metallic permanent stents may be challenging. We explored the feasibility of performing CABG in 1-year Magmaris resorbable scaffold implants in healthy Yucatan pigs. METHODS/MATERIALS: One animal received Magmaris 3.0 × 20.0-mm scaffolds in the left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCA) under fluoroscopy. After 376 days, the animal underwent off-pump CABG at the scaffold site, including a single "end-to-side" anastomosis involving the right internal mammary artery (RIMA) to the LAD. The LAD was grafted in the territory of the previous scaffold as demonstrated by angiogram and the D1 and D2 landmarks. RESULTS: Digital radiography of the intact heart showed all degraded scaffolds widely expanded and uniformly positioned in the vessel wall in their expected locations. The proximal and distal radiopaque markers were clearly visible. The anastomosis was clearly identified by titanium branch clips, and the RIMA bypass was surrounded by connective tissue, which was further dissected before micro-computed tomography (CT) imaging. On the micro-CT images, calcification of the device was rare. The anastomosis site appeared intact, and the LAD at treatment site was widely open. CONCLUSIONS: Our limited early feasibility study in a healthy animal demonstrates the practicality of CABG in a Magmaris scaffold after 1 year despite the persistence of visible degradation product, suggesting that the prior coronary device implant does not preclude future coronary surgery.


Subject(s)
Magnesium , Mammary Arteries , Animals , Coronary Artery Bypass , Swine , Treatment Outcome , X-Ray Microtomography
7.
JACC Cardiovasc Interv ; 14(11): 1169-1180, 2021 06 14.
Article in English | MEDLINE | ID: mdl-34112453

ABSTRACT

Transcatheter aortic valve replacement (TAVR) is approved for all patient risk profiles and is an option for all patients irrespective of age. However, patients enrolled in the low- and intermediate-risk trials were in their 70s, and those in the high-risk trials were in their 80s. TAVR has never been systematically tested in young (<65 years), low-risk patients. Unanswered questions remain, including the safety and effectiveness of TAVR in patients with bicuspid aortic valves; future coronary access; durability of transcatheter heart valves; technical considerations for surgical transcatheter heart valve explantation; management of concomitant conditions such as aortopathy, mitral valve disease, and coronary artery disease; and the safety and feasibility of future TAVR-in-TAVR. The authors predict that balancing these questions with patients' clear preference for less invasive treatment will become common. In this paper, the authors consider each of these questions and discuss risks and benefits of theoretical treatment strategies in the lifetime management of young patients with severe aortic stenosis.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Heart Valve Prosthesis Implantation/adverse effects , Humans , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
8.
JACC Cardiovasc Interv ; 14(9): 941-948, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33958168

ABSTRACT

OBJECTIVES: This study sought to determine the safety of the BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) procedure. BACKGROUND: Transcatheter aortic valve replacement causes coronary artery obstruction in 0.7% of cases, with 40% to 50% mortality. BASILICA is a procedure to prevent coronary obstruction. Safety and feasibility in a large patient cohort is lacking. METHODS: The international BASILICA registry was a retrospective, multicenter, real-world registry of patients at risk of coronary artery obstruction undergoing BASILICA and transcatheter aortic valve replacement. Valve Academic Research Consortium-2 definitions were used to adjudicate events. RESULTS: Between June 2017 and December 2020, 214 patients were included from 25 centers in North America and Europe; 72.8% had bioprosthetic aortic valves and 78.5% underwent solo BASILICA. Leaflet traversal was successful in 94.9% and leaflet laceration in 94.4%. Partial or complete coronary artery obstruction was seen in 4.7%. Procedure success, defined as successful BASILICA traversal and laceration without mortality, coronary obstruction, or emergency intervention, was achieved in 86.9%. Thirty-day mortality was 2.8% and stroke was 2.8%, with 0.5% disabling stroke. Thirty-day death and disabling stroke were seen in 3.4%. Valve Academic Research Consortium-2 composite safety was achieved in 82.8%. One-year survival was 83.9%. Outcomes were similar between solo and doppio BASILICA, between native and bioprosthetic valves, and with the use of cerebral embolic protection. CONCLUSIONS: BASILICA is safe, with low reported rates of stroke and death. BASILICA is feasible in the real-world setting, with a high procedure success rate and low rates of coronary artery obstruction.


Subject(s)
Bioprosthesis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Prosthesis Design , Registries , Retrospective Studies , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
9.
Cardiovasc Revasc Med ; 29: 85-88, 2021 08.
Article in English | MEDLINE | ID: mdl-33965334

ABSTRACT

BACKGROUND: Before its voluntary recall, the mechanically expandable LOTUS Edge transcatheter heart valve (THV) offered a number of unique features, notably sealing against paravalvular leak (PVL) and the ability to be fully deployed, re-captured, and re-deployed. METHODS: We performed a detailed review of all patients at our institution who underwent transcatheter aortic valve replacement (TAVR) using the LOTUS Edge THV from 2019 to 2020. We describe procedural and in-hospital outcomes. RESULTS: In brief, 59 patients underwent TAVR using the LOTUS Edge, of whom 18 were high-risk (most of whom had moderate or severe left ventricular outflow tract [LVOT] calcium), 36 were intermediate-risk enrolled in the REPRISE IV trial (one of whom had a bicuspid valve), and 5 were low-risk bicuspid patients enrolled in the LRT trial. Conduction disturbances were common (new left bundle branch block in 64.4%), with high rates of new permanent pacemaker (PPM) implantation across all risk groups (16.9%). Overall, stroke occurred in 11.9% of patients, and in 3/5 low-risk bicuspid patients, but occurred less frequently in patients with cerebral embolic protection. CONCLUSIONS: In our experience, in patients with heavy LVOT calcium burden and/or bicuspid valves, the LOTUS Edge THV offered excellent seal against PVL. However, the high rates of periprocedural stroke and new PPM implantation were a concern.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/surgery , Humans , Prosthesis Design , Retrospective Studies , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Treatment Outcome
10.
J Cardiovasc Dev Dis ; 7(4)2020 Nov 17.
Article in English | MEDLINE | ID: mdl-33212844

ABSTRACT

The clinical efficacy of neuregulin (NRG) in the treatment of heart failure is hindered by off-target exposure due to systemic delivery. We previously encapsulated neuregulin in a hydrogel (HG) for targeted and sustained myocardial delivery, demonstrating significant induction of cardiomyocyte proliferation and preservation of post-infarct cardiac function in a murine myocardial infarction (MI) model. Here, we performed a focused evaluation of our hydrogel-encapsulated neuregulin (NRG-HG) therapy's potential to enhance cardiac function in an ovine large animal MI model. Adult male Dorset sheep (n = 21) underwent surgical induction of MI by coronary artery ligation. The sheep were randomized to receive an intramyocardial injection of saline, HG only, NRG only, or NRG-HG circumferentially around the infarct borderzone. Eight weeks after MI, closed-chest intracardiac pressure-volume hemodynamics were assessed, followed by heart explant for infarct size analysis. Compared to each of the control groups, NRG-HG significantly augmented left ventricular ejection fraction (p = 0.006) and contractility based on the slope of the end-systolic pressure-volume relationship (p = 0.006). NRG-HG also significantly reduced infarct scar size (p = 0.002). Overall, using a bioengineered hydrogel delivery system, a one-time dose of NRG delivered intramyocardially to the infarct borderzone at the time of MI in adult sheep significantly reduces scar size and enhances ventricular contractility at 8 weeks after MI.

11.
Microb Biotechnol ; 13(6): 1780-1792, 2020 11.
Article in English | MEDLINE | ID: mdl-32476224

ABSTRACT

The cyanobacterium Synechococcus elongatus (SE) has been shown to rescue ischaemic heart muscle after myocardial infarction by photosynthetic oxygen production. Here, we investigated SE toxicity and hypothesized that systemic SE exposure does not elicit a significant immune response in rats. Wistar rats intravenously received SE (n = 12), sterile saline (n = 12) or E. coli lipopolysaccharide (LPS, n = 4), and a subset (8 SE, 8 saline) received a repeat injection 4 weeks later. At baseline, 4 h, 24 h, 48 h, 8 days and 4 weeks after injection, clinical assessments, blood cultures, blood counts, lymphocyte phenotypes, liver function tests, proinflammatory cytokines and immunoglobulins were assessed. Across all metrics, SE rats responded comparably to saline controls, displaying no clinically significant immune response. As expected, LPS rats exhibited severe immunological responses. Systemic SE administration does not induce sepsis or toxicity in rats, thereby supporting the safety of cyanobacteria-mammalian symbiotic therapeutics using this organism.


Subject(s)
Escherichia coli , Synechococcus , Animals , Photosynthesis , Rats , Rats, Wistar
12.
Ann Thorac Surg ; 108(5): e295-e296, 2019 11.
Article in English | MEDLINE | ID: mdl-30986415

ABSTRACT

A 28-year-old man with ventricular septal defect, double-chambered right ventricle with associated right ventricular outflow tract obstruction, and anomalous right coronary artery underwent resection of the double-chambered right ventricle, transaortic ventricular septal defect repair, and unroofing of anomalous right coronary artery. Two years later, he returned with delayed presentation of ventricular septal defect flow funnel-related aortic cusp prolapse and symptomatic severe aortic regurgitation. He underwent reoperative valve-sparing aortic root replacement and aortic cusp repair with an excellent outcome.


Subject(s)
Aortic Valve Insufficiency/surgery , Aortic Valve Prolapse/surgery , Heart Septal Defects, Ventricular/surgery , Postoperative Complications/surgery , Adult , Humans , Male , Reoperation , Time Factors
13.
J Thorac Cardiovasc Surg ; 157(2): 603-610, 2019 02.
Article in English | MEDLINE | ID: mdl-30669225

ABSTRACT

OBJECTIVES: Orthotopic heart transplantation (OHT) remains the gold standard for advanced heart failure. Increased risk (IR) donors were categorized by the United Network for Organ Sharing Database (UNOS) according to the Centers for Disease Control and Prevention (CDC) criteria. However, the impact of CDC IR donor hearts on the outcome of adult OHT recipients remains unclear. The aim of this study was to compare the outcome of adult OHT recipients between CDC IR and non-CDC IR donor grafts. METHODS: Data were obtained from the United Network for Organ Sharing Databas. All adult patients (age ≥18 years) undergoing OHT from 2004 through 2016 were included (n = 24,751). Propensity scores for CDC IR donors were calculated by estimating probabilities of CDC IR donor graft use using a nonparsimonious multivariable logistic regression model. Patients were matched 1:1 using a greedy matching algorithm based on the propensity score of each patient. The impact of CDC IR donors on the post-transplant outcomes, such as 30-day and overall mortalities, was investigated using Cox-proportional hazards. Overall survival probability analyses were performed. RESULTS: Of 24,751 primary heart transplants from 2004 to 2016 with 3584 (14.5%) as IR donors, 6304 transplants were successfully matched (n = 3152 in CDC IR group and non-IR group). There were no significant differences in baseline characteristics in recipients and donors. In the Cox-proportional hazards model for matched subjects, the use of CDC IR grafts was not associated with 30-day (hazard ratio of IR group vs non-IR group 0.97; 95% confidence interval, 0.87-1.08; P = .57) and overall mortalities (hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P = .62). Interestingly, post-transplant acute myocardial rejection episodes during hospital stays were found more often in the CDC-IR group, compared with the non-CDC IR group (CDC IR, n = 358 [11.4%]; non-CDC IR, n = 304 [9.6%] P = .03), whereas post-transplant pacemaker placements were performed less frequently in the CDC IR group (CDC IR, n = 80 [2.6%]; non-CDC IR, n = 111 [3.5%] P = .020). Importantly, there was no significant difference in the overall survival probability between CDC IR and non-IR groups in both unadjusted and adjusted survival analyses. CONCLUSIONS: CDC IR status does not have a significant impact on adult OHT recipient survival probability. Increased use of CDC IR donor grafts can potentially alleviate the persistent and worsening shortage of available donor organs and shorten the waitlist time for heart transplantation.


Subject(s)
Donor Selection , Heart Failure/surgery , Heart Transplantation/methods , Tissue Donors/supply & distribution , Waiting Lists , Adult , Aged , Databases, Factual , Female , Graft Survival , Heart Failure/diagnosis , Heart Failure/mortality , Heart Failure/physiopathology , Heart Transplantation/adverse effects , Heart Transplantation/mortality , Humans , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/surgery , Registries , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
14.
J Am Heart Assoc ; 7(23): e010253, 2018 12 04.
Article in English | MEDLINE | ID: mdl-30511896

ABSTRACT

Background The impact of donor obesity on the outcome of orthotopic heart transplantation has not been studied. The aim of this study was to investigate the impact of donor obesity on the outcomes of adult orthotopic heart transplantation recipients. Methods and Results Data were obtained from the United Network for Organ Sharing database. All adult (age ≥18 years) patients undergoing orthotopic heart transplantation from 2000 through 2016 were included (n=31 920). We stratified the cohort by donor body mass index ( BMI ); 13 015 patients (40.8%) received a heart from a normal-weight donor ( BMI 18.5-24.9), 11 271 patients (35.3%) received a heart from an overweight donor ( BMI 25.0-29.9), 4910 patients (15.4%) received a heart from an obese donor ( BMI 30.0-34.9), and 2724 patients (8.5%) received a heart from an extremely obese donor ( BMI ≥35). The cohort of obese donors was older, included a higher incidence of diabetes mellitus, and had a higher creatinine. Our data also showed that the recipients of obese donor grafts were older, had a higher BMI , creatinine, percentage of diabetes mellitus, and longer total waiting period. There was no significant difference detected in the survival likelihood ( P=0.08) of patients based on a donor's BMI-based categorized cohort. There were no significant differences found in the overall survival probability among 4 groups in the adjusted survival analyses ( P=0.25). Conclusions This study demonstrated that patients receiving higher BMI donor hearts might not be subjected to an increased risk of death, at least during the short term after transplant, compared with those using the normal-weight donors.


Subject(s)
Heart Transplantation , Obesity/complications , Tissue Donors , Adult , Body Mass Index , Databases as Topic , Female , Heart Transplantation/mortality , Heart Transplantation/statistics & numerical data , Humans , Male , Middle Aged , Survival Analysis , Tissue Donors/statistics & numerical data , Treatment Outcome
15.
Sci Adv ; 3(6): e1603078, 2017 06.
Article in English | MEDLINE | ID: mdl-28630913

ABSTRACT

Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.


Subject(s)
Myocardial Ischemia/metabolism , Myocardium/metabolism , Phototrophic Processes , Animals , Biological Therapy , Cyanobacteria , Energy Metabolism , Heart Function Tests , Hypoxia/metabolism , Myocardial Ischemia/physiopathology , Myocardial Ischemia/therapy , Myocytes, Cardiac/metabolism , Photosynthesis , Rats
16.
J Thorac Cardiovasc Surg ; 154(3): 955-963, 2017 09.
Article in English | MEDLINE | ID: mdl-28651946

ABSTRACT

OBJECTIVE: The angiogenic potential of endothelial progenitor cells (EPCs) may be limited by the absence of their natural biologic foundation, namely smooth muscle pericytes. We hypothesized that joint delivery of EPCs and smooth muscle cells (SMCs) in a novel, totally bone marrow-derived cell sheet will mimic the native architecture of a mature blood vessel and act as an angiogenic construct to limit post infarction ventricular remodeling. METHODS: Primary EPCs and mesenchymal stem cells were isolated from bone marrow of Wistar rats. Mesenchymal stem cells were transdifferentiated into SMCs by culture on fibronectin-coated culture dishes. Confluent SMCs topped with confluent EPCs were detached from an Upcell dish to create a SMC-EPC bi-level cell sheet. A rodent model of ischemic cardiomyopathy was then created by ligating the left anterior descending artery. Rats were randomized into 3 groups: cell sheet transplantation (n = 9), no treatment (n = 12), or sham surgery control (n = 7). RESULTS: Four weeks postinfarction, mature vessel density tended to increase in cell sheet-treated animals compared with controls. Cell sheet therapy significantly attenuated the extent of cardiac fibrosis compared with that of the untreated group (untreated vs cell sheet, 198 degrees [interquartile range (IQR), 151-246 degrees] vs 103 degrees [IQR, 92-113 degrees], P = .04). Furthermore, EPC-SMC cell sheet transplantation attenuated myocardial dysfunction, as evidenced by an increase in left ventricular ejection fraction (untreated vs cell sheet vs sham, 33.5% [IQR, 27.8%-35.7%] vs 45.9% [IQR, 43.6%-48.4%] vs 59.3% [IQR, 58.8%-63.5%], P = .001) and decreases in left ventricular dimensions. CONCLUSIONS: The bone marrow-derived, spatially arranged SMC-EPC bi-level cell sheet is a novel, multilineage cellular therapy obtained from a translationally practical source. Interactions between SMCs and EPCs augment mature neovascularization, limit adverse remodeling, and improve ventricular function after myocardial infarction.


Subject(s)
Cell Transdifferentiation , Cell Transplantation/methods , Endothelial Progenitor Cells/cytology , Mesenchymal Stem Cells/cytology , Myocardial Infarction/therapy , Myocytes, Smooth Muscle/transplantation , Animals , Cells, Cultured , Fibrosis/therapy , Heart Ventricles/diagnostic imaging , Magnetic Resonance Imaging , Myocardium/pathology , Neovascularization, Physiologic , Rats, Wistar , Stroke Volume , Ventricular Remodeling
17.
Article in English | MEDLINE | ID: mdl-28337717

ABSTRACT

OPINION STATEMENT: Over the past two decades, the field of cardiovascular medicine has seen the rapid development of multiple different modalities for the treatment of ischemic myocardial disease. Most research efforts have focused on strategies aimed at coronary revascularization, with significant technological advances made in percutaneous coronary interventions as well as coronary artery bypass graft surgery. However, recent research efforts have shifted towards ways to address the downstream effects of myocardial infarction on both cellular and molecular levels. To this end, the broad application of injectable hydrogel therapy after myocardial infarction has stimulated tremendous interest. In this article, we will review what hydrogels are, how they can be bioengineered in unique ways to optimize therapeutic potential, and how they can be used as part of a treatment strategy after myocardial infarction.

18.
Adv Healthc Mater ; 5(21): 2758-2764, 2016 11.
Article in English | MEDLINE | ID: mdl-27709809

ABSTRACT

A family of shear-thinning hydrogels for injectable encapsulation and long-term delivery (SHIELD) has been designed and synthesized with controlled in situ stiffening properties to regulate the stem cell secretome. The authors demonstrate that SHIELD with an intermediate stiffness (200-400 Pa) could significantly promote the angiogenic potential of human adipose-derived stem cells.


Subject(s)
Adipose Tissue/drug effects , Hydrogels/pharmacology , Stem Cells/drug effects , Adipose Tissue/metabolism , Cells, Cultured , Humans , Injections/methods , Intercellular Signaling Peptides and Proteins/metabolism , Rheology , Stem Cells/metabolism
20.
Cytotherapy ; 18(4): 510-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26971679

ABSTRACT

BACKGROUND: Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have shown potential to differentiate into various cell types, including smooth muscle cells (SMCs). The extracellular matrix (ECM) represents an appealing and readily available source of SMCs for use in tissue engineering. In this study, we hypothesized that the ECM could be used to induce MSC differentiation to SMCs for engineered cell-sheet construction. METHODS: Primary MSCs were isolated from the BM of Wistar rats, transferred and cultured on dishes coated with 3 different types of ECM: collagen type IV (Col IV), fibronectin (FN), and laminin (LM). Primary MSCs were also included as a control. The proportions of SMC (a smooth muscle actin [aSMA] and SM22a) and MSC markers were examined with flow cytometry and Western blotting, and cell proliferation rates were also quantified. RESULTS: Both FN and LM groups were able to induce differentiation of MSCs toward smooth muscle-like cell types, as evidenced by an increase in the proportion of SMC markers (aSMA; Col IV 42.3 ± 6.9%, FN 65.1 ± 6.5%, LM 59.3 ± 7.0%, Control 39.9 ± 3.1%; P = 0.02, SM22; Col IV 56.0 ± 7.7%, FN 74.2 ± 6.7%, LM 60.4 ± 8.7%, Control 44.9 ± 3.6%) and a decrease in that of MSC markers (CD105: Col IV 64.0 ± 5.2%, FN 57.6 ± 4.0%, LM 60.3 ± 7.0%, Control 85.3 ± 4.2%; P = 0.03). The LM group showed a decrease in overall cell proliferation, whereas FN and Col IV groups remained similar to control MSCs (Col IV, 9.0 ± 2.3%; FN, 9.8 ± 2.5%; LM, 4.3 ± 1.3%; Control, 9.8 ± 2.8%). CONCLUSIONS: Our findings indicate that ECM selection can guide differentiation of MSCs into the SMC lineage. Fibronectin preserved cellular proliferative capacity while yielding the highest proportion of differentiated SMCs, suggesting that FN-coated materials may be facilitate smooth muscle tissue engineering.


Subject(s)
Cell Transdifferentiation , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Myocytes, Smooth Muscle/physiology , Tissue Engineering/methods , Animals , Cell Proliferation , Cell Separation/methods , Cells, Cultured , Extracellular Matrix/metabolism , Extracellular Matrix Proteins/metabolism , Male , Muscle, Smooth/cytology , Muscle, Smooth/physiology , Rats , Rats, Wistar
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