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1.
J Card Surg ; 31(8): 503-6, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27401021

ABSTRACT

BACKGROUND: Systolic anterior motion (SAM) of the mitral valve, left ventricular outflow tract (LVOT) obstruction, and mitral regurgitation (MR) are known adverse outcomes that can occur after septal myectomy for hypertrophic obstructive cardiomyopathy. The objective of this study was to describe outcomes of a surgical technique to prevent these complications. METHODS: We have adopted a technique where we place an Alfieri stitch in the mitral valve through the aortotomy while performing septal myectomy. A retrospective review was performed and outcomes associated with this technique were noted. RESULTS: Twenty-four patients underwent septal myectomy and mitral valve repair using this technique. Mean age was 57 ± 10 years. Twenty patients were in class III/IV heart failure, and all had documented SAM. Mean LVOT gradient improved from 78 ± 48 mmHg preoperatively to 19 ± 20 mmHg after myectomy (p < 0.001). No patients had postoperative SAM, and no patients required a second aortic crossclamping for mitral repair. Seventeen of 19 patients with ≥mild MR had improvement in MR. During follow-up, 16 patients had no/trivial MR, seven had mild MR, and one had moderate MR. The mean postoperative mitral gradient was 4.5 ± 3.0 mmHg. Thirteen patients had postoperative complications including one death in a patient who developed a ventricular septal defect. CONCLUSIONS: Trans-aortic Alfieri stitch placement during septal myectomy is feasible in most cases as an additional tool to improve MR and minimize SAM. This technique may have a role in addressing mitral disease, such as a long anterior leaflet or fibrotic mitral valve, at the time of myectomy without the need for left atriotomy for mitral exposure.


Subject(s)
Cardiac Surgical Procedures/methods , Cardiomyopathy, Hypertrophic/surgery , Heart Septum/surgery , Suture Techniques/instrumentation , Sutures , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/physiopathology , Echocardiography, Transesophageal , Female , Follow-Up Studies , Heart Septum/diagnostic imaging , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Ventricular Function, Left/physiology
2.
Heart Surg Forum ; 18(1): E1-5, 2015 Feb 27.
Article in English | MEDLINE | ID: mdl-25881214

ABSTRACT

BACKGROUND: Vein graft stenosis after coronary artery bypass grafting (CABG) is common. Identifying genes associated with vein graft stenosis after CABG could reveal novel mechanisms of disease and discriminate patients at risk for graft failure. We hypothesized that genome-wide association would identify these genes. METHODS: We performed a genome-wide association study on a subset of patients presenting for cardiac catheterization for concern of ischemic heart disease, who also underwent CABG and subsequent coronary angiography after CABG for clinical indications (n = 521). Cases were defined as individuals with ≥50% stenosis in any vein graft on any cardiac catheterization, and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization. Multivariable logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) and vein graft stenosis. RESULTS: Sixty-nine percent of patients had vein graft failure after CABG. Seven SNPs were significantly associated with vein graft stenosis, including intronic SNPs in the genes PALLD (Rs6854137, P = 3.77 × 10(-6)), ARID1B (Rs184074, P = 5.97 × 10(-6)), and TMEM123 (Rs11225247, P = 8.25 × 10(-6)); and intergenic SNPs near the genes ABCA13 (Rs10232860, P = 4.54 × 10(-6)), RMI2 (Rs9921338, P = 6.15 × 10(-6)), PRM2 (Rs7198849, P = 7.27 × 10(-6)), and TNFSF4 (Rs17346536, P = 9.33 × 10(-6)). CONCLUSIONS: We have identified novel genetic variants that may predispose to risk of vein graft failure after CABG, many within biologically plausible pathways. These polymorphisms merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.


Subject(s)
Coronary Artery Bypass/statistics & numerical data , Genetic Predisposition to Disease/genetics , Graft Occlusion, Vascular/epidemiology , Graft Occlusion, Vascular/genetics , Polymorphism, Single Nucleotide/genetics , Saphenous Vein/transplantation , Aged , Genetic Predisposition to Disease/epidemiology , Genetic Variation/genetics , Genome-Wide Association Study , Humans , Male , Middle Aged , North Carolina/epidemiology , Prevalence , Risk Factors
3.
Heart Surg Forum ; 18(4): E134-9, 2015 Aug 30.
Article in English | MEDLINE | ID: mdl-26334848

ABSTRACT

BACKGROUND:   Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized.  We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients. METHODS:   Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves.  Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays.  Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test.   RESULTS:   Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4).  The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients.  Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range:  -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissections CONCLUSIONS:   Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms.  The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders.  These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.


Subject(s)
Aorta , Aortic Aneurysm, Thoracic/epidemiology , Aortic Aneurysm, Thoracic/genetics , Aortic Valve/abnormalities , Heart Valve Diseases/epidemiology , Heart Valve Diseases/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Bicuspid Aortic Valve Disease , Comorbidity , Female , Gene Expression Profiling , Genetic Markers/genetics , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Incidence , Male , Middle Aged , North Carolina/epidemiology , Polymorphism, Single Nucleotide/genetics , Risk Factors
4.
J Vasc Surg ; 57(3): 655-67; discussion 666-7, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23186868

ABSTRACT

OBJECTIVE: Hybrid repair of the transverse aortic arch may allow for aortic arch repair with reduced morbidity in patients who are suboptimal candidates for conventional open surgery. We present our results with an algorithmic approach to hybrid arch repair, based on the extent of aortic disease and patient comorbidities. METHODS: Between August 2005 and January 2012, 87 patients underwent hybrid arch repair by three principal procedures: zone 1 endograft coverage with extra-anatomic left carotid revascularization (zone 1; n = 19), zone 0 endograft coverage with aortic arch debranching (zone 0; n = 48), or total arch replacement with staged stented elephant trunk completion (stented elephant trunk; n = 20). RESULTS: The mean patient age was 64 years, and the mean expected in-hospital mortality rate was 16.3% as calculated by the EuroSCORE II. Of operations, 22% (n = 19) were nonelective. Sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest were required in 78% (n = 68), 45% (n = 39), and 31% (n = 27) of patients to allow for total arch replacement, arch debranching, or other concomitant cardiac procedures, including ascending with or without hemiarch replacement in 17% (n = 8) of patients undergoing zone 0 repair. All stented elephant trunk procedures (n = 20) and 19% (n = 9) of zone 0 procedures were staged, with 41% (n = 12) of patients undergoing staged repair during a single hospitalization. The 30-day/in-hospital rates of stroke and permanent paraplegia or paraparesis were 4.6% (n = 4) and 1.2% (n = 1). Of 27 patients with native ascending aorta zone 0 proximal landing zone, three (11.1%) experienced retrograde type A dissection after endograft placement. The overall in-hospital mortality rate was 5.7% (n = 5); however, 30-day/in-hospital mortality increased to 14.9% (n = 13) owing to eight 30-day out-of-hospital deaths. Native ascending aorta zone 0 endograft placement was found to be the only univariate predictor of 30-day in-hospital mortality (odds ratio, 4.63; 95% confidence interval, 1.35-15.89; P = .02). Over a mean follow-up period of 28.5 ± 22.2 months, 13% (n = 11) of patients required reintervention for type 1A (n = 4), type 2 (n = 6), or type 3 (n = 1) endoleak. Kaplan-Meier estimates of survival at 1 year, 3 years, and 5 years were 73%, 60%, and 51%. CONCLUSIONS: Hybrid aortic arch repair can be tailored to patient anatomy and comorbid status to allow complete repair of aortic pathology, frequently in a single stage, with acceptable outcomes. However, endograft placement in the native ascending aorta is associated with high rates of retrograde type A dissection and 30-day/in-hospital mortality and should be approached with caution.


Subject(s)
Algorithms , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation , Decision Support Techniques , Endovascular Procedures , Aged , Aged, 80 and over , Aortic Dissection/diagnosis , Aortic Dissection/mortality , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/mortality , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Cardiopulmonary Bypass , Chi-Square Distribution , Circulatory Arrest, Deep Hypothermia Induced , Comorbidity , Endoleak/etiology , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Odds Ratio , Paraparesis/etiology , Paraplegia/etiology , Reoperation , Risk Assessment , Risk Factors , Sternotomy , Stroke/etiology , Time Factors , Treatment Outcome
5.
J Vasc Surg ; 57(4): 915-25, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23375432

ABSTRACT

OBJECTIVE: Intrathoracic subclavian artery aneurysms (SAAs) are rare aneurysms that often occur in association with congenital aortic arch anomalies and/or concomitant thoracic aortic pathology. The advent of thoracic endovascular aortic repair (TEVAR) methods may complement or replace conventional open SAA repair. Herein, we describe our experience with SAA repair in the TEVAR era. METHODS: A retrospective review was performed of all intrathoracic SAAs repaired at a single institution since United States Food and Drug Administration approval of TEVAR in 2005. RESULTS: Nineteen patients underwent 20 operations to repair 22 (13 native, nine aberrant) SAAs with an intrathoracic component. Mean SAA diameter was 3.1 cm (range, 1.6-6.0 cm). Mean patient age was 57 years (range, 24-80 years). Twenty-one percent (n = 4) of patients had a connective tissue disorder (two Loeys-Dietz, two Marfan). Thirty-six percent (n = 8) of SAAs were repaired by open techniques and 64% (n = 14) via a TEVAR-based approach. All TEVAR cases required proximal landing zone in the aortic arch (zone 0-2), and revascularization of at least one arch vessel was required in 83% (10/12) of patients. Concomitant repair of associated aortic pathology was performed in 50% (n = 10) of operations. Thirty-day/in-hospital rates of death, stroke, and permanent paraplegia/paraparesis were 5% (n = 1), 5% (n = 1), and 0%, respectively. Over mean (standard deviation) follow-up of 24 (21) months, 16% (n = 3) of patients required reintervention for subclavian artery bypass graft revision (n = 2) or type II endoleak (n = 1). CONCLUSIONS: This is the largest single-institution series to date of TEVAR for SAA repair. Modern endovascular techniques expand SAA repair options with excellent results. The majority of SAAs and nearly all aberrant SAAs (Kommerell's diverticulum) can now be repaired using a TEVAR-based approach without the need for sternotomy or thoracotomy.


Subject(s)
Aneurysm/surgery , Aorta, Thoracic/surgery , Aortic Diseases/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Subclavian Artery/surgery , Adult , Aged , Aged, 80 and over , Aneurysm/diagnostic imaging , Aneurysm/mortality , Aorta, Thoracic/abnormalities , Aorta, Thoracic/diagnostic imaging , Aortic Diseases/diagnostic imaging , Aortic Diseases/mortality , Aortography/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Chi-Square Distribution , Endoleak/etiology , Endoleak/surgery , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , North Carolina , Paraparesis/etiology , Paraplegia/etiology , Registries , Reoperation , Retrospective Studies , Stroke/etiology , Subclavian Artery/abnormalities , Subclavian Artery/diagnostic imaging , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
6.
J Vasc Surg ; 56(3): 621-9, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22575483

ABSTRACT

OBJECTIVE: Thoracoabdominal aortic aneurysms (TAAAs) occur most commonly in elderly individuals, who are often suboptimal candidates for open repair because of significant comorbidities. The availability of a hybrid option, including open visceral debranching with endovascular aneurysm exclusion, may have advantages in these patients who are at high-risk for conventional repair. This report details the evolution of our technique and results with complete visceral debranching and endovascular aneurysm exclusion for TAAA repair in high-risk patients. METHODS: Between March 2005 and June 2011, 47 patients (51% women) underwent extra-anatomic debranching of all visceral vessels, followed by aneurysm exclusion by endovascular means at a single institution. A median of four visceral vessels were bypassed. The debranching procedure was initially performed through a partial right medial visceral rotation approach, leaving the left kidney posterior in the first 22 patients, and in the last 25 by a direct anterior approach to the visceral vessels. The debranching and endovascular portions of the procedure were performed in a single operation in the initial 33 patients and as a staged procedure during a single hospital stay in the most recent 14. RESULTS: Median patient age was 71.0 ± 9.8 years. All had significant comorbidity and were considered suboptimal candidates for conventional repair: 55% had undergone previous aortic surgery, 40% were American Society of Anesthesiologists (ASA) class 4, and baseline serum creatinine was 1.5 ± 1.3 mg/dL. The 30-day/in-hospital rates of death, stroke, and permanent paraparesis/plegia were 8.5%, 0%, and 4.3%, respectively, but 0% in the most recent 14 patients undergoing staged repair. These patients had significantly shorter combined operative times (314 vs 373 minutes), decreased intraoperative red blood cell transfusions (350 vs 1400 mL), and were more likely to be extubated in the operating room (50% vs 12%) compared with patients undergoing simultaneous repair. Over a median follow-up of 19.3 ± 18.5 months, visceral graft patency was 97%; all occluded limbs were to renal vessels and clinically silent. There have been no type I or III endoleaks or reinterventions. Kaplan-Meier overall survival is 70.7% at 2 years and 57.9% at 5 years. CONCLUSIONS: Hybrid TAAA repair through complete visceral debranching and endovascular aneurysm exclusion is a good option for elderly high-risk patients less suited to conventional repair in centers with the requisite surgical expertise with visceral revascularization. A staged approach to debranching and endovascular aneurysm exclusion during a single hospitalization appears to yield optimal results.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures , Aged , Aged, 80 and over , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/mortality , Aortography/methods , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Chi-Square Distribution , Comorbidity , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , North Carolina , Odds Ratio , Postoperative Complications/etiology , Postoperative Complications/mortality , Prospective Studies , Registries , Risk Assessment , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
7.
J Vasc Surg ; 53(5): 1398-401, 2011 May.
Article in English | MEDLINE | ID: mdl-21296539

ABSTRACT

Hybrid procedures combining traditional open and newer endovascular techniques are increasingly used to treat complex aortic disease. We present a novel approach for total aortic replacement, including hybrid repair of the arch and thoracoabdominal aorta, in a patient with "mega-aorta syndrome." A two-stage approach using a valve-sparing aortic root replacement, total arch replacement (stage I elephant trunk), and left carotid-axillary bypass was used to treat the root, proximal-mid arch, and left subclavian aneurysmal pathology. This was followed by a hybrid distal arch/Extent II thoracoabdominal aneurysm repair 3 months later. After 15 months follow-up, the patient remains asymptomatic with an intact repair, no endoleak, and normal ventricular and aortic valve function. This case demonstrates a novel "pan-aortic" hybrid approach for repair of extensive thoracic aortic disease.


Subject(s)
Aneurysm/surgery , Aorta, Thoracic/surgery , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Subclavian Artery/surgery , Aged , Aneurysm/diagnostic imaging , Aorta, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortography/methods , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/instrumentation , Brachiocephalic Trunk/surgery , Carotid Artery, Common/surgery , Humans , Ligation , Male , Prosthesis Design , Stents , Subclavian Artery/diagnostic imaging , Syndrome , Tomography, X-Ray Computed , Treatment Outcome
8.
J Heart Valve Dis ; 20(4): 387-95, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21863650

ABSTRACT

BACKGROUND AND AIM OF THE STUDY: Bicuspid aortic valve (BAV) disease is associated with an aortopathy resulting in aneurysmal dilatation spanning the root, ascending, and arch segments. To date, no large series of proximal aortic replacement in this population has been reported. The study aim was to report contemporary surgical outcomes for proximal aortic replacement in BAV disease, and to examine the relationships between valve morphology, valve pathophysiology, and pathology of the thoracic aorta. METHODS: Between September 2005 and December 2009, a total of 100 consecutive patients (mean age 54 +/- 13 years; range: 29-80 years) with BAV and proximal aortic enlargement underwent aortic replacement at a single referral institution. Of these patients, 16% had undergone prior aortic valve replacement (AVR). The aortic repair was individually tailored to treat the aortic valve and thoracic aortic pathology, and included supracoronary ascending aortic (AA) replacement (n = 17), AVR with separate supracoronary AA replacement (n = 39), aortic root replacement (n = 42), and valve-sparing root replacement (n = 2). Concomitant arch replacement was performed in 82 patients (80 hemi-arch, two full arch). Other concomitant cardiac procedures were performed in 28 patients. RESULTS: The 30-day/in-hospital rates of death and stroke were both 1%. The predominant aortic valve pathophysiology was aortic stenosis (AS; 33%), aortic insufficiency (AI; 29%), mixed AS/AI (17%), normally functioning BAV (17%), and unknown (4%). Valve morphology included Sievers Type I, R/L (75%), Type I, R/N (9%), Type I, L/N (2%), Type 0 (7%), and Type II (7%). BAV patients with predominantly AI had more frequent root dilatation (62%) than those with either AS (30%) or normal valve function (35%). Based on BAV morphology, there were no significant differences in maximal thoracic aortic diameters between groups. At a mean follow up of 16 months, there were no late deaths or valve-related complications. CONCLUSION: Proximal aortic replacement in patients with BAV can be performed with low rates of mortality and morbidity. The pathologic anatomy of the thoracic aorta was not predicted by the aortic valve morphology, although dilation of the aortic root was most common in BAV patients with a predominant AI pathophysiology. These findings convey the safety and feasibility of treating concomitant aortopathy, including arch replacement as needed, and may help tailor the specific operation needed to the patient's pathology.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Valve/abnormalities , Heart Valve Diseases/complications , Vascular Surgical Procedures/methods , Adult , Aged , Aged, 80 and over , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/etiology , Echocardiography , Female , Follow-Up Studies , Heart Valve Diseases/congenital , Heart Valve Diseases/diagnosis , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Retrospective Studies , Treatment Outcome
9.
J Reconstr Microsurg ; 27(2): 121-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20981640

ABSTRACT

Patients undergoing free tissue transfer are particularly susceptible to hypothermia. The goal was to investigate the impact of intraoperative core body temperature on free flap thrombosis. Two hundred twelve cases of free flap reconstruction at Yale-New Haven Hospital between 1992 and 2008 were reviewed. Free flap thrombosis was defined by complete flap necrosis or direct visualization of arterial or venous thrombosis. Temperature measurements were calibrated to bladder temperatures as measured by Foley catheter sensor. Through logistic regression analysis, maximum and minimum intraoperative temperatures were determined to be statistically significant predictors of free flap thrombosis. The optimal temperature was calculated to be 36.2 °C, and maximum intraoperative temperatures between 36.0 °C and 36.4 °C showed lower thrombosis rates than super-warmed patients ( P < 0.03). Therefore, free flap patients should be mildly hypothermic at 36.0 °C to 36.4 °C, compared with normothermia at 37.5 °C, as measured in the bladder. A prospective randomized trial investigating thrombosis rates and intraoperative temperature should be undertaken.


Subject(s)
Free Tissue Flaps/blood supply , Hypothermia/diagnosis , Monitoring, Intraoperative/methods , Plastic Surgery Procedures/methods , Thrombosis/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , Body Temperature , Child , Child, Preschool , Cohort Studies , Female , Follow-Up Studies , Free Tissue Flaps/adverse effects , Graft Rejection/prevention & control , Graft Survival , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Postoperative Complications/prevention & control , Predictive Value of Tests , Plastic Surgery Procedures/adverse effects , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
10.
Curr Pharm Des ; 26(2): 265-278, 2020.
Article in English | MEDLINE | ID: mdl-31886747

ABSTRACT

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models. The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Phytochemicals/therapeutic use , Angiogenesis Inhibitors/pharmacology , Animals , Humans , Phytochemicals/pharmacology
11.
J Reconstr Microsurg ; 25(9): 527-31, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19774502

ABSTRACT

We sought to determine the effect of ischemic preconditioning (IPC) on secondary ischemia in myocutaneous flaps in a rat model. Forty rectus abdominis myocutaneous flaps were elevated in 40 rats, and the animals were randomized into control or IPC groups (20 flaps each group). All flaps were then subject to primary ischemia for 2 hours via pedicle clamping. Twenty-four hours later, the control and IPC flaps were randomized to two groups each of 1 or 2 hours of secondary ischemia (4 groups, 10 flaps per group). Flap survival was evaluated on postoperative day 5 by measuring the percentage area of flap survival by a blinded observer. Mean flap survival area and total necrosis rates were compared between the groups. In the 1-hour secondary ischemia groups, IPC improved mean flap survival area from 11 +/- 7% to 36 +/- 22%, and the total necrosis rates from 40 to 0%. These differences were statistically significant (p < 0.006, p < 0.05, respectively). In the 2-hour secondary ischemia groups, differences were not statistically significant (p = 0.2, p = 0.4, respectively). IPC improves the survival of myocutaneous flaps subjected to secondary ischemia of 1 hour in this rat free flap model.


Subject(s)
Ischemia/prevention & control , Ischemic Preconditioning , Surgical Flaps/blood supply , Animals , Male , Models, Animal , Rats , Rats, Sprague-Dawley , Tissue Survival
12.
Ann Thorac Surg ; 108(5): 1325-1329, 2019 11.
Article in English | MEDLINE | ID: mdl-31103387

ABSTRACT

BACKGROUND: This study describes the impact of organism and valve type on surgically managed infective endocarditis (IE) from The Society of Thoracic Surgeons (STS) database. We developed a risk model for surgically managed endocarditis that includes the microbiological organism. METHODS: The STS database was queried for adult patients with surgically managed endocarditis from July 1, 2011, to June 30, 2016. Outcomes were compared based on (1) causative microbiological organism, (2) valve type (native vs prosthetic), and (3) endocarditis on the right (tricuspid) vs left (mitral, aortic) sides. Univariate and risk adjusted models were developed with odds ratios for mortality for each organism type referenced against Streptococcus. RESULTS: The study population included 21,388 operations (93%) for left-sided IE and 1698 (7%) for right-sided IE. Streptococcus (28%) and Staphylococcus (27%) were the most common infecting organisms, followed by Enterococcus (11%). After multivariate adjustment, microbiological organism type was significantly associated with operative mortality for patients with left-sided endocarditis, with an adjusted odds ratio of 2.9 for fungal, 1.4 for Staphylococcus, and 1.3 for culture-negative vs Streptococcus. For right-sided endocarditis, there were no differences in outcomes by organism type. Left-sided prosthetic valve endocarditis had a higher operative mortality than left-sided native valve endocarditis (12% vs 8%, P < .001). In contrast, surgery for right-sided endocarditis carried lower operative mortality, with no mortality difference between prosthetic valve endocarditis and native valve endocarditis (5% vs 4%, P = .6). CONCLUSIONS: Organism type influences the operative mortality for left-sided endocarditis. Surgery for left-sided and prosthetic valve endocarditis is associated with higher operative mortality. Risk adjustment for operative outcomes in endocarditis may need to account for microbiological organism type.


Subject(s)
Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/surgery , Heart Valve Diseases/microbiology , Heart Valve Diseases/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Models, Statistical , Risk Assessment , Treatment Outcome
13.
Nat Genet ; 51(1): 42-50, 2019 01.
Article in English | MEDLINE | ID: mdl-30455415

ABSTRACT

Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)1-3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype.


Subject(s)
Aortic Aneurysm, Thoracic/genetics , Aortic Valve/abnormalities , Heart Valve Diseases/genetics , Mutation/genetics , Receptors, Cell Surface/genetics , Animals , Bicuspid Aortic Valve Disease , Cells, Cultured , Disease Models, Animal , Endothelial Cells/physiology , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Phenotype , Zebrafish
14.
Ann Thorac Surg ; 102(5): e413-e415, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27772595

ABSTRACT

Improved quality of life for patients after left ventricular assist device (LVAD) implantation can be greatly limited by peripheral vascular disease even if heart failure symptoms are resolved by LVAD support. We present a case of concomitant thoracic aortobifemoral bypass and LVAD implantation in a patient with ischemic cardiomyopathy, severe peripheral vascular disease, and multiple previous failed revascularization attempts. In this patient, we used the LVAD outflow to provide the inflow to the femoral artery bypass graft. This graft has remained patent at a 2-year follow-up, without claudication symptoms. Performing concomitant major vascular operations safely and successfully is feasible in patients with LVADs. Quality of life after ventricular assist device placement can be limited by vascular disease, but it can be markedly improved after vascular surgical intervention.


Subject(s)
Aorta, Abdominal/surgery , Arterial Occlusive Diseases/surgery , Femoral Artery/surgery , Heart Failure/surgery , Heart-Assist Devices , Vascular Surgical Procedures/methods , Aged , Anastomosis, Surgical/methods , Angiography , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/diagnosis , Heart Failure/complications , Heart Failure/diagnosis , Heart Ventricles/surgery , Humans , Male , Tomography, X-Ray Computed
15.
J Crit Care ; 31(1): 125-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26700606

ABSTRACT

PURPOSE: In addition to the pulmonary risks associated with cardiopulmonary bypass, thoracic aortic surgery using deep hypothermic circulatory arrest (DHCA) may subject the lungs to further injury. However, this topic has received little investigation to date. MATERIALS AND METHODS: A prospective cohort review was performed on all patients undergoing proximal thoracic aortic surgery with (n = 478) and without (n = 135) DHCA between July 2005 and February 2013 at a single institution. The primary outcome was prolonged postoperative respiratory support (PPRS), defined as any of the following: >1 day of mechanical ventilation at either fraction of inspired oxygen >0.4 and/or positive end-expiratory pressure >5 mm Hg, >2 days of supplemental O2 requirement of at least 2.5 L/min, or discharge with new O2 requirement. Independent risk factors for PPRS were identified using multivariable logistic regression. RESULTS: Postoperative respiratory support was required in 100 patients (20.9%) with and 30 patients (22.2%) without DHCA (P = .74). Independent predictors of PPRS after proximal aortic surgery included the following: age, diabetes, history of stroke, preoperative creatinine, American Society of Anesthesiologists class 4, redo-sternotomy, total arch replacement, and transfusion requirement. Use of DHCA was not an independent risk factor for PPRS in the entire cohort. Subanalysis of only DHCA patients revealed that longer DHCA times were independently associated with PPRS. CONCLUSIONS: Prolonged postoperative respiratory support is common after proximal aortic surgery. The use of DHCA was not associated with this complication in the overall cohort, although longer DHCA times were predictive when only the subset of patients undergoing DHCA was analyzed. Knowledge of the risk factors for PPRS after proximal aortic surgery should improve preoperative risk stratification and postoperative management of these patients.


Subject(s)
Aorta, Thoracic/surgery , Circulatory Arrest, Deep Hypothermia Induced/adverse effects , Adult , Aged , Cardiopulmonary Bypass/adverse effects , Female , Humans , Logistic Models , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Postoperative Period , Prospective Studies , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Time Factors
16.
Ann Thorac Surg ; 101(6): 2341-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27021035

ABSTRACT

BACKGROUND: The present study aimed to describe and compare the operative experience of cardiothoracic surgical residents for basic and advanced cardiac surgical procedures. METHODS: Data were obtained from the 2015 Thoracic Surgery Directors Association Survey administered to all thoracic surgical residents taking the yearly In-Service Training Examination (n = 356). Residents were asked whether they routinely served as the operative surgeon on various cardiac operations and operative tasks. Results were stratified by postgraduate year (PGY), residency type, and primary career interest. RESULTS: The survey response rate was 100%. Considering all training pathways, only 2 of 13 cardiac operations surveyed were routinely performed by graduating chief residents as the operative surgeon: coronary artery bypass grafting (CABG; 92%) and aortic valve replacement (AVR; 88%). Off-pump CABG, minimally invasive mitral valve operation, and transcatheter aortic interventions were infrequently (<30% of the time) performed by graduating residents as the operative surgeon. These results were similar when residents with a career interest in general thoracic surgery were excluded from the analysis. For the operative progression of integrated 6-year (I-6) residents, most began to routinely cannulate for cardiopulmonary bypass, perform proximal coronary anastomoses, and harvest the mammary artery during PGY3. The majority (>50%) of I-6 residents performed CABG as the operative surgeon by PGY4. CONCLUSIONS: There is pronounced heterogeneity in the cardiac operative experience of cardiothoracic surgical residents in the United States, with only CABG and AVR routinely performed by graduating residents as the operative surgeon. This heterogeneity may lead to insufficient training in certain procedures for many graduates.


Subject(s)
Cardiac Surgical Procedures/education , Internship and Residency , Thoracic Surgery/education , Adult , Aortic Valve/surgery , Career Choice , Clinical Competence , Coronary Artery Bypass/education , Female , Heart Valve Prosthesis Implantation/education , Humans , Male , Professional Autonomy , Surveys and Questionnaires , United States
17.
Ann Thorac Surg ; 101(1): 323-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26453419

ABSTRACT

BACKGROUND: With increased time and quality pressures, it may be more difficult for residents in cardiothoracic surgery residency programs to get independent operative experience. That may lead residents to inaccurately report their role as "surgeon" to meet American Board of Thoracic Surgery (ABTS) case requirements. METHODS: The 2013 In-Training Examination surveyed 312 cardiothoracic surgery residents and was used to contrast residents in traditional 2-year and 3-year cardiothoracic surgery residencies (traditional, n = 216) with those in 6-year integrated or 3+4-year programs (integrated, n = 96). RESULTS: Traditional program residents reported a higher percentage of cases that met the ABTS criteria of surgeon than did integrated program residents (p = 0.05) but were less likely to meet requirements if all cases were logged accurately (p = 0.03). The majority of residents in each program believed that their case log accurately reflected their experience as "surgeon." Residents who tended to log cases incorrectly had lower self-reported 2012 In-Training Examination percentiles, were less likely to meet case requirements if logged properly, and felt less prepared for board examinations and eventual practice compared with residents who logged cases correctly (all p < 0.001). Residents who believed they would not meet case requirements if logged correctly cited limited surgical opportunities, poor case diversity, and a compromised training environment but not the 80-hour work week, excessive simulation, or disproportionate number of complex cases as causes. CONCLUSIONS: Overall cardiothoracic surgery residents appear to be satisfied with their training. There were specific subsets of trainees in both traditional and Integrated programs that are misrepresenting their role on cases because they otherwise may not meet the requirements.


Subject(s)
Clinical Competence , Internship and Residency , Physicians/standards , Surveys and Questionnaires , Thoracic Surgery/education , Female , Humans , Male , Retrospective Studies
18.
Ann Thorac Surg ; 102(1): 200-6, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27157051

ABSTRACT

BACKGROUND: The cardiothoracic surgical workforce is changing. Although 5% of practicing surgeons are women, 20% of current cardiothoracic surgery residents are women. The purpose of this study was to evaluate the influence of gender on specialty interest, satisfaction, and career pathways of current residents. METHODS: Responses to the mandatory 2015 Thoracic Surgery Residents Association/Thoracic Surgery Directors Association in-training examination survey taken by 354 residents (100% response rate) were evaluated. The influence of gender was assessed with the use of standard univariate analyses. RESULTS: Women accounted for 20% of residents, and the percentage did not vary with postgraduate year or program type (traditional versus integrated). Although no differences were found between the genders related to specialty interest, academic versus private practice career, or pursuit of additional training, women were more likely to pursue additional training in minimally invasive thoracic surgery (10% versus 2.5%, p = 0.001) and less likely to perform research in their careers (65% versus 88%, p = 0.043). Although women were equally satisfied with their career choice, had similar numbers of interviews and job offers, and felt equally prepared for their boards, graduating women felt less prepared technically (77% versus 90%, p = 0.01) and for practicing independently (71% versus 87%, p = 0.01). Women were less likely to be married (26% versus 62%, p < 0.001) and have children (19% versus 49%, p < 0.001). CONCLUSIONS: Although career satisfaction and specialty interest were similar between the genders, women were less likely to intend to perform research during their careers despite similar previous research experience. Women also demonstrated lower rates of marriage and childbearing compared with their male counterparts.


Subject(s)
Career Choice , Education, Medical, Graduate/methods , Internship and Residency/methods , Job Satisfaction , Specialties, Surgical/education , Thoracic Surgery/education , Adult , Female , Humans , Male , Surveys and Questionnaires , United States
19.
Ann Thorac Surg ; 102(2): 643-50, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27131899

ABSTRACT

BACKGROUND: Traditionally cardiothoracic residents spent dedicated research time during general surgery equipping them for a potential academic career. Recent changes in training paradigms, including integrated programs that may not include research time, could affect the development of future academic cardiothoracic surgeons. METHODS: Responses to the 2015 Thoracic Surgery Directors' Association/Thoracic Surgery Residents' Association survey accompanying the in-training examination taken by current cardiothoracic surgery residents were analyzed. Three hundred fifty-four residents were surveyed with a response rate of 100%, although one was excluded from the analysis because of inconsistencies in responses. Statistical analysis included χ(2), Fisher's exact test, and multinomial logistic regression with significance set at a probability value of 0.05. RESULTS: Two hundred sixty-seven of 353 residents (76%) intended on performing research as part of their careers. Integrated residents as opposed to traditional residents (85% versus 69%; p = 0.003), males (78% versus 65%; p = 0.02), those pursuing additional training (85% versus 69%; p = 0.003), and those interested in academic careers (93% versus 33%; p < 0.001) were more likely to pursue research. Differences were also noted in specialty interest, with congenital and heart failure specialties most likely to pursue research careers (92% and 100%, respectively; p < 0.05). Residents intending on research careers were more likely to have had previous research experience, and the most common type of intended research was clinical outcomes (78%). On multinomial logistic regression, previous clinical outcomes research and academic practice were identified as predictors of a research career (odd ratios of 9.7 and 4.1, respectively; each p < 0.05). CONCLUSIONS: The majority of residents plan on pursuing research during their careers. Previous research experience appears to be a key determinant as well as specialty interest.


Subject(s)
Career Choice , Internship and Residency/methods , Societies, Medical , Specialties, Surgical/education , Surveys and Questionnaires , Thoracic Surgery/education , Female , Humans , Male , United States
20.
Ann Thorac Surg ; 99(4): 1275-81, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25678502

ABSTRACT

BACKGROUND: Loeys-Dietz syndrome (LDS) results from mutations in receptors for the cytokine transforming growth factor-ß leading to aggressive aortic pathology sometimes accompanied by specific phenotypic features including bifid uvula, hypertelorism, cleft palate, and generalized arterial tortuosity. We reviewed our adult surgical experience with LDS in order to validate current recommendations regarding management of this newly described disease. METHODS: All adult (≥ 18 years old) patients with LDS undergoing surgical treatment at a single referral institution from September 1999 to May 2013 were retrospectively reviewed. RESULTS: Eleven adult LDS patients were identified by clinical criteria and genotyping. Seven (64%) experienced acute type A dissection at some point in their lives. All eventually required aortic root replacement, and 73% required multiple vascular surgical interventions. Over a mean follow-up of 65 ± 49 months, 2.8 cardiovascular procedures per patient were performed. In patients with type A dissection, a mean of 3.4 operations were performed versus 1.8 operations for patients without dissection. Total aortic replacement was required in 5 patients (45%) and 2 (18%) required neurosurgical intervention for cerebrovascular pathology. There was 1 late death from infectious complications, and no deaths from vascular catastrophe. CONCLUSIONS: These results confirm the aggressive nature of LDS aortic pathology. However, the improved survival compared with earlier LDS reports suggest that aggressive treatment strategies may alter outcomes and improve the natural history of this syndrome.


Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Cardiac Surgical Procedures/methods , Loeys-Dietz Syndrome/surgery , Vascular Surgical Procedures/methods , Adult , Aortic Dissection/genetics , Aortic Aneurysm, Thoracic/genetics , Cardiac Surgical Procedures/adverse effects , Cohort Studies , Female , Humans , Loeys-Dietz Syndrome/diagnosis , Loeys-Dietz Syndrome/mortality , Male , Middle Aged , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Prognosis , Reoperation/methods , Retrospective Studies , Risk Assessment , Severity of Illness Index , Survival Rate , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Young Adult
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