Cyrus J. Parsa

A novel protective effect of erythropoietin in the infarcted heart

Erythropoietin (EPO) has been shown to protect neurons from ischemic stroke, but can also increase thrombotic events and mortality rates in patients with ischemic heart disease. We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart. We show that preconditioning with EPO protects H9c2 myoblasts in vitro and cardiomyocytes in vivo against ischemic injury. EPO treatment leads to significantly improved cardiac function following myocardial infarction. This protection is associated with mitigation of myocyte apoptosis, translating into more viable myocardium and less ventricular dysfunction. EPO-mediated myocyte survival appears to involve Akt activation. Importantly, cardioprotective effects of EPO were seen without an increase in hematocrit (eliminating oxygen delivery as an etiologic factor in myocyte survival and function), demonstrating that EPO can directly protect the ischemic and infarcted heart.

Midterm Results for Endovascular Repair of Complicated Acute and Chronic Type B Aortic Dissection

BACKGROUND Thoracic endovascular aortic repair (TEVAR) for the management of type B aortic dissections has become more commonplace despite some controversy. Results of endovascular management of complicated acute (<2 weeks from symptom onset) and chronic (>2 weeks) type B aortic dissection with a view towards determining safety, efficacy, and requirement for secondary procedures are reviewed. METHODS Between June 2005 and November 2008, 55 patients (41 men) with a mean age of 59 +/- 12 years (range, 31 to 77 years) underwent TEVAR for the management of complicated acute (n = 22) or chronic (n = 33) type B dissection. Indications in acute dissection included impending or frank rupture in 11 and malperfusion syndromes in 11; the indication in chronic dissections was aneurysmal degeneration in 33. RESULTS Primary technical success was 100%. In-hospital and 30-day rates of death, stroke, and permanent paraplegia/paresis were 2% (n = 1), 0%, and 2% (n = 1), respectively. Median follow-up was 7.1 months (range, 1 to 38 months). Overall actuarial midterm survival was 63% at 38 months, with an aorta-specific actuarial survival of 94%. Two patients (4%) required late conversion to open repair. Postoperative type I or III endoleak occurred in 3 (6%) and type II endoleak in 7 (15%). Two patients underwent subsequent endovascular occlusion. The composite reintervention rate in follow-up was 23.4% (n = 13). CONCLUSIONS Endovascular repair for complicated acute and chronic type B dissection is safe and effective at early midterm follow-up. TEVAR for type B dissection requires more secondary interventions and imaging surveillance than conventional open reconstruction. Longer-term follow-up is needed to determine the durability of this approach.

Midterm results with thoracic endovascular aortic repair for chronic type B aortic dissection with associated aneurysm.

OBJECTIVE Thoracic endovascular aortic repair for chronic type B aortic dissection with associated descending thoracic aneurysm remains controversial. Concerns include potential ischemic complications due to branch vessel origin from the chronic false lumen and continued retrograde false lumen/aneurysm sac pressurization via fenestrations distal to implanted endografts. The present study examines midterm results with thoracic endovascular aortic repair for chronic (>2 weeks) type B aortic dissection with associated aneurysm to better understand the potential role of thoracic endovascular aortic repair for this condition. METHODS Between March 2005 and December 2009, 51 thoracic endovascular aortic repair procedures were performed at a single institution for management of chronic type B dissection. The indication for thoracic endovascular aortic repair was aneurysm in all cases. A subset of 7 patients (14%) underwent placement of the EndoSure wireless pressure measurement system (CardioMEMS, Inc, Atlanta, Ga) in the false lumen adjacent to the primary tear for monitoring aneurysm sac/false lumen pulse pressure after thoracic endovascular aortic repair. RESULTS Mean patient age was 57±12 years (range, 30-82 years); 14 patients (28%) were female. Mean aortic diameter was 6.2±1.4 cm. There were no in-hospital/30-day deaths, strokes, or permanent paraplegia/paresis. There were no complications related to compromise of downstream branch vessels arising from the false lumen. Two patients (3.9%) who had preexisting ascending aortic dilation had retrograde acute type A aortic dissection; both were repaired successfully. Median postoperative length of stay was 4 days. Mean follow-up is 27.0±16.5 months (range, 2-60 months). Actuarial overall survival is 77.7% at 60 months with an actuarial aorta-specific survival of 98% over this same time period. Actuarial freedom from reintervention is 77.3% at 60 months. All patients with the EndoSure wireless pressure measurement system exhibited a decrease in aneurysm sac/false lumen pulse pressure indicating a depressurized false lumen. The aneurysm sac/false lumen pulse pressure ratio decreased from 52%±27% at the predischarge measurement to 14%±5% at the latest follow-up reading (P=.029). CONCLUSIONS Thoracic endovascular aortic repair for chronic type B dissection with associated aneurysm is safe and effective at midterm follow-up. Aneurysm sac/false lumen pulse pressure measurements demonstrate a significant reduction in false lumen endotension, thus ruling out clinically significant persistent retrograde false lumen perfusion and provide proof of concept for a thoracic endovascular aortic repair-based approach. Longer-term follow-up is needed to determine the durability of thoracic endovascular aortic repair for this aortic pathology.

Utility of Remote Wireless Pressure Sensing for Endovascular Leak Detection After Endovascular Thoracic Aneurysm Repair

BACKGROUND The goal of thoracic endovascular aneurysm repair (TEVAR) is to exclude and depressurize the aneurysm sac. Type I and III endovascular leaks (EL) transmit systemic pressure and represent treatment failures. The significance of type II EL is more controversial. Remote pressure sensing is a novel nonradiographic technology for EL detection and monitoring. However, little experience exists with regard to use in the thoracic aorta. We present our experience with the EndoSure wireless pressure measurement system (CardioMEMS, Atlanta, GA) for monitoring aneurysm sac pulse pressure (ASP) after TEVAR. METHODS Beginning May 2006, the EndoSure system was routinely implanted in TEVAR patients with suitable anatomy (36 aneurysm patients; 7 chronic dissection patients). The ASP measurements were taken predischarge and at scheduled follow-up visits. Computed tomography angiograms were performed at scheduled follow-up appointments. Data were prospectively maintained in an institutional aortic database. RESULTS Through June 2008, 43 patients (34% of TEVARs performed during this interval) underwent implantation. In 10 patients (23%), the device was suboptimally positioned between the endovascular graft and the aortic wall, rather than in an area of thrombus-free lumen, with subsequent transmission of systemic pressure despite no radiographic evidence of EL. In patients with well-positioned sensors, predischarge ASP averaged 43% +/- 22% of systemic. In 2 patients, systemic ASP measurements before discharge prompted imaging, confirming type I EL; both patients were treated successfully with cuff extension. One patient exhibited reduced ASP before discharge but exhibited increased ASP (70% systemic) at 1 month; computed tomography scan confirmed a type I EL. Additional TEVAR sealed the EL and reduced ASP to 39% systemic. For all patients at midterm follow-up, ASP decreased further, averaging 19% +/- 12% systemic (p = 0.019); this correlates with computed tomography imaging demonstrating a 5 mm or greater reduction in aortic diameter in 76% of patients (25 of 33) with follow-up of 6 months or longer. No patients manifested a recurrent type I or type III EL at latest follow-up. The device has also been used to follow 8 patients with type II EL with low ASP. CONCLUSIONS Implantation of a wireless ASP sensor provides useful information regarding type I and type III EL after TEVAR and permits serial observation of type II EL. This information may guide clinical therapy and improve outcomes. Longer term follow-up will define sensor reliability in postoperative surveillance.

A previously unreported complication of apicoaortic conduit for severe aortic stenosis.

Given the aging population, use of an apicoaortic conduit serves as an alternative method to treat severe aortic stenosis, especially in patients with a heavily calcified ascending aorta or prior cardiac surgery. Although an apicoaortic conduit fractionates systemic blood flow, it does so without significant deleterious effects. However, we report a novel complication with thrombosis of the aortic root and subsequent coronary insufficiency that likely resulted from a preponderance of cardiac output though the apicoaortic conduit with stagnation of native antegrade blood flow. Given increasing use of the apicoaortic conduit procedure, surgeons considering this approach should be familiar with this potential complication.

Twenty-five-year outcomes after multiple internal thoracic artery bypass

OBJECTIVE Coronary artery bypass grafting with multiple internal thoracic artery grafts is currently controversial. This study assessed single institutional outcomes with multiple internal thoracic artery grafting for guidance with future clinical decisions. METHODS In 19,482 patients undergoing multivessel coronary artery bypass grafting (1984-2009), baseline characteristics were recorded in a prospective databank, and follow-up was obtained by questionnaires, phone contact, or National Death Index. Outcomes examined were subsequent myocardial infarction, percutaneous coronary intervention, reoperative coronary artery bypass grafting, all-cause death, and a composite of the 4. Three groups were defined: (1) no internal thoracic artery graft (1874/19,482 or 9%); (2) single internal thoracic artery grafts and adjunctive venous conduits (single internal thoracic artery; 16,881/19,482 or 87%); and (3) multiple internal thoracic artery grafts (728/19,482 or 4%). Multivariable Cox modeling adjusted for differences in baseline characteristics, and comparisons were performed using area under the curve analysis. RESULTS Differences in baseline characteristics for the no internal thoracic artery graft, single internal thoracic artery, and multiple internal thoracic artery groups were as follows: median age 66, 64, and 59 years, respectively; congestive heart failure 22%, 18%, and 13%, respectively; ejection fraction 0.50, 0.52, and 0.51, respectively; reoperation 10%, 3%, and 7%, respectively; diabetes 27%, 30%, and 15%, respectively; and female gender 33%, 28%, and 20%, respectively. No differences existed in the median number of diseased vessels (3, 3, and 3, respectively) or number of grafts per patient (3, 3, and 3, respectively). Composite outcome improved with increasing internal thoracic artery grafts, whether assessing unadjusted or risk-adjusted data. Compared with no internal thoracic artery graft, the adjusted hazard ratio was 0.79 (confidence interval, 0.74-0.83) for single internal thoracic artery grafting and 0.70 (confidence interval, 0.62-0.80) for multiple internal thoracic artery grafting (both P < .001), reducing risk by 21% and 30%, respectively. CONCLUSIONS This study confirms improved patient outcomes with multiple internal thoracic artery grafting, achieving half again as much benefit as single internal thoracic artery grafting alone. The data suggest that increasing application of multiple internal thoracic artery grafting should be encouraged to mitigate the inherent risks and costs of long-term cardiac events.

Catheter-mediated subselective intracoronary gene delivery to the rabbit heart: introduction of a novel method.

Recent studies suggest that gene therapy using replication‐deficient adenoviruses will benefit treatment of cardiovascular diseases including heart failure. A persistent hurdle is the effective and reproducible delivery of a transgene to the myocardium with minimal iatrogenic morbidity. In this study, we sought to design a relatively non‐invasive percutaneous gene delivery system that would maximize cardiac transgene expression and minimize mortality after intracoronary adenovirus injection.

Gene interventions in the β-adrenergic system for treating heart failure

Abstract Cardiovascular disease accounts for nearly 40% of all deaths annually in this country. Prevention management and advances in medical treatments have dramatically reduced the overall mortality rate due to heart disease. However, death due to chronic heart failure (HF) continues to rise, and effective therapy, particularly for end-stage HF, has been elusive. The myocardial β-adrenergic receptor (βAR) system is critical not only in chronic HF but also in acute settings where cardiac function is compromised. Adding to its importance is the fact that drugs that act by altering βAR signal transduction are at the forefront of conventional HF therapeutic strategies. Accordingly, the ability to genetically manipulate βAR signaling in the heart is of great interest since it may provide unique inotropic support and improve existing therapeutic strategies for HF.