Hongchang Luo

Hyaluronic acid-human blood hydrogels for stem cell transplantation

Tissue engineering-based approaches have the potential to improve stem cell engraftment by increasing cell delivery to the myocardium. Our objective was to develop and characterize a naturally-derived, autologous, biodegradable hydrogel in order to improve acute stem cell retention in the myocardium. HA-blood hydrogels (HA-BL) were synthesized by mixing in a 1:1(v/v) ratio, lysed whole blood and hyaluronic acid (HA), whose carboxyl groups were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS). We performed physical characterization and measured survival/proliferation of cardiosphere-derived cells (CDCs) encapsulated in the hydrogels. Hydrogels were injected intra-myocardially or applied epicardially in rats. NHS-activated carboxyl groups in HA react with primary amines present in blood and myocardium to form amide bonds, resulting in a 3D hydrogel bound to tissue. HA-blood hydrogels had a gelation time of 58±12 s, swelling ratio of 10±0.5, compressive and elastic modulus of 14±3 and 1.75±0.6 kPa respectively. These hydrogels were not degraded at 4 wks by hydrolysis alone. CDC encapsulation promoted their survival and proliferation. Intra-myocardial injection of CDCs encapsulated in these hydrogels greatly increased acute myocardial retention (p=0.001). Epicardial application of HA-blood hydrogels improved left ventricular ejection fraction following myocardial infarction (p=0.01). HA-blood hydrogels are highly adhesive, biodegradable, promote CDC survival and increase cardiac function following epicardial application after myocardial infarction.

Effect of the mitral valve on diastolic flow patterns

The leaflets of the mitral valve interact with the mitral jet and significantly impact diastolic flow patterns, but the effect of mitral valve morphology and kinematics on diastolic flow and its implications for left ventricular function have not been clearly delineated. In the present study, we employ computational hemodynamic simulations to understand the effect of mitral valve leaflets on diastolic flow. A computational model of the left ventricle is constructed based on a high-resolution contrast computed-tomography scan, and a physiological inspired model of the mitral valve leaflets is synthesized from morphological and echocardiographic data. Simulations are performed with a diode type valve model as well as the physiological mitral valve model in order to delineate the effect of mitral-valve leaflets on the intraventricular flow. The study suggests that a normal physiological mitral valve promotes the formation of a circulatory (or “looped”) flow pattern in the ventricle. The mitral valve leaflets also increase the strength of the apical flow, thereby enhancing apical washout and mixing of ventricular blood. The implications of these findings on ventricular function as well as ventricular flow models are discussed.

Comparison of Outcomes in Patients With Nonobstructive, Labile-Obstructive, and Chronically Obstructive Hypertrophic Cardiomyopathy

Patients with nonobstructive hypertrophic cardiomyopathy (HC) are considered low risk, generally not requiring aggressive intervention. However, nonobstructive and labile-obstructive HC have been traditionally classified together, and it is unknown if these 2 subgroups have distinct risk profiles. We compared cardiovascular outcomes in 293 patients HC (96 nonobstructive, 114 labile-obstructive, and 83 obstructive) referred for exercise echocardiography and magnetic resonance imaging and followed for 3.3 ± 3.6 years. A subgroup (34 nonobstructive, 28 labile-obstructive, 21 obstructive) underwent positron emission tomography. The mean number of sudden cardiac death risk factors was similar among groups (nonobstructive: 1.4 vs labile-obstructive: 1.2 vs obstructive: 1.4 risk factors, p = 0.2). Prevalence of late gadolinium enhancement (LGE) was similar across groups but more non-obstructive patients had late gadolinium enhancement ≥20% of myocardial mass (23 [30%] vs 19 [18%] labile-obstructive and 8 [11%] obstructive, p = 0.01]. Fewer labile-obstructive patients had regional positron emission tomography perfusion abnormalities (12 [46%] vs nonobstructive 30 [81%] and obstructive 17 [85%], p = 0.003]. During follow-up, 60 events were recorded (36 ventricular tachycardia/ventricular fibrillation, including 30 defibrillator discharges, 12 heart failure worsening, and 2 deaths). Nonobstructive patients were at greater risk of VT/VF at follow-up, compared to labile obstructive (hazed ratio 0.18, 95% confidence interval 0.04 to 0.84, p = 0.03) and the risk persisted after adjusting for age, gender, syncope, family history of sudden cardiac death, abnormal blood pressure response, and septum ≥3 cm (p = 0.04). Appropriate defibrillator discharges were more frequent in nonobstructive (8 [18%]) compared to labile-obstructive (0 [0%], p = 0.02) patients. In conclusion, nonobstructive hemodynamics is associated with more pronounced fibrosis and ischemia than labile-obstructive and is an independent predictor of VT/VF in HC.

LEFT ATRIAL STRAIN RATE AS A PREDICTOR OF LOW EXERCISE CAPACITY IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS

Methods/Results: We included 151 patients, being 100(66%) men, 76(50%) with the obstructive HCM, age 55±17yrs. Left ventricular (LV) ejection fraction (EF) was 69±9%, LV mass index was 139±47g/m2, basal and mid septum thickness were 2.0±0.5cm and 1.9±0.6cm, respectively and gradient was 31±34mmHg. Regarding diastolic function, HCM patients had 247±76ms of deceleration time, E/A ratio of 1.3±0.6 and E/e’ ratio of 23±11. Pulmonary pressure by tricuspid regurgitation gradient was 33±13mmHg. On univariate analysis, LAST and LASR showed significant association with LEC, and LASR showed the highest odds ratio when compared to all other variables. After multivariate regression, LASR was also significantly associated with LEC after adjusting by age and E/e’ ratio (OR=9.6, 95%CI=1.1-91, p=0.04) (Table 1).

EFFECTS OF BETA BLOCKERS ON MYOCARDIAL MECHANICS IN HYPERTROPHIC CARDIOMYOPATHY

Beta-blockers (BB) are the primary medical therapy in obstructive and nonobstructive hypertrophic cardiomyopathy (HCM). However, the effects of BB therapy on cardiac mechanics are unknown. In particular, it is unclear if decreasing gradients have salutary effects on myocardial mechanics or if BB