Juan A. Crestanello

Automated quantitative 3-dimensional modeling of the aortic valve and root by 3-dimensional transesophageal echocardiography in normals, aortic regurgitation, and aortic stenosis: comparison to computed tomography in normals and clinical implications.

Background—We tested the ability of a novel automated 3-dimensional (3D) algorithm to model and quantify the aortic root from 3D transesophageal echocardiography (TEE) and computed tomographic (CT) data. Methods and Results—We compared the quantitative parameters obtained by automated modeling from 3D TEE (n=20) and CT data (n=20) to those made by 2D TEE and targeted 2D from 3D TEE and CT in patients without valve disease (normals). We also compared the automated 3D TEE measurements in severe aortic stenosis (n=14), dilated root without aortic regurgitation (n=15), and dilated root with aortic regurgitation (n=20). The automated 3D TEE sagittal annular diameter was significantly greater than the 2D TEE measurements (P=0.004). This was also true for the 3D TEE and CT coronal annular diameters (P<0.01). The average 3D TEE and CT annular diameter was greater than both their respective 2D and 3D sagittal diameters (P<0.001). There was no significant difference in 2D and 3D measurements of the sinotubular junction and sinus of valsalva diameters (P>0.05) in normals, but these were significantly different (P<0.05) in abnormals. The 3 automated intercommissural distance and leaflet length and height did not show significant differences in the normals (P>0.05), but all 3 were significantly different compared with the abnormal group (P<0.05). The automated 3D annulus commissure coronary ostia distances in normals showed significant difference between 3D TEE and CT (P<0.05); also, these parameters by automated 3D TEE were significantly different in abnormal (P<0.05). Finally, the automated 3D measurements showed excellent reproducibility for all parameters. Conclusions—Automated quantitative 3D modeling of the aortic root from 3D TEE or CT data is technically feasible and provides unique data that may aid surgical and transcatheter interventions.

Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect

BACKGROUND Cardiac ischemia reperfusion (I/R) injury causes coronary vascular dysfunction. Coenzyme Q10 (CoQ), which preserves cardiac mechanical function after I/R, recently has been recognized as a free radical scavenger. We hypothesized that CoQ protects coronary vascular reactivity after I/R via an antioxidant mechanism. METHODS Rats were pretreated with either CoQ (20 mg/kg intramuscular and 10 mg/kg intraperitoneal [CoQ group]) or a vehicle (Control) before the experiment. Isolated perfused rat hearts were subjected to 25 minutes of global normothermic ischemia and 40 minutes of reperfusion. The reperfusion-induced oxidative burst was directly assessed by lucigenin enhanced chemiluminescence. Coronary flow was measured at equilibration and after reperfusion with or without bradykinin, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator. The effect of intracoronary infusion of hydrogen peroxide (H2O2 0.1 mumol/gm body weight given over 5 minutes), simulating the free radical burst after I/R, also was evaluated. RESULTS I/R decreased the bradykinin-induced change in coronary flow (-5% +/- 4% versus 26% +/- 3% at equilibration; p < 0.05) and the SNP-induced change (+20% +/- 6% versus +56% +/- 5% at equilibration; p < 0.05). The coronary vasculature after H2O2 infusion revealed a similar loss in vasodilatory responsiveness (+4% +/- 4% in response to bradykinin, +35% +/- 8% in response to SNP; p < 0.05 versus equilibration). Pretreatment with CoQ improved BK-induced vasorelaxation after I/R (+12% +/- 2%; p < 0.05 versus control I/R) or H2O2 infusion (18% +/- 4%; p < 0.05 versus control I/R) but failed to improve SNP-induced vasorelaxation. The CoQ pretreatment decreased the I/R-induced maximal free radical burst (9.3 +/- 0.8 x 10(3) cpm versus 11.5 +/- 1.1 x 10(3) cpm; p < 0.05) during the early period of reperfusion. CONCLUSIONS Endothelium-dependent vasorelaxation is more sensitive than endothelium-independent relaxation to I/R injury. Via a direct antioxidant effect, CoQ preserved endothelium-dependent vasorelaxation by improving tolerance to I/R injury.

Placement of Long-term Implantable Ventricular Assist Devices Without the Use of Cardiopulmonary Bypass

BACKGROUND Implantation of ventricular assist devices for cardiac support is normally performed using cardiopulmonary bypass. Post-operative complications could be minimized by the placement of these devices without the use of cardiopulmonary bypass. METHODS We hypothesize that left ventricular assist devices (LVADs), in selected patients, can be implanted safely off-pump. RESULTS In 25 patients, LVADs were implanted off-pump (mean age 50 years; 64% male, 36% female; average left ventricular ejection fraction 15%). Pre-operatively 68% of patients were on inotropes, 25% had an intra-aortic ballon pump, and 44% had a previous sternotomy. Blood utilization intra- and post-operatively was relatively minimal with 1 re-exploration for bleeding. There were 3 deaths. CONCLUSIONS We describe a technique for successful placement of a left ventricular assist device without the use of cardiopulmonary bypass.

Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 +/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/- 0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.

Toward a Definitive, Totally Thoracoscopic Procedure for Atrial Fibrillation

PURPOSE Evolution of anti-arrhythmia surgery beyond the Cox maze III has been hampered by the difficulty in implementing a complete lesion set in a truly minimally invasive approach. In this study, we introduce a true port-access procedure that addresses both autonomic and anatomic sources of atrial fibrillation, with real-time verification of all technical endpoints. DESCRIPTION A total of 32 patients with persistent or longstanding persistent atrial fibrillation underwent the totally thoracoscopic anti-arrhythmia procedure incorporating pulmonary vein isolation, mapping of epicardial autonomics, extended linear ablations across critical segments of atrial substrate, and ligation of the left atrial appendage. All aspects of the procedure were confirmed with intraoperative electrophysiologic testing. EVALUATION With 1 week of continuous rhythm surveillance at 3, 6, and 13 months postoperatively in all patients, 21 of 24 patients with 6-month follow-up are in sinus rhythm with no anti-arrhythmia medications. CONCLUSIONS An anti-arrhythmia operation that is highly effective in patients with advanced forms of atrial fibrillation can be safely performed through a totally port-access approach.

Ischemic Preconditioning Decreases Mitochondrial Proton Leak and Reactive Oxygen Species Production in the Postischemic Heart

BACKGROUND Proton leak (H(+) leak) dissipates mitochondrial membrane potential (mΔΨ) through the re-entry of protons into the mitochondrial matrix independent of ATP synthase. Changes in H(+) leak may affect reactive oxygen species (ROS) production. We measured H(+) leak and ROS production during ischemia-reperfusion and ischemic preconditioning (IPC) and examined how changing mitochondrial respiration affected mΔΨ and ROS production. MATERIALS AND METHODS Isolated rat hearts (n = 6/group) were subjected to either control-IR or IPC. Rate pressure product (RPP) was measured. Mitochondria were isolated at end reperfusion. Respiration was measured by polarography and titrated with increasing concentrations of malonate (0.5-2 mM). mΔΨ was measured using a tetraphenylphosphonium electrode. H(+) leak is the respiratory rate required to maintain membrane potential at -150 mV in the presence of oligomycin-A. Mitochondrial complex III ROS production was measured by fluorometry using Amplex-red. RESULTS IPC improved recovery of RPP at end reperfusion (63% ± 4% versus 21% ± 2% in control-IR, P < 0.05). Ischemia-reperfusion caused increased H(+) leak (94 ± 12 versus 31 ± 1 nmol O/mg protein/min in non-ischemic control, P < 0.05). IPC attenuates these increases (55 ± 9 nmol O/mg protein/min, P < 0.05 versus control-IR). IPC reduced mitochondrial ROS production compared with control-IR (31 ± 2 versus 40 ± 3 nmol/mg protein/min, P < 0.05). As mitochondrial respiration decreased, mΔΨ and mitochondrial ROS production also decreased. ROS production remained lower in IPC than in control-IR for all mΔΨ and respiration rates. CONCLUSIONS Increasing H(+) leak is not associated with decreased ROS production. IPC decreases both the magnitude of H(+) leak and ROS production after ischemia-reperfusion.

Aortic valve thrombosis after implantation of temporary left ventricular assist device

The use of assist devices for ventricular support after myocardial infarction with cardiogenic shock has become common practice. Thrombosis, bleeding, and infection are common complications. However, native valve thrombosis is a rare complication. We present a case of aortic valve thrombosis after implantation of a left ventricular assist device (LVAD) treated with thrombus removal at time of device exchange.

The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury

It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol. CoQ pretreatment improved myocardial function after ischemia reperfusion. CoQ pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ. Similarly it was hypothesized that CoQ protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R. We conclude that CoQ pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.

Giant papillary fibroelastoma of the right atrium: an unusual presentation.

Papillary fibroelastomas are small tumors of the valvular endocardium with a propensity to embolize. Fibroelastomas originating in the nonvalvular endocardium are rare. We report a giant papillary fibroelastoma of the right atrial septum presenting with hemodynamic compromise that resolved after surgical excision. The current literature and the diagnostic and therapeutic strategies are reviewed.

Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve implantation

Objective: Valve‐in‐valve procedures using transcatheter aortic valves are increasingly performed to treat degenerated bioprosthetic surgical aortic valves because they are less invasive than redo aortic valve replacement. The objective of this study is to quantify the changes in aortic sinus blood flow dynamics before and after a valve‐in‐valve procedure to gain insight into mechanisms for clinical and subclinical thrombosis of leaflets. Methods: A detailed description of the sinus hemodynamics for valve‐in‐valve implantation was performed in vitro. A Medtronic Hancock II (Medtronic Inc, Minneapolis, Minn) porcine bioprosthesis was modeled as a surgical aortic valve, and Medtronic CoreValve and Edwards Sapien (Edwards Lifesciences, Irvine, Calif) valves were used as the transcatheter aortic valves. High‐resolution particle image velocimetry was used to compare the flow patterns from these 2 valves within both the left coronary and noncoronary sinuses in vitro. Results: Velocity and vorticity within the surgical valve sinuses reached peak values of 0.7 m/s and 1000 s−1, with a 70% decrease in peak fluid shear stress near the aortic side of the leaflet in the noncoronary sinus. With the introduction of transcatheter aortic valves, peak velocity and vorticity were reduced to approximately 0.4 m/s and 550 s−1 and 0.58 m/s and 653 s−1 without coronary flow and 0.60 m/s and 631 s−1 and 0.81 m/s and 669 s−1 with coronary flow for the CoreValve and Sapien valve‐in‐valve implantations, respectively. Peak shear stress was approximately 38% higher along the aortic side of the coronary versus noncoronary transcatheter aortic valve leaflet. Conclusions: Decreased flow and shear stress in valve‐in‐valve procedures indicate a higher risk of leaflet thrombosis secondary to flow stasis, perhaps more so in the noncoronary sinus.