Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

BACKGROUND: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults (non-coronary artery disease [CAD]) and patients diagnosed with CAD. METHODS: Human arterioles were dissected from discarded surgical adipose tissue (n=166), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO and mitochondrial hydrogen peroxide (H2O2) production were measured in arterioles using fluorescence microscopy. H2O2 fluorescence was assessed in isolated human umbilical vein endothelial cells. RESULTS: Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to NOX-2 (NADPH-oxidase 2)-dependent H2O2-mediated flow-induced dilation. Endothelial dysfunction was prevented by treatment with sphingosine-1-phosphate (S1P) and partially prevented by C2-ceramide and an agonist of S1P-receptor 1 (S1PR1); the inhibition of the S1P/S1PR1 signaling axis induced endothelial dysfunction via NOX-2. Ceramide increased NO production in arterioles from non-CAD adults, an effect that was diminished with inhibition of S1P/S1PR1/S1P-receptor 3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired the overall ability to induce mitochondrial H2O2 production and subsequently dilate to flow, an effect not restored with exogenous S1P. Acute ceramide administration to arterioles from patients with CAD promoted H2O2 as opposed to NO production, an effect dependent on S1P-receptor 3 signaling. CONCLUSION: These data suggest that despite differential downstream signaling between health and disease, NSmase-mediated ceramide formation is necessary for proper functioning of the human microvascular endothelium. Therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.

Reduced Morbidity and Mortality Associated With Minimally Invasive Single-vessel Coronary Artery Bypass Compared With Conventional Sternotomy.

OBJECTIVE: We aimed to describe the safety and clinical benefits of minimally invasive, nonsternotomy coronary artery bypass grafting (MICABG) using data from The Society of Thoracic Surgeons (STS) National Database. BACKGROUND: MICABG has gained popularity, owing to expected lower perioperative morbidity and shorter recovery. Despite this, concerns remain regarding anastomotic quality and the validity of proposed perioperative benefits. METHODS: We queried the STS National Database for all patients who underwent single-vessel coronary artery bypass grafting (CABG) from January 2014 to December 2016 to compare outcomes of MICABG with conventional CABG. Patients who underwent concomitant or emergent procedures were excluded. Propensity-weighted cohorts were compared by operative approach with adjustment for variability across institutions. RESULTS: Of 12,406 eligible patients, 2688 (21.7%) underwent MICABG, and 9818 (78.3%) underwent conventional CABG. Propensity weighting produced excellent balance in patient characteristics, including completeness of revascularization, body mass index, and STS predictive risk scores. MICABG was associated with significant reduction of in-hospital mortality [odds ratio (OR)=0.32, absolute reduction (AR)=0.91%, P <0.0001]; 30-day mortality (OR=0.51, AR=0.88%, P =0.001), duration of ventilation (8.62 vs 12.6 hours, P <0.0001), prolonged hospitalization (OR=0.77, AR=1.6, P =0.043), deep wound infection (OR=0.33, AR=0.68, P <0.004), postoperative transfusions (OR=0.52, AR=7.7%, P <0.0001), and STS composite morbidity (OR=0.72, AR=1.19%, P =0.008). Subgroup analysis of only off-pump left internal mammary artery-left anterior descending CABG showed similar findings. Major adverse cardiac events and graft occlusion did not differ between groups. CONCLUSIONS: MICABG is associated with lower mortality and perioperative morbidity compared with conventional sternotomy CABG. MICABG may have a role in treating single-vessel disease.

One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.

BACKGROUND: Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System). METHODS: Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated. RESULTS: A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients ( P=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (-8.0 mL versus -12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% ( P=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure ( P<0.0001). CONCLUSIONS: Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov . Unique identifiers: NCT00209274, NCT01940120, and NCT01931956.

Proof of Concept: Development of a Mitral Annuloplasty Ring With Crosshatch Net.

OBJECTIVE: Here we report our preclinical, proof-of-concept testing to assess the ability of a novel device to correct mitral regurgitation. The Milwaukee Heart device aims to enable any cardiac surgeon to perform high-quality mitral valve repair using a standard annuloplasty ring with a crosshatch of microporous, monofilament suture. METHODS: Hemodynamic, echocardiographic, and videographic data were collected at baseline, following induction of mitral regurgitation, and after repair using porcine hearts in an ex vivo biosimulator model. A commercially available cardiac prosthesis assessment platform was then used to assess the hydrodynamic characteristics of the study device. RESULTS: Porcine biosimulator pressure and flow metrics exhibited successful correction of mitral regurgitation following device implantation with similar values to baseline. Hydrodynamic results yielded pressure gradients and an effective orifice area comparable to currently approved prostheses. CONCLUSIONS: The study device effectively reduced mitral valve regurgitation and improved hemodynamics in our preclinical model with similar biophysical metrics to currently approved devices. Future in vivo trials are needed to evaluate the efficacy, biocompatibility, and freedom from the most likely adverse events, such as device thrombosis, embolic events, and hemolysis.

Subclinical Aortic Insufficiency Causing Cardiogenic Shock Years After Impella Placement.

A 28-year-old male with atrial fibrillation and thyrotoxicosis-induced heart failure underwent multiple interventions, including extracorporeal membrane oxygenation (ECMO), multiple valve repair/replacement, and Impella placement/removal. However, after a period of three years, the patient developed progressive aortic insufficiency (AI), which was attributed to damage caused by the prolonged use of the Impella device. The discussion highlights the importance of adhering to manufacturer guidelines for device use and emphasizes the need for careful examination during placement to minimize potential complications.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults and patients with coronary artery disease (CAD). Methods: Human arterioles were dissected from otherwise discarded surgical adipose tissue (n=123), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO production was measured in arterioles using fluorescence microscopy. Hydrogen peroxide (H2O2) fluorescence was assessed in isolated human umbilical vein endothelial cells. Results: Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to H2O2-mediated flow-induced dilation within 30 minutes. In endothelial cells, NSmase inhibition acutely increased H2O2 production. Endothelial dysfunction in both models was prevented by treatment with C2-ceramide, S1P, and an agonist of S1P-receptor 1 (S1PR1), while the inhibition of S1P/S1PR1 signaling axis induced endothelial dysfunction. Ceramide increased NO production in arterioles from healthy adults, an effect that was diminished with inhibition of S1P/S1PR1/S1PR3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired dilation to flow. This effect was not restored with exogenous S1P. Although, inhibition of S1P/S1PR3 signaling impaired normal dilation to flow. Acute ceramide administration to arterioles from patients with CAD also promoted H2O2 as opposed to NO production, an effect dependent on S1PR3 signaling. Conclusion: These data suggest that despite key differences in downstream signaling between health and disease, acute NSmase-mediated ceramide formation and its subsequent conversion to S1P is necessary for proper functioning of the human microvascular endothelium. As such, therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.

Simple technique to verify CO(2) diffusion with the CarbonAid™ device.

It has become common practice in cardiac surgery to flood the operative field with CO(2) to facilitate deairing of the heart. However, CO(2) delivery is variable and verification of CO(2) delivery can be challenging. We report a simple, reliable method to confirm CO(2) delivery. This technique ensures that the benefits of CO(2) delivery are provided to the patient during the operation.

Venovenous Extracorporeal Membrane Oxygenation to Facilitate Removal of Endobronchial Tumors.

Short-term extracorporeal membrane oxygenation is a useful adjunct to thoracic procedures. We report the cases of 2 middle-aged men who were supported with venovenous extracorporeal membrane oxygenation to facilitate tumor debulking and recanalization of the carina and mainstem bronchi. Neither patient had major complications or adverse events. These cases suggest that short-term extracorporeal membrane oxygenation is safe in patients undergoing complex resection or debulking of endobronchial lesions.

Effect of the effluent released from the canine internal mammary artery after intraluminal and extraluminal perfusion of acetylcholine and adenosine diphosphate.

Segments of the canine internal mammary artery (35 mm in length) were suspended in vitro in an organ chamber containing physiological salt solution (95% O2/5% CO2, pH = 7.4, 37 degrees C). Segments were individually cannulated and perfused at 5 ml/minute using a roller pump. Vasorelaxant activity of the effluent from the perfused internal mammary arteries was bioassayed by measuring the decrease in tension induced by the effluent of the coronary artery endothelium-free ring which had been contracted with prostaglandin F2alpha (2 x 10(-6) M). Intraluminal perfusion of adenosine diphosphate (10(-5) M) induced significant increase in relaxant activity in the effluent from the perfused blood vessel. However, when adenosine diphosphate (10(-5) M) was added extraluminally to the internal mammary artery, no change in relaxant activity in the effluent was noted. In contrast, acetylcholine produced significant increase in the relaxant activity on the effluent of the perfused internal mammary artery with both intraluminal and extraluminal perfusion. The intraluminal and extraluminal release of endothelium-derived relaxing factor (EDRF) by acetylcholine (10(-5) M) can be inhibited by site-specific administration of atropine (10(-5) M). These experiments indicate that certain agonists can induce the release of EDRF only by binding to intravascular receptors while other agonists can induce endothelium-dependent vasodilatation by acting on neural side receptors.

Comparisons of the release of vasodilator substances from left and right cardiac chambers of the isolated perfused rabbit heart: implications for intraventricular thrombus formation.

Prostacyclin (PgI(2)) and endothelium-derived nitric oxide (EDNO) are produced by the arterial and venous endothelium. In addition to their vasodilator action on vascular smooth muscle, both act together to inhibit platelet aggregation and promote platelet disaggregation. EDNO also inhibits platelet adhesion to the endothelium. EDNO and PgI(2) have been shown to be released from the cultured endocardial cells. In this study, we examined the release of vasoactive substances from the intact endocardium by using isolated rabbit hearts perfused with physiological salt solution (95% O(2)/5% CO(2), T=37 degrees C). The right and left cardiac chambers were perfused through separate constant-flow perfusion loops (physiological salt solution, 8 ml min(-1)). Effluent from left and right cardiac, separately, was bioassayed on canine coronary artery smooth muscle, which had been contracted with prostaglandin F(2alpha_)(2 x 10(-6)M) and no change in tension was exhibit. However, addition of calcium ionophore A23187 (10(-6)M) to the cardiac chambers' perfusion line induced vasodilation of the bioassay coronary ring, 61.4+/-7.4% versus 70.49+/-6.1% of initial prostaglandin F(2alpha) contraction for the left and right cardiac chambers perfusate, respectively (mean+/-SEM, n=10, p>0.05). Production of vasodilator was blocked totally in the left heart but, only partially blocked in the right heart by adding indomethacin (10(-5)M) to the perfusate, respectively, 95.2+/-2.2% versus 41.5+/-4.8% (mean+/-SEM, n=10, p<0.05). 6-Keto prostaglandin F(1alpha), measured in the endocardial superfusion effluent was also higher for the left cardiac chambers than for the right at the time of stimulation with the A23187, respectively, 25385.88+/-5495 pg/ml (n=8) versus 13,132.45+/-1839.82 pg/ml (n=8), (p<0.05). These results showed that cyclooxygenase pathway plays major role in generating vasoactive substances for the left cardiac chamber endocardium; while it is not the main pathway for the right ventricular endocardium at which EDNO and PgI(2) could act together and potentiate their antithrombogenic activities in isolated perfused rabbit heart. This may be an explanation for the intraventricular thrombus mostly seen in left ventricle rather than in right ventricle as a complication of myocardial infarction.

Role of Echocardiography in Transcatheter Mitral Valve Replacement in Native Mitral Valves and Mitral Rings.

Adaptation and evolution of transcatheter aortic valve replacement (TAVR) technologies has led to approval of TAVR for consideration in patients at intermediate risk for surgical aortic valve intervention. As TAVR becomes more mainstream, attention is shifting toward percutaneous mitral valve (MV) repair and transcatheter MV replacement (TMVR) techniques. Transcatheter heart valves (both purpose-built and off-label-use TAVR valves) are being implanted during TMVR procedures to treat clinically significant MV disease (native disease, degenerated bioprosthetic valves, and dysfunctional surgical MV annuloplasty repairs) when the risk of open heart MV surgery is prohibitive. The success of these high-risk procedures is directly related to accurate periprocedural imaging with echocardiography and other modalities. Although a multidisciplinary heart valve team approach is necessary for optimal patient selection, a multimodality team-based imaging approach and comprehensive understanding of the MV are required for safe procedural planning. Collaboration between noninvasive cardiac imagers and the intraprocedural interventional imaging team and translation of the periprocedural imaging to the implanting team are crucial to the success of TMVR technology. Currently, the TMVR procedures discussed here are conducted either as part of clinical research or off label. The US Food and Drug Administration-approved mitral valve-in-valve procedures for the treatment of degenerated mitral bioprosthetic valves are not discussed here.

Lysophosphatidic acid acts on LPA1 receptor to increase H2 O2 during flow-induced dilation in human adipose arterioles.

BACKGROUND AND PURPOSE: NO produces arteriolar flow-induced dilation (FID) in healthy subjects but is replaced by mitochondria-derived hydrogen peroxide (mtH2 O2 ) in patients with coronary artery disease (CAD). Lysophosphatidic acid (LPA) is elevated in patients with risk factors for CAD, but its functional effect in arterioles is unknown. We tested whether elevated LPA changes the mediator of FID from NO to mtH2 O2 in human visceral and subcutaneous adipose arterioles. EXPERIMENTAL APPROACH: Arterioles were cannulated on glass micropipettes and pressurized to 60 mmHg. We recorded lumen diameter after graded increases in flow in the presence of either NOS inhibition (L-NAME) or H2 O2 scavenging (Peg-Cat) ± LPA (10 µM, 30 min), ±LPA1 /LPA3 receptor antagonist (Ki16425) or LPA2 receptor antagonist (H2L5186303). We analysed LPA receptor RNA and protein levels in human arterioles and human cultured endothelial cells. KEY RESULTS: FID was inhibited by L-NAME but not Peg-Cat in untreated vessels. In vessels treated with LPA, FID was of similar magnitude but inhibited by Peg-Cat while L-NAME had no effect. Rotenone attenuated FID in vessels treated with LPA indicating mitochondria as a source of ROS. RNA transcripts from LPA1 and LPA2 but not LPA3 receptors were detected in arterioles. LPA1 but not LPA3 receptor protein was detected by Western blot. Pretreatment of vessels with an LPA1 /LPA3 , but not LPA2 , receptor antagonist prior to LPA preserved NO-mediated dilation. CONCLUSIONS AND IMPLICATIONS: These findings suggest an LPA1 receptor-dependent pathway by which LPA increases arteriolar release of mtH2 O2 as a mediator of FMD.

Arterial Cutaneous Femoral Fistulous Tract Closure Using Surgiflo Hemostatic Matrix: A Novel Adjunct for Post-TAVR Access-Site Management.

Several options are available to address hemostasis at the end of a cardiac catheterization or percutaneous transfemoral transcatheter aortic valve replacement (TAVR) when conventional options are ineffective. To date, there have been few studies exploring the use of a topical thrombin preparation, as one of its main contraindications is that it cannot be used intravascularly due to risk of embolization. The following case shows safe utilization of Surgiflo hemostatic gel matrix under fluoroscopic guidance against an inflated balloon in order to achieve closure of a fistulous tract from a femoral artery access site during percutaneous TAVR.

Endothelium-dependent relaxation to poly-L-arginine in canine coronary arteries.

The endothelium-dependent relaxation elicited by poly-L-arginine was investigated in canine coronary arteries. Poly-L-arginine (10(-11) to 10(-7) M) induced concentration-dependent endothelium-dependent relaxation in segments of canine coronary arteries incubated with indomethacin. In the presence of indomethacin, arteries contracted with prostaglandin F2alpha and exposed also to ouabain, oxyhemoglobin, or N(omega)-nitro-L-arginine, as well as those contracted with 20 mM of KCl, presented reduced endothelium-dependent relaxation to poly-L-arginine. The combination of N(omega)-nitro-L-arginine with indomethacin produced further reduction of endothelium-dependent relaxation in arteries contracted with prostaglandin F2alpha as well as in arteries contracted with 20 mM of KCl. However, only quinacrine or calmidazolium, both in presence of N(omega)-nitro-L-arginine plus indomethacin, abolished the endothelium-dependent relaxation elicited by poly-L-arginine. The relaxation to poly-L-arginine was not significantly affected by glybenclamide. The present study demonstrates that in addition to the prostacyclin and nitric oxide-dependent mechanisms, poly-L-arginine also elicits endothelium-dependent relaxation in canine coronary arteries, stimulating the release of endothelial relaxing factor(s) produced by the phospholipase A2 pathway, but independent of the cyclooxygenase pathway, which may cause hyperpolarization of the vascular smooth muscle.

Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation.

OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37 C and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2 and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.

Effect of arginine vasopressin on the canine epicardial coronary artery: experiments on V1-receptor-mediated production of nitric oxide.

OBJECTIVE: To determine whether arginine vasopressin releases endothelium-derived nitric oxide (EDNO) from the epicardial coronary artery. METHODS: We studied segments of canine left circumflex coronary arteries suspended in organ chambers to measure isometric force. The coronary artery segments were contracted with prostaglandin F2alpha (2 x 10-6M) and exposed to a unique, strong arginine vasopressin concentration (10-6M) or titrated concentrations (10-9 a 10-5 M). RESULTS: The unique dose of arginine vasopressin concentration (10-6M) induced transient, but significant (p<0.05), relaxation in arterial segments with endothelium, and an increase, not significant, in tension in arteries without endothelium. Endothelium-dependent relaxation to arginine vasopressin was inhibited by Ng-monomethyl-L-arginine (L-NMMA, 10-5M) or N G-nitro-L-arginine (L-NOARG) (10-4M), 2 inhibitors of nitric oxide synthesis from L-arginine. Exogenous L-arginine (10-4M), but not D-arginine (10-4M), reversed the inhibitory effect of L-NMMA on vasopressin-mediated vasorelaxation. Endothelium dependent relaxation to vasopressin was also reversibly inhibited by the vasopressin V1-receptor blocker d(CH2)5Try(Me) arginine vasopressin (10-6M) (n=6, P<0.05). CONCLUSION: Vasopressin acts through V1 endothelial receptors to stimulate nitric oxide release from L-arginine.

Isolated mitral valve surgery risk in 77,836 patients from the Society of Thoracic Surgeons database.

BACKGROUND: Understanding the operative outcomes of mitral valve (MV) surgery across the spectrum of predicted risk of mortality (PROM) is necessary to determine the best use of novel percutaneous approaches. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was utilized to study isolated MV operations during two time periods: era 1 (2002 to 2006, n = 37,743) and era 2 (2007 to 2010, n = 40,093). In each era, four PROM groups were defined: low risk (PROM 0% to <4%); intermediate risk (PROM 4% to <8%); high risk (PROM 8% to <12%); and extreme risk (PROM ≥ 12%). In each risk group, mortality rates and observed to expected mortality ratios were compared across eras. RESULTS: A total of 63,645 cases (82%) were classified as low risk, 8,032 (10%) as intermediate risk, 2,765 (4%) as high risk, and 3,394 (4%) as extreme risk. Sixty-seven percent of MV repairs (n = 30,488) and 18% of MV replacements (n = 5,749) had a PROM less than 1%. PROM less than 4% was seen for 93% of MV repairs (n = 42,196) and 66% of replacements (n = 21,449). Across the two eras, the MV repair rate increased from 54.8% to 61.8% (p = 0.0017); and a significant reduction in operative mortality was observed in high risk and extreme risk cohorts (p < 0.05). CONCLUSIONS: The frequency with which MV repair for isolated MV disease is performed has increased over time and is associated with very low early mortality. A significant reduction in mortality among patients at highest risk has occurred, and must be considered as patients are evaluated for percutaneous therapies.

Left atrial appendage occlusion: lessons learned from surgical and transcatheter experiences.

Since the 1950s, the pathophysiologic role of the left atrial appendage (LAA) has been known in thromboembolic disease. A variety of surgical techniques have been described to close the LAA, with various degrees of efficacy. Today, transcatheter devices for LAA occlusion may offer a less invasive solution. This review looks at the surgical experience with LAA occlusion, with a focus on the techniques of closure, the prospects for stroke reduction, and the percutaneous trials completed so far, to formulate some meaningful conclusions about the status of LAA closure today.

High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries.

OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10(-9)-10(-4) M), Ach (10(-9)-10(-4) M) and NaF (0.5-9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10(-9)-10(-5) M) or SNP (10(-9)-10(-6) M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.