Ophthalmic findings associated with Australian tick paralysis (holocyclotoxicity) in hospitalized domestic dogs and cats.

OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.

Feline distichiasis treated with cryoepilation: A retrospective study of 15 cats (27 eyes).

OBJECTIVE: To describe the clinical features of cats diagnosed with distichiasis and report on the outcomes following cryoepilation. ANIMALS STUDIED: Fifteen cats (27 eyes). PROCEDURES: Medical records of domestic cats with distichiasis that underwent a double freeze-thaw cycle with a -80°C cryoprobe applied to the palpebral conjunctiva, with hair then epilated were retrospectively studied. The patient signalment, distichiae locations, concurrent ocular diseases, recurrences, complications, and outcomes were recorded. RESULTS: The mean (std dev) age at the time of diagnosis and treatment was 2.2 years (2.8 years). All (15/15) cats were of the domestic shorthair (DSH) breed. Concurrent ocular findings at the initial examination were observed in 17/27 (63%) eyes, with upper lateral eyelid hypoplasia the most prevalent, present in 9/27 (33.3%) eyes. Recurrence of distichiae occurred in 8/27 (29.6%) eyes. The clinical presentation in the instances of recurrence was judged as asymptomatic and not of a clinical concern in 3/27 (11.1%) eyes, with a second procedure deemed necessary to alleviate symptoms in 5/27 (18.5%) eyes. All eyes treated with a second procedure had no recurrence of distichiae or symptoms. Complications following cryoepilation occurred in 4/27 (14.8%) eyes, with two cats developing bilateral entropion post-procedure. CONCLUSIONS: Treatment of distichiasis in cats utilizing cryoepilation was effective at alleviating symptoms, though some cats needed a second procedure. The development of post-procedural entropion was seen occasionally.

Retrospective assessment of ophthalmic disease development in domestic dogs and cats when hospitalised with tick paralysis caused by Ixodes holocyclus.

OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.

Initial clinical experience with Myxo-ETlogix mitral valve repair ring.

OBJECTIVE: Complexity of mitral valve repair for myxomatous disease has led to low adoption. We report initial experience with a new ring designed specifically for myxomatous disease, the Myxo-ETlogix (Edwards Lifesciences LLC, Irvine, Calif). METHODS: From March 15, 2006, through November 19, 2007, 129 patients underwent mitral valve surgery for pure myxomatous disease, and 124 valves (96.1%) were repaired. The Myxo-ETlogix ring was used in 100 cases and the Physio ring (Edwards) in 24. The Myxo-ETlogix design includes a 3-dimensional shape to reduce systolic anterior motion and a larger orifice to accommodate elongated leaflets and decrease need for sliding plasty. Direct mitral valve measurements were made. Sizing was based on A2 height, and choice of ring type was based on unresected leaflet heights. RESULTS: There was no operative mortality or lasting perioperative morbidity. The Myxo-ETlogix group had taller A2, P1, P2, and P3 leaflet segments than the Physio group (P < or = .003). Only 1 sliding plasty was performed for asymmetry in the Myxo-ETlogix group. Predischarge and follow-up echocardiograms (n = 338 in 124 patients) disclosed transient nonobstructive chordal systolic anterior motion in 3 echocardiograms in 3 patients. No patients had 2+ or greater mitral regurgitation. At discharge, 5.7% had 1+ mitral regurgitation; this proportion was 17.3% at last follow-up (mean 6.1 +/- 4.4 months). CONCLUSION: In initial experience with the Myxo-ETlogix ring, nonobstructive systolic anterior motion has been rare and obstructive systolic anterior motion not observed. Ongoing prospective echocardiographic and clinical studies will elucidate the role of this etiology-specific ring.

Early and late rejection and HLA sensitization at the time of heart transplantation in patients bridged with left ventricular assist devices.

Over the years, the frequency of heart transplant candidates with HLA sensitization has increased as a result of the number of patients bridged to transplant using left ventricular assist devices (LVAD). Here we have examined 119 patients who were bridged to transplant with LVAD for a relationship between HLA antibodies and early (30 days) and late (2 years or more) rejection, as evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody reactions against a panel of T lymphocytes (T-PRA) and the percentage of transplants that occurred across a positive class I flow cross-match were examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs of the other biopsy grades were significantly higher (P < .001). A similar pattern was seen with the highest biopsy results at 2 years or later (P < .001). None of the patients who had a grade 0 biopsy at 30 days posttransplant had a positive flow cytometry class I cross-match (P = .02), although the same pattern did not occur later due to a small number of patients (n = 3) who had negative biopsies. Thus, when biopsy results were examined early or late posttransplant, patients with negative biopsy results tended to have less HLA sensitization. While the methods of HLA sensitization involve humoral responses, more aggressive immunosuppression might be warranted to attempt to reduce cellular rejection posttransplant if HLA class I antibodies are present at the time of transplant.

Curative surgery for atrial fibrillation. Current status and minimally invasive approaches.

Atrial fibrillation (AF) is the most common disorder of heart rhythm. Affecting 2.2 million Americans and millions more worldwide, AF is a dangerous and costly epidemic. AF is associated with an increased risk of stroke, premature death, and billions of dollars in health care expenditures. Traditional treatments of AF, which include medications aimed at rate or rhythm control, have been disappointing, leaving most patients in AF and failing to eliminate the risk of stroke. In contrast, advances in surgical and catheter-based therapies offer the chance to cure AF. With more than a decade of experience, surgical treatment AF is the most effective means of curing this arrhythmia. The classic Maze procedure eliminates AF in more than 90% of patients. A complex but safe operation, the Maze procedure is applied by relatively few surgeons. Recently, however, there has been a resurgence of interest in surgical treatment of AF. Advances in the understanding of the pathogenesis of AF and development of new ablation technologies enable surgeons to perform pulmonary vein ablation and create linear left atrial lesions rapidly and safely. Such procedures, which are generally applied to patients with AF and valvular heart disease, add 15 minutes to operative time and cure AF in approximately 80% of patients. New ablation technologies have been adapted to enable thoracoscopic and minimally invasive surgical AF ablation in patients with isolated AF, extending the possibility of cure to large numbers of patients.

Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation.

BACKGROUND: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively. OBJECTIVE: To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation. METHODS: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion. RESULTS: Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%). CONCLUSIONS: Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Is repair preferable to replacement for ischemic mitral regurgitation?

OBJECTIVE: This study was undertaken to compare mitral valve repair and replacement as treatments for ischemic mitral regurgitation. METHODS: From 1985 through 1997, a total of 482 patients with ischemic mitral regurgitation underwent either valve repair (n = 397) or valve replacement (n = 85). Patients more likely (P < or =.01) to undergo repair had functional mitral regurgitation or coronary revascularization with an internal thoracic artery graft; those more likely to receive valve replacement were in higher New York Heart Association functional classes or underwent emergency operations. These factors were used for multivariable propensity matching. Risk factors for early and late death were identified by multivariable, multiphase hazard function analysis. RESULTS: Within the propensity-matched better-risk group, survivals after valve replacement were 81%, 56%, and 36% at 30 days, 1 year, and 5 years, but survivals after repair were 94%, 82%, and 58% at these intervals (P =.08). In contrast, within the poor-risk group, survivals after repair and replacement were similar (P =.4). Risk factors (P < or =.01) included older age, higher functional class, greater wall motion abnormality, and renal dysfunction. Approximately 70% of patients were predicted to benefit from repair; the benefit lessened or was negated if an internal thoracic artery graft was not used, if a lateral wall motion abnormality was present, or if the mitral regurgitation jet pattern was complex. Freedom from repair failure at 5 years was 91%. CONCLUSION: Late survival is poor after surgery for ischemic mitral regurgitation. Most patients with ischemic mitral regurgitation benefit from mitral valve repair. In the most complex, high-risk settings, survivals after repair and replacement are similar.

Surgical treatments for heart failure.

The surgical options for CHF are a part of a larger paradigm shift in management. Viable and effective surgical options other than cardiac transplant and ventricular assist devices clearly exist and are applicable to a large portion of patients with CHF. These surgical therapies are of acceptable risk before decompensated CHF develops. The rapidly evolving therapies for altering LV remodeling, which underlies CHF progression, are an exciting area that may be joined in the future by molecular advances in myoblast transfer and gene therapy. These therapies are the basis of the discipline of CHF surgery within cardiovascular surgery.

Relationship between early diastolic intraventricular pressure gradients, an index of elastic recoil, and improvements in systolic and diastolic function.

BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.

Device-based change in left ventricular shape: a new concept for the treatment of dilated cardiomyopathy.

OBJECTIVE: We tested a unique new device, the Myosplint device (Myocor, Inc, Maple Grove, Minn), which is designed to change left ventricular shape, reduce left ventricular wall stress, and improve left ventricular systolic function. METHODS: Heart failure was induced in 15 dogs over 27 days by rapid pacing (230 beats/min). Seven animals underwent sham surgery, and 8 animals received 3 transventricular Myosplint devices each. Myosplint devices were tightened to create a symmetric bilobular left ventricular shape and were adjusted to produce a calculated 20% reduction in wall stress. Hemodynamic, 2-dimensional, and 3-dimensional echocardiographic studies were recorded at baseline, immediately after Myosplint placement (acute change), and at 1 month after both groups had a reduced rate (190 beats/min) of pacing designed to maintain heart failure. RESULTS: The Myosplint group had significant sustained improvements in left ventricular ejection fraction from baseline, to the acute change, to 1 month (19% +/- 5%; 36% +/- 8%; 39% +/- 13%) and reductions of left ventricular end-systolic volumes (73 +/- 9 mL; 34 +/- 5 mL; 42 +/- 12 mL) and end-systolic wall stress by 39% (341 +/- 68 10(3) dynes x cm(- 2) to 206 +/- 28 10(3) dynes x cm(-2)) acutely and 31% (372 +/- 83 10(3) dynes x cm(-2) to 250 +/- 40 10(3) dynes x cm(-2)) at 1 month. There were no significant changes in mitral regurgitation. CONCLUSION: Application of a Myosplint device to a dilated impaired left ventricle resulted in reduced wall stress and improved left ventricular systolic function that was sustained at 1 month. Device-based shape change is a promising new opportunity to treat patients with dilated cardiomyopathy.

Nosocomial bloodstream infections in patients with implantable left ventricular assist devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) are used as a bridge to transplantation but are associated with a high risk of infection including nosocomial bloodstream infections (BSI). METHODS: We retrospectively reviewed the medical records of all patients with implantable LVAD at the Cleveland Clinic with 72 hours or longer of LVAD support from January 1992 through June 2000, to determine the attack rate, incidence, and impact of nosocomial BSI in patients with LVAD. A nosocomial BSI was defined using Centers for Disease Control and Prevention definition. An LVAD-related BSI was defined as one where the same pathogen is cultured from the device and the blood with no other obvious source. Two hundred fourteen patients were included in the study (17,831 LVAD-days). RESULTS: One hundred forty BSI were identified in 104 patients for an attack rate of 49% and incidence of 7.9 BSI per 1000 LVAD-days. Thirty-eight percent of the BSI were LVAD associated. The most common pathogens causing BSI were coagulase-negative staphylococci (n = 33), Staphylococcus aureus, and Candida spp. (19 each), and Pseudomonas aeruginosa (16 each). A Cox proportional hazard model found BSI in patients with LVAD to be significantly associated with death (hazard ratio = 4.02, p < 0.001). Fungemia had the highest hazard ratio (10.9), followed by gram-negative bacteremia (5.1), and gram-positive bacteremia (2.2). CONCLUSIONS: Patients with implantable LVAD have a high incidence of BSI, which are associated with a significantly increased mortality. Strategies for prevention of infection in LVAD recipients should focus on the drive line exit site until technical advances can achieve a totally implantable device.

Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation.

Atrial fibrillation (AF), the most common chronic arrhythmia, increases the risk of stroke and is an independent predictor of mortality. Available pharmacological treatments have limited efficacy. Once initiated, AF tends to self-perpetuate, owing in part to electrophysiological remodeling in the atria; however, the fundamental mechanisms underlying this process are still unclear. We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following cardiac surgery. In chronically instrumented dogs, we found that rapid (400 min(-1)) atrial pacing was associated with attenuation of the atrial effective refractory period (ERP). Treatment with ascorbate, an antioxidant and peroxynitrite decomposition catalyst, did not directly modify the ERP, but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing. Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration (a biomarker of peroxynitrite formation). Oral ascorbate supplementation attenuated both of these changes. To evaluate the clinical significance of these observations, supplemental ascorbate was given to 43 patients before, and for 5 days following, cardiac bypass graft surgery. Patients receiving ascorbate had a 16.3% incidence of postoperative AF, compared with 34.9% in control subjects. In combination, these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia. The full text of this article is available at http://www.circresaha.org.

Mechanical unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in the failing human heart.

BACKGROUND: Mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in clinically documented reversal of chamber dilation and improvement of cardiac function. We tested the hypothesis that LVAD support normalizes the ability of cardiac muscle to respond to sympathetic nervous system stimulation by reversing the downregulation of beta-adrenergic receptors. METHODS AND RESULTS: Human LV tissue was obtained from nonfailing hearts of unmatched organ donors and failing hearts at the time of transplantation, with or without LVAD. Baseline contractile parameters and inotropic response to a beta-adrenergic agonist were measured in isolated trabecular muscles. beta-Adrenergic receptor density was quantified by radioligand binding. Results showed a significant increase in the response to beta-adrenergic stimulation after LVAD (developed tension increased by 0.76+/-0.09 g/mm(2) in nonfailing, 0.38+/-0.07 in failing, and 0.68+/-0.10 in failing+LVAD; P<0.01), accompanied by an increased density of beta-adrenergic receptors (58.7+/-9.6 fmol/mg protein in nonfailing, 26.2+/-3.8 in failing, and 63.0+/-8.3 in failing+LVAD; P<0.05). These changes were unrelated to the duration of support. CONCLUSIONS: Data demonstrate that mechanically supporting the failing human heart with an LVAD can reverse the downregulation of beta-adrenergic receptors and restore the ability of cardiac muscle to respond to inotropic stimulation by the sympathetic nervous system. This indicates that functional impairment of cardiac muscle in human heart failure is reversible.

A novel miniature ventricular assist device for hemodynamic support.

The HemoDynamics Systems enabler is a new cardiac assist pump that can expel blood from the left ventricle and provide pulsatile flow in the aorta. We evaluated the efficacy of the 18 Fr enabler. The enabler was inserted from the left ventricular apex into the ascending aorta in eight sheep. Heart failure (mild, moderate, and severe) was induced by microsphere injection into the coronary arteries to reduce cardiac output by 10-30%, 31-50%, and more than 50% from baseline, respectively. The enabler was activated, and its flow was increased to approximately 2.0 L/min. Hemodynamic variables were recorded before and after activation. In moderate heart failure, cardiac output and mean aortic pressure increased from 2.3 +/- 0.6 L/min and 59 +/- 12 mm Hg before assist to 2.8 +/- 0.6 L/min and 70 +/- 8 mm Hg at 30 minutes after activation, respectively (p < 0.01). Left atrial pressure decreased from 17 +/- 3 to 13 +/- 4 mm Hg (p < 0.05). Similar findings were observed in mild and severe heart failure. Despite its small diameter, the enabler significantly improved the hemodynamics of failing hearts and may potentially serve as a means of peripheral left ventricular support. Further study is warranted.

Clinical experience with 202 adults receiving extracorporeal membrane oxygenation for cardiac failure: survival at five years.

OBJECTIVES: We sought to determine 5-year survival after extracorporeal membrane oxygenation for cardiac failure and its predictors, to assess survival and its predictors after bridging to transplantation or weaning from extracorporeal membrane oxygenation, and to identify factors influencing the likelihood of these outcomes. METHODS: Two hundred two adults (mean age, 55 +/- 14 years) were supported with extracorporeal membrane oxygenation between 1992 and July 1999 after cardiac failure. Follow-up extended to 7.5 years (mean, 3.8 +/- 2 years). Multivariable hazard function analysis identified predictors of survival, and logistic regression identified the determinants of bridging or weaning. RESULTS: Survival at 3 days, 30 days, and 5 years was 76%, 38%, and 24%, respectively. Patients surviving 30 days had a 63% 5-year survival. Risk factors (P <.1) included older age, reoperation, and thoracic aorta repair. Forty-eight patients were bridged to transplantation, and 71 were weaned with intent for survival. Survival was similar after either outcome (44% vs 40% 5-year survival, respectively). Failure to bridge or wean included (P <.03) renal and hepatic failure on extracorporeal membrane oxygenator support, occurrence of a neurologic event, and absence of infection. The dominant modes of death were cardiac failure and multisystem organ failure. CONCLUSIONS: Extracorporeal membrane oxygenation is versatile and salvages some patients who would otherwise die. Improvement in intermediate-term outcome will require a multidisciplinary approach to protect organ function and limit organ injury before and during this support.

Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with severe contractile dysfunction and structural and electrophysiological remodeling. Mechanisms responsible for impaired contractility are undefined, and current therapies do not address this dysfunction. We have found that myofibrillar creatine kinase (MM-CK), an important controller of myocyte contractility, is highly sensitive to oxidative injury, and we hypothesized that increased oxidative stress and energetic impairment during AF could contribute to contractile dysfunction. Methods and Results-- Right atrial appendages were obtained from AF patients undergoing the Maze procedure and from control patients who were in normal sinus rhythm and undergoing cardiac surgery. MM-CK activity was reduced in AF patients compared with controls (25.4+/-3.4 versus 18.2+/-3.8 micromol/mg of myofibrillar protein per minute; control versus AF; P<0.05). No reduction in total CK activity or myosin ATPase activity was detected. This selective reduction in MM-CK activity was associated with increased relative expression of the beta-myosin isoform (25+/-6 versus 63+/-5%beta, CTRL versus AF; P<0.05). Western blotting of AF myofibrillar isolates demonstrated no changes in protein composition but showed increased prevalence of protein oxidation as detected by Western blotting for 3-nitrotyrosine (peroxynitrite biomarker) and protein carbonyls (hydroxyl radical biomarker; P<0.05). Patterns of these oxidative markers were distinct, which suggests discrete chemical events and differential protein vulnerabilities in vivo. MM-CK inhibition was statistically correlated to extent of nitration (P<0.01) but not to carbonyl presence. CONCLUSIONS: The present results provide novel evidence of oxidative damage in human AF that altered myofibrillar energetics may contribute to atrial contractile dysfunction and that protein nitration may be an important participant in this condition.

High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound.

BACKGROUND: Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. METHODS AND RESULTS: Intravascular ultrasound was performed in 262 heart transplant recipients 30.9+/-13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4+/-13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness >/=0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects >/=50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08+/-0.48 mm and 32.7+/-15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). CONCLUSIONS: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

Novel device to change left ventricular shape for heart failure treatment: device design and implantation procedure.

The Myocor Myosplint is designed to decrease left ventricular (LV) wall stress by changing LV shape, thus improving contractile function in dilated hearts. This shape change is accomplished by surgically placing three Myosplints perpendicular to the LV long axis, drawing the LV walls inward, and creating a symmetric, bilobular LV. Specially designed instruments aid in the precise delivery of these devices. The purpose of this study was to test the safety and feasibility of the procedure in dogs. Dilated cardiomyopathy was induced in 40 healthy dogs (26.3+/-1.7 kg) by ventricular pacing at 230 beats per minute for an average of 25+/-4 days. Using epicardial echocardiography, we placed the Myosplints across the LV chamber, avoiding the major coronary arteries, papillary muscles, and mitral valve. Once placed, the Myosplints were used to draw the LV walls inward to a prescribed distance. In all cases, we successfully implanted three Myosplints without using cardiopulmonary bypass. There were no complications related to the device or procedure. Myosplint implantation to change LV shape is safe and repeatable on a beating cardiomyopathic canine heart. Further study of the procedure will be needed in humans.