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.

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.

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.

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.

Cardiac exercise hemodynamics late after partial left ventriculectomy.

BACKGROUND: Although some patients report favorable activity levels late after partial left ventriculectomy (PLV), their exercise physiology has not been well described. METHODS AND RESULTS: We performed upright bicycle hemodynamics in 10 patients (9 men) aged 56+/-12 years at 1.7 years after PLV. Ejection fraction was 25+/-4%. Patients biked 10+/-7 minutes. With exercise, the mean pulmonary arterial pressure rose from 36+/-12 to 52+/-10 mm Hg (P:=0.0003). The mean pulmonary capillary wedge pressure rose from 25+/-14 to 36+/-9 mm Hg (P:=0.0566), and the cardiac index rose from 2.2+/-0.5 to 3.8+/-1.6 L. min(-1). m(-2) (P:=0.0077). The mixed venous oxygenation with exercise declined from 44+/-9% to 24+/-17% (P:=0. 0220), and the pulmonary vascular resistance increased from 2.0+/-0. 9 to 2.3+/-1.1 Wood units (P:=0.5566). CONCLUSIONS: In late follow-up after PLV with exercise, the cardiac index is significantly augmented. However, there are further rises in pulmonary artery and pulmonary capillary wedge pressures, suggesting abnormal compliance, with marked decline in mixed venous oxygenation. Elucidating late physiology after PLV may help pave the way for future innovative heart failure surgeries.

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.

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.

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.

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy.

BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays.

BACKGROUND: Failing human hearts are characterized by altered cytoskeletal and myofibrillar organization, impaired signal transduction, abnormal protein turnover, and impaired energy metabolism. Thus, expression of multiple classes of genes is likely to be altered in human heart failure. METHODS AND RESULTS: We used high-density oligonucleotide arrays to explore changes in expression of approximately 7000 genes in 2 nonfailing and 2 failing human hearts with diagnoses of end-stage ischemic and dilated cardiomyopathy, respectively. We report altered expression of (1) cytoskeletal and myofibrillar genes (striated muscle LIM protein-1 [SLIM1], myomesin, nonsarcomeric myosin regulatory light chain-2 [MLC(2)], and ss-actin); (2) genes responsible for degradation and disassembly of myocardial proteins (alpha(1)-antichymotrypsin, ubiquitin, and gelsolin); (3) genes involved in metabolism (ATP synthase alpha-subunit, succinate dehydrogenase flavoprotein [SDH Fp] subunit, aldose reductase, and TIM17 preprotein translocase); (4) genes responsible for protein synthesis (elongation factor-2 [EF-2], eukaryotic initiation factor-4AII, and transcription factor homologue-HBZ17); and (5) genes encoding stress proteins (alphaB-crystallin and mu-crystallin). In 5 additional failing hearts and 4 additional nonfailing controls, we then compared expression of proteins encoded by the differentially expressed genes, alphaB-crystallin, SLIM1, gelsolin, alpha(1)-antichymotrypsin, and ubiquitin. In each case, changes in protein expression were consistent with changes in transcript measured by microarray analysis. Gelsolin protein expression was also increased in cardiomyopathic hearts from tropomodulin-overexpressing (TOT) mice and rac1-expressing (racET) mice. CONCLUSIONS: Altered expression of the genes identified in this study may contribute to development of the heart failure phenotype and/or represent compensatory mechanisms to sustain cardiac function in failing human hearts.

Results of partial left ventriculectomy for dilated cardiomyopathy: hemodynamic, clinical and echocardiographic observations.

OBJECTIVES: The study was done to prospectively measure the echocardiographic, hemodynamic and clinical outcomes after partial left ventriculectomy (PLV). BACKGROUND: Although PLV can improve symptoms of advanced heart failure, immediate postoperative echocardiographic findings remain abnormal. METHODS: Fifty-nine patients with cardiomyopathy and advanced heart failure underwent PLV and concomitant mitral valve surgery between May 1996 and December 1997. Thirty-nine percent were on inotropic therapy. All were New York Heart Association (NYHA) functional class III or IV. Mechanical circulatory support (LVAD) and transplant were provided for rescue therapy when hemodynamic compromise occurred. Patients were followed for a mean of 405+/-168 days, and clinical, echocardiographic and hemodynamic measures were obtained preoperatively, immediately postoperatively, and at 3 and 12 months prospectively. RESULTS: Comparing preoperative and 12-month postoperative values in event-free survivors, we found: NYHA functional class improved from 3.6 to 2.1, p < 0.0001; peak oxygen consumption increased from 10.8 to 16.0 ml/kg/min, p < 0.0001; LV ejection fraction increased from 13+/-6.0% to 24+/-6.9%, p < 0.0001; LV end diastolic diameter decreased from 8.2+/-1.03 to 6.2+/-0.64 cm, p < 0.0001, and volume was reduced from 167+/-60 to 105+/-38 ml/m2, p = 0.02. Central hemodynamics did not normalize after surgery. CONCLUSIONS: Partial left ventriculectomy can provide structural remodeling of the heart that may result in temporary improvement in clinical compensation. However, perioperative failures and the return of heart failure limit the propriety of this procedure.

Noninvasive estimation of transmitral pressure drop across the normal mitral valve in humans: importance of convective and inertial forces during left ventricular filling.

OBJECTIVES: We hypothesized that color M-mode (CMM) images could be used to solve the Euler equation, yielding regional pressure gradients along the scanline, which could then be integrated to yield the unsteady Bernoulli equation and estimate noninvasively both the convective and inertial components of the transmitral pressure difference. BACKGROUND: Pulsed and continuous wave Doppler velocity measurements are routinely used clinically to assess severity of stenotic and regurgitant valves. However, only the convective component of the pressure gradient is measured, thereby neglecting the contribution of inertial forces, which may be significant, particularly for nonstenotic valves. Color M-mode provides a spatiotemporal representation of flow across the mitral valve. METHODS: In eight patients undergoing coronary artery bypass grafting, high-fidelity left atrial and ventricular pressure measurements were obtained synchronously with transmitral CMM digital recordings. The instantaneous diastolic transmitral pressure difference was computed from the M-mode spatiotemporal velocity distribution using the unsteady flow form of the Bernoulli equation and was compared to the catheter measurements. RESULTS: From 56 beats in 16 hemodynamic stages, inclusion of the inertial term ([deltapI]max = 1.78+/-1.30 mm Hg) in the noninvasive pressure difference calculation significantly increased the temporal correlation with catheter-based measurement (r = 0.35+/-0.24 vs. 0.81+/-0.15, p< 0.0001). It also allowed an accurate approximation of the peak pressure difference ([deltapc+I]max = 0.95 [delta(p)cathh]max + 0.24, r = 0.96, p<0.001, error = 0.08+/-0.54 mm Hg). CONCLUSIONS: Inertial forces are significant components of the maximal pressure drop across the normal mitral valve. These can be accurately estimated noninvasively using CMM recordings of transmitral flow, which should improve the understanding of diastolic filling and function of the heart.

Left ventricular diastolic filling with an implantable ventricular assist device: beat to beat variability with overall improvement.

OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.

Left ventricular echocardiographic and histologic changes: impact of chronic unloading by an implantable ventricular assist device.

OBJECTIVES: We studied the effects of chronic left ventricular unloading by a ventricular assist device and assessed left ventricular morphologic and histologic changes. BACKGROUND: The implantable left ventricular assist device has been effective as a "bridge" to cardiac transplantation. Although there are reports documenting its circulatory support, little is known about the effects of chronic left ventricular unloading on the heart itself. METHODS: We performed intraoperative transesophageal echocardiography at the insertion and explanation of a HeartMate left ventricular assist device in 19 patients with end-stage heart failure. They were supported by the assist device for 3 to 153 days (mean [+/-SD] 68 +/- 33). Measurements were taken retrospectively to obtain left atrial and ventricular diameters and interventricular septal and posterior wall thicknesses. Histologic examinations were made from the left ventricular myocardial specimens of 15 patients at the times of insertion and explanation for heart transplantation. Insertion and explanation specimens were compared qualitatively (0 to 3 scale) for wavy fibers, contraction band necrosis and fibrosis, with quantitative measurement of minimal myocyte diameter across the nucleus. RESULTS: Left atrial and left ventricular diastolic and systolic diameters decreased immediately after insertion of the left ventricular assist device (from 46 to 35, 63 to 41 and 59 to 36 mm, respectively, all p < 0.001). Left ventricular wall thickness increased from 10 to 14 mm (p < 0.001) for the interventricular septum and from 10 to 13 mm for the posterior wall (p<0.001). No echocardiographic measurements showed significant subsequent changes at the chronic stage. Myocardial histologic findings demonstrated a reduction in myocyte damage (from 1.9 to 0.5, p<0.001, for wavy fiber and from 1.3 to 0.2, p<0.01, for contraction band necrosis) and an increase in fibrosis (from 1.3 to 1.9, p<0.05), but without significant change in myocyte diameter (from 15.6 to 16.8 micrometer, p=0.065). CONCLUSIONS: Left ventricular unloading with the implantable assist device induces an immediate increase in wall thickness, consistent with the reduction in chamber size, thereby decreasing wall stress. Chronic unloading allows myocardial healing and fibrosis without evidence for ongoing myocyte damage or atrophy. Left ventricular assist device insertion may have a role in "resting" the ventricle for selected patients with heart failure.

Noninvasive assessment of left atrial maximum dP/dt by a combination of transmitral and pulmonary venous flow.

OBJECTIVES: The study assessed whether hemodynamic parameters of left atrial (LA) systolic function could be estimated noninvasively using Doppler echocardiography. BACKGROUND: Left atrial systolic function is an important aspect of cardiac function. Doppler echocardiography can measure changes in LA volume, but has not been shown to relate to hemodynamic parameters such as the maximal value of the first derivative of the pressure (LA dP/dt(max)). METHODS: Eighteen patients in sinus rhythm were studied immediately before and after open heart surgery using simultaneous LA pressure measurements and intraoperative transesophageal echocardiography. Left atrial pressure was measured with a micromanometer catheter, and LA dP/dt(max) during atrial contraction was obtained. Transmitral and pulmonary venous flow were recorded by pulsed Doppler echocardiography. Peak velocity, and mean acceleration and deceleration, and the time-velocity integral of each flow during atrial contraction was measured. The initial eight patients served as the study group to derive a multilinear regression equation to estimate LA dP/dt(max) from Doppler parameters, and the latter 10 patients served as the test group to validate the equation. A previously validated numeric model was used to confirm these results. RESULTS: In the study group, LA dP/dt(max) showed a linear relation with LA pressure before atrial contraction (r = 0.80, p < 0.005), confirming the presence of the Frank-Starling mechanism in the LA. Among transmitral flow parameters, mean acceleration showed the strongest correlation with LA dP/dt(max) (r = 0.78, p < 0.001). Among pulmonary venous flow parameters, no single parameter was sufficient to estimate LA dP/dt(max) with an r2 > 0.30. By stepwise and multiple linear regression analysis, LA dP/dt(max) was best described as follows: LA dP/dt(max) = 0.1 M-AC +/- 1.8 P-V - 4.1; r = 0.88, p < 0.0001, where M-AC is the mean acceleration of transmitral flow and P-V is the peak velocity of pulmonary venous flow during atrial contraction. This equation was tested in the latter 10 patients of the test group. Predicted and measured LA dP/dt(max) correlated well (r = 0.90, p < 0.0001). Numerical simulation verified that this relationship held across a wide range of atrial elastance, ventricular relaxation and systolic function, with LA dP/dt(max) predicted by the above equation with r = 0.94. CONCLUSIONS: A combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of LA systolic function.

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.

Regional heterogeneity of function in nonischemic dilated cardiomyopathy.

OBJECTIVE: To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS: MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS: DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS: A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

Intra-arterial thrombolysis for perioperative stroke after open heart surgery.

Recent major surgery is an exclusion criterion for thrombolysis. Six patients with acute ischemic stroke underwent intra-arterial thrombolysis after recent open heart surgery without clinically significant bleeding complications, although one patient developed a small, asymptomatic cerebellar hemorrhage. Intra-arterial thrombolysis may be an option for patients with cerebral embolism in the perioperative period.