Sporadic and rapidly progressive arrhythmogenic right ventricular cardiomyopathy in a 12-year-old boy who was diagnosed with epilepsy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the leading causes of sudden cardiac death amongst young people and athletes. In this genetic disease, arrhythmia and fibro-fatty changes in the right ventricular myocardium are the main characteristics of the disease. Here, we report a case of ARVC in a 12-year-old boy who was previously diagnosed with epilepsy, the patient's condition manifested sporadically and was complicated by rapid progression, and unfortunate fatal deterioration after admission into the pediatric emergency room due to fatigue, dizziness and palpitation. A diagnosis of ARVC was established, even though a family history was absent. Due to possible rapid deterioration, as described in this case, we recommend immediate primary and secondary prevention of arrhythmias in these patients, and to take in consideration of the potential risks of using sodium valproate in these patients.

Epigastric pain associated with herpes esophagitis: case report.

BACKGROUND: Herpes esophagitis is uncommon disease caused by Herpes simplex virus (HSV). While the disease most often occurs in immunocompromised patients, including post-chemotherapy, immunosuppression with organ transplants, and in AIDS, Herpes esophagitis can also occur in immunocompetent individuals. CASE PRESENTATION: We report a case of herpes esophagitis in a 72 year- old woman who was presumed to be immunocompromised following prolonged radiotherapy and chemotherapy for lymphoma. Her main symptom was epigastric pain. Upper endoscopy showed multiple rounded ulcers in lower esophagus. The diagnosis was confirmed histologically by multiple biopsies. The patient received Valacyclovir for 2 weeks and started to get better within 3 days of treatment. CONCLUSION: Although there are few published cases of Herpes esophagitis disease in the medical literature, we recommend that this disease should be considered as one of the differential diagnoses when assessing immuno-compromised patients presenting with non-specific abdominal symptoms.

A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole-Genome Sequencing.

In many countries, Mycobacterium tuberculosis isolates are routinely subjected to variable-number tandem-repeat (VNTR) typing to investigate M. tuberculosis transmission. Unexpectedly, cross-border clusters were identified among African refugees in the Netherlands and Denmark, although transmission in those countries was unlikely. Whole-genome sequencing (WGS) was applied to analyze transmission in depth and to assess the precision of VNTR typing. WGS was applied to 40 M. tuberculosis isolates from refugees in the Netherlands and Denmark (most of whom were from the Horn of Africa) that shared the exact same VNTR profile. Cluster investigations were undertaken to identify in-country epidemiological links. Combining WGS results for the isolates (all members of the central Asian strain [CAS]/Delhi genotype), from both European countries, an average genetic distance of 80 single-nucleotide polymorphisms (SNPs) (maximum, 153 SNPs) was observed. The few pairs of isolates with confirmed epidemiological links, except for one pair, had a maximum distance of 12 SNPs. WGS divided this refugee cluster into several subclusters of patients from the same country of origin. Although the M. tuberculosis cases, mainly originating from African countries, shared the exact same VNTR profile, most were clearly distinguished by WGS. The average genetic distance in this specific VNTR cluster was 2 times greater than that in other VNTR clusters. Thus, identical VNTR profiles did not represent recent direct M. tuberculosis transmission for this group of patients. It appears that either these strains from Africa are extremely conserved genetically or there is ongoing transmission of this genotype among refugees on their long migration routes from Africa to Europe.

LONG-TERM OUTCOMES AND INCIDENCE OF RECURRENCE OF NEOVASCULARIZATION IN TREATED EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the long-term visual outcome and incidence of recurrence of neovascular age-related macular degeneration (NAMD) treated with intravitreal anti-VEGF injections (IVAI). METHODS: One hundred and thirty-two consecutive eyes treated with IVAI for NAMD based on an as-needed regimen with a follow-up ≥5 years (mean 7.55, range 5-9.67) were retrospectively reviewed. Main outcome measures included visual acuity, yearly number of IVAI, and occurrence of a long-term remission, defined as no recurrence of NAMD for ≥12 consecutive months. RESULTS: Mean baseline visual acuity was 20/100. Mean final visual acuity change was -3.41 letters. Mean overall IVAI number was 22.8 ± 17.4 (range 2-71), decreasing from 4.6 during Year 1 to 2.21 during Year 8. A significant positive correlation was found between the number of IVAI during the first year of treatment and the overall number of IVAI during 5 years, 6 years, 7 years, or 8 years follow-up (r = 0.67-0.70, P <0.0001). Long-term remission occurred at least once in 83/132 eyes (63%) and was associated with a better visual outcome (-1.04 vs. -7.43 letters, P = 0.034). Incidence of yearly remission of NAMD increased from 28% during Year 2 to 59% during Year 8, fitting along a single straight line (+5.231%/year, R = 0.9511). CONCLUSION: The incidence of recurrence of treated NAMD decreases slowly but steadily during follow-up. The number of years of follow-up is the main factor to assess the proportion of treated eyes at remission at a given moment. Incidence of recurrence of neovascularization during year 1 and length of follow-up are significant factors when tailoring an optimal long-term follow-up regimen.

Intertrochanteric fracture under an arthrodesed hip.

PATIENT: Female, 30. PRIMARY DIAGNOSIS: Intertrochanteric fracture under an arthrodesed hip. CO-EXISTING DISEASES: Developmental dysplasia of the hip. MEDICATION: Pain • inability to walk. CLINICAL PROCEDURE: Open reduction and internal fixation. SPECIALTY: Orthopedics and traumatology. OBJECTIVE: Rare disease, Unusual setting of medical care. BACKGROUND: An intertrochanteric fracture among elderly people is common, but it is rare to see such a fracture under a longstanding hip arthrodesis. Its surgical management represents a real challenge to orthopedic surgeons. CASE REPORT: A 30-year-old female teacher with long-standing hip arthrodesis was involved in a traffic accident. Clinical and radiological examination revealed the presence of a displaced intertrochanteric fracture under an arthrodesed hip and high neck shaft angle. Before embarking on surgery, we have to consider many factors such as patient personality (a young active and ambitious woman) and the mature of the fracture (a displaced fracture, coxa valga, and atrophied muscles). After a deep discussion and evaluation of the available devices, we selected a heavy duty locked plate and cannulated screws to fix the fracture. CONCLUSIONS: Because of the rarity of intertrochanteric fracture under an arthrodesis hip, the proper surgical treatment is controversial. Nevertheless, we were fortunate in successfully treating this unusual fracture using a locked plate and cannulated screws, which are implants that can be useful in treatment of such fractures.

Comparison of 2 types of intrastromal corneal ring segments for keratoconus.

PURPOSE: To assess the effectiveness and safety of 2 types of 6.0 mm intrastromal corneal ring segments (ICRS) in patients with mild to severe keratoconus. SETTING: Lebanese American University, Beirut, Lebanon. DESIGN: Retrospective comparative case series. METHODS: Eyes had implantation of Intacs SK ICRS (Group 1) or Keraring SI6 ICRS (Group 2). Visual acuity (logMAR), refraction, keratometry, and higher-order aberrations were compared 6 months and 1 year postoperatively. RESULTS: Group 1 comprised 66 eyes and Group 2, 107 eyes. The groups were comparable preoperatively. One-year postoperatively, the mean uncorrected distance visual acuity improved by 0.62 logMAR ± 0.19 (SD) in Group 1 and by 0.67 ± 0.17 logMAR in Group 2 (P=.211). The mean corrected distance visual acuity improved by 0.12 ± 0.11 logMAR and by 0.08 ± 0.13, respectively (P=.301). The spherical equivalent decreased by a mean of 2.80 ± 2.87 D and 2.65 ± 3.00 D, respectively (P=.572). Keratometry (K) flat and K steep decreased by a mean of 1.51 ± 1.57 D and 2.24 ± 1.61 D, respectively, in Group 1 and by 1.10 ± 2.00 D and 1.44 ± 1.64 D, respectively, in Group 2 (P=.667 and P=.184, respectively). Primary coma root mean square decreased by a mean of 1.09 ± 0.66 µm in Group 1 and 0.99 ± 0.72 µm in Group 2 (P=.716). CONCLUSION: Both ICRS models significantly improved visual function in patients with keratoconus, with comparable postoperative profiles and no major complications. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Surgical management of low grade isthmic spondylolisthesis; a randomized controlled study of the surgical fixation with and without reduction.

BACKGROUND: spondylolisthesis is a condition in which a vertebra slips out of the proper position onto the bone below it as a result of pars interarticularis defect. The slipped segment produces abnormal positioning of the vertebrae in relation to each other along the spinal column and causes mechanical back pain and neural breach. MATERIALS AND METHODS: A randomized and double blinded study consisted of 41 patients aged 36-69 years (18 females and 28 males) treated for symptomatic spondylolisthesis between December,2006 and December, 2009. All patients were randomly distributed into two groups I and II. Twenty patients were in Group I; they underwent reduction of the slipped vertebrae by using Reduction-Screw Technique and posterior lumbar interbody fixation (PLIF). Group II consisted of twenty one patients who underwent only surgical fixation (PLIF) without reduction. All patients in this study had same pre and post operative management. RESULTS: only one case had broken rod in group I that required revision. Superficial wound infection was experienced in two patients and one patient, from group II, developed wound hematoma. The outcome in both groups was variable on the short term but was almost the same on the long term follow up. CONCLUSION: surgical management of symptomatic low grade spondylolisthesis should include neural decompression and surgical fixation. Reduction of slipped vertebral bodies is unnecessary as the ultimate outcome will be likely similar.

Efficacy of laser in situ keratomileusis in correcting anterior and non-anterior corneal astigmatism: comparative study.

PURPOSE: To compare the efficacy of conventional laser in situ keratomileusis (LASIK) in treating corneal astigmatism and in treating noncorneal ocular residual astigmatism. SETTING: Private practice, Nashville, Tennessee, USA. DESIGN: Retrospective case series. METHODS: The records of dominant eyes of consecutive patients who had LASIK were retrospectively analyzed to compare the efficacy of LASIK in eyes with predominantly anterior corneal astigmatism with the efficacy in eyes with predominantly ocular residual astigmatism (ORA). The ORA was determined by vector analysis using refractive cylinder and topographic astigmatism. Preoperatively, the ratio of ORA to preoperative refractive cylinder (R) was used to divide the patients into 2 groups; that is, eyes with predominantly anterior corneal astigmatism (ORA/R ratio <1.0) and eyes with predominantly ORA (ORA/R ratio ≥1.0). Efficacy was determined by examining the magnitude of the remaining uncorrected astigmatism and comparing the index of success (proportion of preoperative refractive astigmatism that remained uncorrected by LASIK) between the 2 groups. RESULTS: The study evaluated 61 eyes of 61 patients. Conventional LASIK was twice as efficacious in the low-ORA group as in the high-ORA group. The index of success was 0.24 and 0.50, respectively, and the difference between groups was statistically significant (P = .036). CONCLUSION: The efficacy of astigmatic correction by LASIK was significantly higher in eyes in which the preoperative refractive astigmatism was located mainly on the anterior corneal surface than in eyes in which it was mainly located posterior to the anterior corneal surface.

Unusual case of difficult double-lumen endotracheal tube removal.

A reusable Robertshaw red rubber double-lumen endotracheal tube (DLT) was placed to facilitate lung isolation for thoracoscopy in a 49-year-old atopic patient. In spite of its smooth insertion, it was then not possible to remove the DLT. Direct laryngoscopy showed severe laryngeal edema. After 48 hours of medical treatment with steroids, the trachea was extubated. The laryngeal edema could have been the result of physical and chemical irritation by the reusable rubber DLT itself, or from the substances formed during repeated cleaning and sterilization of the DLT. Atopic patients who are prone to developing latex allergy are also more liable to develop severe reactions to chemical, mechanical, and physical irritation from reusable red rubber DLTs or from the chemical solution used for its cleaning and sterilization.

Improvement in glycemic control in morbidly obese type 2 diabetic subjects by gastric stimulation.

BACKGROUND: Gastric electrical stimulation synchronized to the refractory period of gastric electrical activity and applied during meals was evaluated for safety and for improvement of body weight and glycemic control in obese type 2 diabetes. METHODS: The study involved obese diabetic type 2 (ODM) patients in a multicenter open-label European feasibility trial. A total of 24 ODM (nine males, 15 females) treated with insulin and/or oral hyperglycemic agents and body mass index between 33.3 to 49.7 kg/m(2) were implanted laparoscopically with a TANTALUS system. RESULTS: There were 18 adverse events related to the implant procedure or the device reported in 12 subjects. All were short lived and resolved with no sequelae. In the 21 subjects that reached the 1-year visit weight was reduced by 4.5 +/- 2.7 kg (p < 0.05) and HbA1c by 0.5 +/- 0.3% (p < 0.05). In a subgroup (n = 11) on stable or reduced oral medication, weight was reduced by 6.3 +/- 3.4 kg (p < 0.05) and HbA1c by 0.9 +/- 0.4% (p < 0.05). The group on insulin (n = 6) had no significant changes in weight and HbA1c. CONCLUSIONS: The TANTALUS system is well tolerated in obese type 2 diabetic subjects. Gastric electrical stimulation can potentially improve glucose metabolism and induce weight loss in obese diabetic patients, who are not well controlled on oral antidiabetic therapy. Further evaluation is required to determine whether this effect is due to induced weight loss and/or to direct signal dependent mechanisms.

Treatment of type 2 diabetes using meal-triggered gastric electrical stimulation.

BACKGROUND: The TANTALUS System (MetaCure Limited) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date. OBJECTIVES: To re-analyze previously reported datafrom different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterized the significance of baseline A1c in the determination of the expected clinical outcome. METHODS: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., we identified 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM on a stable regime of oral medication for 3 months prior to implant. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline. RESULTS: Data after 24 weeks demonstrated a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 +/- 0.1%. The average weight loss was 5.5 +/- 0.7 kg. CONCLUSIONS: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Electrical stimulation of the gut for the treatment of type 2 diabetes: the role of automatic eating detection.

BACKGROUND: Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes. METHODS: Obese T2DM (n = 12) were implanted with gastric leads and the TANTALUS device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake. RESULTS: The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated (R(2) = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was -1 +/- 0.4%) but not with changes in body weight (average drop -4.7 +/- 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction (R(2) = 0.27, p < 0.05). CONCLUSIONS: Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.

Association between gastric electromechanical activity and satiation in dogs.

OBJECTIVE: The objective of this study was to validate the use of impedance for measurement of antral contractions and to determine the relationship between food-induced changes in gastric motility and satiation. RESEARCH METHODS AND PROCEDURES: In Experiment 1, three dogs were implanted with an antral strain gauge and bipolar electrodes for measurement of local tissue impedance. Impedance and strain gauge recordings were obtained simultaneously during antral contractions to correlate impedance changes with contractile events. In Experiment 2, seven dogs were implanted with two pairs of gastric electrodes for simultaneous recording of slow wave activity and impedance. The changes in the rate of slow waves and of antral contractions assessed by impedance during food intake were characterized. RESULTS: Variations in strain gauge amplitude were highly correlated with changes in antral impedance (R2: 0.70 to 0.82, p < 0.05). In Experiment 2, slow wave rate was significantly reduced after food intake and reached a nadir at satiation (5.0 +/- 0.3 vs. 3.8 +/- 0.5 events/min, p < 0.001). Likewise, the amplitude of antral contractions assessed by variations in impedance was significantly increased after food intake, peaking at satiation (5.3 +/- 1.4 vs. 12.2 +/- 4.3 Ohms, p < 0.01). DISCUSSION: Measurement of impedance is a reliable tool for assessing gastric contractility. Food ingestion significantly reduces slow wave rate and enhances antral contractions. Peak changes in these two variables occur at the time of satiation. Electrical measurements of both slow waves and impedance may be used to estimate gastric motility and satiation.

The TANTALUS system for obesity: effect on gastric emptying of solids and ghrelin plasma levels.

BACKGROUND: Gastric electrical stimulation (GES), using the implantable TANTALUS System, is being explored as a treatment for obesity. The system delivers nonstimulatory electrical signals synchronized with gastric slow waves, resulting in stronger contractions. We hypothesized that this GES may enhance gastric emptying and as a result affect plasma ghrelin and insulin homeostasis. The aim was to test the effect of GES on gastric emptying of solids and on ghrelin and insulin blood levels in obese subjects. METHODS: The system consists of 3 pairs of gastric electrodes connected to an implantable pulse generator. Gastric emptying test (GE) of solids was performed twice, on separate days, a few weeks after implantation, before and after initiation of stimulation. Blood samples for ghrelin and insulin were taken at baseline and at 15, 30, 60 and 120 min after the test meal. RESULTS: There were 11 females, 1 male, mean age 39.1 +/- 8.9 years, mean BMI 41.6 +/- 3.4. Data is available from 11 subjects; GE was normal in 9 subjects and accelerated in 2 subjects. GES significantly accelerated GE compared to control: percent retention at 2 hours 18.7 +/- 12.2 vs 31.9 +/- 16.4, respectively (P < 0.01). Overall, there was no significant change in ghrelin or insulin profile after food intake. Ghrelin levels fell significantly at 60 min compared to baseline during stimulation (P = 0.014) and control (P = 0.046). CONCLUSION: GES results in a significant acceleration of gastric emptying of solids in obese subjects. GES did not have a significant effect on postprandial ghrelin levels when compared to control.

Photodynamic therapy vs limited macular translocation in the management of subfoveal choroidal neovascularization in pathologic myopia: a two-year study.

PURPOSE: To compare the results of limited macular translocation and photodynamic therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of nonrandomized interventional clinical study. METHODS: Retrospective review of 66 consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by PDT and 32 operated on with the translocation technique. Translocation was considered principally when the lesion size was adequate (nasal inferior margin of the membrane less than half a disk diameter away from the center of the fovea) with duration of symptoms of less than four months. Main outcome measure was the postoperative change in visual acuity. RESULTS: In the translocation group, mean gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8 line, respectively, P = .001). In the translocation group, 55% of eyes gained 3 lines or more at two years compared with 10% in the PDT group. Sixty percent of eyes in the translocation group vs 40% in the PDT group had an improvement of at least five letters. Mean foveal displacement after translocation was 906 mum; postoperative complications included retinal detachment (three eyes), macular fold (one eye), and transient diplopia (four eyes). In young patients, the postoperative gain was better in both groups. In the translocation group, mean survival time for choroidal neovascularization recurrence was 40 months for patients younger than 40 years and 20 months for older patients. CONCLUSIONS: Translocation showed better results than PDT at two years. Further studies are required to confirm these findings.

Assessment of the corneal endothelium in acute ultraviolet keratitis.

BACKGROUND: The purpose of this prospective case-control study was to investigate whether exposure to ultraviolet (UV) light produces detectable damage to the corneal endothelium in patients presenting with acute UV keratitis. MATERIAL/METHODS: Non-contact specular microscopy was performed on 20 consecutive patients who presented to our clinic from July 2000 to July 2002 with acute UV keratitis and similarly on 20 age-matched healthy controls. Both the coefficient of variation in mean cell size (CV) and the mean cell density (CD) were compared in these two groups using the Student t-test. RESULTS: Mean age was 28.6 years in the study group and 28.4 years in the control group. The mean CD in the patient group was 2609.6 (SD = 103.47) and in the control group 2632.87 (SD = 117.05). No statistically significant difference was found between the mean CDs in these two groups (p = 0.93). The mean CV in the patient group was 46.7 (SD = 4.40) and in the control group 45.4 (SD = 5.60). Similarly, there was no statistically significant difference between the mean CVs in these two groups (p = 0.85). CONCLUSIONS: UV light exposure does not seem to have a direct immediate effect on the corneal endothelium in humans with acute UV keratitis. Whether UV light produces cumulative and/or longer-term damage requires further studies with a larger number of patients and a longer follow-up time.

LASIK for high myopic astigmatism resulting from perforating ocular injury.

PURPOSE: To present a case of successful treatment of high myopic astigmatism after a perforating injury with significant corneal laceration and pupil ectopia using excimer LASIK. METHODS: A 30-year-old man presented for treatment of high myopic astigmatism in his right eye resulting from perforating ocular trauma, which occurred 8 years prior to presentation. The corneoscleral wound repair was performed with posterior chamber intraocular lens implantation. Uncorrected visual acuity (UCVA) in the right eye was counting fingers at 1 m, best corrected to 20/30 with -7.00 + 5.00 x 110. Visual acuity in the left eye was 20/20 with -1.5 D. The patient was unable to tolerate spectacles and contact lenses because of asthenopia and high astigmatism, respectively. As an alternative, LASIK with the Allegretto Wave excimer laser was performed. RESULTS: Three months postoperatively, UCVA was 20/25 in the right eye and 20/15 in the left eye. CONCLUSIONS: This case indicates that LASIK can be a useful surgical method for correcting high myopic astigmatism resulting from ocular trauma with significant corneoscleral laceration.

Corneal intrastromal gatifloxacin crystal deposits after penetrating keratoplasty.

BACKGROUND: An 85-year-old man developed faint crystallike white precipitates in the mid peripheral stroma of his left cornea 3 weeks after undergoing penetrating keratoplasty. The patient had been initially treated with 1% prednisolone acetate ophthalmic suspension and 0.3% gatifloxacin eyedrops to his left eye from the first day postoperatively. Three weeks later, the precipitates were more numerous, larger, and diffuse in distribution. Gatifloxacin was discontinued and substituted with a neomycin-polymixin B-dexamethasone ophthalmic ointment. METHODS: A detailed history, physical examination, laboratory workup, and tandem scanning confocal microscopy were performed. RESULTS: Tandem scanning corneal confocal microscopy confirmed the presence of crystals in the cornea. CONCLUSIONS: Gatifloxacin, a fourth-generation fluoroquinolone, can cause intrastromal macroscopic crystalline deposits through a compromised corneal epithelium, similar to what has been described for ciprofloxacin, a second-generation fluoroquinolone.

Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs.

OBJECTIVE: We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS: Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. RESULTS: In control dogs, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV) increased (64+/-5 ml vs. 75+/-6 ml, P=0.003; 46+/-4 ml vs. 57+/-4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28+/-1% vs. 23+/-1%, P=0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66+/-4 vs. 73+/-5 ml, P=0.01), no change in ESV, and an increase in EF from 31+/-1 to 34+/-2% (P=0.04) after 3 months of therapy. CONCLUSIONS: In dogs with HF, long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.