Bariatric surgery, osteoarthritis and arthroplasty of the hip and knee in Swedish Obese Subjects - up to 31 years follow-up of a controlled intervention study.

OBJECTIVE: To study the long-term effect of obesity and bariatric surgery on incidences of osteoarthritis and arthroplasty of hip and knee. DESIGN: Hazard ratios (HR) and incidence rates (IR) of osteoarthritis and arthroplasty of hip and knee were studied in the prospective, controlled, non-randomized Swedish Obese Subjects (SOS) study (bariatric surgery group, n = 2007; matched controls given usual obesity care, n = 2040) and the SOS reference cohort (n = 1135, general population). Osteoarthritis diagnosis and arthroplasty for osteoarthritis were captured from the National Swedish Patient Register. Median follow-up time was 21.2 (IQR 16.4-24.8), 22.9 (IQR 19.1-25.7), and 20.1 years (IQR 18.7-20.9) for the control group, surgery group and reference cohort, respectively. RESULTS: The surgery group displayed lower incidence of hip osteoarthritis (IR 5.3, 95% CI 4.7-6.1) compared to controls (IR 6.6, 95% CI 5.9-7.5, adjHR 0.83, 95% CI 0.69-1.00) but similar incidence of hip arthroplasty. Similar incidence of knee osteoarthritis was observed in the surgery group and controls, but knee arthroplasty was more common in the surgery group (IR 7.4, 95% CI 6.6-8.2 and 5.6, 95% CI 4.9-6.4, adjHR 1.45, 95% CI 1.22-1.74). The reference cohort displayed lower incidences of osteoarthritis and arthroplasty of hip and knee compared with the surgery group and controls. CONCLUSION: Bariatric surgery did not normalize the increased risk of knee and hip osteoarthritis in patients with obesity but was associated with an increased incidence of knee arthroplasty compared to the control group. With the limitations inherent to the present data, additional studies are needed to confirm these results. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01479452.

Elevated adiponectin predicts the development of rheumatoid arthritis in subjects with obesity.

Objective The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results During a follow-up for up to 29 years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12-2.60 for an increase in adiponectin of 10 mg/L, p = 0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25-6.31, p = 0.01). Conclusions In this cohort of subjects with obesity followed up for up to 29 years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452.

Allergic disease in 8-year-old children is preceded by delayed B cell maturation.

BACKGROUND: We previously reported that exposure to a farming environment is allergy-protective, while high proportions of neonatal immature/naïve CD5+ B cells and putative regulatory T cells (Tregs) are risk factors for development of allergic disease and sensitization up to 3 years of age. OBJECTIVE: To examine if B and T cell maturation are associated with allergic disease and farming environment over the first 8 years in life. METHODS: In the prospective FARMFLORA study, including both farming and non-farming families, 48 of 65 children took part in the 8-year follow-up study. Various B and T cell maturation variables were examined in blood samples obtained at several occasions from birth to 8 years of age and related to doctors' diagnosed allergic disease and sensitization, and to farming environment. RESULTS: We found that the incidence of allergic disease was lower among farmers' compared to non-farmers' children during the 8-year follow-up period, and that farmers' children had higher proportions of memory B cells at 8 years of age. Moreover, a high proportion of neonatal CD5+ B cells was a risk factor for and may predict development of allergic disease at 8 years of age. A high proportion of Tregs was not protective against development of these conditions. CONCLUSION AND CLINICAL RELEVANCE: High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment.

The incidence of albuminuria after bariatric surgery and usual care in Swedish Obese Subjects (SOS): a prospective controlled intervention trial.

BACKGROUND: Obesity is associated with increased risk of chronic kidney disease and albuminuria is a predictor of renal impairment. Bariatric surgery reduces body weight in obese subjects, but it is not known whether surgery can prevent development of albuminuria. This study aims to determine the long-term effect of bariatric surgery on the incidence of albuminuria. SUBJECTS: The Swedish Obese Subjects study is a non-randomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden. Between 1 September 1987 and 31 January 2001, 2010 participants who underwent bariatric surgery and 2037 controls were recruited. Inclusion criteria were age 37-60 years and BMI ⩾ 34 in men and BMI ⩾ 38 in women. In this analysis, we included 1498 patients in the surgery group and 1610 controls without albuminuria at baseline. Patients in the bariatric surgery group underwent banding (18%), vertical banded gastroplasty (69%) or gastric bypass (13%); controls received usual obesity care. Date of analysis was 1 January 2011. Median follow-up was 10 years, and the rates of follow-up were 87%, 74 and 52% at 2, 10 and 15 years, respectively. The main outcome of this report is incidence of albuminuria (defined as urinary albumin excretion >30 mg per 24 h) over up to 15 years. RESULTS: During the follow-up, albuminuria developed in 246 participants in the control group and in 126 in the bariatric surgery group, corresponding to incidence rates of 20.4 and 9.4 per 1000 person years, respectively (adjusted hazard ratio, 0.37; 95% confidence interval, 0.30-0.47; P < 0.001). The expected number of surgeries needed to prevent the development of albuminuria in one patient at 10 years was nine. CONCLUSIONS: Bariatric surgery is associated with reduced incidence of albuminuria compared with usual obesity care.

Genetic diagnosis of familial hypercholesterolaemia by targeted next-generation sequencing.

OBJECTIVES: The aim of this study was to combine clinical criteria and next-generation sequencing (pyrosequencing) to establish a diagnosis of familial hypercholesterolaemia (FH). DESIGN, SETTING AND SUBJECTS: A total of 77 subjects with a Dutch Lipid Clinic Network score of ≥ 3 (possible, probable or definite FH clinical diagnosis) were recruited from the Lipid Clinic at Sahlgrenska Hospital, Gothenburg, Sweden. Next-generation sequencing was performed in all subjects using SEQPRO LIPO RS, a kit that detects mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDLR adapter protein 1 (LDLRAP1) genes; copy-number variations in the LDLR gene were also examined. RESULTS: A total of 26 mutations were detected in 50 subjects (65% success rate). Amongst these, 23 mutations were in the LDLR gene, two in the APOB gene and one in the PCSK9 gene. Four mutations with unknown pathogenicity were detected in LDLR. Of these, three mutations (Gly505Asp, Ile585Thr and Gln660Arg) have been previously reported in subjects with FH, but their pathogenicity has not been proved. The fourth, a mutation in LDLR affecting a splicing site (exon 6-intron 6) has not previously been reported; it was found to segregate with high cholesterol levels in the family of the proband. CONCLUSIONS: Using a combination of clinical criteria and targeted next-generation sequencing, we have achieved FH diagnosis with a high success rate. Furthermore, we identified a new splicing-site mutation in the LDLR gene.

Laparoscopic sleeve gastrectomy as first stage or definitive intent in 300 consecutive cases.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) was originally used as a bridge to definitive surgery in high-risk patients. Recently it has been considered as a stand-alone procedure due to its effectiveness on weight loss and comorbidities resolution. This study was designed to evaluate the results of SG on complications, body mass index (BMI), and comorbidities resolution in 300 consecutive obese patients and to analyze the lesson learned from this experience. METHODS: From October 2002 to November 2009, 300 patients underwent SG. In the first 100 cases (group 1: mean BMI, 54.4±9.3), SG was intended as a first stage of biliopancreatic diversion with duodenal switch in high risk super-obese patients. In the last 200 cases (group 2: mean BMI, 45.5±7.3), SG was intended as a definitive procedure. No routine reinforcement was performed in group 1. In group 2, oversewn reinforcement was performed routinely. SG was redo surgery in 21 patients (7%). RESULTS: Mean operative time was 119±48.6 min in group 1 and 72±33.8 in group 2. Conversion rate was 0.6% (massive hepatomegaly). Mortality was 0.6%. Major postoperative complications were registered in 15 patients in group 1 and 11 in group 2. In 3 cases, a reoperation was needed. The mean BMI in group 1 was 46, 43, 39, and 31 at 6, 12, 24, and 36 months, respectively. In group 2, the mean BMI was 32.9, 30.6, and 31.7 at 6, 12, and 18 months. At 12 months, the diabetes, hypertension, and OSAS were cured on 69%, 62%, and 50% in group 1 and 88%, 57%, and 58% in group 2. In group 2, no patient required second stage. CONCLUSIONS: SG is a safe and effective treatment for morbid obesity at mid-term follow-up. SG is effective for comorbidities resolution, especially for the treatment of diabetes. Suture line reinforcement allows a significant reduction of bleeding.

First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis.

BACKGROUND: The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes. METHODS: Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined. RESULTS: In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups. CONCLUSIONS: Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent.

CONTEXT: The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic steatosis. Intriguingly, initial findings in cohorts with a mean body mass index (BMI) of 30 kg m(-2) also suggested that it is associated with elevated liver enzymes but not with insulin resistance and dyslipidaemia. OBJECTIVE: To determine whether the PNPLA3 variant alters the susceptibility of morbidly obese subjects to develop liver injury and metabolic sequelae. PARTICIPANTS AND METHODS: The study was carried out in 678 obese Italians (mean BMI = 41 kg m(-2)) who were genotyped for the I148M variant. All participants provided fasting blood samples and then underwent oral glucose tolerance tests. MAIN OUTCOME MEASURES: Indices of liver injury (alanine transaminase (ALT), aspartate transaminase (AST)), glucose tolerance and insulin resistance were measured. RESULTS: Markers of hepatic injury such as ALT and AST were significantly higher in carriers of the 148M allele (P = 2.2 x 10(-5) and 0.001, respectively). In all, 50% of 148M risk allele homozygotes had pathological levels of ALT (>40 U l(-1)) compared with 25% of 148I allele homozygotes (P = 0.005). Glucose tolerance and insulin sensitivity were similar in all three genotypes. CONCLUSION: Obese Southern Europeans carrying the 148M allele have increased indices of liver damage uncoupled from proxy measures of insulin resistance.

Floral transition and nitric oxide emission during flower development in Arabidopsis thaliana is affected in nitrate reductase-deficient plants.

The nitrate reductase (NR)-defective double mutant of Arabidopsis thaliana (nia1 nia2) has previously been shown to present a low endogenous content of NO in its leaves compared with the wild-type plants. In the present study, we analyzed the effect of NR mutation on floral induction and development of A. thaliana, as NO was recently described as one of the signals involved in the flowering process. The NO fluorescent probes diaminofluorescein-2 diacetate (DAF-2DA) and 1,2-diaminoanthraquinone (1,2-DAA) were used to localize NO production in situ by fluorescence microscopy in the floral structures of A. thaliana during floral development. Data were validated by incubating the intact tissues with DAF-2 and quantifying the DAF-2 triazole by fluorescence spectrometry. The results showed that NO is synthesized in specific cells and tissues in the floral structure and its production increases with floral development until anthesis. In the gynoecium, NO synthesis occurs only in differentiated stigmatic papillae of the floral bud, and, in the stamen, only anthers that are producing pollen grains synthesize NO. Sepals and petals do not show NO production. NR-deficient plants emitted less NO, although they showed the same pattern of NO emission in their floral organs. This mutant blossomed precociously when compared with wild-type plants, as measured by the increased caulinar/rosette leaf number and the decrease in the number of days to bolting and anthesis, and this phenotype seems to result from the markedly reduced NO levels in roots and leaves during vegetative growth. Overall, the results reveal a role for NR in the flowering process.

Preliminary experience with a hybrid nonthoracotomy defibrillating system that includes a biphasic device: comparison with a standard monophasic device using the same lead system.

OBJECTIVES: This study analyzed the advantage of combining a biphasic device with a transvenous system and compared the results with those obtained with a standard monophasic device. BACKGROUND: Available lead systems use monophasic pulses and may require lengthy intraoperative testing to achieve adequate defibrillation threshold in a conspicuous number of patients. The option of biphasic waveform may provide further benefits. However, clinical experience with a permanent implant is lacking. METHODS: Fifty-five patients underwent testing and received a permanent implant using the Endotak lead system associated with a CPI monophasic device. The remaining 36 patients received a permanent implant with the Endotak lead system connected to a biphasic device. In both groups a subcutaneous patch was combined when needed to obtain acceptable defibrillation thresholds. RESULTS: Biphasic pulses resulted in lower mean (+/- SD) defibrillation thresholds (monophasic 15 +/- 4.7 J vs. biphasic 12 +/- 5 J, p = 0.03) and a better implantation rate (100% biphasic vs. 89% monophasic, p = 0.07). Biphasic pulses allowed implantation with less ventricular fibrillation induction (7.4 +/- 3.2 vs. 3.5 +/- 1.8, p < 0.01) and a mean shorter procedure time (168 +/- 39 vs. 111 +/- 30 min, p < 0.01). With the biphasic waveform a greater proportion of patients met the implantation criteria with the lead system alone (83% vs. 45%, p < 0.01). When needed, the left prepectoral location of the patch electrode was always sufficient in left subscapular position was required in 15 patients in the monophasic group. Implantation of the biphasic device was associated with a shorter mean hospital stay (3.8 +/- 0.8 vs. 5.4 +/- 2.2 days, p < 0.01). CONCLUSIONS: Incorporation of a biphasic device in a transvenous implantable cardioverter-defibrillator uniformly increases the efficacy of the system and the ease of implantation.

Feasibility of atrial fibrillation detection and use of a preceding synchronization interval as a criterion for shock delivery in humans with atrial fibrillation.

OBJECTIVES: This study assessed the feasibility of detecting atrial fibrillation (AF) and delivery of appropriately timed R wave shocks using an implantable atrial defibrillator. BACKGROUND: For atrial defibrillation therapy to be feasible in an implantable form, AF must be detected in a specific fashion, and the risk of ventricular proarrhythmia should be minimized. METHODS: Eleven patients with AF underwent testing with an implantable atrial defibrillator (METRIX 3000 Automatic Atrial Defibrillator, InControl, Inc.). Wideband electrograms (EGMs) were recorded from the right ventricular (RV) bipolar catheter and from the multipolar catheters located in the right atrium (RA) and coronary sinus (CS). Atrial fibrillation detection was performed using two serial algorithms-quiet interval analysis and baseline crossing analysis-that detect atrial activity on the RA-CS channel. Ventricular sensing using a minimal preceding synchronization interval of 500 ms as a criterion for synchronous shock delivery was performed from filtered RV and RV-CS EGMs. RESULTS: The AF detection algorithms were applied to 53 AF data segments and 18 normal sinus rhythm data segments. Atrial fibrillation was detected appropriately in 49 instances, and the specificity for detecting AF and normal sinus rhythm was 100%. Synchronization criterion efficacy was assessed by delivering shock markers and shocks. Of the 2,025 R waves processed, 557 (27.5%) were marked as suitable for shock delivery. In addition, 69 therapeutic and 11 test shocks were delivered during AF. All shock markers and shocks were delivered synchronously with the R wave, and the synchronization criterion was never violated. CONCLUSIONS: Atrial fibrillation can be detected in a specific fashion using the RA-CS lead configuration and serial detection algorithms for atrial sensing. The delivery of properly timed shocks is feasible and should minimize the risk of ventricular proarrhythmia.

Recurrence of neurocardiogenic syncope without pharmacologic interventions.

In 54 patients with positive tilt and who refused medical therapy, we observed a significant decrease in the frequency of syncopal spells after diagnosis and counseling. However, symptoms were reported at follow-up by 64.8% of the patients and were predicted by the frequency and total number of syncope episodes before upright tilt.

Bariatric surgery: early results with a multidisciplinary team.

BACKGROUND: Bariatric surgery depends on complete preoperative study of morbid obesity, in order to obtain the treatment of choice. A multidisciplinary group was founded in 1998 at the University of Siena. METHODS: During 1998, 16 patients, with median weight 121.8 +/- 31 kg and median body mass index (BMI) 43 +/- 6, underwent bariatric surgery. A multidisciplinary assessment was used in order to evaluate psychological status, food intake problems and patient compliance, and hemodynamic, respiratory, metabolic and arthritic functions. 13 patients were submitted to laparoscopic surgery: in 11 adjustable gastric banding was performed and 2 were submitted to a vertical gastroplasty plus adjustable gastric banding. Three patients were operated via traditional laparotomy, due to previous abdominal surgery in 2 cases (submitted to an adjustable gastric banding) and one woman was submitted to a bilio-intestinal bypass according to the Hallberg technique, for her psychiatric troubles and coexisting systolic hypertension and uncontrolled diabetes. Monthly follow-up for each patient continues after 6 months. RESULTS: No morbidity or mortality has occurred. The median weight loss at three months, was 19.5 kg. Two cases required injection of 1 ml more of fluid into the port, respectively at 4 and 9 months. Fifteen days after surgery, seven patients (46%) had vomiting episodes, due to rapid food intake. All patients have shown an improvement of their comorbidities after surgery. CONCLUSION: Early results via the multidisciplinary team and laparoscopic banding have been satisfactory thus far.

Implantable atrial defibrillator and detection of atrial flutter.

The implantable atrial defibrillator (IAD) is designed to detect and treat atrial fibrillation (AF) with low energy synchronized shocks. A patient with a history of persistent AF was implanted with an IAD after ineffective treatment with procainamide and sotalol. Through four months of follow-up, the IAD performed appropriate detection and treatment of AF. During the fifth month, the patient was put on flecainide in an attempt to minimize the AF recurrence rate. On flecainide the patient experienced typical atrial flutter which required IAD reprogramming for appropriate detection and therapy delivery. This case report examines the optimization of the IAD to detect atrial flutter. Six months of follow-up after optimization the IAD has shown appropriate detection of both atrial flutter and AF. During the entire follow-up period the IAD had appropriate detection of sinus rhythm (no false positive detection, i.e. sinus rhythm as AF).

[Diverticulosis and neoplasms of the colon]. / Diverticolosi e neoplasie del colon.

About half of the carcinomas and polyps of the large intestine is placed in the descendent colon and in the sigma, where most frequently the diverticula are found. Literature refers to them as varying percentage of association diverticulosis-carcinoma between 2 to 8 percent. The increase of the frequency of neoplasms and diverticula in the same population classes may indicate common factors in their development. The study includes 1149 cases of colo-rectal neoplasms examined in the Department of Scienze Chirurgiche--University of Siena, from january 1981 to december 1993. The association of carcinomas and diverticula has been found in 8.96% of the cases (103 pts) and the tumours with stenosis in 59,2% of the cases. The colonoscopy is very important for a more precise differential diagnosis especially in occlusive forms, in which a multiple biopsy is indispensable. Referring to the data of literature, the authors consider that patients with symptomatic diverticular disease have a major general risk for cancer of the large intestine; the existence of certain common symptoms in either disease (especially the bleeding) may not exclude the presence of a tumor in patients with diverticular disease.

Prediction of QTc length as function of BMI: a clinical tool to establish arrhythmias risk in obesity.

AIMS: Among the electrocardiographic alterations used for stratifying the cardiovascular risk of life threatening arrhythmias (LFA) and sudden death (SD) there is the increment of the corrected QT(QTc). This increment is usually observable in obese patients (OP). Therefore, a study has been planned to investigate the possibility to predict QTc values in OP simply by detecting the best fitting regression method that represents the relationship between QTc and Body Mass Index (BMI). MATERIALS AND METHODS: The study has been carried on 144 individuals classified as a function of their BMI in normoponderal subjects (NPS, No. 24; F/M=15/9; BMI=21.8± 1.7 kg/m(2)), Class I OP (No. 24; F/M=17/7; BMI=32.5± 1.1 kg/m(2)); Class II OP (No. 24; F/M=17/7; BMI=37.7± 1.5 kg/m(2)). Class IIIa (No. 24, F/M=15/9; BMI=44.4± 27 kg/m(2)), Class IIIb (No. 24; F/M=14/10; BMI 54.3± 2.7 kg/m(2)); Class IIIc (No. 24; F/M=14/10; BMI=63.3± 4.5 kg/m(2)). Both linear and non-linear fitting modes have been tested. RESULTS: While the BMI progressively increases in classified OP, the QTc shows an intergroup difference that is not only not constant but also declining in Class IIIc obesity. The optimal regressive model was found to be the following fourth order degree polynomial: QTc=317,15+(7,47xBMI)+(-0,28*BMI(2))+(0,005xBMI(3))+ (-0,00003xBMI(4)). CONCLUSION: By entering the BMI of a given OP into the above-cited formula, the QTc can be easily predicted and compared to that of NPS. Importantly, to have the possibility for a pre-electrocardiographic estimation of QTc allows all the medical and paramedical personnel, involved in the multidisciplinary treatment of obesity, to immediately establish the cardiovascular risk in the OP under observation.

Ventricular fibrillation and polymorphic ventricular tachycardia with critical coronary artery stenosis: does bypass surgery suffice?

INTRODUCTION: Previous studies have suggested that coronary artery bypass surgery is sufficient to prevent recurrence of sudden death in patients with critical coronary artery stenosis presenting with ventricular fibrillation or polymorphic ventricular tachycardia. We present our experience in patients with one or more episodes of sudden death associated with documented ventricular fibrillation or polymorphic ventricular tachycardia and severe operable coronary artery disease who underwent defibrillator implant at the time of bypass surgery. METHODS AND RESULTS: Fifty-eight consecutive patients (age 63 +/- 8 years) were included in this study. Eighteen of the 58 patients had no evidence of previous myocardial infarction. The mean ejection fraction was 37 +/- 13%. All patients underwent electrophysiologic study before and after revascularization. At the time of first defibrillator discharge, each patient was reevaluated to exclude the presence of ischemia. The benefits of defibrillator implant were estimated comparing the projected survival based upon defibrillator discharge preceded by syncope or presyncope with survival curves generated including total death and sudden plus cardiac death. After a mean follow-up of 4.6 +/- 2 years, 22 patients received appropriate shocks preceded by syncope or presyncope, and an additional 19 patients received asymptomatic shocks. At 4 years, survival free of total death was 71.2%, and the projected survival was 58.8% (P < 0.05). Multivariate analysis showed that ejection fraction lower than 30% and induction of arrhythmia with one or two extrastimuli (S2, S3) were independent predictors for defibrillator discharge. None of the remaining variables including age, gender, number of bypasses, history of myocardial infarction, and type of arrhythmias induced were predictive for death and occurrence of shocks. CONCLUSIONS: In patients with ventricular fibrillation and polymorphic ventricular tachycardia, bypass surgery does not protect from recurrence of life-threatening arrhythmias, and, as in our population, defibrillator implant may have significant impact on survival.

Efficacy of midodrine hydrochloride in neurocardiogenic syncope refractory to standard therapy.

INTRODUCTION: Some patients with neurocardiogenic syncope continue to have recurrent syncope or presyncope despite the use of currently available drug therapy. The purpose of this study was to determine whether midodrine hydrochloride, a selective adrenergic agonist, could be effective in patients resistant to, or intolerant of, currently used medications in the treatment of neurocardiogenic syncope. METHODS AND RESULTS: Eleven patients with a history of recurrent syncope or presyncope in whom hypotension with syncope or presyncope could be provoked during head-up tilt testing were included. There were 4 men and 7 women with a mean age (+/-SD) age of 34 +/- 13 years. In all patients, standard therapy with beta-adrenergic receptor blocking agents, ephedrine, theophylline, disopyramide, fludrocortisone, and sertraline hydrochloride, was either ineffective, poorly tolerated, or contraindicated. Midodrine was initially administered orally at a dose of 2.5 mg three times daily. After adjustment of dosage over 2 to 4 weeks, patients were followed-up clinically. Midodrine was discontinued in one patient because of side effects. Frequency of syncope or presyncope during the 3 months prior to starting treatment was compared during a mean follow-up of 17 +/- 4 weeks after starting treatment with midodrine. There was significant (P < 0.01) reduction in syncopal and presyncopal episodes on midodrine. Five patients had complete resolution of symptoms, while four patients had significant improvement. Symptoms did not improve in one patient. CONCLUSIONS: Midodrine hydrochloride can be effective in preventing recurrent symptoms in selected patients with neurocardiogenic syncope unresponsive to, or intolerant of, standard drug therapy.

Termination of atrioventricular nodal reentrant tachycardia by premature stimulation from ablating catheter. A reliable guide to identify site for slow-pathway ablation.

BACKGROUND: Slow-pathway ablation is currently used more frequently to control atrioventricular nodal reentrant tachycardia (AVNRT). However, in patients with the common type of AVNRT, successful ablation of the slow pathway can be difficult and time-consuming. We tested a simple method to predict a site for slow-pathway ablation in patients with AVNRT of the common variety. METHODS AND RESULTS: Twenty patients with symptomatic common AVNRT (13 women and 7 men; mean age, 41 +/- 21 years) were included in the study. Once the AVNRT had a stable cycle length (+/- 10 ms) for at least 20 cycles, single extrastimuli were delivered from the ablating catheter tip beginning with 20 ms less than the tachycardia cycle length and decrementing by 10 ms until tachycardia terminated or loss of capture occurred at the pacing site. The pacing protcol was performed systematically in a stepwise fashion at four adjacent sites starting from the posterior/inferior interatrial septum near the tricuspid annulus and moving progressively more anteriorly. The pacing protocol was then repeated in the same sequence, followed by delivery of radiofrequency current at each site to determine its effect at sites where AVNRT could not be terminated with a pacing protocol. AVNRT could be terminated in the anterograde direction from at least one site in 19 patients. Tachycardia could be terminated at two or more adjacent sites in 5 patients. The longest atrial coupling interval at the site of tachycardia termination was 67 +/- 27 ms (range, 30 to 130 ms) less than the AVNRT cycle length. Resetting of subsequent His bundle depolarization (H2), producing an H-H2 interval prolongation of 26 +/- 24 ms (range, 10 to 80 ms), occurred in 17 patients before termination of the tachycardia. In 18 of the 19 patients, the slow pathway was successfully ablated at the site at which AVNRT was terminated at the longest atrial coupling interval. CONCLUSIONS: Termination of tachycardia in the anterograde direction at the longest atrial coupling interval by extrastimuli delivered from the ablating catheter can be helpful for identification of an optimal site for slow-pathway ablation in patients with the common variety of AVNRT.

Experience with two different nonthoracotomy systems for implantable defibrillator in 170 patients.

Implantation of a nonthoracotomy system (Medtronic PCD or CPI Endotak) was attempted in 170 patients with ventricular tachycardia (VT) or ventricular fibrillation (VF) not requiring concomitant cardiac surgery. A nonthoracotomy system could be successfully implanted in 95 of the 115 patients with the PCD system and 49 of 55 patients receiving the Endotak lead system. In 26 patients with failed nonthoracotomy system because of defibrillation threshold (DFT) > 25 joules (J), an epicardial system was implanted at the same setting. Patients receiving the two lead systems were comparable with regard to age, sex, and ejection fraction. However, since the PCD system offers tiered therapy multiprogrammable options, all attempts were made to implant this lead system in patients with VT that could be pace terminated. Mean DFT (15 +/- 4.7 vs 17 +/- 4.6 J; P = 0.03) and implant time (2.5 +/- 0.6 vs 3.3 +/- 0.7 hours; P = 0.02) were less with the Endotak lead system. There was no perioperative mortality. During a mean follow-up of 20 +/- 4 months, there were eight instances of lead dislodgment in patients receiving the PCD system. There were four nonsudden cardiac deaths and one sudden death in the Endotak group and three nonsudden deaths in the PCD group. Sudden cardiac death and total survival using the intention-to-treat analysis during this follow-up period were 99% and 95%, respectively. In conclusion, successful implantation, perioperative mortality, and survival rate are comparable with both lead systems; however, incorporating two defibrillating electrodes in one lead minimizes lead dislodgment and reduces implant time.