Factor XI deficiency is not associated with an increased risk of pneumonia and pneumonia-related mortality.

INTRODUCTION: Drugs targeting factor XI (FXI) shows promising results in reducing postoperative VTE. Recently, researchers have shown that FXI knockout mice had a worse outcome when infected with pathogens for pneumonia, raising concerns about the safety of these drugs. AIM: To investigate the effect of FXI deficiency on the incidence of pneumonia and outcomes of pneumonia in humans. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified adults who were tested for FXI activity between January of 2002 and December of 2014 (n = 10 193). Patients were followed up until December of 2016 for the occurrence of pneumonia and pneumonia requiring hospitalization as a proxy of severe pneumonia. RESULTS: A total of 8958 (87.9%) had normal FXI activity, 804 (7.9%) had partial deficiency and 431 (4.2%) had severe deficiency; 722 individuals had pneumonia during 70 881 person-years of follow-up (incidence rate: 10.2 per 1000 person-years). Compared to those with normal FXI activity, the adjusted HR for pneumonia was 0.87 (95% CI, 0.67-1.14), and 0.95 (0.69-1.30) for those with partial and severe FXI deficiency, respectively. Overall, 256 individuals were hospitalized for pneumonia during 72 209 person-years of follow-up (incidence rate: 3.5 per 1000 person-years). The corresponding HR for severe pneumonia was 1.0 (0.70-1.48) and 0.86 (0.53-1.40) in those with partial and severe FXI deficiency, respectively. FXI deficiency was not significantly associated with 30-day and 90-day mortality among patients with pneumonia. CONCLUSION: FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short-term mortality among patients with pneumonia.

Tyrosine kinase-targeting drugs-associated heart failure.

BACKGROUND: The impact of cancer therapies on cardiac disease in the general adult cancer survivor population is largely unknown. Our objective was to evaluate which tyrosine kinase-targeting drugs are associated with greater risk for new-onset heart failure (HF). METHODS: A nested case-control analysis was conducted within a cohort of 27 992 patients of Clalit Health Services, newly treated with a tyrosine kinase-targeting, and/or chemotherapeutic drug, for a malignant disease, between 1 January 2005 and 31 December 2012. Each new case of HF was matched to up to 30 controls from the cohort on calendar year of cohort entry, age, gender, and duration of follow-up. Main outcome measure was odds ratio (OR) with 95% confidence interval (CI) of new-onset HF. RESULTS: There were 936 incident cases of HF during 71 742 person-years of follow-up. Trastuzumab (OR 1.90, 95% CI 1.46-2.49), cetuximab (OR 1.72, 1.10-2.69), panitumumab (OR 3.01, 1.02-8.85), and sunitinib (OR 3.39, 1.78-6.47) were associated with increased HF risk. Comorbidity independently associated with higher risk in a multivariable conditional regression model was diabetes mellitus, hypertension, chronic renal failure, ischaemic heart disease, valvular heart disease, arrhythmia, and smoking. CONCLUSIONS: Trastuzumab, cetuximab, panitumumab, and sunitinib are associated with increased risk for new-onset HF.

The relationship between obesity and the increase in serum 25(OH)D levels in response to vitamin D supplementation.

UNLABELLED: This study examines the relationship between obesity and the increase in serum 25(OH)D levels in response to vitamin D supplementation among adults with baseline serum 25(OH)D levels<50 nmol/L. This study revealed that the increase in serum 25(OH)D in response to vitamin D supplementation was higher in lean subjects as compared to obese subjects. INTRODUCTION: Serum 25(OH)D is lower among obese than non-obese. This study examines the relationship between obesity and the increase in serum 25(OH)D in response to vitamin D supplementation in a large sample of adults with baseline serum 25(OH)D<50 nmol/L, relatively long average treatment duration and large average daily cholecalciferol. METHODS: The computerized database of the Clalit Health Services, which the largest nonprofit health maintenance organization in Israel, was retrospectively searched for all subjects aged≥20 years who performed serum 25(OH)D test in 2011. Subjects with more than one test at different occasions in 2011 were identified and were included if the result of the first test was <50 nmol/L, and were treated with cholecalciferol between the first and the last test in 2011 (n=16,540 subjects). RESULTS: The mean increase in serum 25(OH)D level after treatment was 28.7 (95% confidence interval (CI), 28.0-29.4) nmol/L, 23.6 (23.0-24.2) nmol/L, and 20.1 (19.6-20.6) nmol/L in subject with BMI of <25, 25-29.9, and ≥30 kg/m2, respectively (P<0.001). The results were similar after adjustment for the potential confounders. Similarly, the proportion of subjects who achieved serum 25(OH)D≥50 nmol/L after treatment was inversely associated with BMI; 65.1, 58.3, and 49.1% for BMI of <25, 25-29.9, and ≥30 kg/m2, respectively. Compared to BMI of ≥30 kg/m2, the adjusted odds ratio for achieving levels of ≥50 nmol/L were 2.12 (95 % CI, 1.94-2.31) and 1.42 (1.31-1.54) for BMI of <25 kg/m2, and BMI of 25-29.9 kg/m2, respectively. CONCLUSIONS: BMI is inversely associated with the increase in serum 25(OH)D levels in response to vitamin D supplementation.

Serum 25(OH)D concentrations in sunny Israel.

SUMMARY: This study assesses vitamin D status in Israel. Serum 25(OH)D levels <25 and <50 nmol/L are common in Israel with noted differences between Arabs and Jews, Arab females were particularly at high risk. These findings may require public health intervention at the population level. INTRODUCTION: Small studies from Israel have suggested a high prevalence of hypovitaminosis D. The objective of this study was to evaluate the extent of hypovitaminosis D among demographic subgroups in Israel. METHODS: The data of this study are from the Clalit Health Services (CHS) which is a non-for-profit health maintenance organization (HMO) covering more than half of the Israeli population. We included all CHS members for whom a 25(OH)D test result in 2009 was available and who were not taking vitamin D supplements in 2008-2009 before that 25(OH)D result. Complete data were available for 198,834 members. RESULTS: The mean level of 25(OH)D was 51.9 ± 24.5 nmol/L and was higher in summer compared to winter (P < 0.0001). Level <25, <37.5, and <50 nmol/L were detected in 14.4%, 30.7%, and 49.9% of tests; 16.4% had levels >75 nmol/L. Females had higher prevalence of 25(OH)D levels < 50 nmol/L which were found in 51.8% of females versus 45.0% in males (P < 0.0001); 76.7% of the Arabs had levels <50 nmol/L versus 46.5% in Jews (P < 0.0001). Arabs females were particularly at high risk for 25(OH)D <50 nmol/L; 84.8% of them had levels <50 nmol/L versus 48.1% of Jewish females (P < 0.0001). The relation of 25(OH)D levels with age had a sinusoidal shape among Jews, a U-shape in Arab females, and inverse linear pattern in Arab males. CONCLUSIONS: 25(OH)D levels <25 and <50 nmol/L are common in Israel. Public health measures are needed for values lesser than about 30 nmol/L and further monitoring of concentrations between about 30 and 50 nmol/L to determine if there are adverse health effects.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference was held in Halifax, Nova Scotia, 20-22 September 2018. Experts in radiation oncology, medical oncology, surgical oncology, and pathology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of pancreatic cancer, pancreatic neuroendocrine tumours, hepatocellular cancer, and rectal and colon cancer, including ■ surgical management of pancreatic adenocarcinoma,■ adjuvant and metastatic systemic therapy options in pancreatic adenocarcinoma,■ the role of radiotherapy in the management of pancreatic adenocarcinoma,■ systemic therapy in pancreatic neuroendocrine tumours,■ updates in systemic therapy for patients with advanced hepatocellular carcinoma,■ optimum duration of adjuvant systemic therapy for colorectal cancer, and■ sequence of therapy in oligometastatic colorectal cancer.

A rare case of primary thyroid amyloidosis.

INTRODUCTION: Amyloid goiter is due to the deposition of amyloid in the thyroid, resulting with enlargement of the gland and compressive symptoms. CASE: We herein present a case of a 45-year-old male patient who complained of a big swelling in the neck. Ultrasound showed an enlarged thyroid gland with mediastinal involvement. The multinodular appearance was consistent with the diagnosis of multinodular goiter. He had a history of multiple myeloma but no sign of systemic amyloidosis. DISCUSSION: Thyroid gland was removed and the histopathological examination revealed a diffuse deposition of amyloid associated with metaplastic lipomatosis of the stroma. CONCLUSIONS: The treatment of choice in patients with amyloid goiter is total thyroidectomy to solve compression symptoms.

Systemic lupus erythematosus and inflammatory bowel disease.

We hereby summarize a case reported by the authors, as well as all of the previously reported cases, of patients suffering from both systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD) that have been published in the English literature. In most cases, SLE was diagnosed prior to IBD, and the latter was of the ulcerative colitis subtype. Interestingly, the first disease diagnosed was almost never active at the time the second disease manifested itself. Patients with both diseases tended to have less photosensitivity, less arthritis, and less serositis than patients with SLE alone. There were no cases with neurological disorders or overt nephritis. All of these patients had anti-dsDNA and there was a tendency towards more anemia and thrombocytopenia. These patients had a relatively benign course with no flare-ups of lupus during follow-up and a favorable course of their bowel disease as well.

The role of CHADS2 and CHA2 DS2 -VASc scores in the prediction of stroke in individuals without atrial fibrillation: a population-based study.

UNLABELLED: Essentials CHADS2 and CHA2 DS2 -VASc scores are used to predict stroke in atrial fibrillation (AF). These scores were calculated for a large cohort from the largest healthcare provider in Israel. The risk of stroke gradually increased with an increase in the scores in individuals without AF. Both scores have a relatively high performance for stroke prediction in individuals without AF. Click to hear Prof. Lowe's perspective on Arterial Thrombosis, Pathogenesis and Epidemiology SUMMARY: Background CHADS2 and CHA2 DS2 -VASc are validated scores used to predict stroke in patients with atrial fibrillation (AF). We aimed to examine the performance of these scores in predicting stroke in individuals without AF. Methods Using the computerized database of the largest HMO in Israel, we identified all not-anticoagulated adults, aged 50 years or older on 1 January 2012. The cohort was followed for the occurrence of stroke or transient ischemic attack (TIA) until 31 December 2014. Results Of 1 053 871 individuals without AF at baseline, 34 215 developed stroke/TIA during a follow-up of 3 014 002 person-years (stroke/TIA incidence rate, 1.14 per 100 person-years). The incidence rate of stroke/TIA increased in a graded manner with increasing CHADS2 score: 0.36, 0.89, 1.89, 2.96, 4.31, 5.37 and 6.62 per 100 person-years for CHADS2 scores of 0 to 6 points, respectively (P < 0.001). Results were similar for the CHA2 DS2 -VASc score. A similar graded increasing trend in the stroke/TIA incidence rate was observed in a cohort of 46 657 patients with AF at baseline; however, stroke/TIA rates were higher in each score stratum compared with the rates of individuals without AF. The area under the receiver operating characteristic curve was 0.718 (95% CI, 0.715-0.721) and 0.714 (0.711-0.717) for CHADS2 and CHA2 DS2 -VASc scores, respectively, in individuals without AF, and 0.606 (0.598-0.614) and 0.610 (0.602-0.618), respectively, in individuals with AF. Conclusions CHADS2 and CHA2 DS2 -VASc scores have a relatively high performance for prediction of stroke/TIA in individuals without AF, which is comparable to their performance in patients with AF.

First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation.

BACKGROUND: Standard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. METHODS AND RESULTS: Fifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the vein. The median number of lesions per patient required to isolate 1 pulmonary vein was 4 (range, 1 to 29). After ablation, no evidence of narrowing was seen with repeat venography or follow-up computed tomography scan. After a mean follow-up of 35+/-6 weeks, 5 patients had recurrence of atrial fibrillation. Three responded to drugs that were previously ineffective, and 2 remained in atrial fibrillation. CONCLUSIONS: This novel ultrasound ablation system can successfully isolate multiple pulmonary veins. At early follow-up, this approach seems to be effective in preventing recurrent atrial fibrillation in a significant number of patients.

Ventricular tachycardias arising from the aortic sinus of valsalva: an under-recognized variant of left outflow tract ventricular tachycardia.

OBJECTIVES: To describe a normal heart left bundle branch block, inferior axis ventricular tachycardia (VT), that could not be ablated from the right or left ventricular outflow tracts. BACKGROUND: Whether these VTs are epicardial and can be identified by a specific electrocardiographic pattern is unclear. METHODS: Twelve patients with normal heart left bundle branch block, inferior axis VT and previously failed ablation were included in this study. Together with mapping in the right and left ventricular outflow tracts, we obtained percutaneous epicardial mapping in the first five patients and performed aortic sinus of Valsalva mapping in all patients. RESULTS: No adequate pace mapping was observed in the right and left ventricular outflow tracts. Earliest ventricular activation was noted in the epicardium and the aortic cusps. All patients were successfully ablated from the aortic sinuses of Valsalva (95% CI 0% to 18%). The electrocardiographic pattern associated with this VT was left bundle branch block, inferior axis and early precordial transition with Rs or R in V2 or V3. Ventricular tachycardia from the left sinus had rS pattern in lead I, and VT from the noncoronary sinus had a notched R wave in lead I. None of the patients had complications and all remained arrhythmia-free at a mean follow-up of 8 +/- 2.6 months. CONCLUSIONS: Normal heart VT with left bundle branch block, inferior axis and early precordial transition can be ablated in the majority of patients from either the left or the noncoronary aortic sinus of Valsalva.

Higher energy synchronized external direct current cardioversion for refractory atrial fibrillation.

OBJECTIVES: We sought to evaluate the safety and efficacy of higher energy synchronized cardioversion in patients with atrial fibrillation refractory to standard energy direct current (DC) cardioversion. BACKGROUND: Standard external electrical cardioversion fails to restore sinus rhythm in 5% to 30% of patients with atrial fibrillation. METHODS: Patients with atrial fibrillation who failed to achieve sinus rhythm after at least two attempts at standard external cardioversion with 360 J were included in the study. Two external defibrillators, each connected to its own pair of R-2 patches in the anteroposterior position, were used to deliver a synchronized total of 720 J. RESULTS: Fifty-five patients underwent cardioversion with 720 J. Mean weight was 117 +/- 23 kg (body mass index 48.3 +/- 4.1 kg/m2). Structural heart disease was present in 76% of patients. Mean left ventricular ejection fraction was 45 +/- 12%. Atrial fibrillation was present for over three months in 55% of the patients. Sinus rhythm was achieved in 46 (84%) of the 55 patients. No major complications were observed. No patient developed hemodynamic compromise and no documented cerebrovascular accident occurred within one month after cardioversion. Of the 46 successful cardioversions, 18 patients (39%) remained in sinus rhythm over a mean follow-up of 2.1 months. CONCLUSIONS: External higher energy cardioversion is effective in restoring sinus rhythm in patients with atrial fibrillation refractory to standard energy DC cardioversion. This method is safe and does not result in clinical evidence of myocardial impairment. It may be a useful alternative to internal cardioversion because it could be done within the same setting of the failed standard cardioversion and obviates the need to withhold protective anticoagulation for internal cardioversion.

Radiofrequency catheter ablation for management of symptomatic ventricular ectopic activity.

OBJECTIVES: This study assessed the useful role of intracardiac mapping and radiofrequency catheter ablation in eliminating drug-refractory monomorphic ventricular ectopic beats in severely symptomatic patients. BACKGROUND: Ventricular ectopic activity is commonly encountered in clinical practice. Usually, it is not associated with life-threatening consequences in the absence of significant structural heart disease. However, frequent ventricular ectopic beats can be extremely symptomatic and even incapacitating in some patients. Currently, reassurance and pharmacologic therapy are the mainstays of treatment. There has been little information on the use of catheter ablation in such patients. METHODS: Ten patients with frequent and severely symptomatic monomorphic ventricular ectopic beats were selected from three tertiary care centers. The mean frequency +/- SD of ventricular ectopic activity was 1,065 +/- 631 beats/h (range 280 to 2,094) as documented by baseline 24-h ambulatory electrocardiographic (ECG) monitoring. No other spontaneous arrhythmias were documented. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 5 +/- 3 antiarrhythmic drugs. The site of origin of ventricular ectopic activity was accurately mapped by using earliest endocardial activation time during ectopic activity or pace mapping, or both. RESULTS: During electrophysiologic study, no patient had inducible ventricular tachycardia. The ectopic focus was located in the right ventricular outflow tract in nine patients and in the left ventricular posteroseptal region in one patient. Frequent ventricular ectopic beats were successfully eliminated by catheter-delivered radiofrequency energy in all 10 patients. The mean number of radiofrequency applications was 2.6 +/- 1.3 (range 1 to 5). No complications were encountered. During a mean follow-up period of 10 +/- 4 months, no patient had a recurrence of symptomatic ectopic activity, and 24-h ambulatory ECG monitoring showed that the frequency of ventricular ectopic activity was 0 beat/h in seven patients, 1 beat/h in two patients and 2 beats/h in one patient. CONCLUSIONS: Radiofrequency catheter ablation can be successfully used to eliminate monomorphic ventricular ectopic activity. It may therefore be a reasonable alternative for the treatment of severely symptomatic, drug-resistant monomorphic ventricular ectopic activity in patients without significant structural heart disease.

Sweet's syndrome and sarcoidosis.

In this review we summarize a number of cases of Sweet's syndrome (SS) associated with sarcoidosis that have been reported in the English literature. In all of the cases, the two disorders were diagnosed simultaneously. Patients with both disorders were younger and had a higher rate of fever than patients with SS alone. In this group of patients, we found a trend toward less skin involvement of the face and trunk, more involvement of the upper limbs, and more atypical skin lesions, particularly papules. The association of the two disorders seems to be more related to a subset of acute sarcoidosis (Lofgren's syndrome). All of the patients in this group had a benign course and self-limiting disease. Thus, SS in association with sarcoidosis could be considered a favorable prognostic factor. Although SS has a high rate of recurrence, no recurrence occurred in this group of patients during follow-up.

Neutrophil to lymphocyte ratio and risk of a first episode of stroke in patients with atrial fibrillation: a cohort study.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is associated with increased risk of cardiovascular morbidity and mortality. We aimed to assess the association between NLR and first episode of stroke in patients with atrial fibrillation. METHODS: Using the computerized database of the largest HMO in Israel, we identified a cohort of adults, aged 20 years or older, with atrial fibrillation diagnosed before 1 January 2012. Eligible subjects had no prior stroke or TIA, were not on anticoagulants at baseline, and had at least one blood cell count performed in 2011. The cohort (32,912 subjects) was followed for the first event of stroke or TIA until 31 December 2012. RESULTS: Overall 981 subjects developed stroke during a follow-up of 30,961 person-years (stroke rate, 3.17 per 100 person-years). The incidence rate of stroke increased across NLR quartiles: 2.27, 2.72, 3.26 and 4.54 per 100 person-years, respectively. Cox proportional hazard regression analysis adjusting for the individual CHA2 DS2 -VASc score risk factors showed that, compared with the lowest NLR quartile, the HR for stroke was 1.11 (95% CI, 0.91-1.35), 1.25 (1.03-1.51) and 1.56 (1.29-1.88) for the second, third and highest quartile, respectively. On stratified analysis, NLR refined the risk of stroke across all CHA2 DS2 -VASc score strata. Adding NLR to the CHA2 DS2 -VASc score increased the AUC from 0.627 (95% CI, 0.612-0.643) to 0.635 (0.619-0.651) (P = 0.037). CONCLUSIONS: The neutrophil to lymphocyte ratio is directly associated with the risk of stroke in patients with atrial fibrillation. Future studies are needed to replicate these findings.

Glycated hemoglobin and risk of first episode stroke in diabetic patients with atrial fibrillation: A cohort study.

BACKGROUND: Diabetes is associated with an increased risk of stroke in patients with atrial fibrillation. Whether glycemic control, evaluated by glycated hemoglobin, affects the risk of stroke in diabetic patients with atrial fibrillation remains unknown. OBJECTIVE: To examine the association between glycated hemoglobin and risk of first episode stroke in diabetic patients with atrial fibrillation. METHODS: By using the computerized database of the largest health maintenance organization in Israel, we identified a cohort of adults (age ≥20 years) in whom atrial fibrillation was diagnosed before January 1, 2012. Eligible subjects had no previous stroke or transient ischemic attack and were not on anticoagulants at baseline. The cohort (37,358 subjects) was followed for the first episode stroke or transient ischemic attack up to December 31, 2012. RESULTS: A total of 1052 subjects had stroke during 35,278 person-years of follow-up (stroke rate 2.98 per 100 person-years). Cox proportional hazards regression analysis adjusting for CHA2DS2-VASc score risk factors revealed that compared with subjects without diabetes, the hazard ratio for stroke was 1.04 (95% confidence interval [CI] 0.83-1.30) for the lowest glycated hemoglobin quartile (<6.35%), 1.14 (95% CI 0.92-1.42) for the second quartile (6.35%-6.90%), 1.46 (95% CI 1.19-1.79) for the third quartile (>6.90%-7.70%), and 1.63 (95% CI 1.33-2.00) for the highest quartile(>7.70%) (for trend, P < .001). In diabetic patients (n = 11,176), the hazard ratio for stroke was 1.17 (95% CI 1.09-1.26) for every 1% increment in glycated hemoglobin level. The area under the receiver operating characteristic curve was 0.585 for the CHA2DS2-VASc score, which increased to 0.604 when glycated hemoglobin was included in the model (P = .038). CONCLUSION: Glycated hemoglobin is directly associated with stroke risk, and it improves the predictive accuracy for stroke in diabetic patients with atrial fibrillation.

Transiliac permanent pacemaker implantation after extraction of infected pectoral pacemaker systems.

Infected pectoral pacemaker systems were extracted in 5 patients and new pacemakers were reimplanted in a pelvic pocket through the iliac veins. In patients who have infected pectoral pacemaker systems, this easy and safe technique provides an alternate route for reimplantation of permanent pacemakers.

Comparison of echocardiographic assessment of cardiac hemodynamics in the intensive care unit with right-sided cardiac catheterization.

Estimation of left ventricular filling pressure and cardiac index is important in the management of patients requiring right heart catheterization. Doppler echocardiography can provide a noninvasive measure of these parameters, but its accuracy in individual measurements, predicting hemodynamic subgroups, and in tracking serial changes in critically ill patients remains to be elucidated. Left ventricular filling pressure and cardiac index were assessed in 49 critically ill patients requiring right heart catheterization and Doppler echocardiographic studies. Two or more serial studies were performed in 18 of these subjects. Patients were placed into 1 of 4 hemodynamic subgroups for each technique based on the acquired hemodynamic parameters. Left ventricular filling pressure and cardiac index by Doppler echocardiography and right heart catheterization were similar (21 +/- 8 vs 20 +/- 8 mm Hg; 3.0 +/- 1.2 vs 2.9 +/- 1.2 L/min/m2, respectively) and correlated well with each other (left ventricular filling pressure, r = 0.88; cardiac index, r = 0.92). The Doppler technique accurately placed 73 of 76 studies into the correct hemodynamic subgroup. The noninvasive technique also reliably tracked serial hemodynamic measurements. We conclude that Doppler echocardiography accurately assesses left heart hemodynamics in critically ill patients. Since this technique can be readily acquired, it can be ideal for the rapid assessment of hemodynamic parameters in critically ill patients, especially when right heart catheterization is delayed or is problematic.

Long-term follow-up of heart transplant recipients requiring permanent pacemakers.

BACKGROUND: Permanent pacemaker implantation after heart transplantation is contentious. Indications for these devices in this population are uncertain. The goals of this project were to (1) analyze the time course of donor sinus node dysfunction and atrioventricular block after heart transplantation; (2) evaluate which selected parameters (donor age, ischemic time, heart rate before pacer insertion, and number of rejection episodes) might relate to persistent permanent pacing need, and (3) assess pacemaker complications during follow-up. METHODS: A retrospective analysis of pacemaker implantations (22 cases) was performed in 286 consecutive heart transplantations performed between February 1984 and April 1994 at The Methodist Hospital and Baylor College of Medicine, Houston, Texas. RESULTS: Permanent pacemakers were inserted early after transplantation in 19 patients (mean 24 days); 14 pacemakers were for sinus node dysfunction (bradycardia in five, sinus arrest with junctional escape in eight, and optimization of hemodynamics in one). Symptomatic complete heart block prompted insertion late in two patients (3 and 47 months), and symptomatic sinus pause was the indication for late insertion in one. Recipient mean age was 52.4 years, with mean donor age 29.7 years in patients with pacemakers. By 3 months, 13 of 19 patients receiving pacemakers early (mean preinsertion heart rate 58.3 beats/min) became pacer independent with subsequent mean intrinsic heart rate of 97 beats/min. Recipient or donor age, ischemic time, and rejection episodes did not appear related to long-term pacing need early or late after transplantation. CONCLUSIONS: Inferences from these observations include the fact that many patients with early sinus node dysfunction and bradycardia are not pacer dependent at 3 months. However, those with atrioventricular block early appear to require long-term pacing support. However, the possibility that more aggressive and long-term oral chronotropic medication use after transplantation would obviate early permanent pacemaker need is not addressed. Finally, prospective clinical trials are necessary to precisely characterize benefit of permanent pacemakers and define optimal pacing modes after heart transplantation.

Ventricular tachycardia syndromes.

Better understanding of the underlying mechanism and substrate of different VTs has made it possible to tailor treatment strategies properly. The advent of sophisticated device-based therapy and of more precise and effective catheter ablation approaches will expand clinicians' ability to gain control of this multifaceted arrhythmia syndrome.

Dofetilide (Tikosyn): a new drug to control atrial fibrillation.

UNLABELLED: Dofetilide, a new class III antiarrhythmic agent, selectively blocks a specific cardiac potassium channel, IKr, increasing the effective refractory period of the myocyte and thereby terminating reentrant arrhythmias. Given orally, it appears to effectively convert atrial fibrillation and atrial flutter to sinus rhythm and maintain sinus rhythm after conversion in appropriately selected patients. This paper reviews the pharmacology of dofetilide, the evidence of its effectiveness, and the appropriate precautions in using it. KEY POINTS: Dofetilide is generally well tolerated but like other class III drugs can cause torsades de pointes. The risk is dose-dependent and can be minimized by adjusting the dosage according to creatinine clearance and QT interval, by excluding patients with known risk factors for long QT syndrome and torsades de pointes, and by starting treatment in an inpatient monitored setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase the mortality rate in clinical studies in postmyocardial infarction patients or those with congestive heart failure at high risk for sudden cardiac death. Concomitant use of drugs that increase the plasma level of dofetilide is contraindicated; these include cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil.