Abnormal vascular function in PR-interval prolongation

Background:

Underlying mechanisms of PR‐interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function.

Hypothesis:

We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function.

Methods:

We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community‐based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12‐lead electrocardiogram. Vascular function was noninvasively assessed by flow‐mediated dilation (FMD) using high‐resolution ultrasound and brachial‐ankle pulse wave velocity (PWV) using a vascular profiling system.

Results:

Only 3 subjects had a PR‐interval length longer than the conventional cutoff of 200 ms. The PR‐interval length was associated inversely with FMD (Pearson r = ?0.30, P = 0.004) and positively with PWV (r = 0.40, P < 0.001). Adjusting for potential confounders, increased PR‐interval length by each 25 ms was independently associated with reduced FMD by ?1 unit (absolute %, B = ?0.04 [95% confidence interval: ?0.080 to ?0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6–7.6, P = 0.023]).

Conclusions:

This study shows that PR‐interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism. © 2011 Wiley Periodicals, Inc. This study was supported by the CRCG Small Project Funding of the University of Hong Kong (Project No. 200907176063) and the Sun ChiehYeh Heart Foundation, Hong Kong, China. Yap‐Hang received a Best Paper Award at the Third Asian Preventive Cardiology and Cardiac Rehabilitation Conference, Hong Kong, China, December 11–12, 2010. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

Type A aortic intramural hematoma: clinical features and outcomes in Chinese patients

Background

The purpose of this study was to describe the clinical characteristics and clinical outcomes for Chinese patients with type A intramural hematoma (IMH).

Methods and Results

We studied 90 patients with Stanford type A acute aortic syndrome who presented to our institution from 1998 to 2005 and evaluated the presentation, management, and clinical outcomes of acute IMH by comparing these patients with those diagnosed with classical aortic dissection (AD). A total of 34 patients had IMH and they tended to be older (69.7 ± 12.4 versus 60.5 ± 16.2 years; p = 0.006). The development of pericardial effusion was more frequent in patients with IMH than in patients with AD. They were also less likely to receive surgery as compared to AD patients (26.5% versus 73.2%; p < 0.0001). Overall mortality of IMH was not significantly higher than that of classic AD (29.4% versus 21.4%; p = 0.45). For IMH patients, the mortality rate with medical treatment was 32%. Ten (40%) of the 25 medically treated patients developed adverse outcomes. However, no independent predictors of adverse outcomes were identified in the study. In follow‐up imaging studies of 15 patients who survived IMH without surgical repair, 14 patients showed complete resolution of IMH and 1 progressed into classical AD.

Conclusion

Acute type A IMH in Chinese patients showed a high mortality rate with medical treatment. It has a highly unpredictable course with no reliable clinical and anatomical predictors. Surgical therapy should be the treatment of choice for Chinese patients with acute IMH, especially those who are younger and have less comorbidities. © 2011 Wiley Periodicals, Inc.     

Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice

Autosomal dominant hypophosphatemic rickets (ADHR) is unique among the disorders involving Fibroblast growth factor 23 (FGF23) because individuals with R176Q/W and R179Q/W mutations in the FGF23 (176)RXXR(179)/S(180) proteolytic cleavage motif can cycle from unaffected status to delayed onset of disease. This onset may occur in physiological states associated with iron deficiency, including puberty and pregnancy. To test the role of iron status in development of the ADHR phenotype, WT and R176Q-Fgf23 knock-in (ADHR) mice were placed on control or low-iron diets. Both the WT and ADHR mice receiving low-iron diet had significantly elevated bone Fgf23 mRNA. WT mice on a low-iron diet maintained normal serum intact Fgf23 and phosphate metabolism, with elevated serum C-terminal Fgf23 fragments. In contrast, the ADHR mice on the low-iron diet had elevated intact and C-terminal Fgf23 with hypophosphatemic osteomalacia. We used in vitro iron chelation to isolate the effects of iron deficiency on Fgf23 expression. We found that iron chelation in vitro resulted in a significant increase in Fgf23 mRNA that was dependent upon Mapk. Thus, unlike other syndromes of elevated FGF23, our findings support the concept that late-onset ADHR is the product of gene-environment interactions whereby the combined presence of an Fgf23-stabilizing mutation and iron deficiency can lead to ADHR.     

Rapid control of a hospital-wide outbreak caused by extensively drug-resistant OXA-72-producing Acinetobacter baumannii

Extensively drug-resistant Acinetobacter baumannii (XDRAb) emerges as an important pathogen of health care-associated infections and outbreaks worldwide. During January and February 2006, there was a hospital-wide outbreak of XDRAb at a medical center in Taiwan. Without limiting the usage of carbapenems or the closure of any ward, this outbreak was effectively controlled. We investigated the molecular epidemiology and reported the infection control experiences. XDRAb is defined as A baumannii that is resistant to multiple antibiotics but susceptible to tigecycline and polymyxin B. During the outbreak, the clinical and environmental XDRAb isolates were collected and studied by antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and polymerase chain reaction for Verona integron-encoded metallo-beta-lactamases, imipenemases, and oxacillinases (OXA). Our measures to control the outbreak included private room isolation of patients until there were three successive negative cultures, reinforcement of contact precautions, daily environmental cleansing with room-dedicated cleaning tools and sodium hypochlorite, and careful auditing of adherence. During the outbreak, 32 clinical XDRAb isolates came from 13 patients who were hospitalized in four intensive care units and three wards. Most (7 of 13, 53.8%) cases were associated with a surgical intensive care unit. The results from pulsed-field gel electrophoresis study indicated that all isolates were of one genotype. All 32 isolates harbored ISAba1-bla(OxA-51-like) and bla(OxA-72) genes. After this outbreak till August 2010, further incidences of XDRAb were sporadic cases of XDRAb with different clones and did not reach the level of outbreak. To our knowledge, this is the first reported hospital-wide outbreak caused by OXA-72 carbapenemase-producing A baumannii in the Asia-Pacific region, with successful and sustained control. Although the source or vehicle of the outbreak was not identified, our results suggest that a hospital-wide outbreak can be successfully managed with strict infection control measures, and that the limitation of the use of carbapenems and closure of wards may not be necessary.     

Low molecular weight heparin versus unfractionated heparin for thromboprophylaxis in patients with acute atrial fibrillation: a randomized control trial

While long-term anticoagulation prevents ischemic stroke in high-risk patients with atrial fibrillation (AF), the optimal initial anti-thrombotic regime in acute AF is less well defined. We randomized 96 patients with new onset acute AF in an emergency admission ward to receive (1) once-daily preparation of low molecular weight heparin (LMWH), tinzaparin or (2) conventional intravenous unfractionated heparin (target APTT 50-70 s). 5 patients in unfractionated heparin group compared with no patients in LMWH group (0%, P = 0.04) developed ischemic stroke/transient ischemic attack during the first 48 h. An initial subcutaneous LMWH was safe and effective in ischemic stroke prevention in patients with acute AF.     

Myocardial ischemia secondary to congenital hypoplastic left coronary cusp in adult

Coronary arterial obstruction associated with congenital aortic valve disease is rare in childhood, and has not been reported in adult. Here we reported a 49-year-old healthy woman with hypoplastic left coronary cusp resulting in myocardial ischemia in the territory of left main coronary artery.     

Prevalence of and factors associated with psychiatric morbidity in chronic pain patients

Objective

The reported prevalence of psychiatric morbidity in chronic pain patients (CCPs) was high, although it varied tremendously since structured diagnostic instruments were seldom used for diagnosis in previous studies. Study in this area after the launching of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was scarce. This study serves to estimate the prevalence of psychiatric morbidity in patients attending a chronic pain clinic by using the Structured Clinical Interview for DSM-IV (SCID) Axis I disorders and to identify factors highly associated with psychiatric disorders, particularly depression, which is treatable.

Method

Consecutive patients attending a chronic pain clinic were recruited during a 6-month period. Psychiatric diagnoses were made by using the SCID. Logistic regression was used to identify factors predicting overall psychiatric morbidity and depression.

Results

Prevalence of psychiatric disorders in this 89-patient sample was 62.9%. Current major depressive disorder was present in 31.5% and somatoform disorders in 33.7%. Anxiety disorders and current substance use disorders each constituted 18. “Younger age of onset of pain” (odds ratio [OR]=0.956, P<.05) and “higher pain intensity” (OR=1.544, P<.001) were independently associated with presence of psychiatric disorders. “Higher pain intensity” (OR=13.7, P<.05), “negative pain cognition” (OR=0.967, P<.05) and “problems with social and leisure activities” (OR=38.5, P<.05) were associated with depression.

Conclusion

Prevalence of psychiatric disorders in this Chinese chronic pain clinic sample with reference to the DSM-IV was similar to that reported in previous studies. Specific factors were identified to alert pain physicians to underlying psychiatric disorders.