Outcomes of primary vs. delayed strategy of implanting a cardiac monitor for unexplained syncope.

OBJECTIVE: Implantable cardiac monitors (ILR) have an important role in diagnosing unexplained syncope. However, outcomes of primary vs. delayed ILR implantation after initial syncope evaluation have not been explored. METHODS: A total of 1705 patients with unexplained syncope were prospectively enrolled in the SYSTEMA (Syncope Study of Unselected Population in Malmö) cohort. Patients who underwent cardiovascular autonomic testing (CAT) and ILR were grouped into those referred to CAT after ILR implantation (primary ILR) and those in whom ILR was indicated after CAT (post-CAT ILR). RESULTS: One-hundred-and-fifteen patients (6.7%) received ILRs. ILR recipients were older (58 vs. 52 years; p = 0.002), had more syncope recurrences (6 vs. 4; p < 0.001), more traumatic falls (72% vs. 53%; p < 0.001), and less prodrome (40% vs. 55%; p = 0.005) than patients without ILRs. During follow-up ≥16 months after ILR, 67 (58%) had normal sinus rhythm, 10 (8.7%) had sinus arrest, 10 (8.7%) AV-block, 13 (11.3%) atrial fibrillation, 9 (7.8%) supraventricular tachycardia, 4 (3.5%) sinus tachycardia and 2 (1.7%) ventricular tachycardia with clinical symptom reproduction. There were 52 patients (45%) in the primary-ILR group and 63 (55%) in the post-CAT ILR group. Proportions of negative ILR monitoring (17/52 vs. 25/63; p = 0.56) and pacemaker implantations (7/52 vs. 15/63; p = 0.23) did not differ between groups. Baseline ECG conduction disorders predicted pacemaker implantation (n = 11/17; odds ratio:10.6; 95%CI: 3.15-35.3; p < 0.001). CAT was more often positive (73% vs. 40%; p < 0.001) in primary-ILR group. CONCLUSIONS: Primary ILR implantation was associated with more positive CAT compared with delayed ILR implantation, but negative monitoring and pacemaker implantations were not different between groups. ECG conduction disorders predicted subsequent pacemaker implantation

Orthostatic hypotension: clinical review and case study

Transient loss of consciousness (TLOC) accounts for 3% of all attendance in emergency departments within the UK. More than 90% of TLOC presentations are due to epileptic seizures, psychogenic seizures or syncope. However, in England and Wales in 2002, it was estimated that 92000 patients were incorrectly diagnosed with epilepsy, at an additional annual cost to the NHS of up to £189 million. This article will reflect on the case study of a 54-year-old female patient who presented with a possible TLOC, and had a background of long-term depression. Differential diagnoses will be discussed, but the article will focus on orthostatic hypotension. Being diagnosed with this condition is independently associated with an increased risk of all-cause mortality. Causes of orthostatic hypotension and the pathophysiology behind the condition will be discussed, highlighting the importance of obtaining an accurate clinical history. This is extremely pertinent if a patient collapses in an NHS setting and this is witnessed by nurses because they can contribute to the history of the type of collapse, to aid diagnosis and correct treatment. In addition, nurses have a valuable role to play in highlighting polypharmacy to doctors, and non-medical prescribers, as a contributing factor to orthostatic hypotension is polypharmacy. It is therefore important to accurately distinguish TLOC aetiology, not only to provide appropriate management, but to also identify patients at risk of morbidity/mortality related to underlying disease.N/

Cardiovascular autonomic dysfunction is the most common cause of syncope in paced patients

Introduction: Syncope and orthostatic intolerance in paced patients constitute a common clinical dilemma. We, thus, aimed to determine the etiology of syncope and/or symptoms of orthostatic intolerance in paced patients. Methods: Among 1,705 patients with unexplained syncope and/or orthostatic intolerance that were investigated by cardiovascular autonomic tests, including Valsalva maneuver, active standing, carotid sinus massage, and tilt-testing, 39 patients (2.3%; age 65.6 years; 39% women) had a cardiac implantable electronic device (CIED). We explored past medical history, diagnoses found during cardiovascular autonomic tests, and the further clinical workup, in case of negative initial evaluation. Results: An etiology was identified during cardiovascular autonomic tests in 36 of the 39 patients. Orthostatic hypotension (n = 16; 41%) and vasovagal syncope (n = 12; 31%) were the most common diagnoses. There were no cases of pacemaker dysfunction. The original pacing indications followed guidelines (sick-sinus-syndrome in 16, atrioventricular block in 16, atrial fibrillation with bradycardia in five). Twenty-two of the 39 patients (56%) had experienced syncope prior to the original CIED implantation. Orthostatic hypotension was diagnosed in seven (32%) and vasovagal syncope in nine (41%) of these patients. Of the 17 patients that had not experienced syncope prior to the original CIED implantation, nine patients (53%) were diagnosed with orthostatic hypotension and vasovagal syncope was diagnosed in three (18%). Of the 39 patients, two had implantable cardioverter-defibrillators to treat malignant ventricular arrhythmias diagnosed after syncopal episodes. Conclusion: Cardiovascular autonomic tests reveal the etiology of syncope and/or orthostatic intolerance in the majority of paced patients. The most common diagnosis was orthostatic hypotension (40%) followed by vasovagal syncope (30%), whereas there were no cases of pacemaker dysfunction. Our results emphasize the importance of a complete diagnostic work-up, including cardiovascular autonomic tests, in paced patients that present with syncope and/or orthostatic intolerance

Genetic analysis of acd6-1 reveals complex defense networks and leads to identification of novel defense genes in Arabidopsis

Pathogen infection leads to the activation of defense signaling networks in plants. To study these networks and the relationships between their components, we introduced various defense mutations into acd6-1, a constitutive gain-of-function Arabidopsis mutant that is highly disease resistant. acd6-1 plants show spontaneous cell death, reduced stature, and accumulate high levels of camalexin (an anti-fungal compound) and salicylic acid (SA; a signaling molecule). Disruption of several defense genes revealed that in acd6-1, SA levels/signaling were positively correlated with the degree of disease resistance and defense gene expression. Salicylic acid also modulates the severity of cell death. However, accumulation of camalexin in acd6-1 is largely unaffected by reducing the level of SA. In addition, acd6-1 shows ethylene- and jasmonic acid-mediated signaling that is antagonized and therefore masked by the presence of SA. Mutant analysis revealed a new relationship between the signaling components NPR1 and PAD4 and also indicated that multiple defense pathways were required for phenotypes conferred by acd6-1. In addition, our data confirmed that the size of acd6-1 was inversely correlated with SA levels/signaling. We exploited this unique feature of acd6-1 to identify two genes disrupted in acd6-1 suppressor (sup) mutants: one encodes a known SA biosynthetic component (SID2) and the other encodes an uncharacterized putative metalloprotease (At5g20660). Taken together, acd6-1 is a powerful tool not only for dissecting defense regulatory networks but also for discovering novel defense genes.We thank Drs Mauricio Bustos, Ho Won Jung, Jiyoung Lee, and Stephen Miller for critical reading of this manuscript and useful discussions. We thank members of the Arabidopsis thaliana Research Initiative at the University of Maryland for suggestions and inputs into this study. We thank Susan Ferrari at the University of Chicago for initial help with generating suppressor mutants. We thank Dr Joy Bergelson at UC for sharing the usage of her HPLC instrument and Dr Charles Bieberich at University of Maryland Baltimore County for sharing his dissecting microscope with us. We thank Tim Ford for taking pictures for this publication. This work was supported by start-up funds from UMBC to HL and National Science Foundation (IOB-0450207) and National Institutes of Health (R01 GM54292) grants to JTG. SS was supported by Minority Access to Research Career (funded by NIGMS/NIH), Meyerhoff (funded by Meyerhoff and NSF), and the Provost Undergraduate Research award at UMBC.https://onlinelibrary.wiley.com/doi/10.1111/j.1365-313X.2009.03791.