Morten Lock Hansen

Prognosis Among Healthy Individuals Discharged With a Primary Diagnosis of Syncope

OBJECTIVES This study sought to examine the risk of major cardiac adverse events and death in a nationwide cohort of patients without previous comorbidity admitted for syncope. BACKGROUND Syncope is a common clinical event, but knowledge of prognosis is not fully elucidated in healthy individuals. METHODS Patients without previous comorbidity admitted for syncope in Denmark from 2001 to 2009 were identified in nationwide administrative registries and matched by sex and age with 5 control subjects from the Danish population. The risk of death or recurrent syncope, implantation of pacemaker or implantable cardioverter-defibrillator, and cardiovascular hospitalization were analyzed with multivariable Cox proportional hazard models. RESULTS We identified 37,017 patients with a first-time diagnosis of syncope and 185,085 control subjects; their median age was 47 years (interquartile range, 32 to 63 years) and 47% were male. A total of 3,023 (8.2%) and 14,251 (7.1%) deaths occurred in the syncope and the control population, respectively, yielding an event rate of 14.3 per 1,000 person-years (PY) in the syncope population. Multivariable Cox regression analysis demonstrated a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.02 to 1.10), cardiovascular hospitalization event rate of 26.5 per 1,000 PY (HR: 1.74; 95% CI: 1.68 to 1.80), recurrent syncope event rate of 45.1 per 1,000, stroke event rate of 6.8 per 1,000 PY (HR: 1.35; 95% CI: 1.27 to 1.44), and pacemaker or implantable cardioverter-defibrillator event rate of 4.2 per 1,000 PY (HR: 5.52; 95% CI: 4.67 to 5.73; p < 0.0001). CONCLUSIONS The first admission for syncope among healthy individuals significantly predicts the risk of all-cause mortality, stroke, cardiovascular hospitalization, device implantation, and recurrent syncope.

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently - despite elusive mechanisms of action - bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

Comparison of Incidence, Predictors, and the Impact of Co-Morbidity and Polypharmacy on the Risk of Recurrent Syncope in Patients <85 Versus ≥85 Years of Age

Recurrent syncope is a major cause of hospitalizations and may be associated with cardiovascular co-morbidities. Despite this, prognostic factors and the clinical characteristics among patients are not well described. Therefore, we identified and analyzed data on all patients >50 years of age discharged after a first-time episode of syncope in the period 2001 to 2009 through nationwide administrative registries. We identified the clinical characteristics of 5,141 patients ≥85 years of age and 23,454 patients <85 years of age. Multivariate Cox models were used to assess prognostic factors associated with the end point of recurrent syncope according to age. We found that those with syncope and ≥85 years were more often women (65% vs 47%) and generally had a greater prevalence of noncardiovascular co-morbidities, whereas the prevalence of cardiovascular co-morbidities was more heterogeneously distributed across age groups. Overall, significant baseline predictors of recurrent syncope were aortic valve stenosis (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.31 to 1.68), impaired renal function (HR 1.34, 95% CI 1.15 to 1.58), atrioventricular or left bundle branch block (HR 1.32, 95% CI 1.16 to 1.51), male gender (HR 1.18, 95% CI 1.12 to 1.24), chronic obstructive pulmonary disorder (HR 1.10, 95% CI 1.02 to 1.19), heart failure (HR 1.10, 95% CI 1.02 to 1.21), atrial fibrillation (HR = 1.09, 95% CI 1.01 to 1.19), age per 5-year increment (HR 1.09, 95% CI 1.07 to 1.10), and orthostatic medications per increase (HR 1.06, 95% CI 1.03 to 1.09). Atrial fibrillation and impaired renal function both exhibited less prognostic importance for recurrent syncope in the elderly compared with younger population (p for interactions <0.01). In conclusion, predictive factors of recurrent syncope were closely associated with increased cardiovascular risk profile age and gender. The use of multiple orthostatic medications additively increased the risk of recurrences representing a need for strategies to reduce unnecessary polypharmacy.

Thromboembolic risk stratification of patients hospitalized with heart failure in sinus rhythm: a nationwide cohort study

Patients with heart failure in sinus rhythm are at an increased risk of thromboembolic complications. So far, validated risk stratification tools are lacking for such patients, which makes the decision to initiate anti‐thrombotic treatment difficult.

Incidence and Influence of Hospitalization for Recurrent Syncope and Its Effect on Short- and Long-Term All-Cause and Cardiovascular Mortality

Recurrence of syncope is a common event, but the influence of recurrent syncope on the risk of death has not previously been investigated on a large scale. We examined the prognostic impact of recurrent syncope in a nationwide cohort of patients with syncope. All patients (n = 70,819) hospitalized from 2001 to 2009 in Denmark with a first-time diagnosis of syncope aged from 15 to 90 years were identified from national registries. Recurrence of syncope was incorporated as a time-dependent variable in multivariable-adjusted Cox models on the outcomes of 30-day, 1-year, and long-term all-cause mortality and cardiovascular death. During a mean follow-up of 3.9 ± 2.6 years, a total of 11,621 patients (16.4%) had at least 1 hospitalization for recurrent syncope, with a median time to recurrence of 251 days (33 to 364). A total of 14,270 patients died, and 3,204 deaths were preceded by a hospitalization for recurrent syncope. The long-term risk of all-cause death was significantly associated with recurrent syncope (hazard ratio 2.64, 95% confidence interval 2.54 to 2.75) compared with those with no recurrence. On 1-year mortality, recurrent syncope was associated with a 3.2-fold increase in risk and on 30-day mortality associated with a threefold increase. The increased mortality risk was consistent over age groups 15 to 39, 40 to 59, and 60 to 89 years, and a similar pattern of increase in both long-term and short-term risk of cardiovascular death was evident. In conclusion, recurrent syncope is independently associated with all-cause and cardiovascular mortality across all age groups exhibiting a high prognostic influence. Increased awareness on high short- and long-term risk of adverse events in subjects with recurrent syncope is warranted for future risk stratification.

Clarithromycin use and risk of death in patients with ischemic heart disease.

Objectives: To examine whether treatment with clarithromycin was associated with an increased risk of death in patients with preexisting ischemic heart disease (IHD). Methods: Employing nationwide registers, all patients with IHD events from 1997 to 2007 who subsequently claimed prescriptions for dual antibiotic treatment for eradication treatment were identified. The primary endpoint was all-cause mortality. Results: The study included 214,330 individuals with IHD; 5,265 (2.5 %) of these claimed prescriptions for dual antibiotics. Compared with IHD patients not undergoing eradication therapy, no increase in the risk of all-cause mortality was demonstrated (HR 1.02; 95% CI 0.84–1.23, p = 0.87) after 5 years. Conclusions: The use of clarithromycin in the setting of eradication treatment for Helicobacter pylori in patients with IHD was not associated with an increased risk of death.

Unexplained Syncope and Diagnostic Yield of Tests in Syncope According to the ICD-10 Discharge Diagnosis.

Background The etiology of syncope according to the discharge diagnosis from hospital admissions has not been examined before. Therefore the aims of this study were to examine the diagnostic yield of tests and frequency of unexplained cases during admission and after workup after an ICD-10 diagnosis of syncope. Methods A retrospective chart review of 600 patients discharged with the primary ICD-10 discharge diagnosis of syncope R55.9 was performed. Causes and clinical characteristics of syncope according to the physician were noted both after initial discharge and after workup. Results During a mean follow-up period of 2.5 years (SD: ± 1.30) several diagnostic tests were used (mean number of tests per patient was 4.7 (SD: ± -2.0)) and the mean length of admission was 2.1 days (± 1.5).The final diagnosis after workup was reflex syncope in 21%, cardiac 18%, orthostatic hypotension 10%, other causes 4% and unknown/unexplained syncope in 48% with wide age differences. The diagnostic yield of tests was generally low and differed widely depending on usage during admission or usage during subsequent workup. Conclusions The underlying etiology of syncope remains difficult to establish despite the high use of diagnostic tests and the diagnostic yield of many tests implemented in the care path is generally low.

Risk of death and stroke associated with anticoagulation therapy after mitral valve repair

Objective Guidelines generally recommend oral anticoagulation to be considered the first 3 months after mitral valve repair based on small studies and consensus. However, in several studies no benefit of anticoagulation has been found. Methods From the national registries we identified all Danish patients who underwent mitral valve repair during the period between 1997 and 2012. Medication, hospitalisation and mortality data were studied. The association of use of vitamin K antagonists (VKAs) at discharge and risk of stroke/death was evaluated by means of Cox regression, landmark analyses and propensity matched models. Results 2188 patients without prior VKA use, stroke or death day 7 after discharge were included and median follow-up was 4.9 years (0–13.7). 859 (39%) were discharged on VKAs and 523 (24%) experienced death or stroke, 60 of these occurred within the first 3 months and 24 between 3 and 6 months. Compared with patients without post-discharge VKA, patients on VKA had a lower risk of death/stroke at 3 months (HR=0.28, CI (0.13 to 0.62), p=0.002) and in the time period from 3 to 6 months (HR=0.85, CI (0.35 to 2.07), p=0.72). Risk of significant bleeding complications within 3 months were comparable in the two groups with 23 (2%) among patients without VKA and 6 (1%) among VKA-treated. Conclusion VKA treatment after mitral valve repair is associated with a markedly lower risk of adverse events as stroke or death without excess major bleeding risk during the first 3 months following surgery.