Comparison of Different Strategies to Measure Medication Adherence via Claims Data in Patients With Chronic Heart Failure.

Medication adherence correlates with morbidity and mortality in patients with chronic heart failure (CHF), but is difficult to assess. We conducted a retrospective methodological cohort study in 3,808 CHF patients, calculating adherence as proportion of days covered (PDC) utilizing claims data from 2010 to 2015. We aimed to compare different parameters' influence on the PDC of elderly CHF patients exemplifying a complex chronic disease. Investigated parameters were the assumed prescribed daily dose (PDD), stockpiling, and periods of hospital stay. Thereby, we investigated a new approach using the PDD assigned to different percentiles. The different dose assumptions had the biggest influence on the PDC, with variations from 41.9% to 83.7%. Stockpiling and hospital stays increased the values slightly. These results queries that a reliable PDC can be calculated with an assumed PDD. Hence, results based on an assumed PDD have to be interpreted carefully and should be presented with sensitivity analyses to show the PDC's possible range

Causal hierarchy within the thalamo-cortical network in spike and wave discharges

Background: Generalised spike wave (GSW) discharges are the electroencephalographic (EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges. Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was ∼1. Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo-(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy. © 2009 Vaudano et al

“Pure” severe aortic stenosis without concomitant valvular heart diseases:echocardiographic and pathophysiological features

Purpose!#!In echocardiography the severity of aortic stenosis (AS) is defined by effective orifice area (EOA), mean pressure gradient (mPG!##!Methods and results!#!Patients (n = 306) with asymptomatic (n = 133) and symptomatic (n = 173) 'pure' severe AS (mean age 78 ± 9.5 years) defined by indexed EOA < 0.6 cm!##!Conclusion!#!In patients with 'pure' AS according to current guidelines the presence of combined LVH, DD and PAH as accepted pathophysiological sequelae of severe AS cannot be confirmed. Probably, the detection of these secondary cardiac alterations might improve the diagnostic algorithm to avoid overestimation of AS severity

Pharmacy-based interdisciplinary intervention for patients with chronic heart failure: results of the PHARM-CHF randomized controlled trial.

AIMS:Medication non-adherence is frequent and is associated with high morbidity and mortality in patients with chronic heart failure (CHF). We investigated whether an interdisciplinary intervention improves adherence in elderly CHF patients. METHODS AND RESULTS:The study population (mean age 74 years, 62% male, mean left ventricular ejection fraction 47%, 52% in New York Heart Association class III) consisted of 110 patients randomized into the pharmacy care and 127 into the usual care group. The median follow-up was 2.0 years (interquartile range 1.2-2.7). The pharmacy care group received a medication review followed by regular dose dispensing and counselling. Control patients received usual care. The primary endpoint was medication adherence as proportion of days covered (PDC) within 365 days for three classes of heart failure medications (beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and mineralocorticoid receptor antagonists). The main secondary outcome was the proportion of adherent patients (PDC ≥ 80%). The primary safety endpoint was days lost due to unplanned cardiovascular hospitalizations (blindly adjudicated) or death. Pharmacy care compared with usual care resulted in an absolute increase in mean adherence to three heart failure medications for 365 days [adjusted difference 5.7%, 95% confidence interval (CI) 1.6-9.8, P = 0.007]. The proportion of patients classified as adherent increased (odds ratio 2.9, 95% CI 1.4-5.9, P = 0.005). Pharmacy care improved quality of life after 2 years (adjusted difference in Minnesota Living with Heart Failure Questionnaire scores -7.8 points (-14.5 to -1.1; P = 0.02), compared to usual care. Pharmacy care did not affect the safety endpoints of hospitalizations or deaths. CONCLUSION:Pharmacy care safely improved adherence to heart failure medications and quality of life

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Epileptic networks in focal cortical dysplasia revealed using electroencephalography-functional magnetic resonance imaging.

Surgical treatment of focal epilepsy in patients with focal cortical dysplasia (FCD) is most successful if all epileptogenic tissue is resected. This may not be evident on structural magnetic resonance imaging (MRI), so intracranial electroencephalography (icEEG) is needed to delineate the seizure onset zone (SOZ). EEG-functional MRI (fMRI) can reveal interictal discharge (IED)-related hemodynamic changes in the irritative zone (IZ). We assessed the value of EEG-fMRI in patients with FCD-associated focal epilepsy by examining the relationship between IED-related hemodynamic changes, icEEG findings, and postoperative outcome

Improving exercise capacity and quality of life using non-invasive heart failure treatments: evidence from clinical trials

Endpoints of large-scale trials in chronic heart failure have mostly been defined to evaluate treatments with regard to hospitalizations and mortality. However, patients with heart failure are also affected by very severe reductions in exercise capacity and quality of life. We aimed to evaluate the effects of heart failure treatments on these endpoints using available evidence from randomized trials. Interventions with evidence for improvements in exercise capacity include physical exercise, intravenous iron supplementation in patients with iron deficiency, and – with less certainty – testosterone in highly selected patients. Erythropoiesis-stimulating agents have been reported to improve exercise capacity in anaemic patients with heart failure. Sinus rhythm may have some advantage when compared with atrial fibrillation, particularly in patients undergoing pulmonary vein isolation. Studies assessing treatments for heart failure co-morbidities such as sleep-disordered breathing, diabetes mellitus, chronic kidney disease and depression have reported improvements of exercise capacity and quality of life; however, the available data are limited and not always consistent. The available evidence for positive effects of pharmacologic interventions using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists on exercise capacity and quality of life is limited. Studies with ivabradine and with sacubitril/valsartan suggest beneficial effects at improving quality of life; however, the evidence base is limited in particular for exercise capacity. The data for heart failure with preserved ejection fraction are even less positive, only sacubitril/valsartan and spironolactone have shown some effectiveness at improving quality of life. In conclusion, the evidence for state-of-the-art heart failure treatments with regard to exercise capacity and quality of life is limited and appears not robust enough to permit recommendations for heart failure. The treatment of co-morbidities may be important for these patient-related outcomes. Additional studies on functional capacity and quality of life in heart failure are required