Cystatin C Identifies Patients with Stable Chronic Heart Failure at Increased Risk for Adverse Cardiovascular Events

Background—Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect, and cystatin C (CysC) is promoted as a better marker of glomerular filtration rate. This study compares the prognostic use of CysC and derived glomerular filtration rate estimates with other measures of renal function in patients with chronic heart failure. Methods and Results—We measured serum CysC levels in 823 patients with heart failure undergoing coronary angiography with follow-up of major adverse cardiovascular events (death, myocardial infarction, stroke). CysC levels strongly correlated with creatinine (r=0.73), blood urea nitrogen (r=0.70), and estimated glomerular filtration rate by the 4-variable modification of diet in renal disease equation (r=−0.62) (all P\u3c0.001). However, the correlation was lower in estimated glomerular filtration rate ≥60 mL/min per 1.73 m2. CysC-based measures significantly improved areas under the receiver operating characteristic curve for the prediction of major adverse cardiovascular events, especially in estimated glomerular filtration rate ≥60 mL/min per 1.73 m2 (P\u3c0.01). Net reclassification improvement was 22.2% (P\u3c0.001) in this group. CysC remained an independent predictor of major adverse cardiovascular events (P\u3c0.001) after adjustment for traditional risk factors and brain natriuretic peptide. Conclusions—CysC is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with preserved renal function

Cystatin C Identifies Patients with Stable Chronic Heart Failure at Increased Risk for Adverse Cardiovascular Events

Background—Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect, and cystatin C (CysC) is promoted as a better marker of glomerular filtration rate. This study compares the prognostic use of CysC and derived glomerular filtration rate estimates with other measures of renal function in patients with chronic heart failure. Methods and Results—We measured serum CysC levels in 823 patients with heart failure undergoing coronary angiography with follow-up of major adverse cardiovascular events (death, myocardial infarction, stroke). CysC levels strongly correlated with creatinine (r=0.73), blood urea nitrogen (r=0.70), and estimated glomerular filtration rate by the 4-variable modification of diet in renal disease equation (r=−0.62) (all P\u3c0.001). However, the correlation was lower in estimated glomerular filtration rate ≥60 mL/min per 1.73 m2. CysC-based measures significantly improved areas under the receiver operating characteristic curve for the prediction of major adverse cardiovascular events, especially in estimated glomerular filtration rate ≥60 mL/min per 1.73 m2 (P\u3c0.01). Net reclassification improvement was 22.2% (P\u3c0.001) in this group. CysC remained an independent predictor of major adverse cardiovascular events (P\u3c0.001) after adjustment for traditional risk factors and brain natriuretic peptide. Conclusions—CysC is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with preserved renal function

Drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in nine southern African countries: a modelling study.

INTRODUCTION: The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) threatens antiretroviral therapy's long-term success (ART). NNRTIs will remain an essential drug for the management of HIV-1 due to safety concerns associated with integrase inhibitors. We fitted a dynamic transmission model to historical data from 2000 to 2018 in nine countries of southern Africa to understand the mechanisms that have shaped the HIV-1 epidemic and the rise of pretreatment NNRTI resistance. METHODS: We included data on HIV-1 prevalence, ART coverage, HIV-related mortality, and survey data on pretreatment NNRTI resistance from nine southern Africa countries from a systematic review, UNAIDS and World Bank. Using a Bayesian hierarchical framework, we developed a dynamic transmission model linking data on the HIV-1 epidemic to survey data on NNRTI drug resistance in each country. We estimated the proportion of resistance attributable to unregulated, off-programme use of ART. We examined each national ART programme's vulnerability to NNRTI resistance by defining a fragility index: the ratio of the rate of NNRTI resistance emergence during first-line ART over the rate of switching to second-line ART. We explored associations between fragility and characteristics of the health system of each country. RESULTS: The model reliably described the dynamics of the HIV-1 epidemic and NNRTI resistance in each country. Predicted levels of resistance in 2018 ranged between 3.3% (95% credible interval 1.9-7.1) in Mozambique and 25.3% (17.9-33.8) in Eswatini. The proportion of pretreatment NNRTI resistance attributable to unregulated antiretroviral use ranged from 6% (2-14) in Eswatini to 64% (26-85) in Mozambique. The fragility index was low in Botswana (0.01; 0.0-0.11) but high in Namibia (0.48; 0.16-10.17), Eswatini (0.64; 0.23-11.8) and South Africa (1.21; 0.83-9.84). The combination of high fragility of ART programmes and high ART coverage levels was associated with a sharp increase in pretreatment NNRTI resistance. CONCLUSIONS: This comparison of nine countries shows that pretreatment NNRTI resistance can be controlled despite high ART coverage levels. This was the case in Botswana, Mozambique, and Zambia, most likely because of better HIV care delivery, including rapid switching to second-line ART of patients failing first-line ART

Prognostic Role of Cardiac Power Index in Ambulatory Patients with Advanced Heart Failure

BACKGROUND: Cardiac pump function is often quantified by left ventricular ejection fraction by various imaging modalities. As the heart is commonly conceptualized as a hydraulic pump, cardiac power describes the hydraulic function of the heart. We aim to describe the prognostic value of resting cardiac power index (CPI) in ambulatory patients with advanced heart failure. METHODS AND RESULTS: We calculated CPI in 495 sequential ambulatory patients with advanced heart failure who underwent invasive haemodynamic assessment with longitudinal follow-up of adverse outcomes (all-cause mortality, cardiac transplantation, or ventricular assist device placement). The median CPI was 0.44 W/m(2) (interquartile range 0.37, 0.52). Over a median of 3.3 years, there were 117 deaths, 104 transplants, and 20 ventricular assist device placements in our cohort. Diminished CPI (\u3c0.44 W/m(2) ) was associated with increased adverse outcomes [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.8-3.1, P \u3c 0.0001). The prognostic value of CPI remained significant after adjustment for age, gender, pulmonary capillary wedge pressure, cardiac index, pulmonary vascular resistance, left ventricular ejection fraction, and creatinine [HR 1.5, 95% CI 1.03-2.3, P = 0.04). Furthermore, CPI can risk stratify independently of peak oxygen consumption (HR 2.2, 95% CI 1.4-3.4, P = 0.0003). CONCLUSION: Resting cardiac power index provides independent and incremental prediction in adverse outcomes beyond traditional haemodynamic and cardio-renal risk factors

Heart failure is associated with accelerated age related metabolic bone disease

Background:The heart failure (HF)-syndrome is associated with neuro-hormonal activation, chronic kidney disease (CKD), inflammation and alterations in the phosphorus-metabolism, all of which are involved in regulation of mineral bone density. However, the role of HF as an independent factor associated with metabolic bone disease (MBD) remains unclear. Methods:HF-patients undergoing dual X-ray absorptiometry (DEXA) were matched in a 1:2 fashion against age and gender matched controls without HF, to determine the proportion of osteoporosis (T-score <-2.5). HF-status was tested against known predictors of MBD. Correlation analysis and Z-score analysis were used to assess the impact of HF on age-related bone demineralisation. Results:A total of 190 HF-patients (age = 80 +/- 10 years, female = 61%) were age and gender matched to 380 controls. HF-patients had a higher proportion of osteoporosis (26 vs 17%;p = .007). HF patients had a lower averaged mineral bone density expressed in g/cm(2) (p = .030), T-scores (p = .001) and Z-scores (p <.001). After adjusting for the individual osteoporosis risk-factors of the FRAX-score, difference in baseline features, kidney function and phosphorus-metabolism alterations, heart failure remained independently associated with a lower averaged T-score (Adjusted beta= -0.189;p = .017). Heart failure was associated with an accelerated age-related decline in mineral bone density (p = .0418). Therapies with ACE-I or ARBs and beta-blockers associated with ameliorated bone demineralisation (p = .023, respectivelyp = .029), while loop diuretic associated with worsened bone demineralization (p <.001). Conclusion:Heart failure independently associates with MBD and higher prevalence of osteoporosis. Heart failure aggravates the aged related loss in mineral bone density while treatment with neuro-hormonal blockers seemed to ameliorate this finding

Tailored algorithms for the detection of the atmospheric boundary layer height from common automatic lidars and ceilometers (ALC)

A detailed understanding of atmospheric boundary layer (ABL) processes is key to improve forecasting of pollution dispersion and cloud dynamics in the context of future climate scenarios. International networks of automatic lidars and ceilometers (ALC) are gathering valuable data that allow for the height of the ABL and its sublayers to be derived in near real time. A new generation of advanced methods to automatically detect the ABL heights now exist. However, diversity in ALC models means these algorithms need to be tailored to instrument-specific capabilities. Here, the advanced algorithm STRATfinder is presented for application to high signal-to-noise ratio (SNR) ALC observations, and results are compared to an automatic algorithm designed for low-SNR measurements (CABAM). The two algorithms are evaluated for application in an operational network setting. Results indicate that the ABL heights derived from low-SNR ALC have increased uncertainty during daytime deep convection, while high-SNR observations can have slightly reduced capabilities in detecting shallow nocturnal layers. Agreement between the ALC-based methods is similar when either is compared to the ABL heights derived from temperature profile data. The two independent methods describe very similar average diurnal and seasonal variations. Hence, high-quality products of ABL heights may soon become possible at national and continental scales

Prognostic Role of Pulmonary Arterial Capacitance in Advanced Heart Failure

Background—Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. Methods and Results—We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=−0.64) and wedge pressure (r=−0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P\u3c0.0001) and higher PVR (P\u3c0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84–1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s–1·cm–5, P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P\u3c0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P\u3c0.0001). Conclusions—PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy

Differential Response to Cardiac Resynchronization Therapy and Clinical Outcomes According to QRS Morphology and QRS Duration

ObjectivesThe goal of this study was to examine the relative impact of QRS morphology and duration in echocardiographic responses to cardiac resynchronization therapy (CRT) and clinical outcomes.BackgroundAt least one-third of all patients treated with CRT fail to derive benefit. Patients without left bundle branch block (LBBB) or patients with smaller QRS duration (QRSd) respond less or not at all to CRT.MethodsWe retrospectively assessed baseline characteristics, clinical and echocardiographic response, and outcomes of all patients who received CRT at our institution between December 2003 and July 2007. Patients were stratified into 4 groups according to their baseline QRS morphology and QRSd.ResultsA total of 496 patients were included in the study; 216 (43.5%) had LBBB and a QRSd ≥150 ms, 85 (17.1%) had LBBB and QRSd <150 ms, 92 (18.5%) had non-LBBB and a QRSd ≥150 ms, and 103 (20.8%) had non-LBBB and QRSd <150 ms. Echocardiographic response (change in ejection fraction) was better in patients with LBBB and QRSd ≥150 ms (12 ± 12%) than in those with LBBB and QRSd <150 ms (8 ± 10%), non-LBBB and QRSd ≥150 ms (5 ± 9%), and non-LBBB and QRSd <150 ms (3 ± 11%) (p < 0.0001). In a multivariate stepwise model with change in ejection fraction as the dependent variable, the presented classification was the most important independent variable (p = 0.0003). Long-term survival was better in LBBB patients with QRSd ≥150 ms (p = 0.02), but this difference was not significant after adjustment for other baseline characteristics (p = 0.15).ConclusionsQRS morphology is a more important baseline electrocardiographic determinant of CRT response than QRSd

Use and caregiver-reported efficacy of medical cannabis in children and adolescents in Switzerland.

Evidence on the use and efficacy of medical cannabis for children is limited. We examined clinical and epidemiological characteristics of medical cannabis treatment and caregiver-reported effects in children and adolescents in Switzerland. We collected clinical data from children and adolescents (< 18 years) who received Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), or a combination of the two between 2008 and 2019 in Switzerland. Out of 205 contacted families, 90 agreed to participate. The median age at the first prescription was 11.5 years (interquartile range (IQR) 6-16), and 32 patients were female (36%). Fifty-one (57%) patients received CBD only and 39 (43%) THC. Patients were more likely to receive THC therapy if one of the following symptoms or signs were present: spasticity, pain, lack of weight gain, vomiting, or nausea, whereas seizures were the dominant indication for CBD therapy. Improvements were reported in 59 (66%) study participants. The largest treatment effects were reported for pain, spasticity, and frequency of seizures in participants treated with THC, and for those treated with pure CBD, the frequency of seizures. However, 43% of caregivers reported treatment interruptions, mainly because of lack of improvement (56%), side effects (46%), the need for a gastric tube (44%), and cost considerations (23%).Conclusions: The effects of medical cannabis in children and adolescents with chronic conditions are unknown except for rare seizure disorders, but the caregiver-reported data analysed here may justify trials of medical cannabis with standardized concentrations of THC or CBD to assess its efficacy in the young. What is Known: • The use of medical cannabis (THC and CBD) to treat a variety of diseases among children and adolescents is increasing. • In contrast to adults, there is no evidence to support the use of medical cannabis to treat chronic pain and spasticity in children, but substantial evidence to support the use of CBD in children with rare seizure disorders. What is New: • This study provides important insights into prescription practices, dosages, and treatment outcomes in children and adolescents using medical cannabis data from a real-life setting. • The effects of medical cannabis in children and adolescents with chronic conditions shown in our study support trials of medical cannabis for chronic conditions