Biatrial Remodeling in Patients with Cystic Fibrosis

BACKGROUND: Previous studies have focused on left and right ventricular remodeling in cystic fibrosis (CF), whereas atrial function has not been assessed in detail so far. We sought to investigate left and right atrial (LA and RA) function in patients with CF. METHODS: This retrospective investigation included 82 CF patients (64 survivors and 18 non-survivors) who were referred to CF department over the period of four years, as well as 32 control subjects matched by age and gender. All participants underwent an echocardiographic examination including a strain analysis, which was performed offline and blinded for groups. RESULTS: LA and RA volume indexes were significantly higher in CF patients than in controls and were particularly high in CF non-survivors. LA conduit and reservoir functions were significantly worse in CF survivors and non-survivors, compared with control subjects. RA phasic function was not different between controls, CF survivors and non-survivors. The parameters of lung function (forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)) and the LA and RA volume indexes were predictors of mortality in CF patients. However, in a multivariate analysis, only FVC was an independent predictor of mortality in CF patients. CONCLUSIONS: Our results suggest that both atria are enlarged, but only LA function is impaired in CF patients. LA reservoir and conduit function is particularly deteriorated in CF patients. Though statistical significance was not reached due to our limited sample size, there was a trend of deterioration of LA and RA function from controls across CF survivors to CF non-survivors. LA and RA enlargement represented predictors of mortality in CF patients

Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure

The cardiac lipid panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to four commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham risk score (FRS), Barcelona bio-HF (BCN Bio-HF) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, BCN Bio-HF 0.72, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients

Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure

The cardiac lipid panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to four commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham risk score (FRS), Barcelona bio-HF (BCN Bio-HF) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, BCN Bio-HF 0.72, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients

Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure

The cardiac lipid panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to four commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham risk score (FRS), Barcelona bio-HF (BCN Bio-HF) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, BCN Bio-HF 0.72, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients

Incremental prognostic value of a novel metabolite‐based biomarker score in congestive heart failure patients

Aims: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has shown to improve the diagnostic value of N terminal pro B type natriuretic peptide (NT-proBNP). However, little is known about its usefulness in predicting outcomes. In this study, we developed a risk score for 4-year cardiovascular death in elderly chronic heart failure (CHF) patients using the CLP. Methods and results: From the Cardiac Insufficiency Bisoprolol Study in Elderly trial, we included 280 patients with CHF aged >65 years. A targeted metabolomic analysis of the CLP biomarkers was performed on baseline serum samples. Cox regression was used to determine the association of the biomarkers with the outcome after accounting for established risk factors. A risk score ranging from 0 to 4 was calculated by counting the number of biomarkers above the cut-offs, using Youden index. During the mean (standard deviation) follow-up period of 50 (8) months, 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve for the model based on clinical variables was 0.84, the second model with NT-proBNP was 0.86, and the final model with the CLP was 0.90. The categorical net reclassification index was 0.25 using three risk categories: 0-60% (low), 60-85% (intermediate), and >85% (high). The continuous net reclassification index was 0.772, and the integrated discrimination index was 0.104. Conclusions: In patients with CHF, incorporating a panel of three metabolite-based biomarkers into a risk score improved the prognostic utility of NT-proBNP by predicting long-term cardiovascular death more precisely. This novel approach holds promise to improve clinical risk assessment in CHF patients

Incremental prognostic value of a novel metabolite-based biomarker score in congestive heart failure patients

Aims: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has shown to improve the diagnostic value of N terminal pro B type natriuretic peptide (NT-proBNP). However, little is known about its usefulness in predicting outcomes. In this study, we developed a risk score for 4-year cardiovascular death in elderly chronic heart failure (CHF) patients using the CLP. Methods and results: From the Cardiac Insufficiency Bisoprolol Study in Elderly trial, we included 280 patients with CHF aged \u3e65 years. A targeted metabolomic analysis of the CLP biomarkers was performed on baseline serum samples. Cox regression was used to determine the association of the biomarkers with the outcome after accounting for established risk factors. A risk score ranging from 0 to 4 was calculated by counting the number of biomarkers above the cut-offs, using Youden index. During the mean (standard deviation) follow-up period of 50 (8) months, 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve for the model based on clinical variables was 0.84, the second model with NT-proBNP was 0.86, and the final model with the CLP was 0.90. The categorical net reclassification index was 0.25 using three risk categories: 0–60% (low), 60–85% (intermediate), and \u3e85% (high). The continuous net reclassification index was 0.772, and the integrated discrimination index was 0.104. Conclusions: In patients with CHF, incorporating a panel of three metabolite-based biomarkers into a risk score improved the prognostic utility of NT-proBNP by predicting long-term cardiovascular death more precisely. This novel approach holds promise to improve clinical risk assessment in CHF patients

Regional differences among female patients with heart failure from the Cardiac Insufficiency BIsoprolol Study in ELDerly (CIBIS-ELD)

Background: The aim of our study was to examine regional differences in the demographics, etiology, risk factors, comorbidities and treatment of female patients with heart failure (HF) in the Cardiac Insufficiency BI soprolol Study in ELDerly (CIBIS-ELD) clinical trial.Methods and results: One hundred and fifty-nine female patients from Germany and 169 from Southeastern (SE) Europe (Serbia, Slovenia and Montenegro) were included in this subanalysis of the CIBIS-ELD trial. Women comprised 54% of the study population in Germany and 29% in SE Europe. German patients were significantly older. The leading cause of HF was arterial hypertension in German patients, 71.7% of whom had a preserved ejection fraction. The leading etiology in SE Europe was the coronary artery disease; 67.6% of these patients had a reduced left ventricular ejection fraction (34.64 ± 7.75%). No significant differences were found in the prevalence of traditional cardiovascular risk factors between the two regions (hypertension, diabetes, hypercholesterolemia, smoking and family history of myocardial infarction). Depression, chronic obstructive pulmonary disease and malignancies were the comorbidities that were noted more frequently in the German patients, while the patients from SE Europe had a lower glomerular filtration rate. Compared with the German HF patients, the females in SE Europe received significantly more angiotensin converting enzyme inhibitors, loop diuretics and less frequently angiotensin receptor blockers and mineralocorticoid receptor antagonists.Conclusions: Significant regional differences were noted in the etiology, comorbidities and treatment of female patients with HF despite similar risk factors. Such differences should be considered in the design and implementation of future clinical trials, especially as women remain underrepresented in large trial populations.

Untersuchung eines neuen Aspekts der Lebensqualität und Vergleich mit der physischen und psychischen Komponente der generischen Lebensqualität

Background: Heart failure (HF) is a severe condition with high mortality and hospitalization rates. Therapy optimization, like beta-blocker titration, is often accompanied by adverse events (AEs). Besides improvement of survival and reduction of re-hospitalizations, enhancement of self-rated health (SRH) and quality of life (QoL) have been recognized as important therapy targets. However, little is known about the relationship between SRH and AEs; and about the determinants of change in QoL. Physical well-being is thought to be one component of QoL and can be assessed with the innovative questionnaire FEW16. Yet, it hasn’t been validated in HF. Aim: 1\. What is the relation between SRH and AEs in HF patients undergoing beta-blocker titration? 2\. What are the determinants of change in QoL during beta-blocker titration in HF? 3\. Can the FEW16 questionnaire be validated for its use in HF? Methods: These are prespecified analyses of CIBIS-ELD trial in elderly HF patients (≥65yrs), randomized to bisoprolol or carvedilol. Patients were examined at baseline, 12 weeks, and 2-4 years with the Short Form Health Survey (SF-36), Fragebogen für die Erhebung des körperlichen Wohlbefindens (FEW 16) and Patient Health Questionnaire for Depression (PHQD). Results: More patients reported fair/poor SRH at baseline (36% vs. 30%, p=0.012); after 12 weeks, SRH improved in 34% and worsened in 8% (p=0.001). In 64 % AEs were reported. SRH predicted AEs in a multivariate model along with age, 6-min. walk test distance and ejection fraction. During the treatment mean psychosocial and physical QoL improved. Baseline QoL and depression, and change in depression were main determinants of changes in QoL, cardiac severity markers were weaker predictors. At baseline, after 3 months and after 2-4 years mean FEW16 scores were 3.04 ± 1.04; 3.19 ± 0.94; and 2.77 ± 0.94. Cronbach’s alpha for subscales resilience: 0.84; ability to enjoy: 0.80; vitality: 0.88; inner peace: 0.87; total score: 0.95. Intraclass correlation coefficient (ICC) was 0.87 (95% CI 0.84–0.89, ICC (1.4). Pearson’s correlations of FEW16 with SF36 and PHQ-D were significant. FEW16 total score correlated with six minutes walking distance and heart rate. Conclusion: SRH seems to be an independent predictor of AEs during titration of betablockers. Depression was the main determinant of change of QoL, whereas clinical Parameters were less associated. FEW16 questionnaire showed high validity through its reliability, internal consistency, and intraclass correlation. The FEW-16-scores correlated well with SF36-scores (physical and mental) and clinical markers of exercise tolerance.Hintergrund: Herzinsuffizienz (HI) ist eine schwerwiegende Erkrankung mit hoher Sterblichkeit und hohen Hospitalisierungsraten. Therapieoptimierung, wie Betablocker-Titration, ist oft mit unerwünschten Ereignissen (AEs) vergesellschaftet. Neben der Verbesserung der Sterblichkeit und Reduktion der Rehospitalisierungen, wurde die Steigerung der selbsteingeschätzten Gesundheit (SRH) und der Lebensqualität als wichtige Therapieziele erkannt. Dennoch ist bislang wenig bekannt über den Zusammenhang zwischen SRH und AEs und über die Determinanten einer Veränderung der Lebensqualität. Körperliches Wohlbefinden wird als eine Komponente der Lebensqualität angesehen und kann mit dem innovativen FEW-16- Fragebogen erhoben werden. Jedoch wurde dieser noch nicht bei Herzinsuffizienz validiert. Ziele: 1\. Wie ist der Zusammenhang zwischen SRH und AEs bei Patienten mit Herzinsuffizienz während einer Betablocker- Titration? 2\. Was sind die Determinanten einer Veränderung der Lebensqualität? 3\. Kann der FEW-16-Fragebogen bei Patienten mit Herzinsuffizienz validiert werden? Methoden: Dies sind vordefinierte Analysen der CIBIS-ELD-Studie über ältere Herzinsuffizienzpatienten (≥65 Jahre), randomisiert zu Bisoprolol oder Carvedilol. Die Patienten wurden bei Einschluss, nach 12 Wochen und nach 2-4 Jahren mit dem Short-Form-Health- Survey (SF-36), dem Fragebogen für die Erhebung des körperlichen Wohlbefindens (FEW 16) und dem Patient-Health-Questionnaire for Depression (PHQ-D) untersucht. Ergebnisse: Mehr Patienten berichteten mäßige/schlechte SRH bei Einschluss (36% vs. 30%, p=0.012); nach 12 Wochen verbesserte sich SRH bei 34% und verschlechterte sich bei 8% (p=0.001). Bei 64% der Patienten traten AEs auf. SRH war neben dem Alter, der 6-Minuten- Gehtest-Distanz und der Ejektionsfraktion ein unabhängiger Prädiktor für das Auftreten von AEs. Während der Behandlung verbesserte sich die mittlere psychosoziale und physische Komponente der Lebensqualität. Die Lebensqualität und Depression bei Einschluss sowie Veränderung der Depression waren die stärksten Determinanten einer Veränderung der Lebensqualität. Klinische Parameter waren schwächere Prädiktoren. Bei Einschluss, nach 3 Monaten und nach 2-4 Jahren war der mittlere FEW-Score 3.04 ± 1.04; 3.19 ± 0.94; und 2.77 ± 0.94. Cronbachs Alpha war für die Subskala “Belastbarkeit” 0.84; “Genussfähigkeit” 0.80; “Vitalität” 0.88; “Innerer Frieden” 0.87; Gesamtscore 0.95. Der Intraclass Korrelationskoeffizient war 0.87 (95% CI 0.84–0.89, ICC (1.4). Die Korrelation nach Pearson vom FEW16 mit SF36 und PHQ-D waren signifikant. Der absolute FEW- Score korrelierte mit der 6-Minuten-Gehtest-Distanz und der Herzfrequenz. Schlussfolgerung: Die selbsteingeschätzte Gesundheit ist ein unabhängiger Prädiktor für das Auftreten von AEs während Betablocker-Titration. Depression war die Hauptdeterminante von Veränderungen der Lebensqualität. Klinische Parameter hingegen spielten eine untergeordnete Rolle. Der FEW16-Fragebogen zeigte eine gute Reliabilität, interne Konsistenz und intraclass Korrelation. Die FEW16-Scores korrelierten gut mit physischen und psychischen SF36-Scores der Lebensqualität und klinischen Parametern der Belastbarkeit

Multilayer myocardial strain improves the diagnosis of heart failure with preserved ejection fraction

Aims: The diagnostic and treatment of patients with heart failure with preserved ejection fraction (HFpEF) are both hampered by an incomplete understanding of the pathophysiology of the disease. Novel imaging tools to adequately identify these patients from individuals with a normal cardiac function and respectively patients with HF with reduced EF are warranted. Computing multilayer myocardial strain with feature tracking is a fast and accurate method to assess cardiac deformation. Our purpose was to assess the HFpEF diagnostic ability of multilayer strain parameters and compare their sensitivity and specificity with other established parameters. Methods and results: We included 20 patients with a diagnosis of HFpEF and, respectively, 20 matched controls. We assessed using feature-tracking cardiac magnetic resonance longitudinal and circumferential myocardial strain at three distinct layers of the myocardium: subendocardial (Endo-), mid-myocardial (Myo-), and subepicardial (Epi-). Comparatively, we additionally assessed various others clinical, imaging, and biochemical parameters with a putative role in HFpEF diagnostic: left ventricular end-diastolic volume (LVEDV), left ventricular mass (LVM), interventricular septum (IVS) wall thickness and free wall thickness, left atrial volume and strain, septal and lateral mitral annular early diastolic velocity (e`), E/e' ratio, and plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Global longitudinal strain (GLS) is significantly impaired at Endo (-20.8 ± 4.0 vs. -23.2 ± 3.4,P = 0.046), Myo- (-18.0 ± 3.0 vs. -21.0 ± 2.5,P = 0.002), and Epi- (-12.2 ± 2.0 vs. -16.2 ± 2.5,P < 0.001) levels. Compared with any other imaging parameter, an Epi-GLS lower than 13% shows the highest ability to detect patients with HFpEF [area under the curve (AUC) = 0.90 (0.81-1),P < 0.001] and in tandem with NT-proBNP can diagnose with maximal sensibility (93%) and specificity (100%), patients with HFpEF from normal, composed variable [AUC = 0.98 (0.95-1),P < 0.001]. In a logistic regression model, a composite predictive variable taking into account both GLS Epi and NT-proBNP values in each individual subject reached a sensitivity of 89% and a specificity of 100% with an AUC of 0.98 (0.95-1),P < 0.001, to detect HFpEF. Conclusions: Epi-GLS is a promising new imaging parameter to be considered in the clinical assessment of HFpEF patients. Given its excellent specificity, in tandem with a highly sensitive parameter such as NT-proBNP, Epi-GLS holds the potential to greatly improve the current diagnostic algorithms

Syncopes and clinical outcome in heart failure: results from prospective clinical study data in Germany

Aims Whereas syncopal episodes are a frequent complication of cardiovascular disorders, including heart failure (HF), little is known whether syncopes impact the prognosis of patients with HF. We aimed to assess the impact of a history of syncope (HoS) on overall and hospitalization-free survival of these patients. Methods and results We pooled the data of prospective, nationwide, multicentre studies conducted within the framework of the German Competence Network for Heart Failure including 11 335 subjects. Excluding studies with follow-up periods <10 years, we assessed 5318 subjects. We excluded a study focusing on cardiac changes in patients with an HIV infection because of possible confounding factors and 849 patients due to either missing key parameters or missing follow-up data, resulting in 3594 eligible subjects, including 2130 patients with HF [1564 patients with heart failure with reduced ejection fraction (HFrEF), 314 patients with heart failure with mid-range ejection fraction, and 252 patients with heart failure with preserved ejection fraction (HFpEF)] and 1464 subjects without HF considered as controls. HoS was more frequent in the overall cohort of patients with HF compared with controls (P < 0.001)-mainly driven by the HFpEF subgroup (HFpEF vs. controls: 25.0% vs. 12.8%, P < 0.001). Of all the subjects, 14.6% reported a HoS. Patients with HFrEF in our pooled cohort showed more often syncopes than subjects without HF (15.0% vs. 12.8%, P = 0.082). Subjects with HoS showed worse overall survival [42.4% vs. 37.9%, hazard ratio (HR) = 1.21, 99% confidence interval (0.99, 1.46), P = 0.04] and less days alive out of hospital [HR = 1.39, 99% confidence interval (1.18, 1.64), P < 0.001] compared with all subjects without HoS. Patients with HFrEF with HoS died earlier [30.3% vs. 41.6%, HR = 1.40, 99% confidence interval (1.12, 1.74), P < 0.001] and lived fewer days out of hospital than those without HoS. We could not find these changes in mortality and hospital-free survival in the heart failure with mid-range ejection fraction and HFpEF cohorts. HoS represented a clinically high-risk profile within the HFrEF group-combining different risk factors. Further analyses showed that among patients with HFrEF with HoS, known cardiovascular risk factors (e.g. age, male sex, diabetes mellitus, and anaemia) were more prevalent. These constellations of the risk factors explained the effect of HoS in a multivariable Cox regression models. Conclusions In a large cohort of patients with HF, HoS was found to be a clinically and easily accessible predictor of both overall and hospitalization-free survival in patients with HFrEF and should thus routinely be assessed