Christian Zugck

Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables.

Objective: To assess health related quality of life of patients with congestive heart failure; to compare their quality of life with the previously characterised general population and in those with other chronic diseases; and to correlate the different aspects of quality of life with relevant somatic variables. Setting: University hospital. Patients and design: A German version of the generic quality of life measure (SF-36) containing eight dimensions was administered to 205 patients with congestive heart failure and systolic dysfunction. Cardiopulmonary evaluation included assessment of New York Heart Association (NYHA) functional class, left ventricular ejection fraction, peak oxygen uptake, and the distance covered during a standardised six minute walk test. Results: Quality of life significantly decreased with NYHA functional class (linear trend: p < 0.0001). In NYHA class III, the scores of five of the eight quality of life domains were reduced to around one third of those in the general population. The pattern of reduction was different in patients with chronic hepatitis C and major depression, and similar in patients on chronic haemodialysis. Multiple regression analysis showed that only the NYHA functional class was consistently and closely associated with all quality of life scales. The six minute walk test and peak oxygen uptake added to the explanation of the variance in only one of the eight quality of life domains (physical functioning). Left ventricular ejection fraction, duration of disease, and age showed no clear association with quality of life. Conclusions: In congestive heart failure, quality of life decreases as NYHA functional class worsens. Though NYHA functional class was the most dominant predictor among the somatic variables studied, the major determinants of reduced quality of life remain unknown.

Respiratory Muscle Dysfunction in Congestive Heart Failure Clinical Correlation and Prognostic Significance

BackgroundIn congestive heart failure (CHF), the prognostic significance of impaired respiratory muscle strength has not been established. Methods and ResultsMaximal inspiratory pressure (Pimax) was prospectively determined in 244 consecutive patients (207 men) with CHF (ischemic, n=75; idiopathic dilated cardiomyopathy, n=169; age, 54±11 years; left ventricular ejection fraction [LVEF], 22±10%). Pimax was lower in the 244 patients with CHF than in 25 control subjects (7.6±3.3 versus 10.5±3.7 kPa;P =0.001). The 57 patients (23%) who died during follow-up (23±16 months; range, 1 to 48 months) had an even more reduced Pimax (6.3±3.2 versus 8.1±3.2 kPa in survivors;P =0.001). Kaplan-Meier survival curves differentiated between patients subdivided according to quartiles for Pimax (P =0.014). Pimax was a strong risk predictor in both univariate (P =0.001) and multivariate Cox proportional hazard analyses (P =0.03); multivariate analyses also included NYHA functional class, LVEF, peak oxygen consumption (peak ˙Vo2), and norepinephrine plasma concentration. The areas under the receiver-operating characteristic curves for prediction of 1-year survival were comparable for Pimax and peak ˙Vo2 (area under the curve [AUC], 0.68 versus 0.73;P =0.28), and they improved with the triple combination of Pimax, peak ˙Vo2, and LVEF (AUC, 0.82;P =0.004 compared with AUC of Pimax). ConclusionsIn patients with CHF, inspiratory muscle strength is reduced and emerges as a novel, independent predictor of prognosis. Because testing for Pimax is simple in clinical practice, it might serve as an additional factor to improve risk stratification and patient selection for cardiac transplantation.

Depression increasingly predicts mortality in the course of congestive heart failure.

Congestive heart failure (CHF) is frequently associated with depression. However, the impact of depression on prognosis has not yet been sufficiently established.

Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

OBJECTIVES The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. BACKGROUND AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. METHODS Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. RESULTS After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p < 0.0001), diastolic dysfunction (p < 0.01), the pathologic free light chains (p < 0.05), cardiac troponin-T (cTnT) (p < 0.01), and the Karnofsky index (p < 0.001) remained as independent predictors. 2D-GLS delineated a superior prognostic value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and serological biomarkers. CONCLUSIONS In the largest serial investigation reported so far, reduced LV longitudinal function served as an independent predictor of survival in AL amyloidosis and offered incremental information beyond standard clinical and serological parameters.

Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy

Objective Owing to its variable clinical course, risk stratification is of paramount importance in non-ischaemic dilated cardiomyopathy (DCM). The goal of this study was to investigate the long-term prognostic significance of late gadolinium enhancement (LGE) as detected by contrast-enhanced cardiovascular magnetic resonance (CE-CMR) in patients with DCM. Design Observational cohort study. Setting University hospital. Patients 184 consecutive patients with DCM. Measurements CE-CMR was performed on a 1.5 T clinical scanner. Presence, extent and patterns of LGE were determined by two independent observers. Outcome measures Patients were followed for the composite end point of cardiac death, hospitalisation for decompensated heart failure, or appropriate implantable cardioverter defibrillator discharge for a mean±SEM of 685±30 days. Results LGE was detected in 72/184 patients (39%) and was associated with a lower left ventricular (LV) ejection fraction (31% (20.9–42.2%) vs 44% (33.1–50.9%), p<0.001), higher LV end-diastolic volume index (133 (116–161) ml/m2 vs 109 (92.7–137.6) ml/m2, p<0.001) and higher LV mass (80 (67.1–94.8) g/m2 vs 65.8 (55.2–82.9) g/m2, p<0.001). Patients in whom LGE was present were more likely to experience the composite end point (15/72 vs 6/112, p=0.002). Receiver operating characteristic curve analysis revealed a LGE of >4.4% of LV mass as optimal discriminator for the composite end point. When entered into multivariate Cox regression analysis, LGE retained its independent predictive value, yielding an associated HR of 3.4 (95% CI 1.26 to 9). Conclusion The presence of LGE in this large DCM patient cohort is associated with pronounced LV remodelling, functional impairment and an adverse outcome. Further research is necessary to determine whether these findings will aid the clinical management of DCM patients.

Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure

OBJECTIVES This prospective study tested whether transmitral flow patterns add incremental value to peak oxygen consumption (VO2) in determining the prognosis of patients with chronic congestive heart failure (CHF) and systolic dysfunction. BACKGROUND Peak VO2 is an objective marker of functional capacity and is routinely used as a criterion to identify heart transplant candidates. Diastolic dysfunction limits functional capacity, but its prognostic importance relative to that of peak VO2 is unknown. METHODS Peak VO2 and mitral inflow velocities were prospectively measured in 311 consecutive patients (mean age 54 years, 84% male) with impaired left ventricular function (ejection fraction <40%; 88 patients with ischemic and 223 with dilated cardiomyopathy) who were evaluated for heart transplant candidacy. RESULTS During a mean follow-up period of 512 +/- 314 days, 65 patients died and 43 patients underwent heart transplantation. Diastolic filling patterns, peak VO2 and left ventricular end-diastolic diameters were independent predictors of cardiac mortality. In patients with peak VO2 < or = 14 ml/min per kg body weight, the outcome was markedly poorer in the presence of restrictive filling patterns as compared with their absence (two-year survival rate 52% vs. 80%). Similarly, despite peak VO2 levels >14 ml/min per kg, the outcome was less favorable in the presence of restrictive filling patterns (two-year survival rate 80% vs. 94%). A risk-stratification model based on the identified independent noninvasive predictors separated groups into those with high (93%), intermediate (65%) and low (39%) two-year survival rates. CONCLUSIONS Transmitral flow patterns add incremental value to peak VO2 in determining the prognosis of patients with CHF and impaired systolic function.

Osteopontin, a New Prognostic Biomarker in Patients With Chronic Heart Failure

Background—Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several animal models of cardiac failure and may thus represent a new biomarker that facilitates risk stratification in patients with heart failure. We therefore tested whether osteopontin plasma levels are elevated in patients with chronic heart failure and whether they provide independent prognostic information. Methods and Results—We analyzed osteopontin plasma levels in 420 patients with chronic heart failure due to significantly impaired left ventricular systolic function and correlated the results with disease stage and prognostic information (median follow-up of 43 months). We found that osteopontin plasma levels were significantly elevated in patients with heart failure as compared with healthy control subjects (532 versus 382 ng/mL, P=0.008), irrespective of heart failure origin (ischemic versus dilated cardiomyopathy). Furthermore, osteopontin levels were higher in patients with moderate to severe heart failure than in patients with no or mild symptoms (672 ng/mL for New York Heart Association class III/IV versus 479 ng/mL for class I/II, P<0.0001). Estimated 4-year death rates in patients with osteopontin levels above or below a cutoff value derived from receiver operating characteristic analyses were 56.5% and 28.4%, respectively (hazard ratio 3.4, 95% confidence interval 2.2 to 5.3, P<0.0001). In a multivariable model that included demographic, clinical, and biochemical parameters such as N-terminal prohormone brain natriuretic peptide, osteopontin emerged as an independent predictor of death (hazard ratio 2.3, 95% confidence interval 1.4 to 3.5, P<0.001). Conclusion—Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with chronic heart failure.

Risk stratification in middle-aged patients with congestive heart failure: prospective comparison of the Heart Failure Survival Score (HFSS) and a simplified two-variable model

The performance of a US‐American scoring system (Heart Failure Survival Score, HFSS) was prospectively evaluated in a sample of ambulatory patients with congestive heart failure (CHF). Additionally, it was investigated whether the HFSS might be simplified by assessment of the distance ambulated during a 6‐min walk test (6′WT) instead of determination of peak oxygen uptake (peak VO2).

HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy

Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM. We show that a 600-kb region of linkage disequilibrium (LD) on 5q31.2-3, harboring multiple genes, is associated with cardiomyopathy in three independent Caucasian populations (combined P-value = 0.00087). Functional assessment in zebrafish demonstrates that at least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents. Evolutionary analysis across multiple vertebrate genomes suggests that this heart failure-associated LD block emerged by a series of genomic rearrangements across amphibian, avian, and mammalian genomes and is maintained as a cluster in mammals. Taken together, these observations challenge the simple notion that disease phenotypes can be traced to altered function of a single locus within a haplotype and suggest that a more detailed assessment of causality can be necessary.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy

AIMS Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. METHODS AND RESULTS Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. CONCLUSION The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.