Heart rate variability: reference values and role for clinical profile and mortality in individuals with heart failure.

AIMS: To establish reference values and clinically relevant determinants for measures of heart rate variability (HRV) and to assess their relevance for clinical outcome prediction in individuals with heart failure. METHODS: Data from the MyoVasc study (NCT04064450; N = 3289), a prospective cohort on chronic heart failure with a highly standardized, 5 h examination, and Holter ECG recording were investigated. HRV markers were selected using a systematic literature screen and a data-driven approach. Reference values were determined from a healthy subsample. Clinical determinants of HRV were investigated via multivariable linear regression analyses, while their relationship with mortality was investigated by multivariable Cox regression analyses. RESULTS: Holter ECG recordings were available for analysis in 1001 study participants (mean age 64.5 ± 10.5 years; female sex 35.4%). While the most frequently reported HRV markers in literature were from time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Age, sex, dyslipidemia, family history of myocardial infarction or stroke, peripheral artery disease, and heart failure were strongly related to HRV in multivariable models. In a follow-up period of 6.5 years, acceleration capacity [HRperSD 1.53 (95% CI 1.21/1.93), p = 0.0004], deceleration capacity [HRperSD: 0.70 (95% CI 0.55/0.88), p = 0.002], and time lag [HRperSD 1.22 (95% CI 1.03/1.44), p = 0.018] were the strongest predictors of all-cause mortality in individuals with heart failure independently of cardiovascular risk factors, comorbidities, and medication. CONCLUSION: HRV markers are associated with the cardiovascular clinical profile and are strong and independent predictors of survival in heart failure. This underscores clinical relevance and interventional potential for individuals with heart failure. GOV IDENTIFIER: NCT04064450.

FEV1 Predicts Cardiac Status and Outcome in Chronic Heart Failure.

BACKGROUND: COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV1 in chronic HF. RESEARCH QUESTION: Is pulmonary function related to the progression of chronic HF? STUDY DESIGN AND METHODS: The MyoVasc study (ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF. RESULTS: Overall 2,998 participants (age range, 35-84 years) with available FEV1 data were eligible for analysis. Linear multivariate regression analysis revealed an independent relationship of FEV1 (per -1 SD) with deteriorated systolic and diastolic left ventricle (LV) function as well as LV hypertrophy under adjustment of age, sex, height, cardiovascular risk factors (CVRFs), and clinical profile (LV ejection fraction: ß-estimate, -1.63% [95% CI, -2.00% to -1.26%]; E/E' ratio: ß-estimate, 0.82 [95% CI, 0.64-0.99]; and LV mass/height2.7: ß-estimate, 1.58 [95% CI, 1.07-2.10]; P < .001 for all). During a median time to follow-up of 2.6 years (interquartile range, 1.1-4.1 years), worsening of HF occurred in 235 individuals. In Cox regression model adjusted for age, sex, height, CVRF, and clinical profile, pulmonary function (FEV1 per -1 SD) was an independent predictor of worsening of HF (hazard ratio [HR], 1.44 [95% CI, 1.27-1.63]; P < .001). Additional adjustment for obstructive airway pattern and C-reactive protein mitigated, but did not substantially alter, the results underlining the robustness of the observed effect (HRFEV1, 1.39 [95% CI, 1.20-1.61]; P < .001). The predictive value of FEV1 was consistent across subgroups, including individuals without obstruction (HR, 1.55 [95% CI, 1.34-1.77]; P < .001) and nonsmokers (HR, 1.72 [95% CI, 1.39-1.96]; P < .001). INTERPRETATION: FEV1 represents a strong candidate to improve future risk stratification and prevention strategies in individuals with chronic, stable HF. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04064450; URL: www.clinicaltrials.gov.

HLA Class II Allele Analyses Implicate Common Genetic Components in Type 1 and Non-Insulin-Treated Type 2 Diabetes.

CONTEXT: Common genetic susceptibility may underlie the frequently observed co-occurrence of type 1 and type 2 diabetes in families. Given the role of HLA class II genes in the pathophysiology of type 1 diabetes, the aim of the present study was to test the association of high density imputed human leukocyte antigen (HLA) genotypes with type 2 diabetes. OBJECTIVES AND DESIGN: Three cohorts (Ntotal = 10 413) from Leipzig, Germany were included in this study: LIFE-Adult (N = 4649), LIFE-Heart (N = 4815) and the Sorbs (N = 949) cohort. Detailed metabolic phenotyping and genome-wide single nucleotide polymorphism (SNP) data were available for all subjects. Using 1000 Genome imputation data, HLA genotypes were imputed on 4-digit level and association tests for type 2 diabetes, and related metabolic traits were conducted. RESULTS: In a meta-analysis including all 3 cohorts, the absence of HLA-DRB5 was associated with increased risk of type 2 diabetes (P = 0.001). In contrast, HLA-DQB*06:02 and HLA-DQA*01:02 had a protective effect on type 2 diabetes (P = 0.005 and 0.003, respectively). Both alleles are part of the well-established type 1 diabetes protective haplotype DRB1*15:01~DQA1*01:02~DQB1*06:02, which was also associated with reduced risk of type 2 diabetes (OR 0.84; P = 0.005). On the contrary, the DRB1*07:01~DQA1*02:01~DQB1*03:03 was identified as a risk haplotype in non-insulin-treated diabetes (OR 1.37; P = 0.002). CONCLUSIONS: Genetic variation in the HLA class II locus exerts risk and protective effects on non-insulin-treated type 2 diabetes. Our data suggest that the genetic architecture of type 1 diabetes and type 2 diabetes might share common components on the HLA class II locus.