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.

Sex-Specific Relationship Between Parathyroid Hormone and Platelet Indices in Phenotypes of Heart Failure-Results From the MyoVasc Study.

Background: Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF. Aim: This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF. Methods and Results: PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [ß = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [ß = -7.6 (-15; -0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF). Conclusion: This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.

The impact of platelet indices on clinical outcome in heart failure: results from the MyoVasc study.

AIMS: Platelet indices have been associated with traditional cardiovascular risk factors, cardiovascular diseases and all-cause mortality. This study aimed to investigate the role of platelet count, mean platelet volume (MPV) and platelet-to-leukocyte ratio, including platelet-to-monocyte and platelet-to-lymphocyte ratio with cardiac function, heart failure (HF) phenotypes and clinical outcome, worsening of HF. METHODS AND RESULTS: Univariate and multivariable linear and Cox regression analyses were used to investigate the associations between platelet indices, cardiac function and worsening of HF in 3250 subjects enrolled in the MyoVasc study. Higher MPV, lower platelet count, lower platelet-to-leukocyte and platelet-to-monocyte ratios have been associated with reduced left ventricular ejection fraction (beta estimate [ß]MPV [fL]  = -0.05 [-0.09; -0.02], ßplatelet count (× 10/L)9  = 3.4 [1.2; 5.6], ßplatelet-to-leukocyte ratio  = 1.4 [1.1; 1.8], ßplatelet-to-monocyte ratio  = 28 [20; 36]) and increased E/E' ratio (ß MPV [fL]  = 0.04 [0.003; 0.07], ßplatelet count (× 10/L)9  = -3.1 [-5.3; -0.92], ßplatelet-to-leukocyte ratio  = -0.83 [-1.2; -0.46], ßplatelet-to-monocyte ratio  = -20 [-28; -12]), independent of age and sex. Cox regression demonstrated an increased risk for worsening of HF in subjects with MPV > 75th percentile (hazard ratio [HR] = 1.47 [1.16; 1.87]), platelet count < 25th percentile (HR = 1.36 [1.07; 1.74]), platelet-to-leukocyte < 25th percentile (HR = 1.53 [1.20; 1.95]), platelet-to-monocyte < 25th percentile (HR = 1.38 [1.08; 1.77]) and platelet-to-lymphocyte > 75th percentile (HR = 1.50 [1.17; 1.93]) ratios, independent of potential confounders. MPV > 75th percentile and platelet count < 25th percentile were strongly related to outcome in HFpEF vs. HFrEF (P for difference = 0.040). Platelet-to-leukocyte ratios were associated with worse outcome in both HF phenotypes, without a significant difference between HFpEF and HFrEF. CONCLUSIONS: Platelet indices are linked with worse cardiac function and adverse clinical outcome, independent of subjects' underlying cardiovascular profile. This study emphasizes their important value to provide additional information on pathophysiology and risk stratification in HF syndrome.

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure.

Importance: Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited. Objective: To assess the factors associated with GLS and its prognostic value in patients with chronic HF. Design, Setting, and Participants: The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participants with stages A to D HF according to American Heart Association (AHA) criteria were examined at a dedicated study center. Echocardiography was performed with GLS measurement by independent reviewers. Data were analyzed from September 2, 2019, to January 15, 2020. Main Outcomes and Measures: All-cause and cardiac mortality were recorded by structured follow-up and validated via death certificates. Results: In the study sample, data on GLS were available on 2440 individuals, of whom 2186 (mean [SD] age, 65.0 [10.5] years; 1418 [64.9%] men) were classified as having AHA HF stages A to D. Mean (SD) GLS worsened across AHA stages from stage A (n = 434; -19.44 [3.15%]) to stage B (n = 629; -18.01 [3.46%]) to stages C/D (n = 1123; -15.52 [4.64%]). Age (ß = -0.27; 95% CI, -0.47 to -0.067; per decade, P = .009), female sex (ß = -1.2; 95% CI, -1.6 to -0.77; per decade, P < .001), obesity (ß = 0.64; 95% CI, 0.25-1.0; P = .001), atrial fibrillation (ß = 1.2; 95% CI, 0.69-1.6; P < .001), myocardial infarction (ß = 1.5; 95% CI, 1.00-2.1; P < .001), and estimated glomerular filtration rate (ß = -0.53; 95% CI, -0.73 to -0.32; per SD, P < .001) were independently associated with GLS in multivariable regression analysis. Global longitudinal strain was associated with the severity of HF as reflected by N-terminal prohormone B-type natriuretic protein (NT-proBNP) levels after additionally adjusting for cardiac structure and function (P < .001). During follow-up, GLS was associated with all-cause mortality (hazard ratio [HR] per SD, 1.55; 95% CI, 1.19-2.01; P < .001) and cardiac death (HR per SD, 2.32; 95% CI, 1.57-3.42; P < .001) independent of image quality, observer variability, clinical profile, HF medications, NYHA class, and cardiac structure and function. After further adjustment for the NT-proBNP level, GLS remained associated with cardiac death (HR per SD, 1.60; 95% CI, 1.07-2.41; P = .02) but not all-cause mortality (HR per SD, 1.26; 95% CI, 0.95-1.66; P = .11). Conclusions and Relevance: In patients with chronic HF, GLS was associated with clinical and cardiac status, reflected neurohormonal activation, and was associated with cardiac mortality independent of clinical and cardiac status. These findings suggest that GLS may serve as a useful tool to improve risk stratification in patients with HF.

Safety of transradial and transfemoral left ventricular compared with transfemoral right ventricular endomyocardial biopsy.

AIMS: With the present study, we sought to determine the safety of three different endomyocardial biopsy (EMB) access routes in 514 patients admitted for diagnostic workup of heart failure of unknown aetiology. METHODS AND RESULTS: In this retrospective monocentric cohort study, we analysed 514 consecutive patients with heart failure without evidence of significant coronary artery disease or valvular disease undergoing EMB between November 2013 and December 2018, stratified in three access route groups: transradial arterial left ventricular (LV-)EMB (323 patients), transfemoral LV-EMB (138 patients), and transfemoral right ventricular (RV-)EMB (53 patients). Patients undergoing selective transradial LV-EMB were older compared with patients undergoing selective transfemoral LV-EMB or RV-EMB [transradial LV-EMB: 56.0 (45.0/64.0) vs. transfemoral LV-EMB: 53 (42.5/64.5), P = 0.455; transradial LV-EMB: 56 (45.0/64.0) vs. RV-EMB: 53 (42.5/64), P = 0.695] and presented more often in New York Heart Association-functional class III and IV. A total of eight major complications including permanent atrioventricular block requiring pacemaker implantation, pericardial tamponade necessitating pericardiocentesis, stroke and transient cerebral ischaemic attack as well as severe valvular damage, vascular access site complications, and ventricular fibrillation were documented with no significant differences between the groups (8/514, 1.5%). Minor complications such as transient chest pain, non-sustained electrocardiogram abnormalities, and transient atrioventricular block were rare and equally distributed between groups. CONCLUSIONS: Transradial LV-EMB is a safe procedure for experienced radial operators and non-inferior compared with transfemoral LV-EMB and RV-EMB. An accurate peri-procedural and post-procedural monitoring and follow-up care should be recommended for all patients undergoing this procedure in order to identify potential complications.

Direct oral anticoagulants and vitamin K antagonists are linked to differential profiles of cardiac function and lipid metabolism.

BACKGROUND: Experimental data indicate that direct acting oral anticoagulants (DOAC) and vitamin K antagonists (VKA) may exert differential effects on cardiovascular disease. METHODS: Data from the prospective, observational, single-center MyoVasc Study were used to examine associations of DOAC as compared to VKA with subclinical markers of cardiovascular disease, cardiac function, and humoral biomarkers in heart failure (HF). RESULTS: Multivariable analysis adjusted for age, sex, traditional cardiovascular risk factors, comorbidities, and medications with correction for multiple testing demonstrated that DOAC therapy was among all investigated parameters an independent significant predictor of better diastolic function (E/E': ß - 0.24 [- 0.36/- 0.12]; P < 0.0001) and higher levels of ApoA1 (ß + 0.11 g/L [0.036/0.18]; P = 0.0038) compared to VKA therapy. In propensity score-weighted analyses, the most pronounced differences between DOAC and VKA-based therapy were also observed for E/E' (∆ - 2.36) and ApoA1 (∆ + 0.06 g/L). Sensitivity analyses in more homogeneous subsamples of (i) individuals with AF and (ii) individuals with asymptomatic HF confirmed the consistency and robustness of these findings. In the comparison of factor IIa and Xa-directed oral anticoagulation, no differences were observed regarding cardiac function (E/E' ratio: ßIIa inhibitor - 0.22 [- 0.36/- 0.08] vs. ßXa inhibitor - 0.24 [- 0.37/- 0.11]) and lipid metabolism (ApoA1: ßIIa inhibitor 0.10 [0.01/0.18] vs. ßXa inhibitor 0.12 [0.04/0.20]) compared to VKA therapy. CONCLUSION: This study provides the first evidence for differential, non-conventional associations of oral anticoagulants on cardiac function and lipid metabolism in humans. The potentially beneficial effect of DOACs in the highly vulnerable population of HF individuals needs to be further elucidated and may have implications for individually tailored anticoagulation therapy.

Management of Oral Anti-Coagulation in Patients with Heart Failure-Insights from the ThrombEVAL Study.

Patients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.