Cardiogenic Shock: Focus on Non-Cardiac Biomarkers.

PURPOSE OF REVIEW: To examine the evolving multifaceted nature of cardiogenic shock (CS) in the context of non-cardiac biomarkers that may improve CS management and risk stratification. RECENT FINDINGS: There are increasing data highlighting the role of lactate, glucose, and other markers of inflammation and end-organ dysfunction in CS. These biomarkers provide a more comprehensive understanding of the concurrent hemo-metabolic and cellular disturbances observed in CS and offer insights beyond standard structural and functional cardiac assessments. Non-cardiac biomarkers both refine the diagnostic accuracy and improve the prognostic assessments in CS. Further studies revolving around novel biomarkers are warranted to support more targeted and effective therapeutic and management interventions in these high-risk patients.

Patient Focus: Moving Beyond Step Count: An Explanation of Real-World Walking Behaviors Are Associated With Early-Stage Heart Failure: A Project Baseline Health Study.

In this issue of the Journal of Cardiac Failure, Dr. Sooyoon Shin and colleagues look at whether information from wearable devices, or activity trackers, could improve how a medical team monitors activity limitations for people who are at risk of developing heart failure symptoms.

Sex Disparities in Longitudinal Use and Intensification of Guideline-Directed Medical Therapy Among Patients With Newly Diagnosed Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established. METHODS: Patients with incident HFrEF were identified from the 2016 to 2020 Optum deidentified Clinformatics Data Mart Database, which is derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The primary outcome was the use of optimal GDMT within 12 months of HFrEF diagnosis. Consistent with the guideline recommendations during the time period of the study, optimal GDMT was defined as ≥50% of the target dose of evidence-based beta-blocker plus ≥50% of the target dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, or any dose of angiotensin receptor neprilysin inhibitor plus any dose of mineralocorticoid receptor antagonist. The probability of achieving optimal GDMT on follow-up and predictors of optimal GDMT were evaluated with time-to-event analysis with adjusted Cox proportional hazard models. RESULTS: The study cohort included 63 759 patients (mean age, 71.3 years; 15.2% non-Hispanic Black race; 56.6% male). Optimal GDMT use was achieved by 6.2% of patients at 12 months after diagnosis. Female (compared with male) patients with HFrEF had lower use across every GDMT class and lower use of optimal GDMT at each time point at follow-up. In an adjusted Cox model, female sex was associated with a 23% lower probability of achieving optimal GDMT after diagnosis (hazard ratio [HR], 0.77 [95% CI, 0.71-0.83]; P<0.001). The sex disparities in GDMT use after HFrEF diagnosis were most pronounced among patients with commercial insurance (females compared with males; HR, 0.66 [95% CI, 0.58-0.76]) compared with Medicare (HR, 0.85 [95% CI, 0.77-0.92]); Pinteraction sex×insurance status=0.005) and for younger patients (age <65 years: HR, 0.65 [95% CI, 0.58-0.74]) compared with older patients (age ≥65 years: HR, 87 [95% CI, 80-96]) Pinteraction sex×age=0.009). CONCLUSIONS: Overall use of optimal GDMT after HFrEF diagnosis was low, with significantly lower use among female (compared with male) patients. These findings highlight the need for implementation efforts directed at improving GDMT initiation and titration.

Oxygen Uptake Efficiency Slope and Prognosis in Heart Failure With Reduced Ejection Fraction.

The prognostic utility of the oxygen uptake efficiency slope (OUES) in heart failure with reduced ejection fraction is uncertain. In this post hoc analysis of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial (n = 2,074), we tested for associations of OUES and peak oxygen uptake (VO2) with heart failure hospitalization or cardiovascular death in multivariable Cox regression models, adjusting for minute ventilation/carbon dioxide production (VE/VCO2) slope and other important confounders. Harrell's C-statistics assessed the discriminatory performance of OUES and peak VO2. Lower OUES was associated with increased risk of the outcome (quartile 1 vs 4: hazard ratio 2.1 [1.5 to 2.9, p <0.001]). Peak VO2 had greater discrimination than OUES in comparable models (e.g., C-statistic = 0.73 vs 0.70, p <0.001, respectively). In the subgroup with respiratory exchange ratio <1 (n = 358), peak VO2 was associated with the outcome (p <0.001) but OUES was not (p = 0.96). In conclusion, whereas OUES was associated with clinical outcomes independently of VE/VCO2 slope, its prognostic utility was inferior to that of peak VO2, even when measured at submaximal effort.

Comparison of Accuracy of Estimation of Cardiac Output by Thermodilution Versus the Fick Method Using Measured Oxygen Uptake.

The thermodilution (TD) method is routinely used for the estimation of cardiac output (Q̇C). However, its accuracy, compared with the gold-standard Fick method, where systemic oxygen uptake (V̇O2) is directly measured, and Q̇C calculated from V̇O2 and the arterio-venous oxygen difference ("direct" Fick), has not been well validated. The present study determined the agreement between TD and Fick methods in consecutive patients who underwent pulmonary artery catheterization for a broad range of clinical conditions. This is a subanalysis of a previous study comparing the indirect versus Fick method based on a prospective, consecutive patient registry of 253 patients who underwent pulmonary artery catheterization for clinical indications at a single center between 1999 and 2005. We included patients that had an estimation of Q̇C both by the Fick method using measured V̇O2 by exhaled gas analyses from timed Douglas bag collections and by TD. Cardiac index was classified as low when ≤2.2 L/min/m2 or normal when >2.2 L/min/m2. The median (25th, 75th percentile) age of the cohort was 59 (50,67) years, and 50% were female. A total of 43.5% had normal left ventricular function by ventriculography, and 25.7% had ischemic heart disease. Median overall Fick and TD Q̇C were 4.4 (3.5, 5.5) and 4.3 (3.7, 5.2) L/min, respectively (p = 0.04). The median absolute percent error between Fick and TD Q̇C was 17.5 (7.7, 28.4)%, with a typical error of 0.88 L/min (95% confidence interval [CI] 0.82 to 0.95). Median absolute percent error was comparable in the low (n = 118) and normal Q̇CI (n = 135) groups (16.9% vs 18.9%, respectively, p = 0.88). typical error was 0.3 (95% CI 0.27 to 0.33) and 0.49 (95% CI 0.45 to 0.55) L/min/m2 in that comparison. Percent error >25% between Fick and TD Q̇C was observed in over 30% of patients. Overall, Fick and TD Q̇C modestly correlated (Rs = 0.64, p <0.001), with a nondirectional error introduced by TD Q̇C [mean bias of 0.21 (-2.2, 2.7) L/min]. There was poor agreement between TD and the gold-standard Fick method, highlighting the limitations of making clinical decisions based on TD.

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

INTRODUCTION: Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory. METHODS: REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook. RESULTS: Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook. CONCLUSIONS: Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.