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Background and Aims In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. Methods The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. Results The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P -values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (P interaction =.03; adjusted P interaction =.33) and diabetics (P interaction =.01; adjusted P interaction =.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. Conclusions This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients. [ABSTRACT FROM AUTHOR]

Aims: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF. Methods and results: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia‐Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self‐reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient‐years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively. Conclusions: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF‐related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early‐stage intervention, since haemodynamic congestion precedes clinical symptoms. Methods: The BioMEMS study, a substudy of the MONITOR‐HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR‐HF trial were collected at baseline, 3‐, 6‐, and 12‐month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS‐HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. Conclusion: Since the prognostic value of single baseline measurements of biomarkers like N‐terminal pro‐B‐type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively. [ABSTRACT FROM AUTHOR]

Aims: Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline‐directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real‐world TITRATE‐HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long‐term outcomes in patients with de novo, chronic, and worsening HF. Methods and results: A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow‐up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF‐related hospitalizations, HF‐related urgent visits with a need for intravenous diuretics, all‐cause mortality, and cardiovascular mortality. Conclusions: TITRATE‐HF is a real‐world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients. [ABSTRACT FROM AUTHOR]

In a previous study we demonstrated that the institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after the institution of cardiac resynchronization therapy (CRT) has predictive value for midterm response. One day after implantation of a CRT device in 33 CHF patients (27 male/6 female; age, 66.5 [+ or -] 9.5 yr; left ventricular ejection fraction, 28 [+ or -] 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). Echocardiography was performed before implantation (baseline) and 6 mo after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end-systolic volume at follow-up had decreased by [greater than or equal to]15%. Responders (69.7%) and nonresponders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% (P = 0.03); this differed significantly (P = 0.02) from the average BRS change (-2%) in the nonresponders. CRT also increased HRV by 30% in responders (P = 0.02), but there was no significant difference found compared with the increase in HRV (8%) in the nonresponders. Receiver-operating characteristic curve analysis revealed that the percent BRS increase had predictive value for the discrimination of responders and nonresponders (area under the curve, 0.69; 95% confidence interval, 0.510.87; maximal accuracy, 0.70). Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodeling. heart failure; arterial baroreflex; heart rate variability; pacing