Johan Bodegard

Background and Aims: Ambulatory patients presenting with signs or symptoms of heart failure (HF) should undergo natriuretic peptide testing. Rates of death, HF hospitalization, and healthcare costs were examined in patients thus identified with suspected de novo HF. Methods: This population-based study (REVOLUTION HF) encompassing two large healthcare regions in Sweden examined patients who presented to outpatient care for the first time between 1 January 2015 and 31 December 2020, who had a recorded sign (peripheral oedema) or symptom (dyspnoea) of HF, and whose N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured >300 ng/L within ±30 days of that sign or symptom. Characteristics, outcomes, healthcare patterns, and healthcare costs for these patients were followed for 1 year. Comparisons were made with matched controls without history of HF, its signs, its symptoms, or elevated NT-proBNP. Results: Overall, 5942 patients (median age 78.7 years; 54% women) presented with suspected de novo HF. Within 1 year, 29% had received a HF diagnosis. Patients with suspected de novo HF had higher rates of all-cause death (11.7 vs. 6.5 events/100 person-years) and HF hospitalizations (12.5 vs. 2.2 events/100 person-years) than matched controls (n = 2048), with the highest event rates in the weeks after presentation. Rates were higher with higher NT-proBNP levels. Although some patients already used HF guideline-directed medical therapies for other indications, initiation of new medications was variable. Healthcare costs were higher in patients with suspected de novo HF than in matched controls, driven mostly by HF and chronic kidney disease. Conclusions: Patients with suspected HF and elevated NT-proBNP had high mortality and morbidity in the weeks after presentation, and accrued substantial healthcare costs, highlighting an urgent need for prompt identification, evaluation, and treatment of HF.

Background: Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%–49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high. Methods and Results: We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within‐person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within‐person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later. Conclusions: LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.

Key Points: Newly detected, moderately progressed CKD is associated with high clinical risks and health care costs. Most patients with moderately progressed CKD do not have diabetes and are at the same clinical risk as those with diabetes. Substantial inertia with kidney-protective treatment is observed when moderately progressed CKD is detected. Background: Kidney-protective treatments (renin–angiotensin system inhibitors and sodium–glucose cotransporter-2 inhibitors [SGLT-2is]) can delay CKD progression, cardiovascular events, and death. Methods: This observational cohort study used electronic health records and claims data from Japan, Sweden, and the United States to assess 1-year mortality/hospitalization event rates per 100 patient-years (PYs), cumulative hospital health care costs per patient, and kidney-protective treatment use before/after SGLT-2i (dapagliflozin) approval for CKD (2021) for patients with CKD stage 3–4 with/without type 2 diabetes (T2D). Results: Among 449,232 patients (across-country median age range 74–81 years), 79% did not have T2D. Prevalence ranges for atherosclerotic cardiovascular disease and heart failure were 20%–36% and 17%–31%, respectively. Baseline kidney-protective treatment (renin–angiotensin system inhibitor and/or SGLT-2i) use was limited, especially among patients without T2D. Event rates were high for CKD (11.4–44.4/100 PYs) and heart failure (7.4–22.3/100 PYs). Up to 14.6% of patients had died within 1 year. Hospital costs were higher for CKD and heart failure than for atherosclerotic cardiovascular disease. After incident CKD, kidney-protective treatment initiation was low (8%–20%) and discontinuation was high (16%–27%), especially among patients without T2D. Conclusions: Incident CKD was associated with substantial morbidity, mortality, costs, and undertreatment, especially in patients without T2D, who represented the majority of patients. This highlights an urgent need for early CKD detection and better kidney-protective treatment use in moderate CKD.

Objective Digital healthcare systems could provide insights into the global prevalence of heart failure (HF). We designed the CardioRenal and Metabolic disease (CaReMe) HF study to estimate the prevalence, key clinical adverse outcomes and costs of HF across 11 countries. Methods Individual level data from a contemporary cohort of 6 29 624 patients with diagnosed HF was obtained from digital healthcare systems in participating countries using a prespecified, common study plan, and summarised using a random effects meta-analysis. A broad definition of HF (any registered HF diagnosis) and a strict definition (history of hospitalisation for HF) were used. Event rates were reported per 100 patient years. Cumulative hospital care costs per patient were calculated for a period of up to 5 years. Results The prevalence of HF was 2.01% (95% CI 1.65 to 2.36) and 1.05% (0.85 to 1.25) according to the broad and strict definitions, respectively. In patients with HF (broad definition), mean age was 75.2 years (95% CI 74.0 to 76.4), 48.8% (40.9–56.8%) had ischaemic heart disease and 34.5% (29.4–39.6%) had diabetes. In 51 442 patients with a recorded ejection fraction (EF), 39.1% (30.3–47.8%) had a reduced, 18.8% (13.5–24.0%) had a mildly reduced and 42.1% (31.5–52.8%) had a preserved left ventricular EF. In 1 69 518 patients with recorded estimated glomerular filtration rate, 49% had chronic kidney disease (CKD) stages III–V. Event rates were highest for cardiorenal disease (HF or CKD) and all cause mortality (19.3 (95% CI 11.3 to 27.1) and 13.1 (11.1 to 15.1), respectively), and lower for myocardial infarction, stroke and peripheral artery disease. Hospital care costs were highest for cardiorenal diseases. Conclusions We estimate that 1–2% of the contemporary adult population has HF. These individuals are at significant risk of adverse outcomes and associated costs, predominantly driven by hospitalisations for HF or CKD. There is considerable public health potential in understanding the contemporary burden of HF and the importance of optimising its management.

Aim: To examine how the development of cardiovascular and renal disease (CVRD) translates to hospital healthcare costs in individuals with type 2 diabetes (T2D) initially free from CVRD. Methods: Data were obtained from the digital healthcare systems of 12 nations using a prespecified protocol. A fixed country‐specific index date of 1 January was chosen to secure sufficient cohort disease history and maximal follow‐up, varying between each nation from 2006 to 2017. At index, all individuals were free from any diagnoses of CVRD (including heart failure [HF], chronic kidney disease [CKD], coronary ischaemic disease, stroke, myocardial infarction [MI], or peripheral artery disease [PAD]). Outcomes during follow‐up were hospital visits for CKD, HF, MI, stroke, and PAD. Hospital healthcare costs obtained from six countries, representing 68% of the total study population, were cumulatively summarized for CVRD events occurring during follow‐up. Results: In total, 1.2 million CVRD‐free individuals with T2D were identified and followed for 4.5 years (mean), that is, 4.9 million patient‐years. The proportion of individuals indexed before 2010 was 18% ( n = 207 137); 2010‐2015, 31% (361 175); and after 2015, 52% (609 095). Overall, 184 420 (15.7%) developed CVRD, of which cardiorenal disease was most frequently the first disease to develop (59.7%), consisting of 23.0% HF and 36.7% CKD, and more common than stroke (16.9%), MI (13.7%), and PAD (9.7%). The total cumulative cost for CVRD was US$1 billion, of which 59.0% was attributed to cardiorenal disease, 3‐, 5‐, and 6‐fold times greater than the costs for stroke, MI, and PAD, respectively. Conclusion: Across all nations, HF or CKD was the most frequent CVRD manifestation to develop in a low‐risk population with T2D, accounting for the highest proportion of hospital healthcare costs. These novel findings highlight the importance of cardiorenal awareness when planning healthcare.

Background: Routinely captured data could provide insights into the global prevalence of CKD. We designed the CaReMe CKD study to estimate the prevalence, key clinical adverse outcomes and costs of CKD across 11 countries. Methods: Individual-level data of 2·4 million contemporaneous CKD patients was obtained from digital healthcare systems in participating countries using a pre-specified common protocol; summarized using random effects meta-analysis. CKD and its stages were defined in accordance with current Kidney Disease: Improving Global Outcomes (KDIGO) criteria. CKD was defined by laboratory values or by a diagnosis code. Findings: The pooled prevalence of possible CKD was 10·0% (95% confidence interval 8.5‒11.4; mean pooled age 75, 53% women, 37% diabetes, 60% using renin-angiotensin-aldosterone system inhibitors). Two out of three CKD patients identified by laboratory criteria did not have a corresponding CKD-specific diagnostic code. Among CKD patients identified by laboratory values, the majority (42%) were in KDIGO stage 3A; and this fraction was fairly consistent across countries. The share with CKD based on UACR alone (KDIGO stages one and two) was 29%, with a substantial heterogeneity between countries. Adverse events were common; 6% were hospitalized for CKD or heart failure, and 6% died, annually. Costs for renal events and heart failure were consistently higher than costs for atherosclerotic events in CKD patients across all countries. Interpretation: We estimate that CKD is present in one out of ten adults. These individuals experience significant adverse outcomes with associated costs. The prevalence of CKD is underestimated when using diagnostic codes alone. There is considerable public health potential in diagnosing CKD and providing treatments to those currently undiagnosed. Funding: The study was sponsored by AstraZeneca. Declaration of Interest: J.S. reports stock ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer, Takeda and AstraZeneca. J.B. holds a full-time position at AstraZeneca as an epidemiologist. A.B. reports no competing interests.