Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry.

PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

Prevalence and clinical profile of kidney disease in patients with chronic heart failure. Insights from the Spanish cardiorenal registry.

INTRODUCTION AND OBJECTIVES: Patients with combined heart failure (HF) and chronic kidney disease (CKD) have been underrepresented in clinical trials. The prevalence of CKD in these patients and their clinical profile require constant evaluation. This study aimed to analyze the prevalence of CKD, its clinical profile, and patterns of use of evidence-based medical therapies in HF across CKD stages in a contemporary cohort of ambulatory patients with HF. METHODS: From October 2021 to February 2022, the CARDIOREN registry included 1107 ambulatory HF patients from 13 HF clinics in Spain. RESULTS: The median age was 75 years, 63% were male, and 48% had heart failure with reduced left ventricular ejection fraction (HFrEF). A total of 654 (59.1%) had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, and 122 (11%) patients with eGFR ≥ 60 mL/min/1.73 m2 had a urine albumin-creatinin ratio ≥ 30 mg/g. The most important variables associated with lower eGFR were age (R2=61%) and furosemide dose (R2=21%). The proportion of patients receiving an angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin II receptor blockers (ARB), an angiotensin receptor-neprilysin inhibitor (ARNi), a sodium-glucose cotransporter 2 inhibitor (SGLT2i), or a mineralocorticoid receptor antagonist (MRA) progressively decreased with lower eGFR categories. Notably, 32% of the patients with HFrEF and an eGFR <30 mL/min/1.73 m2 received the combination of ACEI/ARB/ARNi+beta-blockers+MRA+SGLT2i. CONCLUSIONS: In this contemporary HF registry, 70% of patients had kidney disease. Although this population is less likely to receive evidence-based therapies, structured and specialized follow-up approaches within HF clinics may facilitate the adoption of these life-saving drugs.

Congestion as a crucial factor determining albuminuria in patients with cardiorenal disease.

Background: Albuminuria could potentially emerge as a novel marker of congestion in acute heart failure. However, the current evidence linking albuminuria and congestion in patients with congestive heart failure (CHF) remains somewhat scarce. This study aimed to evaluate the prevalence of albuminuria in a cohort of patients with CHF, identify the independent factors associated with albuminuria and analyse the correlation with different congestion parameters. Methods: This is a subanalysis of the Spanish Cardiorenal Registry, in which we enrolled 864 outpatients with heart failure and a value of urinary albumin:creatinine ratio (UACR) at the first visit. Results: The median age was 74 years, 549 (63.5%) were male and 438 (50.7%) had a reduced left ventricular ejection fraction. A total of 350 patients (40.5%) had albuminuria. Among these patients, 386 (33.1%) had a UACR of 30-300 mg/g and 64 (7.4%) had a UACR >300 mg/g. In order of importance, the independent variables associated with higher UACR were estimated glomerular filtration rate determined by the Chronic Kidney Disease Epidemiology Collaboration equation (R2 = 57.6%), systolic blood pressure (R2 = 21.1%), previous furosemide equivalent dose (FED; R2 = 7.5%), antigen carbohydrate 125 (CA125; R2 = 6.1%), diabetes mellitus (R2 = 5.6%) and oedema (R2 = 1.9%). The combined influence of oedema, elevated CA125 levels and the FED accounted for 15.5% of the model's variability. Conclusions: In patients with chronic stable heart failure, the prevalence of albuminuria is high. The risk factors of albuminuria in this population are chronic kidney disease and hypertension. Congestion parameters are also associated with increased albuminuria.

Usefulness of antigen carbohydrate 125 and N-terminal pro-b-type natriuretic peptide for assessing congestion in chronic heart failure: Insights from the CARDIOREN registry.

INTRODUCTION AND OBJECTIVES: A comprehensive assessment of congestion, including circulating biomarkers, is recommended in patients with acute heart failure. The circulating biomarkers natriuretic peptides (NPs) and carbohydrate antigen-125 (CA125) could be useful for congestion assessment in ambulatory chronic heart failure (CHF), but there is only limited information about their applicability in this context. Therefore, this study aimed to examine the association of plasma CA125 and NP levels with clinical and ultrasound congestion parameters in CHF. METHODS: This is a cross-sectional substudy of the Cardioren Spanish Registry, which enrolled 1107 patients with CHF from 13 tertiary hospitals in Spain between October 2021 and February 2022. Through ambulatory visits, we performed a comprehensive assessment of congestion-related parameters, including clinical variables (orthopnea, peripheral edema, and jugular engorgement, represented by the composite congestion score [CCS]), echocardiography variables (lung B-lines and inferior vena cava [IVC] diameter), and circulating biomarkers (CA125 and NPs). The association of the NP and CA125 levels with the clinical and echocardiographic congestion parameters was examined by multiple linear and logistic regression analyses. RESULTS: This substudy included 802 patients for whom all the biomarker parameters were available (median age, 74 [IQR, 63-81] years; 65% male). The proportion of patients with left ventricular ejection fraction 50% and estimated glomerular filtration rate <60 was 34% and 58%, respectively. The median CCS was 0 (interquartile range [IQR]: 0-1), with 45% of the sample exhibiting a median CCS of ≥1. The jugular engorgement, peripheral edema, and orthopnea rates were 32%, 21%, and 21%, respectively. A total of 35% of patients who underwent ultrasound examination showed lung B-lines, and the median IVC diameter was 16 mm. The median CA125 and NTproBNP levels were 14 U/mL (IQR: 9-28) and 1382 pg/mL (IQR: 563-3219), respectively. Multivariate analysis showed that higher CA125 levels were independently associated with higher odds of peripheral edema (p = 0.023) and lung B-lines (p < 0.001). Further, NTproBNP was positively associated with jugular engorgement (p < 0.001), orthopnea (p = 0.034), and enlarged IVC diameter (p = 0.031). CONCLUSIONS: Clinical signs of congestion are frequent in CHF. In the ambulatory setting, NTproBNP was associated with parameters linked to intravascular congestion such as orthopnea, jugular engorgement, and IVC diameter, whereas CA125 was associated with extravascular volume overload parameters (peripheral edema and lung B-lines). .

Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild-type transthyretin amyloidosis is the most frequent form of ATTR-CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR-CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population. METHODS AND RESULTS: Prevalence of ATTRv in elderly ATTR-CM patients (≥70 years) was assessed in a cohort of 300 consecutive ATTR-CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% female, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95% confidence interval [CI] 3.1-8.8) and 13 (5.3%; 95% CI 5.6-26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR-CM was 13% (95% CI 2.1-23.5). Univariate analysis identified female sex (odds ratio [OR] 3.66; 95% CI 1.13-11.85; p = 0.03), black ancestry (OR 46.31; 95% CI 3.52-Inf; p = 0.005), eye symptoms (OR 6.64; 95% CI 1.20-36.73; p = 0.03) and polyneuropathy (OR 10.05; 95% CI 3.09-32.64; p < 0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR-CM patients allowed initiation of transthyretin-specific drug treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers. CONCLUSIONS: Hereditary transthyretin amyloidosis is present in a substantial number of ATTR-CM patients aged ≥70 years. Identification of ATTRv in elderly patients with ATTR-CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR-CM regardless of age.