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BACKGROUND: Pulmonary hypertension (pH) is a well-known complication among patients with chronic kidney disease (CKD). Arteriovenous fistulae (AVF) have been associated with pH mainly by increasing cardiac output. However, the burden of precapillary pH in individuals with CKD and an AVF is unclear. OBJECTIVES: To better and more fully understand the mechanism and development of precapillary pH in patients with AVF, as well as the consequences of precapillary pH in these patients. METHODS: This was a large retrospective study of patients with CKD stage 4 or 5 who underwent right heart catheterization (RHC) from 2018 to 2023. The data were stratified according to the presence of AVF. To determine if AVF was independently associated with precapillary pH, we used a multivariable logistic regression analysis adjusting for demographics and potential comorbidities associated with precapillary pH, including diagnosis of chronic lung disease, obstructive sleep apnea, connective tissue disease, history of venous thromboembolism, chronic anemia, and heart failure. RESULTS: Of 651 patients with CKD4 or CKD5, 145 (22 %) had AVF and 506 (78 %) did not have AVF. Within the AVF group, the median age was 64 years (IQR 54-71), and they were predominantly males (61 %, n = 88) and African American (77 %, n = 111). A total of 31 % (n = 45) had evidence of precapillary pH, 30 % (n = 43) of combined pH, and 14 % (n = 20) of isolated postcapillary pH. Compared to the non-AVF group, precapillary pH was more likely in the AVF group (31% vs 17 %, p < 0.0001). On multivariable analysis, AVF was independently associated with precapillary pH (OR 2.47, CI 1.56-3.89; p < 0.0001). The median time from dialysis initiation to RHC date (and precapillary pH diagnosis) was 6 years (IQR 3-8). CONCLUSION: Based on RHC findings, almost one-third of patients with CKD and AVF had precapillary pH. The presence of AVF was independently associated with precapillary pH.
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BACKGROUND: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF. METHODS: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities. RESULTS: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality. CONCLUSION: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.
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AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.
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Tasa de Filtración Glomerular , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Veteranos , Humanos , Masculino , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Anciano , Veteranos/estadística & datos numéricos , Estados Unidos/epidemiología , Persona de Mediana Edad , Creatinina/sangre , Estudios RetrospectivosRESUMEN
Congestive nephropathy is an underappreciated manifestation of cardiorenal syndrome and is characterized by a potentially reversible kidney dysfunction caused by a reduced renal venous outflow secondary to right-sided heart failure or intra-abdominal hypertension. To date, the histological diagnostic criteria for congestive nephropathy have not been defined. We herein report a case of acute renal dysfunction following cardiac allograft failure and present a review of the relevant literature to elucidate the current understanding of the disease. Our case demonstrated that congestion-driven nephropathy may be histopathologically characterized by markedly dilated veins and peritubular capillaries, focally accentuated low-grade acute tubular damage, small areas of interstitial fibrosis, and tubular atrophy on a background of normal glomeruli and predominantly normal tubular cell differentiation.
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Insuficiencia Cardíaca , Humanos , Masculino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/diagnóstico , Persona de Mediana Edad , Biopsia , Trasplante de Corazón , Riñón/patología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnósticoRESUMEN
OBJECTIVE: This study aimed to assess whether an obesity paradox (lower event rates with higher body mass index [BMI]) exists in participants with advanced chronic kidney disease (CKD) and chronic coronary disease in the International Study of Comparative Health Effectiveness of Medical and Invasive Approaches (ISCHEMIA)-CKD, and whether BMI modified the effect of initial treatment strategy. METHODS: Baseline BMI was analyzed as both a continuous and categorical variable (< 25, ≥ 25 to < 30, ≥ 30 kg/m2). Associations between BMI and the primary outcome of all-cause death or myocardial infarction (D/MI), and all-cause death, cardiovascular death, and MI individually were estimated. Associations with health status were also evaluated using the Seattle Angina Questionnaire-7, the Rose Dyspnea Scale, and the EuroQol-5D Visual Analog Scale. RESULTS: Body mass index ≥ 30 kg/m2 vs < 25 kg/m2 demonstrated increased risk for MI (hazard ratio [HR] [95% confidence interval] = 1.81 [1.12-2.92]) and for D/MI (HR 1.45 [1.06-1.96]) with a HR for MI of 1.22 (1.05-1.40) per 5 kg/m2 increase in BMI in unadjusted analysis. In multivariate analyses, a BMI ≥ 30 kg/m2 was marginally associated with D/MI (HR 1.43 [1.00-2.04]) and greater dyspnea throughout follow-up (P < .05 at all time points). Heterogeneity of treatment effect between baseline BMI was not evident for any outcome. CONCLUSIONS: In the ISCHEMIA-CKD trial, an obesity paradox was not detected. Higher BMI was associated with worse dyspnea, and a trend toward increased D/MI and MI risk. Larger studies to validate these findings are warranted.
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Enfermedad Coronaria , Infarto del Miocardio , Insuficiencia Renal Crónica , Humanos , Índice de Masa Corporal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Enfermedad Coronaria/complicaciones , Disnea/etiología , Estado de Salud , Factores de RiesgoRESUMEN
BACKGROUND: Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. METHODS: The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets. RESULTS: Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P=0.01). CONCLUSIONS: PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.
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Aterosclerosis , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Creatinina , Hemoglobina Glucada , American Heart Association , Factores de Riesgo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Albúminas , Medición de RiesgoRESUMEN
PURPOSE OF REVIEW: This review aims to explore the current evidence regarding cardiovascular and kidney outcomes in patients who undergo treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) post kidney transplantation. RECENT FINDINGS: Summary findings from individual studies included in this review showed largely favorable results in the kidney transplant recipients (KTRs) being treated with SGLT2i.These outcomes included parameters such as allograft function, glycemic control, proteinuria, blood pressure, weight loss and safety profile, among others. Almost all the studies reported an initial 'dip' in eGFR, followed by recovery, after the initiation of SGLT2i treatment. None of the studies reported significant interaction of SGLT2i with immunosuppressive medications. The most common adverse effects noted in these studies were infection-related including UTI and genital mycosis. None of the studies reported acute graft rejection attributable to SGLT2i therapy. SUMMARY: SGLT2i can play a significant role in improving health outcomes in KTRs. However, clinical trials with larger representation of KTRs longer follow-up period are needed to draw more substantial conclusions.
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Diabetes Mellitus Tipo 2 , Trasplante de Riñón , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversosRESUMEN
BACKGROUND: Heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) are common and interrelated conditions, each with a significant burden of disease. HF and kidney disease progress through pathophysiologic pathways that culminate in end-stage disease, for which T2DM is a major risk factor. Intervention within these pathways can disrupt disease processes and improve patient outcomes. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been investigated in patient populations with combinations of T2DM, CKD, and/or HF. However, until recently, the effect of these agents in patients with HF with preserved ejection fraction (HFpEF) was not well studied. MAIN BODY: The aim of this review is to summarize key information regarding the interaction between HFpEF, CKD, and T2DM and discuss the role of SGLT2 inhibition in the management of patients with comorbid HFpEF and CKD, with or without T2DM. Literature was retrieved using Boolean searches for English-language articles in PubMed and Google Scholar and included terms related to SGLT2is, HFpEF, T2DM, and CKD. The reference lists from retrieved articles were also considered. CONCLUSION: SGLT2is are efficacious and safe in treating HFpEF in patients with comorbid CKD with and without T2DM. The totality of evidence from clinical trials data suggests there are benefits in using SGLT2is across the spectrum of left ventricular ejection fractions, but there may be a potential for different renal effects in the different ejection fraction groups. Further analysis of these clinical trials has highlighted the need to obtain more accurate phenotypes for patients with HF and CKD to better determine which patients might respond to guideline-directed medical therapies, including SGLT2is. CI confidence interval, EF ejection fraction, eGFR estimated glomerular filtration rate, HF heart failure, HHF hospitalization for HF, HR hazard ratio, LVEF left ventricular ejection fraction, SGLT2i sodium-glucose cotransporter-2 inhibitor, UACR urine albumin-creatinine ratio. a Mean value, unless otherwise stated, b SGLT2i vs. placebo, c Data reanalyzed using more conventional endpoints (≥ 50% sustained decrease in eGFR, and including renal death) (UACR at baseline not stated in trial reports).
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico , Transportador 2 de Sodio-Glucosa , Función Ventricular Izquierda , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Glucosa , SodioRESUMEN
Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.
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Aterosclerosis , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Masculino , Adulto , Femenino , Estados Unidos/epidemiología , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , American Heart Association , Medición de Riesgo , Riñón , Factores de RiesgoRESUMEN
A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.
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Enfermedades Cardiovasculares , Síndrome Metabólico , Insuficiencia Renal Crónica , Estados Unidos/epidemiología , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Síndrome Metabólico/terapia , American Heart Association , Factores de Riesgo , Riñón , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapiaRESUMEN
Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Síndrome Metabólico , Estados Unidos/epidemiología , Humanos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Síndrome Metabólico/terapia , American Heart Association , Factores de Riesgo , RiñónRESUMEN
AIMS: This analysis evaluates whether proportional serial cardiac troponin (cTn) change predicts benefit from an early versus delayed invasive, or conservative treatment strategies across kidney function in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Patients diagnosed with NSTE-ACS in the Veterans Health Administration between 1999 and 2022 were categorized into terciles (<20%, 20 to ≤80%, >80%) of proportional change in serial cTn. Primary outcome included mortality or rehospitalization for myocardial infarction at 6 and 12 months, in survivors of index admission. Adjusted hazard ratio (HR) with 95% confidence Intervals (95% confidence interval [CI]) were calculated for the primary outcome for an early invasive (≤24 h of the index admission), delayed invasive (>24 h of index admission to 90-days postdischarge), or a conservative management. RESULTS: Chronic kidney disease (CKD) was more prevalent (45.3%) in the lowest versus 42.2% and 43% in middle and highest terciles, respectively (p < 0.001). Primary outcome is more likely for conservative versus early invasive strategy at 6 (HR: 1.44, 95% CI: 1.37-1.50) and 12 months (HR: 1.44, 95% CI: 1.39-1.50). A >80% proportional change demonstrated HR (95% CI): 0.90 (0.83-0.97) and 0.93 (0.88-1.00; p = 0.041) for primary outcome at 6 and 12 months, respectively, when an early versus delayed invasive strategy was used, across CKD stages. CONCLUSIONS: Overall, the invasive strategy was safe and associated with improved outcomes across kidney function in NSTE-ACS. Additionally, >80% proportional change in serial troponin in NSTE-ACS is associated with benefit from an early versus a delayed invasive strategy regardless of kidney function. These findings deserve confirmation in randomized controlled trials.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Humanos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Troponina , Cuidados Posteriores , Resultado del Tratamiento , Alta del Paciente , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Riñón , Intervención Coronaria Percutánea/efectos adversos , Angiografía CoronariaRESUMEN
BACKGROUND: Cardiorenal syndrome (CRS) complicates 33% of acute decompensated heart failure (ADHF) admissions, and patients with persistent congestion at discharge have high 30-day event rates. OBJECTIVES: The purpose of this study was to evaluate a novel catheter-deployed intra-aortic entrainment pump (IAEP) in patients with ADHF with CRS and persistent congestion. METHODS: A multicenter (n = 14), nonrandomized, single-arm, safety and feasibility study of IAEP therapy was conducted. Within patient changes (post-pre IAEP therapy) in fluid loss, hemodynamics, patient-reported dyspnea, and serum biomarkers were assessed using Wilcoxon signed-rank testing. RESULTS: Of 21 enrolled patients, 18 received Aortix therapy. Mean ± SD patient age was 60.3 ± 7.9 years. The median left ventricular ejection fraction was 22.5% (25th-75th percentile: 10.0%-53.5%); 27.8% had a left ventricular ejection fraction ≥50%. Pre-therapy, patients received 8.7 ± 4.1 days of loop diuretic agents and 44% were on inotropes. Pump therapy averaged 4.6 ± 1.6 days, yielding net fluid losses of 10.7 ± 6.5 L (P < 0.001) and significant (P < 0.01) reductions in central venous pressure (change from baseline: -8.5 mm Hg [25th-75th percentile: -3.5 to -10.0 mm Hg]), pulmonary capillary wedge pressure (-11.0 mm Hg [25th-75th percentile: -5.0 to -14.0 mm Hg]), and serum creatinine (-0.2 mg/dL [25th-75th percentile: -0.1 to -0.5 mg/dL]) with improved estimated glomerular filtration rate (+5.0 mL/min/1.73 m2 [25th-75th percentile: 2.0-9.0 mL/min/1.73 m2]) and patient-reported dyspnea score (+16 [25th-75th percentile: 3-37]). Dyspnea scores, natriuretic peptides, and renal function improvements persisted through 30 days. CONCLUSIONS: This pilot study of patients with ADHF, persistent congestion, and worsening renal function due to CRS supports the potential for safely achieving decongestion using IAEP therapy. These initial promising results provide the basis for future randomized clinical trials of this novel pump. (An Evaluation of the Safety and Performance of the Aortix System for Intra-Aortic Mechanical Circulatory Support in Patients with Cardiorenal Syndrome [The Aortix CRS Pilot Study]; NCT04145635).
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Síndrome Cardiorrenal , Insuficiencia Cardíaca , Anciano , Humanos , Persona de Mediana Edad , Disnea/etiología , Proyectos Piloto , Volumen Sistólico , Función Ventricular Izquierda , Estudios de FactibilidadAsunto(s)
Diabetes Mellitus Tipo 2 , Enfermedades Renales , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Riñón , Hipoglucemiantes/uso terapéuticoAsunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD). METHODS: We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m2) were recorded per year. The proportion of trials with advanced CKD was logtransformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson's correlation and univariate linear regression. RESULTS: A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year. CONCLUSION: In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased.
Asunto(s)
Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Humanos , Sistema Renina-Angiotensina , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Aldosterona/farmacología , Aldosterona/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Volumen Sistólico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Disfunción Ventricular Izquierda/tratamiento farmacológicoRESUMEN
Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.
Asunto(s)
COVID-19 , Síndrome Cardiorrenal , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Humanos , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/etiología , Síndrome Cardiorrenal/terapia , COVID-19/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Insuficiencia Renal Crónica/complicaciones , BiomarcadoresRESUMEN
The burden of adverse cardiorenal outcomes among patients with the trifecta of diabetes, heart failure (HF) and chronic kidney disease (CKD) remains high. Steroidal mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in patients with HF, however, there is significant underutilization of these agents, especially in patients with advanced CKD. Non-steroidal MRAs are an emerging therapeutic option for patients with diabetic kidney disease and are now guideline-supported in this population. Non-steroidal MRAs have a unique pharmacological profile distinct from their steroidal counterparts that retains the class-specific cardiorenal benefits but may help mitigate adverse effects, especially hyperkalaemia, in patients with CKD. In this review we summarize the current evidence on the use of non-steroidal MRAs for improving cardiorenal outcomes in patients with CKD and diabetes, as well as for combination use alongside other foundational medical therapies used in HF and CKD.