Cardiorenal Patients Research Articles

P0321OUR EXPERIENCE OF PATIROMER (VELTASSA) USE AND POTENTIAL COST-BENEFITS AT SOUTH TYNESIDE AND SUNDERLAND NHS FT, U.K

Abstract Background and Aims Patiromer is a new medication used to manage hyperkalaemia and acts as a bowel cation-exchange polymer with a simpler dosing and more favourable side effect profile than existing agents. In May 2018, South Tyneside and Sunderland NHS Foundation Trust (STSFT) implemented a protocol for the use of Patiromer in managing chronic hyperkalaemia to enhance options for managing cardio-renal patients in clinic. Conditional on our successful formulary application, was an audit against the protocol aiming to understand utility. Our second aim was to identify potential cost-benefits of patiromer. In particular, we were interested in preventing hospital admissions, bed days saved, temporary venous lines and dialysis sessions. It is important to note this analysis is subject to interpretation based on likely outcome should patiromer not have been given. Method To be eligible, patients had to have eGFR <30 and either a potassium >5.5 precluding the use of RAASi/MRAs or a recurrent potassium >6. Using electronic patient record system, we investigated 49 patients commenced on patiromer between October 2018 and October 2019. Results Only 14% of the incident prescriptions were in clinic with over half starting at a higher than UK licensed dose (once daily). The distribution of hyperkalaemia was varied as defining hyperkalaemia onset is challenging and what we found as more emergency use. We also identified the following clinical savings: 12 fewer bed days, 15 temporary lines and a minimum of 25 dialysis sessions avoided. Interestingly, we also found that in 2 cases, physicians utilised patiromer and avoided a referral to the renal team. Furthermore, we identified 11 uses of patiromer in the conservative/palliative setting allowing patients to withdraw from dialysis and to prevent discussions on commencing renal replacement therapy for concerns around hyperkalaemia. It would also provide a quality of life benefit avoiding recurrent cannulation to facilitate the standardised medical management of hyperkalaemia. Conclusion In conclusion, whilst this may not demonstrate an objective cost benefit, it does show the versatility of patiromer use in clinical practice. We have found an emphasis on usage in the inpatient setting to avoid dialysis and its attendant costs, rather than where its evidence base originates: as a renin-aldosterone blockade enabler in the outpatient setting. We have demonstrated awareness of adhering to the protocol criteria, whilst understanding the pitfalls of the protocol and why the medication has been administered out with of it, especially with regards to dosing. We wish to share our experience with clinicians and raise awareness of their growing armamentarium.

SAT-LB106 Metabolic and Brown Adipose Tissue-Specific Effects of the Novel Non-Steroidal Mineralocorticoid Receptor Antagonist Finerenone in a Mouse Model of Diet-Induced Obesity

In this work we studied the metabolic effects of the novel non-steroidal MR antagonist Finerenone (FIN) in mice fed a high-fat diet (HFD, 60% kcal as fat). We also investigated the signaling pathways underlying the beneficial metabolic effects of MR antagonism. After 3 months of HFD, mice treated with FIN showed an improvement of glucose tolerance compared to control mice as shown by intraperitoneal glucose tolerance tests. Despite this metabolic improvement, FIN-treated mice did not show a reduction in body weight compared to control mice. In order to elucidate the favourable effect of FIN on glucose tolerance we performed histological and molecular analyses at level of different adipose depots. We did not observe significant differences in classical white adipose depots (subcutaneous and visceral) between control and FIN-treated mice. Interestingly, interscapular brown adipose tissue (iBAT) of FIN-treated mice showed an increased multilocularity and a reduced size of lipid droplets, suggesting an iBAT-specific effect of FIN. We than analyzed mRNA and protein expression of uncoupling protein 1 (UCP-1) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PCG1-alpha), showing a significant increase of both markers at iBAT level in FIN-treated mice. Furthermore, leptin and adenylate cyclase 5 (Adyc5) (specific white adipose tissue markers) mRNA expression was reduced at level of iBAT in FIN-treated mice. Finally, we demonstrated that FIN-induced MR antagonism determined an increased activation of AMP-activated protein kinase (AMPK) which, in turn, stimulated adipose triglyceride lipase (ATGL) activity, with subsequent up-regulation of genes involved in fatty acids oxidation, tricarboxylic acid cycle and thermogenesis, in iBAT. In summary, our study shows that FIN protects from iBAT dysfunction and improves glucose tolerance in HFD-fed mice. Importantly, FIN effects on iBAT are mediated by a MR-AMPK-ATGL-UCP-1 signaling cascade. Therefore, MR antagonism by FIN in clinical settings might offer metabolic advantages, on top of its anti-fibrotic action, in multi-morbid cardiorenal patients.

Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia.

Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.

Cardiorenal status using amino-terminal pro–brain natriuretic peptide and cystatin C on cardiac resynchronization therapy outcomes: From the BIOCRT Study

Cardiorenal syndrome comprises a heterogeneous group of disorders characterized by acute or chronic cardiac and renal dysfunction. The purpose of this study was to determine the effect of cardiorenal status using a dual-marker strategy with amino-terminal pro-brain natriuretic peptide (NT-proBNP) and cystatin C on cardiac resynchronization therapy (CRT) outcomes. In 92 patients (age 66 ± 13 years; 80% male; left ventricular ejection fraction 26% ± 7%), NT-proBNP and cystatin C levels were measured at CRT implantation and at 1 month. NT-proBNP >1000 pg/mL and cystatin C >1 mg/L were considered high. Baseline cardiorenal patients were defined as having high NT-proBNP and cystatin C. At 1 month, CRT patients were categorized as (1) irreversible cardiorenal if cystatin C was persistently high; (2) progressive cardiorenal with transition from low to high cystatin C; (3) reversible cardiorenal with transition from high to low cystatin C; and (4) "normal" with stable low cystatin C. Outcomes were 6-month clinical and echocardiographic CRT response and 2 -year major adverse cardiovascular event (MACE). Compared to patients with low NT-proBNP and cystatin C, cardiorenal patients had >9-fold increase risk of CRT nonresponse (odds ratio uncompensated 9.0; compensated 36.4; both P ≤.004) and >6-fold risk of MACE (hazard ratio uncompensated 8.5; P=.005). Compared to "normal" and reversible patients (referent), irreversible patients had a 9-fold increase for CRT nonresponse (odds ratio 9.1; P <.001) and had >4-fold risk of MACE (adjusted hazard ratio 5.1; P <.001). Irreversible patients were most likely echocardiographic CRT nonresponders. Cardiorenal status by NT-proBNP and cystatin C can identify high-risk CRT patients, and those with both elevated concentrations have worse prognosis.

Iperkalemia cronica nei pazienti cardio – renali: q &amp; a per il cardionefrologo pratico

Chronic hyperkalemia in cardiorenal patients: Q&A for the cardio-nephrologists.Chronic hyperkalemia is a serious medical condition often present in patients with chronic kidney disease (CKD) and he...

Pulmonary Artery Pressure Changes Detected by CardioMEMS in Temporal Relation to Hemodialysis in Heart Failure Patients with End-Stage Renal Disease

Background Cardiorenal syndrome impacts many heart failure (HF) patients, and the need for hemodialysis (HD) is associated with worsening HF and increased risk of death. The CardioMEMS system (Abbott Medical) was shown to have efficacy in the CHAMPION trial, but cardiorenal patients were excluded from enrollment. Our aim is to determine pulmonary artery (PA) pressure characteristics for HF outpatients receiving routine HD. Methods Eight HD-HF patients (54 ± 9 yrs, male =4, LVEF = 28 ± 8%) received the CardioMEMS system and were prospectively followed on an outpatient basis. PA pressures were transmitted twice on HD days (pre- and post- HD), and once on non-HD days. PA pressure was monitored weekly to observe long-term characteristics of parameter changes occurring at baseline and during meaningful clinical events (defined as emergent HD sessions or hospital encounter for volume overload). PA pressure was considered baseline if >21 days prior to clinical event or post-medication change. Paired t-test was used for comparisons; P-value Results PA pressures were elevated at implant (mean PA diastolic pressure [PADP] = 29 ± 10 mmHg), remained consistently high even though patients were at dry weight, and were highest on HD days prior to dialysis ( Figure 1 ). There were significant differences in PA pressure in temporal relation to HD schedule ( Figure 2 A), with the exception of PADP when compared between non-HD vs post-HD values. 3 patients had a HF event (3 emergent HD, 1 hospitalization) and, compared to patients without HF events, PA pressures exhibited loss of cyclical pressure variation with progressive elevation prior to decompensation ( Figure 2 B). Conclusions HF outpatients with cardiorenal syndrome demonstrate elevated PA pressures at dry weight. CardioMEMS reveals expected PA pressure changes in temporal association with HD-related fluid removal. Those experiencing HF decompensation do not demonstrate this pattern. Future studies are needed to determine if PA pressures can be used to determine HD-related fluid removal protocols to avoid HF decompensation in these patients.

Lower risk of hospitalizations and higher quality of life in cardiorenal patients using once-nightly Icodextrin peritoneal exchanges

Lower risk of hospitalizations and higher quality of life in cardiorenal patients using once-nightly Icodextrin peritoneal exchanges

Impact of hyperkalaemia in managing cardiorenal patients – a healthcare professional perspective

Impact of hyperkalaemia in managing cardiorenal patients – a healthcare professional perspective

Hemodialysis treatment of cardiorenal syndrome.

We evaluated the impact of hemodialysis on mortality and hospital readmission in patients with cardiorenal syndrome. All patients were NYHA IV functional class and underwent laboratory testing, echocardiography, and cardiac functional testing. Hemodialysis was indicated in patients with progressive decline of kidney function and consequent failure to titrate heart failure medication as well as in patients with hypervolemia that was resistant to conservative treatment with more than 4 annual hospitalizations due to heart failure and/or concomitant chronic kidney disease stage III-IV. Patients were treated with low-efficacy bicarbonate hemodialysis with permanent central venous catheter used as vascular access. Since 2004, 67 patients were started on hemodialysis because of cardiorenal syndrome. Hospital readmission rate due to heart failure decreased (1year before dialysis vs. 1 year after dialysis: 0.79±1.32 vs. 0.22±0.65 hospitalizations per year, p=0.001) together with the duration of annual hospital stay (11.4±21.4 vs. 3.7±10.4 days, p=0.011). 1-, 2-, 3-, 4- and 5-year survival for our patients was 81%, 61%, 52%, 47%, and 39%, respectively. Chronic renal replacement therapy with hemodialysis and strict uremic, electrolyte, and volume control may be more beneficial for patients with advanced heart failure with preserved or reduced LVEF than ultrafiltration alone. We have observed better survival of terminal cardiorenal patients treated with hemodialysis than in the general NYHA IV population, with lower hospital readmission rate and less hospitalized days for heart failure. .

Abstract 17471: Cardiorenal Syndrome Patients With High NT-proBNP and Cystatin C Levels and Patients With Irreversible Cardiorenal Syndrome Identified by Persistently High Levels of Cystatin C Have Worse Outcomes in Cardiac Resynchronization Therapy: The BIOCRT Study

Introduction: Cardiorenal syndrome comprises of a heterogeneous group of acute and chronic cardiac and renal dysfunction. We examine the association of a dual marker strategy using amino-terminal pro brain natriuretic peptide (NT-proBNP, heart failure) and cystatin C (CysC, renal function) with major adverse cardiac events (MACE) in cardiac resynchronization therapy (CRT) patients. Methods: In 92 patients (age 66±13; 80% male; ejection fraction 26±7%), NT-proBNP and CysC levels were measured at CRT implantation, and 1 month. NT-proBNP&gt;1000 pg/mL and CysC&gt;1mg/L were considered high. At baseline, cardiorenal patients were defined as having high NT-proBNP and CysC. One month after implant, we categorized CRT patients as (1) irreversible cardiorenal if CysC was persistently high, (2) progressive cardiorenal with low transition to high CysC, (3) reversible cardiorenal with high transition to low CysC, and (4) "normal" with stable low CysC. MACE was defined as death, cardiac transplant, left ventricular assist device, and heart failure hospitalization by 2 years. Results: There were 25 (27%) MACE. Prior to CRT, 34 (37%) patients had cardiorenal syndrome. Compared to patients with low NT-proBNP and CysC levels, cardiorenal patients had &gt;6-fold risk of MACE (adjusted HR 6.3, p=0.02) with an estimated 52% probability of having MACE (Figure A). One month after CRT, 33 (36%) patients were irreversible, 15 (16%) progressive, 7 (8%) reversible, and 37 (40%) "normal". Compared to "normal" and reversible patients (referent), irreversible patients had &gt;4-fold risk of MACE (adjusted HR 4.7, p=0.002) with an estimated 52% probability of having MACE (Figure B) while progressors had similar MACE risk (adjusted HR 1.0, p=1.0). Conclusions: CRT patients with cardiorenal syndrome, especially irreversible, have worse prognosis compared to those with acute renal injury or "normal" renal function. Cardiorenal status by NT-proBNP and CysC can identify high-risk CRT patients.

Cardiorenal Syndrome

One hundred years ago, in November of 1913, Thomas Lewis from University College Hospital, London, delivered a lecture entitled “Paroxysmal Dyspnoea in Cardio–Renal Patients,” in which he provided his clinical observations on a number of patients with dyspnea related to advanced heart and

Clinical outcome in cardiorenal patients related to coronary computed tomography angiography and serum adrenomedullin

Background: Adrenomedullin is present in numerous human body tissues and its powerful vasodilatatory activity is thought to play role in cardiovascular/renal homeostasis and possibly in atherosclerosis. We conducted a prospective 2-year study of one hundred twenty-three patients with chronic kidney disease (CKD). Clinical outcome was analyzed to coronary computed tomography angiography (CCTA) findings and serum adrenomedullin levels. Methods: We determined plasma mid-regional pro-adrenomedullin (MR-proADM) levels using sandwich immunoassay in patients (pts) on stage 2 to 5 CKD (glomerular filtration rate - GFR < 90 ml/min/1.73 m2). Coronary artery calcification (CAC) and noninvasive coronary angiograms were performed by 64-multi-detector computed tomography (Siemens, Germany). The presence of stenosis ≥ 50% during CCTA was considered as significant. The degree of coronary artery calcification was assessed using the Agatston calcium score method. Results: We studied consecutive 123 pts with suspected coronary artery disease (mean age 62.5±10.7 years, 57.7% male, arterial hypertension 89.2%, type 2 diabetes 25.2%, 29.0% had a history of tobacco use and 38.2% were on regular haemodialysis- mean 51.7 months, ranging from 3 to 252 months). On CCTA, 76 pts (65.0%) had no coronary artery disease (CAD),in 29 pts (24.8%) one significant epicardial stenosis and in 12 (10.3%) multivessel disease were documented. The mean MR-proADM plasma levels and CAC score were 1.4 nmol/l and 472.8, respectively. MR-proADM correlated with CAC (r=0.20; p=0.02), GFR (r=-0.75; p<0.001), total cholesterol and LDL-cholesterol (r=-0.36; p=0.02 and r=-0.34; p= 0.001). During follow-up period (18.4±6.2 months) 7 cardiovascular deaths were occurred and 1 patient underwent percutaneous coronary intervention for unstable angina. The main characteristics in pts with cardiac events or eventfree survival were the following: serum MR-proADM (2.5 vs 1.3 nmol/l), CAC (663.7 vs 462.5). When we compared these variables to cardiac events only significant difference was documented in MR-proADM levels (p=0,04). Otherwise, areas under receiver operating characteristic curve (AUC) for prediction of cardiovascular mortality were 0.82 (95% CI 0.67-0.97), 0.75 (95% CI 0.50-0.99) and 0.64 (95% CI 0.29-0.99) for MR-proADM vs duration of hemodialysis and CAC. Conclusions: Coronary computed tomography angiography and serum adrenomedullin represent new alternative diagnostic tools for risk stratification in special group of cardiorenal patients.

Target hemoglobin can be achieved with intravenous iron alone in cardio-renal patients

Target hemoglobin can be achieved with intravenous iron alone in cardio-renal patients

Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging

BackgroundAtherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.MethodsThe EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).ResultsMR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.ConclusionsARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.

Determinants of Red Cell Distribution Width (RDW) in Cardiorenal Patients: RDW is Not Related to Erythropoietin Resistance

BackgroundStudies have shown that red cell distribution width (RDW) is related to outcome in chronic heart failure (CHF). The pathophysiological process is unknown. We studied the relationship between RDW and erythropoietin (EPO) resistance, and related factors such as erythropoietic activity, functional iron availability and hepcidin. Methods and ResultsIn the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome (EPOCARES) study, which investigates the role of EPO in 54 iron-supplemented anemic patients with CHF and chronic kidney disease (CKD) (n = 35 treated with 50 IU/kg/wk Epopoetin beta, n = 19 control), RDW was not associated with EPO resistance. We defined EPO resistance by EPO levels (r = 0.12, P = .42), the observed/predicted log EPO ratio (r = 0.12, P = .42), the increase in reticulocytes after 2 weeks of EPO treatment (r = −0.18, P = .31), and the increase of hemoglobin after 6 months of EPO treatment (r = 0.26, P = .35). However, RDW was negatively correlated with functional iron availability (reticulocyte hemoglobin content, r = −0.48, P < .001, and transferrin saturation, r = −0.39, P = .005) and positively with erythropoietic activity (soluble transferrin receptor, r = 0.48, P < .001, immature reticulocyte fraction, r = 0.36, P = .01) and positively with interleukin-6 (r = 0.48, P < .001). No correlation existed between hepcidin-25 and RDW. ConclusionsEPO resistance was not associated with RDW. RDW was associated with functional iron availability, erythropoietic activity, and interleukin-6 in anemic patients with CHF and CKD.

Cardiorenal syndrome: still not a defined entity

Because of the increasing incidence of cardiac failure and chronic renal failure due to the progressive aging of the population, the extensive application of cardiac interventional techniques, the rising rates of obesity and diabetes mellitus, coexistence of heart failure and renal failure in the same patient are frequent. More than half of subjects with heart failure had renal impairment, and mortality worsened incrementally across the range of renal dysfunctions. In patients with heart failure, renal dysfunction can result from intrinsic renal disease, hemodynamic abnormalities, or their combination. Severe pump failure leads to low cardiac output and hypotension, and neurohormonal activation produces both fluid retention and vasoconstriction. However, the cardiorenal connection is more elaborate than the hemodynamic model alone; effects of the renin-angiotensin system, the balance between nitric oxide and reactive oxygen species, inflammation, anemia and the sympathetic nervous system should be taken into account. The management of cardiorenal patients requires a tailored therapy that prioritizes the preservation of the equilibrium of each individual patient. Intravascular volume, blood pressure, renal hemodynamic, anemia and intrinsic renal disease management are crucial for improving patients' survival. Complications should be foreseen and prevented, looking carefully at basic physical examination, weight and blood pressure monitoring, and blood, urine urea and electrolytes measurement.

The cardiorenal connection in heart failure

Heart failure (HF) and renal dysfunction frequently coexist; this combination is commonly referred to as the "cardiorenal syndrome." The intersection of cardiac and renal dysfunction has important therapeutic and prognostic implications in patients with HF. Approximately 60% to 80% of patients hospitalized for HF have at least stage III renal dysfunction; this comorbid renal insufficiency (RI) is associated with significantly increased morbidity and mortality risk. Comorbid RI can result from intrinsic renal disease and inadequate renal perfusion. HF and RI stimulate neurohormonal activation, increasing preload and afterload and reducing cardiac output. Inotropic agents augment this neurohormonal activation. Managing cardiorenal patients requires successful negotiation of the delicate balance between adequate volume reduction and adequate renal function. There is a compelling need for additional studies in this patient population.

A Clinical Lecture ON PAROXYSMAL DYSPNOEA IN CARDIORENAL PATIENTS: WITH SPECIAL REFERENCE TO "CARDIAC" AND "URAEMIC" ASTHMA: Delivered at University College Hospital, London, November 12th, 1913

A Clinical Lecture ON PAROXYSMAL DYSPNOEA IN CARDIORENAL PATIENTS: WITH SPECIAL REFERENCE TO "CARDIAC" AND "URAEMIC" ASTHMA: Delivered at University College Hospital, London, November 12th, 1913