Ignite Creation Date:
2024-05-06 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 12:54 PM
Study NCT ID:
NCT03672591
Status:
COMPLETED
Last Update Posted:
2019-07-10
First Post:
2018-09-04
Brief Title:
Renal Hemodynamics in Patients With HFpEF
Sponsor:
University of Erlangen-Nürnberg Medical School
Organization:
University of Erlangen-Nürnberg Medical School
Study Overview
Official Title:
Cross-sectional Observational Single-center Study to Evaluate Renal Hemodynamics in Patients With Heart Failure and Preserved Ejection Fraction
Status:
COMPLETED
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Impaired renal function and heart failure with preserved ejection fraction HFpEF are two often co-existing medical conditions and are known to be associated with adverse cardiovascular outcome and increased mortality The relationship between HFpEF and renal impairment is bidirectional On the one hand renal dysfunction has been shown to be an independent risk factor for the development of HFpEF On the other hand an increase in central venous pressure leading to renal dysfunction by a reduction of renal blood flow RBF and perfusion pressure RPP as well as activation of the renin-angiotensin-aldosterone system RAAS in patients with HFpEF has been previously described
In the literature several studies aimed to investigate the association between renal dys- function and HFpEF In all these studies renal function was assessed by determination of standard kidney function parameters such as serum creatinine eGFR and urinary albumin to creatinine ratio UACR Constant infusion input clearance technique however offers a more detailed evaluation of renal function and hemodynamics To the best of knowledge renal hemodynamics in patients with HFpEF have not yet been investigated by clearance technique Therefore the aim of the present study is to evaluate renal function and hemodynamics by means of constant infusion input clearance technique with sodium p-aminohippuric acid PAH and Iohexol in 40 patients with HFpEF The constant infusion input clearance technique offers an exact evaluation of renal function by measuring not estimating glomerular filtration rate and renal hemodynamic parameters such as renal plasma flow RPF filtration fraction FF and intraglomerular pressure IGP These results will be compared to 140 subjects without HFpEF that have participated in various studies and have been analyzed with the same constant infusion input clearance technique performed in the Clinical Research Center of the University Hospital Erlangen-Nuremberg Additionally flow mediated vasodilation FMD pulse wave velocity and parameters of retinal vascular remodeling by means of scanning laser Doppler flowmetry SLDF will be assessed in patients with HFpEF thereby allowing to examine the relationship between vascular remodeling in the systemic and renal circulation
In the literature several studies aimed to investigate the association between renal dys- function and HFpEF In all these studies renal function was assessed by determination of standard kidney function parameters such as serum creatinine eGFR and urinary albumin to creatinine ratio UACR Constant infusion input clearance technique however offers a more detailed evaluation of renal function and hemodynamics To the best of knowledge renal hemodynamics in patients with HFpEF have not yet been investigated by clearance technique Therefore the aim of the present study is to evaluate renal function and hemodynamics by means of constant infusion input clearance technique with sodium p-aminohippuric acid PAH and Iohexol in 40 patients with HFpEF The constant infusion input clearance technique offers an exact evaluation of renal function by measuring not estimating glomerular filtration rate and renal hemodynamic parameters such as renal plasma flow RPF filtration fraction FF and intraglomerular pressure IGP These results will be compared to 140 subjects without HFpEF that have participated in various studies and have been analyzed with the same constant infusion input clearance technique performed in the Clinical Research Center of the University Hospital Erlangen-Nuremberg Additionally flow mediated vasodilation FMD pulse wave velocity and parameters of retinal vascular remodeling by means of scanning laser Doppler flowmetry SLDF will be assessed in patients with HFpEF thereby allowing to examine the relationship between vascular remodeling in the systemic and renal circulation
Detailed Description:
Several studies evaluating the outcome among patients with HFpEF revealed that this entity of heart failure HF is associated with high mortality rates and some studies even indicate that mortality is similar to patients with heart failure and reduced ejection fraction HFrEF Hospitalization for HFpEF is increasing relative to HFrEF highlighting the need for a better understanding of the pathogenetic processes in order to develop new treatment strategies for this type of HF Recently the PARAMOUNT study revealed that in patients with HFpEF treatment with the dual-acting angiotensin receptor neprilysin inhibitor ARNI LCZ696 was associated with lower levels of creatinine and higher estimated glomerular filtration rates eGFR indicating a better preservation of renal function in comparison to treatment with valsartan only Another observation of this study was an increase in urinary albumin to creatinine ratio UACR in the group of LCZ696-treatment which was not visible in patients randomized to the valsartan group Additionally analysis of the relation between albuminuria andor decreased eGFR and cardiovascular function and structure revealed that renal dysfunction was common in this group of patients and associated with cardiac remodeling and dysfunction
Up to two thirds of patients with HFpEF are suffering from chronic kidney disease CKD A bidirectional cardiorenal relation has been recently described and is known to be associated with adverse cardiovascular outcome and increased mortality On the one hand renal dysfunction has been shown to be an independent risk factor for the development of HFpEF due to inflammatory processes and endothelial dysfunction On the other hand an increase in central venous pressure leading to renal dysfunction by a reduction of renal blood flow RBF and perfusion pressure RPP as well as activation of the renin-angiotensin-aldosterone system RAAS in patients with HFpEF has been previously described
This association has also been demonstrated for patients with HFrEF However several studies comparing patients with the two subtypes of HF in the context of CKD indicate that this association is more pronounced in patients with HFpEF For example a community-based cohort study by Brouwers et al including 8592 subjects of the PREVEND trial showed that renal function parameters such as urinary albumin excretion UAE and cystatin C were associated with a high risk for the development of HFpEF but not HFrEF Ahmed et al even reported a higher CKD-related mortality in HFpEF than in HFrEF patients with an underlying graded-response relation as CKD-associated mortality increased with higher left ventricular ejection fraction LVEF These findings suggest different pathogenetic processes for these two subtypes of HF Therefore detailed exploration of the pathophysiological mechanisms behind the relationship of HFpEF and renal function represents a matter of major research interest
Recently several studies aimed to investigate the association between renal dys- function and HFpEF Unger et al retrospectively examined the relationship between renal function and echocardiographic parameters in 299 patients with HFpEF The analysis revealed that CKD was independently associated with worse cardiac mechanics and outcomes in this population9 Studying 217 participants from the PARAMOUNT trial with HFpEF Gori et al demonstrated that renal dysfunction was associated with abnormal left ventricular geometry lower midwall fractional shortening and higher NT-proBNP In both studies renal function was assessed with commonly used tests such as determination of serum creatinine eGFR and urinary albumin to creatinine ratio UACR However these parameters only allow an approximate estimation of renal function Constant infusion input clearance technique offers a more complete approach towards evaluation of renal function and perfusion allowing an exact quantification of glomerular filtration rate GFR and renal hemodynamic parameters such as renal plasma flow RPF filtration fraction FF and intraglomerular hemodynamics
The definition of HFpEF in literature is rather inconsistent In some studies HFpEF was defined by an ejection fraction of 45 whereas other authors used a cut-off value of 50 In the present study the categorization of heart failure as HFpEF will follow the 2016 European Society of Cardiology ESC guidelines for the diagnosis and treatment of acute and chronic heart failure applying a cut-off value of 50
The purpose of the present study is to evaluate renal function and hemodynamics by means of constant infusion input clearance technique with PAH and Iohexol in 40 patients with HFpEF with the aim to better characterize the relationship between renal dysfunction and HFpEF These results will be compared to 140 subjects without HFpEF who participated in different studies during which renal clearance examination has been performed with the constant infusion input clearance technique in the Clinical Research Center of the University Hospital Erlangen-Nuremberg In parallel pulse wave velocity flow mediated vasodilation and other vascular parameters reflecting the vascular wall properties of small and large arteries will be assessed Additionally there will be a non-invasive retinal examination to assess vascular remodeling of retinal arterioles wall to lumen ratio WLR retinal capillary flow RCF and capillary rarefaction
Up to two thirds of patients with HFpEF are suffering from chronic kidney disease CKD A bidirectional cardiorenal relation has been recently described and is known to be associated with adverse cardiovascular outcome and increased mortality On the one hand renal dysfunction has been shown to be an independent risk factor for the development of HFpEF due to inflammatory processes and endothelial dysfunction On the other hand an increase in central venous pressure leading to renal dysfunction by a reduction of renal blood flow RBF and perfusion pressure RPP as well as activation of the renin-angiotensin-aldosterone system RAAS in patients with HFpEF has been previously described
This association has also been demonstrated for patients with HFrEF However several studies comparing patients with the two subtypes of HF in the context of CKD indicate that this association is more pronounced in patients with HFpEF For example a community-based cohort study by Brouwers et al including 8592 subjects of the PREVEND trial showed that renal function parameters such as urinary albumin excretion UAE and cystatin C were associated with a high risk for the development of HFpEF but not HFrEF Ahmed et al even reported a higher CKD-related mortality in HFpEF than in HFrEF patients with an underlying graded-response relation as CKD-associated mortality increased with higher left ventricular ejection fraction LVEF These findings suggest different pathogenetic processes for these two subtypes of HF Therefore detailed exploration of the pathophysiological mechanisms behind the relationship of HFpEF and renal function represents a matter of major research interest
Recently several studies aimed to investigate the association between renal dys- function and HFpEF Unger et al retrospectively examined the relationship between renal function and echocardiographic parameters in 299 patients with HFpEF The analysis revealed that CKD was independently associated with worse cardiac mechanics and outcomes in this population9 Studying 217 participants from the PARAMOUNT trial with HFpEF Gori et al demonstrated that renal dysfunction was associated with abnormal left ventricular geometry lower midwall fractional shortening and higher NT-proBNP In both studies renal function was assessed with commonly used tests such as determination of serum creatinine eGFR and urinary albumin to creatinine ratio UACR However these parameters only allow an approximate estimation of renal function Constant infusion input clearance technique offers a more complete approach towards evaluation of renal function and perfusion allowing an exact quantification of glomerular filtration rate GFR and renal hemodynamic parameters such as renal plasma flow RPF filtration fraction FF and intraglomerular hemodynamics
The definition of HFpEF in literature is rather inconsistent In some studies HFpEF was defined by an ejection fraction of 45 whereas other authors used a cut-off value of 50 In the present study the categorization of heart failure as HFpEF will follow the 2016 European Society of Cardiology ESC guidelines for the diagnosis and treatment of acute and chronic heart failure applying a cut-off value of 50
The purpose of the present study is to evaluate renal function and hemodynamics by means of constant infusion input clearance technique with PAH and Iohexol in 40 patients with HFpEF with the aim to better characterize the relationship between renal dysfunction and HFpEF These results will be compared to 140 subjects without HFpEF who participated in different studies during which renal clearance examination has been performed with the constant infusion input clearance technique in the Clinical Research Center of the University Hospital Erlangen-Nuremberg In parallel pulse wave velocity flow mediated vasodilation and other vascular parameters reflecting the vascular wall properties of small and large arteries will be assessed Additionally there will be a non-invasive retinal examination to assess vascular remodeling of retinal arterioles wall to lumen ratio WLR retinal capillary flow RCF and capillary rarefaction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None