Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review.

BACKGROUND: Cardiorenal syndromes constitute a spectrum of disorders involving heart and kidney dysfunction modulated by a complex interplay of neurohormonal, inflammatory, and hemodynamic derangements. The management of such patients often poses a diagnostic and therapeutic challenge to physicians owing to gaps in understanding of pathophysiology, paucity of objective bedside diagnostic tools, and individual biases. SUMMARY: In this narrative review, we discuss the role of clinician who performed bedside ultrasound in the management of patients with cardiorenal syndromes. Novel sonographic applications such as venous excess ultrasound score (VExUS) are reviewed in addition to the lung and focused cardiac ultrasound. Further, underrecognized causes of heart failure such as high-flow arteriovenous fistula are discussed. KEY MESSAGE: Bedside ultrasound allows a comprehensive hemodynamic characterization of cardiorenal syndromes.

18F-FDG PET/MRI Imaging in a Preclinical Rat Model of Cardiorenal Syndrome-An Exploratory Study.

Cardiorenal syndrome (CRS) denotes the bidirectional interaction of chronic kidney disease and heart failure with an adverse prognosis but with a limited understanding of its pathogenesis. This study correlates biochemical blood markers, histopathological and immunohistochemistry features, and 2-deoxy-2-fluoro-D-glucose positron emission tomography (18F-FDG PET) metabolic data in low-dose doxorubicin-induced heart failure, cardiorenal syndrome, and renocardiac syndrome induced on Wistar male rats. To our knowledge, this is the first study that investigates the underlying mechanisms for CRS progression in rats using 18F-FDG PET. Clinical, metabolic cage monitoring, biochemistry, histopathology, and immunohistochemistry combined with PET/MRI (magnetic resonance imaging) data acquisition at distinct points in the disease progression were employed for this study in order to elucidate the available evidence of organ crosstalk between the heart and kidneys. In our CRS model, we found that chronic treatment with low-dose doxorubicin followed by acute 5/6 nephrectomy incurred the highest mortality among the study groups, while the model for renocardiac syndrome resulted in moderate-to-high mortality. 18F-FDG PET imaging evidenced the doxorubicin cardiotoxicity with vascular alterations, normal kidney development damage, and impaired function. Given the fact that standard clinical markers were insensitive to early renal injury, we believe that the decreasing values of the 18F-FDG PET-derived renal marker across the groups and, compared with their age-matched controls, along with the uniform distribution seen in healthy developing rats, could have a potential diagnostic and prognostic yield in cardiorenal syndrome.

Cardiorenal syndrome: Pathophysiology as a key to the therapeutic approach in an under-diagnosed disease.

Cardiorenal syndrome is a clinical condition that impacts both the heart and the kidneys. One organ's chronic or acute impairment can lead to the other's chronic or acute dysregulation. The cardiorenal syndrome has been grouped into five subcategories that describe the etiology, pathophysiology, duration, and pattern of cardiac and renal dysfunction. This classification reflects the large spectrum of interrelated dysfunctions and underlines the bidirectional nature of heart-kidney interactions. However, more evidence is needed to apply these early findings in medical practice. Understanding the relationship between these two organs during each organ's impairment has significant clinical implications that are relevant for therapy in both chronic and acute conditions. The epidemiology, definition, classification, pathophysiology, therapy, and outcome of each form of cardiorenal syndrome are all examined in this review.

Echocardiography is a good way to diagnose and monitor type 1 cardiorenal syndrome in ICU.

BACKGROUND: Type-one cardiorenal syndrome (CRS) is defined by acute decompensated heart failure leading to secondary acute kidney injury. No study evaluates the reliability of transthoracic echocardiography as a help tool for diagnosis and optimization of CRS. Therefore, the aim of this study was to assess echocardiographic parameters in patients with CRS in the Intensive Care Unit. METHODS: We conducted an observational, prospective, single-center study in the ICU department of a general hospital. Patients admitted in the ICU and presenting with type 1 CRS were included. Transthoracic echocardiography was performed at baseline and at day end after treatment by the same trained operator for the same patients. We report various echocardiographic indices at these two timepoints. RESULTS: Twenty-seven patients were included. At baseline 96.3% of patients had signs of congestion (IVC dilation >2 cm), 76% had an altered S-wave (<11.5 cm/s), 72.73% had an altered TAPSE (<17 mm), 85.19% had an elevated RV/LV diameter ratio (>0.6). Between baseline and D end, IVC size and, the number of patients with an elevated RV/LV diameter ratio significantly decreased. Weight decreased, whereas natriuresis significantly increased, and the amount of vasopressors support decreased. Diuresis, and S-wave velocity showed non-significant changes. CONCLUSIONS: Main echocardiographic findings at baseline in patients with type 1 CRS consist of a right ventricular dysfunction associated an IVC dilation. We report that weight, RV/LV diameter ratio, and IVC diameter might constitute good follow-up parameters to monitor treatment response.

Evaluation of the diagnostic value of the renal resistive index as a marker of the subclinical development of cardiorenal syndrome in MMVD dogs.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) in dogs inevitably causes renal dysfunction. These interactions are known as the cardiorenal syndrome (CRS). The main aims of the study were to evaluate whether renal resistive index (RRI) may be useful as a non-invasive marker in subclinical stage of kidney injury in dogs with MMVD and to compare RRI with SDMA and Cyst C. METHODS: Forty-four dogs were divided into two groups: control-15 healthy dogs and the heart group-29 dogs with MMVD (ACVIM class Cc). Study protocol included: anamnesis, clinical examination, electrocardiography, echocardiography, chest radiography, abdominal ultrasonography with measurements of the renal resistive index (RRI), urine, and blood analysis. RESULTS: The RRI in the heart group was significantly higher 0.725 ± 0.035 versus control group 0.665 ± 0.028 (p < 0.00085). The RRI cut-off point in dogs with stable chronic heart failure (CHF) under 8 years is 0.775, in older 0.64. RRI was similar in MMVD dogs treated with ACE-I + furosemide and dogs treated ACE-I + torasemide + pimobendan + spironolactone. There was no correlation between RRI and SDMA or Cyst C. CONCLUSION: RRI is more sensitive than creatinine, SDMA and Cyst C to reveal kidney injury in MMVD dogs class Cc younger than 8 years.

Value of Renal Vascular Doppler Sonography in Cardiorenal Syndrome Type 1.

OBJECTIVES: Worsening of renal function in a patient with acute decompensated heart failure is called cardiorenal syndrome (CRS) type 1. Recent studies have shown an association of persistent systemic venous congestion with renal dysfunction. This trial was set up to investigate the changes of renal Doppler parameters with diuretic therapy in patients with CRS type 1. METHODS: Cases of CRS type 1 were identified among patients hospitalized for decompensated heart failure. Serial measurements of the renal venous impedance index (VII) and arterial resistive index (ARI) were calculated by pulsed wave Doppler sonography. RESULTS: A total of 30 patients who had creatinine improvement with diuresis (group 1) and 34 patients without any improvement (group 2) were analyzed. Patients in group 1 had higher median VII and ARI (VII, 0.86 versus 0.66; P < .001; ARI, 0.78 versus 0.65; P < .001) on admission. A high ARI on admission (odds ratio, 6.25; 95% confidence interval, 1.84-14.3; P = .003) predicted the improvement of serum creatinine levels with diuretic therapy independent of confounding factors in patients with CRS type 1. CONCLUSIONS: Renal vascular Doppler parameters might offer guidance on the diagnostic and therapeutic strategies in prescribing decongestive therapy for decompensated heart failure.

Cardiorenal syndrome: Clinical and echocardiographic aspects. / Síndrome cardiorrenal: aspectos clínicos y ecocardiográficos.

El síndrome cardiorrenal (SCR) es un trastorno en el que intervienen el corazón y los riñones, interactuando y produciendo una disfunción entre ellos en forma aguda o crónica. Existen diferentes fenotipos clínicos bien identificados como «desórdenes del corazón y riñón en los que la disfunción aguda o crónica en un órgano induce la disfunción aguda o crónica del otro¼. La alta incidencia de morbimortalidad cardiovascular presente en los pacientes con enfermedad renal crónica terminal (ERCT), en especial la insuficiencia cardiaca (IC), origina inicialmente una lesión miocárdica que conlleva remodelamiento ventricular, lo cual induce a la activación de mecanismos compensadores, entre los cuales el riñón es pieza fundamental, ya que regula la homeostasis hidroelectrolítica y así el volumen circulante, siendo esto en la etapa dialítica más evidente. Los cambios funcionales y anatómicos cardiovasculares que se producen en estos pacientes son muy prevalentes e incluyen las interacciones hemodinámicas del corazón y los riñones en la insuficiencia cardiaca, y el impacto de la enfermedad aterosclerótica en ambos sistemas de órganos. También describimos estrategias diagnósticas y terapéuticas aplicables al síndrome cardiorrenal, que determinan la importancia de la ecocardiografía como modelo de diagnóstico útil. Finalmente, se analizan las posibilidades de tratamiento y la remisión de las alteraciones funcionales cardiacas con el trasplante renal en los pacientes con ERCT.Cardiorenal syndrome (CRS) is a disorder in which the heart and kidneys are involved, interacting and producing a dysfunction between them in an acute or chronic way. There are different clinical phenotypes well identified as "heart and kidney disorders in which acute or chronic dysfunction in one organ induces acute or chronic dysfunction in the other". The high incidence of cardiovascular morbimortality in patients with chronic terminal kidney disease (CKD), especially heart failure (HF), initially causes a myocardial lesion that leads to ventricular remodeling, which induces the activation of compensatory mechanisms, among which the kidney is a fundamental part since it regulates the hydroelectrolytic homeostasis and thus the circulating volume, being this in the dialytic stage more evident. The functional and anatomical changes at cardiovascular level that occur in these patients are very prevalent, and include hemodynamic interactions of the heart and kidneys in heart failure and the impact of atherosclerotic disease in both organ systems. We also describe diagnostic and therapeutic strategies applicable to cardiorenal syndrome, which determine the importance of echocardiography as a useful diagnostic model. Finally, we analyze the possibilities of treatment and remission of cardiac functional alterations with renal transplantation in patients with T-CKD.

Síndrome cardiorrenal: aspectos clínicos y ecocardiográficos / Cardiorenal syndrome: Clinical and echocardiographic aspects

Resumen El síndrome cardiorrenal (SCR) es un trastorno en el que intervienen el corazón y los riñones, interactuando y produciendo una disfunción entre ellos en forma aguda o crónica. Existen diferentes fenotipos clínicos bien identificados como «desórdenes del corazón y riñón en los que la disfunción aguda o crónica en un órgano induce la disfunción aguda o crónica del otro¼. La alta incidencia de morbimortalidad cardiovascular presente en los pacientes con enfermedad renal crónica terminal (ERCT), en especial la insuficiencia cardiaca (IC), origina inicialmente una lesión miocárdica que conlleva remodelamiento ventricular, lo cual induce a la activación de mecanismos compensadores, entre los cuales el riñón es pieza fundamental, ya que regula la homeostasis hidroelectrolítica y así el volumen circulante, siendo esto en la etapa dialítica más evidente. Los cambios funcionales y anatómicos cardiovasculares que se producen en estos pacientes son muy prevalentes e incluyen las interacciones hemodinámicas del corazón y los riñones en la insuficiencia cardiaca, y el impacto de la enfermedad aterosclerótica en ambos sistemas de órganos. También describimos estrategias diagnósticas y terapéuticas aplicables al síndrome cardiorrenal, que determinan la importancia de la ecocardiografía como modelo de diagnóstico útil. Finalmente, se analizan las posibilidades de tratamiento y la remisión de las alteraciones funcionales cardiacas con el trasplante renal en los pacientes con ERCT.

Abstract Cardiorenal syndrome (CRS) is a disorder in which the heart and kidneys are involved, interacting and producing a dysfunction between them in an acute or chronic way. There are different clinical phenotypes well identified as "heart and kidney disorders in which acute or chronic dysfunction in one organ induces acute or chronic dysfunction in the other". The high incidence of cardiovascular morbimortality in patients with chronic terminal kidney disease (CKD), especially heart failure (HF), initially causes a myocardial lesion that leads to ventricular remodeling, which induces the activation of compensatory mechanisms, among which the kidney is a fundamental part since it regulates the hydroelectrolytic homeostasis and thus the circulating volume, being this in the dialytic stage more evident. The functional and anatomical changes at cardiovascular level that occur in these patients are very prevalent, and include hemodynamic interactions of the heart and kidneys in heart failure and the impact of atherosclerotic disease in both organ systems. We also describe diagnostic and therapeutic strategies applicable to cardiorenal syndrome, which determine the importance of echocardiography as a useful diagnostic model. Finally, we analyze the possibilities of treatment and remission of cardiac functional alterations with renal transplantation in patients with T-CKD.

Successful Peritoneal Dialysis for the Treatment of Inotrope-Dependent End-Stage Heart Failure.

Extra- and/or intracorporeal renal replacement therapy can improve the cardiorenal hemodynamics in patients with advanced heart failure (HF) refractory to medical therapy and renal failure. Here, we report the case of a 51-year-old woman with inotrope-dependent end-stage HF and chronic renal failure due to anthracycline-induced cardiomyopathy, in whom the induction of hemodiafiltration and subsequent chronic peritoneal dialysis (PD) provided a dramatic improvement of her cardiac hemodynamics from restrictive to almost normal physiology assessed by echocardiography and cardiac catheterization. The patient returned to office work with New York Heart Association functional class I-II symptoms for at least 3 years with continuous ambulatory PD after hospital discharge.

Echocardiographic Findings in Patients with Mild to Moderate Chronic Kidney Disease without Symptomatic Heart Failure: A Population-Based Study.

BACKGROUND: Renal dysfunction is an established risk factor for cardiovascular disease, but early disease states in both organs are poorly studied. OBJECTIVE: This cross-sectional population-based study aims to investigate if there is an early association between kidney function and echocardiographic markers of cardiac structure and diastolic function. METHODS: The study population consisted of 1,504 individuals with no prior history of congestive heart failure or asymptomatic left ventricular ejection fraction ≤40% and an estimated glomerular filtration rate (eGFR) based on cystatin C >15 mL/min/1.73 m2. The participants were categorized according to eGFR ≥90, 75-89, 60-74, 45-59, 30-44, and 15-29 mL/min/1.73 m2. We evaluated associations between eGFR categories and echocardiographic findings specific to cardiac structure and diastolic function. RESULTS: Associations between eGFR categories and echocardiographic findings were found for left atrium area/body surface area (p = 0.013) indicating structural changes, and peak early mitral valve velocity (A; p = 0.003), peak late atrial mitral valve velocity/peak systolic myocardial velocity at mitral annulus in the lateral wall (E/Élat; p = 0.002), É mean of lateral and septal wall/Á mean of lateral and septal wall (mean É/Á; p = 0.027) indicating diastolic dysfunction. Associations between E/Élat and mean É/Á and eGFR categories were already present in individuals with eGFR 45-60 mL/min/1.73 m2. In sex-specific analysis these associations were only significant among men. CONCLUSION: A significant association between mild to moderate impairment of renal function and echocardiographic markers of cardiac structure and diastolic function was observed, supporting the hypothesis that interaction between the kidney and heart exists even in the early stages of renal impairment.

Three-dimensional speckle-tracking echocardiography for evaluating myocardial motion in patients with cardiorenal syndrome.

Because of better awareness and understanding of its pathophysiology, the cardiorenal syndrome (CRS) is more often diagnosed and better managed. The echocardiographic evaluation of CRS now benefits from three-dimensional speckle tracking echocardiography (3D-STE), which allows multidimensional and real-time evaluation of regional myocardial and overall cardiac function, and helps assessing the degree of myocardial damage. This article describes the application of 3D-STE in evaluating the myocardial motion in patients with CRS.

The Cardiorenal Axis: Myocardial Perfusion, Metabolism, and Innervation.

PURPOSE OF THE REVIEW: Cardiorenal syndrome (CRS), defined as concomitant heart and kidney disease, has been a focus of attention for nearly a decade. As more patients survive severe acute and chronic heart and kidney diseases, CRS has emerged as an "epidemic" of modern medicine. Significant advances have been made in unraveling the complex mechanisms that underlie CRS based on classification of the condition into five pathophysiologic subtypes. In types 1 and 2, acute or chronic heart disease results in renal dysfunction, while in types 3 and 4, acute or chronic kidney diseases are the inciting factors for heart disease. Type 5 CRS is defined as concomitant heart and kidney dysfunction as part of a systemic condition such as sepsis or autoimmune disease. RECENT FINDINGS: There are ongoing efforts to better define subtypes of CRS based on historical information, clinical manifestations, laboratory data (including biomarkers), and imaging characteristics. Systematic evaluation of CRS by advanced cardiac imaging, however, has been limited in scope and mostly focused on type 4 CRS. This is in part related to lack of clinical trials applying advanced cardiac imaging in the acute setting and exclusion of patients with significant renal disease from studies of such techniques in chronic HF. Advanced cardiac nuclear imaging is well poised for assessment of the pathophysiology of CRS by offering a myriad of molecular probes without the need for nephrotoxic contrast agents. In this review, we examine the current or potential future application of advanced cardiac imaging to evaluation of myocardial perfusion, metabolism, and innervation in patients with CRS.

Alterations in Doppler-derived renal venous stasis index during recompensation of right heart failure and fluid overload in a patient with pulmonary hypertension.

Renal congestion is becoming recognized as a potential contributor to cardiorenal syndromes. Adequate control of congestion with simultaneous preservation of renal function has been proposed as a central goal of the management of heart failure. We report our care of a 48-year-old woman suffering from right heart failure and massive fluid overload due to severe pulmonary hypertension secondary to a combination of left-heart disease and status after recurrent pulmonary embolisms. Alterations in Doppler-derived intrarenal venous flow patterns and a novel renal venous stasis index were used to evaluate improvement in renal venous congestion during recompensation. Due to refractory congestion despite optimal medical treatment and continuous veno-venous hemodialysis, a peritoneal dialysis catheter was placed to relieve the massive ascites. The paracentesis of ascites led to a significant loss of weight, normalization of hydration status with subsequent termination of continuous veno-venous hemodialysis, and a significant improvement in clinical and echocardiographic parameters. Renal Doppler ultrasonography showed continuous improvement in intrarenal venous flow patterns and the renal venous stasis index indicative of effective decongestion up to a normal intrarenal venous flow pattern and renal venous stasis index. Furthermore, residual renal function increased during follow-up. This case demonstrates the feasibility of renal Doppler ultrasonography as a simple, non-invasive, and integrative measure of renal congestion. The renal venous stasis index and intrarenal venous flow patterns may be useful to evaluate the treatment response and to guide therapy in patients with right heart failure.

Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat.

This study tested the hypothesis that early administration of empagliflozin (Empa), an inhibitor of glucose recycling in renal tubules, could preserve heart function in cardiorenal syndrome (CRS) in rat. Chronic kidney disease (CKD) was caused by 5/6 subtotal nephrectomy and dilated cardiomyopathy (DCM) by doxorubicin (DOX) treatment. In vitro results showed that protein expressions of cleaved-caspase3 and autophagy activity at 24 h/48 h in NRK-52P cells were significantly upregulated by para-Creso treatment; these were significantly downregulated by Empa treatment. Flow cytometric analysis showed that annexin-V (i.e., early/late apoptosis) in NRK-52P cells expressed an identical pattern to cleaved-caspase3 between the two groups (all p < 0.001). Adult-male-SD rats (n = 18) were equally categorized into group 1 (sham-control), group 2 (CRS) and group 3 [CRS + Empa; 20 mg/kg/day]. By day-42 after CRS induction, left-ventricular ejection fraction (LVEF) level exhibited an opposite pattern, whereas LV end-diastolic dimension and creatinine level displayed the same pattern, to cleaved-caspase3 among the three groups (all p < 0.0001). In LV tissues, protein expressions of inflammatory (tumor-necrosis factor-α/nuclear-factor-κB/interleukin-1ß/matrix-metalloprotianse-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP), fibrotic (transforming-growth factor-ß/Smad3), DNA/mitochondrial-damage (γ-H2AX/cytosolic-cytochrome-C) and heart failure (brain natriuretic peptide (BNP) levels displayed an opposite pattern to LVEF among the three groups (all p < 0.0001). Additionally, cellular expressions of DNA-damage/heart-failure (γ-H2AX+//XRCC1+CD90+//BNP+) biomarkers and histopathological findings of fibrotic/condensed collagen-deposition areas and apoptotic nuclei showed an identical pattern, whereas connexin43 and small-vessel number exhibited an opposite pattern, to inflammation among the three groups (all p < 0.0001). In conclusion, Empa therapy protected heart and kidney against CRS injury.

Renal intraparenchymal resistive index: the ultrasonographic answer to many clinical questions.

The use of renal resistive indices (RRIs) for the study of renal microcirculation has in the past been proposed for the identification of renal organ damage or even to specifically identify injury to some areas of the renal parenchyma. Nevertheless, according to the most recent evidences from literature this organ-based conception of RRIs has been proven to be partial and unable to explain the RRIs variations in clinical settings of sepsis or combined organ failure of primitively extrarenal origin or, more generally, the deep connection between RRIs and hemodynamic factors such as compliance and pulsatility of the large vessels. The aim of this review is to explain the physiopathological basis of RRIs determination and the most common interpretative errors in their analysis. Moreover, through a comprehensive vision of these Doppler indices, the traditional and emerging clinical application fields for RRIs are discussed.

A novel model of reno-cardiac syndrome in the C57BL/ 6 mouse strain.

BACKGROUND: The end stage renal disease population has a 20 fold higher incidence of cardiovascular mortality compared to the overall population. The development of reno-cardiac syndrome in these patients will result in cardiovascular events to be the cause of 50% of fatalities. There is therefore a need to research improved therapeutic strategies to combat renal cardiac pathologies. Murine in vivo models contribute greatly to such research allowing for specific genetic modification and reduced miscellany, however there is currently no reliable model of reno-cardiac syndrome in the most common genetically modified mouse strain, the C57BL/6. In this study we have manipulated an established model of chronic renal disease using adenine infused diet and prolonged the course of its pathology achieving chronic renal failure and subsequent reno-cardiac syndrome in the C57BL/6 mouse. METHODS: Eight week-old male C57BL/ 6 mice were acclimatised for 7 days before administration of a 0.15% adenine diet or control diet for 20 weeks. Cardiac function was assessed in mice at week 20 by echocardiography. At experiment termination blood and urine samples were analysed biochemically and organ dysfunction/injury was determined using immunoblotting and immunohistochemistry. RESULTS: Administration of 0.15% adenine diet caused progressive renal failure resulting in reno-cardiac syndrome. At endpoint uraemia was confirmed by blood biochemistry which in the adenine fed mice showed significant increases in serum creatinine, urea, calcium (P < 0.0001) potassium (P < 0.05), and a significantly reduced glomerular filtration rate (P < 0.05). Reno-cardiac syndrome was confirmed by a significantly increased heart to body weight ratio (P < 0.0001) and echocardiography which showed significant reductions in percentage of ejection fraction, fractional shortening, fractional area change, (P < 0.0001) and an increase in left ventricular end diastolic volume (P < 0.05). Immunoblotting of kidney and heart tissue showed increased apoptosis (caspase 3) and fibrosis (fibronectin) and increases in the cardiac levels of phosphorylated Akt, and renal total Akt. Immunohistochemistry for α-SMA, collagen 1 and collagen 3 further confirmed fibrosis. CONCLUSIONS: We present a novel regimen of adenine diet which induces both chronic kidney disease and reno-cardiac syndrome in the C57/BL6 mouse strain. The non-surgical nature of this model makes it highly reproducible compared to other models currently available.

Selective abdominal venous congestion to investigate cardiorenal interactions in a rat model.

Abdominal congestion may play an important role in the cardiorenal syndrome and has been demonstrated to drive disease progression. An animal model for abdominal congestion, without other culprit mechanisms that are often present in patients such as low cardiac output or chronic kidney disease, might be interesting to allow a better study of the pathophysiology of the cardiorenal syndrome. The objective of this study was to develop a clinically relevant and valid rat model with abdominal venous congestion and without pre-existing heart and/or kidney dysfunction. To do so, a permanent surgical constriction (20 Gauge) of the thoracic inferior vena cava (IVC) was applied in male Sprague Dawley rats (IVCc, n = 7), which were compared to sham-operated rats (SHAM, n = 6). Twelve weeks after surgery, abdominal venous pressure (mean: 13.8 vs 4.9 mmHg, p < 0.01), plasma creatinine (p < 0.05), plasma cystatin c (p < 0.01), urinary albumin (p < 0.05), glomerular surface area (p < 0.01) and width of Bowman's space (p < 0.05) of the IVCc group were significantly increased compared to the SHAM group for a comparable absolute body weight between groups (559 vs 530g, respectively, p = 0.73). Conventional cardiac echocardiographic and hemodynamic parameters did not differ significantly between both groups, indicating that cardiac function was not compromised by the surgery. In conclusion, we demonstrate that constriction of the thoracic IVC in adult rats is feasible and significantly increases the abdominal venous pressure to a clinically relevant level, thereby inducing abdominal venous congestion.

Science to Practice: Can Functional MR Imaging Be Useful in the Evaluation of Cardiorenal Syndrome?

Functional magnetic resonance (MR) imaging of the kidneys has gained interest recently, especially in the detection of early changes in acute kidney injury or to predict progression of chronic kidney disease (CKD). The application of these methods to cardiorenal syndrome (CRS) is novel. CRS is widely accepted as a complex clinical problem routinely faced by clinicians. In this issue, Chang et al ( 1 ) present their preliminary experience applying blood oxygen level-dependent (BOLD) MR imaging to the kidneys in mice with experimental myocardial infarction. They showed that R2* in the kidney increases after induced myocardial infarction and that the response was higher in animals with larger infarcts and over time. The authors also for the first time correlated the BOLD MR imaging findings against hypoxia-inducible factor-1α (HIF-1α) expression, an independent marker of renal hypoxia. In addition, they showed evidence for renal injury by using a kidney injury marker, kidney injury molecule-1 (KIM-1). The results of their study support the use of renal BOLD MR imaging in subjects with heart failure, in whom the risk of subsequent renal ischemia and/or hypoxia is known to exist. These results, along with those of other recent reports ( 2 ), suggest that functional imaging methods could play a key role in evaluating changes in both the primary and secondary organs involved in complex disease processes such as CRS. Availability of such methods could facilitate translation to the clinic and improve the mechanistic understanding of the complicated and interrelated pathophysiology.

Heart functional and structural compendium of cardiosplenic and cardiorenal networks in acute and chronic heart failure pathology.

Heart failure (HF) secondary to myocardial infarction (MI) is linked to kidney complications that comprise cellular, structural, functional, and survival indicators. However, HF research is focused on left ventricular (LV) pathology. Here, we determined comprehensive functional analysis of the LV using echocardiography in transition from acute heart failure (AHF) to progressive chronic heart failure (CHF) pathology and developed a histological compendium of the cardiosplenic and cardiorenal networks in pathological remodeling. In surgically induced MI using permanent coronary ligation, the LV dysfunction is pronounced, with myocardium necrosis, wall thinning, and 20-30% LV rupture events that indicated AHF and CHF pathological remodeling in C57BL/6 male mice (2-4 mo old, n = 50). Temporal LV function analysis indicated that fractional shortening and strain are reduced from day 1 to day 5 in AHF and sustained to advance to CHF from day 28 to day 56 compared with naïve control mice ( n = 6). During the transition of AHF ( day 1 to day 5) to advanced CHF ( day 28 to day 56), histological and cellular changes in the spleen were definite, with bimodal inflammatory responses in kidney inflammatory biomarkers. Likewise, there was a unidirectional, progressive, and irreversible deposition of compact collagen in the LV along with dynamic changes in the cardiosplenic and cardiorenal networks post-MI. The renal histology and injury markers suggested that cardiac injury triggers irreversible dysregulation that actively alters the cardiosplenic and cardiorenal networks. In summary, the novel strategies or pathways that modulate comprehensive cardiosplenic and cardiorenal networks in AHF and CHF would be effective approaches to study either cardiac repair or cardiac pathology. NEW & NOTEWORTHY The present compendium shows irreversible ventricular dysfunction as assessed by temporal echocardiography while histological and structural measurements of the spleen and kidney added a novel direction to study cardiosplenic and cardiorenal networks in heart failure pathology. Therefore, the consideration of systems biology and integrative approach is essential to develop novel treatments.