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RHF and CRS journal presentation(1).pptx
- 1. Right Heart Failure and Cardio – Renal Syndrome Thida Tabucanon, MD, W. H. Wilson Tang, MD Cardiol Clin. 2020 May ; 38(2): 185–202. doi:10.1016/j.ccl.2020.01.004.
- 2. Inflammation and Cardio – Renal Syndrome Heart Failure Production of Pro inflammatory cytokines • Neurohormonal activation • Venous Congestion Decrease cardiac function Vascular Dysfunction Renal fibrosis Progressive renal dysfunction Increase vascular Permeability Promote absorption of pro inflammatory endotoxin from bowel Cardio Renal Syndrome
- 3. Neurohormonal activation in HF RAAS Angiotensin II TNF 𝛼 biosynthesis in myocardium and renal tissue activated NF kappa B IL6, MCP 1 and other inflammatory cytokine in kidney SNS Increase HR Increase TNF 𝛼, IL-6 and IL 1𝛽 in myocardium cells and cardiac blood vessel
- 4. Venous Congestion Mesenteric venous congestion bowel wall edema and increased vascular permeability Gram negative bacterial translocation through the endothelial cells of intestinal villi and endotoxin release (LPS) LPS promotes secretion of inflammatory cytokines (TNF-α, IL-1 family, IL-6, IL-8, IL-10 family, IL-12 family, IL-15 & TGF-β Intravascular Volume Expansion Vascular inflammation and endothelial cell activation (NO and prostacyclin) Peripheral congestion release inflammatory marker (IL-6 and endothelin 1) RV dysfunction and dilatation ventricular interdependence LV remodeling reduce CO and renal arterial pressure CARDIO RENAL SYNDROME
- 5. Diagnostic Strategies for Congestion and CRS Serum and Urine Biomarkers Renal Ultrasono- graphy Intra abdominal Pressure
- 6. Serum and Urine Biomarkers BNP – NT pro BNP Cardiac Marker for myocardial Stretch, associated with renal dysfunction Troponin and glactin 3 Cardiac biomarker elevated in CRS, associated with mortality rate NGAL Urine NGAL = proximal tubular injury Serum NGAL = HF with renal dysfunction Cystatin C (CysC) Renal biomarker from tubules measure GFR Albumin in Urine Diagnostic and Prognostic, associated with mortality and admission for HF CysC + Troponin + NT pro BNP Prognostic value for adverse events in AHF
- 7. Renal Ultrasonography ● Renal vein flow pattern using doppler ultrasound depend on RAP and strongly correlated with clinical outcomes ● Continuous renal flow pattern = normal rap, discontinuous renal flow pattern = increased RAP and monophasic pattern = highest RAP and poor outcomes (<40% survival at 1 year). ● Renal flow pattern > renal resistive index (RI) to have incremental prognostic value that reflect renal venous congestion ● Limitation : require expertise to perform, and needs validation for consistency of Doppler waveform sampling by operators and in a diverse group of patients
- 8. Intra-abdominal Pressure ● Splanchnic congestion due to RHF ● Measuring IAP could be using intra-bladder pressure using intra bladder catheter connected to transducer ● Increased IAP elevated pressure greater than normal range (5 – 7 mmHg)
- 9. Medical Treatment Options for RHF and CRS DECONGESTION Reduce Systemic Congestion Return Balance Diuretic, UF and Dialysis Diuretic Resistance LOOP DIURETIC Loop of Henle, Short Peak of action Natriuresis, reduce volume overload Protein bound anion Furosemide, Torsemide, Bumetanide
- 10. Loop Diuretic ● Higher dose is needed to achieve same therapeutic effect higher dose is associated with greater diuresis, weight loss and transient WRF ● DOSE-AHF trial continuous vs bolus strategy of diuretic administration no difference in symptom relief and in change of renal function, neither in mortality ● Continuous administration associated with more hyponatremia, need for vasopressors, rehospitalization and death at 6 months ● Transition to oral therapy depend on medication half life (4-6 hr for furosemide and bumetanide, 8-12h for torsemide)
- 11. Progressive impedance of venous return from kidney in venous congestion, effective decongestion may improve renal perfusion and increase diuresis and natriuresis Excessive diuresis without adequate right heart reserve can reduce preload and impair CO Relative iv hypovolemia and decrease diuresis and natriuresis
- 12. Diuretic Resistance ● Diuretic resistance diminished or loss of diuretic response before reach the therapeutic goal of relief from edema. ● Measuring diuretic efficacy or resistance weight loss, net fluid loss, urine output after 40mg iv furosemide and natriuresis ● No cut off or standard definition of diuretic resistance ● Braking phenomena diminished diuretic induced natriuresis contributors to diuretic resistance ○ Hemodynamic braking ○ Neurohormonal braking ● Nephron Remodeling determine diuretic efficacy ● Add non loop diuretic overcome braking phenomenon and nephron remodeling augment natriuresis
- 13. Vasoactive and inotropic drugs used in RHF, clinical trial evidence has been lacking, most literature based upon cardio-centric optimization in advance HF patients Selective pulmonary vasodilator successfully used for acute RHF where PH is a major contributor, evidence in CRS is still lacking Other medical therapies
- 14. SUMMARY Clinical assessment of extra-cellular fluid status remains important to keep the balance between hypervolemia and dehydration. Decongestion is still the mainstay strategy in HF with CRS and is clinically challenging. Prevention should be the most important goal. The heart and kidney have complex bidirectional interlinks termed CRS Correlation of venous congestion and renal dysfunction in HF which represents the significant influence from the right heart.
- 15. THANKS! Always listen to your heart! It may on your left, but it mostly always RIGHT!
Editor's Notes
- Production of pro inflammatory cytokines as a consequence of HF could be from : Neurohormonal activation Venous congestion local congestion (splanchnic congestion and intra renal venous congestion) or systemic venous congestion Cytokines Tumor necrotic factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) have direct biological effects to structural and functional damage to various end organs (heart, vasculature and kidney) correlate with poor clinical outcomes Inflammation depressed cardiac function, vascular dysfunction, renal fibrosis and pr ogressive renal dysfunction Inflammation increase vascular permeability and promote absorption of pro inflammatory endotoxins from the bowel
- Increased activity of RAAS and SNS in HF chronic inflammation Angiotensin II (AII) increases TNF 𝛼 biosynthesis in myocardium that mediated through angiotensin 1 receptor. Also in animal AII increases renal tissue expression of TNF 𝛼 (at glomeruli, mainly at endothelium of tubules and vasculature), activated NF kappa B and induced renal synthesis of IL6, MCP 1 coexisting with glomerular and interstitial inflammatory cells in kidney SNS isoproterenol infusion increase expression of TNF 𝛼, IL-6 and IL-1𝛽 in myocardium cells and cardiac blood vessels and beta blocker administration decreases these effects
- Venous and tissue congestion promotes inflammatory response by various mechanism Mesenteric venous congestion bowel wall edema and increased vascular permeability gram negative bacterial translocation through the endothelial cells of intestinal villi and endotoxin release Endotoxin : LPS promotes secretion of inflammatory cytokines LPS and cytokines levels increased in edematous chronic HF reduction after acute diuretic treatment Higher endotoxin levels In hepatic vein compared to LV in acute HF suggest bacterial or endotoxin translocation from bowel to blood stream Intravascular volume expansion vascular inflammation and endothelial cell activation through cytokine secretion itself and alter other bioactive molecules such as NO and prostacyclin function In human study, peripheral congestion created through applied pressure using tourniquet on the arms release inflammatory markers, IL-6 and endothelin 1 Systemic inflammation in HF contribute to CRS development also leads to end organ damage RHF increased RV filling pressure RV dysfunction and dilatation ventricular interdependence leftward shift of interventricular septum and alter LV geometry Reducing LV distensibility, preload and reducing CO reducing renal arterial pressure CRS Most often in isolated RHF in advanced Pulmonary Arterial Hypertension
- Venous and tissue congestion promotes inflammatory response by various mechanism Mesenteric venous congestion bowel wall edema and increased vascular permeability gram negative bacterial translocation through the endothelial cells of intestinal villi and endotoxin release Endotoxin : LPS promotes secretion of inflammatory cytokines LPS and cytokines levels increased in edematous chronic HF reduction after acute diuretic treatment Higher endotoxin levels In hepatic vein compared to LV in acute HF suggest bacterial or endotoxin translocation from bowel to blood stream Intravascular volume expansion vascular inflammation and endothelial cell activation through cytokine secretion itself and alter other bioactive molecules such as NO and prostacyclin function In human study, peripheral congestion created through applied pressure using tourniquet on the arms release inflammatory markers, IL-6 and endothelin 1 Systemic inflammation in HF contribute to CRS development also leads to end organ damage RHF increased RV filling pressure RV dysfunction and dilatation ventricular interdependence leftward shift of interventricular septum and alter LV geometry Reducing LV distensibility, preload and reducing CO reducing renal arterial pressure CRS Most often in isolated RHF in advanced Pulmonary Arterial Hypertension
- Provide a wide spectrum of prevention, early diagnosis, treatment and outcomes of organ injury (including heart and kidney) BNP Marker of myocardial stretch has diagnostic and prognostic roles in HF and CRS higher BNP in HF with impaired renal function compared with normal renal function impaired renal excretion, volume overload and cardiomyopathy associated with renal dysfunction Cardiac Troponin and glactin 3 cardiac biomarker elevated in CRS higher level, higher mortality rate in HF Neutrophil Gelatinase associated Lipocalin (NGAL) large lysosomal enzyme originating in proximal tubular cell detection urine NGAL = proximal tubular injury, elevated serum NGAL = HF with renal dysfunction, elevated serum and urine NGAL = predictor for dialysis and death in AKI patients. Serial measurement of NGAL in AHF patients is an accurate predictor of Worsening Renal Function Cystatin C (CysC) renal biomarker that secreted by renal tubules better than creatinine for measuring GFR CysC + NT pro BNP and Cardiac Troponin additive prognostic value for adverse events in AHF Albuminuria in HF without concomitant comorbidity has diagnostic power for CRS than using GFR, also associated with increased mortality and admission for HF
- Renal vein flow pattern using doppler ultrasound depend on RAP and strongly correlated with clinical outcomes continuous renal flow pattern = normal rap, discontinuous renal flow pattern = increased RAP and monophasic pattern = highest RAP and poor outcomes (<40% survival at 1 year). Renal flow pattern > renal resistive index (RI) to have incremental prognostic value that reflect renal venous congestion Limitation : require expertise to perform, and needs validation for consistency of Doppler waveform sampling by operators and in a diverse group of patients
- Cornerstone Decongestion reduce systemic venous congestion, return balance in hemodynamic, neurohormonal and biological activation Decongestion diuretics, ultrafiltration and dialysis Most challenging of decongestion in CRS diuretic resistance Loop Diuretic inhibit Na+K+2Cl- co transporter at thick ascending limb of loop of henle with short peak of action (1—30 min for iv and 1-1.5 hours for oral administration) Loop Diuretic cause natriuresis, net negative water and salt balance, and reduced volume overload Most used diuretic Furosemide, Torsemide, Bumetanide Loop diuretic protein bound anion hypoalbuminemia decreased its transportation to site of action; NSAID drug, bile acid and uremic toxin reduced its efficacy
- Dose response to diuretic curve in HF shifts downward and to the right higher dose is needed to achieve same therapeutic effect higher dose is associated with greater diuresis, weight loss and transient WRF DOSE-AHF trial continuous vs bolus strategy of diuretic administration no difference in symptom relief and in change of renal function, neither in mortality Continuous administration associated with more hyponatremia, need for vasopressors, rehospitalization and death at 6 months Transition to oral therapy depend on medication half life (4-6 hr for furosemide and bumetanide, 8-12h for torsemide) A stepwise pharmacologic strategy has been proposed and studied in post hoc analysis of 3 randomized controlled trials in acute HF with CRS, including DOSE-AHF(153), the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF)(156) and Renal Optimization Strategies Evaluation in AHF (ROSE-AHF) trial(157). These studies showed superiority to standard decongestive therapy (including non-adjusted diuretic dose) without WRF and superiority to ultrafiltration in preservation of renal function at 96 hours
- Diuretic efficacy in HF has been shown as a strong predictor for mortality and morbidity including all-cause death, HF readmission and renal related readmission after correction with baseline eGFR Braking phenomena diminished diuretic induced natriuresis contributors to diuretic resistance Hemodynamic braking diuretic reduces extracellular fluid SNS and RASS activation increases sodium reabsorption at proximal tubules Neurohormonal braking diuretic increases urine sodium and activates TGFeedback renin production afferent arteriolar vasoconstriction reduces sodium filtration Nephron remodeling (distal tubular hypertrophy and hyperplasia) as a consequence of prolonged use of loop diuretic is also considered a determinant of diuretic efficacy Hence, addition of non-loop diuretics (i.e. thiazide or potassium sparing diuretic), which is termed “segmental nephron blockage,” may be reasonable and also might overcome the braking phenomenon and nephron remodeling thereby augmenting natriuresis(171) without compromising GFR
- selective pulmonary vasodilators have been used with success (e.g., inhaled nitric oxide, prostacyclin and iloprost), although there is limited data to support the role of phosphodiesterase type 5 inhibitors for this indication.