Cardio-renal interactions
Introducing nephro-cardiology
{ or cardio-nephrology }
Where are we in 2022 with HFpEF ?CKD in HFpEF { or HFpEF in CKD } Cardiorenal
Syndrome .Four-step
HFA-PEFF diagnostic algorithm
heterogeneity in patients with HFpEF.Phenotyping HFpEF :
Beyond EF.Management of HFpEF .patients with HF on dialysis
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Linking HFpEF and Chronic kidney disease
1. Magdy El-Masry
Prof. of Cardiology
Tanta University
Linking HFpEF and CKD
What is the Link? Targets of Care?
2. Despite renal mass accounts only for 0.5% of total body mass, 25% of cardiac output is delivered to the kidney, which consumes the 7% of the whole
body oxygen consumption.
Renal oxygen consumption is mostly connected to the selective reabsorption of glomerular filtrate that corresponds to approximately to 180 L/day, while
daily urine output is restricted to 1.2–1.8 L/day.
In the kidney, the largest amount of O2 consumption occurs in the cortex, where the blood flow is prominently directed to generate the GFR that, in turn,
is linked to the Na+ reuptake in the proximal tubular segment. The reabsorption process is based on ATP utilization. In the normal subject the average GFR
is 180 L/day while the normal urine output ranges from 1.2 to 1.8 L/day, meaning that roughly 1% of the glomerular filtered load is excreted .
Int. J. Mol. Sci. 2022, 23, 11987.
Kidneys are amazing organs of our body
3. “ Today we’ll be talking about Cardio-renal interactions ”
Introducing nephro-cardiology
{ or cardio-nephrology }
Where are we in 2022 with HFpEF ?
CKD in HFpEF
{ or HFpEF in CKD }
4. Introducing nephro-cardiology { or cardio-nephrology }
“ The heart and the kidneys are like a married couple.
If one is not happy, the other one probably isn’t either ”
→→ the term nephrocardiology , or
in some instances cardionephrology
5. Cardiorenal Interactions : A Historical Note
In 1842, Carl Ludwig proposed the hypothesis that urine is
the result of a filtration process by the glomeruli promoted
by the force of blood pressure
[Ludwig, C. De Viribus Physicis Secretionem Urinae Adjuvantibus: Commentatio Quam Pro
Venia Legendi Gratioso Medicorum Marburgensium Ordini. Elwert. 1842. ]
Carl Ludwig
(1816–1895) ,
a pioneer of physiology ,
presented a new
concept of renal
function and cardiorenal
interaction.
7. The nine elements of the interaction between nephrology and cardiovascular medicine that compose
the subject matter of nephrocardiology.
Therefore, nephrocardiology is defined as the study of the interaction between nephrology and cardiovascular
medicine, which is the multidirectional interplay of cardiovascular diseases and nephrology-related conditions
from the standpoints of pathophysiology, epidemiology, prevention, diagnosis, prognosis, monitoring, therapy,
risk factors, and the systemic diseases that involve both nephrology-related conditions and cardiovascular
diseases. CJASN February 2022, 17 (2) 311-313
Figure demonstrates the elements of nephrocardiology according to this definition.
8. Nephrology Dialysis Transplantation
“Published : 11 October 2022”
Translation of CKD risk classes (as defined by KDIGO in 2012)
into CVD risk classes (as defined by the ESC in the 2021
guideline on CVD prevention ).
Numbers within cells represent prevalence in the general
population.
9. Bidirectional mechanisms in cardiorenal axis pathophysiology. CRS presents a common pathogenesis characterized by
hemodynamic, neurohormonal, inflammatory mechanisms also involving the atherosclerotic degeneration. RAAS system plays a
major role in CRS pathophysiology, tipping the scale in the delicate balance between heart and kidney. Biomolecules 2021, 11, 1581
Cardiorenal
Syndrome :
one disease –
two paths?
Organ-Crosstalk:
The crosstalk
between the
heart and the
kidney is clearly
evidenced but
not fully
understood.
10.
11. An Updated Classification of Cardiorenal Syndrome
information on the presence or absence of valvular heart disease and
on the presence of hyper- or hypovolemia is added.
J. Clin. Med. 2022, 11(10)
Thus, CRS is specified as “acute” (type-I, type-III or type-V CRS) or “chronic” (type-II, type-IV or type-V) CRS, as
“valvular” or “nonvalvular” CRS, and as “hyper-” or “hypovolemia-associated” CRS if euvolemia is absent.
12. Paradigm of interstitial and intravascular volume
expansion in chronic heart failure.
Volume Status in CRS Patients
Normally, the fluid capacity of the interstitial compartment is ≈3× to 4× that of the intravascular compartment with the volume of interstitial fluid
being a fairly direct determinant of the volume of the intravascular compartment.
A marked expansion in the interstitial compartment volume is thus one of the most persistent and significant responses to systolic HF, and
depending on the volume compliance of the interstitial compartment may exceed the normal 3 to 4:1 interstitial to plasma volume (PV) ratio by several
fold to a point, where this fluid compartment may no longer be adequately responsive to standard diuretic therapy and as a result refractory volume
overload develops over time. Circulation: Heart Failure. 2016;9
13. Key components of the POCUS evaluation of the fluid volume status
Kidney360 August 2021, 2 (8) 1326-1338
Assessment of Fluid Volume Status by POCUS “Point-of-Care Ultrasonography”
Bedside Assessment
*Extravascular Lung Water
B-lines, which are vertical hyperechoic artifacts, occur
when the air content in the lung decreases due to
interstitial thickening (typically from fluid).
*
15. Management of Cardiorenal Syndrome and Heart Failure
Because patients with cardiorenal syndrome have been
excluded from many heart failure trials, literature supporting
appropriate management and treatment of cardiorenal
syndrome is lacking and remains largely empirical.
Most treatment plans focus on improving hemodynamic
abnormalities and congestion
“Treatment of cardiorenal syndrome consists of optimizing
hemodynamics and maintaining effective decongestion”
MAP mean arterial pressure, CO cardiac output, CVP central venous pressure
Use of intravenous route is more effective
Bolus dosing may be as affective as continuous infusion
Start the initial dose at 2–2.5 times the ordinary oral dose
Increase dose until the adequate symptom relief is achieved
– in case of hypotension consider continuous infusion
Multiple dosing more effective than single dosing
Consider adding low-dose thiazide diuretics in case of
resistance; monitor electrolytes carefully
Loop
diuretics
? Hypertonic saline with furosemide
16. Classification of WRF in AHF
RIFLE (an acute rise in SCr over 7d)
AKIN (an acute rise in SCr within 48 h)
When discussing modification in
kidney function in HF, the terms
“WRF” and “AKI”
are frequently employed
17. SGLT2 inhibitors trials : CV outcomes & Kidney outcomes
Nature Reviews , Nephrology Reviews ,Volume 18 , May 2022 , 295
From
MACE (Major
Adverse Cardiac
Events)
To
MARCE (Major
Adverse Renal &
Cardiac Events)?
“Target
clinical end
point in
cardiorenal
trials”
18. Ronco C, Ronco F, McCullough PA. A call to action to develop integrated curricula in cardiorenal medicine. Blood Purif. 2017;44:251–259. doi: 10.1159/000480318
From MACE to MARCE?
Given the importance of both sets of outcomes and the link between CV and renal, this makes sense!
19. Where are we in 2022 with HFpEF ?
HF?EF
Chronic Heart Failure
Preseved EF
Mildly reduced EF
Reduced EF
20. Classifications of HF according to EF
Journal of Cardiac Failure
Vol. 27 No. 4 April 2021
≤40% 41-49% ≥50%
≥ 10% LVEF improvement
22. The term “diastolic” HF was abandoned
Diastolic
HF
and replaced by HFpEF
HFpEF
Heart Failure With Preserved Ejection Fraction (HFpEF):
a New Term for an Old Disease
HFpEF : More than diastolic dysfunction
Clinically, HFpEF and diastolic dysfunction are not synonymous
24. Filling by pulling or sucking
“pulling” or “sucking” of blood into the LV
from LA by good relaxation in subjects with
normal diastolic function
Normal
Diastolic Dysfunction
Filling by pushing
“pushing” of blood into the LV by increased
filling pressure in patients with abnormal
relaxation due to severe diastolic
dysfunction
PULL
PUSH
26. Cardiovascular Research, Volume 117, Issue 4, 1 April 2021, Pages 999–1014
Time to reconsider the person with
shortness of breath :
HFpEF
vs
Non-cardiac dyspnea
E/e’ as a measure of
LV diastolic filling pressures
The demonstration of ↑LV filling
pressure is crucial in diagnosing HFpEF in
euvolemic patients with dyspnea.
27. In current guidelines
Clinical manifestation: Symptoms and signs of HF
LVEF: ≥ 50%
Natriuretic peptides: BNP ≥ 35 pg/mL or
NT-proBNP ≥ 125 pg/mL
Imaging: LV diastolic dysfunction
However, the diagnosis of HFpEF remains challenging.
Therefore, new diagnostic algorithms for HFpEF have been published
Diagnostic of HFpEF
29. HFA-PEFF diagnostic algorithm
HF heart failure, AF atrial fibrillation, CAD coronary artery disease, MetS metabolic syndrome, CKD chronic
kidney disease, COPD chronic obstructive pulmonary disease, SDB sleep-disordered breathing, NPs natriuretic
peptides, Hb hemoglobin, HbA1C hemoglobin A1C, Scr serum creatinine, eGFR estimated glomerular filtration
rate, ALT alanine aminotransferase, TSH thyroid stimulating hormone, LVEF left ventricular ejection
fraction, LVH left ventricular hypertrophy, LAE left atrial enlargement, 6MWT 6 min walk
test, CPET cardiopulmonary exercise testing, TR tricuspid regurgitation, PASP pulmonary artery systolic
pressure, GLS global longitudinal strain, LAVI left atrial volume index, LVMI left ventricular mass
index, RWT relative wall thickness, LV left ventricular, SR sinus rhythm, NT-proBNP N-terminal pro-B-type
natriuretic peptide, BNP B-type natriuretic peptide, LVEDP left ventricular end-diastolic
pressure, PCWP pulmonary capillary wedge pressure, CT computed tomography, PET positron emission
tomography, HCM hypertrophic cardiomyopathy, RCM restrictive cardiomyopathy, CHD congenital heart
disease, VHD valvular heart disease
30. Diagnostic of HFpEF
A group of experts from Mayo clinic → H2FPEF Score :
to estimate the probability of HFpEF
versus non-cardiac causes of dyspnea
Six clinical and echo variables : the H₂FPEF score
2018
31. H2FPEF score of 0–1:
Low probability (<20%)
→unlikely HFpEF
H2FPEF score of 2–5: Intermediate
probability
H2FPEF score of 6–9:
High probability (>90%) →HFpEF is
likely
H2FPEF score used to determine the probability of HFpEF
33. Noninvasive
diastolic stress test
“echo”
Add E/e’ with exercise
The diastolic stress test refers to the evaluation of diastolic function,
either invasively or noninvasively, during exercise
Frequently, symptoms of diastolic dysfunction occur only during exercise ,
as LV filling pressure is normal at rest , but increases with exercise .
This implies that LV filling pressures should also be measured not only at rest but also during exercise.
34. Nowadays
All Heart Failure Patients
By Year 2050
HFpEF HFpEF
HFpEF :
Yet this form
of HF remains
a diagnostic
and
therapeutic
challenge..
HFpEF:
“heterogeneous
Syndrome”
heterogeneity is
often viewed as
a major obstacle
in preclinical/
clinical HFpEF
research
35. Clinical application of personalized medicine: HFpEF
European Heart Journal Supplements (2020) 22 (Supplement L), L124–L128
Pathophysiological heterogeneity in patients with HFpEF
The failure of previous clinical trials in HFpEF
might have resulted from the
Pathophysiological heterogeneity in patients
with HFpEF , and thus there is a growing
interest in HFpEF phenotyping.
Thus, “HFpEF” as a diagnosis subsumes
multiple pathophysiological entities
making a uniform management plan for
“HFpEF” impossible.
36. There is urgent need of improving its
phenotyping due to the high degree of
disease heterogeneity within HFpEF
that lead to the failure of randomized
clinical trials in demonstrating a
remarkable impact of drugs in
improving its morbidity and mortality.
37. Main HFpEF sub-phenotypes identified across phenomapping studies.
NP natriuretic peptide, CV cardiovascular, T2DM type 2 diabetes mellitus, LV left ventricular, CVP central venous
pressure, PAH pulmonary arterial hypertension.
Heinzel, F.R., Shah, S.J. The future of heart failure with preserved ejection fraction. Herz 47, 308–323 (2022).
HFpEF is a truly
heterogeneous syndrome :
up to five common HFpEF
sub-phenotypes
(HF“phenomapping”studies)
39. The normal cardiac phenotype
The isolated LV phenotype (in compensated hypertensive heart disease
— short history)
The isolated LA phenotype (in paroxysmal lone AF)
The isolated RA/RV phenotype (in chronic pulmonary hypertension due
to repetitive pulmonary thromboembolism)
The combined LA and LV phenotype (in compensated hypertensive heart disease
—long history)
The combined LA, LV, and RA/RV phenotype (in amyloidosis)
41. In the absence of recommendations regarding disease-modifying therapies, treatment should be aimed at reducing symptoms of
congestion with diuretics. Loop diuretics are preferred, although thiazide diuretics may be useful for managing hypertension.
Reducing body weight in obese patients and increasing exercise may further improve symptoms and exercise capacity and should
therefore be considered in appropriate patients.
It is important to identify and treat the underlying risk factors, aetiology, and coexisting comorbidities in HFpEF (e.g. hypertension,
CAD , amyloidosis , AF , and valvular heart disease).
Undoubtably, treatment of some of the underlying phenotypes of the the HFpEF syndrome leads to improved outcomes.
HFpEF 2021 ESC
42. Clinical Research in Cardiology ,
109, 1079–1098(2020)
Comorbidities →Systemic
inflammation →HFpEF
44. Recommendations for Patients With Preserved LVEF
(≥50%)
*Greater benefit in patients with LVEF closer to 50%.
EBM is still the best kind of medicine
45. The victory against an old enemy !!
SGLT2I is the first and only HF therapy to demonstrate
a statistically significant risk reduction in CV death and hHF, regardless of LVEF
2021
2022
2021-2022
Worsening HF= hHF or urgent visit for HF
46. *hospitalization for heart failure or urgent visit for heart failure **total number of worsening heart failure events and
* *
** **
47. Schneider, C.A., Pfister, R. Treatment of heart failure with preserved ejection fraction with SGLT2 inhibitors: new therapy
standard?. Herz (2022). https://doi.org/10.1007/s00059-022-05134-6
48. Trial Treatment Participants
Primary
outcomes/
endpoints
Follow-up
(average)
Population Reference
CHARM-P
Candesartan vs.
placebo
LVEF ≥ 50%
CVD; recurrent
HFH
2.9 years n = 1953 Lund et al. (2018)
I-PRESERVE
Irbesartan vs.
placebo
Age ≥ 60 years;
LVEF > 45%
CVD, HFH, and all-
cause mortality
according to with
or without T2D
4.1 years n = 4128
Kristensen et al.
(2017)
TOPCAT
Spironolactone or
placebo
Age ≥ 50 years;
LVEF ≥ 45%
CVD death;
cardiac arrest;
HFH
3.3 years n = 3445 Pitt et al. (2014)
PARAGON-HF
Sacubitril–
valsartan or
valsartan
Age ≥ 50 years;
LVEF ≥ 45%
CVD; HFH 26 months n = 4800
Solomon et al.
(2019)
Earlier clinical trials of non-SGLT2 inhibitor medications in HFpEF patients → Neutral Finding*
*One hypothesis that may explain the lack of therapies that reduce hard outcomes in
HFpEF is the variety of phenotypes that constitute HFpEF as a syndrome.
49. 55
50
45
40
35
30
25
20
15
10
5
0
Mean
Cumulative
Events
per
100
patients
0
*Semiparametric LWYY method. CV,
cardiovascular; HF, heart failure
Solomon S, et al. N Engl J Med. 2019 (In press)
1 2
Years
3 4
Valsartan (n = 2389)
1009 events, 14.6 per 100 pt-years
Sacubitril/valsartan (n = 2407) 894 events,
12.8 per 100 pt-years
13% reduction in the risk of the primary endpoint
(rate ratio [RR]: 0.87; 95% CI: 0.75 to 1.005; p=0.058)
Primary endpoint: Recurrent event analysis of total HF hospitalizations and CV death*
Sacubitril–valsartan did not result in a significantly
lower rate of total hospitalizations for heart failure and
death from cardiovascular causes among patients with
heart failure and an ejection fraction of 45% or higher.
50.
51. Management of HFpEF : 4 Take Home Points Herz (2022)
Dapagliflozin
ARNI
Phenotype-specific HFpEF treatment
strategy
52. CKD in HFpEF {or HFpEF in CKD }
The CKD Phenotype of HFpEF
HF is highly prevalent in patients with CKD, with HFpEF
accounting for half of these cases.
CKD is independently associated with worse outcomes and
higher mortality rates in patients with HFpEF.
53. Summary of pathophysiological processes linking HFpEFand CKD.
HFpEF and CKD share common risk factors including diabetes, hypertension and obesity, but also a number of
pathophysiological processes contribute to the interplay between cardiac and renal dysfunction.
Rev. Cardiovasc. Med. 2022; 23(2): 069
54. Proposed relationship between renal dysfunction and HFpEF.
The direction of causality may prove to be in the opposite direction and most probably will be bidirectional.
IL-6, interleukin-6; TNFα, tumour necrosis factor-α; sST2, soluble ST2; ROS, reactive oxygen species; NO, nitric oxide; cGMP, cyclic guanosine
monophosphate; PKG, protein kinase G; TGFβ, transforming growth factor-β.
J.M. ter Maatenet al. Connecting heart failure with preserved ejection fraction and renal dysfunction: the role of endothelial dysfunction and
inflammation European Journal of Heart Failure (2016)18, 588–598
55. Signaling and cross-talk leading to kidney fibrosis
Whether in the heart or in the kidney, fibrosis is the common consequence of inflammation- and oxidative
stress–related endothelial dysfunction in aging, hypertension, diabetes mellitus, and obesity, ultimately leading
to cardiovascular disease, heart failure, and CKD
Fibrosis as a Unifying Pathophysiology of the Cardiorenal Syndrome Continuum
Circulation. 2018;138:929–944
56. Patient with CKD and suspected HFpEF
Are you sure your patient has Cardiorenal Syndrome?
Right Here and Right Now
CV assessment
Renal assessment
Breathless patient
The coexistence of CKD in HFpEF (CRS type 2 and 4) is common
CV clinical presentation
Renal clinical presentation
Main symptoms are dyspnea and exercise intolerance
57. Suggested algorithm for CRS diagnosis.
HFpEF, heart failure with preserved ejection fraction; CRS, cardiorenal syndrome; eGFR, estimated glomerular filtration rate; LA, left atria; TR, tricuspid
regurgitation; SR, sinus rhythm; AF, atrial fibrillation; NTproBNP, N-terminal prohormone of brain natriuretic peptide; CA-125, cancer antigen 125.
Clinical Kidney Journal, 2022, vol. 15, no. 10, 1807–1815
58.
59.
60. Competing diagnoses that can mimic Cardiorenal Syndrome
‘HFpEF mimickers’
Clinical Research in Cardiology,Published: 04 June 2022
Clinical Kidney Journal,
2022, vol. 0, no. 0, 1–14
62. Drug and device treatments for heart failure according to LVEF
Lancet Diabetes Endocrinol. 2022; 10: 689-691
There is strong evidence that sacubitril and valsartan, selected β blockers (bisoprolol, carvedilol, and metoprolol succinate), mineralocorticoid receptor
antagonists (MRA; eplerenone and spironolactone), and SGLT2 inhibitors (dapagliflozin and empagliflozin) reduce the risk of death from cardiovascular causes
and admission to hospital for worsening HFrEF. Sacubitril and valsartan, MRA, and possibly beta-blockers, are probably also beneficial in patients with
HFmrEF. SGLT2 inhibitors are beneficial across the full spectrum of left ventricular ejection fraction, including patients with HFpEF.
12-lead ECG is important in assessing eligibility for ivabradine (if a persistently high sinus rate), an anticoagulant (if atrial fibrillation), and cardiac
resynchronisation therapy if a persistently low LVEF and left bundle branch block. An implantable cardioverter defibrillator is indicated to reduce the risk of
sudden death in patients with an LVEF of 35% or less despite 3–6 months of treatment with optimal pharmacological therapy.
Foundational Pillars
of HF treatment
63. The effects of heart failure drugs on renal physiology. J. Clin. Med. 2022, 11(8), 2243
AA: afferent arteriole; ACE In.: angiotensin converting enzyme inhibitors; ARBs: angiotensin receptor blockers; ARNI: angiotensin receptor neprilisin inhibitor; ATII:
angiotensin II; BB: beta blockers; BP: blood pressure; cGMP: cyclic guanosine monophosphate; eGFR: estimated glomerular filtration rate; EA: efferent arteriole;
HypT: hypertension; Kf : glomerular capillary ultrafiltration coefficient; MRA: mineralcorticoid receptor antagonist; NPs: natriuretic peptides; RAAS: renin
angiotensin aldosterone system; RBF: renal blood flow; SGLT2 In.: sodium glucose transporter protein 2 inhibitors; SNS: sympathetic nervous system.
Negotiating renal
dysfunction when
treating patients with
HF→Therefore,
finding a balance
between the
optimization of cardiac
and renal outcomes is a
real negotiation in the
everyday clinical
practice.
64. Summary of pharmacological treatment options in HFpEF and renal considerations
Class of agent Effect on HFpEF Renal considerations
Loop diuretics
Symptomatic benefit when treating fluid
overload
Possible association with greater decline in renal function
Renin-angiotensin-
aldosterone system
inhibitors
Prognostic benefit not demonstrated
Can potentially slow CKD progression via blood pressure control
and reduction of proteinuria;
May precipitate renal hypoperfusion;
Risk of hyperkalaemia
Mineralocorticoid
receptor antagonists
(MRAs)
Mortality benefit not demonstrated
Reduction of albuminuria ;
Lower risk of composite endpoint of cardiovascular mortality,
heart failure hospitalisation or aborted cardiac arrest in those
with estimated GFR 30–60 mL/min/1.73 m22 ;
May be associated with reduced
hospitalisations for heart failure
Risk of adverse events including hyperkalaemia and worsening
renal function
Sacubitril-valsartan
No reduction in composite endpoint of death
from cardiovascular causes or hospitalisations
for heart failure
No differing treatment effect between those with eGFR 30–60
or >>60 mL/min/1.73 m22;
Reduction in renal composite endpoint (≥50% decrease in eGFR,
development of end-stage renal disease, or death from renal
causes) when in combination with MRA, compared to MRA +
valsartan alone
Sodium-glucose
cotransporter 2
inhibitors
Reduction in cardiovascular mortality and
hospitalisations for heart failure
Promising results regardless of LVEF
Rev. Cardiovasc. Med. 2022; 23(2): 069
65. Säemann, M., Cejka, D., Schmaldienst, S. et al. Value of SGLT-2 inhibitors in the treatment of chronic kidney disease.
Wien Klin Wochenschr (Published17 October 2022).
*SGLT-2 inhibitors
Recently, several large-scale
studies with SGLT-2i have
demonstrated profound
nephroprotective and
cardioprotective properties in
patients with T2D with both
CKD and HF.
*
66. Conclusion
Sacubitril/valsartan, compared with valsartan, attenuates the decline of eGFR
and reduces clinically relevant kidney events similarly among patients with
HFpEF with and without diabetes
67. In patients not able to tolerate guideline-
recommended spironolactone doses, lower
doses should be preferred and the treatment
should not be stopped.
68. My Last Few Words Before I Leave
Research Gap
What-Why-How
69. Frequent exclusions of patients on dialysis from pivotal RCTs of HF therapies
Lack of trial-evidence for patients with HF on dialysis
Inconsistent engagement between cardiologists and nephrologists
regarding the co-management of patients with HF on dialysis
72. Current barriers and
possible solutions
for managing HF in
patients on dialysis
Journal of Cardiac Failure
Published:October 12, 2022
73. The key objective of the group is to highlight the important clinical overlap that exists between
patients presenting with a primary cardiovascular or renal problem.
Regular Semi-annual (i.e., every six months) Meeting
74. 2022 : The Year That Cardiology and Nephrology Are Friends
Multidisciplinary clinic for CKD patients with HF
The figure highlights the importance of close collaboration between primary care, HF nurses, cardiologists and
nephrologists and close monitoring of blood pressure, weight, fluid balance and laboratory parameters.
75. Russian novelist & poet
[born 1818, died 1883]
The coexistence of CKD in HFpEF (CRS type 2 and 4) : Cardio-Renal Clinical Challenges
Editor's Notes
Massive dehydration leads to exsiccosis.=volume depletion
In patients with acute heart failure (AHF), we can discern between two distinct phenotypes: patients with baseline renal dysfunction, defined as CKD, and patients developing worsening renal function (WRF) during hospitalization [17]. A new classification of WRF has been proposed, according to the time frame resolution or persistence. The first clinical scenario was a patient with good renal function and occurrence of a “pseudo” WRF during hospitalization for acute HF, that was considered secondary to the decongestion therapy. The increase of in-hospital creatinine did not usually persist after discharge, without consequences for the prognosis if the patient was well treated, with efficient decongestion at discharge. The second scenario was a patient with true WRF due to congestion (increased renal venous pressure) and hypoperfusion (reduced arterial perfusion), in which renal deterioration persisted, with an increase in creatinine also in the post-discharge period and with a higher burden of HF re-hospitalization [18]. Finally, in the third scenario, WRF could occur in the presence of CKD related to reduced cortical blood flow and chronic glomerulosclerosis with reduced cortical wall. This subtype was common in older patients with several comorbidities, where WRF reflected the real deterioration of the renal function, with worse prognostic value. Current classification was uncompleted, because it did not account for serial kidney evaluation after discharge and the severity of an effective estimated glomerular filtration rate (eGFR) impairment (Table 1).
Sarcopenia is the age-related progressive loss of muscle mass and strength.
Cumulative expression of the shown comorbidities and risk factors can cause systemic inflammation which can then lead to development of HFpEF [2]. ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, CCB calcium channel blocker, MRA mineralocorticoid receptor antagonist, PDE5 hosphodiesterase-5, sCG soluble guanylate cyclase, SGLT2 sodium-glucose cotransporter-2.
During a median of 2.3 (IQR, 1.7-2.8) years of follow-up, a primary outcome event was identified among 16.4% (n=512) of the dapagliflozin group and among 19.5% (n=610) of the placebo group (HR, 0.82 [95% CI, 0.73-0.92]; P <.001), with investigators noting similar results observed for those with an ejection fraction of less than 60% compared to those of the overall population (HR, 0.83 [95% CI, 0.73-0.95]; P=.009). When assessing individual components of the primary outcome, a reduction in rate of hospitalization for heart failure or urgent visit for heart failure (HR, 0.79 [95% CI, 0.69-0.91]) and cardiovascular death (HR, 0.88 [95% CI, 0.74-1.05]) was observed for the dapagliflozin group compared to the placebo group.
Among secondary outcomes of interest, investigators highlighted a significant reduction in total number of worsening heart failure events and cardiovascular deaths with dapagliflozin use, with 815 such events occurring in the dapagliflozin arm and 1057 occurring in the placebo arm (HR, 0.77 [95% CI, 0.67-0.89]; P <.001). In safety analyses, serious adverse events, including death, were identified among 43.5% (n=1361) of the dapagliflozin group and among 45.5% (n=1423) of the placebo group, with investigators also noting discontinuation due to adverse events among 5.8% of the dapagliflozin group and 5.8% of the placebo group.