# 🫀 HFpEF as Renal Disease: Roundtable Preparation

[🏠 Main Nephrology Index](https://urinenephrology.org/index.html) [📚 UDPA Lectures Home](https://urinenephrology.org/2025_UDPA_Lectures_Live/index.html) [❤️ Cardiorenal Lecture](https://urinenephrology.org/2025_UDPA_Lectures_Live/cardiorenal-disease/index.html)

## 📋 Executive Summary

This document provides comprehensive preparation for a nephrology roundtable discussion on heart failure with preserved ejection fraction (HFpEF) as a fundamentally renal disease. Key themes include:

#### 🔬 Pathophysiology

The central role of the kidney in HFpEF pathogenesis through MR overactivation, galectin-3 mediation, and hemodynamic interactions

#### 📊 CKM Framework

The emerging cardiovascular-kidney-metabolic syndrome framework integrated with KDIGO staging

#### 💊 GDMT Evidence

Guideline-directed medical therapy evidence including FINEARTS-HF and CONFIDENCE

#### 🩺 Clinical Implementation

Practical strategies and positioning of finerenone across the HFpEF spectrum

## Part I: HFpEF as Fundamentally Renal Disease

### 🔬 The Paulus-Tschöpe Paradigm

The Paulus-Tschöpe paradigm establishes **comorbidity-driven coronary microvascular endothelial inflammation**—rather than ischemic cardiomyocyte death—as the central mechanism of HFpEF.

#### The Mechanism Chain:

Comorbidities → IL-6, TNF-α, CRP → Endothelial dysfunction → ↓NO/cGMP → Titin hypophosphorylation → **Diastolic dysfunction**

### 🫘 The Kidney's Central Role

#### 1. MR Overactivation

Mineralocorticoid receptor overactivation occurs simultaneously in cardiomyocytes, fibroblasts, endothelial cells, and immune cells, stimulating TGF-β, IL-6, and PAI-1 production.

**Key insight:** Obesity and hyperglycemia cause *ligand-independent* MR activation even without elevated aldosterone levels.

#### 2. Galectin-3 Mediation

Galectin-3 functions as a bidirectional mediator linking kidney injury to cardiac fibrosis. It amplifies TGF-β signaling by stabilizing TGFBR2.

Serum galectin-3 correlates with diastolic dysfunction severity (E/e' ratio): severe HFpEF 19.4 ± 12.4 ng/mL vs mild HFpEF 6.8 ± 5.3 ng/mL (p \< 0.001)

#### 3. Hemodynamic Interactions

A self-perpetuating cycle: reduced GFR → ↓sodium filtration → RAAS activation → volume expansion → hypertension → LVH → elevated CVP → "renal tamponade" → ↓GFR

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## 🧬 Galectin-3: The Molecular Bridge

### Molecular Architecture

Galectin-3 is a 30-kDa protein encoded by the *LGALS3* gene—the only chimeric member of the galectin family. It consists of:

**C-terminal CRD:** Binds β-galactoside moieties on cell surface glycoproteins **N-terminal domain:** Mediates oligomerization, enabling extracellular lattice formation

### The Adoptive Transfer Evidence

**Landmark experiments:** In unilateral ureteral obstruction models, galectin-3 knockout mice developed markedly less fibrosis despite normal macrophage recruitment. Adoptive transfer of wild-type macrophages into galectin-3 null mice fully restored the fibrotic phenotype. This proves macrophage-derived galectin-3 is the critical mediator.

### 2025 Mechanistic Update

Recent research has elucidated the molecular mechanism: extracellular galectin-3 binds directly to TGF-β receptor 2 (TGFBR2) through its CRD, inhibiting receptor ubiquitination and proteasomal degradation—prolonging receptor half-life and amplifying TGF-β signaling.

### Clinical Correlations

r = −0.71

Correlation between reduced GFR and elevated galectin-3

OR 3.21

Galectin-3 predicts type 1 cardiorenal syndrome

HR 1.97

Per doubling of galectin-3 levels (FDA validated)

**Clinical Pearl:** Unlike natriuretic peptides (confounded by reduced clearance in CKD), galectin-3's prognostic value for cardiac outcomes is preserved in patients with renal impairment—reflecting its role as a mechanistic mediator rather than a clearance marker. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## 📈 Albuminuria as Cardiovascular Risk Indicator

Albuminuria serves as both a kidney injury marker and an independent cardiovascular risk indicator, reflecting systemic endothelial injury affecting both the glomerular barrier and coronary microcirculation.

### ARIC Study Evidence (n=10,975)

**Continuous graded relationship even within "normal" range:**

| UACR Category                  | HF Hazard Ratio |
|--------------------------------|-----------------|
| Optimal (\<5 mg/g)             | Reference       |
| Intermediate-normal (5-9 mg/g) | HR 1.54         |
| High-normal (10-29 mg/g)       | HR 1.91         |
| Microalbuminuria (30-299 mg/g) | HR 2.49         |
| Macroalbuminuria (≥300 mg/g)   | HR 3.47         |

**Each doubling of UACR = 15% increased HF risk (HR 1.15), independent of eGFR**

### CHARM HFpEF Subset

**Microalbuminuria vs Normoalbuminuria** HR 1.43

(95% CI 1.21-1.69, p\<0.0001)

**Macroalbuminuria vs Normoalbuminuria** HR 1.75

(95% CI 1.39-2.20, p\<0.0001)

**TOPCAT Finding:**Albuminuria is a prognostic marker; a fall in UACR should not be converted directly into a fixed reduction in HF hospitalization risk. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## 🗺️ HFpEF Phenomapping: The CKD-Dominant Phenotype

### Shah Phenogroups (Circulation 2016)

Hierarchical clustering on 397 HFpEF patients using 67 phenotypic variables identified three distinct phenogroups:

#### Phenogroup 3: CKD-Dominant (Highest Risk)

**Characteristics:**

- Older age (median 75 years)
- CKD as defining feature
- 43% atrial fibrillation
- Pulmonary hypertension
- RV dysfunction
- Overt diastolic dysfunction

HR 4.2

(95% CI 2.0-9.1, p\<0.001)

for HF hospitalization vs other phenogroups

TOPCAT did not significantly reduce its primary composite outcome overall. Exploratory subgroup findings should not be presented as a validated phenotype-specific treatment effect or a fixed number needed to treat. Consider mineralocorticoid receptor antagonists in selected patients using current guidance and kidney function/potassium monitoring. [TOPCAT primary report](https://pubmed.ncbi.nlm.nih.gov/24716680/).

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## Part II: Interactive CKM-KDIGO Risk Heat Map

### 🎯 Integrated KDIGO-CKM Risk Stratification: The Visual Guide

**This interactive heat map combines KDIGO CKD staging with AHA CKM syndrome classification.** Click any cell to see detailed risk profiles and therapeutic recommendations.

**Critical insight:** Albuminuria is the dominant driver of cardiovascular risk—often more predictive than eGFR decline alone. A patient with eGFR 85 and UACR 400 faces higher CV risk than one with eGFR 35 and UACR 15.

|  |  | Albuminuria Categories (UACR mg/g) — PRIMARY RISK DRIVER |  |  |
|----|----|----|----|----|
|  |  | A1 \<30 Normal-mild | A2 30-300 Mod increased | A3 \>300 Severely increased |

### 

#### Risk Profile

#### Therapeutic Recommendations

#### 🎨 Risk Color Legend

Low Risk (CKM 0-1) Moderate Risk (CKM 2) High Risk (CKM 2) Very High Risk (CKM 2-3) Very High Risk (CKM 3) Highest Risk (CKM 3-4b) **CV≡** = Cardiovascular Risk Equivalent (eGFR \<30)

#### ⚠️ Albuminuria Dominance: The Key Insight

• **G1A3 (eGFR ≥90, UACR \>300):** HF risk 3.47× — similar to G3b/A1!

• CKD progression steepens **MORE** across A categories than G categories

• CV risk exceeds kidney failure risk in early albuminuric CKD

• eGFR \<30 = **automatic CV risk equivalent** regardless of UACR

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## ⚠️ Albuminuria: The Dominant Driver of Risk Progression

#### The Critical Principle:

**Albuminuria is a more powerful predictor of adverse outcomes than eGFR decline, and the risk gradient steepens dramatically with increasing albuminuria severity.**

### The Clinical Comparison

#### Patient A

eGFR 85 mL/min/1.73m² + UACR 400 mg/g

(G2A3)

HF Risk: 3.47×

**HIGHER CV risk** despite excellent eGFR

#### Patient B

eGFR 35 mL/min/1.73m² + UACR 15 mg/g

(G3bA1)

HF Risk: 1.91×

**LOWER CV risk** despite poor eGFR

### The Albuminuria Paradox

In adults with albuminuria and preserved eGFR, the absolute risk of cardiovascular events **substantially exceeds** the risk of progressing to dialysis. A patient with eGFR 75 and UACR 200 faces low short-term risk of kidney failure but substantially elevated cardiovascular risk.

**Reframe the conversation:** In early-stage albuminuric CKD, we are primarily preventing cardiovascular events, with kidney protection as an important co-benefit.

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## Part III: CKM Syndrome Framework

### 📋 AHA Presidential Advisory (2023)

CKM syndrome is defined as a **"systemic disorder with pathophysiological interactions among metabolic risk factors, CKD, and cardiovascular system leading to multiorgan dysfunction and high adverse cardiovascular outcomes."**

**Rationale:** One in three US adults have 3+ CKM risk factors. Emerging therapies (SGLT2i, GLP-1 RA, finerenone) provide simultaneous CV and kidney benefits. Siloed subspecialty care fails to address integrated disease.

### 🖼️ CKM Staging Framework (AHA 2023)

![AHA CKM Staging Framework showing stages 0-4 with KDIGO integration](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c69/11149035/93f5eaba7286/jasn-35-649-g001.jpg)

**Figure 1:** Stages of the American Heart Association CKM Health Syndrome.\
*Source: Bansal N, Weiner D, Sarnak M. JASN 2024;35(5):649-652. [PMC11149035](https://pmc.ncbi.nlm.nih.gov/articles/PMC11149035/)*

### 🔢 CKM Staging with KDIGO Integration

#### Stage 0-1: No/Low Risk

**KDIGO:** G1-G2/A1 without metabolic disease

**Action:** Lifestyle modification, annual screening

**Screen:** UACR even at Stage 1 (adiposity)

#### Stage 2: Metabolic Risk or Mod-High CKD

**KDIGO:** G3a/A1, G1-G2/A2-A3, or metabolic risk factors

**Key insight:** Stage 2 can be triggered by albuminuria alone

**Action:** SGLT2i (eGFR ≥20), optimize RAASi, consider finerenone

#### Stage 3: CV Risk Equivalent

**KDIGO:** G4-G5 (any albuminuria), G3a-G3b/A3, or PREVENT ≥20%

**Critical:** eGFR \<30 = automatic CKM Stage 3

**Action:** All four pillars, cardiology referral

#### Stage 4: Clinical CVD + CKM

**4a:** CKD without ESKD

**4b:** ESKD (10-20× mortality vs general population)

**Action:** Multidisciplinary, maximize tolerated therapy, RRT planning

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## Part IV: Guideline-Directed Medical Therapy Evidence

### 💊 SGLT2 Inhibitors: Class I, Level A for HFpEF

#### EMPEROR-Preserved (n=5,988)

Empagliflozin vs placebo in LVEF \>40%

**Primary endpoint (CV death + HF hospitalization):**

HR 0.79 (p\<0.001)

NNT = 30 over 26.2 months

Benefit consistent regardless of diabetes status

#### DELIVER (n=6,263)

Dapagliflozin vs placebo in LVEF \>40%

**Primary endpoint:**

HR 0.82 (p\<0.001)

Benefit maintained even in LVEF ≥60%

**2023 ESC Focused Update:** SGLT2 inhibitors elevated to Class I, Level A recommendation for HFmrEF and HFpEF—the only treatments with this strength of recommendation in HFpEF. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

### 🎯 Finerenone: FINEARTS-HF (September 2024)

**6,001 patients with symptomatic HF and LVEF ≥40% across 634 sites in 37 countries**

16%

Relative risk reduction in CV death + worsening HF events

RR 0.84 (95% CI 0.74-0.95, p=0.007)

18%

Reduction in worsening HF events alone

RR 0.82 (p=0.007)

#### Consistent Across LVEF Spectrum (p-interaction 0.75)

**LVEF \<50%**\
RR 0.83 **LVEF 50-60%**\
RR 0.79 **LVEF \>60% (True HFpEF)**\
RR 0.82

#### Hyperkalemia Profile

K+ \>5.5 mmol/L: 14.3% finerenone vs 6.9% placebo (2.6× increase)

Hyperkalemia hospitalizations: 0.5% vs 0.2% (uncommon)

**No deaths attributable to hyperkalemia**

**FDA Expansion (July 2025):** Finerenone indication expanded to include reducing CV death, HF hospitalization, and urgent HF visits in adults with HF and LVEF ≥40%. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

### ⚖️ Finerenone vs Steroidal MRAs

#### Finerenone Advantages

- Non-steroidal structure: no affinity for androgen/progesterone receptors
- Eliminates gynecomastia, breast pain, menstrual irregularities
- Lower hyperkalemia risk (ARTS trial: 5% vs 12% with spironolactone)
- Balanced heart-kidney tissue distribution

#### TOPCAT Issues

Americas cohort: HR 0.82 (31.8% placebo event rate)

Russia/Georgia: HR 1.10 (8.4% placebo event rate)

[de Denus et al. (2017)](https://pubmed.ncbi.nlm.nih.gov/28445660/) found regional discrepancies between reported spironolactone use and detectable canrenone in TOPCAT biorepository participants from Russia versus the United States/Canada.

#### AMBER Trial Comparison

K+ ≥5.5 in CKD with resistant HTN:

**Spironolactone without K+ binder:** 64.2%

**Finerenone (FIDELITY):** 11.6%

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## Part V: Clinical Implementation

🌟 KEY TRIAL FOR ROUNDTABLE

## 🔬 CONFIDENCE Trial (NEJM 2025): Practice-Changing Evidence

**First prospective evidence supporting simultaneous finerenone + SGLT2i initiation in diabetic kidney disease**

*"Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes"*\
N Engl J Med 2025;393:533-43. DOI: 10.1056/NEJMoa2410659

52%

UACR Reduction

with combination therapy at Day 180

29%

Greater Than Finerenone Alone

Additive benefit demonstrated

32%

Greater Than Empagliflozin Alone

Complementary mechanisms

8.1%

Hyperkalemia with SGLT2i

vs 18.7% without SGLT2i (FIDELITY)

### 📋 Roundtable Talking Points

**1. Safety Signal:** SGLT2i co-administration substantially reduces finerenone-associated hyperkalemia through natriuretic and kaliuretic effects.

**2. Efficacy Signal:** The 52% UACR reduction with combination therapy exceeds what would be expected from simple addition of effects—suggesting synergistic mechanisms.

**3. Practical Implications:** In patients with stable K+ (\<4.5), eGFR ≥45, and significant albuminuria, simultaneous initiation is now evidence-supported.

**4. Clinical Integration:** This supports the "four-pillar" approach to cardiorenal protection rather than sequential addition of therapies.

**Bottom Line:** CONFIDENCE transforms our approach from "add one at a time and wait" to "initiate comprehensive protection early." For appropriate patients, the combination of SGLT2i + finerenone is now the evidence-based standard. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

### 🔍 HFpEF Screening in Nephrology Practice

#### NT-proBNP Thresholds

**Outpatient (eGFR ≥60):** \<125 pg/mL rules out HF **CKD (eGFR \<60):** Use 200-400 pg/mL threshold

#### H2FPEF Score (Simpler Alternative)

| Feature                                   | Points |
|-------------------------------------------|--------|
| BMI \>30                                  | 2      |
| Multiple antihypertensives (≥2)           | 1      |
| Atrial fibrillation                       | 3      |
| Pulmonary hypertension (PA systolic \>35) | 1      |
| Age \>60                                  | 1      |
| Elevated E/e' (\>9)                       | 1      |

**Score ≥6:** High probability of HFpEF

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

### 💊 Finerenone Dosing and Monitoring

#### Dosing by Baseline eGFR

**eGFR ≥60:** Start 20mg daily, target 20-40mg **eGFR 25-\<60:** Start 10mg daily, target 20mg **eGFR \<25:** Not recommended

#### Critical Monitoring Protocol

**4 weeks post-initiation:** K+ and eGFR (mandatory)

**Uptitrate if:** K+ ≤4.8 mEq/L with stable eGFR

**Ongoing:** Every 4 months

#### If K+ \>5.5 mEq/L:

Hold finerenone until K+ ≤5.0, then restart at lower dose. Consider potassium binders (patiromer, SZC) for recurrent hyperkalemia.

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## Part VI: Roundtable Question Responses

Q: Are you aware of the CKM concept? How do you prioritize comorbidity management in CKD plus type 2 diabetes?

CKM syndrome (AHA 2023) formalizes the pathophysiological interconnections nephrologists observe clinically. The staging system (0-4) provides actionable structure:

- **Stage 2** (metabolic risk or moderate-to-high-risk CKD) → SGLT2i initiation
- **Stage 3** (subclinical CVD or eGFR \<30) → Add finerenone if UACR \>30 on ACEi/ARB

**Prioritization follows KDIGO 2024:** Optimize RAASi → Add SGLT2i (eGFR ≥20) → Add finerenone if persistent albuminuria (UACR ≥30, eGFR ≥25, K+ ≤5.0) → Consider GLP-1 RA.

Q: Do you screen diabetic patients for heart failure?

Yes. The ADA 2024 Standards now recommend screening for asymptomatic HF in diabetes using BNP or NT-proBNP.

**Practical approach:** Annual NT-proBNP in all T2D + CKD patients. NT-proBNP ≥125 pg/mL (≥200 if eGFR \<45) triggers echocardiography. Early detection enables SGLT2i initiation before symptomatic HF develops.

**Key stat:** FIGARO demonstrated 32% new-onset HF reduction with finerenone in patients without baseline HF.

Q: How do you communicate increased CV risk with persistently elevated UACR?

**The "smoke detector" analogy:** "UACR functions as an early warning system for your kidneys and heart—like a smoke detector that detects damage before it becomes irreversible."

**Quantify risk:** "Your UACR \>300 mg/g increases heart failure risk by 1.7-2.7 times—but this is modifiable with treatment."

**Set concrete goals:** "We're targeting at least 30% UACR reduction."

**Connect to outcomes:**Albuminuria is a prognostic marker; a fall in UACR should not be converted directly into a fixed reduction in HF hospitalization risk.

Q: Do you perform simultaneous initiation of pillars (SGLT2i + finerenone)?

**CONFIDENCE (NEJM 2025)** provides first prospective evidence supporting simultaneous initiation: finerenone + empagliflozin achieved 52% UACR reduction (29% greater than finerenone alone) with similar safety.

**My algorithm:**

- **Simultaneous initiation:** Stable patients with high albuminuria, K+ \<4.5, eGFR ≥45
- **Sequential initiation:** Borderline K+ (4.5-4.8), uncertain volume status, or eGFR \<45 → SGLT2i first, reassess K+ at 4 weeks, then add finerenone

**Key safety finding:** SGLT2i co-administration reduces finerenone hyperkalemia (8.1% vs 18.7%).

Q: Are you aware of finerenone data in HF with LVEF ≥40%?

**FINEARTS-HF (September 2024, n=6,001)** demonstrated finerenone reduced CV death + worsening HF events by 16% (RR 0.84, p=0.007) in symptomatic HF with LVEF ≥40%.

**Remarkably consistent across LVEF spectrum** (p-interaction 0.75):

- HFmrEF (LVEF \<50%): RR 0.83
- LVEF 50-60%: RR 0.79
- True HFpEF (LVEF \>60%): RR 0.82

This addresses concerns from TOPCAT about heterogeneous MRA effects in HFpEF. **FDA expanded finerenone indication (July 2025)** to include HF with LVEF ≥40%.

[↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc)

## 🎯 Key Clinical Pearls

**1.** HFpEF is fundamentally a renal disease—the kidney plays central pathophysiological and therapeutic roles. **2.** CKD-dominant HFpEF phenotype carries highest risk (HR 4.2) yet responds best to targeted therapy including MRAs. **3.** Albuminuria is both kidney marker and CV risk indicator—routine UACR monitoring identifies high-risk patients. **4.** eGFR \<30 = CV risk equivalent under CKM framework—warranting intensive prevention even without overt CVD. **5.** SGLT2i achieved Class I, Level A for HFpEF. Finerenone is the first definitively proven MRA for HFpEF. **6.** Simultaneous SGLT2i + finerenone is safe and effective (CONFIDENCE: 52% UACR reduction). **7.** SGLT2i mitigates finerenone-associated hyperkalemia (8.1% vs 18.7% in FIDELITY). **8.** Galectin-3 is a "culprit" biomarker mechanistically involved in cardiorenal fibrosis (r = −0.71 with eGFR). **9.** Four pillars (RAASi, SGLT2i, finerenone, GLP-1 RA) address complementary mechanisms for comprehensive protection. **10.** Albuminuria is a prognostic marker; a fall in UACR should not be converted directly into a fixed reduction in HF hospitalization risk. [↑ Back to Table of Contents](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/index.html#toc) 📚 SUPPLEMENTAL RESOURCES

## ❤️🫘 Comprehensive Cardiorenal Disease Evidence Synthesis

**Complete evidence-based analysis of modern guideline-directed medical therapy for cardiorenal disease**

#### 📄 Comprehensive Cardiorenal Report

31 pages \| 82 references \| Complete RAAS inhibitor hierarchy, four-pillar GDMT evidence, population health impact analysis

#### 📄 Heart Failure Neurohormonal Report

27 pages \| 30 references \| MRA phenotype specificity, natriuretic peptide resistance, therapeutic strategies

#### 🎯 Key Evidence Highlights

- **RAAS Inhibitor Hierarchy in Heart Failure:** ARNIs \> ACE-I \> ARBs for HF mortality (NNT 36, 70, 446 respectively)
- **ACE-I Benefits:** Mortality reduction attenuated when combined with comprehensive GDMT (beta-blockers, MRAs, SGLT2i)
- Jhund PS, Talebi A, Henderson AD, et al. Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis. Lancet. 2024;404(10458):1119-1131. [PubMed](https://pubmed.ncbi.nlm.nih.gov/39232490/)
- **CONFIDENCE Trial:** 52% UACR reduction with simultaneous SGLT2i + finerenone initiation
- **Population Impact:** 253 lives saved per 100K annually, \$39.4M cost savings, 4.8:1 ROI
- **Four-Pillar Synergy:** 40-50% mortality reduction with comprehensive GDMT

[📥 Access Complete Evidence Synthesis & Download PDFs](https://urinenephrology.org/2025_UDPA_Lectures_Live/hfpef-roundtable/supplemental-materials.html)

## 📚 Sources

1.  **Solomon SD, McMurray JJV, Vaduganathan M, et al; FINEARTS-HF Investigators.** Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. *N Engl J Med.* 2024;391(16):1475-1485. [PMID: 39225278](https://pubmed.ncbi.nlm.nih.gov/39225278/). *— FINEARTS-HF: composite RR 0.84 (16% RRR, NNT 17); benefit consistent across LVEF spectrum.*
2.  **Anker SD, Butler J, Filippatos G, et al; EMPEROR-Preserved Trial Investigators.** Empagliflozin in Heart Failure with a Preserved Ejection Fraction. *N Engl J Med.* 2021;385(16):1451-1461. [PMID: 34449189](https://pubmed.ncbi.nlm.nih.gov/34449189/). *— EMPEROR-Preserved: composite HR 0.79; NNT 30 over 26.2 months; N=5,988.*
3.  **Solomon SD, McMurray JJV, Claggett B, et al; DELIVER Trial Committees and Investigators.** Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. *N Engl J Med.* 2022;387(12):1089-1098. [PMID: 36027570](https://pubmed.ncbi.nlm.nih.gov/36027570/). *— DELIVER: composite HR 0.82; benefit maintained in LVEF ≥60% subgroup.*
4.  **Shah SJ, Katz DH, Selvaraj S, et al.** Phenomapping for novel classification of heart failure with preserved ejection fraction. *Circulation.* 2015;131(3):269-279. [PMID: 25398313](https://pubmed.ncbi.nlm.nih.gov/25398313/). *— Shah phenogroup analysis; HR 4.2 for adverse-phenogroup CV outcomes.*
5.  **Heerspink HJL, Stefansson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees.** Dapagliflozin in Patients with Chronic Kidney Disease. *N Engl J Med.* 2020;383(15):1436-1446. [PMID: 32970396](https://pubmed.ncbi.nlm.nih.gov/32970396/). *— DAPA-CKD primary composite HR 0.61; supports SGLT2i in cardiorenal continuum.*
6.  **Bakris GL, Agarwal R, Anker SD, et al; FIDELIO-DKD Trial.** Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. *N Engl J Med.* 2020;383(23):2219-2229. [PMID: 33264825](https://pubmed.ncbi.nlm.nih.gov/33264825/). *— FIDELIO-DKD; non-steroidal MRA evidence base.*
7.  **Pitt B, Filippatos G, Agarwal R, et al; FIGARO-DKD Trial.** Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. *N Engl J Med.* 2021;385(24):2252-2263. [PMID: 34449181](https://pubmed.ncbi.nlm.nih.gov/34449181/). *— FIGARO-DKD CV outcomes.*
8.  **Agarwal R, Filippatos G, Pitt B, et al.** Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. *Eur Heart J.* 2022;43(6):474-484. [PMID: 35023547](https://pubmed.ncbi.nlm.nih.gov/35023547/). *— FIDELITY: pooled FIDELIO + FIGARO; comprehensive cardiorenal outcomes in T2DM-CKD.*
9.  **Pitt B, Pfeffer MA, Assmann SF, et al; TOPCAT Investigators.** Spironolactone for heart failure with preserved ejection fraction. *N Engl J Med.* 2014;370(15):1383-1392. [PMID: 24716680](https://pubmed.ncbi.nlm.nih.gov/24716680/). *— TOPCAT: spironolactone in HFpEF; primary composite no benefit overall, regional heterogeneity (Americas vs Russia/Georgia) prompted post-hoc reanalysis.*

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*Document prepared for Bayer-sponsored HFpEF Roundtable Discussion*

*December 2025*


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