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September 2, 2026BiomedicinesOpen Access

SGLT2 inhibitors reduce resting PCWP by ~4 mmHg in HFpEF but show inconsistent LV volume effects in HFrEF.

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Why the study?

Imaging-derived and hemodynamic changes accompanying SGLT2 inhibitor benefits in heart failure remain incompletely characterized, and whether cardiac remodeling patterns differ between HFrEF and HFpEF is unknown.

Do SGLT2 inhibitors improve cardiac remodeling parameters (imaging and hemodynamics) in adults with chronic heart failure compared to non-SGLT2-inhibitor comparators?

Population

1232 participants across 13 unique RCTs in adults with chronic HF

Comparison

SGLT2 inhibitors vs non-SGLT2-inhibitor comparator

Design

Systematic review of randomized controlled trials

Follow-up

At least three months

Key result

SGLT2 inhibitors reduced resting pulmonary capillary wedge pressure by 3.5 mmHg (95% CI -6.6 to -0.4) in HFpEF, while effects on left ventricular volumes in HFrEF were inconsistent.

Authors

DBDiana Evelyne BuzziTMTeodora Mateoc-SirbSASamuel Ardelean

Discussion

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Overview

Suggests phenotype-specific hemodynamic relief in HFpEF; extends mechanistic data but very low-certainty evidence leaves practice implications open.

Key Points

  • To synthesize randomized trial evidence evaluating the effects of SGLT2 inhibitors on cardiac imaging and hemodynamic remodeling parameters across heart failure ejection fraction phenotypes.
  • Searched PubMed/MEDLINE, Scopus, and Embase (February 2016 to March 2026) for randomized controlled trials comparing SGLT2 inhibitors against non-SGLT2-inhibitor controls over at least 3 months in adults with chronic heart failure.
  • Assessed cardiac structure, function, and loading via echocardiography, cardiac magnetic resonance, or cardiac catheterization.
  • Evaluated risk of bias with Cochrane RoB 2, certainty of evidence with GRADE, and conducted a narrative synthesis following SWiM guidelines across 14 publications from 13 unique RCTs (N=1,232).
  • In reduced ejection fraction, SGLT2 inhibitors reduced left ventricular end-systolic volume index (-6.0 mL/m², 95% CI -10.8 to -1.2) and end-diastolic volume index (-8.2 mL/m², 95% CI -13.7 to -2.6) in SUGAR-DM-HF, alongside modest global longitudinal strain improvement in core-lab evaluated trials (EFFORT: -1.44%, 95% CI -2.42 to -0.46).
  • In preserved ejection fraction, structural volumes, ejection fraction, mass, and strain remained unchanged, but dapagliflozin significantly lowered resting pulmonary capillary wedge pressure by 3.5 mmHg (95% CI -6.6 to -0.4) and peak exercise pressure by 5.7 mmHg (95% CI -10.8 to -0.7) in CAMEO-DAPA.
  • NT-proBNP results were inconsistent across trials with neutral primary endpoints (Empire HF, CANDLE), and overall certainty of evidence was rated very low for 18 of 20 profiles and low for 2.

Study Design

Type

Systematic Review (n=1,232)

Structured PICO

Do SGLT2 inhibitors improve cardiac remodeling parameters (imaging and hemodynamics) in adults with chronic heart failure compared to non-SGLT2-inhibitor comparators?

P
Population
1,232 adults with chronic heart failure from 13 randomized trials assessing the effects of SGLT2 inhibitors on cardiac remodeling over at least three months.
I
Intervention
SGLT2 inhibitors as a class
C
Comparator
Non-SGLT2-inhibitor comparator
O
Outcome
Cardiac structure, function or loading assessed by echocardiography, cardiac magnetic resonance (CMR) or cardiac catheterization over at least three monthssurrogate

SGLT2 inhibitors appear to induce phenotype-specific cardiac remodeling in heart failure, with structural reverse remodeling seen primarily in reduced ejection fraction and hemodynamic improvements in preserved ejection fraction.

Limitations

  • limited number of studies
  • substantial heterogeneity
  • overall low certainty of evidence

Cite This Study

Buzzi et al. (2026) conducted a systematic review in chronic heart failure (n=1,232). SGLT2 inhibitors vs. non-SGLT2-inhibitor comparator was evaluated on cardiac structure, function or loading parameters. SGLT2 inhibitors reduced resting pulmonary capillary wedge pressure by 3.5 mmHg (95% CI -6.6 to -0.4) in HFpEF, while effects on left ventricular volumes in HFrEF were inconsistent.

synapsesocial.com/papers/6a97e305c562ede874ec78e9https://doi.org/10.3390/biomedicines14091961
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