Diastolic heart failure
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Summary
Diastolic heart failure (MONDO:0006727) is a disease with 2 GWAS associations across 4 studies and 61 clinical trials. Top therapeutic interventions include perhexiline, eplerenone, and ranolazine. A subtype of congestive heart failure — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 2
- Clinical trials: 61
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | diastolic heart failure |
| Mondo ID | MONDO:0006727 |
| EFO | EFO:1000899 |
| MeSH | D054144 |
| DOID | DOID:9775 |
| SNOMED CT | 418304008 |
| UMLS | C1135196 |
| MedGen | 210051 |
| MedDRA | 10069211 |
| Is cancer (heuristic) | no |
Data availability: 2 GWAS associations (4 studies).
Disease family
This is a subtype of congestive heart failure. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart failure › congestive heart failure › diastolic heart failure
Related subtypes (4): rheumatic congestive heart failure, cor pulmonale, systolic heart failure, left ventricular failure
Genetics & variants
GWAS landscape
2 GWAS associations across 4 studies. Top hits map to 1 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs55872725 | 4e-15 | FTO | C | 0.08 |
| rs1421085 | 3e-14 | FTO | T | 0.08 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90475984 | Verma A | 2024 | 19,682 | 419,065 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90477963 | Verma A | 2024 | 5,379 | 113,041 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90480183 | Verma A | 2024 | 5,379 | 113,041 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90477962 | Verma A | 2024 | 1,573 | 57,263 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 2 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 2 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 2 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs55872725 | 16 | 53775211 | C>G,T | 0.404 | intron_variant | FTO | 4e-15 | Tier 4: intronic/intergenic |
| rs1421085 | 16 | 53767042 | T>C | 0.334 | intron_variant | FTO | 3e-14 | Tier 4: intronic/intergenic |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated for this disease
0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Spironolactone | Phase 3 (in late-stage trials) |
| Udenafil | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dapagliflozin, Ivabradine, Perhexiline, Potassium Chloride, Ranolazine, Ubidecarenone.
Clinical trials & evidence
Clinical trials
Clinical trials: 61.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 40 |
| PHASE2 | 8 |
| PHASE4 | 6 |
| PHASE3 | 2 |
| PHASE2/PHASE3 | 2 |
| PHASE1/PHASE2 | 2 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04160000 | PHASE4 | RECRUITING | Treatment Of Atrial Fibrillation In Preserved Cardiac Function Heart Failure |
| NCT00083772 | PHASE4 | TERMINATED | Use of Nesiritide in the Management of Acute Diastolic Heart Failure |
| NCT00293150 | PHASE4 | TERMINATED | Reversing Endothelial and Diastolic Dysfunction and Improving Collagen Turnover in Diastolic Heart Failure |
| NCT01944384 | PHASE4 | COMPLETED | Impacts of Aldosterone Blockade on Myocardial Remodeling in Hypertensive Patients With Diastolic Failing Heart |
| NCT02053246 | PHASE4 | TERMINATED | Improving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure |
| NCT02589977 | PHASE4 | COMPLETED | Myocardial Perfusion, Oxidative Metabolism, and Fibrosis in HFpEF |
| NCT00123955 | PHASE3 | COMPLETED | PIE II: Pharmacological Intervention in the Elderly II |
| NCT01156636 | PHASE2/PHASE3 | COMPLETED | Phosphodiesterase-5 (PDE5) Inhibition and Pulmonary Hypertension in Diastolic Heart Failure |
| NCT01583881 | PHASE2/PHASE3 | TERMINATED | Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction |
| NCT01599117 | PHASE3 | UNKNOWN | A Randomized Trial of Udenafil Therapy in Patients With Heart Failure With Preserved Ejection Fraction [ULTIMATE-HFpEF] |
| NCT05408559 | PHASE1/PHASE2 | RECRUITING | Prevention of Age-associated Cardiac and Vascular Dysfunction Using Avmacol ES |
| NCT00303498 | PHASE2 | COMPLETED | A Study of the Effectiveness of Sitaxsentan Sodium in Patients With Diastolic Heart Failure |
| NCT00309868 | PHASE1/PHASE2 | COMPLETED | Study of Nesiritide in Diastolic Heart Failure. |
| NCT00662116 | PHASE2 | TERMINATED | Beginning a Randomized Evaluation of the AGE Breaker Alagebrium in Diastolic Heart Failure (BREAK-DHF-I) |
| NCT00757055 | PHASE2 | WITHDRAWN | If Channel Blockade With Ivabradine in Patients With Diastolic Heart Failure |
| NCT00839228 | PHASE2 | COMPLETED | Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome |
| NCT01163734 | PHASE2 | COMPLETED | Ranolazine in Diastolic Heart Failure |
| NCT01913301 | PHASE2 | TERMINATED | A Randomized Double-Blind, Placebo-Controlled, Multiple-Dose Study to Evaluate the Effects of Alagebrium on Exercise in Subjects With Diastolic Heart Failure |
| NCT02256345 | PHASE2 | COMPLETED | Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF |
| NCT03882710 | PHASE2 | COMPLETED | Metoprolol XR in Heart Failure With Normal Ejection Fraction |
| NCT01185067 | PHASE1 | COMPLETED | Physiological Effects of Grape Seed Extract in Diastolic Heart Failure |
| NCT05064709 | Not specified | RECRUITING | Assessment of CCM in HF With Higher Ejection Fraction |
| NCT06015776 | Not specified | RECRUITING | Purinergic Signaling and the Postmenopausal Heart |
| NCT06805253 | Not specified | RECRUITING | Left Ventricular Reverse Remodeling Evaluation After Surgical Correction of Aortic Regurgitation |
| NCT00505336 | Not specified | COMPLETED | The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure |
| NCT00574756 | Not specified | TERMINATED | Effect of Ranolazine on Echocardiographic Indices of Diastolic Dysfunction |
| NCT00585611 | Not specified | TERMINATED | Effects of Statin Therapy on Vascular Properties and Outcomes in Diastolic Heart Failure Patients |
| NCT00709241 | Not specified | COMPLETED | Psychosocial Patterns and Prognosis in Patients With Heart Failure |
| NCT00718939 | Not specified | COMPLETED | Rheos® Diastolic Heart Failure Trial |
| NCT00720525 | Not specified | COMPLETED | Pulsatile and Steady State Hemodynamics in Diastolic Heart Failure |
| NCT00773084 | Not specified | WITHDRAWN | Aliskiren and Renin Inhibition in Diastolic Heart Failure |
| NCT00846404 | Not specified | UNKNOWN | Markers of Oxidative Stress Diastolic Dysfunction |
| NCT00939640 | Not specified | COMPLETED | Effects of the Dietary Approaches to Stop Hypertension(DASH) Sodium-restricted Diet in Diastolic Heart Failure |
| NCT01030991 | Not specified | COMPLETED | Classification of Heart Failure With Preserved Ejection Fraction |
| NCT01047631 | Not specified | COMPLETED | Role of Exercise in Diastolic Heart Failure |
| NCT01157481 | Not specified | UNKNOWN | Diastolic Heart Failure Management by Nifedipine |
| NCT01431027 | Not specified | COMPLETED | Left Ventricular Torsional Hysteresis: A Global Parameter for Diastolic Function |
| NCT01778894 | Not specified | TERMINATED | Mathematical Modeling to Determine Basic Muscle Properties in the Failing Heart |
| NCT01942395 | Not specified | TERMINATED | Dietary Approaches to Stop Hypertension in ‘Diastolic’ Heart Failure 2 (DASH-DHF 2) |
| NCT02018497 | Not specified | UNKNOWN | Essential Hypotension and Allostasis Registry |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| PERHEXILINE | 4 | 3 |
| EPLERENONE | 4 | 2 |
| RANOLAZINE | 4 | 2 |
| REGADENOSON ANHYDROUS | 4 | 2 |
| SPIRONOLACTONE | 4 | 2 |
| IVABRADINE | 4 | 1 |
| NEBIVOLOL | 4 | 1 |
| NESIRITIDE | 4 | 1 |
| POTASSIUM CHLORIDE | 4 | 1 |
| SULFORAPHANE | 3 | 1 |
| UDENAFIL | 3 | 1 |
| ALAGEBRIUM | 2 | 2 |
| CHEMBL4071327 | 0 | 1 |
| CHEMBL2365658 | 0 | 1 |
| CHEMBL3526436 | 0 | 1 |
| CHEMBL4303537 | 0 | 1 |
| CHEMBL1562223 | 0 | 1 |
| CHEMBL30458 | 0 | 1 |