Age: 40+
Healthy Volunteers: Not accepted
Inclusion Criteria:
1. Subjects ≥ 40 years of age,
2. Chronic symptomatic HF and left ventricular ejection fraction (LVEF) > 40% within 12 months prior to screening visit (regardless of the imaging modality) and one of the following abnormalities:
2a. HF requiring hospitalization and IV diuretics within 12 months of study entry, or 2b. NTproBNP > 150pg/ml in sinus rhythm or NTproBNP > 450pg/ml in chronic atrial fibrillation, 3. The presence of coronary microvascular dysfunction (CMD) at baseline assessed using dipyridamole-based PET imaging and defined as myocardial functional reserve (MFR) < 2.0, 4. Symptoms of HF requiring current treatment with loop diuretics for ≥ 30 days, 5. NYHA functional class II to (ambulatory) IV, 6. High-sensitivity C-reactive protein (hs-CRP) > 5mg/L at baseline, 7. Subjects with the capacity to provide informed consent.
Exclusion Criteria:
1. Patients with a diagnosis of infiltrative cardiomyopathy,
2. Presence of primary severe valvular heart disease (functional MR/TR are not excluded),
3. Presence of active infection within the 3 months prior to enrollment needing antibiotics,
4. Acute decompensated HF, acute coronary syndrome (including MI), cardiac surgery, other major cardiovascular surgery, or urgent PCI within the 3 months prior to enrollment,
5. Known or clinically judged significant (i.e., angina with CCS class > 2/4) epicardial coronary artery disease (CAD) that has not been revascularized (revascularized CAD is defined by a history of myocardial infarction, percutaneous intervention, or coronary artery bypass grafting),
6. History of hypersensitivity to colchicine,
7. Evidence of hepatic disease as determined by any 1 of the following: SGOT (AST) or SGPT (ALT) values exceeding 3× the upper limit of normal at enrollment; or patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease,
8. Patients with at most moderate renal impairment defined as an eGFR < 59 ml/min/1.73 m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at enrollment,
9. Subject with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea,
10. Patient with pre-existent progressive neuromuscular disease,
11. Patient currently taking colchicine for other indications (Familial Mediterranean Fever, gout or post MI). There is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment,
12. Patients under long-term systemic steroid medication or any chronic use of anti- inflammatory medication (including Non-steroidal Anti-inflammatory Drugs, NSAIDS),
13. Contra-indications to dipyridamole use (PET-imaging): Patients with bronchospastic lung disease with ongoing wheezing; Acute myocardial infarction or unstable angina in the past 48h; Uncontrolled hypertension (systolic pressure of over 200 mmHg or a diastolic pressure of over 110 mmHg); Symptomatic hypotension; Untreated second- or third-degree atrioventricular block; Known hypersensitivity to dipyridamole; Caffeine intake in the previous 12 hours
14. Contra-indications to aminophylline use (PET-imaging): epilepsy, peptic ulcer (active) and hypersensitivity to aminophylline, theophylline, ethylenediamine, or any component of the formulation
15. Positive pregnancy test result at the screening visit, and females of childbearing potential who do not agree to use adequate method of contraception for the duration of the study; acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner,
16. History or presence of any other disease with a life expectancy of <1 year,
17. Patient considered by the investigator, for any reason, to be an unsuitable candidate for the study,
18. Drug-drug interaction (competitive inhibition of CYP3A4 and P-gp): Patients treated with amiodarone, dronedarone, quinidine, propafenone, diltiazem, azithromycin or high-intensity statin therapy.