AimsThe REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction.Methods and resultsSixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups.ConclusionThis is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.
Our study emphasises the importance of access to CMR for heart attack centres. If myocarditis is suspected, CMR scanning should be performed within 14 days. Myocarditis should not be regarded as benign, even when EF is preserved.
There is evidence that MRA treatment reduces heart failure hospitalisation in heart failure with preserverd ejection fraction, however the effects on mortality related outcomes and quality of life remain unclear. The available evidence for beta-blockers, ACEI, ARB and ARNI is limited and it remains uncertain whether these treatments have a role in the treatment of HFpEF in the absence of an alternative indication for their use. This comprehensive review highlights a persistent gap in the evidence that is currently being addressed through several large ongoing clinical trials.
BackgroundDiffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.MethodsIn a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.ResultsLate gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m2; female > 78 g/m2). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).ConclusionIn well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.
Our objective was to establish a cardiovascular magnetic resonance (CMR) cardiac function clinic to provide an assessment of cardiac volume, mass, and function in patients with heart failure on the same day as their cardiology outpatient clinic appointment. Sixty-four patients attended the CMR function clinic. The reproducibility, patient acceptability, and time efficiency of the CMR clinic were assessed and compared with radionuclide ventriculography (RNV) and echocardiography (echo). Reports were available in the cardiology outpatient clinic within 2 hr of the CMR appointment time. The reproducibility of volumes, ejection fraction, and mass in this heart failure population was good and comparable with CMR studies in the normal population. CMR was more acceptable to the patients than both RNV and echo (p < 0.05). The total time for CMR was less than that of RNV (42 +/- 4 and 61 +/- 4 min, respectively; p < 0.001) but more than that of echo (echo, 23 +/- 2 min; p < 0.001). Comparison of ejection fractions revealed a correlation between CMR and RNV of 0.7, but Bland-Altman limits of agreement were wide (-10.5% to 18.9%). For CMR versus echo, the correlation was 0.6, and the limits of agreement were wider (-29.9% to 23.3%). The correlation between RNV and echo was 0.2 with wider limits of agreement (-29.8% to 24. 9%). In conclusion, CMR can provide a rapid, reproducible, and patient acceptable assessment of cardiac function in heart failure patients, whereas other methods appear to have a wider variance. The high reproducibility of CMR lends itself to the follow-up of clinical progression and the effect of treatment in patients with heart failure.
AimsThe effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta‐analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony‐stimulating factor (G‐CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow‐derived cells (BMCs) improves cardiac function.Methods and resultsNinety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo‐controlled, single‐centre REGENERATE‐IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G‐CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33–9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT‐proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post‐hoc between‐group comparisons.ConclusionWe have shown that G‐CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in ‘no option’ patients and needs further exploration in a larger study.
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