Therapies that target scar formation after myocardial infarction (MI) could prevent ensuing heart failure or death from ventricular arrhythmias. We have previously shown that recombinant human platelet-derived growth factor-AB (rhPDGF-AB) improves cardiac function in a rodent model of MI. To progress clinical translation, we evaluated rhPDGF-AB treatment in a clinically relevant porcine model of myocardial ischemia-reperfusion. Thirty-six pigs were randomized to sham procedure or balloon occlusion of the proximal left anterior descending coronary artery with 7-day intravenous infusion of rhPDGF-AB or vehicle. One month after MI, rhPDGF-AB improved survival by 40% compared with vehicle, and cardiac magnetic resonance imaging showed left ventricular (LV) ejection fraction improved by 11.5%, driven by reduced LV end-systolic volumes. Pressure volume loop analyses revealed improved myocardial contractility and energetics after rhPDGF-AB treatment with minimal effect on ventricular compliance. rhPDGF-AB enhanced angiogenesis and increased scar anisotropy (high fiber alignment) without affecting overall scar size or stiffness. rhPDGF-AB reduced inducible ventricular tachycardia by decreasing heterogeneity of the ventricular scar that provides a substrate for reentrant circuits. In summary, we demonstrated that rhPDGF-AB promotes post-MI cardiac wound repair by altering the mechanics of the infarct scar, resulting in robust cardiac functional improvement, decreased ventricular arrhythmias, and improved survival. Our findings suggest a strong translational potential for rhPDGF-AB as an adjunct to current MI treatment and possibly to modulate scar in other organs.

Aims Atrial fibrillation (AF) is more common in athletes and may be associated with adverse left atrial (LA) remodelling. We compared LA structure and function in athletes and non-athletes with and without AF. Methods and results Individuals (144) were recruited from four groups (each n = 36): (i) endurance athletes with paroxysmal AF, (ii) endurance athletes without AF, (iii) non-athletes with paroxysmal AF, and (iv) non-athletic healthy controls. Detailed echocardiograms were performed. Athletes had 35% larger LA volumes and 51% larger left ventricular (LV) volumes vs. non-athletes. Non-athletes with AF had increased LA size compared with controls. LA/LV volume ratios were similar in both athlete groups and non-athlete controls, but LA volumes were differentially increased in non-athletes with AF. Diastolic function was impaired in non-athletes with AF vs. non-athletes without, while athletes with and without AF had normal diastolic function. Compared with non-AF athletes, athletes with AF had increased LA minimum volumes (22.6 ± 5.6 vs. 19.2 ± 6.7 mL/m2, P = 0.033), with reduced LA emptying fraction (0.49 ± 0.06 vs. 0.55 ± 0.12, P = 0.02), and LA expansion index (1.0 ± 0.3 vs. 1.2 ± 0.5, P = 0.03). LA reservoir and contractile strain were decreased in athletes and similar to non-athletes with AF. Conclusion Functional associations differed between athletes and non-athletes with AF, suggesting different pathophysiological mechanisms. Diastolic dysfunction and reduced strain defined non-athletes with AF. Athletes had low atrial strain and those with AF had enlarged LA volumes and reduced atrial emptying, but preserved LV diastolic parameters. Thus, AF in athletes may be triggered by an atrial myopathy from exercise-induced haemodynamic stretch consequent to increased cardiac output.

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Background and purpose Ischaemic stroke frequently has a cardioembolic (CE) source. Clinical and echocardiographic parameters associated with CE stroke were evaluated. Methods In all, 93 consecutive ischaemic stroke patients who underwent a transthoracic echocardiogram were retrospectively analysed; strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Echocardiographic parameters related to CE stroke, including left atrial volumes and function, were compared to 73 healthy controls. Results Of 93 patients (mean age 66.1 years, 56% male), nine (10%) had large artery atherosclerosis, 38 (41%) CE stroke, two (2%) small vessel disease, two (2%) other and 42 (45%) undetermined aetiology. Left atrial (LA) maximum volumes (LAVImax) and minimum volumes (LAVImin) were larger in the CE group than the non‐CE group (45 vs. 32 ml/m2, 32 vs. 13 ml/m2, respectively, P < 0.001), whilst LA function indices including LA emptying fraction and LA function index (LAFI) were lower in the CE group (34% vs. 55%, and 0.12 vs. 0.35, respectively, P < 0.001). Adjusting for clinical characteristics, LAFI ≤0.3 was an independent predictor of CE stroke (adjusted odds ratio 5.3, P = 0.001). Additionally, LAVImax and LAVImin were larger (61 vs. 44 and 32 vs. 24 ml/m2 respectively, P < 0.01) and LAFI significantly lower (0.34 vs. 0.52, P < 0.001) in the undetermined aetiology group versus healthy controls. Conclusions Left atrial enlargement with reduced LA function was associated with CE stroke and LAFI was the best independent predictor. LA parameters were also altered in the undetermined aetiology group, suggesting an underlying LA myopathy in this subset.

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