Caveolin-1-deficient (cav1−/−) mice display a severely diseased cardiac phenotype with systolic and diastolic heart failure. Accumulating evidence supports a causative role of uncoupled endothelial nitric oxide synthase in the development of these abnormalities. Interestingly, a similar molecular mechanism was proposed for anthracycline-induced cardiomyopathy. Currently, dexrazoxane is approved for the prevention of anthracycline-induced cardiomyopathy. Given the molecular similarities between the anthracycline-induced cardiomyopathy and the cardiomyopathy in cav1−/− mice, we questioned whether dexrazoxane may also prevent the evolution of the cardiac pathologies in cav1−/− mice. We evaluated dexrazoxane treatment for 6 weeks in cav1−/− mice and wild-type controls. This study provides the first evidence for a reduced reactive oxygen species formation in the vessels of dexrazoxane-treated cav1−/− mice. This reduced oxidative stress resulted in a markedly reduced rate of apoptosis, which finally was translated into a significantly improved heart function in dexrazoxane-treated cav1−/− mice. These hemodynamic improvements were accompanied by significantly lowered proatrial natriuretic peptide levels. Notably, these protective properties of dexrazoxane were not evident in wild-type animals. Taken together, these novel findings indicate that dexrazoxane significantly reduces vascular reactive oxygen species formation cav1−/−. Because this is paralleled by an improved cardiac performance in cav1−/− mice, our data suggest dexrazoxane as a novel therapeutic strategy in this specific cardiomyopathy.

(1) Background: The modified anterior line (MAL) has been described as an alternative to the mitral isthmus line. Despite better ablation results, achieving a bidirectional line block can be challenging. We aimed to investigate the ablation parameters that determine a persistent scar on late-gadolinium enhancement magnet resonance imaging (LGE-MRI) as a surrogate parameter for successful ablation 3 months after MAL ablation. (2) Methods: Twenty-four consecutive patients who underwent a MAL ablation have been included. The indication for MAL was perimitral flutter (n = 5) or substrate ablation in the diffuse anterior left atrial (LA) low-voltage area in persistent atrial fibrillation (AF) (n = 19). The MAL was divided into three segments: segment 1 (S1) from mitral annulus to height of lower region of left atrial appendage (LAA) antrum; segment 2 (S2) height of lower region of LAA antrum to end of upper LAA antrum; segment 3 (S3) from end of upper LAA antrum to left superior pulmonary vein. Ablation was performed using a contact force irrigated catheter with a power of 40 Watt and guided by automated lesion tagging and the Ablation Index (AI). The AI target was left to the operator’s choice. An inter-lesion distance of ≤6 mm was recommended. The bidirectional block was systematically evaluated using stimulation maneuvers at the end of procedure. All patients underwent LGE-MRI imaging at 3 months, regardless of symptoms, to identify myocardial lesions (scars). (3) Results: Bidirectional MAL block was achieved in all patients. LGE-MRI imaging revealed scarring in 45 of 72 (63%) segments. In all three segments of MAL, ablation time and AI were significantly higher in scarred areas compared with non-scar areas. The mean AI value to detect a durable scar was 514.2 in S1, 486.7 in S2 and 485.9 in S3. The mean ablation time to detect a scar was 20.4 s in S1, 22.1 s in S2 and 20.2 s in S3. Mean contact force and impedance drop were not significantly different between scar and non-scar areas. (4) Conclusions: Targeting optimal AI values is crucial to determine persistent left atrial scars on an LGE-MRI scan 3 months after ablation. AI guided linear left atrial ablation seems to be effective in producing durable lesions.