Experimental data suggest that cryoenergy is associated with less endothelial damage and thrombus formation than radiofrequency energy. This study aimed to compare the impact of pulmonary vein isolation (PVI) on the endothelial damage, myocardial damage, inflammatory response, and prothrombotic state between the two latest technologies, second-generation cryoballoon (CB2) and contact force-sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial fibrillation (AF) patients (55 men; 65 ± 12 years) underwent PVI with either the CB2 (n = 64) or CFRF (n = 22). Markers of the endothelial damage (L-arginine/asymmetric dimethylarginine [ADMA]), myocardial injury (creatine kinase-MB [CK-MB], troponin-T, and troponin-I), inflammatory response (high-sensitive C-reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer complex, and thrombin-antithrombin complex) were determined before and up to 24-h post-procedure. The total application time was shorter (1,460 ± 287 vs. 2,395 ± 571 [sec], p < 0.01) and total procedure time tended to be shorter (199 ± 37 vs. 218 ± 38 [min], p = 0.06) with CB2 than CFRF ablation. The amount of myocardial injury was greater (CK-MB: 45 ± 17 vs. 11 ± 3 [IU/l], p < 0.01) with CB2 than CFRF ablation. The L-arginine/ADMA ratio was lower (160 ± 51 vs. 194 ± 38, p = 0.028) after CB2 than CFRF ablation. Inflammatory and all prothrombotic markers were significantly elevated post-ablation; however, the magnitude was similar between the two groups. During a mean follow-up of 20 ± 6 months, the single-procedure AF freedom was similar between the CB2 and CFRF groups (60/64 vs. 20/22, p = 0.82). CB2-PVI produces significantly lesser endothelial damage with greater myocardial injury than CFRF-PVI; however, similar anticoagulant regimens are required during the peri-procedural periods in both technologies.

AimsMatrix metalloproteinase (MMP) is up‐regulated during heart failure (HF) and influences ventricular remodeling. We hypothesized that disparity between MMP‐9 and tissue inhibitors of MMP‐1 (TIMP‐1) results in clinical manifestations and is related to prognostic risk in patients with chronic HF.Methods and resultsPlasma levels of MMP‐9, TIMP‐1, and brain natriuretic peptide (BNP) were measured in 173 patients with chronic HF. Combined endpoints of worsening HF events were assessed during follow‐up (median 109 months). MMP‐9 and TIMP‐1 levels and the MMP‐9/TIMP‐1 ratio increased with increasing severity of the New York Heart Association class (P for trend = 0.003, 0.011, and 0.005, respectively). Patients with HF events (n = 35) had significantly higher MMP‐9 than those without HF events (P = 0.004). Kaplan–Meier analysis demonstrated a higher probability of HF events with high MMP‐9 values (>23.2 ng/mL; P = 0.005). A multivariate Cox proportional hazard model showed that high MMP‐9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03–13.46; P = 0.043). In patients with lower BNP levels (≤210 pg/mL), the adjusted hazard ratio for HF events was 3.63 (95% CI, 1.20–11.02; P = 0.023) among patients with high MMP‐9 values compared with patients with low BNP and low MMP‐9 values.ConclusionsMMP‐9 and TIMP‐1 levels correlate with the severity of chronic HF. MMP‐9 is a strong predictor of HF events, suggesting that a disparity between MMP‐9 and TIMP‐1 levels and increased MMP‐9 levels may help predict HF events.

BackgroundThe relationship between the serum levels of matrix metalloproteinase (MMP) and tissue inhibitors of MMP (TIMP) and left ventricular (LV) reverse remodeling (LV‐RR) after an acute myocardial infarction (AMI) has not been sufficiently examined.Methods and ResultsIn 25 patients with successful reperfusion after an AMI and 15 normal control subjects, the serum MMP‐2 and TIMP‐2 levels were measured on days 1, 2, 3, and 7 and at 1 and 6 months after the AMI onset. LV‐RR was defined as a >15% decrease in the LV end‐systolic volume index at 6 months after the AMI. The MMP‐2 level on day 1 and TIMP‐2 levels throughout the study period were comparable between the patients with and without LV‐RR. The MMP‐2 on day 7 (P<0.05) and the changes in the MMP‐2 from day 1 to day 7 (∆MMP‐2; P<0.01) were lower in patients with than in those without LV‐RR. The ∆MMP‐2 was strongly correlated with the changes in the LV volume and ejection fraction from 1 month to 6 months after the AMI. The ∆MMP‐2 value of <−158.5 ng/mL predicted LV‐RR with a high accuracy (91.7% sensitivity and 76.9% specificity; area under the curve=0.82).ConclusionsChanges in MMP‐2 are associated with LV‐RR after an AMI. The ΔMMP‐2 might be a useful predictor of subsequent LV‐RR.

Background: The utility of pressure waveform analyses to assess pulmonary vein (PV) occlusions has been reported in cryoballoon PV isolation (CB‐PVI) using first‐generation CBs. This prospective randomized study compared the procedural and clinical outcomes of pressure‐guided and conventional CB‐PVI. Methods and Results: Sixty patients with paroxysmal atrial fibrillation underwent CB‐PVI with 28‐mm second‐generation CBs. PV occlusions were assessed either by real‐time pressure waveforms without contrast utilization (pressure‐guided group) or contrast injections (conventional group) and randomly assigned. Before the randomization, 24 patients underwent pressure‐guided CB‐PVIs. In the derivation study, a vein occlusion was obtained in 88/96 (91.7%) PVs among which 86 (97.7%) were successfully isolated by the application. In the validation study, the nadir balloon temperature and total freezing time did not significantly differ per PV between the two groups. The positive predictive value of the vein occlusion for predicting successful acute isolations was similar (93 of 103 [90.2%] and 89 of 98 [90.8%] PVs; P = 1.000), but the negative predictive value was significantly higher in pressure‐guided than angiographical occlusions (14 of 17 [82.3%] vs 7 of 22 [31.8%]; P = .003). Both the procedure (57.7 ± 14.2 vs 62.6 ± 15.8 minutes; P = .526) and fluoroscopic times (16.3 ± 6.4 vs 20.1 ± 6.1; P = .732) were similar between the two groups, however, the fluoroscopy dose (130.6 ± 97.7 vs 353.2 ± 231.4 mGy; P < .001) and contrast volume used (0 vs 17.5 ± 7.7 mL; P < .001) were significantly smaller in the pressure‐guided than conventional group. During 27.8 (5‐39) months of follow‐up, the single procedure arrhythmia freedom was similar between the two groups (P = .438). Conclusions: Pressure‐guided second‐generation CB‐PVIs were similarly effective and as safe as conventional CB‐PVIs. This technique required no contrast utilization and significantly reduced radiation exposure more than conventional CB‐PVIs.

Azelnidipine, but not indapamide, combined with olmesartan, improved arterial stiffness and were associated with significant decrease in OPG, MMP-2, and hs-CRP concentrations. These results suggest that the beneficial effects of the combination treatments of olmesartan/azelnidipine on arterial stiffness are mediated by alteration in bone-remodeling and inflammatory markers.