Reducing Aortic Barotrauma and Vascular Extracellular Matrix Degradation by Pacemaker-Mediated QRS Widening.

Background The extent of pressure-related damage might be related to acceleration rate of the applied pressure (peak dP/dt) in the vascular system. In this study, we sought to determine whether dP/dt applied to the aortic wall (aortic dP/dt) and in turn vascular extracellular matrix degradation can be mitigated via modulation of left ventricular (LV) contractility (LV dP/dt) by pacemaker-mediated desynchronization. Methods and Results First, in 34 patients, changes in aortic dP/dt values in 3 aortic segments in response to pacemaker-mediated stepwise QRS widening leading to gradual desynchronization of the LV contraction by means of steadily changed atrioventricular delay (AVD) with temporary dual-chamber pacing was examined before and after beta-blocker (15 mg IV metoprolol) administration. Second, serum matrix metalloproteinase-9 levels were measured in the 20 patients with permanent pacemaker while they were on sinus rhythm with normal QRS width and 3 weeks after wide QRS rhythm ensured by dual pacing, dual sensing, and dual response to sensing with short AVD. LV dP/dt substantially correlated with dP/dt measured in ascending (r=0.83), descending (r=0.89), and abdominal aorta (r=0.96). QRS width strongly correlated with dP/dt measured in ascending (r=-0.95), descending (r=-0.92), and abdominal (r=-0.96) aortic segments as well. In patients with permanent pacemaker, wide QRS rhythm led to a significant reduction in serum matrix metalloproteinase-9 levels (from 142.5±32.9 pg/mL to 87.5±32.4 pg/mL [P<0.001]) at the end of 3 weeks follow-up. Conclusions QRS prolongation by short AVD dual pacing, dual sensing, and dual response to sensing results in concomitant decreases in peak dP/dt values in the LV and in all aortic segments with or without background beta-blocker administration, which in turn led to a significant reduction in circulating matrix metalloproteinase-9 levels. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03665558.

Intrarenal application of N-acetylcysteine for the prevention of contrast medium-induced nephropathy in primary angioplasty.

OBJECTIVE: Contrast medium-induced nephropathy (CIN) is a well-known complication of coronary angiographic procedures, especially in patients treated with primary angioplasty. To prevent CIN, we examined using a local application of N-acetylcysteine (NAC) for the prevention of CIN during primary angioplasty. We hypothesized that a local application of NAC into the renal arteries would provide the benefit of a higher local concentration, lower first-pass metabolism, and faster efficacy. To evaluate the effects of NAC by the intrarenal route, we performed a prospective, randomized clinical study in patients with acute myocardial infarction treated with primary angioplasty. METHODS: Participants were 312 patients with ST-segment elevation myocardial infarction undergoing primary angiography. Eligible patients were randomly assigned to receive intravenous NAC, intrarenal NAC, or placebo. RESULTS: Overall, CIN occurred in 74 (23.7%) of the 312 patients. The rate of CIN was 25% in the intravenous NAC group, 22.9% in the intrarenal NAC group, and 23.2% in the placebo group, with no significant effect seen for either treatment (P=0.64). We did find a significant correlation between CIN and ejection fraction (P=0.05) and baseline renal function (P=0.01). CONCLUSION: Both intrarenal and intravenous applications of NAC failed to show any benefit over placebo in the prevention of CIN. This result shows that NAC application does not have any prophylactic effect, dose dependent or otherwise, on CIN, as previously reported. Our results suggest that more attention should be paid to optimize hemodynamic variables for the prevention of CIN.

A patient treated with tilt training and midodrine after 68 seconds asystole during head-up tilt table testing.

Neurocardiogenic syncope is a relatively common cause of syncope and is diagnosed by head-up tilt testing. A 21-year-old man was examined for frequent syncope episodes which occurred after episodes of blood drawing and standing in queue. Syncope developed in tilt table testing. After about 68 seconds, sinus rhythm returned. Recent reports have shown that tilt training is a very effective therapy for recurrent neurocardiogenic syncope. In our case, the patient was treated with midodrine 2.5 mg once a day and a tilt training programme. Therapy resulted in improvement and during a follow-up of six months, no major events occurred.