Flow measurement at the aortic root:impact of location of through-plane phase contrast velocity mapping

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the gold standard of cardiac volumetric measurements. Flow in the aortic root is often measured at the sinotubular junction, even though placing the slice just above valve level may be more precise. It is unknown how much flow measurements vary at different levels in the aortic root and which level corresponds best to left ventricle volumetry. METHODS: All patients were older than 70 years presenting with at least one of the following diagnoses: diabetes, hypertension, prior stroke and/or heart failure. Patients with arrhythmias during CMR and aortic stenosis were excluded from the analyses. Stroke volumes were measured volumetrically (SV(ref)) from steady-state free precision short axis images covering the entire left ventricle, excluding the papillary muscles and including the left ventricular outflow tract. Flow sequences (through-plane phase contrast velocity mapping) were obtained at valve level (SV(V)) and at the sinotubular junction (SV(ST)). Firstly, SV(V) and SV(ST) were compared to each other and secondly, after excluding patients with mitral regurgitations to ensure that stroke volumes measured volumetrically would theoretically be equal to flow measurements, SV(V) and SV(ST) were compared to SV(ref). RESULTS: Initially, 152 patients were included. 22 were excluded because of arrhythmias during scans and 9 were excluded for aortic stenosis. Accordingly, data from 121 patients were analysed and of these 63 had visually evident mitral regurgitation on cine images. On average, stroke volumes measured with flow at the sinotubular junction was 13–16 % lower than when measured at valve level (70.0 mL ±13.8 vs. 81.8 mL ±15.5). This was in excess of the expected difference caused by the outflow to the coronary arteries. In the 58 patients with no valvulopathy, stroke volumes measured at valve level (79.0 mL ±12.4) was closest to the volumetric measurement (85.4 mL ±12.0) but still significantly lower (p < 0.001). Flow measured at the ST-junction (68.1 mL ±11.6) was significantly lower than at valve level and the volumetric measurements. The mean difference between SV(ref)–SV(V) (6.4 mL) and SV(ref)-SV(ST) (18.2 mL) showed similar variances (SD 7.4 vs. 8.1 respectively) and hence equal accuracy. CONCLUSIONS: Aortic flow measured at valve level corresponded best with volumetric measurements and on average flow measured at the sinotubular junction underestimated flow approximately 15 % compared to valve level. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02036450. Registered 08/01/2014

Systolic Blood Pressure and Effects of Screening for Atrial Fibrillation With Long-Term Continuous Monitoring (a LOOP Substudy)

BACKGROUND: Hypertension is a well-known risk factor for atrial fibrillation (AF) and stoke, but data on the interaction between systolic blood pressure (SBP) and effects of AF screening are lacking. METHODS: The LOOP Study randomized AF-naïve individuals aged 70 to 90 years with additional stroke risk factors to either screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care. In total, 5997 participants with available baseline SBP measurements were included in this substudy. Outcomes were analyzed according to the time-to-first-event principle using cause-specific Cox models. RESULTS: The hazard ratio of stroke or systemic arterial embolism for ILR versus control decreased with increasing SBP. ILR screening yielded a 44% risk reduction of stroke or systemic arterial embolism among participants with SBP ≥150 mm Hg (adjusted hazard ratio, 0.56 [0.37–0.83]). Within the ILR group, SBP≥150 mm Hg was associated with a higher incidence of AF episodes ≥24 hours than lower SBP (adjusted hazard ratio, 1.70 [1.08–2.69]) but not with the overall occurrence of AF (adjusted P>0.05). CONCLUSIONS: The impact of AF screening on thromboembolic events increased with increasing blood pressure. SBP≥150 mm Hg was associated with a >1.5-fold increased risk of AF episodes ≥24 hours, along with an almost 50% risk reduction of stroke or systemic arterial embolism by ILR screening compared to lower blood pressure. These findings should be considered hypothesis-generating and warrant further study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02036450

Severity and Etiology of Incident Stroke in Patients Screened for Atrial Fibrillation vs Usual Care and the Impact of Prior Stroke:A Post Hoc Analysis of the LOOP Randomized Clinical Trial

IMPORTANCE: Atrial fibrillation (AF) screening trials have failed to demonstrate a significant reduction in stroke risk. The impact on stroke severity and the importance of prior strokes are unknown. OBJECTIVE: To assess stroke characteristics in patients undergoing implantable loop recorder (ILR) screening for AF vs usual care and assess the importance of prior stroke. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals (LOOP) randomized clinical trial. Persons 70 years or older without known AF but diagnosed with 1 or more of the following, hypertension, diabetes, heart failure, or prior stroke, were screened for inclusion. Four sites in Denmark recruited participants by letter between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Data were analyzed from April 1 to May 31, 2022. INTERVENTIONS: ILR screening for AF and anticoagulation initiation if AF duration of 6 minutes or longer was detected (ILR group) vs usual care (control group). MAIN OUTCOMES AND MEASURES: Adjudicated stroke, classified according to the modified Rankin Scale (mRS) using a score of 3 or more as a cutoff for severe (disabling or lethal) stroke, and according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for ischemic strokes. RESULTS: A total of 6205 individuals were screened for inclusion, and 6004 were randomized and included in the analysis; 4503 participants (75%; mean [SD] age, 74.7 [4.1] years; 2375 male [52.7%]) were assigned to the control group and 1501 participants (25%; mean [SD] age, 74.7 [4.1] years; 792 male [52.8%]) were assigned to the ILR group. A total of 794 of 4503 participants (17.6%) in the control group had a history of prior stroke compared with 262 of 1501 participants (17.5%) in the ILR group. During follow-up, AF was diagnosed in 1027 participants (control group, 550 [12%] vs ILR group, 477 [32%]), and anticoagulation was initiated in 89% of these (910). A total of 315 participants (5.2%) had a stroke (control group, 249 [5.5%] vs ILR group, 66 [4.4%]), and the median (IQR) mRS score was 2 (1-3) with no difference across the groups. A total of 272 participants (4.5%) had ischemic stroke (control group, 217 [4.8%] vs ILR group, 55 [3.7%]), and 123 (2.0%) had severe stroke (control group, 100 [2.2%] vs ILR group, 23 [1.5%]), and the hazard ratios comparing the control and ILR groups were 0.76 (95% CI, 0.57-1.03; P = .07) and 0.69 (95% CI, 0.44-1.09; P = .11), respectively. For participants without prior stroke, the hazard ratios were 0.68 (95% CI, 0.48-0.97; P = .04) and 0.54 (95% CI, 0.30-0.97; P = .04), respectively. CONCLUSIONS AND RELEVANCE: This post hoc analysis of the LOOP randomized clinical trial found that ILR screening for AF did not result in a significant decrease in ischemic or severe strokes compared with usual care. Exploratory subgroup analyses indicated a possible reduction of these outcomes among participants without prior stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0203645

Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH