A prospective multicenter validation study for a novel angiography-derived physiological assessment software: Rationale and design of the radiographic imaging validation and evaluation for Angio-iFR (ReVEAL iFR) study.

Angiography-derived physiological assessment of coronary lesions has emerged as an alternative to wire-based assessment aiming at less-invasiveness and shorter procedural time as well as cost effectiveness in physiology-guided decision making. However, current available image-derived physiology software have limitations including the requirement of multiple projections and are time consuming. METHODS/DESIGN: The ReVEAL iFR (Radiographic imaging Validation and EvALuation for Angio-iFR) trial is a multicenter, multicontinental, validation study which aims to validate the diagnostic accuracy of the Angio-iFR medical software device (Philips, San Diego, US) in patients undergoing angiography for Chronic Coronary Syndrome (CCS). The Angio-iFR will enable operators to predict both the iFR and FFR value within a few seconds from a single projection of cine angiography by using a lumped parameter fluid dynamics model. Approximately 440 patients with at least one de-novo 40% to 90% stenosis by visual angiographic assessment will be enrolled in the study. The primary endpoint is the sensitivity and specificity of the iFR and FFR for a given lesion compared to the corresponding invasive measures. The enrollment started in August 2019, and was completed in March 2021. SUMMARY: The Angio-iFR system has the potential of simplifying physiological evaluation of coronary stenosis compared with available systems, providing estimates of both FFR and iFR. The ReVEAL iFR study will investigate the predictive performance of the novel Angio-iFR software in CCS patients. Ultimately, based on its unique characteristics, the Angio-iFR system may contribute to improve adoption of functional coronary assessment and the workflow in the catheter laboratory.

The IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact (IMPROVE) trial: Study design and rationale.

Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) has been shown in clinical trials, registries, and meta-analyses to reduce recurrent major adverse cardiovascular events after PCI. However, IVUS utilization remains low. An increasing number of high-risk or complex coronary artery lesions are treated with PCI, and we hypothesize that the impact of IVUS in guiding treatment of these complex lesions will be of increased importance in reducing major adverse cardiovascular events while remaining cost-effective. The "IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact" trial (registered on clinicaltrials.gov: NCT04221815) is a multicenter, international, clinical trial randomizing subjects to IVUS-guided versus angiography-guided PCI in a 1:1 ratio. Patients undergoing PCI involving a complex lesion are eligible for enrollment. Complex lesion is defined as involving at least 1 of the following characteristics: chronic total occlusion, in-stent restenosis, severe coronary artery calcification, long lesion (≥28 mm), or bifurcation lesion. The clinical investigation will be conducted at approximately 120 centers in North America and Europe, enrolling approximately 2,500 to 3,100 randomized subjects with an adaptive design. The primary clinical end point is the rate of target vessel failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. The co-primary imaging end point is the final post-PCI minimum stent area assessed by IVUS. The primary objective of this study is to assess the impact of IVUS guidance on the PCI treatment of complex lesions.

Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: Pre-ROSC IntraNasal Cooling Effectiveness).

BACKGROUND: Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge. METHODS AND RESULTS: Witnessed cardiac arrest patients with a treatment interval

The amplitude spectrum area correctly predicts improved resuscitation and facilitated defibrillation with head cooling.

OBJECTIVES: When systemic hypothermia was maintained before inducing cardiac arrest, the likelihood of successful defibrillation and meaningful survival was increased. When hypothermia is induced during cardiopulmonary resuscitation, mortality is also improved. With the introduction of the amplitude spectrum area as a predictor of the success of electrical defibrillation, we investigated the effect of preferential head cooling initiated coincident with cardiopulmonary resuscitation on amplitude spectrum area as a predictor. We hypothesized that rapid head cooling initiated coincident with cardiopulmonary resuscitation improves amplitude spectrum area, and therefore is predictive of successful defibrillation. DESIGN: Prospective randomized controlled study. SETTING: University-affiliated research institute. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs, weighing 40.6 +/- 1.4 kg, were randomized to the hypothermia (n = 8), or control (n = 8) group. Ventricular fibrillation was induced and untreated for 10 mins. Cardiopulmonary resuscitation was then initiated for 5 mins followed by attempted defibrillation with a biphasic 150-J electric shock. Coincident with starting cardiopulmonary resuscitation, hypothermia was induced with evaporative intranasal cooling using a perfluorochemical. If spontaneous circulation was not restored after defibrillation, cardiopulmonary resuscitation was resumed for 1 min before the next defibrillation attempt until the animal was either successfully resuscitated or for a total of 15 mins. The target core temperature was 34 degrees C. Control animals were identically treated except for hypothermia. MEASUREMENTS AND MAIN RESULTS: Five seconds of ventricular fibrillation waveform were recorded immediately preceding delivery of a shock. The ventricular fibrillation waveforms were analyzed using the amplitude spectrum area algorithm. A smaller epinephrine dose (60 +/- 32.1 vs. 30 +/- 0 mg/mL, p = .01) and shorter cardiopulmonary resuscitation duration (365 +/- 42 sec vs. 600 +/- 243 sec, p = .01) were required to achieve return of spontaneous circulation in the hypothermia group, compared with control. Five minutes after starting cardiopulmonary resuscitation, head temperature was reduced from 38 degrees C to 34 degrees C in the hypothermia group (p = .028). Hypothermia improved the success of electrical shocks before return of spontaneous circulation (88 +/- 18% vs. 66 +/- 19%, p = .034). Both the amplitude spectrum area values of initial shock (26.1 +/- 5.3 vs. 21.4 +/- 2.16 mV-Hz, p = .049) and total shocks (26.1 +/- 5.3 vs. 21.4 +/- 2.16 mV-Hz, p = .006) were significantly higher in the hypothermia group than control. CONCLUSIONS: Amplitude spectrum area served as a useful predictor for improved resuscitation and facilitated defibrillation in the setting of rapid head cooling initiated coincident with cardiopulmonary resuscitation.

A comparison between head cooling begun during cardiopulmonary resuscitation and surface cooling after resuscitation in a pig model of cardiac arrest.

OBJECTIVE: Employing transnasal head-cooling in a pig model of prolonged ventricular fibrillation, we compared the effects of 4 hrs of head-cooling started during cardiopulmonary resuscitation with those of 8 hrs of surface-cooling started at 2 hrs after resuscitation on 96-hr survival and neurologic outcomes. DESIGN: Prospective controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Twenty-four male pigs were subjected to 10 min of untreated ventricular fibrillation followed by 5 min of cardiopulmonary resuscitation. In the head-cooling group, hypothermia was started with cardiopulmonary resuscitation and continued for 4 hrs after resuscitation. In the surface-cooling group, systemic hypothermia with a cooling blanket was started, in accord with current clinical practices, at 2 hrs after resuscitation and continued for 8 hrs. Methods in the control animal studies were identical except for temperature interventions. MEASUREMENTS AND MAIN RESULTS: All animals were resuscitated except for one animal in each of the surface-cooling and control groups. After 5 min of cardiopulmonary resuscitation, jugular vein temperature was significantly decreased in the head-cooled animals. However, there were no differences in pulmonary artery temperatures among the three groups at that time. Nevertheless, both head-cooled and surface-cooled animals had an improved 96-hr survival after resuscitation. Significantly better neurologic outcomes were observed in early head-cooled animals in the first 3 days after resuscitation. CONCLUSION: Early head-cooling during cardiopulmonary resuscitation continuing for 4 hrs after resuscitation produced favorable survival and neurologic outcomes in comparison with delayed surface-cooling of 8 hrs duration.

Intra-arrest rapid head cooling improves postresuscitation myocardial function in comparison with delayed postresuscitation surface cooling.

OBJECTIVE: To compare resuscitation outcomes and myocardial function among intra-arrest head cooling, delayed surface cooling, and uncooled controls. DESIGN: Prospective animal study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Twenty-four male domestic pigs. INTERVENTIONS: Ventricular fibrillation remained untreated for 10 mins after which animals were assigned into three groups: 1) intra-arrest head cooling, 2) postresuscitation surface cooling, and 3) uncooled controls. Head cooling by evaporative perfluorochemical began coincident with the start of cardiopulmonary resuscitation and continued for a total of 4 hrs. Surface cooling using a cooling blanket began at 2 hrs after return of spontaneous circulation and continued for 8 hrs. Control animals were treated identically with the exception for cooling. MEASUREMENTS AND MAIN RESULTS: Return of spontaneous circulation was achieved in eight of eight head-cooled animals, in seven of eight surface-cooled animals, and in seven of eight of controls. Myocardial functions measured by transthoracic echocardiography were significantly better in the head-cooled animals than in surface-cooled and controls. All head-cooled animals survived for more than 96 hrs. This contrasted with six of eight survivors after surface cooling, and only two of eight among controls. CONCLUSIONS: Both intra-arrest head cooling and delayed surface cooling improved postresuscitation myocardial dysfunction. The beneficial effects were greatest with head cooling initiated with cardiopulmonary resuscitation.

Ultrarapid, convection-enhanced intravascular hypothermia: a feasibility study in nonhuman primate stroke.

BACKGROUND AND PURPOSE: Hypothermia has been shown to be neuroprotective in a variety of clinical settings. Unfortunately, poor delivery techniques and insufficient data in appropriate preclinical models have hampered its development in human stroke. To address these limitations, we have devised a 10F intravascular catheter capable of rapid systemic cooling of nonhuman primates. METHODS: Placed in the inferior vena cava via a transfemoral approach, the catheter was used to induce mild systemic hypothermia 3 hours after the onset of hemispheric stroke in baboons. RESULTS: Cooling was achieved at a rate of 6.3+/-0.8 degrees C/h. Target brain temperatures (32.2+/-0.2 degrees C) were reached at the same time (47.7+/-6.32 minutes) as target esophageal temperatures (32.0+/-0.0 degrees C). Hypothermia was maintained for 6 hours in all animals. Animals did not experience the infections, coagulopathy, or cerebral edema commonly seen with surface cooling methods in human stroke. CONCLUSIONS: These data suggest that a brief episode of mild core hypothermia instituted at a clinically relevant time point can be achieved in primate stroke and that our intravascular cooling technique provides safe, rapid, and reproducible hypothermia.

Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model.

OBJECTIVE: This study was undertaken to assess the acute safety and feasibility of rapidly inducing, maintaining, then reversing hypothermia using a novel heat transfer catheter and a closed-loop automatic feedback temperature control system to overcome limitations imposed by current clinical practices used for perioperative cooling and warming. METHODS: Six swine (mean mass, 53.8 +/- 3.6 kg) were studied. The heat transfer catheter was placed in the inferior vena cava via the femoral vein. Hypothermia to 32 degrees C was induced, maintained for 6 hours, then reversed to 36 degrees C. The time needed to induce and reverse hypothermia was recorded via continuous temperature monitoring of the lower esophagus, cerebrum, and rectum. Electrocardiography provided continuous monitoring, and blood draws were made at baseline and at 2-hour intervals. Examination of the catheter in situ was performed after the animals were killed. RESULTS: Cooling from 36.2 to 32.0 degrees C was rapid and uniform (mean, 7.3 +/- 0.7 degrees C/h), with animals reaching the target temperature within 60 minutes. Rewarming was also easily controlled, with animals' temperatures reaching 36 degrees C within 130 minutes. No arrhythmia was observed, and all hematological variables were within the normal range for swine. There was no evidence of hemolysis or platelet changes. Little to no thrombosis was observed. CONCLUSION: The data presented here suggest that rapid induction and reversal of hypothermia are technically possible using a core intravenous cooling catheter; this method would provide a safe, rapid, and exquisitely reproducible way to induce hypothermia with subsequent restoration of normothermia.