Clinical Research Directory

Longitudinal Validation of CIRC Technologies

Cardiovascular disease is the leading cause of death worldwide. Advanced cardiovascular imaging using Magnetic Resonance Imaging (MRI) has proven to be effective in providing gold standard myocardial tissue characterization. Moreover, the intrinsic advantage of MRI's lack of exposure to ionizing radiation is particularly beneficial. At the same time, blood work can be very useful in early detection of certain cardiomyopathy, such as amyloid. However, there is a lack of agreement of on which markers are the most sensitive. This multi-study will allow the unique opportunity to form a more comprehensive understanding for various cardiovascular diseases. The study team has developed novel cardiac MRI techniques that leverages endogenous tissue properties to reveal a milieu of deep tissue phenotypes including myocardial inflammation, fibrosis, metabolism, and microstructural defects. Among these phenotypes, myocardial microstructure has proven to be most sensitive to early myocardial tissue damage and is predictive of myocardial regeneration. In this study, the investigators aim to further study the importance of cardiac microstructure revealed by MRI in patient and healthy population and compare this novel technology with conventional clinical biomarkers.

Emergency Resuscitative Endovascular Balloon Occlusion of the Aorta in Out of Hospital Cardiac Arrest

This study will assess the feasibility of performing pre-hospital resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct to conventional Advanced Life Support (ALS) in patients suffering from non-traumatic out of hospital cardiac arrest (OHCA). As well as providing valuable insights into the technical feasibility of performing this procedure as part of a resuscitation attempt, the study will also document the beneficial physiological effects of REBOA in this group of patients.

Early Double Sequential Defibrillation in Out of Hospital Cardiac Arrest

Some of the patients affected by Out-of-hospital cardiac arrest (OHCA) with ventricular fibrillation (VF)/ventricular tachycardia (VT) do not respond to initial defibrillation. The survival decreases with number of defibrillations required to terminate VF/VT. In 2022, one prospective cluster randomized trial showed increased survival among (OHCA) patients in refractory VF using Double Sequential Defibrillation (DSD). If DSD can increase survival among all patients in VF that dont respond to one defibrillation, i.e. before it has become refractory is not known. The aim of this trial is to assess survival with a double defibrillation strategy initiated as soon as possible among patients with Out of Hospital Cardiac Arrest with initial shockable rhythm and at least one failed standard defibrillation, compared with continued resuscitation using standard defibrillation.

Predicting Severe Cardiac Arrhythmias in the Perioperative Period Using AI-ECG

During the preoperative examination, in addition to the standard examination recommended before high-risk cardiac surgeries, a digital single-lead ECG is recorded using portable CardioQUARK devices. This ECG is analyzed for time, amplitude, and frequency parameters-more than 200 parameters per cardiac cycle. Additionally, the available parameters of a standard 12-lead ECG recording are determined. All parameters of both single-lead and 12-lead ECGs will be included in a multivariate regression analysis to determine the optimal method for predicting atrial fibrillation, life-threatening cardiac arrhythmias, and conduction abnormalities in the perioperative period after high-risk cardiac procedures. The study will include patients undergoing high-risk cardiac surgeries, such as those on the heart, aorta, esophagus, pancreas, liver, and lungs, as well as high-risk oncological surgeries. A partial analysis will also be performed depending on the type of intervention. Rhythm and conduction disturbances will be recorded during surgery, as well as in the postoperative period, using ECG monitors, 24-hour ECG monitoring, and repeated recordings of a standard ECG when complaints or signs of unstable hemodynamics arise

Study Evaluating Dexmedetomidine in the Acute Treatment of Electrical Storm

The objective of this study is to determine if there is a meaningful benefit to using the sedative medication dexmedetomidine in the acute treatment of patients with recurrent ventricular arrhythmias, known as electrical storm. This will be a multi-centre, double-blinded, placebo-controlled, randomized trial. Patients with electrical storm will be randomized to receive 48 to 72 hours of dexmedetomidine or placebo as part of their initial treatment in an intensive care unit.

Epinephrine Dose: Optimal Versus Standard Evaluation Trial

The objective of this randomized controlled trial is to evaluate the effectiveness of a low cumulative dose of epinephrine compared to a standard cumulative dose of epinephrine during resuscitation from ventricular fibrillation (VF) or ventricular tachycardia (VT) in adult out-of-hospital cardiac arrest (OHCA) patients.

Assessment of a Chronically Implanted Parasternally Delivered EV-ICD Lead (ASCEND EV) Study

The ASCEND EV Study is a prospective, multi-center, single-arm, non-randomized study without concurrent or historical controls. The purpose of the study is to evaluate the Investigational Devices through at least 3-months of follow-up to inform the design of a subsequent pivotal clinical investigation. The objectives of the study are to: 1) preliminarily validate safety and effectiveness of the Atala™ lead as a permanent ICD lead when used with a compatible ICD pulse generator, 2) evaluate suitability of clinical study testing methods and 3) inform statistically powered primary safety and effectiveness endpoints in a subsequent pivotal clinical investigation.

Prehospital Resuscitation Intranasal Cooling Effectiveness Survival Study 2

The aim of this clinical trial is to study the impact of ultra-early transnasal evaporative cooling after cardiac arrest and subsequent hypothermia at hospital, on survival with complete neurologic recovery, compared to currently recommended normothermia. The study population will consist of patients 18-79 years old, with out-of-hospital cardiac arrest with initial shockable rhythm. The main research question it aims to answer is whether there is a difference in survival with complete neurologic recovery at 90 days after cardiac arrest between the group of patients that received ultra-early cooling, compared to the group that was treated with normothermia. Participants will be randomized to two groups. One group (the intervention group) will receive ultra-early trans-nasal evaporative cooling initiated by EMS personnel at the scene of the cardiac arrest, and subsequent systemic hypothermia for 24 hours at hospital arrival. The other group (the control group), will receive standard of care (advanced cardiac life support and normal body temperature (normothermia)).

Assessment of Combined CCM and ICD Device in HFrEF

The goal of this clinical trial is to demonstrate that the OPTIMIZER® Integra CCM-D System (the "CCM-D System") can safely and effective convert induced ventricular fibrillation (VF) and spontaneous ventricular tachycardia and/or ventricular fibrillation (VT/VF) episodes in subjects with Stage C or D heart failure who remain symptomatic despite being on guideline-directed medical therapy (GDMT), are not indicated for cardiac resynchronization therapy (CRT), and have heart failure with reduced left ventricular ejection fraction (LVEF ≤40%). Eligible subjects will be implanted with the CCM-D System. A subset of subjects will be induced into ventricular fibrillation "on the table" in the implant procedure room. During the follow-up period, inappropriate shock rate and device-related complications will be evaluated. The follow-up period is expected to last at least two years.

Using Heart Electrical Signals to Study How Well Treatments Prevent Dangerous Heart Rhythms in Active People

The goal of this observational study is to learn if two specific heart electrical signal patterns can help in detecting the risk of dangerous heart rhythms in athletes, and to see if exercise-based tests can be used instead of invasive hospital procedures to record this electrical signals. The main questions it aims to answer are: 1. Can special ECG action potential duration markers (R2I2 and PERS) identify athletes who are at higher risk of sudden heart rhythm problems. 2. Can an exercise test give the same information as a non-invasive electrophysiology study. Researchers will compare athletes who have an implanted heart device (ICD) with athletes who do not, to see if there are differences in these heart signals. Participants will undergo: 1. ECG recordings during rest and exercise. 2. If they have an ICD or pacemaker, an ECG will be recorded during a non invasive stimulation. 3. A continuous 24 hour ECG.

In-hospital Stellate Ganglion Block for Arrhythmic Storm

Arrhythmic storm is a real emergency and its treatment could be challenging. Antiarrhythmic drugs are few and often ineffective. Neuromodulation has been grown in evidences but no large multicentric studies are present in literature about safety and effectiveness of Percutaneous Stellate Ganglion Block (PSGB). Patients with an electrical storm refractory to at least one antiarrhythmic drug will receive PSGB and will be enrolled in the present study. The number of defibrillations before and after the treatment will be compared, complications will be annotated.

Initial Double Sequential External Defibrillation in Out of Hospital Cardiac Arrest

Double Sequential External Defibrillation (DSED) represents an alternative treatment of refractory ventricular fibrillation (rVF) in out-of-hospital cardiac arrest (OHCA). The procedure consists of two defibrillators that administer shocks at the same time. Currently, the procedure is not initiated before at least three failed attempts with one defibrillator. This can delay the potential benefits of establishing DSED earlier in the treatment. Studies have shown that early defibrillation is crucial for survival in OHCA patients, and in 2022, a clinical trial showed that survival in patients treated with DSED was higher compared to standard treatment. The effect of initiating OHCA treatment is unknown. The DUALDEFIB trial seeks to investigate if treating OHCA patients with DSED as an initial treatment will increase survival and provide improved neurological outcome.

Computational Cardiac Imaging Analysis to Guide Ventricular Tachycardia Ablation Procedures (AI-VT)

The purpose of this study is to evaluate the clinical outcomes (clinical efficacy and safety) of using supplemental non-invasive computational ECG and cardiac imaging analysis tools to help guide ablation of ventricular tachycardia.

Evolution of Intracardiac Electrograms Recorded by Left Bundle Branch Pacing Lead in Patients With ICD or CRT-D

The goal of this observational study is to investigate the changes of LBB EGM during daily activities and overdrive pacing at the time of peri-implantation and up to 6-month follow-ups of ICD/CRT-D patients. The main question it aims to answer is: • Does the LBBP lead can provide accurate, stable, and valid EGM for ICD/CRT-D sensing and detection of ventricular tachyarrhythmia events? In each patient intracardiac EGMs of LBBP lead will be collected by ambulatory Holter monitor at the time of peri-implantation and up to 6-month follow-up. EGM collection will be collected at resting and walking conditions and overdrive pacing.

Development of CIRC Technologies

Cardiovascular disease is the leading cause of death worldwide. Advanced cardiovascular imaging using Magnetic Resonance Imaging (MRI) has proven to be effective in providing gold standard myocardial tissue characterization. Moreover, the intrinsic advantage of MRI's lack of exposure to ionizing radiation is particularly beneficial. At the same time, blood work can be very useful in early detection of certain cardiomyopathy, such as amyloid. However, there is a lack of agreement of on which markers are the most sensitive. This multi-study will allow us the unique opportunity to form a more comprehensive understanding for various cardiovascular diseases. Our team has developed novel cardiac MRI techniques that leverages endogenous tissue properties to reveal a milieu of deep tissue phenotypes including myocardial inflammation, fibrosis, metabolism, and microstructural defects. Among these phenotypes, myocardial microstructure has proven to be most sensitive to early myocardial tissue damage and is predictive of myocardial regeneration. In this study, the investigators aim to further study the importance of cardiac microstructure revealed by MRI in patient and healthy population and compare this novel technology with conventional clinical biomarkers.

The OSIRIS ECPR Trial

The OSIRIS trial is an investigator-initiated, multicenter, multinational, open-label, randomized controlled trial with a 2:1 concealed allocation of refractory out-of-hospital cardiac arrest (OHCA) patients to the extracorporeal cardiopulmonary resuscitation (ECPR) based approach versus the conventional cardiopulmonary resuscitation (CCPR) approach.

A Danish ICD-study in Patients with Coronary Artery Disease Resuscitated from Ventricular Fibrillation

DanICD is a randomized, controlled study to with the aim to assess whether there is a benefit of ICD-implantation in patients with coronary artery disease (including acute myocardial infarction), who survive cardiac arrest due to ventricular fibrillation/sustained ventricular tachycardia and undergo revascularization and with an LVEF above 35%.

ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing

The goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated. Participants \[patients over 18 years old with an indication to receive a definitive pacemaker/intracardiac defibrillator implant\] will receive a permanent cardiac pacing implant as requested according to European Society of Cardiology (ESC) guidelines; the investigators will evaluate procedural efficacy and safety of different implantation approaches.

MAgnetic Resonance Imaging-guided implanTation of Cardioverter DEFibrillators

Implantable cardioverter-defibrillators (ICD) are currently recommended for the primary prevention of sudden cardiac death (SCD) in patients with a remote (\>6 weeks) myocardial infarction (MI) and a low (≤35%) left ventricular ejection fraction (LVEF). Ventricular tachycardia (VT) and/or ventricular fibrillation (VF), which are responsible for most SCDs, result from the presence of surviving myocytes embedded within fibrotic MI-scar. The presence of these surviving myocytes, as well as their specific arrhythmic characteristics, is not captured by LVEF. Hence, the use of LVEF as a unique risk-stratifier of SCD results in a low proportion (17 to 31%) of appropriate ICD device therapy at 2 years. Consequently, most patients with a prophylactic ICD do not present VT/VF requiring ICD therapy prior to their first-ICD battery depletion. Thus, many patients are exposed to ICD complications, such as inappropriate shocks, without deriving any health benefit. Therefore, the current implantation strategy of prophylactic ICDs, based on LVEF only, needs to be improved in post-MI patients.

Registry of Device Implantation

The implantable device therapy for cardiac arrhythmias has been an established therapy, and one of the common standard procedures in cardiac clinical practice. Pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy have been developed since 1960s, and the technologies in this field are still progressively developing. Not only these "traditional" implantable devices, there are multiple new devices for cardiac diseases, such as implantable loop recorder, vagal nerve stimulator and barostimulator. The aim of this registry is to demonstrate the efficacy and the safety of standard device implantation procedures and to evaluate/ identify specific factors, including clinical characteristics, laboratory data and procedural data, which predict the prognosis/complication of the patients. These identification will result in further improvement of patients' care.