Ida Skrinde Leren

Ida Skrinde Leren, MD, PhD

Ida Skrinde Leren got her Medical Degree at the University of Oslo, and started as a PhD fellow at the CCI in March 2013 after finishing her medical internship in Lillehammer. Her PhD work focused on myocardial function and prediction of arrhythmias in different cardiomyopathies, with emphasis on imaging modalities, especially echocardiography.

She successfully defended her thesis "Ventricular arrhythmias in cardiac ion channel diseases; occurrence, treatment and risk stratification" in June 2016. Her supervisors were Associate Professor Kristina Hermann Haugaa, MD, PhD and Professor Thor Edvardsen, MD, PhD.

Dr. Leren was awarded with His Majesty the King’s Gold Medal for Best Doctoral Thesis within Medicin anno 2016.

The findings in the thesis gained wide international attention and helped change clinical practice and guidelines for the treatment of CPVT (catecholaminergic polymorphic ventricular tachycardia). The recommendations now state that asymptomatic family members receive pre-treatment with beta-blockers as preventative care. The follow-up study examined differences in the treatment effect of different beta-blockers at CPVT and indicated that the beta-blocker nadolol was better in protecting against severe rhythm disturbances than the traditional beta- blockers. This finding has been important for the selection of drugs for these young patients and is the largest study of its kind. The third article illustrated the connection between the electrical and mechanical function of the heart utilizing sensitive image surveys developed at OUH.

 

About the thesis:

Doctor and researcher Ida Leren has in her PhD-thesis focused on investigating the occurance, risk markers and treatment of ventricular arrhythmias in patients with the ion channelopathies CPVT (catecholaminergic polymorphic ventricular tachycardia) and LQTS (long QT syndrome). In addition she, together with her fellow researchers, has investigated myocardial mechanical alterations in patients with LQTS. Channelopathies are diseases caused by disturbed function of ion channel subunits or the protein that regulate these units. These diseases are often caused by a mutation, or several mutations, in the encoding genes, or they can be caused by an autoimmune attack on an ion channel. Ion channels serve many functions, amongst them electrical signal transduction, chemical signaling, and regulation of cell volume.

Ion channel disorders are emerging causes of both morbidity and mortality in modern cardiology. Genetic testing has become an important part of the diagnostic workup in a patient with arrhythmias or cardiac arrests of uncertain genesis, and is also a part of post mortem investigations. This has implications for the patient in question, but possibly an even larger impact on the patient’s family members; the genetic era has provided us with the ability to test for disease prior to the development of signs and symptoms. The ultimate goal of genetic testing is to prevent sudden cardiac death, but this also generates questions about follow-up, possible treatment and interventions in seemingly healthy individuals.

Long QT syndrome is characterized by prolongued QT interval on ECG (electrocardiography; the process of recording the electrical activity of the heart over a period of time using electrodes placed on the skin) and a propensity for malignant ventricular arrhythmias, syncope and sudden cardiac death. Genetically determined LQTS has an estimated prevalence of 1:2000. Mutations in genes encoding ion channel subunits have been found in 60-75% of clinically diagnosed LQTS patients, often affecting potassium channels.

CPVT is an inheritable, arrhythmogenic, cardiac ion channelopathy. Even though the prevalence is estimated at only 1:10 000, CPVT is an important cause of sudden cardiac death in young individuals. In about 60% of cases mutations in the ryanodine receptor-2 (RyR2) gene are found. CPVT is most commonly treated with beta blockers. In the published journal article High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening (Europace. 2010;12:417-23) Leren & co seeked to determine the occurrence of ventricular arrhythmias and the effect of beta blocker treatment by exercise testing in CPVT mutation positive family members.

The second study (Nadonol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with beta 1-selective beta-blockers in patients with catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2016;13:433-440) investigated the antiarrhythmic effect of different beta blockers in CPVT, showing that nadonol was more effective compared to selective beta blockers in surpressing ventricular arrhythmias in CPVT patients. This study was also featured on unikard.org in late 2015 after the online publication of the above mentioned article. Dr. Leren also won the best poster award in her category for her abstract titled Nadolol seems to have superior anti arrhythmic effect compared to selective beta blockers in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) presented at the CHFR Symposium in 2015.

The third article Cardiac mechanical alterations and genotype specific differences in subjects with long QT syndrome (JACC Cardiovasc. Imaging. 2015;8:501-510) investigated echocardiographic characteristics of LQTS patients and explored detailed myocardial mechanics, with spesific focus on potential genotype spesific differences between subjects with LQTS type 1 and 2, as different potassium channels are affected. The study showed that LQTS patients had subtle, but widespread changes in cardiac mechanics present during both systole and diastole. Systolic function by global longitudinal strain was more reduced in LQT2 compared to LQT1 subjects, indicating that spesific ion channel dysfunction may have different consequenses for cardiac mechanics. Dr. Leren won the Oslo University Hospital prize for an outstanding research article for this publication and the study was also featured on unikard.org. Ida Leren has also been interviewed by forskning.no in regards long QT syndrome and the research around the disease. The abstract Long QT syndrome - an electro mechanical disease presented at the CHFR Symposium in 2014 won the best poster award in its category.

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