Ischemic heart disease poses a significant burden on society and affects many Danes
annually. With more than 300,000 citizens in Denmark living with cardiovascular disease,
and more than 17,500 cardiovascular deaths annually, the need for effective diagnosis and
treatment is crucial. Cardiac Computed Tomography Angiography (CCTA) has become an
important tool in diagnosing arteriosclerotic obstructive coronary artery disease (CAD)
in patients with typical or atypical chest pain, but the increasing use of this method
requires a more efficient selection of patients before initial testing. Early and
accurate risk stratification could improve patient management, reduce morbidity, and
improve patient outcomes, highlighting the importance of optimizing diagnostic pathways.
At Gødstrup Hospital, novel clinical likelihood (CL) models have been developed to assess
the pre-test probability of obstructive CAD. Based on sex, age, and symptom
characteristics, and including traditional cardiovascular risk factors, the risk
factor-weighted clinical likelihood (RF-CL) model improves discrimination of obstructive
CAD and prognosis compared to traditional models. Additionally, the utilization of a
coronary artery calcium score (CACS) in conjunction with the RF-CL model, i.e., the
CACS-weighted clinical likelihood (CACS-CL) model, further enhances patient management in
external validation cohorts. Recently, both CL models have been implemented in the
European guidelines on CAD management. However, the CL models have only been applied in
observational studies, and no randomized trials substantiate their use in clinical
practice.
It is hypothesized that a diagnostic strategy based on an assessment including the CL
models is non-inferior to the current standard strategy, as measured by the number of
asymptomatic patients during follow-up. Secondly, it is assumed that the CL-based
strategy reduces unnecessary diagnostic tests and improve resource utilization without
compromising patient safety.
Emerging alongside these developments is Laser Speckle Contrast Imaging (LSCI), a
promising non-invasive technique for assessing microvascular function. Several studies
have suggested a link between reduced microcirculation in the skin and heart among
patients with angina and non-significant calcification, compared to healthy controls.
LSCI measures red blood cell movement to quantify blood flow, making it an effective,
fast, and cost-efficient tool already in use in other medical fields. If a correlation
between peripheral and cardiac microcirculation is established, LSCI could address a
diagnostic gap in detecting microvascular dysfunction, particularly for angina patients
without significant coronary calcification. Integrating LSCI into the diagnostic process
offers potential to further refine patient selection for testing and provide more
targeted diagnostic pathways.
This study will increase the evidence for utilizing the RF-CL and CACS-CL models in
clinical practice. Currently, the use of pre-test likelihood models is only recommended
with a IB recommendation and deferral of diagnostic testing in individuals with CL>=5%
with IIa B recommendation due to a lack of randomized studies. The study will focus on
symptomatic endpoints and investigate quality of life measurements in patients deferred
for testing based on the CL estimation. Secondary endpoints include both effectiveness
and safety metrics.
This project is an ambitious endeavor that builds on previous work performed within our
research group. The supervisors are experienced researchers with substantial expertise in
this area and conducting randomized studies. The findings from this study have the
potential to significantly impact clinical practice by providing evidence-based
recommendations (Level/Class of evidence 1A) for the use of CL models in the diagnostic
pathway of ischemic heart disease.
By demonstrating that using the CL model in the management of patients with new-onset
chest pain substantially and safely reduces the necessity for cardiac CT and other
advanced diagnostic procedures, resource utilization could improve and costs be lowered
for the healthcare system. Additionally, as tests could be deferred without compromising
safety, patient-related quality of life could improve. Finally, the findings are expected
to contribute to clinical guidelines and practices, benefiting the broader field of
cardiology. By validating the CL models in a large, diverse patient population, this
study could provide strong evidence for their broader implementation in clinical
practice.
The incorporation of LSCI into this framework also presents an exciting avenue for
further improving diagnostic precision. If LSCI can reliably identify microvascular
dysfunction, it could serve as a complementary tool in optimizing diagnostic strategies,
particularly for patients in whom obstructive CAD has been ruled out but who still
experience angina-like symptoms.
If CL model utilization proves capable of safely reducing the necessity for CCTA and
other advanced diagnostic procedures in patients with obstructive CAD, resource
utilization could improve, lowering costs for the healthcare system while maintaining or
enhancing patient quality of life.
The present research addresses a significant gap in current diagnostic strategies and has
the potential to shift clinical practices towards more personalized and efficient care
pathways for stable chest pain.