Diagnostic Study for Heart Disease

Overseen By Nathaniel Smilowitz

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: NYU Langone Health

Must be taking: Aspirin

Must not be taking: NSAIDs, Platelet antagonists

Disqualifiers: Anemia, Thrombocytosis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

175 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking NSAIDs (like ibuprofen or naproxen) within 3 days and any platelet antagonists other than aspirin and thienopyridines within 7 days before participation.

What data supports the effectiveness of the treatment for Coronary Microvascular Disease?

Research shows that coronary microvascular dysfunction is linked to a higher risk of death and major heart problems, suggesting the importance of effective treatment strategies for this condition. ^{1 2 3 4 5}

How is the treatment Diagnostic Coronary Angiography with Non-Obstructive CAD different from other treatments for heart disease?

This treatment is unique because it focuses on diagnosing and treating heart disease that originates in the small blood vessels (microcirculation) rather than the larger coronary arteries, which are often the focus of traditional heart disease treatments. It helps identify and manage conditions like microvascular angina, which are often overlooked in patients with normal-looking coronary arteries. ^{6 7 8 9 10}

What is the purpose of this trial?

Among patients with stable ischemic heart disease who are referred for coronary angiography, a substantial proportion have non-obstructive coronary artery disease (CAD). Ischemia based on symptoms or stress testing may be due to coronary microvascular dysfunction in up to 40% of these patients. However, the mechanisms and optimal treatment of coronary microvascular dysfunction are unknown. Aberrant platelet activity and inflammation have been hypothesized as mechanisms of microvascular dysfunction. Investigators plan to evaluate association between platelet activity, inflammation, and coronary microvascular dysfunction in stable women referred for coronary angiography, and to identify non-invasive correlates of coronary microvascular dysfunction in these patients.

Research Team

Nathaniel Smilowitz, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This study is for adult women over 18 with stable ischemic heart disease, who are taking aspirin and referred for coronary angiography. It's not suitable for those with severe heart failure, recent heart attacks, certain blood disorders or bleeding risks, pregnancy, or known allergies to adenosine.

Inclusion Criteria

I am a woman over 18 referred for a heart vessel check.

My heart condition is stable, with symptoms or test results showing reduced blood flow to my heart.

I have taken aspirin before having a heart catheterization.

Exclusion Criteria

I have had heart surgery or a procedure to improve blood flow to my heart.

Pregnancy

Pre-Cath Exclusion criteria:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Evaluation

Participants undergo diagnostic coronary angiography and invasive measures of coronary microvascular physiology are obtained

1 day

1 visit (in-person)

Sample Collection and Analysis

Blood is collected for analysis of platelet activity, inflammation, and isolation of coronary endothelial cells

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after diagnostic procedures

4 weeks

Treatment Details

Interventions

• Adenosine
• Bivalirudin
• Diagnostic Coronary Angiography with Non-Obstructive CAD
• Guiding Catheter
• Heparin
• Pressure-Temperature Sensor Guidewire

Trial Overview The trial investigates the link between platelet activity, inflammation and coronary microvascular dysfunction using a Pressure-Temperature Sensor Guidewire during angiography. Medications like Bivalirudin, Adenosine and Heparin will be used alongside standard procedures.

Participant Groups

Group I: Non-Obstructive CAD Experimental Treatment 5 Interventions

After diagnostic coronary angiography, invasive measures of coronary microvascular physiology will be obtained. Blood will be collected for platelet activity, inflammation and isolation of coronary endothelial cells.

Diagnostic Coronary Angiography with Non-Obstructive CAD is already approved in European Union, United States for the following indications:

Approved in European Union as Statins, ACE inhibitors, Beta blockers, Calcium channel blockers for:

• Coronary microvascular dysfunction
• Non-obstructive coronary artery disease

Approved in United States as Statins, ACE inhibitors, Beta blockers, Calcium channel blockers for:

• Coronary microvascular dysfunction
• Non-obstructive coronary artery disease

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

In a study of 3265 patients with varying degrees of coronary artery disease, those with non-obstructive coronary artery disease (20-50% blockage) had a significantly worse long-term cardiovascular prognosis compared to those with normal coronary arteries, with a hazard ratio of 1.72.

This increased risk was particularly pronounced in non-diabetic patients (hazard ratio 2.12), women (hazard ratio 1.75), and those who had experienced an acute coronary syndrome (hazard ratio 2.07), indicating that non-obstructive coronary artery disease is a serious condition that warrants attention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Implication of Non-Obstructive Coronary Lesions: A New Classification in Different Settings. Rodríguez-Capitán, J., Sánchez-Pérez, A., Ballesteros-Pradas, S., et al.[2021]

Coronary microvascular dysfunction (CMD) is linked to a nearly 4-fold increase in all-cause mortality, with 9.3% of patients with CMD dying compared to only 2.6% of those without it, based on a meta-analysis of 6631 patients.

Patients with CMD also experience a 5-fold increase in major adverse cardiac events, indicating a significant risk associated with CMD that necessitates further research into effective diagnostic and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Isolated Coronary Microvascular Dysfunction With Mortality and Major Adverse Cardiac Events: A Systematic Review and Meta-Analysis of Aggregate Data. Gdowski, MA., Murthy, VL., Doering, M., et al.[2021]

A significant portion (60-70%) of patients undergoing invasive coronary angiography for angina and myocardial ischemia do not have obstructive coronary disease, with coronary microvascular angina being the cause in nearly 50% of these cases.

Coronary microvascular angina is linked to poor prognosis and quality of life, but advancements in diagnostic methods and treatment options are improving management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coronary Microvascular Angina: A State-of-the-Art Review. Spione, F., Arevalos, V., Gabani, R., et al.[2022]

Approximately 15% of patients with myocardial infarction (MI) have non-obstructive coronary artery disease (CAD), which is not benign and has a two-year adverse outcome rate of 4.6%, significantly higher than the 2.2% rate in age and sex matched individuals without cardiovascular disease.

Patients with non-obstructive CAD tend to be younger, more likely to be women, and have lower risk factors compared to those with obstructive CAD, yet they receive less aggressive secondary prevention treatment, highlighting a need for better management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial Infarction Without Obstructive Coronary Artery Disease is Not a Benign Condition (ANZACS-QI 10). Barr, PR., Harrison, W., Smyth, D., et al.[2018]

Patients with myocardial infarction and nonobstructive coronary artery disease (MINOCA) have a significantly higher risk of major adverse cardiovascular events (MACE) compared to those with nonobstructive CAD and negative troponin levels, with a hazard ratio of 2.37.

Treatment with statins and ACE inhibitors after angiography was associated with a reduced risk of MACE, highlighting the potential for targeted medical therapy in improving outcomes for patients with MINOCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Patients With Nonobstructive Coronary Artery Disease With Versus Without Myocardial Infarction (from the VA Clinical Assessment Reporting and Tracking [CART] Program). Kovach, CP., Hebbe, A., O'Donnell, CI., et al.[2021]

In a study of 244 patients diagnosed with MINOCA (6.6% of acute coronary syndrome cases), those with non-obstructive coronary artery disease (noCAD) were older and had more cardiovascular risk factors, leading to more aggressive secondary prevention therapy.

Patients with normal coronary arteries (NCA) showed a higher occurrence of anterior ST-segment elevation on ECG, suggesting different underlying mechanisms for MINOCA that warrant further diagnostic evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and electrocardiographic features of patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA). Dal Fabbro, J., Candreva, A., Rossi, VA., et al.[2021]

Patients with chest pain are often misclassified as having noncardiac chest pain when they actually have microvascular angina, which is a form of ischemic heart disease not caused by obstructive coronary artery disease.

Recent advancements in diagnostic tools and conceptual frameworks have improved our understanding of microvascular angina, allowing for better diagnosis and treatment of myocardial ischemia in patients with normal-appearing coronary arteries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microvascular angina: an update on diagnosis and treatment. Titterington, JS., Hung, OY., Wenger, NK.[2015]

Nonobstructive coronary artery disease (CAD) is prevalent in 67% of patients with stable angina and 13% in those with non-ST-segment elevation acute coronary syndrome, indicating a significant number of patients may have this condition without severe blockages.

While nonobstructive CAD has a better prognosis than obstructive CAD, it still carries a higher risk of cardiac events compared to patients with no angiographic CAD, highlighting the need for improved risk assessment and management strategies for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and Prognosis of Nonobstructive Coronary Artery Disease in Patients Undergoing Coronary Angiography or Coronary Computed Tomography Angiography: A Meta-Analysis. Wang, ZJ., Zhang, LL., Elmariah, S., et al.[2018]

In a study of 11,462 patients with nonobstructive coronary artery disease (CAD), both men and women showed similar annual rates of major adverse cardiovascular events (MACE), including myocardial infarction and death, over an average follow-up of 2.3 years.

Nonobstructive CAD was associated with an increased risk of MACE for both genders, indicating that even without significant blockages, patients are at risk for serious cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study. Leipsic, J., Taylor, CM., Gransar, H., et al.[2022]

A study involving 42 patients demonstrated that 128-multi detector row computed tomography coronary angiography (MDCTCA) has excellent diagnostic accuracy for detecting coronary artery disease, achieving 100% sensitivity and 91% specificity for >50% luminal narrowing.

MDCTCA also showed high accuracy for detecting >70% luminal narrowing, indicating it is a reliable noninvasive alternative to conventional coronary angiography for diagnosing coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of 128-row multidetector computed tomography coronary angiography in the diagnosis of significant coronary artery stenosis. Chaosuwannakit, N., Kiatchoosakun, S., Makarawate, P.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic Implication of Non-Obstructive Coronary Lesions: A New Classification in Different Settings. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Association of Isolated Coronary Microvascular Dysfunction With Mortality and Major Adverse Cardiac Events: A Systematic Review and Meta-Analysis of Aggregate Data. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Coronary Microvascular Angina: A State-of-the-Art Review. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Myocardial Infarction Without Obstructive Coronary Artery Disease is Not a Benign Condition (ANZACS-QI 10). [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of Patients With Nonobstructive Coronary Artery Disease With Versus Without Myocardial Infarction (from the VA Clinical Assessment Reporting and Tracking [CART] Program). [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical and electrocardiographic features of patients with myocardial infarction with non-obstructive coronary artery disease (MINOCA). [2021]

7. England pubmed.ncbi.nlm.nih.gov

Microvascular angina: an update on diagnosis and treatment. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Prevalence and Prognosis of Nonobstructive Coronary Artery Disease in Patients Undergoing Coronary Angiography or Coronary Computed Tomography Angiography: A Meta-Analysis. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study. [2022]

10. Thailand pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of 128-row multidetector computed tomography coronary angiography in the diagnosis of significant coronary artery stenosis. [2022]