PRedictOrs, PHEnotypes and Timing of Obstructive Sleep Apnea in Acute Coronary Syndrome (PROPHET-ACS)

PRedictOrs, PHEnotypes and Timing of Obstructive Sleep Apnea in Acute Coronary Syndrome (PROPHET-ACS)

Obstructive Sleep Apnea (OSA) is a well-known disorder of upper airways collapse during sleep time leading to oxygen desaturation and sleep fragmentation. Despite being increasingly recognized as cardiovascular risk, the effect of OSA on clinical outcomes after Acute Coronary Syndrome (ACS) is not fully defined. Also, OSA syndrome is highly prevalent in ACS and may be related to the deterioration of cardiac function resulting in worsening of the severity of sleep apnea or the intermittent hypoxia could be cardio-protective via the ischemic preconditioning event. Serial sleep studies have shown the progressive reduction of the Apnea / Hypopnea Index (AHI) from the admission in Coronary Care Unit (CCU) to 6 weeks, 12 weeks and 6-month follow up, making necessary to re-assess the severity of OSA after discharge. Therefore, further research in this field is necessary to screen and predict those ACS patients who may experience a change in their AHI index over time.

Study Overview

• Status: Unknown
• Conditions: Sleep; ST Elevated Myocardial Infarction; Sleep-Disordered Breathing; NSTEMI - Non-ST Segment Elevation MI
• Intervention / Treatment: Diagnostic test: Polygraphy

Detailed Description

Obstructive Sleep Apnea (OSA) is a well-known disorder of upper airways collapse during sleep time leading to oxygen desaturation, sleep fragmentation, tissue suffering and hypercapnia. The repeated airways collapse leads to a fall of blood saturation levels during sleep time and it is linked to daytime sleepiness, road traffic accidents, cognitive deficits, depression, myocardial infarction, pulmonary hypertension and stroke.

Despite being increasingly recognized as a major cardiovascular risk, the effect of OSA on clinical outcomes after Coronary Artery Disease (CAD) is not fully defined. The presentation of Acute Coronary Syndrome (ACS) can be unstable angina, non-ST Elevation Myocardial Infarction (NSTEMI) or ST-Elevation Myocardial Infarction (STEMI). Sleep apnea prevalence in the context of acute coronary syndromes (ACS) is sizeable, varying from 36.9%-82% when polysomnography is executed briefly after admission in Cardiovascular Care Unit (CCU). The high prevalence of OSA in ACS may be related to the deterioration of cardiac function resulting in worsening of the severity of sleep apnea. In converse, OSA has also been proposed as a protective factor in CAD. The intermittent hypoxia related to OSA could have a cardio-protective role during acute ACS via the phenomenon of "ischemic preconditioning", showing that in acute MI patients higher AHI was associated with lower peak troponin-T levels in partially and fully adjusted models.

Furthermore, the improvement of cardiac outcomes at the follow-up post-discharge seems to positively influence the severity of OSA. In particular, serial sleep studies have interestingly shown a progressive reduction of the AHI at 6 weeks, 12 weeks and 6-month follow up, making necessary to re-assess the severity of OSA after discharge. Therefore, further research in this field is necessary to screen and predict those ACS patients with a diagnosis of OSA made at admission in CCU who may experience a change in their AHI index over time, in order to identify those with a potential unfavourable prognosis.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Contact: Pier-Valerio Mari, MD; Phone Number: (+39) 3313881904; Email: piervalerio.mari@gmail.com
    • Principal Investigator: Pier-Valerio Mari, MD
    • Sub-Investigator: Veronica Melita, MD
    • Sub-Investigator: Matteo Siciliano, MD
    • Sub-Investigator: Giovanni Diana, MD
    • Sub-Investigator: Flaminio Mormile, MD
    • Sub-Investigator: Giampaolo Niccoli, MD
    • Sub-Investigator: Gaetano Antonio Lanza, MD
    • Sub-Investigator: Filippo Crea, MD
    • Sub-Investigator: Luca Richeldi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a diagnosis of ACS (STEMI or NSTEMI) admitted to CCU of our institution within 72 hours from Myocardial Infarct (MI)
• Age between 18 and 85 years old

Exclusion Criteria:

• Previous diagnosis of OSA or ongoing CPAP treatment
• Chronic/Home Oxygen therapy
• Cardiogenic shock
• Heart failure exacerbation
• use of mechanical ventilation
• Active use of benzodiazepines
• Pregnancy or breastfeeding
• Unable to sign the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with Acute Coronary Syndrome (ACS); Patients admitted to a Coronary Care Unit (CCU) with a new diagnosis of ST Elevation Myocardial Infarction (STEMI) or Non ST Elevation Myocardial Infarction (NSTEMI). Patients are eligible within 72 hours from the admission in CCU. All patients admitted to CCU are going to perform the following procedures/exams as standard clinical practice: coronary angiogram, blood samples, echocardiogram, 24-hour Holter EKG Monitoring. The experimental arm will also perform a polygraphy during CCU stay, a bioelectrical impedance and will complete baseline questionnaires assessing daytime sleepiness such as Epworth Sleepiness Scale (ESS), STOP-BANG and Mallampati score. After the discharge from CCU, patients that had a diagnosis of Obstructive Sleep Apnea Syndrome are going to complete a follow up visit in 90 days undergoing a new polygraphy, bioelectrical impedance, questionnaires (ESS, STOP-BANG and Mallampati Score), echocardiogram.

Diagnostic test: Polygraphy; Patients will perform polygraphy during the CCU stay (baseline) and, if found to have a diagnosis of Obstructive Sleep Apnea (OSA) syndrome, will complete the study with a follow-up visit at 90-day (follow-up). Diagnosis of OSA syndrome will require an Apnea / Hypopnea Index (AHI) more than 5 events per hour.; Other Names: VitalNight Plus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evolution of Obstructive Sleep Apnea severity in Acute Coronary Syndrome	Change of Obstructive Sleep Apnea (OSA) severity from baseline to 90 days in patients affected by an Acute Coronary Syndrome (ACS). Within 72 hours from admission, patients will perform a polygraphy and the Apnea / Hypopnea Index (AHI) will be determined. OSA syndrome is defined by AHI more than 5.0 per hour and can be mild (AHI between 5.0 and 15), moderate (AHI between 15.0 and 30.0) or severe (AHI more than 30.0). When a diagnosis of OSA is confirmed, the patient will have a follow up visit with a new polygraphy and AHI will be defined again. Patients are not going to receive any treatment for the sleep-disorder breathing between baseline and 90-day. The difference between AHI baseline and AHI of the follow-up will define the evolution of OSA severity and will show an improved, stable or worsened sleep-disorder.	Baseline, 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Coronary	Culprit vessel as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Echocardiography	Ejection fraction (EF) and Systolic Pulmonary Artery Pressure (SPAP) as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline, 90 days
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - EKG Holter	Arrhythmias, mean heart rate, SDNN, r-MSSD, pNN50%, Mean Log LF/HF as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Bioelectrical impedance	Resistance and reactance as a 90-day predictors of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The primary statistic of interest will be the effect size.	Baseline, 90 days
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - ESS	Epworth Sleepiness Scale (ESS) as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The primary statistic of interest will be the effect size.	Baseline, 90 days
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - STOP-BANG	STOP-BANG as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. The test is a baseline screening evaluation of Obstructive Sleep Apnea (OSA) diagnosis. A score <3 is not predictive of OSA while a final result ≥3 is suggestive of OSA. The primary statistic of interest will be the effect size.	Baseline, 90 days
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Mallampati Score	Mallampati Score as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography. It is a baseline evaluation of the back of a patient's throat by asking the patient to open the mouth and extend the tongue. The anatomy of the oral cavity is visualized; specifically, the assessor notes whether the base of the uvula, faucial pillars and soft palate are visible. A Mallampati Score ≤2 is not predictive of OSA while a final result <3 is suggestive of OSA. The primary statistic of interest will be the effect size.	Baseline
Predictors of spontaneous reduction of Obstructive Sleep Apnea severity - Serological domain	Blood samples result such as CK, Creatin kinase, Glucose, Cholesterol, nt-proBNP, CRP, Creatinin as a 90-day predictor of spontaneous reduction of at least 15.0 events per hour of Apnea / Hypopnea Index (AHI) from baseline evaluation with polysomnography.	Baseline
Prevalence of Obstructive Sleep Apnea (OSA)	Prevalence expressed as the number of events per hour of the sleep apneas due to obstructive cause in patients with a diagnosis of Obstructive Sleep Apnea (OSA) Syndrome assessed with polysomnography. Obstructive Sleep Apnea will be defined as an Obstructive Apnea Index per hour more than 5.0/h in polysomnography.	Baseline, 90 days
Evolution of Obstructive Sleep Apnea Syndrome	The change of the Obstructive Apnea Index (expressed as the number of events per hour) from the baseline to the 90-day evaluation.	Baseline, 90 days
Prevalence of Central Sleep Apnea (CSA)	Prevalence expressed as the number of events per hour of the sleep apneas due to central cause in patients with a diagnosis of Obstructive Sleep Apnea (OSA) Syndrome assessed with polysomnography. Central Sleep Apnea will be defined as a Central Apnea Index per hour more than 5.0/h in polysomnography.	Baseline, 90 days
Evolution of Central Sleep Apnea (CSA)	The change of the Central Apnea Index (expressed as the number of events per hour) from the baseline to the 90-day evaluation.	Baseline, 90 days
Culprit vessel	Evaluate the baseline prevalence of the culprit vessel responsible for Acute Coronary Syndrome (ACS). Culprit's vessels are one or more of the following: Left Anterior Descending Artery; Circumflex artery; Right Coronary Artery	Baseline
Blood samples characteristics	Evaluate the baseline prevalence and the potential correlation in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of serological biomarkers such as: Troponins, creatinkinase, Creatinin, nt-proBNP, C reactive protein, Glucose, Cholesterol.	Baseline
Bioelectrical impedance characteristics	Evaluate the baseline prevalence and the changing after 90 days in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of bioelectrical impedance, in particular, reactance and impedance.	Baseline, 90 days
Evaluation of Ejection Fraction	Ejection fraction (EF) is a measurement made by echocardiography and expressed as a percentage that describes how much blood the left ventricle pumps out with each contraction. Evaluation of EF will be performed in baseline and after 90 days with echocardiography. The EF is classified as: EF≥55%: Normal EF 40%<EF<55%: Heart failure with preserved ejection fraction (HFpEF) EF≤40%: Heart failure	Baseline, 90 days
Evaluation of Systolic Pulmonary Artery Pressure (SPAP)	The Systolic Pulmonary Artery Pressure (SPAP) is an echocardiographic value expressed as mercury millimetres (mmHg) that describes the likelihood of the presence of Pulmonary Hypertension (PH). Evaluation of Systolic Pulmonary Artery Pressure (SPAP) will be performed in baseline and after 90 days with echocardiography. The SPAP is classified as: SPAP≤35 mmHg: Normal 35mmHg<SPAP≤50mmHg: Possible PH SPAP>50mmHg: Likely PH	Baseline, 90 days
Evolution of Ejection Fraction	Ejection fraction (EF) is a measurement made by echocardiography and expressed as a percentage that describes how much blood the left ventricle pumps out with each contraction. The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a change of at least 8% of the EF baseline value.	Baseline, 90 days
Evolution of Systolic Pulmonary Artery Pressure (SPAP)	The Systolic Pulmonary Artery Pressure (SPAP) is an echocardiographic value expressed as mercury millimetres (mmHg) that describes the likelihood of the presence of Pulmonary Hypertension (PH). The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a change of at least 5mmHg from the SPAP baseline value.	Baseline, 90 days
Polysomnographic characteristics	Within 72 hours from admission in Coronary Care Unit (CCU), patients will perform a polygraphy and the Apnea / Hypopnea Index (AHI) will be determined. OSA syndrome is defined by AHI more than 5.0 per hour and can be mild (AHI between 5.0 and 15), moderate (AHI between 15.0 and 30.0) or severe (AHI more than 30.0). When a diagnosis of OSA is confirmed, the patient will have a follow up visit with a new polygraphy and AHI will be defined again.	Baseline, 90 days
Evaluation of daytime sleepiness	Assessment of sleepiness status using the questionnaire "Epworth Sleepiness Score" (ESS). The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. A result in ESS score more than 10 is suggestive for daytime sleepiness.	Baseline, 90 days
Evolution of daytime sleepiness	Change from baseline to 90 days of the questionnaire "Epworth Sleepiness Score" (ESS). The total score ranges from 0 to 24. Respondents are asked to rate, on a 4-point scale (0-1-2-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The difference from baseline to 90 days will be calculated. The minimal important difference is defined as a reduction of at least 2 points of the baseline value.	Baseline, 90 days
Baseline screening of Obstructive Sleep Apnea	Baseline screening evaluation of Obstructive Sleep Apnea (OSA) diagnosis using the validated questionnaire "STOP-BANG". A score <3 is not predictive of OSA while a final result ≥3 is suggestive of OSA.	Baseline, 90 days
Baseline prediction of Obstructive Sleep Apnea	Baseline evaluation of the back of a patient's throat by asking the patient to open the mouth and extend the tongue. The anatomy of the oral cavity is visualized; specifically, the assessor notes whether the base of the uvula, faucial pillars and soft palate are visible. Four classes can be distinguished: Class I: Soft palate, uvula, fauces, pillars visible. Class II: Soft palate, major part of uvula, fauces visible. Class III: Soft palate, base of uvula visible. Class IV: Only hard palate visible. A Mallampati Score ≤2 is not predictive of OSA while a final result <3 is suggestive of OSA.	Baseline
24 hours-EKG Holter baseline characteristics	Evaluate the baseline prevalence and the potential correlation in acute coronary syndrome (ACS) with obstructive sleep apnea (OSA) of 24 hours EKG Holter using values such as: arrhythmias, mean heart rate, SDNN, r-MSSD, pNN50%, Mean Log LF/HF.	Baseline

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Study Director: Luca Richeldi, PhD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

Helpful Links

• "Determinants and evolution of obstructive sleep apnea syndrome after myocardial infarction". The sample size of the trial PROPHET-ACS was derived from this pilot study presented as abstract at the European Sleep and Breathing Conference 2019, Marseille.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2019
• Primary Completion (Anticipated): September 15, 2019
• Study Completion (Anticipated): December 15, 2019

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: OSA; Sleep Apnea; STEMI; NSTEMI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Myocardial Infarction; Infarction; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; ST Elevation Myocardial Infarction; Acute Coronary Syndrome
• Other Study ID Numbers: 2589

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No