diagnosis and management of syncope

Diagnosis and Management of Diagnosis and Management of SyncopeSyncope

Robert Helm, M.D.Robert Helm, M.D.Assistant Professor of MedicineAssistant Professor of Medicine

Boston University School of MedicineBoston University School of Medicine

August 2013August 2013

Case 1Case 1

53 year-old obese gentleman with diabetes, hypertension and 53 year-old obese gentleman with diabetes, hypertension and

hyperlipidemia who presented with syncope. This occurred after working hyperlipidemia who presented with syncope. This occurred after working

at the boat yard on a very hot day. He was taking a break and drinking at the boat yard on a very hot day. He was taking a break and drinking

a cold slurpee, when he suddenly felt pins and needles in his neck, peri-a cold slurpee, when he suddenly felt pins and needles in his neck, peri-

oral numbness, and tingling of his forehead. As he was calling for wife, oral numbness, and tingling of his forehead. As he was calling for wife,

he lost consciousness and fell to the ground. According to his wife, he he lost consciousness and fell to the ground. According to his wife, he

was unconscious for about a minute and his entire body was quivering. was unconscious for about a minute and his entire body was quivering.

Upon regaining consciousness, he was confused and disoriented. His Upon regaining consciousness, he was confused and disoriented. His

wife reports that he was cold, clammy, and very diaphoretic. He wife reports that he was cold, clammy, and very diaphoretic. He

sustained some minor bruising of left shoulder but no head injuries.sustained some minor bruising of left shoulder but no head injuries.

No prior syncope but two weeks ago he did a “pirouette” No prior syncope but two weeks ago he did a “pirouette”

due to sudden brief episode of lightheadedness and loss of due to sudden brief episode of lightheadedness and loss of

balance. He did not lose consciousness. He consulted balance. He did not lose consciousness. He consulted

with his internist, who found relative low blood pressure with his internist, who found relative low blood pressure

(100/54 mmHg) and reduced his Lisinopril by half (40 to 20 (100/54 mmHg) and reduced his Lisinopril by half (40 to 20

mg daily). His blood sugars have been well controlled. mg daily). His blood sugars have been well controlled.

Case 1Case 1

Past Medical HistoryPast Medical HistoryDiabetes (HgBA1C 5.8)Diabetes (HgBA1C 5.8)HypertensionHypertensionHyperlipidemiaHyperlipidemia? myocardial infarction? myocardial infarctionObstructive sleep apneaObstructive sleep apnea

Social HistorySocial History Non-smokerNon-smoker No alcohol or drugsNo alcohol or drugs

Family HistoryFamily History Mother had MI at 60Mother had MI at 60 Brother died suddenly at 48Brother died suddenly at 48

Review of systemReview of system Negative. Good functional Negative. Good functional capacity.capacity.

AllergiesAllergies NoneNone

MedicationsMedications Cardizem cd 120 mg dailyCardizem cd 120 mg daily Lisinopril 20 mg dailyLisinopril 20 mg daily Lantus 40 units at nightLantus 40 units at night Novalog 12 units with mealsNovalog 12 units with meals Aspirin 81 mg dailyAspirin 81 mg daily Lasix 80 mg dailyLasix 80 mg daily Simvastatin 80 mg at nightSimvastatin 80 mg at night Fenofibrate 134 mg dailyFenofibrate 134 mg daily Percocet 5/325 mg as needed for painPercocet 5/325 mg as needed for pain Viagra 100 mg – last used 2 days priorViagra 100 mg – last used 2 days prior Nitroglycerin 0.4 mg SL – never usedNitroglycerin 0.4 mg SL – never used

Case 1Case 1

PPhysical examinationhysical examination

BP 124/62 mmHg. Not orthostatic. Normal carotid palpation and BP 124/62 mmHg. Not orthostatic. Normal carotid palpation and

auscultation. Normal cardiovascular exam. Bruised right hip. auscultation. Normal cardiovascular exam. Bruised right hip.

LaboratoryLaboratory

BUN 27 ng/dl Creatinine 1.47 ng/dl. Electrolytes and blood count BUN 27 ng/dl Creatinine 1.47 ng/dl. Electrolytes and blood count

normal.normal.

EchocardiogramEchocardiogram – normal 1 month ago. – normal 1 month ago.

Case 1Case 1

Case 1

Case 1Case 1

Admitted for 24 hour observation and hydration. Admitted for 24 hour observation and hydration.

Diagnosis:Diagnosis: “Vaso-vagal syncope” “Vaso-vagal syncope”

PollThe correct statement is:The correct statement is:

A.A. The patient has been correctly diagnosed.The patient has been correctly diagnosed.

B.B. The patient should be referred for urgent pacemaker.The patient should be referred for urgent pacemaker.

C.C. The patient should be referred for electrophysiologic study.The patient should be referred for electrophysiologic study.

D.D. The patient should be referred for 30 day event recorder.The patient should be referred for 30 day event recorder.

E.E. The patient should be referred for tilt-table study.The patient should be referred for tilt-table study.

61 year old gentleman with history of cocaine use who 61 year old gentleman with history of cocaine use who

presented with syncope. “He was in kitchen making presented with syncope. “He was in kitchen making

Thanksgiving dinner and developed lightheadedness. He Thanksgiving dinner and developed lightheadedness. He

sat on a step stool and the next thing he remember is being sat on a step stool and the next thing he remember is being

on the floor and his son calling his name. He felt like he on the floor and his son calling his name. He felt like he

couldn’t move. The kitchen was really hot and and he had couldn’t move. The kitchen was really hot and and he had

missed lunch. He reports using cocaine “months ago”.missed lunch. He reports using cocaine “months ago”.

Case 2Case 2

Past Medical HistoryPast Medical Historynonenone

Social HistorySocial History history of cocainehistory of cocaine

Family HistoryFamily History no premature CAD or SCDno premature CAD or SCD

Review of systemReview of system Negative. Negative.

AllergiesAllergies NoneNone

MedicationsMedications NoneNone

Case 2Case 2

PPhysical examinationhysical examination

BP 145/91 mmHg. Not orthostatic. Normal carotid BP 145/91 mmHg. Not orthostatic. Normal carotid

palpation and auscultation. Normal cardiovascular exam. palpation and auscultation. Normal cardiovascular exam.

Minor bruise on elbow.Minor bruise on elbow.

LaboratoryLaboratory

BUN 26 ng/dl Creatinine 1.1 ng/dl. Electrolytes and blood BUN 26 ng/dl Creatinine 1.1 ng/dl. Electrolytes and blood

count normal.count normal.

Case 2Case 2

Case 2Case 2

a. Check toxicology screen. If positive then a. Check toxicology screen. If positive then attribute syncope to cocaine use. attribute syncope to cocaine use.

b. Continuous-loop event monitoring.b. Continuous-loop event monitoring.c. Increase fluid intake and reassure patient.c. Increase fluid intake and reassure patient.d. Electrophysiology study to assess for inducible d. Electrophysiology study to assess for inducible

VTVTe. Tilt-table study. e. Tilt-table study.

f. Implant loop recorder (ILR).f. Implant loop recorder (ILR). g. Echocardiogram.g. Echocardiogram.

h. B and then D if event monitoring is negative.h. B and then D if event monitoring is negative. i. B and then F if event monitoring is negative.i. B and then F if event monitoring is negative. j. G and if ejection fraction is < 35% then Dj. G and if ejection fraction is < 35% then D

PollPoll

The correct next step is:The correct next step is:

Why is syncope a difficult problem?Why is syncope a difficult problem?

• Physiologic response to a wide variety of medical conditions Physiologic response to a wide variety of medical conditions

• By definition it is a transient conditionBy definition it is a transient condition

• Occurs with unpredictable and random pattern Occurs with unpredictable and random pattern

• Difficult to establish definitive “diagnosis”Difficult to establish definitive “diagnosis”

• ““Another patient with syncope….”Another patient with syncope….”

• History from patient may not be reliable.History from patient may not be reliable.

Amnesia for Loss of Consciousness in Amnesia for Loss of Consciousness in Carotid Sinus SyndromeCarotid Sinus Syndrome

FallsFalls (n=34)(n=34)

SyncopeSyncope (n=34)(n=34) P valueP value

Mean max asystole (s)Mean max asystole (s) 5.15.1 5.45.4 0.420.42

Right Positive CSMRight Positive CSM 24 (71%)24 (71%) 29 (85%)29 (85%) 0.920.92

CSM positive uprightCSM positive upright 20 (59%)20 (59%) 9 (26%)9 (26%) 0.240.24

LOC during CSMLOC during CSM 22 (64%)22 (64%) 15 (44%)15 (44%) 0.1440.144

Amnesia for LOCAmnesia for LOC 21 (95%)21 (95%) 4 (27%)4 (27%) <0.001<0.001

Perry S, et al: J Am Coll Cardiol 2005;45:1840Perry S, et al: J Am Coll Cardiol 2005;45:1840

Causes of SyncopeCauses of Syncope

Classification of SyncopeClassification of Syncope

Common and benignCommon and benignOrthostaticOrthostaticNeurocardiogenicNeurocardiogenic

Common and not so benignCommon and not so benignSinus node dysfunction, carotid sinus hypersensitivitySinus node dysfunction, carotid sinus hypersensitivityParoxysmal AV blockParoxysmal AV block

Less common, lethalLess common, lethalVentricular tachycardia, ventricular fibrillationVentricular tachycardia, ventricular fibrillationTorsade de pointesTorsade de pointes

Everything elseEverything else

Emergency Visits with SyncopeEmergency Visits with SyncopeEuropean Society of Cardiology GuidelinesEuropean Society of Cardiology Guidelines

CauseCause NumberNumber PercentPercent

Neurally mediated 309 66

Orthostatic Hypotension 46 10

Cardiac Arrhythmias 53 11

Cardiovascular 21 5

Unknown 11 2

Non-syncopal attack 25 5

Brignole M, Brignole M, et al. et al. European Heart Journal 2006;27:76-82European Heart Journal 2006;27:76-82

465 patients465 patients

Neurally - mediatedNeurally - mediated

Reflex syncope Reflex syncope Vasovagal Vasovagal Carotid sinus hypersensitivityCarotid sinus hypersensitivitySituationalSituationalPost-exercise Post-exercise Glossopharyngeal and trigeminal Glossopharyngeal and trigeminal neuralgia neuralgia

Orthostatic syncope Orthostatic syncope Primary autonomic failure Primary autonomic failure Secondary autonomic failure Secondary autonomic failure Volume depletionVolume depletionDrugs and alcohol Drugs and alcohol

Reflex Mechanism - Bezold JarischReflex Mechanism - Bezold Jarisch

Chang-Sing P. Cardiol Clinics. 1991;9(4):641-651Chang-Sing P. Cardiol Clinics. 1991;9(4):641-651

InotropyInotropy

ContractilityContractility

Venous returnVenous return

TriggerTrigger

BPBP

SympatheticSympathetictonetone

ArterialArterialtonetone

BPBP

HRHR

VasodilationVasodilation

BPBP

SyncopeSyncope

VagalVagalefferentefferentSmall ventricleSmall ventricle

Vagal Vagal afferentafferent

SympatheticSympatheticwithdrawalwithdrawal

Wall stretchWall stretch

ReflexReflexC-fibersC-fibersReflexReflexC-fibersC-fibers

When is History and Physical SufficientWhen is History and Physical Sufficient

• Young patient with single presentation or clear Young patient with single presentation or clear

situational dependency situational dependency

• Normal physical examinationNormal physical examination

• Normal ECGNormal ECG

• No significant injuryNo significant injury

• Low risk occupationLow risk occupation

What about the rest of the patients?What about the rest of the patients?

History & physical exam including CSMHistory & physical exam including CSM

ECGECG

Tilt table testTilt table test

EchocardiogramEchocardiogram

Electrophysiology studyElectrophysiology study

Holter monitor / Event recorder / Implantable Loop Holter monitor / Event recorder / Implantable Loop Recorder (ILR)Recorder (ILR)

Neurological evaluationNeurological evaluation

Psychiatric evaluationPsychiatric evaluation

Role of history in differentiating NMS from Role of history in differentiating NMS from cardiac syncopecardiac syncope

Warm PlaceWarm Place Abdominal DiscomfortAbdominal Discomfort WeaknessWeakness

Feeling warmFeeling warm Awareness about to Awareness about to faintfaint YawningYawning

Syncope while Syncope while standingstanding NauseaNausea Feeling tiredFeeling tired

Standing in one placeStanding in one place VomitingVomiting Feeling coldFeeling cold

LightheadednessLightheadedness ProdromeProdrome History > 4 yrsHistory > 4 yrs


Alboni P, et al: J Am Coll Cardiol 2001;37:1921-28

Abdominal DiscomfortAbdominal Discomfort

Standing in one placeStanding in one place Feeling coldFeeling cold

History > 4 yrsHistory > 4 yrs




Warm PlaceWarm Place Abdominal DiscomfortAbdominal Discomfort WeaknessWeakness

Feeling warmFeeling warm Awareness about to Awareness about to faintfaint YawningYawning

Syncope while Syncope while standingstanding NauseaNausea Feeling tiredFeeling tired

Standing in one placeStanding in one place VomitingVomiting Feeling coldFeeling cold

LightheadednessLightheadedness ProdromeProdrome History > 4 yrsHistory > 4 yrs

191 patients 191 patients with cardiac diseasewith cardiac disease



History > 4 yrsHistory > 4 yrs

191 patients 191 patients with cardiac diseasewith cardiac disease



Case 2Case 2

53 year-old obese gentleman with diabetes, hypertension and 53 year-old obese gentleman with diabetes, hypertension and

hyperlipidemia who presented with syncope. This occurred after working hyperlipidemia who presented with syncope. This occurred after working

at the boat yard on a at the boat yard on a very hot dayvery hot day. He was taking a break and drinking . He was taking a break and drinking

a a cold slurpeecold slurpee, when he suddenly felt , when he suddenly felt pins and needles pins and needles inin his neck, his neck, peri-peri-

oral numbnessoral numbness, and , and tinglingtingling of his forehead. As he was calling for wife, of his forehead. As he was calling for wife,

he lost consciousness and fell to the ground. According to his wife, he he lost consciousness and fell to the ground. According to his wife, he

was unconscious for about a minute and his entire was unconscious for about a minute and his entire body was quiveringbody was quivering. .

Upon regaining consciousness, he was Upon regaining consciousness, he was confusedconfused and and disorienteddisoriented. His . His

wife reports that he was wife reports that he was cold, clammycold, clammy, and very , and very diaphoreticdiaphoretic. He . He

sustained some sustained some minor bruising minor bruising of left shoulder but of left shoulder but no head injuriesno head injuries..

Case 2

FunctionalFunctional

Vagal toneVagal tone

MedicationsMedications

Structural Structural

AV nodal or His Purkinje fibrosisAV nodal or His Purkinje fibrosis

Mitral annular calcificationMitral annular calcification

InfiltrativeInfiltrative

GeneticGenetic

Prolonged PR / heart blocksProlonged PR / heart blocks

Short PR Short PR

Bundle branch blocksBundle branch blocks

Long QTLong QT

Short QTShort QT

ECG – Abnormal conductionECG – Abnormal conduction

AV nodeAV node HisHis

Intra-cardiac recordingIntra-cardiac recording

AHAH HVHV

PR interval

What about the rest of the patients?What about the rest of the patients?

History & physical exam including CSMHistory & physical exam including CSM

ECGECG



Electrophysiology studyElectrophysiology study

Holter monitor / Event recorder / Implantable Loop Holter monitor / Event recorder / Implantable Loop Recorder (ILR)Recorder (ILR)

Neurological evaluationNeurological evaluation

Psychiatric evaluationPsychiatric evaluation

Tilt Table Response consistent with NMSTilt Table Response consistent with NMS

Sra JS. Ann Intern Med. 1991;114:1013-1019.Sra JS. Ann Intern Med. 1991;114:1013-1019.

Pretest 1 min 12.5 min RecoveryPretest 1 min 12.5 min Recovery

ECG

BloodPressure(mmHg)

TiltTilt 0 70 70 0 0 70 70 0 HR (BPM) 77 HR (BPM) 77 94 94 4040 46 46BP (mmHg) 115/70 125/80 BP (mmHg) 115/70 125/80 55/30 55/30 98/55 98/55

SyncopeSyncope


• Strongly consider for all patientsStrongly consider for all patients

• Screen for hypertrophic cardiomyopathyScreen for hypertrophic cardiomyopathy

• Stratification for EP studyStratification for EP study

Ejection fraction < 30% - meet criteria for ICDEjection fraction < 30% - meet criteria for ICD

35-50% - test for inducibility of VT35-50% - test for inducibility of VT

Electrophysiology Study

• Risk stratification of ventricular arrhythmias – assess Risk stratification of ventricular arrhythmias – assess for inducibilityfor inducibility

• It is poor at diagnosing bradycardic arrhythmiasIt is poor at diagnosing bradycardic arrhythmias

• It is highly sensitive for tachycardias.It is highly sensitive for tachycardias.

Holter MonitorHolter Monitor

Yield: Yield: Arrhythmia with symptoms = 2%Arrhythmia with symptoms = 2% Symtoms without arrhythmia = 15%Symtoms without arrhythmia = 15%

Gibson TC et al Am J Cardiol 1984;53:1013-17Gibson TC et al Am J Cardiol 1984;53:1013-17

Comparison of Loop Recorders versus Comparison of Loop Recorders versus Holter Monitor (COLAPS)Holter Monitor (COLAPS)

Sivakumaran S, et al. Am J Med 2003;115:1-5Sivakumaran S, et al. Am J Med 2003;115:1-5

Event recorder in patient with syncopeEvent recorder in patient with syncope

Implantable Loop Recorders (ILR)Implantable Loop Recorders (ILR)

ILR

Patient Assist Device

Automatically detectsAutomatically detects bradycardiabradycardia tachycardiatachycardia asystoleasystole

Records rhythm atRecords rhythm at time of triggertime of trigger

ILRsILRs

Example tracing from ILRExample tracing from ILR

ILR in unexplained syncope ILR in unexplained syncope with normal conventional work-upwith normal conventional work-up

TachycardiaTachycardia

56%56%

11%11%

33%

Asystole /Asystole /bradycardiabradycardia

No arrhythmiaNo arrhythmia

Diagnostic yield: 35%Diagnostic yield: 35%(175/506 patients)(175/506 patients)

Brignole et al. Europace 2009;11,671-687Brignole et al. Europace 2009;11,671-687

Suspect Pacemaker malfuctionSuspect Pacemaker malfuction

1.1. EKGEKG

2. Interrogate pacemaker – check lead integrity with 2. Interrogate pacemaker – check lead integrity with provocative maneuversprovocative maneuvers

3. Chest X-ray3. Chest X-ray

Importance of Interrogating PPM or ICDImportance of Interrogating PPM or ICD

Atrial lead

Ventricular lead

Atrial leadRight ventricular lead2

A.A. Syncope resulting in injurySyncope resulting in injury

B.B. Syncope during exerciseSyncope during exercise

C.C. Syncope in the supine positionSyncope in the supine position

D.D. Suspected or known structural heart diseaseSuspected or known structural heart disease

E.E. ECG abnormalityECG abnormality

Pre-excitation (WPW)Pre-excitation (WPW)

Long QTLong QT

Bundle-branch blockBundle-branch block

HR<50 bpm or pauses > 3 secondsHR<50 bpm or pauses > 3 seconds

Mobitz I or more advanced heart blockMobitz I or more advanced heart block

Documented tachyarrhythmiaDocumented tachyarrhythmia

Myocardial infarctionMyocardial infarction

F.F. Family history of sudden deathFamily history of sudden death

G.G. Frequent episodes (>2 per year)Frequent episodes (>2 per year)

H.H. Implanted pacemaker or defibrillatorImplanted pacemaker or defibrillator

I.I. High risk occupation (bus driver, pilot etc.)High risk occupation (bus driver, pilot etc.)

Syncope – Syncope – red flagsred flags

Advanced Age

Case 1 - reviewCase 1 - review

Discharged after 24 observation with diagnosis of “Vaso-vagal syncope”Discharged after 24 observation with diagnosis of “Vaso-vagal syncope”

2 days later…2 days later…

Witnessed collapse while seated.Witnessed collapse while seated.

Episode of syncope with complete heart block noted on telemetry.Episode of syncope with complete heart block noted on telemetry.

Dual chamber pacemaker implanted.Dual chamber pacemaker implanted.

Discharged home the next day.Discharged home the next day.

Case 1 Case 1

Suspected or known structural heart disease - prior MISuspected or known structural heart disease - prior MI

Abnormal EKG – trifasicular blockAbnormal EKG – trifasicular block

Family history of sudden death – brother died at 45Family history of sudden death – brother died at 45

Frequent episodes – “pirouette” 2 weeks prior Frequent episodes – “pirouette” 2 weeks prior

Case 2 - reviewCase 2 - review

Discharged after 24 observation with diagnosis of “Vaso-vagal syncope”Discharged after 24 observation with diagnosis of “Vaso-vagal syncope”

3 month later..3 month later..

Cardiac arrest at home and successfully defibrillated but prolonged down Cardiac arrest at home and successfully defibrillated but prolonged down

time.time.

Had slow neurologic recovery.Had slow neurologic recovery.

ICD implanted for secondary prevention.ICD implanted for secondary prevention.

Case 2Case 2

Which of the following historical findings are useful for Which of the following historical findings are useful for predicting neurally-mediated syncope in patients with heart predicting neurally-mediated syncope in patients with heart disease and recurrent syncope?disease and recurrent syncope?

a. Feeling warm.a. Feeling warm.b. Awareness of being about to faint.b. Awareness of being about to faint.c. Recovery duration lasting longer than 60 minutes.c. Recovery duration lasting longer than 60 minutes.d. Confusion during recovery.d. Confusion during recovery.e. Time (years) between first and last syncopal e. Time (years) between first and last syncopal

episodes.episodes.

Test questionsTest questions

Which of the following historical findings are useful for Which of the following historical findings are useful for predicting neurally-mediated syncope in patients with heart predicting neurally-mediated syncope in patients with heart disease and recurrent syncope?disease and recurrent syncope?

a. Feeling warm.a. Feeling warm.b. Awareness of being about to faint.b. Awareness of being about to faint.c. Recovery duration lasting longer than 60 minutes.c. Recovery duration lasting longer than 60 minutes.d. Confusion during recovery.d. Confusion during recovery.e. Time (years) between first and last syncopal e. Time (years) between first and last syncopal

episodes.episodes.

An 80 year-old frail woman presents to you after falling while An 80 year-old frail woman presents to you after falling while ambulating to the bathroom at night. This is the second time ambulating to the bathroom at night. This is the second time she has fallen in the last month. Echocardiogram shows she has fallen in the last month. Echocardiogram shows diastolic dysfunction and moderate mitral annular diastolic dysfunction and moderate mitral annular calcification. ECG is essentially normal with exception of calcification. ECG is essentially normal with exception of first degree AV block. After her first fall one month ago, she first degree AV block. After her first fall one month ago, she was told by her physician that she needs to use a cane and was told by her physician that she needs to use a cane and to rise slowly out of bed. Her daughter is very concerned to rise slowly out of bed. Her daughter is very concerned and wants a second opinion. You recommend which of the and wants a second opinion. You recommend which of the following:following:

a. Discontinuing evening dose of Lasix.a. Discontinuing evening dose of Lasix.b. Tilt-table study to diagnosis the etiology of b. Tilt-table study to diagnosis the etiology of falls and reassure her daughter.falls and reassure her daughter.c. Electrophysiologic test to assess for c. Electrophysiologic test to assess for

bradyarrhythmias.bradyarrhythmias.d. Continuous-loop event monitoring.d. Continuous-loop event monitoring.e. Physical therapy to improve gait stability.e. Physical therapy to improve gait stability.

A 16 year-old girl presents to you after a syncopal event A 16 year-old girl presents to you after a syncopal event while playing field hockey on an unusually hot day. She while playing field hockey on an unusually hot day. She was running when she developed profound lightheadedness was running when she developed profound lightheadedness just prior to losing consciousness. Upon regaining just prior to losing consciousness. Upon regaining consciousness, she was diaphoretic and confused to consciousness, she was diaphoretic and confused to surroundings. She felt nauseated for the rest of the day. surroundings. She felt nauseated for the rest of the day. She has no cardiac history and her exam is unremarkable She has no cardiac history and her exam is unremarkable except for mild orthostasis. Her EKG is normal. You except for mild orthostasis. Her EKG is normal. You recommend which of the following:recommend which of the following:

a. Genetic testing for long QT channelopathy.a. Genetic testing for long QT channelopathy.b. Continuous-loop event monitoring.b. Continuous-loop event monitoring.c. Increasing fluid intake and reassure parents.c. Increasing fluid intake and reassure parents.d. Refer to electrophysiology. d. Refer to electrophysiology. e. Tilt-table study. e. Tilt-table study.

diagnosis and management of syncope

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