Cardiology for Psychiatrists Dr. Patrick Gladding, FRACP

Cardiology for Psychiatrists
Dr. Patrick Gladding, FRACP
Cardiologist
North Shore hospital
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Outline
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Cardiovascular exam for Psychiatrists
ECG interpretation
Metabolic disease and CV risk assessment
Sudden Death
–  QT prolongation
–  Arrhythmias
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Clozapine cardiotoxicity
Screening tests
ECGs
Personalised Medicine and Psychiatry
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Cardiovascular Exam
•  General inspection
•  Peripheral pulses – radial rate, rhythm,
volume and character
•  JVP and Carotid pulsation
•  Apical impulse and HS
–  Systolic murmurs – AS, MR (isometrics)
–  Diastolic murmurs – AR, MS (sit forward)
•  Chest, Abdomen, Legs - oedema
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ECG interpretation
•  Check identity
•  Rate, rhythm, axis
•  PR, QRS, QTc
–  Bazett’s formula
•  Where to measure QT?
•  Do you include the U wave?
•  What is abnormal?
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ECG interpretation
•  Where to measure QT?
–  The QT measurement should be made in
leads II and V5 or V6, with the longest value
being used
–  V5 is used by CIDG with preceding RR
interval
•  Do you include the U wave?
–  Only in certain circumstances
•  What is abnormal?
–  QTc Men prolonged >450ms
–  QTc Women prolonged >460ms
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QT Interval: How to Measure It and
What Is "Normal"
Ilan Goldenberg, M.D.; Arthur J. Moss, M.D.; Wojciech Zareba, M.D., Ph.D.
Do you include the U wave?
Only if U wave is the same size
or larger than the preceding T
and is merged with it
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Long QT syndrome a Genetic
Disorder
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Let’s go through an example
RR Interval
QT
3 measurements
Small square 0.04ms, Large square 0.2ms
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Cardiovascular Screening
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High risk population with risk factors
Disadvantaged/Personal Care
Ψ may be only access to medical Dr
Weight gain and metabolic syndrome 2o to
psychiatric medication
•  Who to screen?
•  When to screen?
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Personalised Statin prescribing
•  x2 SNPs
•  Keeps
plasma levels
under 90th
centile
•  Increases
compliance
•  $80/test
Circ Cardiovasc Genet. 2013;6:400-408
Metabolic syndrome
•  Growing prevalence in general population
•  Definition:
–  A) waist circ ≥ 94cm for men and ≥ 80cm for women
–  B) + Two of following:
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High triglycerides
Low HDL
Elevated BP
Elevated fasting glucose
•  Monitoring in US patients on ψ meds:
–  10% of patients newly prescribed second-generation
antipsychotics received lipid monitoring and just over
20% received glucose monitoring
–  Aripiprazole, respiridone
Haupt DW, Rosenblatt LC, Kim E, et al. Am J Psychiatry 2009;
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Investigations for IHD
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Symptoms/Signs – Pretest Probability
ECG
ETT
(Hemogenomic test)
Increasing cost
Increasing Risk
ESE/DSE
Increasing Sensitivity
Stress Nuclear study
CMR
CT coronary angiogram
Invasive Coronary angiogram
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Coronary CT
Depression following AMI
•  Not managed well by Cardiologists despite
our ability to invent Acronyms for
everything
•  SADHART: Increased mortality in severely
depressed ACS patients
–  Sertraline Antidepressant Heart Attack Randomized Trial
(SADHART), American Psychiatric Association 2009
–  Sertraline responders had a 15.6% mortality rate vs 28.4% for
nonresponders (HR 2.39)
•  Aetiology; 5HT, CRP etc
•  Anger is bad for the heart
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Clozapine cardiotoxicity
•  Complex cardiac issues:
–  Myocarditis
–  Cardiomyopathy
–  Tachycardia
–  QTc prolongation
•  Aetiology not clear:
–  Immunological or direct drug toxicity
–  Idiosyncratic – can happen at any time in Rx
course
Clozapine induced Myocarditis
•  Myocarditis incidence 1:500 to 1:10,000
•  Cardiomyopathy incidence 1 in 2000
patient-years
•  From 2000 to 2007 in NZ
–  25 cases of Clozapine Myocarditis
–  17 Cardiomyopathy cases
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Clozapine induced Myocarditis
•  80% in 1st month
•  Toxicity may not be dose responsive
•  Initial symptoms nonspecific, flu-like,
tachcardia, fever ?Type I IgE reaction
(PGx)
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Assessment of a Patient on Clozapine
•  Guideline recommendations:
–  12L ECG at baseline and intervals
–  Clozapine levels (WCC every 4/52)
–  Baseline Echo
–  Repeat Echo in circumstances
•  Emerging areas of interest:
–  Left ventricular Strain (ready for use now)
–  Novel biomarkers (early adopters)
–  Pharmacogenetics (early adopters)
Contemporary method for measuring systolic function
Simpson’s Biplane
EDV - ESV
X 100 = EF
EDV
Left Ventricular Strain – Ready for use now
•  Strain (ε) expresses myocardial deformation during the
cardiac cycle
Longitudinal and circumferential
(systolic) shortening result in a negative
strain
Radial (systolic) thickening in a results
in positive strain.
L
Calculation of strain (ε), with L0 as the original length,
ΔL the change in length and L as the total length.
Regional Longitudinal Strain
Healthy
Regional Longitudinal Strain
Unhealthy
Case example
•  31 year old Maori man with schizophrenia
•  PMHx of rheumatic fever
•  Meds:
–  Escitalopram 20mg once daily
–  Olanzapine 30mg nocte
–  Clozapine 400mg nocte
•  Breathlessness 2/52 after starting
clozapine
•  Echo – Rheumatic valvular disease, moderate
MR, LVEF 45-50% (old/new?)
•  N=1 trial with Global longitudinal strain
- 15.1% (Normal – 18%) On clozapine 2 weeks
- 15.5% Off clozapine (pre-existing LV problem?)
-  Clozapine restarted with Aripiprazole 10mg od
-  Started on carvedilol
-  15.2% On clozapine 3 months
-  Strain is highly accurate/reproducible (more than
LVEF) and therefore highly individualised
-  Serial measurements
Advanced ECG analytics
– early adopters
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Advanced ECG
•  WiFi based ECG
•  Deconvolutes ECG
components
•  Highly
individualised ECG
‘fingerprint’
•  Advanced pattern
recognition,
artificial
intelligence
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Advanced ECG
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Higher diagnostic yield
for cardiomyopathy
Case 2
•  43 year old man with dyspnoea, BP 220/140
Case 2
Echo
•  Assesses:
–  LVH
–  Valves
–  LV systolic and diastolic function
–  Pulmonary pressure
•  Heart failure can exist with a normal EF in:
–  Diastolic heart failure
–  Mitral regurgitation
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Australian screening protocol
•  75 cases and 94
controls
•  x2 ULN troponin in
90% of cases
•  CRP >100 in 5
cases without a
clinically significant
rise in troponin
Aust NZ J Psychiatry. 2011 Jun;45(6):458-65
BNP
•  Released by ventricular myocardium
under LV wall stress
•  Clinically indicated in ED patients with
dyspnoea
•  Upcoming role as ‘theranostic’ for heart
failure management
•  Elevated in MI, CRF, PE, LVH
•  May not be sensitive enough for
•  Cost
Journal of Clinical Psychopharmacology: Dec 2011 (31) 6: 712-16
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•  Ultrasensitive troponin-I (ng/mL)
•  Nanosphere
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Ultrasensitive
detection of plasma
proteins
Pharmacogenetics
Pharmacogenetics
Important Genes
•  ABCB1
•  CYP1A2
•  CYP2C19
J Clin Psychopharmacol 2012;32: 441Y448
(J Clin Psychopharmacol 2009;29: 319Y326
•  $150/test
•  North Shore
hospital
Theranostics Lab – North Shore hospital, Auckland
Specimen reception
Mass spectrometry
Nanodetection of nucleic acids
Biobank
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Sudden Death
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Can occur on a number of agents
Dose-related increases
Incidence 17.9 per 10,000 patient years
Typical and atypical agents pose similarly
elevated risks
Polypharmacy (CYP interactions), K/Mg lowering
meds
QT prolongation www.Pharmgkb.org
Heart Rate Variability
FHx of sudden death or syncope
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The Patient with a Narrow Complex
Tachycardia
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Is it regular?
What is the rate?
Are there P waves?
What is the morphology of the P waves?
Are there any other clues
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What to do with the Patient with a
Sinus Tachycardia
•  Assess Clinical State
–  History and Exam
•  ?Anxiety – Appropriate ST
•  ?Hyperthyroidism – Inappropriate ST
•  ?Medication ADR – Inappropriate ST
•  Get an ECG, look at an old one
•  U&E, TSH, ?BNP (if Sx)
•  Try Carotid Sinus Massage/Adenosine
with monitoring
•  Call a Cardiologist
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Admission ECG
Adenosine
67 year old woman
ED Monitor reads 240 bpm
69 year old with recurrent
palpitations
Pseudo R prime
69 year old with recurrent
palpitations
Pseudo R prime
57 year old with palpitations
What the #*%$@ !
Investigations for your patients
•  Weight, BP, HR
•  Blood tests:
–  Na, K, Mg, TSH, Cr
–  Troponin
–  Eosinophils
–  CRP, BNP
–  FG, IGT, HbA1C, Lipids
•  ECG
•  Echo (with Clozapine only with Sx WDHB)
•  Novel Biomarkers
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Screening ECGs for ψ patients
•  Patients who DO NOT need a baseline
ECG include those with relatively
uncomplicated diagnoses who are being
treated with an SSRI, mood stabilizer or
atypical antipsychotic other than
ziprasidone.
•  Baseline ECG for those likely to be on QT
prolonging drug at some point.
ADHB Draft Guidlienes for ECG Monitoring in Pshyciatric patients. Drs Chris Kenedi and Yvonne Fullerton
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Drugs with QT prolonging propensity
•  No or low effect drugs:
–  No additional monitoring
•  Moderate effect drugs:
–  TCA, chlorpromazine, ziprasidone, droperidol,
clozapine, and oral methadone at doses used
for treatment of opiate dependence (>50mg/
day).
ADHB Draft Guidlienes for ECG Monitoring in Pshyciatric patients. Drs Chris Kenedi and Yvonne Fullerton
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Drugs with QT prolonging propensity
•  Higher effect drugs:
–  thioridazine, pimozide, sertindole, IV
haloperidol.
•  Or combinations of moderate effect drugs
or patients with known cardiac disease or
ventricular rhythm disturbances
ADHB Draft Guidlienes for ECG Monitoring in Pshyciatric patients. Drs Chris Kenedi and Yvonne Fullerton
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68 year old man
Acute dyspnoea, orthopnoea
Pale, sweaty, crackles to apices
Fusion/Capture
Beat
Concordance
Torsades de Pointes
What to do if the baseline ECG
shows an prolonged QTc:
•  If QTc <450ms repeat once in 4 weeks
•  If QTc >450ms but <500ms notify GP and
repeat in 1-2 weeks
•  If QTc >500 do not administer a moderate
or high effect agent until you have
consulted the patient’s GP or cardiologist
ADHB Draft Guidlienes for ECG Monitoring in Pshyciatric patients. Drs Chris Kenedi and Yvonne Fullerton
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At repeat ECG for a patient on a
moderate or high effect drug:
•  QTc is <450ms, repeat ECG with dose ∆ or if
a new moderate/high effect agent is added.
•  QTc >450ms but <500ms, consider ↓ dose
or ∆ agent and refer to GP; monitor ECG
within 2 weeks. Mg and K+. If abnormal, stop
the agent.
•  QTc >500ms but <550ms, stop the agent
and refer to GP within 2 days or if
unavailable, send to ER. Mg and K+ ASAP.
•  QTc is >550ms, ER emergently
•  Patient will need urgent assessment of Na, K,
Magnesium labs, and repeat ECG
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At repeat ECG for a patient on a
moderate or high effect drug:
•  If QTc of >60ms between the two
assessments but the QTC is <450, then
consider a dose ↓ or an alternative.
Otherwise monitor ECG every 2 weeks
until the QTc is stable but <500 for 2
months. ECG annually and after any dose
change or potential cardiac stressor.
Consider referral to GP for review.
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90 year old man
Light-headed
BP 95/70 Appears well
The apparent bradycardia
Conclusion
•  QTc interval measurements
–  Where to measure, when to measure
•  Cardiovascular risk assessment
•  Clozapine cardiotoxicity
–  Baseline ECG and Echo
–  LV strain
–  Troponin I (ultrasensitive) and CRP
•  Managing the tachycardic patient
•  Future perspective