Tips for Decision Making When Faced with Cardiac
Disease:When Should Therapy
Start?
Dan Ohad, DVM, PhD, Diplomate ACVIM
(Cardiology)
האוניברסיטאי מיסודה של האוניברסיטה העבריתהוטרינריבית החולי ם . בית ד ג ן–הק ר יה החקלאית
03-9688533) שעות24( חי רום 03-9688525 – פקס 03-9688588 -טלפון לקביעת תורי ם
Mechanisms of SomeCardiac Drugs
ACE-I (↓Ald, ↓AT-II) ↓Preload, ↓Afterload
Diuretics (↓Na+, ↓Ald) ↓Preload
Digoxin A strong (-)chronotrope,
a weak (+)inotrope
Theo/Aminophylline ↑Φ ofBronchioli
“AAD”↑↓Anti/Pro-arrhythmic?
Heart Disease ≠ Heart Failure
• Myocardial Failure ≠ CongestiveHeart Failure
• Tx for either oneeither one (e.g. Myocardial Failure 20 to DCM, vs. fluid retention 20 to CHF): as soon as it as soon as it is diagnosedis diagnosed
• Treat non-congestive cardiac symptoms when identified (even when no CHF is present)
• The biggest dilemma: Should asymptomatic heart disease be treated?
In Moderate-to-Severe Chronic CHF, Definitely Treat
• Benazepril - ↓62% mortality over 56 days in dogs with CHF; Enalapril -↑survival by >100% (the “BENCH” Study: J Vet Cardiol, 1:7-18, 1999; the “LIVE”Study: JAVMA 213(11):1573-7, 1998 )
ACE-Iinhibitors indicated in systolic heart failure, when tolerated.
• Other cardiac agents indicated PRN
• Side effects (e.g. hypotension =>azotemia => GI signs): rare and result from combination-Tx (“polypharmacy”) responsive to ∆
±
ModerateCHF :
*ACE-I (BID)(± low dose ?Spironolactone)
*Fusid(moderatedose)
Digoxin
C.S. w/oCHF:
*ACE-I(SID)
*Fusid( lowdose)
±Digoxin
Severe CHF :
*ACE-I (BID)+Nitrate+Amlodipineor Hydralazine
*Fusid(highdose)+Thiazide
+PotassiumSparing Diuretic
Digoxin
?Vesnarinone?Pimobendan
RefractoryCHF :
Fusid IV, Oxygen, No Stress
Nitroprusside Dobutamine IV;±Dopamine IV, Amrinone or Milrinone IV
*Fusid (dogs, cats, horses) & Enalapril (dogs) are the only ones approved
or
ACE-I Are the First Line of Defense:
When Already in CHF:
Daily Resting Respiratory Rate
10
35
60
0 5 10 15 20 25 30
Day of Month
RR
(cyc
les/
min
)
Move between stages based on trends of ∆ in RR
Why is it Safe to Use Digitalis Glycosides?
Efficacy
Toxicity
Dose (mg/kg)
Is it Necessary to “Prophylactically” Treat Asymptomatic Patients?
• Chronic Valve Dz is a slowly progressing disease
• After developing murmurs, dogs may remain asymptomatic without any therapy for many years.
• “Prophylactic” therapy for asymptomatic dogs involves treatment over several years (↑$$ / ?↑S.E.)
Mechanisms of Some Cardiac Drugs
ACE-I ↓Preload, ↓Afterload
Diuretics (↓Na+, ↓Ald) ↓Preload
Digoxin A strong (-)chronotrope,
a weak (+)inotrope
Theo/Aminophylline ↑Φ ofBronchioli
“AAD”↑↓Anti/Pro-arrhythmic?
(↓Ald, ↓AT-II)
Should I Use ACE-I in Compensated Heart Dz, Prior
to the Onset of CHF?
• This “should” be beneficial if the disease has already ↑RAAS* (which is ↓by ACE-I).
• ↓8%-28% mortality in mild / asymptomatic heart failure and early activation of the RAAS in humanNON-valvular Dz
• BUT: Tx in most of these cases: polypharmacy; some severe pts included (~↑estimated impact)
* [“RAAS” = “Renin-Angiotensin-Aldosterone System”]
ACE-I Prior to the Onset of CHF? (Cont’)
• ↑survival (601 vs. 314 days) in asymptomatic ("occult") male (>>female) Doberman DCM with ACE-I (O'Grady MR et al, Abst, J. Vet. Int. Med. 11:138, 1997)
• ↑RAAS in some mildly MR-affected CKCS dogs, but many fall within the normal range
• In these MR-dogs, ↓RAAS from 4.6 months prior to decompensation RAAS is not activated at the time of CHF onset
Traditional Recommendations for Tx of
Asymptomatic Mitral Regurgitation:
“Rely on radiographicprogression”
• Start conservative ACE-I when LAE
•↑Aggressiveness when LVE (± RVE)
• Add Digoxin & Furosemide when symptomatic CHF (if echo available, use also %SF).
1. LAE
2. LVE
3. LVE & RVE
4. PE (Interstitial)
5. PE (Alveolar)
Radiographic Progression of MR
CHF:
Reasons for TraditionallyRecommended Tx for Asymptomatic Mitral
Regurgitation
• This strategy might have stemmed out of some pressure from drug-representatives and from RDVMs interested in clear guidelines
• Due to small sample sizes in Vet. Med., it is based on theory / clinical impression / speculation & extrapolation from human pts, rather than on hard evidence.
Human Clinical Trials Consist of Thousands of Patients; Veterinary Studies
Look at < Tens - Hundreds:
• “IMPROVE” Study n = 58J Vet Intern Med. 9(4):234-42, 1995
• “LIVE” Study n = 110
JAVMA 213(11):1573-7, 1998
• “BENCH” Study n = 70J Vet Cardiol, 1:7-18, 1999
• “COVE” Study n = 211
J Vet Int Med 9(4):243-52, 1995
• “VETPROOF” Study n = 139
(Abst) J Vet Intern Med 13:246, 1999• “SVEP” Study
n = 229
(Survival when already in CHF)
(Prevention of CHF)
The Scandinavian Veterinary Enalapril Prevention study:
229 Cavalier King Charles Dogs
J Vet Intern Med 2002;16(1):80-8
The “SVEP” Study of Spontaneous MR in 229
CKCS Dogs (x 4.5 years)• Placebo: n
= 113• Onset of CHF:
1130 d• # of CHF cases: 50
• Enalapril 0.38 mg/kg: n = 116
• Onset of CHF: 1150 d
• # of CHF cases: 48
• ∆ (1.7%) was statisticallyinsignificant
(P=0.8 as per a Kaplan-Meyer analysis)
• “Survival plots” of the 2 groups tracked almost perfectly over time (see next slide)
• It would take ~1200 dogs to show a ∆ of ~40% in this setting: Clinical significanceis questionable at best
≠
Long term Enalapril in asymptomatic dogs did not delay the onset of CHF, regardless of cardiomegaly or dose
% of Dogs Remaining in Study (Until Reaching CHF)
P = non significant
Conclusions Re Onset of ACE-I Tx
• When data available, a drug should be used because it DOES work, NOTbecause it “SHOULD” work
• Okay to start ACE-I ± Dig in asymptomatic DCM
• Not yet justifiable to start Tx in asymptomatic MR
• ↑Aggressiveness (dose / frequency /# of drugs) along with ↑severity /progression of Dz (e.g. RR)
• Know when to refer a case to a specialist
The Ideal Referral Process
The need is recognized by RDVM & client
Reason for referral, clinical info, & expectationsare communicated to specialist
Specialist evaluates patient
Specialist communicatesfindings & recommendations to client & RDVM
Client, RDVM, and specialist decide about future care as a team
1
2
3
5
4
Problems can occur at each of these steps!
Specialists are an extension of your clinic!
They can:–Confirm your Dx –Narrow your DDx-list
–Determine the etiology for CHF
–Provide recommendations for Tx & follow-up visits
–Help with prognostication
Refer when Facing:
• A diagnostic challenge with a clinicallymeaningful dilemma (not any “teaching case”)
• A case refractory to Tx
• A case containing conflicting data.
• An arrhythmia-case that is complicating case-Mngmnt
• A client who wants a second opinion.
Refer when You Need to:
• Confirm your Dx and / or Tx approach in a specific case
• Reduce interpretation error rates.
• Improve the image of your practice.
Whenever you feel you need to
“Know When to Refer”(Cont’)
• Refer BEFORE terminal Dz-stages, when something can still be done for the patient
• Avoid referring following numerous “shotgun”-Tx attempts, especially if the Dx is not final
• NOT every cardiac case should be referred
Know How to Refer:It’s All About
Communication & Expectation-
Management!
• What you consider as inconvenient or too expensive is not always so to your client
• Eventually many clients may expect a referral, being familiar with the concept from human medicine
• Mutual respect & effective communication between parties is key
Know How to Refer (Cont’):
Communicate the following:• Problem(s) / Client Complaint(s)• Relevant test results (not copy of
whole medical record)
• Current medications (dose & frequency)
• Response to these drugs• Previous drugs that are
discontinued and why• What client has been told
about this referral (not “this is a teaching case” at “no charge”)
• Your own expectations from specialist
נ/ ז _____:מ שקל___________:גזע____ :סוג ______ ר"י ד"הופנה ע_____ :גיל
וממ צאי בדי קה פי ז יקל י תהי סטוריה ר לוונטית ל מ ערכת ה לב וכל י הדם
:מבדל ת / אבחנה משוע רת / סיבת ההפניה
________________________________________________________________________
:תצפיות הב על י ם ע י יפות כללית יר ידה ב סבול ת מא מץ ) ופרודוקטי ב ילח/ י בש ( ש י עול
אנורקסיה חו סר מנו חה לילי אורטופנאה טכ יפנאהדיספנאה טכ יקרדיה
Pu / Pd מ שקל יתר קכקסיה ות / עוו ית אבוד הכרהפתע- קריסת ____ ___________________________________________: אחר הג דלת הבטן/התרחבות
:ממצאי בדיקה פיזיקלית (QAR*) ערנות שקטה)∗(BAR גבוהות : רמת הערנות ו הפעילות
דליריו ם ת ש י שות / רביצה / בינונ י / קל (משקל - תת ) ח מור/ ב ינוני / קל ( מ שקל יתר תקין :מצב גופני
לדקה_____ : במנוחהקצב נש י מות אסצי ט ס )ח מור י ב שות לחות:ריר יות
"מוזרקות "ח יו ורות כח ולות/ אפורות בצב ע תקין
בצב ע אדום עזצהובות מה יר מ יד י אי ט י מ ידי במה ירות תקינה:(CRT)מלו י ני מ י ח וזר
) וחזק מהצפוי( הולם חלש חזק ומלאbpm__:דופקנמוש -בלתי
“Pulsus Parvus & Tardus” Jugular Pulse “Pulsus Paradoxus” חוקיות ללאסדירות - אי "מרו חקי ם", חלש י ם חזקים ו ברור י ם :S1(S &2(קולות הלב
-פאן הולוס יס טול י ת___מתוך ___ דרגה :ות / אוושהס י ס טול ית
באמצ ע הס י ס טולה בתח ילת ה ס י ס טולה דיאס טול ית
הלב מ ש מאל - בב ס י ס מ ש מאלהלב- בח ודהלב מ י מ ין- בח וד
) בקו האמצע/ מ ש מאל / מ י מ ין (ס טרנאלית - פארא הצווארי/באזור עורק
Crescendo-Decrescendo (“Diamond-Shaped” = “Ejection Murmur”)Band-Shaped (“Plateau” = “Blowing”) Decrescendo
נעדר/ מזדמן / מת מ יד :(Gallop) ”מקצב דהירה"מפו צל 2S קול"קליק סי ס ט ולי ":קולות לב אחרי ם
ב כל האונות) וס יקולאריי ם-ברו נכו( תקינים :קולות ראה(Wheezes)"שריקות" / "צפצופים "
(Crackles / Rhonchi) קרפיטצ יה ש ל נאדיות :)אונות/ אונה ( מ יקום קולות שא ינם תקינ י ם -
/ אמצע י ת / קדמית ) / (י מנ ית/ ש מאלית () ב טנית/ גב ית ) / (אחור ית
ס וף ה נש יפה/ שא יפה : ע יתו י הופעת ם ב מ חזור הנשי מה-
∗ BAR = Bright, alert & responsive QAR = Quiet, alert & responsive
The Specialist Will:
• Spend more time “milking” relevant Hx from owner
• Examine & perform additional tests as needed
• Explain Dz, Monitoring processes, Tx (including expected response & S.E.),Prognosis, and Follow-up recommendations to owner, orally & in writing
• Often will recommend more frequent monitoring & follow-up visits at RDVM’s
• Communicate the above to RDVM• No major procedures should be
performed prior to discussion with RDVM
The Specialist Should Not:
• “Bad-mouth” the RDVM (or let other personnel in his facility do that)
• Agree to become the primary-care provider of the patient
• Practice a discipline outside his/her area of expertise
• Accept a case w/o a referral,unless has already seen this patient before will also contact RDVM as if a referral
Anti-Arrhythmic Therapy:
VPCs / VT
Types & Frequency of Arrhythmia and Conduction Disturbances in 95 Dogs Screened From 3000
Consecutive Cases
• VPCs43
• APCs14
• Atrial Fib.13
• 10 AVB12
• 20 AVB12
• VT 8
• PAT3
• Atrial Flutter2
• 30 AVB2
• R-BBB2
• L-BBB2
Total: 113
Which of These 2 VPC Cases Needs Tx More?
(http://www.isrvma.org/article/cardiac2.htm)
The QRSComplex
• It's duration is measured from the onset to the offset of the QRS-complex• Represents ventricular depolarization; ( => Has to be followed by a T-wave)
• Can be prolonged (widened) with:
1. ? Myocardial hypertrophy2. ? Hyperkalemia
3. Ventricular Premature Complexes / VT
4. Ventricular Escape Complexes / Rhythms
5. Bundle Branch Block (R-BBB or L-BBB)
The one thing in common to # 3-5, is slowtrans-myocardial conduction, on a cell-to-cell basis (≠ via the fast conducting His-Purkinje system).
T
Ventricular PrematureComplex (VPC): [The most common arrhythmia]
QRS
T
TTp
QRS
T
TTp
Ventricular PrematureComplex (VPC): [The most common arrhythmia]
QRS
T
TTp
Ventricular Tachycardia (VT) (≈a series of VPCs)
["SMVT" vs. "NSMVT" vs. "SPMVT" vs. "NSPMVT"]
Ventricular Escape Complex / Rhythm
(note the long pauses and the dissociation from P-waves)
Bundle Branch Block (note the constant association with P waves)
Ventricular Escape Complex / Rhythm (note the long pauses and the dissociation
from P-waves)
Bundle Branch Block (note the constant association with P waves)
Bundle Branch Block
(≠)
VPCs (the most commonarrhythmia)
(≠)
"Fusion" between Sinus & Ventricular-Escape Mo
TT
P T
When Treating: Do Not Confuse VPCs with Ventricular Escape Complexes
(http://www.isrvma.org/cardiac.htm)
Hemodynamic Effect of APCs ("Pulse Deficits")
Hemodynamic Effects of AF & One VPC ("Pulse D
To Treat, Or Not To Treat?• Depending on rate & duration, rhythm disorders
may have a fundamental effect on the efficiency of the heart as a pump (especially when efficiency is already hampered).
• Many arrhythmias are transient or too sporadic to even compromise hemodynamics, let alone threaten life.
• Cardiac rhythm is easily monitorable arrhythmias are only seldom overlooked, and often distract us from "real" issues.
• Mere recognition does not automatically justify intervention.
• First, use the Hx & PE to determine whether BP & perfusion are compromised. Treat the Dz before you treat the rhythm, unless this is a true emergency .
When You Decide AAD-Tx is Warranted:
If this is not an emergency, Do not use it before:
• Tx of CHF, if present. (when chronicAAD-Tx is considered)
• D/C, followed by ↓ of concurrent, offending drugs (e.g. Digoxin).
• Correction of Acid/Base Imbalance
• Correction of Electrolyte Imbalance (when either acute or chronic AAD-Tx
is considered)
• Correction of Hypoxia
Use Reason, Not Dogma, For Tx of Ventricular
Arrhythmia• VPCs often raise non-proportional concerns
and trigger AAD-Tx based on both unrealistic assessment of risk, and unrealistic expectation for benefit.
• This bias is reinforced by the ease of VPC recognition, by many textbooks, & by extrapolation from human CAD.
• Although SVTs tend to be viewed more tolerantly, in veterinary pts they usually attest to a more severely compromised cardiac function than ventricular arrhythmias do.
Chronic AAD-Tx
• SCD may occur in some DCM or SAS or "Boxer dog Cardiomyopathy" cases that also manifest frequent VPCs, and may warrant AAD-Tx. Tx of the underlying Dz in these high-risk pts should still precede chronic AAD-Tx.
• The merit of chronic AAD-Tx should be periodically challenged by empirical discontinuation.
• ↓ in the # of VPCs can only attest to a pharmacological effect, not to a clinically relevant benefit.
• AAD-Tx should be continued only if some ↓of C.S. is seen.
Chronic AAD-Tx for SCD-Prevention is Ineffective!
• An arrhythmia such as VF can be the manifestation of death, rather than the reason for it. AAD may not necessarily prevent this from happening.
• Although cardiac patients at the greatest risk of dying due to arrhythmia are identifiable, AAD-Tx can often not prevent "arrhythmogenic death". It may actually (sometimes) cause it.
Do not be tempted to use AAD to prevent"sudden, arrhythmogenic death".
• Use AAD to control hypotension / fainting / episodic weakness / intractable or acutely exacerbated heart failure, if these are clearly arrhythmia-related (e.g. based on sustained, severe ↑ or ↓ of HR).
Acute AAD-Tx of "Traumatic Myocarditis"
• Often diagnosed with HBC / GDV / Extra-cardiac Dz.
• Traumatic "Myocarditis" is a speculation & a misconception. There is no ventricular trauma with GDV or splenic neoplasia, & no evidence for myocardial Dz even when trauma *is* present.
• The typical "Accelerated Idioventricular Rhythm" is only ≤ 170/min and does not compromise LV-filling or SV or CO, unless VPCs are both very premature & frequent, and/or independent organic heart Dz is present.
• It is usually self-limiting, and is reversible despite of, not thanks to AAD-Tx. AAD-Tx does not improve survival of GDV cases.
Idioventricular Rhythm
• Typically seen with extra-cardiac Dz (e.g. "Traumatic Myocarditis"...)
• Usually faster than a ventricular escape rhythm, but not much faster than the background NSR 2 foci "compete" over setting the pace
• RSA-driven transition often shows fusion morphology
• Typically hemodynamically stable & self-limiting
Lack of Hemodynamic Effects of an Accelerated(Idio)ventricular Rhythm-
NO NEED FOR TREATMENT!!!
HR~120/min
(HR=260/minVentricularTachycardia:
Be Methodological
• Determine the real (cardiac or extra-cardiac) underlying problem, and establish a cause & effect relationship between ventricular arrhythmia & C.S.
• Use other Tx (e.g. O2-Tx / volume expansion / volume reduction / blood transfusion / anti-CHF-Tx) as needed, prior to acute AAD-Tx, unless arrhythmia directly impairs ventricular function. Otherwise AAD-Tx will fail.
• Once you decide to use AAD-Tx, be fully committed to it: empiricism with drug choice & methodical dose-titration are often inevitable. Don't give up before your options are exhausted.
Again, When AAD-Tx *IS*Warranted :
If possible, Do not use it before:
• Tx of CHF, if present.
• D/C, followed by ↓ of concurrent, offending drugs (e.g. Digoxin).
• Correction of Acid/Base Imbalance
• Correction of Electrolyte Imbalance (e.g. correct ↓K+ or ↓Mg++)
• Correction of Hypoxia
!תוד ה
האוניברסיטאי מיסודה של האוניברסיטה העבריתהוטרינריבית החולי ם . בית ד ג ן–הק ר יה החקלאית
03-9688533) שעות24( חי רום 03-9688525 – פקס 03-9688588 -טלפון לקביעת תורי ם