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Hypertrophic cardiomyopathy is one of the most common causes of Sudden Cardiac Arrest in young adults. What is #HCM exactly?
A 🧵 on Hypertrophic Cardiomyopathy...1/24
We'll cover:
1) Dx criteria
2) Pathophys
3) Prevalence
4) Natural hx & Clinical clues
5) Management & NEW Tx
A 🧵 on Hypertrophic Cardiomyopathy...1/24
We'll cover:
1) Dx criteria
2) Pathophys
3) Prevalence
4) Natural hx & Clinical clues
5) Management & NEW Tx
First, what is #HCM?
Clinically diagnosed: unexplained LVH
➡️ Not accounted by pressure overload: HTN, aortic stenosis
➡️ Not accounted by infiltration: amyloid or Fabry’s
By ECHO in adults:
➡️ Ventricular wall ≥15 mm in absence of other dx
➡️ Family hx of HCM: wall ≥13 mm
/2
Clinically diagnosed: unexplained LVH
➡️ Not accounted by pressure overload: HTN, aortic stenosis
➡️ Not accounted by infiltration: amyloid or Fabry’s
By ECHO in adults:
➡️ Ventricular wall ≥15 mm in absence of other dx
➡️ Family hx of HCM: wall ≥13 mm
/2
What is the pathophys of HCM?
- Pathogenic variants in sarcomere gene
- 75% of “+ve genetic testing” have mutations:
➡️ Myosin binding protein C (MYBPC3)
➡️ Myosin binding heavy chain (MYH7)
📌 Mutations ⬆️ force & ⬇️ sarcomere relaxation
❓ 50% no identified genetic cause
/3
- Pathogenic variants in sarcomere gene
- 75% of “+ve genetic testing” have mutations:
➡️ Myosin binding protein C (MYBPC3)
➡️ Myosin binding heavy chain (MYH7)
📌 Mutations ⬆️ force & ⬇️ sarcomere relaxation
❓ 50% no identified genetic cause
/3
Moving on to Prevalence.
What is the population estimate of hypertrophic cardiomyopathy prevalence?
/4
What is the population estimate of hypertrophic cardiomyopathy prevalence?
/4
Answer: The estimate is 1:500. Around 600,000 cases in the US.
🚨 HCM is the most common monogenic heart disease
How about symptoms to look out for?
- Exertional dyspnea
- Angina
- Palpitations
- Orthopnea/PND
- Syncope or presyncope (esp in pts w/ LVOT obstruction)
/5
🚨 HCM is the most common monogenic heart disease
How about symptoms to look out for?
- Exertional dyspnea
- Angina
- Palpitations
- Orthopnea/PND
- Syncope or presyncope (esp in pts w/ LVOT obstruction)
/5
How about physical exam findings?
- Systolic murmur LSB
- Radiates to RUSB & apex
- Murmur intensify w/ ⬇️ preload (Valsalva, squat-to-stand; see @BradLander18 @mmartinezheart @ACCinTouch
- Murmur soften w/ ⬆️ afterload (passive ⬆️ LE, clench fists)
/6
- Systolic murmur LSB
- Radiates to RUSB & apex
- Murmur intensify w/ ⬇️ preload (Valsalva, squat-to-stand; see @BradLander18 @mmartinezheart @ACCinTouch
- Murmur soften w/ ⬆️ afterload (passive ⬆️ LE, clench fists)
/6
https://twitter.com/BradLander18/status/1632131299400982528
What is the natural history of HCM?
➡️ Most are asymptomatic (~60%)
➡️ Cumulative burden: those dx earlier, ⬆️ events
🚨 Most common dx burden:🫀Failure & Afib
➡️ LVOT: systolic anterior motion of MV & MR
🔑 Outcomes most prevalent after 50y
/7
➡️ Most are asymptomatic (~60%)
➡️ Cumulative burden: those dx earlier, ⬆️ events
🚨 Most common dx burden:🫀Failure & Afib
➡️ LVOT: systolic anterior motion of MV & MR
🔑 Outcomes most prevalent after 50y
/7
What EF defines LV w/ systolic dysfunction or “burned-out” phase in HCM?
/8
/8
Answer: <50%
HCM is normally associated w/ a hyperdynamic LV...so when EF <50%, end-stage HCM has a poor prognosis. Prevalence ~8%.
Natural history of "burned-out" HCM:
🚨 75% experienced adverse event
☠️ 35% death/transplant/LVAD
➡️ At median time 8.4 yrs from recognition
/9
HCM is normally associated w/ a hyperdynamic LV...so when EF <50%, end-stage HCM has a poor prognosis. Prevalence ~8%.
Natural history of "burned-out" HCM:
🚨 75% experienced adverse event
☠️ 35% death/transplant/LVAD
➡️ At median time 8.4 yrs from recognition
/9
Moving on to types of HCM:
1) Non-obstructive HCM (nHCM) ~1/3 of pts
2) Obstructive HCM (oHCM) ~2/3 of pts
➡️ gradients at rest or exercise >30 mmHg
This is an important distinction as this will guide management discussed later.
/10
1) Non-obstructive HCM (nHCM) ~1/3 of pts
2) Obstructive HCM (oHCM) ~2/3 of pts
➡️ gradients at rest or exercise >30 mmHg
This is an important distinction as this will guide management discussed later.
/10
What imaging/tests to order to distinguish nHCM & oHCM?
➡️ Exercise ECHO: provokable gradients
➡️ CMR: identify SAM, LVOT
➡️ LHC: +ve Brockenborough-Braunwald-Morrow sign (1961)
+ve sign: s/p PVC induction⚡️, LV SBP ⬆️ & aortic pulse pressure ⬇️ (see below Fig 2 vs in AS)
/11
➡️ Exercise ECHO: provokable gradients
➡️ CMR: identify SAM, LVOT
➡️ LHC: +ve Brockenborough-Braunwald-Morrow sign (1961)
+ve sign: s/p PVC induction⚡️, LV SBP ⬆️ & aortic pulse pressure ⬇️ (see below Fig 2 vs in AS)
/11
Moving on to management.
Symptoms drive management.
No symptoms? No need for therapy.
For patients with oHCM and symptoms, what is the first line treatment?
/12
Symptoms drive management.
No symptoms? No need for therapy.
For patients with oHCM and symptoms, what is the first line treatment?
/12
A: Metoprolol
2020 ACC/AHA Guidelines (oHCM + symp):
✅ BB 1st-line
✅ Non-dihydropyrid CCBs (if ineffective)
✅ Disopyramide or SRT (symp persist)
Optimize pre + after-load:
⚠️ Cautious w/ diuretics
⛔️ Avoid vasodilators
❗️ Treat tachycardia
✅ IV phenylephrine for acute hypo
2020 ACC/AHA Guidelines (oHCM + symp):
✅ BB 1st-line
✅ Non-dihydropyrid CCBs (if ineffective)
✅ Disopyramide or SRT (symp persist)
Optimize pre + after-load:
⚠️ Cautious w/ diuretics
⛔️ Avoid vasodilators
❗️ Treat tachycardia
✅ IV phenylephrine for acute hypo
Moving on to invasive treatment of symptomatic patients w/ oHCM.
What are the indications for septal reduction therapy? /14
What are the indications for septal reduction therapy? /14
A: Both.
Symptoms impair QoL despite medical therapy.
Usually NYHA functional class III or IV.
2 options:
1⃣ Surgical Myectomy
2⃣ Septal Ablation
Choice depends:
➡️ suitable coronary anatomy (septal perf. artery for ablation)
➡️ extensive LVH or MV dx (favors myectomy)
/15
Symptoms impair QoL despite medical therapy.
Usually NYHA functional class III or IV.
2 options:
1⃣ Surgical Myectomy
2⃣ Septal Ablation
Choice depends:
➡️ suitable coronary anatomy (septal perf. artery for ablation)
➡️ extensive LVH or MV dx (favors myectomy)
/15
How about for patients with end-stage non-obstructive HCM (nHCM)?
A pt w. nHCM + afib p/w volume overload. LVEF <50%.
What changes in management are you considering? /16
A pt w. nHCM + afib p/w volume overload. LVEF <50%.
What changes in management are you considering? /16
A:
✅ Anticoagulation for ALL HCM pts w/ afib
✅ Consider GDMT (ARNi/ACEi/ARB, MRA)
🚫 Stop -ve inotropic agents (verapamil, diltiazem, disopyramide) unless for rate-control AF
✅ Consider ICD for primary prevention
⚠️ RCTs excluded HCM & HF pts; consider on a case-by-case /17
✅ Anticoagulation for ALL HCM pts w/ afib
✅ Consider GDMT (ARNi/ACEi/ARB, MRA)
🚫 Stop -ve inotropic agents (verapamil, diltiazem, disopyramide) unless for rate-control AF
✅ Consider ICD for primary prevention
⚠️ RCTs excluded HCM & HF pts; consider on a case-by-case /17
Moving on to risk stratification for sudden cardiac death.
Which HCM patient below should be considered for an ICD? /18
Which HCM patient below should be considered for an ICD? /18
Answer: All of the above.
All are Class 2A recommendations ("ICD is reasonable") from the ACC/AHA 2020 HCM Guidelines.
If patient has had a prior event (SCD, VF, Sustained VT)
✅ Class 1: ICD recommended
/19
All are Class 2A recommendations ("ICD is reasonable") from the ACC/AHA 2020 HCM Guidelines.
If patient has had a prior event (SCD, VF, Sustained VT)
✅ Class 1: ICD recommended
/19
How about family screening and genetic testing?
A 35 yo man is diagnosed with genetic HCM. You recommend genetic testing and surveillance for his 12 yo son. How often should his son receive surveillance screening? /20
A 35 yo man is diagnosed with genetic HCM. You recommend genetic testing and surveillance for his 12 yo son. How often should his son receive surveillance screening? /20
Answer: Every 1-2 yrs
There is an age-dependent penetrance to HCM. Serial screening is required:
✅ Physical exam
✅ ECHO
✅ ECG
The younger the age of diagnosis, the more frequent the surveillance for 1st degree relatives.
For pt's 50 yo sister. Surveillance every 3-5 yrs
There is an age-dependent penetrance to HCM. Serial screening is required:
✅ Physical exam
✅ ECHO
✅ ECG
The younger the age of diagnosis, the more frequent the surveillance for 1st degree relatives.
For pt's 50 yo sister. Surveillance every 3-5 yrs
How about sports & exercising with HCM?
✅ Mild-mod intensity recreational exercise is recommended
Recently (May 2023), LIVE-HCM Study @JAMACardio showed vigorous exercise in pts w/ HCM did not ⬆️ mortality or ⬆️ incidence of ventric. arrhythmias
Shared decision w/ pts 🔑
/22
✅ Mild-mod intensity recreational exercise is recommended
Recently (May 2023), LIVE-HCM Study @JAMACardio showed vigorous exercise in pts w/ HCM did not ⬆️ mortality or ⬆️ incidence of ventric. arrhythmias
Shared decision w/ pts 🔑
/22
Finally, how about disease-modifying therapy?
In April 2022, @US_FDA approved the only current therapy for symptomatic oHCM:
✅ Mavacamtem: cardiac myosin inhibitor
Dr. Braunwald 1st described "hypertrophic subaortic stenosis” in 1964, elaborates here:
In April 2022, @US_FDA approved the only current therapy for symptomatic oHCM:
✅ Mavacamtem: cardiac myosin inhibitor
Dr. Braunwald 1st described "hypertrophic subaortic stenosis” in 1964, elaborates here:
https://twitter.com/escardio/status/1613937527546867712
The approval was based on:
EXPLORER-HCM:
➡️ Mavacamten vs placebo ⬆️ exercise capacity & health status in oHCM (LVOT>50 mmHg)
VALOR-HCM:
➡️ Mavacamten ⬇️ eligibity for needing SRT vs placebo among oHCM (considering SRT + on max tx)
Aficamten (another CMI) is promising...
/24
EXPLORER-HCM:
➡️ Mavacamten vs placebo ⬆️ exercise capacity & health status in oHCM (LVOT>50 mmHg)
VALOR-HCM:
➡️ Mavacamten ⬇️ eligibity for needing SRT vs placebo among oHCM (considering SRT + on max tx)
Aficamten (another CMI) is promising...
/24
🚨 Takeaways 🚨
📌 Key diagnostic feature: unexplained LVH
📌 Mgmt for symptoms depends on pathophys (oHCM, nHCM, restrictive, LVSD)
📌 Importance of family surveillance + genetic testing
📌NEW + other exciting disease-modifying txs to come...
/Fin
📌 Key diagnostic feature: unexplained LVH
📌 Mgmt for symptoms depends on pathophys (oHCM, nHCM, restrictive, LVSD)
📌 Importance of family surveillance + genetic testing
📌NEW + other exciting disease-modifying txs to come...
/Fin
That was a lot. Thanks for following along!
And thank you to everyone who has played a part in revolutionizing/raising awareness on #HCM
@MasriAhmad @MKIttlesonMD @srihariNaiduMD @ReshadGaranMD @UTahirMD @MJAckermanMDPhD @MartinMaronMD @LindenfeldJoann
And thank you to everyone who has played a part in revolutionizing/raising awareness on #HCM
@MasriAhmad @MKIttlesonMD @srihariNaiduMD @ReshadGaranMD @UTahirMD @MJAckermanMDPhD @MartinMaronMD @LindenfeldJoann
My main source in addition to links in thread:
@YevgeniyBr @HanCardiomd @AHajduczok @akhadilkarMD @DrJohnMcP @VUMCMedicineRes @vumccardsfit @HollyGHeartMedahajournals.org/doi/10.1161/CI…
@YevgeniyBr @HanCardiomd @AHajduczok @akhadilkarMD @DrJohnMcP @VUMCMedicineRes @vumccardsfit @HollyGHeartMedahajournals.org/doi/10.1161/CI…
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