Thread by @EduQuintanaCVS

Very interesting results from Phase 3 #EXPLORER-HCM clinical trial: #mavacamten vs placebo for symptomatic #HOCM at #ESCCongress2020 . A new tool is given consideration for patients with obstructive HCM. The authors have to be congratulated. Excellent presentation by I. Olivotto

Is this the beginning of a dream in the treatment of HCM? Will it challenge and replace invasive septal reduction therapies by achieving sustained resolution of obstruction, complete symptom relief, neutralize risk of SCD without side effects? Let's deep into the study

The primary endpoint involved NYHA and VO2 consumption. The definition of responders requires minimal changes in objective exercise capacity and a drop of only one class. Despite this, only 20% of treated patients fulfilled it at 30 weeks

Interesting to see that even 7,8% of patients receiving placebo could be considered responders. Engagement in a clinical trial with increased medical supervision may produce by itself improvement one can guess.

We know that improvement after septal reduction therapy is larger:

Let's look at the secondary endopoints:

- in terms of symptom improvement (NYHA) it has to be noted that 35% of treated patients did not improve even 1 class

When looking at the physiology #Mavacamten:
- 25% did not achieve resolution of obstruction below thresholds for SRT
- 43% express obstructive physiology with gradients beyond 30 mmHg (known to be associated with detrimental outcomes)
- Complete should be no gradient at all

The safety profile of the drug at 30 weeks has been acceptable under intensive echocardiographic surveillance. Most frequent significant adverse events reported are drops in LVEF. Careful titration and follow up

From a potentially biased surgical perspective the interpretation of the results of this trial:
- the drug effect beats other meds and will move the field widely
- show the potential to temporarily palliate obstruction and improve symptoms
- persistence of obstruction is high

- improvement in O2 consumption ia suboptimal in a young study population (58 y of mean age)
- unclear whether we can give this medication for a lifetime
- potential LV dysfunction requiring titration or discontinuation
- may help poor candidates to invasive interventions

- may lead to acceptance of inferior outcomes for HOCM patients in an attempt to avoid invasive procedures
- on the other side it may help patients where invasive operative expertise is not available
- may open the door to treat diastolic dysfunction in HCM

Eager to know more!

Just a reminder that septal #myectomy is a proven therapy for more than 50 y. A low risk operation with the potential to:

- offer complete resolution of obstruction and mitral regurgitation
- return patients to normal lifestyle with potential normal life span

- minimizes arrhythmia risk (sudden death-related obstruction)
- able to deal with concomitant heart conditions
- most patients do not require medications (bbloc)

..but still is an operation.

The day will come when HCM patients will not require invasive procedures.