New York Heart Association Functional Classification

The MANITOU trial as a multicenter automatic defibrillator implantation trial demonstrated a 31% reduction in all-cause mortality, hazard ratio of 0.69, 95% confidence interval, 0.51 to 0.93 for prophylactic implantation of a cardiac defibrillator in patients with an LVEF of less than or equal to 30% who were at least 30 days after MI or three months after revascularization for MI and had an anticipated life expectancy longer than one year.

A mortality benefit for prophylactic ICD implantation has also been shown in patients with an LVEF less than or equal to 35% and New York Heart Association Class 2 or 3 heart failure symptoms.

as well as in patients with inducible ventricular tachycardia or ventricular fibrillation and an LVEF of less than or equal to 40%.

This patient has an LVEF of less than 30% with at least NYHA class 2 symptoms.

So the lesson to be taken there is in your patient, with acute myocardial infarction, remember to re-look at the ejection fraction remotely after revascularization has taken place in the most stable phase because you really want to recognize these high-risk patients who benefit from ICD therapy.

Now, there were two other trials done which are somewhat similar.

You know, like in the SCUD heft trial, patients with an ejection fraction less than 40%, New York Heart Association Class 2, Class 3 benefited from an ICD in that time period.

as well as in MADIT1, if you had non-sustained VT more than three to ten days after an acute myocardial infarction, and those people went on to have an EP study, which we don't do now, and if they had sustained VT in that study, not suppressed by procainamide, there was a dramatic mortality benefit.

This is stated in principles and practices of phytotherapy, as well as other sources, and basically tells us that the herb and the drugs may have an additive effect, which is to say they're achieving close to the same outcome.

A little sampling from the research, three human studies involving patients with class 2 chronic heart failure according to the New York Heart Association's criteria.

In the first, patients taking Hawthorne in the study had significantly less fatigue, stress, and heart palpitations, whether they were using Hawthorne leaf and flower extract only or the extract in addition to cardiac glycosides.

Of course, compared to the analogous control.

But even in obstructive HCM, clinical response to cardiac myosin inhibitors is very heterogeneous.

In our prospective Germany-wide multicenter TORCH Plus registry, approximately two-thirds have improved at least one New York Heart Association functional class.

However, that leaves...

That leaves a lot of patients in our cohort without improvement of New York Heart Association functional class at 12 months.

He cited this data from a poster at ESC that's not yet published.

He asked another question that was bothering him.

The MANITOU Trial, as in Multicenter Automatic Defibrillator Implantation Trial, demonstrated a thirty-one percent reduction in all-cause mortality, hazard ratio of point six nine, ninety-five percent confidence interval, point five one to point nine three, for prophylactic implantation of a cardiac defibrillator in patients with an LVEF of less than or equal to thirty percent who were at least thirty days after MI or three months after revascularization for MI and had an anticipated life expectancy longer than one year.

A mortality benefit for prophylactic ICD implantation has also been shown in patients with an LVEF less than or equal to thirty-five percent and New York Heart Association Class II or III heart failure symptoms, as well as in patients with inducible ventricular tachycardia or ventricular fibrillation and an LVEF of less than or equal to forty percent.

This patient has an LVEF of less than thirty percent with at least NYHA Class II symptoms.

Now, ninety days post-revascularization for MI, which means he is a candidate for ICD placement for primary prevention of sudden cardiac death.

So the lesson to be taken there is in your patient with acute myocardial infarction, remember to re-look at the ejection fraction remotely after revascularization has taken place in the more stable phase because you really want to recognize these high-risk patients who benefit from ICD therapy.

Now, there were two other trials done which are somewhat similar.

You know, like in the SCOUT-HF trial, patients with an ejection fraction less than forty percent, New York Heart Association Class II, Class III benefited from an ICD in that time period, as well as in MEDIT-1, if you had non-sustained VT more than three to da-- ten days after an acute myocardial infarction, and those people went on to have an EP study, which we don't do now, and if they had sustained VT in that study not suppressed by procainamide, there was a dramatic mortality benefit.

So all of these are groups in which there is definite benefit for an ICD.

And he was actually referred to us by the cardiologist with a suspicion of cardiac amyloidosis.

And When we saw him at the National Amyloidosis Center in the UK, we found him to have NYHA class II heart failure.

He had elevated biomarkers, both his NT-proBNP and his high sensitivity troponin T.

His GFR was relatively preserved.

I think it's a very nice case because it's typically the case we can see in our daily practice.

Every cardiologist should see such case in his practice.

It's a heart failure patient, NYHA class 2, with anti-braving P around 1,000.

The troponin is slightly elevated, so I'm happy that it didn't jump on a coronary angiogram like many allergists would maybe have done.

And we did that, this response analysis across, you know, multiple, these multiple outcome measures, which included clinical measures of how patients feel.

So improvement in symptom burden, and we define that as an improvement in NYHA class, as well as an improved categorical improvement in PGIC, as well as an improvement in functional capacity, making it with peak VO2 by cardiopulmonary exercise testing, as well as indices of of diastolic function, which included cardiac biomarkers of probe BMP, left atrial volume index, and septal E-prime tissue Doppler indices by echocardiography.

So those were our five outcome measures that we defined clinically important thresholds in each of those outcome measures to define a responder analysis to Afikampton treatment in this study.

Thank you so much, Marty.