Anis Rassi Jr, MD, PhD, FAHA, FACC, FACP

Scientific Director and Coordinator of Cardiology Residency Program

Anis Rassi Heart Hospital

Goiânia, GO, Brazil

41st Brazilian Congress

of Cardiac Arrhythmias

October 31 - November 2, 2024

Curitiba, PR, Brazil

No disclosures

CORRECT INTERPRETATION OF THE CHAGASICS

Trial

by Anis Rassi Jr

... highlighting its inumerous flaws

CHAGASICS TRIAL: limitations

• Study with insufficient statistical power
• Major flaws in result interpretation (spin)
• Changes in statistical analysis methodology (from ITT to modified ITT)
• Lack of external adjudication for subjective events, contrary to the original plan
• Errors in secondary outcome analysis (e.g., reduction in heart failure hospitalizations limited to the first three years, while the total FU duration of the trial was 6 years)
• Absurd mistakes in basic percentage calculations (e.g., medication use at study completion)
• Absurd errors in summing data (e.g., ATPs and ICD shocks)
• Misrepresentation or misquotation of previous studies in the discussion section
• Omission of critical information (e.g., amiodarone use in the ICD group)

​

Yet, this study was published after undergoing review by authors, co-authors, editors of JAMA Cardiology, and journal reviewers... A SHAME FOR SCIENCE!

JAMA Cardiol. Published online October 2, 2024

Am Heart J 2013;166:976-982

As the investigator who designed the CHAGASICS trial, I was involved from the study's inception to its completion. However, due to concerns about the planned presentation and interpretation of the findings, I withdrew my authorship before the manuscript was submitted to the journal. Anis Rassi Jr

CHAGASICS: Study design

Chagas heart disease

ICD

N = 550

Minimum follow-up: 3 years

Mean follow-up: 4.5 years

Amiodarone

N = 550

> 1 episode of NSVT on 24h Holter (HR > 120 bpm)

Rassi score > 10 points

Age between 18 and 75 years; NYHA I, II or III

Prospective

Multicenter

Brazilian

Open label

External event adjudication

Primary end point: all cause mortality (intention-to-treat)

R

Martino Martinelli, MD, PhD, Anis Rassi Jr, MD, PhD, José Antonio Marin-Neto, MD, PhD, Angelo Amato Vincenzo de Paola, MD, PhD, Otávio Berwanger, MD, PhD, Maurício Ibraim Scanavacca, MD, PhD, Roberto Kalil, MD, PhD, Sérgio Freitas de Siqueira, Eng, MsC, on behalf of the CHAGASICS Investigators, Brazil. Am Heart J 2013; 166: 976-982.

Primary

Prevention

323 patients

Inconclusive Study

Best example of SPIN

• Be extremely transparent about the study's limitations.
• Discuss extensively the low statistical power and its implications.
• Avoid making any claims about the efficacy (or inefficacy) of the treatments.
• Suggest how the collected data can be useful for future research.
• Discuss the lessons learned and how they can inform the design of future studies.
• Do nor omit important data

Rules for Publishing Studies Like CHAGASICS

ARJ

Design paper

Am Heart J. 2013 Dec;166(6):976-982

Publication paper

JAMA Cardiol. Published online October 2, 2024

323

39

From ITT to modified ITT!

Treatment groups not balanced in many baseline characteristics

JAMA Cardiol. Published online October 2, 2024

Publication paper

Design paper

Am Heart J. 2013 Dec;166(6):976-982

JAMA Cardiol. Published online October 2, 2024

Differences in endpoints between the design paper and the publication paper!

The primary end point is all-cause death, and enrolment will continue until 256 patients have reached this end point.

^bData on hospitalizations were only collected during 3 years of follow-up.

JAMA Cardiol. Published online October 2, 2024

Am Heart J 2013;166:976-982

ALL-CAUSE AND CV DEATHS THE SAME!!!

Never seen in any RCT: primary outcome = 6 years; secondary outcome = 3 years???

JAMA Cardiol. Published online October 2, 2024

Reduction in heart failure hospitalizations = manipulative bias

Amio

Amio

ICD increases HF DEATH but reduces HF hospitalizations – bravo!

ICD

ICD

Conclusions—Patients with chronic ischemic heart disease who are treated with either single chamber or dual-chamber

ICDs have improved survival but an increased risk of HF. The present data suggest that ICD therapy transforms sudden death risk to a subsequent HF risk. These findings should direct more attention to the prevention of HF in patients who

receive an ICD. (Circulation. 2006;113:2810-2817.)

HEART FAILURE HOSPITALIZATION

MADIT II

Perhaps the most striking mistake is the miscalculation of medication usage percentages at the end of follow-up.

All %s

are

wrong

Absurd text!!

How many patients in the ICD group started using amiodarone?

The data exists, BUT IT WAS NOT INFORMED!

CHAGASICS: Epileptiform Pearls in the Discussion

45.5 months

JAMA Cardiol. Published online October 2, 2024

SCD-HeFT trial had a follow-up ten times the duration informed by the authors totaling 45.5 months.

The phrase underlined in blue refers to the meta-analysis conducted by Rassi et al. However, the subsequent statement, underlined in red pertains to a different study, conducted by Carmo et al. UNBELIEVABLE!!!

CHAGASICS

Supplementary Online Content

Martinelli-Filho M, Marin-Neto JA, Scanavacca MI, et al. Amiodarone or implantable cardioverter-defibrillator in Chagas cardiomyopathy: the CHAGASICS randomized clinical trial. JAMA Cardiol. Published online October 2, 2024. doi:10.1001/jamacardio.2024.3169

again

again

Patient with CCC, NSVT, and

RASSI ≥ 10 points

​

​

• Your chance of being hospitalized (100% x 33%) is much higher (or was the ICD implantation performed in an outpatient setting?).
• 2.5% risk of complications related to the procedure.
• 36% chance of receiving a distressful "shock."
• The ICD will not prevent your death.
• Your chances of dying from HF, and worse, not being hospitalized before that, are much higher.
• On the other hand, if you don't receive the ICD, you'll have a more dignified death (sudden), which is what we all wish for.
• You'll have to use amiodarone anyway (not disclosed!).

If you are given a prophylactic ICD: