Medical Director, Advanced Heart Failure Program @MedStarHealth @GUMedicine
Washington, DC
Joined April 2009
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Farooq Sheikh retweeted
🔥 Our thoughts on all things CARDIO-TTRansform
A lot of nuance to unpack here, and hopefully more analyses of this study will shed light on the monotherapy vs combination therapy subgroups.
Attached is our reproduction of the all cause mortality curves for the monotherapy populations across all 4 ATTR-CM trials (Panel A) and the overall study populations (Panel B).
Good news for patients is that we keep creeping closer and closer to the age expected survival in the modern era!
🆕CARDIO-TTRansform, the largest treatment trial yet in ATTR-CM (1,432 patients), missed its primary endpoint: rate ratio 0.89 (95% CI 0.73 to 1.09).
But baseline stabilizer use modified the effect of eplontersen (P for interaction = .017):
• Not on a stabilizer at baseline: RR 0.71 (95% CI 0.54 to 0.93), a nominally 29% lower rate of CV death and recurrent CV events
• Already on a stabilizer: RR 1.14 (95% CI 0.85 to 1.53)
In a Critical Appraisal, @HamzahAliMD, Andrew A. Girard, and @BrettSperryMD argue this reflects the limited incremental benefit of adding a silencer to a stabilizer, not an ineffective drug.
They also unpack why percent TTR knockdown is hard to compare across silencers and reflect on where combination stabilizer and silencer therapy goes from here.
opensourcecardiology.org/doi…
Farooq Sheikh retweeted
🆕CARDIO-TTRansform, the largest treatment trial yet in ATTR-CM (1,432 patients), missed its primary endpoint: rate ratio 0.89 (95% CI 0.73 to 1.09).
But baseline stabilizer use modified the effect of eplontersen (P for interaction = .017):
• Not on a stabilizer at baseline: RR 0.71 (95% CI 0.54 to 0.93), a nominally 29% lower rate of CV death and recurrent CV events
• Already on a stabilizer: RR 1.14 (95% CI 0.85 to 1.53)
In a Critical Appraisal, @HamzahAliMD, Andrew A. Girard, and @BrettSperryMD argue this reflects the limited incremental benefit of adding a silencer to a stabilizer, not an ineffective drug.
They also unpack why percent TTR knockdown is hard to compare across silencers and reflect on where combination stabilizer and silencer therapy goes from here.
opensourcecardiology.org/doi…
Farooq Sheikh retweeted
Steve Kerr says Roger Federer taught his Warriors team the secret to sustained success wasn’t outworking everyone, it was building a life around your craft you never want to escape from
“I’ll tell you a great story about Roger Federer. We were playing in China with the Warriors in 2017. Roger was in Shanghai for the Masters tournament, so we invited him to come speak to the team.”
“Draymond Green asked him, ‘How do you sustain success? How have you managed to win majors 20 years after you first won one?’ Everyone was expecting him to say, ‘I work harder than everybody,’ the will, all the clichés.”
“Roger Federer says, ‘I get up every morning and I make breakfast for my kids. Then I take them to school and drop them off. Then I go practice tennis for about two hours, and I’ve figured out a really good routine where I don’t destroy my body, but I can get all the work in I need.”
“‘Then I go have lunch with my wife. In the evening, we cook dinner together. The kids are all home from school. We ask them about school. There’s so much joy in the house. We put them to bed, and then I put my head on the pillow and go, “Man, that was just a great day.” And I’ve been doing that for 20 years.’”
“And it was like, yes. That’s it. That’s the formula. That’s what leads to sustained success. He loves tennis. He loves his family. He loves life. It’s not outworking everybody and banging your head against the wall, ‘I’m going to be better than everybody.’ It’s allowing your natural talent to shine through with a work ethic, with a great family life, with perspective, with peace, with mindfulness.”
“It’s perspective. It’s joy. It’s passion. It’s mindfulness. It’s an awareness that we are truly lucky. To get the most out of ourselves, it’s our daily rituals and experiences and love and joy.”
Farooq Sheikh retweeted
🧬Precision medicine begins with a diagnosis.
In the largest real-world study to date, only 1.05% of patients with cardiomyopathy underwent genetic testing and just 7% received genetic counseling. Implementation — not evidence — remains the challenge.
🔗 bit.ly/4qpMbvF
Defining advanced heart failure: analyzing SWEDE-HF registry identified high-risk population of advanced heart failure with high risk of morbidity mortality. Addition of NTprobnp showed better prognostic accuracy. However, a less restrictive definition as in GALACTIC-HF identifies larger cohort for early referral for AT. 🫀 #AdvancedHeartFailure #SevereHeartFailure
🔗: jhltonline.org/article/S1053…
Farooq Sheikh retweeted
🚨🚨🚨 CARDIO-TTRansform data presented at @escardio #ESCCongress and simultaneously published in @NEJM. The (very surprising!) topline data was released last month – now we get the full data release. Much to break down – it’s all here in the 🧵 below. (1/25) nejm.org/doi/full/10.1056/NE…
LVAD outcomes have improved markedly. Adoption has not. This paper highlights LVAD underuse as a failure of diffusion driven by referral gaps, learning constraints, and policy misalignment—and offers a path forward. #HeartFailure #LVAD
🔗: jhltonline.org/article/S1053…
Farooq Sheikh retweeted
One major issue in amyloidosis research is the lack of mouse models for ATTR-CM.
Important new work showing humanized TTR knock-in mice (both wild-type and V142I) develop progressive, age-dependent cardiac amyloidosis with diastolic dysfunction and reduced survival, giving us reproducible model that better mirrors the human disease course.
Key insights:
•Vitronectin (VTN) is not just a bystander. It co-localizes with TTR fibrils, actively promotes aggregation, and when knocked down reduces amyloid burden while preserving cardiac function.
•Amyloid suppresses integrin αvβ3/FAK/Akt signaling → marked mitochondrial dysregulation (excessive fission, increased mitophagy, impaired oxidative phosphorylation).
•Low-dose cilengitide restores αvβ3 signaling, normalizes mitochondrial dynamics and bioenergetics, and improves diastolic function despite ongoing amyloid stress.
This may open a complementary therapeutic axis targeting integrin signaling.
Robust models + mechanistic depth + a new therapeutic angle. Worth a close read.
pubmed.ncbi.nlm.nih.gov/4257…
Farooq Sheikh retweeted
Are you a Digoxin Believer or Avoider?
Check out the latest high-yield distillation of contemporary data:
"Digitalis Today: From Doctrine to Disrepute to Disciplined Reconsideration"
onlinejcf.com/article/S1071-…
Farooq Sheikh retweeted
Reach out if you are interested in a position next year as a T32 cardiovascular outcomes research fellow or 4 year combined Cardiology/T32 fellow!
A lot of great clinician researchers have come out of this program
Proud to help promote our @MidAmericaHeart / UMKC T32 Postdoctoral Fellowship Training Program in Cardiovascular Outcomes Research.
This NHLBI-funded program has been a major engine for developing the next generation of cardiovascular outcomes researchers. Fellows receive deep mentorship, hands-on analytic and clinical research experience, access to major registries and trial datasets, and opportunities to develop expertise in quality of care, implementation science, health status measurement, health economics, and cardiovascular clinical research.
The program is a 2-year postdoctoral fellowship, with an option for a combined pathway with clinical cardiovascular fellowship training. Fellows may also pursue an MS in Bioinformatics with emphasis in Clinical Research and a Certificate in Biomedical Technology Entrepreneurship.
Our trainees have built an exceptional record of national presentations, peer-reviewed publications, and early-career awards.
Please share with outstanding applicants interested in using research to improve the quality, value, and outcomes of cardiovascular care.
Contact Danielle Olds, PhD, MPH, RN at
dolds@saint-lukes.org for more information.
Farooq Sheikh retweeted
In HELIOS-B, vutrisiran slowed renal decline in ATTR-CM: fewer ≥40% eGFR drops vs placebo (12.7% vs 21.2%).
Benefits on CV outcomes were consistent across kidney function, even in advanced CKD.
Improves not just CV outcomes but has renal benefits🫀🧪
bit.ly/3Q2hhf1
Read about a novel wireless transcutaneous energy transfer implant designed to eliminate driveline-associated infections by achieving durable cutaneous integration in porcine models - a step towards fully implantable #LVAD systems?
🔗: jhltonline.org/article/S1053…
Farooq Sheikh retweeted
Right ventricular failure is not just a downstream consequence of pulmonary hypertension or left-sided heart disease.
This AHA Scientific Statement reframes RV failure as a distinct, biologically active disease state with unique molecular, metabolic, inflammatory, fibrotic, and imaging features.
Key clinical message: assess the RV as the target organ.
That means going beyond TAPSE or a qualitative “mild/moderate/severe” RV dysfunction label. RV size, strain, RA/venous congestion, pulmonary arterial load, and RV–PA coupling all matter.
In pulmonary hypertension, outcomes are often determined less by the pressure itself than by whether the RV can adapt to the load. In HFpEF, LVAD evaluation, congenital heart disease, and critical illness, RV phenotype and reserve increasingly define prognosis.
The future is likely RV-specific phenotyping and RV-targeted therapy: inflammation, fibrosis, metabolism, mitochondrial dysfunction, and RV–PA coupling.
For practicing cardiologists, the practical takeaway is simple:
Don’t just report the RV.
Characterize it, follow it, and treat it as a central determinant of clinical trajectory.
doi.org/10.1161/CIR.00000000…
Histology says ‘benign,’ but molecular diagnostics tell another story: Quilty lesions show elevated dd-cfDNA & TCMR transcripts on MMDx. This paper highlights the need for molecular surveillance in #HeartTransplant care. 🫀
🔗: jhltonline.org/article/S1053…
Farooq Sheikh retweeted
Cardio TTRansform baseline characteristics presented #HFA2026 by Mat Maurer
Design paper ahajournals.org/doi/10.1161/…
#CardioTwitter
Farooq Sheikh retweeted
🚨 Major ISHLT Consensus Update on Graft Dysfunction after Heart Transplant (10-yr update)!
PGD is now EGD (Early Graft Dysfunction <24h, unknown cause) + sEGD (Subsequent Early Graft Dysfunction 24-72h).
New classification:
• LV/biventricular vs isolated RV
• Severe EGD-LV: immediate (fail to wean CPB) vs delayed presentation (key prognostic difference)
• Severity simplified to non-severe vs severe based on MCS need (goodbye inotrope score!)
This standardization is critical right now as DCD, OCS, TA-NRP, SherpaPak & HOPE rapidly expand the donor pool & change preservation risks. Better risk stratification, prevention & management ahead!
Full consensus: doi.org/10.1016/j.healun.202…
On #JHLTThePodcast, Jon Kobashigawa @CedarsSinai shares an important update to a keystone document—the @ISHLT Consensus Conference on #GraftDysfunction Within the First 72 Hours After #HeartTx."
#PGD #PrimaryGraftDysfunction #HTX