The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Efficacy of a Novel Retrobulbar Extension Shunt to Rescue Eyes with Fibrotic Encapsulated Blebs and Uncontrolled Ocular Hypertension.

PURPOSE: Retrobulbar glaucoma shunts are large-bore fenestrated silicone stents that redirect aqueous humor into the retrobulbar space. They were designed to rescue failed standard tube shunts with fibrotic encapsulation in patients with intractable ocular hypertension. This article evaluates longer-term outcomes of a larger population undergoing retrobulbar aqueous redirection. METHODS: Outcomes of all retrobulbar shunts were placed among this progressive-entry surgical population over an 8-year interval. Implants were produced by New World Medical (NWM) in Rancho Cucamonga, California, and AJL in Bilbao, Spain. Mean and percentage IOP reduction and medications required were evaluated at annual intervals, along with pre-operative and final visual acuity. Significance of change was assessed by two-tailed paired t-test. Failure was designated as any eye requiring placement of another shunt or diode-cyclophotocoagulation. All data are included in this analysis regardless of outcome. RESULTS: Thirty-five retrobulbar shunts were implanted (18M, 17F; mean 54.3 years; mean follow-up 32.5 months). Short-term AJL shunt performance was comparable to that of the 26 NWM shunts, for which there was longer-term follow-up. Three shunts (9%) failed: Two eyes required diode at 6 months, one another standard shunt after > 2 years. Preoperative medications averaged 2.6, reduced to 0.4-0.75 medications at each annual assessment (P < 0.0001). IOP was substantially reduced (by 53-57% from mean baseline 29.9-32.5 mmHg to 16.4-18.4 mmHg; P < 0.0008) at every annual follow-up. Visual acuity remained stable (baseline mean VA 0.27, final VA 0.30; P = 0.68). CONCLUSION: Retrobulbar extension shunts can convert tube shunt failures, with high success rate, to eyes with IOP control comparable to successful primary filtration surgery.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

AIMS: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy. METHODS AND RESULTS: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively. Factors associated with CRT response were identified (defined as improvement in left ventricular ejection fraction [LVEF] ≥5% 6 months post-implant) and the associated impact on the primary outcome of death, implantation of a left ventricular assist device or cardiac transplantation was assessed. We identified 105 patients (mean age 51 ± 10 years) undergoing CRT, including 70 (67%) who underwent CRT as a CIED upgrade. The mean change in LVEF ∼6 months post-CRT was +4 ± 9%. A CRT response occurred in 40 (38%) patients and was associated with lower baseline LVEF or a high percentage of right ventricular pacing prior to CRT in patients with pre-existing CIED. In patients with a European Society of Cardiology class I guideline indication for CRT, response rates were 61%. A CRT response was evident at thresholds of LVEF ≤45% or percent pacing ≥50%. There was a 1.3 year estimated median difference in event-free survival in those who responded to CRT (p = 0.04). CONCLUSION: Systolic function improves in patients with LMNA cardiomyopathy who undergo CRT, especially with strong guideline indications for implantation. Post-CRT improvements in LVEF are associated with survival benefits in this population with otherwise limited options.