Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression. METHODS AND RESULTS: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p = .008). CONCLUSIONS: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous.

Prognostic Value of Standard Heart Failure Medication in Patients with Cardiac Transthyretin Amyloidosis.

Introduction: Cardiac transthyretin amyloidosis (ATTR) is a progressive, fatal disease leading to heart failure due to accumulation of amyloid fibrils in the interstitial space and may occur as a hereditary (ATTRv) or wild-type (ATTRwt) form. Guidelines recommend the use of ACE inhibitors (ACEis) and beta-blockers (BBs) as heart failure therapy (HFT) in all patients with symptomatic heart failure and reduced ejection fraction, independent of the underlying etiology. However, the prognostic benefit of ACEis and BBs in ATTR has not been elucidated in detail yet. We thus sought to retrospectively investigate the outcome of patients with ATTRwt or ATTRv under HFT. Methods: Medical records of 403 patients with cardiac ATTR (ATTRwt: n = 268, ATTRv: n = 135) were screened for long-term medication as well as clinical, laboratory, electrocardiographic and echocardiographic data. Patients were assessed between 2005 and 2020 at the University Hospital Heidelberg. Kaplan-Meier analysis was used to analyze potential differences in survival among different subgroups. Results: The mean follow-up was 28 months. In total, 43 patients (32%) with ATTRv and 140 patients (52%) with ATTRwt received HFT. Survival was significantly shorter in patients receiving HFT in ATTRv (46 vs. 83 months, p = 0.0007) vs. non-HFT. A significantly better survival was observed in patients with comorbidities (coronary artery disease, arterial hypertension) and HFT among ATTRwt patients (p = 0.004). No significant differences in survival were observed in the other subgroups. Conclusions: Survival analysis revealed a potential benefit of HFT in patients with ATTRwt and cardiac comorbidities such as coronary artery disease and/or arterial hypertension. In contrast, HFT should be used with caution in patients with ATTRv.

Preoperative botulinum toxin test injections before muscle lengthening in cerebral palsy.

BACKGROUND: Muscle weakening is a well-known side effect of muscle-tendon lengthening. Botulinum toxin A (BTX-A) weakens the muscle temporarily by blocking the neuromuscular junction. Hence application of the drug is a logical step to test whether weakness deteriorates function prior to an operation. In the present study, BTX-A application is used to test preoperatively whether the gait pattern depends on the strength of the tested muscle. Since 1999, instrumented gait analysis, including kinematic, kinetic, and dynamic electromyographic data, is routinely used to define the individual surgical program. METHODS: In our series of 110 consecutive patients with cerebral palsy (CP) considered for surgical muscle lengthening from 1999 to 2008, BTX-A was applied to identify patients at risk for functional deterioration. Gait analysis was repeated 6 weeks (maximum effect of BTX-A) and 12 weeks (follow-up) after the test injection to check for loss of joint control (excessive ankle dorsiflexion, knee flexion, increased anterior pelvic tilt). RESULTS: In all, 20.9% (n = 23) showed deterioration in gait after preoperative BTX-A test injections (n = 112, two patients had two test trials) in all muscles considered for lengthening. As a consequence, their lengthening surgery was canceled. A total of 68 patients underwent surgery as planned, and in none of them did gait function deteriorate. These clinical data were compared to those of a historical group (n = 105) before this test, where 18% showed functional deterioration after surgery. The similar percentage of patients filtered out by the test suggests that there could be a context to the number of poor results in the historical group. CONCLUSIONS: We conclude that preoperative BTX-A test injection is a reliable tool for filtering out patients with risk of deterioration after muscle lengthening surgery in patients with CP and can be helpful to avoid poor outcomes.