Ten year echocardiographic follow up of a trastuzumab induced cardiomyopathy cohort

Abstract Background Trastuzumab, a treatment option in breast cancers which express HER-2 positivity, is well known to be associated with cardiotoxicity. In 2015, A review of patients treated with trastuzumab, at our centre between 2010 and 2015 (mean age 49.6) found that 11% (n=12) of 109 patients had experienced trastuzumab-related cardiomyopathy (TRC), defined on transthoracic echocardiogram (TTE) by a reduction in left ventricular ejection fraction (LVEF) of 10% or more compared to baseline. Subsequent 7 year follow-up data demonstrated persistent mild systolic dysfunction was evident in 55.6% of this cohort. There were two 2 cancer related deaths and one patient was lost to follow-up. Purpose To characterise the longer term natural course of TRC and the clinical outcomes related to TRC. Methods We carried out further interval TTE follow-up of the nine patients with known TRC to reassess LVEF and reviewed their recent medical records. Results All 9 female patients received further follow up TTEs. Median follow up time was 10.48 years. 55% or patients received sequential Doxorubicin (average cumulative dose 409 mg), 66% received Cyclophosphamide (4045 mg)and mean cumulative trastuzumab dose was 5900mg. At 10 year follow up, 8/9 (89%) of patients had recovered to within 10% of their pre-chemotherapy LVEF. Whilst 6/9 (66%) of patients had an LVEF of 30-40% at their nadir, 7/9 patients' LVEFs had recovered and were ≥50%. 2 out of 9 patients (22%) LVEFs remained in the mid-range of 40-49%. Only 44% patients underwent global longitudinal strain imaging(GLS) assessment, demonstrating persistent impaired strain in 2/4 cases, (mean GLS -17%), one of whom also had a persistently reduced LVEF. 67% patients were on disease modifying therapy for heart failure, 44% were on Beta blockers, 22% were on MRAs, 22% on SGLT2s, 44% were on ACE/ARBs alone or in combination, and one patient was on Ivabradine. Only 67% had BNP measurements (mean 376 pg/ml, range 184 to 993). Only 5/9 patients were reviewed in a cardiology outpatient department. There were no cardiovascular (CV) related hospitalisations with heart failure or new onset of atrial fibrillation recorded and all were in remission from the primary disease. Conclusion This single centre data represents 10 year follow-up post completion of trastuzumab therapy with/without additional chemotherapy in patients with known TRC, with long-term recovery of LVEF in 89% of patients which demonstrates further incremental improvement from previous interval imaging. Most but not all were optimised with GDMT, and not all received cardiology follow up. Our centre is now more active in obtain GLS imaging on this patient cohort. These findings support the need for continuation of GDMT in dedicated cardio-oncology clinics.