Background Fabry disease is a lysosomal storage disorder with multiple organ involvement. Renal and cardiac symptoms can lead to dialysis and myocardial hypertrophy with fibrosis, responsible for heart failure with preserved ejection fraction (HFpEF). Enzyme replacement therapy (ERT) is available for all patients with Fabry disease since 2001, requiring infusions every other week. Since May 2016, the chaperone migalastat represents a novel form of specific therapy as the first oral therapy available for certain Fabry patients. Through this molecule the function of the mutated enzyme α-galactosidase A can be restored. Recent trials have shown positive cardiac effects of chaperone therapy using echocardiography; however, MRI investigations further evaluating these findings are not available yet. Objective To evaluate cardiac effects of migalastat therapy in patients with amenable α-galactosidase A mutations in the prospective monocentric HEAL-FABRY registry (NCT03362164). Methods and results Comprehensive clinical investigations including serial MRI were conducted at baseline before initiation of migalastat therapy and at least one year thereafter in all patients without contraindications such as pacemakers or ICDs. Out of 29 patients included in the study (mean age at start of therapy 52.8±14 years, total range 20–74 years), until then 12 patients with MRI data completed the 1-year follow-up. At 1 year, enzyme activity in leucocytes increased from 0.06 to 0.21 nmol/min/mg protein (p=0.001). Distinctive changes over time were observed not only in diastolic but also systolic parameters. The systolic myocardial mass index was reduced by 2.39% (p=0.10). In the AHA segment number 5, most important for classification of severe myocardial damage in Fabry patients, late gadolinium enhancement was reduced by 8.58% in all 5 patients with verified progressive fibrosis (p=0.14). One patient stopped migalastat therapy due to personal reasons. No significant side effects were observed. Analysis of LGE (systolic phase) Conclusion These preliminary MRI data show positive effects of migalastat therapy in patients with Fabry disease and cardiac involvement. Compared to echocardiography, MRI has the potential to allow for comprehensive additional analyses regarding both cardiac morphology and function.
Background and purpose From the various mechanical cardiac assist devices and indications available, use of the percutaneous intraventricular Impella CP pump is usually restricted to acute ischemic shock or prophylactic indications in high-risk interventions. In the present study, we investigated clinical usefulness of the Impella CP device in patients with non-ischemic cardiogenic shock as compared to acute ischemia. Methods In this retrospective single-center analysis, patients who received an Impella CP between 2013 and 2017 due to non-ischemic cardiogenic shock were age-matched 2:1 with patients receiving the device due to ischemic cardiogenic shock. Inclusion criteria were therapy refractory hemodynamic instability with severe left ventricular systolic dysfunction and serum lactate >2.0 mmol/l at implantation. Basic clinical data, indications for mechanical ventricular support, and outcome were obtained in all patients with non-ischemic as well as ischemic shock and compared between both groups. Continuous variables are expressed as mean ± standard deviation or median (quartiles). Categorical variables are presented as count and percent. Results 25 patients had cardiogenic shock due to non-ischemic reasons, and were compared to 50 patients with cardiogenic shock due to acute myocardial infarction. Resuscitation rates before implantation of Impella CP were high (32 vs 42%; P=0.402). At implantation, patients with non-ischemic cardiogenic shock had lower levels of HsTNT (110.65 [57.87–322.1] vs 1610 [450.8–3861.5] pg/ml; P=0.001) and LDH (377 [279–608] vs 616 [371.3–1109] U/I; P=0.007), while age (59±16 vs 61.7±11; P=0.401), GFR (43.5 [33.2–59.7] vs 48 [35.75–69] ml/min; P=0.290), CRP (5.17 [3.27–10.26] vs 10.97 [3.23–17.2] mg/dl; P=0.195), catecholamine-index (30.6 [10.6–116.9] vs 47.6 [11.7–90] μg/kg/min; P=0.663), and serum lactate (2.6 [2.2–5.8] vs 2.9 [1.3–6.6] mg/dl; P=0.424) were comparable between both groups. There was a trend for longer duration of Impella support in the non-ischemic groups (5 [2–7.5] vs 3 [2–5.25] days, P=0.211). Rates of hemodialysis (52 vs 47%; P=0.680) and transition to ECMO (13.6 vs 22.2%; P=0.521) were comparable. No significant difference was found regarding both 30-days survival (48 vs 30%; P=0.126, Figure 1) as well in-hospital mortality (66.7 vs 74%; P=0.512) although there was a trend for better survival in the non-ischemic group. 30-days survival Conclusions The current results position short-time use of the Impella CP as an alternative in the treatment of patients with cardiogenic shock due to underlying non-ischemic cardiomyopathy and/or complicating additional factors. However, additional studies are needed to test whether these findings can be confirmed in larger patient populations and which subgroups might benefit most from Impella therapy.
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