Research Spotlight

Posted September 16th 2021

Long-term follow-up of renal function in patients treated with migalastat for Fabry disease.

Raphael Schiffmann M.D.

Raphael Schiffmann M.D.

Bichet, D. G., R. Torra, E. Wallace, D. Hughes, R. Giugliani, N. Skuban, E. Krusinska, U. Feldt-Rasmussen, R. Schiffmann and K. Nicholls (2021). “Long-term follow-up of renal function in patients treated with migalastat for Fabry disease.” Mol Genet Metab Rep 28: 100786.

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The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)-naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for ≥2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91.4 mL/min/mL/1.73 m(2)) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m(2)) patients with amenable variants who received migalastat 123 mg every other day for ≥2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR(CKD-EPI)) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were – 1.6 mL/min/1.73 m(2) overall and – 1.8 mL/min/1.73 m(2) and – 1.4 mL/min/1.73 m(2) in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were – 1.6 mL/min/1.73 m(2) overall and – 2.6 mL/min/1.73 m(2) and – 0.8 mL/min/1.73 m(2) in male and female patients, respectively. Mean annualized rate of change in eGFR(CKD-EPI) in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [α-Gal A] activity of <3% of normal and multiorgan system involvement) was -1.7 mL/min/1.73 m(2). When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFR(CKD-EPI) change was minimal (mean: -0.1 and 0.1 mL/min/1.73 m(2) in ERT-naive and ERT-experienced patients, respectively). In conclusion, patients with Fabry disease and amenable GLA variants receiving long-term migalastat treatment (≤8.6 years) maintained renal function irrespective of treatment status, sex, or phenotype.


Posted September 16th 2021

Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.

William C. Roberts M.D.

William C. Roberts M.D.

Roberts, W. C. and M. Jeong (2021). “Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy.” Am J Cardiol Aug 12;S0002-9149(21)00682-2. [Epub ahead of print].

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Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.


Posted September 16th 2021

International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes.

William C. Roberts M.D.

William C. Roberts M.D.

Michelena, H. I., A. Della Corte, A. Evangelista, J. J. Maleszewski, W. D. Edwards, M. J. Roman, R. B. Devereux, B. Fernández, F. M. Asch, A. J. Barker, L. M. Sierra-Galan, L. De Kerchove, S. M. Fernandes, P. W. M. Fedak, E. Girdauskas, V. Delgado, S. Abbara, E. Lansac, S. K. Prakash, M. M. Bissell, B. A. Popescu, M. D. Hope, M. Sitges, V. H. Thourani, P. Pibarot, K. Chandrasekaran, P. Lancellotti, M. A. Borger, J. K. Forrest, J. Webb, D. M. Milewicz, R. Makkar, M. B. Leon, S. P. Sanders, M. Markl, V. A. Ferrari, W. C. Roberts, J. K. Song, P. Blanke, C. S. White, S. Siu, L. G. Svensson, A. C. Braverman, J. Bavaria, T. M. Sundt, G. El Khoury, R. De Paulis, M. Enriquez-Sarano, J. J. Bax, C. M. Otto and H. J. Schäfers (2021). “International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes.” J Thorac Cardiovasc Surg 162(3): e383-e414.

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This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes.


Posted September 16th 2021

Malignancy-Associated Non-Bacterial Thrombotic Endocarditis Causing Aortic Regurgitation and Leading to Aortic Valve Replacement.

William C. Roberts M.D.

William C. Roberts M.D.

Makhdumi, M., D. M. Meyer and W. C. Roberts (2021). “Malignancy-Associated Non-Bacterial Thrombotic Endocarditis Causing Aortic Regurgitation and Leading to Aortic Valve Replacement.” Am J Cardiol 154: 120-122.

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Described herein is a 48-year-old woman with metastatic ovarian cancer who developed aortic regurgitation considered clinically to be the result of infective endocarditis but operative resection of the three aortic valve cusps disclosed the valve lesions to be typical of non-bacterial thrombotic endocarditis (NBTE). Aortic regurgitation as a consequence of NBTE is rare but at least 9 cases have been reported previously.


Posted September 16th 2021

Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional, and research purposes.

William C. Roberts M.D.

William C. Roberts M.D.

Michelena, H. I., A. Della Corte, A. Evangelista, J. J. Maleszewski, W. D. Edwards, M. J. Roman, R. B. Devereux, B. Fernández, F. M. Asch, A. J. Barker, L. M. Sierra-Galan, L. De Kerchove, S. M. Fernandes, P. W. M. Fedak, E. Girdauskas, V. Delgado, S. Abbara, E. Lansac, S. K. Prakash, M. M. Bissell, B. A. Popescu, M. D. Hope, M. Sitges, V. H. Thourani, P. Pibarot, K. Chandrasekaran, P. Lancellotti, M. A. Borger, J. K. Forrest, J. Webb, D. M. Milewicz, R. Makkar, M. B. Leon, S. P. Sanders, M. Markl, V. A. Ferrari, W. C. Roberts, J. K. Song, P. Blanke, C. S. White, S. Siu, L. G. Svensson, A. C. Braverman, J. Bavaria, T. M. Sundt, G. E. Khoury, R. De Paulis, M. Enriquez-Sarano, J. J. Bax, C. M. Otto and H. J. Schäfers (2021). “Summary: International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional, and research purposes.” J Thorac Cardiovasc Surg 162(3): 781-797.

Full text of this article.

This International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type, with 3 phenotypes: right-left cusp fusion, right-non cusp fusion and left-non cusp fusion; 2. 2-sinus type with 2 phenotypes: Latero-lateral and antero-posterior; and 3. Partial-fusion or forme fruste. This consensus recognizes 3 bicuspid-aortopathy types: 1. Ascending phenotype; root phenotype; and 3. extended phenotypes.