Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: the FOCUS study.

BACKGROUND: Patients with Fabry disease (FD) show left ventricular hypertrophy (LVH) mimicking hypertrophic cardiomyopathy (HCM) of sarcomeric origin and might benefit, if detected early, from specific enzyme replacement therapy. The prevalence of FD in patients with LVH of 13 mm or greater, screened using the leucocyte alpha-galactosidase A (α-gal A) activity test, a technique that is difficult to apply routinely, ranged from 0% to 6%. OBJECTIVE: To screen systematically for FD in patients with a diagnosis of HCM (LVH ≥15 mm) in primary cardiology practice, a validated, physician-friendly α-gal A assay was used on dried blood spots using a filter paper test. DESIGN AND PATIENTS: A cohort of 392 adults (278 men) followed for HCM were screened for FD. A standard blood test was used for confirmation in nine men in whom the α-gal A result was 40% or less. RESULTS: Four men (1.5%; 1.8% of men ≥40 years vs 0% <40 years; all with α-gal A <30%), but no women, were diagnosed with FD. Index cases presented with diffuse but asymmetric LVH, with severe obstruction in one case and frequent high-grade atrioventricular conduction block necessitating a pacemaker in three cases. Family screening identified eight additional cases. Genotyping was performed successfully on DNA extracted from the filter papers. CONCLUSION: In male patients diagnosed as having HCM, pure FD cardiac variants are not exceptional and can be specifically identified using a simple filter-paper test. The sensitivity of this test is low in female patients.

Cardiac morphological and functional changes during early septic shock: a transesophageal echocardiographic study.

OBJECTIVE: The objective was to prospectively evaluate cardiac morphological and functional changes using transesophageal echocardiography (TEE) during early septic shock. DESIGN: Prospective, observational study. SETTING: Medical-surgical intensive care unit of a teaching hospital. PATIENTS AND PARTICIPANTS: Ventilated patients with septic shock, sinus rhythm and no cardiac disease underwent TEE within 12h of admission (Day0), after stabilization of hemodynamics by fluid loading (median volume: 4.9l [lower and upper quartiles: 3.7-9.6l]) and vasopressor therapy, and after vasopressors were stopped (Dayn). MEASUREMENTS AND RESULTS: Thirty-five patients were studied (median age: 60 years [range 44-68]; SAPS II: 53 [46-62]; SOFA score: 9 [8-11]) and 9 of them (26%) died while on vasopressors. None of the patients exhibited TEE findings of cardiac preload dependence. Between Day0 and Dayn (7 days [range 6-9]), mean left ventricular (LV) ejection fraction (EF) increased (47 +/- 20 vs. 57 +/- 14%: p < 0.05), whereas mean LV end-diastolic volume decreased (97 +/- 25 vs. 75 +/- 20ml: p < 0.0001). Out of 16 patients (46%) with LV systolic dysfunction on Day0, 12 had normal LVEF on Dayn and 4 patients fully recovered by Day28. Only 4 women had LV dilatation (range, LV end-diastolic volume: 110-148ml) on Day0, but none on Dayn. Doppler tissue imaging identified an LV diastolic dysfunction in 7 patients (20%) on Day0 (3 with normal LVEF), which resolved on Dayn. CONCLUSIONS: This study confirms that LV systolic and diastolic dysfunctions are frequent, but LV dilatation is uncommon in fluid-loaded septic patients on vasopressors. All abnormalities regressed in survivors, regardless of their severity. DESCRIPTORS: Shock: clinical studies (38), Cardiovascular monitoring (34).