Cardiac magnetic resonance diagnosis of Fabry disease leads to incidental diagnosis of Klinefelter syndrome: a case report.

Background: Fabry disease is an X-linked lysosomal storage disorder resulting in deficient activity of alpha-galactosidase. Males are general more severely affected however heterozygous females can variably express the disease depending on the degree of random X chromosome inactivation (Lyonization). We present a case where cardiac magnetic resonance diagnosis of late onset Fabry Disease leads to an incidental diagnosis of Klinefelter syndrome. Case summary: A 55-year-old male was referred for cardiology assessment after developing atrial fibrillation. Echocardiography demonstrated moderate, concentric LVH (left ventricular hypertrophy). Cardiac magnetic resonance imaging confirmed the presence of concentric increase in LV wall thickness and increased LV (left ventricular) mass. T1 mapping values (Shortened Modified Look-Locker Inversion recovery sequences) were elevated in the basal-mid inferolateral segments and low in the remaining segments. Late gadolinium acquisition showed a pattern suggestive of Fabry disease. Genetic testing of the GLA gene revealed a null variant classified as pathogenic. The variant was found to be heterozygous. This raised the possibility of Klinefelter's syndrome and the diagnosis was confirmed by chromosomal microarray and karyotype. The patient was then referred to Fabry clinic for consideration of enzyme replacement therapy and to the endocrine clinic for testosterone replacement. Discussion: The atypical 'cardiac variant' Fabry disease should be included in differential diagnosis of left ventricular hypertrophy. In a 'late onset' presentation of Fabry Disease, the concomitant presence of Klinefelter syndrome cannot be excluded due to GLA variant present in the heterozygous state.

Randomized controlled trial of perhexiline on regression of left ventricular hypertrophy in patients with symptomatic hypertrophic cardiomyopathy (RESOLVE-HCM trial).

BACKGROUND: The presence and extent of left ventricular hypertrophy (LVH) is a major determinant of symptoms in patients with hypertrophic cardiomyopathy (HCM). There is increasing evidence to suggest that myocardial energetic impairment represents a central mechanism leading to LVH in HCM. There is currently a significant unmet need for disease-modifying therapy that regresses LVH in HCM patients. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor, improves myocardial energetics in HCM, and has the potential to reduce LVH in HCM. OBJECTIVE: The primary objective is to evaluate the effects of perhexiline treatment on the extent of LVH, in symptomatic HCM patients with at least moderate LVH. METHODS/DESIGN: RESOLVE-HCM is a prospective, multicenter double-blind placebo-controlled randomized trial enrolling symptomatic HCM patients with at least moderate LVH. Sixty patients will be randomized to receive either perhexiline or matching placebo. The primary endpoint is change in LVH, assessed utilizing cardiovascular magnetic resonance (CMR) imaging, after 12-months treatment with perhexiline. SUMMARY: RESOLVE-HCM will provide novel information on the utility of perhexiline in regression of LVH in symptomatic HCM patients. A positive result would lead to the design of a Phase 3 clinical trial addressing long-term effects of perhexiline on risk of heart failure and mortality in HCM patients.

Mechanical atrial recovery after cardioversion in persistent atrial fibrillation evaluated by bidimensional speckle tracking echocardiography.

BACKGROUND: Atrial fibrillation induces reversible electrical and mechanical modifications (atrial remodeling). Atrial stunning is a mechanical dysfunction with preserved bioelectrical function, occurring after successful atrial fibrillation electrical cardioversion (ECV). Two-dimensional speckle tracking echocardiography is a new technology for evaluating atrial mechanical function. We assessed atrial mechanical function after ECV with serial two-dimensional speckle tracking echocardiography evaluations. The investigated outcome was left atrium mechanical recovery within 3 months. METHODS: A total of 36 patients [mean age 73 (7.9) years, 23 males] with persistent atrial fibrillation underwent conventional transthoracic and transesophageal echocardiography before ECV. Positive global atrial strain (GSA+) was assessed at 3 h, 1, 2, 3, 4 weeks and 3 months after ECV. Mechanical recovery was defined as the achievement of a GSA+ value of 21%. RESULTS: Independent predictors of GSA+ immediately after ECV (basal GSA+) were E/e' ratio and left atrial appendage anterograde flow velocity. During the follow-up, 25% of patients suffered atrial fibrillation recurrence. In 12/36 patients (33%) left atrium mechanical recovery was detected (mechanical recovery group), while in 15/36 (42%) recovery did not occur (no atrial mechanical recovery group). At univariate analysis, the variables associated with recovery, were basal GSA+ (P = 0.015) and maximal velocity left atrial appendage (P = 0.022). Female sex (P = 0.038), N-terminal pro-B type natriuretic peptide (P = 0.013), E/e' (P = 0.042) and the indexed left atrium volume (P = 0.019) were associated with the lack of left atrium mechanical recovery. CONCLUSION: In almost half of the patients, the left atrium did not resume mechanical activity within the 3 months after ECV, despite sinus rhythm recovery. The left atrium of these patients was larger, stiffer and their E/E' was higher, suggesting a higher endocavitary pressure compared with mechanical recovery patients. These findings might suggest an increased thromboembolic risk.

Incremental prognostic value of global left atrial peak strain in women with new-onset gestational hypertension.

BACKGROUND: Left atrial strain and strain rate parameters, measured by bidimensional-speckle tracking echocardiography, have been proposed as predictors of atrial fibrillation, stroke, congestive heart failure and cardiovascular death. However, they have not yet been tested in hypertensive disorders of pregnancy. The aim of this study was to assess the prognostic role of global left atrial peak strain (GLAPS) in a population of pregnant women with new-onset hypertension in a medium-term follow-up. METHODS: Twenty-seven consecutive women with new-onset hypertension after 20 weeks pregnancy and 23 age-matched, race-matched and gestational week-matched consecutive normotensive pregnant women were enrolled in this prospective study. All participants underwent a complete echocardiographic study with bidimensional-speckle tracking echocardiography and carotid examination. At 1-year follow-up, we evaluated the occurrence of persistent hypertension. RESULTS: In comparison with normotensive women, those hypertensive had a higher burden of cardiovascular risk factors, similar left atrial volume indexed (P = 0.14), but severely impaired left atrial strain (P < 0.0001) and strain rate values (P < 0.0001). At 1-year follow-up, persistent hypertension was documented in 59.3% of patients. At the univariate Cox analysis, the variables associated with the occurrence of the investigated outcome in all hypertensive pregnancies were SBP (hazard ratio 1.04, P = 0.04), DBP (hazard ratio 1.11, P = 0.01), mean arterial pressure (hazard ratio 1.09, P = 0.01) values and the GLAPS value (hazard ratio 0.85, P = 0.0019). The latter was significantly associated with the investigated outcome both in preeclamptic (hazard ratio 0.84, P = 0.02) and nonpreeclamptic pregnant women (hazard ratio 0.83, P = 0.04). The receiver operating characteristics curve analysis highlighted that a GLAPS value of 23.5% or less predicted persistent hypertension with sensitivity of 100% and specificity of 90.90%. CONCLUSION: In hypertensive pregnant women a GLAPS value of 23.5% or less reveals a greater severity of atrial cardiomyopathy and might predict postpregnancy persistent hypertension.

Aspirin desensitization in patients undergoing planned or urgent coronary stent implantation. A single-center experience.

INTRODUCTION: Dual antiplatelet therapy (aspirin and ADP-antagonists) is mandatory after stent implantation in order to avoid stent thrombosis, especially in the era of DES. In fact, a delayed re-endothelization process may enlarge the window of occurrence of stent thrombosis beyond 1-year after implantation. Allergy to acid acetylsalicylic is not a rare event and may influence the use and the choice of coronary stent with an important impact in terms of outcome especially in patients at high risk for in-stent restenosis. The aim of this study was to evaluate the safety and efficacy of a new intravenous rapid desensitization protocol in patients with acetylsalicylic acid sensitivity undergoing coronary stent implantation. METHODS: Among a total of 1385 patients undergoing coronary angioplasty at our catheterization laboratory from January 2007 to June 2011, a total of 43 patients (3.1%) had history of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions). Twenty-three patients (53.5%) presented with acute coronary syndromes. All patients underwent a novel rapid desensitization procedure before or after cardiac catheterization (in case of ST-elevation myocardial infarctions, n=5). The desensitization procedure was based on intravenous administration of 9 sequential doses of aspirin (1, 2, 4, 8, 16, 32, 64, 128, 250 mg) over 4.5h without the use of corticosteroids or antihistamines. Patients were followed for at least 30 days and up to 12 months to assess compliance with aspirin therapy and adverse events. RESULTS: The desensitization procedure was successful in 42 patients (97.6%). All patients underwent stent implantation (1.6 stents/patient). Drug-eluting stents were used in 36 patients (85.7%). At follow-up, all patients who successfully responded to the desensitization procedure did not develop any allergic reaction. CONCLUSIONS: This study showed the safety and efficacy of a new rapid intravenous protocol desensitization for patients with history of aspirin sensitivity undergoing planned or urgent coronary stent implantation.