Fabry disease due to D313Y variant with renal failure and possible cardiac involvement: a case report.

Background: This is a case report of a patient with Anderson-Fabry disease (AFD) due to the D313Y variant on the a-galactosidase A (GLA) gene on migalastat treatment and severe chronic kidney disease referred to our unit to assess possible cardiac involvement. Case summary: A 53-year-old man with chronic kidney disease due to AFD and a medical history of revascularized coronary artery disease, chronic atrial fibrillation, and arterial hypertension was referred to our unit for evaluation of possible cardiac involvement in the context of AFD. Biochemical evaluation reported reduced serum alpha-galactosidase A activity and borderline abnormal serum lyso-Gb3 enzyme activity. The patient had also history of acroparesthesias, dermatological presentation of multiple angiokeratomas, severe kidney impairment with an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73m² by the age of 16, and microalbuminuria that cumulatively set the diagnosis of AFD. Transthoracic echocardiogram showed left ventricular concentric hypertrophy with left ventricular ejection fraction of 45%. Cardiac magnetic resonance showed findings in keeping with ischaemic heart disease (IHD), i.e. akinesia and subendocardial scarring of the basal anterior and the entirety of the septum and the true apex; in addition, there was severe asymmetrical hypertrophy of the basal anteroseptum (max 18 mm), evidence of low-grade myocardial inflammation, and mid-wall fibrosis of the basal inferior and inferolateral wall, suggesting a cardiomyopathic process-myocardial disease which could not be explained solely by IHD or well-controlled hypertension. Discussion: This is the first case of possible cardiac involvement in a patient with AFD due to the D313Y variant. This case demonstrates the diagnostic challenges of cardiac involvement in AFD, especially in the presence of a concomitant underlying pathology.

Impact of Evolution of Self-Expandable Aortic Valve Design: Peri-Operative and Short-Term Outcomes.

A few data exist on the differences of implantable aortic valve bio-prostheses. We investigate three generations of self-expandable aortic valves in terms of the outcomes. Patients undergoing transcatheter aortic valve implantation (TAVI) were allocated into three groups according to the valve type: group A (CoreValveTM), group B (EvolutTMR) and group C (EvolutTMPRO). The implantation depth, device success, electrocardiographic parameters, need for permanent pacemaker (PPM), and paravalvular leak (PVL) were assessed. In the study, 129 patients were included. The final implantation depth did not differ among the groups (p = 0.07). CoreValveTM presented greater upward jump of the valve at release (2.88 ± 2.33 mm vs. 1.48 ± 1.09 mm and 1.71 ± 1.35 mm, for groups A, B, and C, respectively, p = 0.011). The device success (at least 98% for all groups, p = 1.00) and PVL rates (67% vs. 58%, vs. 60% for groups A, B, and C, respectively, p = 0.64) did not differ. PPM implantation within 24 h (33% vs. 19% vs. 7% for groups A, B, and C, respectively, p = 0.006) and until discharge (group A: 38% vs. group B: 19% and group C: 9%, p = 0.005) was lower in the newer generation valves. Newer generation valves present better device positioning, more predictable deployment, and fewer rates of PPM implantation. No significant difference in PVL was observed.

Hypertensive crisis and pulmonary edema following rituximab-induced anaphylaxis.

Rituximab is a monoclonal antibody against the protein CD20. Various lymphomas as well as non-malignant immune disorders are treated with this antibody. Hypersensitivity reactions associated with the use of rituximab include urticaria, hypotension, chest tightness, vomiting, oxygen desaturation and bronchospasm. A very uncommon case of hypertensive crisis and pulmonary edema following rituximab-induced hypersensitivity reaction in an 80-year-old man receiving rituximab for non-Hodgkin lymphoma is reported. Anaphylaxis manifesting as coronary vasospasm following drug treatment, including rituximab, could be proved a serious condition in patients who need specific treatment. In these patients desensitization protocols seem to be mandatory.

Comparison of Ticagrelor Versus Clopidogrel on Cerebrovascular Microembolic Events and Platelet Inhibition during Transcatheter Aortic Valve Implantation.

The impact of the antiplatelet regimen and the extent of associated platelet inhibition on cerebrovascular microembolic events during transcatheter aortic valve implantation (TAVI) are unknown. Our aim was to evaluate the effects of ticagrelor versus clopidogrel and of platelet inhibition on the number of cerebrovascular microembolic events in patients undergoing TAVI. Patients scheduled for TAVI were randomized previous to the procedure to either aspirin and ticagrelor or to aspirin and clopidogrel. Platelet inhibition was expressed in P2Y12 reaction units (PRU) and percentage of inhibition. High intensity transient signals (HITS) were assessed with transcranial Doppler (TCD). Safety outcomes were recorded according to the VARC-2 definitions. Among 90 patients randomized, 6 had an inadequate TCD signal. The total number of procedural HITS was lower in the ticagrelor group (416.5 [324.8, 484.2]) (42 patients) than in the clopidogrel group (723.5 [471.5, 875.0]) (42 patients), p <0.001. After adjusting for the duration of the procedure, diabetes, extra-cardiac arteriopathy, BMI, hypertension, aortic valve calcium content, procedural ACT, and pre-implantation balloon valvuloplasty, patients on ticagrelor had on average 256.8 (95% CI: [-335.7, -176.5]) fewer total procedural HITS than patients on clopidogrel. Platelet inhibition was greater with ticagrelor 26 [10, 74.5] PRU than with clopidogrel 207.5 (120 to 236.2) PRU, p <0.001, and correlated significantly with procedural HITS (r = 0.5, p <0.05). In conclusion, ticagrelor resulted in fewer procedural HITS, compared with clopidogrel, in patients undergoing TAVI, while achieving greater platelet inhibition.

One-year clinical and echocardiographic outcomes of direct implantation of a self-expanding valve.

OBJECTIVE: To present 1 year clinical and echocardiographic outcomes of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial. BACKGROUND: Intermediate-term data from randomized studies investigating the safety and efficacy of direct implantation are lacking. METHODS: DIRECT trial randomized 171 consecutive patients with severe aortic stenosis at four tertiary centers to undergo TAVI with the use of self-expanding prostheses with (pre-BAV) or without pre-dilatation (no-BAV). The primary endpoint was device success according to the VARC-2 criteria. All patients underwent a clinical and echocardiographic follow-up at 1 year. All-cause and cardiac mortality, stroke, heart failure hospitalization, and new pacemaker implantation were recorded. RESULTS: At 1 year, four deaths were recorded in pre-BAV group (4.7%) and three deaths in no-BAV group (3.5%). There was no difference in Kaplan-Meier plots between the two groups in all-cause mortality at 1 year (log-rank p = .72). Similarly, there was no difference in the incidence of permanent pacemaker implantation between the two groups at 1 year (27/67-40.3% in no-BAV group versus 20/69-29% in pre-BAV group, log-rank p = .24). There was no significant difference between pre-BAV and no BAV group in aortic valve area (1.84 ± 0.39 cm2 vs. 1.85 ± 0.44 cm2 , p = .90), mean aortic valve gradient (8.36 ± 5.04 vs. 8.00 ± 4.04 mmHg, p = .65) and moderate or severe paravalvular regurgitation (5-6.6 vs. 4-5.7%, respectively) at 1 year. The same applied independently from the performance of post-dilatation at baseline. CONCLUSIONS: Direct, without pre-dilatation, implantation of a self-expanding valve has no impact on one-year clinical and echocardiographic outcomes, independently also from the baseline performance of post-dilatation.

Impact of "high" implantation on functionality of self-expandable bioprosthesis during the short- and long-term outcome of patients who undergo transcatheter aortic valve implantation: Is high implantation beneficial?

AIM: High position of the self-expandable bioprosthesis CoreValve/Evolut R has been proved to affect immediate hemodynamics of the valve. Whether this may have any impact on long-term procedural outcome has not been defined yet. The purpose of this study was to assess whether the final position of aortic bioprosthesis affects its long-term functionality. METHOD: Consecutive patients (pts) who underwent successful TAVI procedure were evaluated and separated into 2 groups according to the implantation depth (ID): Group I: pts with 4 mm