Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy

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Improved left ventricular relaxation during short-term right ventricular outflow tract compared to apical pacing

STUDY OBJECTIVES: Pacing-induced asynchrony may deteriorate left ventricular function; however, limited data exists in humans. The aim of our study was to compare left ventricular hemodynamics during short-term atrioventricular sequential pacing from the right ventricular apex and from the outflow tract of the right ventricle. DESIGN: Three 5-min pacing intervals were applied in a random order, at a rate of 15 beats/min above the resting sinus rate. Atrioventricular sequential pacing from the two sites was compared with atrial pacing. During each pacing mode, left ventricular pressure was recorded, and cardiac output was calculated using Doppler echocardiography. SETTING: Cardiac catheterization laboratory. PATIENTS: Twenty patients (18 male, mean age 62 +/- 11 years) without structural heart disease were studied. RESULTS: During atrial pacing, maximum negative first derivative of pressure (dp/dt) was 1,535 +/- 228 mm Hg/s; during pacing from the apex it decreased to 1,221 +/- 294 mm Hg/s (p = 0.0001), but was not significantly different during pacing from the outflow tract (1,431 +/- 435 mm Hg/s, p > 0.05). Isovolumic relaxation time constant (tau) during atrial pacing was 39.7 +/- 11.9 ms; during pacing from the apex, it increased to 47.9 +/- 14.0 (p = 0.001), but was not significantly different during pacing from the outflow tract (42.5 +/- 11.2, p > 0.05). Peak systolic pressure decreased significantly during atrioventricular sequential pacing from either site; however, it did not differ between the two sites. No differences in end-diastolic pressure, maximum positive dp/dt, or cardiac output could be demonstrated. CONCLUSION: In patients with no structural heart disease, short-term right ventricular outflow tract pacing is associated with more favorable diastolic function, compared to right ventricular apical pacing.Ches

Transcatheter tricuspid valve-in-valve: evolution of tricuspid hydraulic performance and respective changes of right ventricular anatomy and function

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transcatheter tricuspid valve-in-valve replacement (TVIV) is an emerging therapy for dysfunctional surgically implanted bioprostheses. There are few data about the evaluation of hydraulic performance of these valves. Purpose Purpose of this single-center study was to evaluate the evolution of the right ventricular anatomy and function and the respective changes of TVIV hydraulics. Methods Six patients who underwent Sapien S3 TVIV (size 29mm) were studied (age 57 ± 11years, 3/6 in sinus rhythm, all in NYHA class III/IV). Inspiratory (insp) and expiratory (exp) TV mean gradients (mGR) , respective heart rate (HR), right ventricular end-diastolic diameter (RVEDd mm), RV fractional area change (FAC%) and RV free wall longitudinal strain (RV strain) were estimated at baseline (B), 1 month (1m) and later than 6 months (&amp;gt;6m). Results NYHA class fell by at least 1 scale at 1m and remained either stable or further improved at 6m. RVEDd increased early at 1m (B: 33.5 ± 5.3mm vs 1m: 41.3 ± 3.3mm, p = 0.018) and remained unchanged at &amp;gt;6m (&amp;gt;6m: 41 ± 4.2mm vs 1m: 41.3 ± 3.3mm, p = ns). FAC improved late at 6m (B: 42.6 ± 2.8% vs 6m: 56 ± 6.2% p = 0.04). RV strain remained unchanged (B: -17 ± 5.5% vs 1m: 16 ± 7% vs &amp;gt;6m: -20 ± 6%, p = ns). The improvement in both mGR-exp and mGR-insp was evident at 1m and remained unchanged afterwards: (mGR-exp: B 9 ± 4mmHg, 1m: 3 ± 2, &amp;gt;6m: 5 ± 1, both p &amp;lt; 0.05 vs B, mGR-insp: B 15 ± 5mmHg, 1m: 6 ± 2, &amp;gt;6m: 8 ± 2, both p &amp;lt; 0.05 vs B). The respective heart rates during measurements at inspiration and expiration were similar (HR-exp: B 72 ± 22bpm, 1m: 81 ± 22bpm, &amp;gt;6m: 65 ± 9bpm, HR-insp: B 75 ± 27bpm, 1m: 79 ± 18bpm, &amp;gt;6m: 69 ± 3bpm) Absolute values for both mGR-insp and mGR-exp, despite progressive improvement, showed variations exceeding the conventional cut-off for TV prosthetic valve dysfunction of 6 mmHg, despite preserved clinical improvement. Variations of mGR were not related with the respective HR. Conclusion Following TVIV, early clinical improvement was related with a concomitant increase in RV volume, whereas RV functional indices showed a delayed response. Conventional echocardiographic hydraulics showed variability, often exceeding threshold for definition of prosthetic valve dysfunction. Thus, the significance of TV gradient after TVIV should be interpreted in the clinical context, taking into account respiratory changes. </jats:sec

Left ventricular deformation mechanics over time in patients with thalassemia major with and without iron overload

Background: Myocardial iron overload in patients with thalassemia major (TM) is one of the most important complications. The purpose of the study was to identify advanced echocardiography parameters for early identification of myocardial dysfunction during follow-up of patients with TM. Methods: Forty TM patients who were 41 ± 5 years old were included in the study and divided into two groups according to cardiac magnetic resonance T2* results (Group 1: Τ2* &gt; 25 ms, Group 2: Τ2* ≤ 25 ms). Liver T2* parameters were also measured. Conventional and deformational echocardiographic parameters were measured at baseline and approximately 2 years later. Results: Thirty-two patients had Τ2* = 34 ± 4 ms (Group 1), and 8 had Τ2* = 17 ± 9 ms (Group 2). Blood consumption was 185 ± 60 and 199 ± 37 ml/kg/yr (p = 0.64), and liver T2* was 4 ± 5 and 17 ± 21 ms (p = 0.01) in Groups 1 and 2, respectively. At baseline, Group 1 had better left ventricular global longitudinal strain (GLS) (− 22 ± 3 vs. − 18 ± 5, p = 0.01) and similar left ventricular ejection fraction (LVEF) (62 ± 5% vs. 58 ± 10%, p = 0.086) than Group 2. At the 28 ± 11-month follow-up, LVEF, GLS, and T2* values in Group 1 (63 ± 3%, − 21 ± 3%, 34 ± 4 ms) and Group 2 (56 ± 11%, − 17 ± 4%, 17 ± 9 ms) did not change significantly compared to their corresponding baseline values. In 8 patients from Group 1, a worsening (&gt; 15%) in LS (p = 0.001) was detected during follow-up, with a marginal reduction in LVEF. Conclusions: GLS seems to be an efficient echocardiographic parameter for detecting hemochromatosis-related cardiac dysfunction earlier than LVEF. It also seems to be affected by other factors (free radical oxygen, immunogenetic mechanisms or viral infections) in a minority of patients, underscoring the multifactorial etiology of cardiomyopathy. © 2021, The Author(s)