Feasibility and safety of non-invasive ultrasound therapy (NIUT) on an porcine aortic valve.

Calcific aortic stenosis (CAS) is associated with advanced age and comorbidities, therefore a non-invasive therapy for it would be beneficial. We previously demonstrated that ultrasound therapy improved calcified bioprosthetic valve function in an open chest model. For translational applications, we tested non-invasive ultrasound therapy (NIUT) transthoracically on swine aortic valves and investigated the need for antithrombotic treatment as a follow-up. Primary objective: feasibility and safety of NIUT. Secondary objectives: occurrence, severity and evolution of side effects during therapy and at 1 month follow-up. The device (Valvosoft, Cardiawave) consisted of an electronically steered multi-element transducer and a 2D echocardiographic probe. Three groups of swine received treatment on aortic valves: NIUT (group 1; n = 10); NIUT and 1 month antithrombotic treatment (group 2; n = 5); sham group (group 3; n = 4). Feasibility was successfully reached in all treated swine (n = 15) and no life-threatening arrhythmia were detected. Non-sustained ventricular tachycardia occurred during the procedure in seven swine. Decrease or interruption of NIUT ended arrhythmia. Histopathology revealed no valve or surrounding tissue damage and echocardiography revealed no valvular dysfunction. Only one animal had side effects [right ventricle (RV) dilatation], but the RV normalized after therapy cessation with no sequelae at follow-up. No disturbance in biological markers nor valve thrombosis were observed at follow-up. Antithrombotic treatment did not demonstrate any advantage. Survival at 30 d was 100%. We demonstrated, in vivo, the feasibility and safety of transthoracic NIUT on aortic valves in a swine model without serious adverse events. We expect this first-time transthoracic delivery of NIUT to pave the way towards a new non-invasive approach to valve softening in human CAS to restore valve function.

Myocardial Stiffness Evaluation Using Noninvasive Shear Wave Imaging in Healthy and Hypertrophic Cardiomyopathic Adults.

OBJECTIVES: The goal of our study was to investigate the potential of myocardial shear wave imaging (SWI) to quantify the diastolic myocardial stiffness (MS) (kPa) noninvasively in adult healthy volunteers (HVs) and its physiological variation with age, and in hypertrophic cardiomyopathy (HCM) populations with heart failure and preserved ejection function (HFpEF). BACKGROUND: MS is an important prognostic and diagnostic parameter of the diastolic function. MS is affected by physiological changes but also by pathological alterations of extracellular and cellular tissues. However, the clinical assessment of MS and the diastolic function remains challenging. SWI is a novel ultrasound-based technique that has the potential to provide intrinsic MS noninvasively. METHODS: We prospectively included 80 adults: 60 HV (divided into 3 groups: 20- to 39-year old patients [n = 20]; 40- to 59-year-old patients [n = 20]; and 60- to 79-year-old patients [n = 20]) and 20 HCM-HFpEF patients. Echocardiography, cardiac magnetic resonance imaging and biological explorations were achieved. MS evaluation was performed using an ultrafast ultrasound scanner with cardiac phased array. The fractional anisotropy of MS was also estimated. RESULTS: MS increased significantly with age in the HV group (the mean MS was 2.59 ± 0.58 kPa, 4.70 ± 0.88 kPa, and 6.08 ± 1.06 kPa for the 20- to 40-year-old, 40- to 60-year-old, and 60- to 80-year-old patient groups, respectively; p < 0.01 between each group). MS was significantly higher in HCM-HFpEF patients than in HV patients (mean MS = 12.68 ± 2.91 kPa vs. 4.47 ± 1.68 kPa, respectively; p < 0.01), with a cut-off at 8 kPa (area under the curve = 0.993; sensitivity = 95%, specificity = 100%). The fractional anisotropy was lower in HCM-HFpEF (mean = 0.133 ± 0.073) than in HV (0.238 ± 0.068) (p < 0.01). Positive correlations were found between MS and diastolic parameters in echocardiography (early diastolic peak/early diastolic mitral annular velocity, r = 0.783; early diastolic peak/transmitral flow propagation velocity, r = 0.616; left atrial volume index, r = 0.623) and with fibrosis markers in cardiac magnetic resonance (late gadolinium enhancement, r = 0.804; myocardial T1 pre-contrast, r = 0.711). CONCLUSIONS: MS was found to increase with age in healthy adults and was significantly higher in HCM-HFpEF patients. Myocardial SWI has the potential to become a clinical tool for the diagnostic of diastolic dysfunction. (Non-invasive Evaluation of Myocardial Stiffness by Elastography [Elasto-Cardio]; NCT02537041).

Segmental aortic stiffness in patients with bicuspid aortic valve compared with first-degree relatives.

AIMS: To compare the stiffness index in patients with bicuspid aortic valve (BAV) with first-degree relatives at each segment of the thoracic ascending aorta and to compare segmental analysis of aortic stiffness in association with BAV morphotype and function. METHODS: 219 patients with BAV and 148 first-degree relatives (without BAV) were consecutively included at a reference centre for BAV. Ultrasound assessment of aortic and carotid stiffness was based on the variation of the segmental arterial diameters during the cardiac cycle and on blood pressure. RESULTS: Without adjustment, the ascending aorta of patients with BAV seemed stiffer at each segment compared with controls (stiffness index at the sinus of Valsalva: 17.0±10.9 vs 8.9±6.1, p<0.001; tubular aorta: 20.4±31.3 vs 12.7±4.8, p=0.04). However, after adjustment on aortic diameter and age, only the sinus of Valsalva remained stiffer (p<0.001), whereas the tubular aorta no longer differed (p=0.610). In patients with BAV, aortic diameters were not influenced by the valve morphotype, except for the arch, which was more dilated in the case of 1- Non coronary sinus-Right subtype of BAV : 36.1 vs 27.6 mm, p<0.001. Aortic regurgitation was associated with an increase in aortic diameters at the sinus of Valsalva (p<0.001) and the tubular aortic levels (p=0.04). CONCLUSION: Stiffness increase at the sinus of Valsalva level is independent of aortic dilatation in patients with BAV, contrary to the classic relationship between stiffness and dilatation found on the other segments. The relationship between stiffness and clinical impact needs to be assessed at each aortic segment.

Usefulness of Subepicardial Hyperemia on Contrast-Enhanced First-Pass Magnetic Resonance Perfusion Imaging for Diagnosis of Acute Myocarditis.

Hyperemia is a major criterion for the diagnosis of acute myocarditis on cardiac magnetic resonance imaging but its assessment is challenging and time consuming. We evaluated the usefulness of the contrast-enhanced first-pass perfusion (FPP) on magnetic resonance imaging for detecting subepicardial hyperemia in acute myocarditis. Forty-seven consecutive patients (mean age: 42 ± 15.6 years; 35 men) with a definite diagnosis of acute myocarditis according to the state-of-the-art guidelines were included and compared with 16 control subjects. FPP was evaluated by 2 blinded observers and compared with the reference late gadolinium enhancement. Detection of hyperemia was performed on both qualitative and quantitative methods. Relative increased signal intensity (SI) in the subepicardial hyperemic layer was measured with SI ratio (SI of the subepicardial layer/SI of the immediately adjacent subendocardial layer). Twenty-four patients (51%) with acute myocarditis exhibited subepicardial hyperemia, detected with a good interobserver reproducibility (kappa coefficient: 0.75). The SI in the myocardium of myocarditis patients was increased compared with controls (1.08 ± 0.03 vs 0.945 ± 0.04, p = 0.03) and the SI in myocarditis patients with hyperemia compared with those without hyperemia (1.22 ± 0.04 vs 0.94 ± 0.04, p <0.0001). Sensitivity, specificity, positive predictive, and negative predictive values of FPP for detecting hyperemia were 85%, 94%, 85%, and 93%, respectively. In conclusion, contrast-enhanced first-pass magnetic resonance imaging is a fast and useful method for assessing myocardial hyperemia in patients with acute myocarditis.

Prognostic value of the infarct- and non-infarct like patterns and cardiovascular magnetic resonance parameters on long-term outcome of patients after acute myocarditis.

BACKGROUND: Prognostic value of the infarct- and non-infarct like patterns and cardiac magnetic resonance (CMR) parameters on long-term outcome of patients after acute myocarditis is not well known. METHODS: Between 2006 and 2015, 112 consecutive patients with CMR-based diagnosis of acute myocarditis were identified in our institution. Of them, 88 were available for clinical follow-up and represented our studied population. Patients were divided into infarct-like group (n=48) (association of acute chest pain, elevated Troponin levels and ST-elevation) and non-infarct-like group (n=40) with any other presentation. The composite primary endpoint of major cardiovascular events (MACE) included: all-cause mortality, cardiac mortality, recurrence of myocarditis, heart failure, and sustained ventricular tachycardia. RESULTS: During follow-up, 21 patients (24%) experienced MACE and infarct-like patients were significantly more at risk for MACE than non-infarct-like patients (HR 2.4, 95% CI [1.01-5.80] p=0.04). Infarct-like patients exhibited in particular a higher risk of sustained ventricular tachycardia and recurrence of myocarditis (p=0.03). They had lower CMR-derived left (p=0.03) and right (p=0.001) ventricular ejection fractions, and exhibited larger areas of late gadolinium enhancement (LGE) (p=0.001). In multivariate analysis, both initial NYHA functional class >II and LGE mass were independent predictors for long-term MACE occurrence (HR 5.8 and 1.07 per gram respectively, p=0.007). Moreover, a threshold of LGE mass >17g provided a high discrimination for MACE occurrence (AUC of 0.81). CONCLUSIONS: The infarct-like pattern of acute myocarditis is associated with MACE occurrence. Initial NYHA functional class >II and LGE are independent predictive factors of MACE during long-term follow-up after acute myocarditis.