Pislaru, Sorin V.

ObjectivesThe purpose of this study was to compare the prevalence and impact of work‐related musculoskeletal pain in cardiac sonographers to a large control group of peer employees with similar demographics.BackgroundCardiac sonographers are known to have high levels of occupational musculoskeletal pain. Comparative studies with other employees within cardiology/radiology departments have never been performed.MethodsAn electronic survey was administered to Mayo Clinic employees at six major patient care facilities in four different states.ResultsThere were 2682 employees within the departments of cardiology and radiology who were contacted, and 1532 (57%) completed the survey. After excluding those who wore protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers reported work‐related musculoskeletal pain more frequently than the control group (88% vs 40%; P<.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment, and history of preexisting musculoskeletal pain (OR 11.6; [95% CI 5.32, 25.5]; P<.001). Cardiac sonographers sought medical care for their work‐related pain more often (55% vs 21%; P<.001) and missed more work due to pain (35% vs 12%, P<.001). In a secondary analysis, cardiac sonographers also experienced more work‐related musculoskeletal pain than nurses, technicians, and physicians working in the interventional laboratory who regularly wear a protective lead apron (P<.001).ConclusionsIn this multisite cross‐sectional study, cardiac sonographers experienced significantly more work‐related pain and missed more work due to pain than peer employees within cardiology/radiology departments.

ObjectivesThis study sought to assess the learning curve for TMVR for treatment of primary mitral regurgitation (MR).BackgroundData are lacking regarding the technical experience required to achieve optimal clinical outcomes with transcatheter mitral valve repair (TMVR) using the edge‐to‐edge MitraClip technique.MethodsWe examined the sequential experience of the first 75 patients (age 80 ± 9 years; 77% male) who underwent TMVR at our institution. A sequence number of each patient was assigned as a continuous variable and in tertiles for analysis.ResultsTMVR with MitraClip was successful in 97% with an average procedural time of 106 ± 39 minutes. The 30‐day rate of major adverse cardiovascular events was 7%. With increased case experience, there were decreases in procedural time, fluoroscopy time, length of hospital stay, and major adverse cardiovascular events. Procedural success, residual mitral regurgitation and NYHA functional classification at 30‐day follow‐up remained unchanged throughout the experience.ConclusionsThe learning curve for TMVR with MitraClip for treatment of primary MR is characterized by a sequential reduction in procedure time, fluoroscopy time, procedural complications, and hospital length of stay at a tertiary academic medical center. Thirty‐day procedural results are favorable and similar during the initial learning period.

Low-flow, low-gradient (LF/LG) severe aortic stenosis (AS) with preserved ejection fraction refers to the condition of AS with aortic valve area ≤1 cm2, stroke volume index <35 mL/m2, mean aortic valve gradient <40 mm Hg and left ventricular ejection fraction ≥50%. This mismatch of aortic valve area suggesting severe stenosis and ‘low’ gradient in some patients has led to confusion as to the severity of stenosis. Conditions previously labelled as LF/LG severe AS include a spectrum, with measurement error probably being the most common cause of marked inconsistency between gradient, valve area and patient presentation. The presence of LG severe AS may be overestimated in petite patients, who may have aortic valve area slightly less than 1 cm2 with only moderate AS. Concomitant cardiac conditions besides AS, including significant mitral and tricuspid regurgitation, intracardiac shunts and constrictive pericarditis, may contribute to reduced stroke volume, and evidence for these must be sought at the time of echocardiography. True LF/LG severe AS is associated with a unique and probably maladaptive remodelling pattern with smaller ventricles, increasing relative wall thickness, progressive worsening of diastolic function and higher afterload, as demonstrated by lower systemic arterial compliance, higher systemic vascular resistance and higher valvuloarterial impedance. Control of hypertension is essential to the appropriate management of patients with AS. Aortic valve replacement should be considered in patients with compelling evidence of severe AS who remain symptomatic despite optimal treatment of hypertension.

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF <60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF <30%, would affect a minuscule number of patients (0.3%). Conversely, EF <45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF >60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF <45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF <45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges >60%, with EF dropping <60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

Robust shear-wave motion detection is essential for producing reliable shear elasticity measurements for ultrasound shear-wave elastography (SWE). However, because shear-wave motion is extracted from radiofrequency signals which can be heavily contaminated by noise, shear-wave motion detection can be very challenging, especially for in vivo applications. This study investigated the implementation of harmonic imaging (HI) to facilitate more robust shear-wave tracking based on HI’s effectiveness in suppressing imaging noise associated with ultrasound reverberation, phase aberration, and clutter noise. A HI shear-wave tracking sequence was developed combining the pulse-inversion HI method with the plane wave imaging technique to transmit phase-inverted pulses at a high frame rate of several kilohertz. The backscattered ultrasound signals from phase-inverted pulses were added to suppress the fundamental and enhance the second harmonic component, from which the shear-wave motion was extracted. A pork belly phantom experiment showed that HI could significantly improve shear-wave motion detection by producing almost three-fold less underestimation of shear-wave motion and over ten-fold more precision for shear-wave speed measurements than fundamental imaging. An in vivo transthoracic case study of a human heart showed that HI substantially improved the success rate of shear-wave motion detection and could provide consistent estimates of the left ventricle myocardium stiffness.

Ultrasound (US) enhancement of plasmid-based gene transfer is an emerging technique. Our hypothesis was that two contrast agents (Optison and PESDA), and two US exposure modalities (dedicated continuous wave system and diagnostic scanner) may have different effects. Luciferase plasmid with or without contrast agent was added to vascular smooth muscle cells and endothelial cells, followed by US exposure. Luciferase activity was measured 24 h later. US exposure consistently induced higher transfection rates than all controls. PESDA was superior to Optison in both cell lines. In vitro, continuous wave and diagnostic US were not significantly different. In vivo, Lux and PESDA were injected into skeletal muscles of rats (IM or intra-arterial) followed or not by US exposure. In separate animals, adenovirus encoding for luciferase was injected IM and was not followed by US exposure. Gene transfer efficacy was 8–10 fold higher with US and PESDA than with plasmid alone, but 2 fold lower than with adenovirus. However, as opposed to adenovirus, US-enhanced plasmid gene transfer was highly localized to the injected muscle, with no expression at distal sites. Our results support the hypothesis that contrast agents and exposure modalities are not equivalent with regard to gene transfer efficacy.

Background Three‐dimensional transthoracic echocardiography (3D‐ TTE ) with dedicated software permits quantification of mitral annulus dynamics and papillary muscle motion throughout the cardiac cycle. Methods and Results Mitral apparatus 3D‐ TTE was acquired in controls (n=42), patients with left ventricle dysfunction and functional mitral regurgitation ( LVD ‐ FMR ; n=43) or without FMR ( LVD ‐no MR , n=35). Annulus in both normal and LVD ‐no MR subjects displayed saddle shape accentuation in early‐systole (ratio of height to intercommissural diameter, 10.6±3.7 to 13.5±4.0 in normal and 9.1±4.3 to 12.6±3.6 in LVD ‐no MR ; P <0.001 for diastole to early‐systole motion, P = NS between those groups). In contrast, saddle shape was unchanged from diastole in FMR patients (10.0±6.4 to 8.0±5.2; P = NS , P <0.05 compared to both other groups). Papillary tips moved symmetrically towards to the midanterior annulus in control and LVD ‐no MR subjects, maintaining constant ratio of the distances between both tips to midannulus (Pt AR ) throughout systole. In LVD ‐ FMR patients midsystolic posterior papillary tip to anterior annulus distance was increased, resulting in higher Pt AR ( P =0.05 compared to both other groups). Mechanisms of early‐ and midsystolic FMR differed between different etiologies of LV dysfunction. In patients with anterior MI and global dysfunction annular function and dilatation were the dominant parameters, while papillary muscle motion was the predominant determinant of FMR in patients with inferior MI . Conclusions Inadequate early‐systolic annular contraction and saddle‐shape accentuation in patients with impaired LV contribute to early–mitral incompetency. Asymmetric papillary tip movement towards the midanterior annulus is a major determinant of mid‐ and late‐systolic functional mitral regurgitation.

Background— Respiratory dependence of tricuspid regurgitation (TR), a long-held concept suggested by murmur variation, remains unproven and of unclear mechanisms. Methods and Results— In 41 patients with mild or greater TR (median age, 67 years), we performed triple Doppler echocardiographic quantification (TR severity, right ventricular, and right atrial quantification) with simultaneous respirometer recording of respiratory phases. Expiration to inspiration changes (median) affected TR peak velocity (−40 cm/s; 25th to 75th percentile, −60 to −30 cm/s), duration (−12 milliseconds; 25th to 75th percentile, −45 to 2 milliseconds), and time-velocity integral (−17 cm; 25th to 75th percentile, −23.4 to −10 cm; all P <0.001), consistent with decreased TR driving force. Nevertheless, inspiratory TR augmentation was demonstrated by increased effective regurgitant orifice (0.21 cm 2 ; 25th to 75th percentile, 0.09 to 0.34 cm 2 ) and volume (18 mL per beat; 25th to 75th percentile, 10 to 25 mL per beat; all P <0.001) infrequently detected clinically (2 of 41, 5). As a result of reduced TR driving force, regurgitant volume increased less than effective regurgitant orifice (120 [25th to 75th percentile, 78.6 to 169] versus 169 [ 25th to 75th percentile, 12.9 to 226.1]; P <0.001). During inspiration, right ventricular area increased (diastolic, 27.8 [25th to 75th percentile, 22.6 to 36.3] versus 26.5 [21.1 to 31.9]; P <0.0001) with widening of right ventricular shape (length-to-width ratio, 1.6 [ 25th to 75th percentile, 1.37 to 1.95] versus 1.7 [1.46 to 2.1]; P <0.0001), increased systolic annular diameter ( P =0.003), valve tenting height ( P <0.0001) and area ( P <0.0001), and reduced valvular-to-annular ratio ( P =0.006). Effective regurgitant orifice during inspiration was independently determined by inspiratory valvular-to-annular ratio ( P =0.026) and inspiratory change in right ventricular length-to-width ratio ( P =0.008) and valve tenting area ( P =0.015). Conclusions— TR is dynamic with almost universal respiratory changes of large magnitude and complex pathophysiology. During inspiration, a large increase in effective regurgitant orifice causes, despite a decline in regurgitant gradient, a notable increase in regurgitant volume. Effective regurgitant orifice changes are independently linked to inspiratory annular enlargement (decreased valvular coverage) and to inspiratory right ventricular shape widening with increased valvular tenting. These novel physiological insights into TR respiratory dependence underscore right-side heart plasticity and are important for clinical TR severity evaluation.

Background— Endothelial progenitor cells (EPCs) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intrarenal microvascular injury and remodeling. We investigated whether replenishment with EPCs would protect the renal microcirculation in chronic experimental renovascular disease. Methods and Results— Single-kidney hemodynamics and function were assessed with the use of multidetector computed tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal infusion of autologous EPCs, and controls. Renal microvascular remodeling and angiogenic pathways were investigated ex vivo with the use of micro–computed tomography, histology, and Western blotting. EPCs increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs normalized the blunted renal microvascular and filtration function. Conclusions— The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs involved not only generation of new vessels but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease.