The Subclinical Cardiomyopathy of Friedreich's Ataxia in a Pediatric Population.

BACKGROUND: Identification of a subclinical cardiomyopathy in pediatric patients with Friedreich's ataxia (FA) has not been well-described. METHODS: We performed echocardiography (Echo), cardiac magnetic resonance imaging (cMRI), and neurologic assessment in a cross-sectional analysis of 48 genetically confirmed FA subjects aged 9-17 years with moderate neurologic impairment but without a cardiovascular history. Echo- and cMRI-determined left ventricular mass were indexed (LVMI) to height in grams/m2.7. LV remodeling was categorized as concentric remodeling (CR), concentric hypertrophy (CH), or eccentric hypertrophy based upon Echo- determined relative LV wall thickness. RESULTS: Echo LVMI exceeded age-based normal values in 85% of subjects, and cMRI-determined LVMI correlated with depression of both diastolic and systolic tissue Doppler velocity (E': r = -0.65, P < .001, S': r = -0.46, P < .001) as well as increased early diastolic Doppler flow velocity/tissue velocity ratio (r= 0.55, P < .001), a marker of elevated LV filling pressure. Similar associations were found with echo-determined LV mass. Evidence of depressed LV relaxation and increased LV stiffness were observed in 88% and 71%, of subjects, respectively, despite a normal LV ejection fraction in almost all cases (mean = 60% + 7%). CR and CH were present in 40% and 44% of the study group, respectively, although significant depressions of E' and S' were observed only in subjects with CH (P < .005). CONCLUSIONS: A subclinical hypertrophic cardiomyopathy is common in pediatric FA patients and CH is associated with both diastolic and systolic dysfunction.

Device closure of paravalvular defects following transcatheter aortic valve replacement with the Edwards Sapien valve.

Paravalvular aortic insufficiency (AI) is observed in the majority of patients undergoing transcatheter aortic valve replacement (TAVR). While paravalvular AI is most commonly modest following TAVR, moderate or severe AI was seen in 10.5% and 6.8% of the PARTNER inoperable and high-risk cohorts at 1 year and has been reportedly associated with dyspnea and diminished survival. We report two cases of transcatheter heart valve (THV) associated paravalvular defects closed using catheter delivered devices. Both patients derived hemodynamic and symptomatic improvement from device closure. Additional research is warranted to define the adverse consequences of THV associated AI, indications for treatment, and risks associated with device closure of these defects.

A novel flexible endoluminal stapling device for use in NOTES colotomy closure: a feasibility study using an ex vivo porcine model.

BACKGROUND: With advances in endoscopic diagnosis of early-stage gastrointestinal pathology, the need to offer minimally invasive treatment is attracting significant interest. It is essential that secure and consistent closure of full-thickness colonic resections and colotomy access be provided in natural orifice translumenal surgery (NOTES). This ex vivo porcine study aimed to evaluate a novel prototype flexible endoscopic stapler device for use in closure of full-thickness colonic defects. METHODS: A feasibility study using ex vivo porcine colon was undertaken to explore the potential of the prototype stapler to close and seal a colotomy. A standardized linear colotomy was created in 30 colons. The novel flexible endostapler was used to close 20, interrupted hand-sewn sutures to close 5, and a well-validated linear stapler to close 5 of these colotomies. The colons were subsequently subjected to leak pressure testing. RESULTS: The colotomy closure using the prototype stapler endoluminally required a median time of 280 s. No statistically significant difference in leak pressures between the stapler and the other techniques was described. Although the endostapler without any colotomy was found to have the highest median leak pressures and the interrupted sutures the lowest pressures, no significant difference could be demonstrated (p = 0.52). Furthermore, no significant difference was demonstrated when the closure integrity created by the flexible stapler was compared with that created by the well-validated linear stapler. CONCLUSION: The results suggest that the flexible endoscopic stapler is an effective device for the safe closure of a visceral defect, which in this feasibility study was equivalent to other well-established techniques. Further studies will focus on in vivo application of the prototype stapling device in the setting of full-thickness colonic resection.

Artificial Intelligence and Echocardiography: A Primer for Cardiac Sonographers.

Artificial intelligence (AI) is emerging as a key component in diagnostic medical imaging, including echocardiography. AI with deep learning has already been used with automated view labeling, measurements, and interpretation. As the development and use of AI in echocardiography increase, potential concerns may be raised by cardiac sonographers and the profession. This report, from a sonographer's perspective, focuses on defining AI, the basics of the technology, identifying some current applications of AI, and how the use of AI may improve patient care in the future.

Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia.

Cardiac calsequestrin (Casq2) is thought to be the key sarcoplasmic reticulum (SR) Ca2+ storage protein essential for SR Ca2+ release in mammalian heart. Human CASQ2 mutations are associated with catecholaminergic ventricular tachycardia. However, homozygous mutation carriers presumably lacking functional Casq2 display surprisingly normal cardiac contractility. Here we show that Casq2-null mice are viable and display normal SR Ca2+ release and contractile function under basal conditions. The mice exhibited striking increases in SR volume and near absence of the Casq2-binding proteins triadin-1 and junctin; upregulation of other Ca2+ -binding proteins was not apparent. Exposure to catecholamines in Casq2-null myocytes caused increased diastolic SR Ca2+ leak, resulting in premature spontaneous SR Ca2+ releases and triggered beats. In vivo, Casq2-null mice phenocopied the human arrhythmias. Thus, while the unique molecular and anatomic adaptive response to Casq2 deletion maintains functional SR Ca2+ storage, lack of Casq2 also causes increased diastolic SR Ca2+ leak, rendering Casq2-null mice susceptible to catecholaminergic ventricular arrhythmias.

Randomized controlled trial of the efficacy of aerobic exercise in reducing metabolic risk in healthy older people: The Hertfordshire Physical Activity Trial.

BACKGROUND: While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group. METHODS/DESIGN: We aim to recruit 100 participants born between 1931-1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing. DISCUSSION: Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN60986572.

A Summary of the American Society of Echocardiography Foundation Value-Based Healthcare: Summit 2014: The Role of Cardiovascular Ultrasound in the New Paradigm.

Value-Based Healthcare: Summit 2014 clearly achieved the three goals set forth at the beginning of this document. First, the live event informed and educated attendees through a discussion of the evolving value-based healthcare environment, including a collaborative effort to define the important role of cardiovascular ultrasound in that environment. Second, publication of these Summit proceedings in the Journal of the American Society of Echocardiography will inform a wider audience of the important insights gathered. Third, moving forward, the ASE will continue to build a ''living resource'' on its website, http://www.asecho.org, for clinicians, researchers, and administrators to use in advocating for the value of cardiovascular ultrasound in the new value-based healthcare environment. The ASE looks forward to incorporating many of the Summit recommendations as it works with its members, legislators, payers, hospital administrators, and researchers to demonstrate and increase the value of cardiovascular ultrasound. All Summit attendees shared in the infectious enthusiasm generated by this proactive approach to ensuring cardiovascular ultrasound's place as ''The Value Choice'' in cardiac imaging.

Percutaneous closure of a mitral perivalvular leak using three dimensional real time and color flow imaging.

The role of echocardiography, including three-dimensional (3D) echocardiography, during interventional procedures in the cardiac catheterization laboratory is continuing to expand as interventional cardiologists perform more catheter-based interventions. Echocardiography often complements angiographic imaging of cardiac structures and sometimes provides additional information not available by angiography and fluoroscopy. The closure of perivalvular leaks using catheter-based techniques is one of the areas in which 3D echocardiography can be helpful. This case report describes the use of 3D real-time and color flow imaging during the closure of a mitral perivalvular leak. Three-dimensional echocardiography was used to assess the leak prior to intervention and the success of the intervention at the completion of the case.

A predictive instrument using contrast echocardiography in patients presenting to the emergency department with chest pain and without ST-segment elevation.

OBJECTIVE: Risk stratification of patients presenting to the emergency department (ED) with suspected cardiac chest pain (CP) and an undifferentiated electrocardiogram (ECG) is difficult. We hypothesized that in these patients a risk score incorporating clinical, ECG, and myocardial contrast echocardiography (MCE) variables would accurately predict adverse events occurring within the next 48 hours. METHODS: Patients with CP lasting for 30 minutes or more who did not have ST-segment elevation on the ECG, were enrolled. Regional function (RF) and myocardial perfusion (MP) were assessed by MCE. A risk model was developed in the initial 1166 patients (cohort 1) and validated in subsequent 720 patients (cohort 2). Any abnormality or ST changes on ECG (odds ratio [OR] 2.5; 95% confidence interval [CI], 1.4-4.5, P = .002, and OR 2.9, 95% CI, 1.7-4.8, P < .001, respectively), abnormal RF with normal MP (OR 3.5, 95% CI, 1.8-6.5, P < .001), and abnormal RF with abnormal MP (OR 9.6, 95% CI, 5.8-16.0, P < .001) were found to be significant multivariate predictors of nonfatal myocardial infarction or cardiac death. RESULTS: The estimate of the probability of concordance for the risk model was 0.82 for cohort 1 and 0.83 for cohort 2. The risk score in both cohorts stratified patients into 5 distinct risk groups with event rates ranging from 0.3% to 58%. CONCLUSION: A simple predictive instrument has been developed from clinical, ECG, and MCE findings obtained at the bedside that can accurately predict events occurring within 48 hours in patients presenting to the ED with suspected cardiac CP and an ECG that is not diagnostic for acute ischemic injury. Its application could enhance care of patients with CP in the ED. For instance, patients with a risk score of 0 could be discharged from the ED without further workup. However, this needs to be validated in a multicenter study.

A novel non-invasive method to assess aortic valve opening in HeartMate II left ventricular assist device patients using a modified Karhunen-Loève transformation.

BACKGROUND: Thrombus formation on or near the aortic valve has been reported in HeartMate II (Thoratec, Pleasanton, CA) left ventricular assist device (LVAD) patients whose aortic valves do not open. With an akinetic valve, thrombogenesis is more likely. Thrombus formation may lead to neurologic events, placing the patient at greater risk. Aortic valve stenosis and/or regurgitation have also been observed with akinetic aortic valves. Assessing aortic valve opening is crucial when optimizing rotations per minute (rpm) to minimize embolic risk and aortic valve stenosis but presently relies solely on echocardiography, intermittent decreases in rpms to force aortic valve opening, and monitoring of pulse pressure. We hypothesized the electrical current waveforms of the HeartMate II would reveal whether the aortic valve was opening due to pressure changes in the left ventricle to allow for continuous monitoring and control of aortic valve opening ratios. METHODS: Electrical HeartMate II current waveforms of patients from 2008 to 2009 that were recorded at the time of echocardiograph procedures were analyzed using a modified Karhunen-Loève transformation with a training set of electrical waveforms from 8,860 HeartMate II electrical current recordings from 2001 to 2009. RESULTS: The study included 6 patients. The electrical current magnitude of the projection of the electrical current waveforms onto the training set's eigenvectors was statistically significantly greater in 4 of the 6 patients when the aortic valve was closed, confirmed by echocardiography. The 2 patients who did not have a large increase in the magnitude had mild aortic valve regurgitation. CONCLUSION: Electrical current analysis for rotary non-pulsatile pumps is a means to develop a physiologic feedback algorithm for an auto-mode, which currently does not exist. Constant regulation and optimization of rotary non-pulsatile LVADs would minimize patients' risk for neurologic events and aortic valve stenosis.

Risk factors predictive of right ventricular failure after left ventricular assist device implantation.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation appears to be associated with increased mortality. However, the determination of which patients are at greater risk of developing postoperative RVF remains controversial and relatively unknown. We sought to determine the preoperative risk factors for the development of RVF after LVAD implantation. The data were obtained for 175 consecutive patients who had received an LVAD. RVF was defined by the need for inhaled nitric oxide for >/=48 hours or intravenous inotropes for >14 days and/or right ventricular assist device implantation. An RVF risk score was developed from the beta coefficients of the independent variables from a multivariate logistic regression model predicting RVF. Destination therapy (DT) was identified as the indication for LVAD implantation in 42% of our patients. RVF after LVAD occurred in 44% of patients (n = 77). The mortality rates for patients with RVF were significantly greater at 30, 180, and 365 days after implantation compared to patients with no RVF. By multivariate logistic regression analysis, 3 preoperative factors were significantly associated with RVF after LVAD implantation: (1) a preoperative need for intra-aortic balloon counterpulsation, (2) increased pulmonary vascular resistance, and (3) DT. The developed RVF risk score effectively stratified the risk of RV failure and death after LVAD implantation. In conclusion, given the progressively growing need for DT, the developed RVF risk score, derived from a population with a large percentage of DT patients, might lead to improved patient selection and help stratify patients who could potentially benefit from early right ventricular assist device implantation.

Assessment of the right ventricle by echocardiography: a primer for cardiac sonographers.

The assessment of right ventricular (RV) structure and function by echocardiography has been improved by advancements that include Doppler tissue imaging, strain imaging, and three-dimensional imaging. Doppler tissue imaging and strain imaging can be useful for the assessment of regional RV systolic and diastolic function. Three-dimensional imaging has been reported to determine RV volumes and ejection fraction, which have previously been cumbersome to measure with conventional two-dimensional echocardiography. This article addresses the role of conventional and newer methods of echocardiography to assist sonographers in understanding the technical considerations, limitations, and pitfalls of image acquisition and analysis of RV structure and function.

Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium.

OBJECTIVE: Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart. METHODS: Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry. RESULTS: Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/-0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02, and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls, P=.03, respectively). The number of blood vessels >50 mum in diameter was significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015). CONCLUSION: BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.