Wild type cardiac amyloidosis: is it time to order a nuclear technetium pyrophosphate SPECT imaging study?

Transthyretin (ATTR) amyloidosis is a debilitating systemic disease often associated with symptomatic cardiac involvement. Diagnosis has dramatically changed with the advent of Technetium-99 m pyrophosphate (Tc-PYP) single-photon emission computed tomography (SPECT). With the ability to diagnose ATTR amyloidosis noninvasively and offer newer therapies, it is increasingly important to identify which patients should be referred for this testing. Relative apical sparing of longitudinal strain on echocardiogram can be potentially used to screen such patients. We sought to describe electrocardiogram (ECG) and echocardiogram (TTE) findings, including relative apical sparing of longitudinal strain, in ATTR amyloidosis patients diagnosed non-invasively with 99mTc-PYP imaging. This was a single-center, retrospective study with 64 patients who underwent 99mTc-PYP imaging between June 2016 and February 2019. Relative apical longitudinal strain was calculated from left ventricular longitudinal strain (LV LS) values. No ECG parameters were meaningfully associated with of 99 m Tc-PYP positive patients. LV mass index (p = 0.001), IVSd (p < 0.001), and LVPWd (< 0.001) demonstrated a highly significant difference between positive and negative 99mTc-PYP groups. 99mTc-PYP positive patients had a higher relative apical sparing of LV LS (p < 0.001), and notably, no 99mTc-PYP negative patient had a ratio > 1.0. The finding of relative apical sparing of longitudinal strain can reliably guide clinicians in triaging which patients to consider ordering 99mTc-PYP imaging for the noninvasive diagnosis of wild type cardiac amyloidosis. A patient with clinically suggestive features and an LV LS relative apical sparing ratio > 0.8 can be considered for 99mTc-PYP imaging to evaluate for ATTR cardiac amyloidosis.

Deep Learning-Based Automated Echocardiographic Quantification of Left Ventricular Ejection Fraction: A Point-of-Care Solution.

BACKGROUND: We have recently tested an automated machine-learning algorithm that quantifies left ventricular (LV) ejection fraction (EF) from guidelines-recommended apical views. However, in the point-of-care (POC) setting, apical 2-chamber views are often difficult to obtain, limiting the usefulness of this approach. Since most POC physicians often rely on visual assessment of apical 4-chamber and parasternal long-axis views, our algorithm was adapted to use either one of these 3 views or any combination. This study aimed to (1) test the accuracy of these automated estimates; (2) determine whether they could be used to accurately classify LV function. METHODS: Reference EF was obtained using conventional biplane measurements by experienced echocardiographers. In protocol 1, we used echocardiographic images from 166 clinical examinations. Both automated and reference EF values were used to categorize LV function as hyperdynamic (EF>73%), normal (53%-73%), mildly-to-moderately (30%-52%), or severely reduced (<30%). Additionally, LV function was visually estimated for each view by 10 experienced physicians. Accuracy of the detection of reduced LV function (EF<53%) by the automated classification and physicians' interpretation was assessed against the reference classification. In protocol 2, we tested the new machine-learning algorithm in the POC setting on images acquired by nurses using a portable imaging system. RESULTS: Protocol 1: the agreement with the reference EF values was good (intraclass correlation, 0.86-0.95), with biases <2%. Machine-learning classification of LV function showed similar accuracy to that by physicians in most views, with only 10% to 15% cases where it was less accurate. Protocol 2: the agreement with the reference values was excellent (intraclass correlation=0.84) with a minimal bias of 2.5±6.4%. CONCLUSIONS: The new machine-learning algorithm allows accurate automated evaluation of LV function from echocardiographic views commonly used in the POC setting. This approach will enable more POC personnel to accurately assess LV function.

Utility of a Deep-Learning Algorithm to Guide Novices to Acquire Echocardiograms for Limited Diagnostic Use.

Importance: Artificial intelligence (AI) has been applied to analysis of medical imaging in recent years, but AI to guide the acquisition of ultrasonography images is a novel area of investigation. A novel deep-learning (DL) algorithm, trained on more than 5 million examples of the outcome of ultrasonographic probe movement on image quality, can provide real-time prescriptive guidance for novice operators to obtain limited diagnostic transthoracic echocardiographic images. Objective: To test whether novice users could obtain 10-view transthoracic echocardiographic studies of diagnostic quality using this DL-based software. Design, Setting, and Participants: This prospective, multicenter diagnostic study was conducted in 2 academic hospitals. A cohort of 8 nurses who had not previously conducted echocardiograms was recruited and trained with AI. Each nurse scanned 30 patients aged at least 18 years who were scheduled to undergo a clinically indicated echocardiogram at Northwestern Memorial Hospital or Minneapolis Heart Institute between March and May 2019. These scans were compared with those of sonographers using the same echocardiographic hardware but without AI guidance. Interventions: Each patient underwent paired limited echocardiograms: one from a nurse without prior echocardiography experience using the DL algorithm and the other from a sonographer without the DL algorithm. Five level 3-trained echocardiographers independently and blindly evaluated each acquisition. Main Outcomes and Measures: Four primary end points were sequentially assessed: qualitative judgement about left ventricular size and function, right ventricular size, and the presence of a pericardial effusion. Secondary end points included 6 other clinical parameters and comparison of scans by nurses vs sonographers. Results: A total of 240 patients (mean [SD] age, 61 [16] years old; 139 men [57.9%]; 79 [32.9%] with body mass indexes >30) completed the study. Eight nurses each scanned 30 patients using the DL algorithm, producing studies judged to be of diagnostic quality for left ventricular size, function, and pericardial effusion in 237 of 240 cases (98.8%) and right ventricular size in 222 of 240 cases (92.5%). For the secondary end points, nurse and sonographer scans were not significantly different for most parameters. Conclusions and Relevance: This DL algorithm allows novices without experience in ultrasonography to obtain diagnostic transthoracic echocardiographic studies for evaluation of left ventricular size and function, right ventricular size, and presence of a nontrivial pericardial effusion, expanding the reach of echocardiography to clinical settings in which immediate interrogation of anatomy and cardiac function is needed and settings with limited resources.

Transcatheter Tricuspid Valve-in-Valve Intervention for Degenerative Bioprosthetic Tricuspid Valve Disease.

Isolated reoperative tricuspid valve replacement is one of the highest risk operations classified in the Society of Thoracic Surgeons registry, particularly in the setting of preexisting right ventricular dysfunction. Transcatheter tricuspid valve-in-valve implantation represents an attractive alternative to redo surgery in patients with tricuspid bioprosthetic valve degeneration who are considered high-risk or unsuitable surgical candidates. In this review article, the authors discuss the emergence of transcatheter tricuspid valve-in-valve therapy, preprocedural echocardiographic assessment of tricuspid bioprosthetic valve dysfunction, periprocedural imaging required for tricuspid valve-in-valve implantation, and postprocedural assessment of tricuspid transcatheter device function.

Imaging Assessment of the Interatrial Septum for Transcatheter Atrial Septal Defect and Patent Foramen Ovale Closure.

Transcatheter closure of atrial septal defects and patent foramen ovale has become increasingly common with advances in device and imaging technology. The percutaneous approach is now the preferred method of closure when anatomically suitable. Two-dimensional and 3-dimensional echocardiography determines anatomic suitability by characterizing the interatrial defect and its surrounding structures, and is critical for intraprocedural guidance and postprocedure follow-up. This article provides an overview of interatrial anatomy as it pertains to interventional considerations and discusses the transthoracic, transesophageal, and intracardiac echocardiographic modalities used for periprocedural and intraprocedural imaging of the interatrial septum.

Left ventricular outflow tract velocity time integral outperforms ejection fraction and Doppler-derived cardiac output for predicting outcomes in a select advanced heart failure cohort.

BACKGROUND: Left ventricular outflow tract velocity time integral (LVOT VTI) is a measure of cardiac systolic function and cardiac output. Heart failure patients with low cardiac output are known to have poor cardiovascular outcomes. Thus, extremely low LVOT VTI may predict heart failure patients at highest risk for mortality. METHODS: Patients with heart failure and extremely low LVOT VTI were identified from a single-center database. Baseline characteristics and heart failure related clinical outcomes (death, LVAD) were obtained at 12 months. Correlation between clinical endpoints and the following variables were analyzed: ejection fraction (EF), pulmonary artery systolic pressure (PASP), NYHA class, renal function, Doppler cardiac output (CO), and LVOT VTI. RESULTS: Study cohort consisted of 100 patients. At the 12-month follow up period, 30 events (28 deaths, 2 LVADs) were identified. Occurrence of death and LVAD implantation was statistically associated with a lower LVOT VTI (p = 0.039) but not EF (p = 0.169) or CO (p = 0.217). In multivariate analysis, LVOT VTI (p = 0.003) remained statistically significant, other significant variables were age (p = 0.033) and PASP (p = 0.022). Survival analysis by LVOT VTI tertile demonstrated an unadjusted hazard ratio of 4.755 (CI 1.576-14.348, p = 0.006) for combined LVAD and mortality at one year. CONCLUSIONS: Extremely low LVOT VTI strongly predicts adverse outcomes and identifies patients who may benefit most from advanced heart failure therapies.

Can hospital rounds with pocket ultrasound by cardiologists reduce standard echocardiography?

BACKGROUND: Frequently, hospitalized patients are referred for transthoracic echocardiograms. The availability of a pocket mobile echocardiography device that can be incorporated on bedside rounds by cardiologists may be a useful and frugal alternative. METHODS: This was a cross-sectional study designed to compare the accuracy of pocket mobile echocardiography images with those acquired by transthoracic echocardiography in a sample of hospitalized patients. Each patient referred for echocardiography underwent pocket mobile echocardiography acquisition and interpretation by a senior cardiology fellow with level II training in echocardiography. Subsequently, transthoracic echocardiography was performed by skilled ultrasonographers and interpreted by experienced echocardiographers. Both groups were blinded to the results of the alternative imaging modality. Visualizability and accuracy for all key echocardiographic parameters (ejection fraction, wall motion abnormalities, left ventricular end-diastolic dimension, inferior vena cava size, aortic and mitral valve pathology, and pericardial effusion) were determined and compared between imaging modalities. RESULTS: A total of 240 hospitalized patients underwent echocardiography with pocket mobile echocardiography and transthoracic echocardiography. The mean age was 71 ± 17 years. Pocket mobile echocardiography imaging time was 6.3 ± 1.5 minutes. Sensitivity of pocket mobile echocardiography varied by parameter and was highest for aortic stenosis (97%) and lowest for aortic insufficiency (76%). Specificity also varied by parameter and was highest for mitral regurgitation (100%) and lowest for left ventricular ejection fraction (92%). Equivalence testing revealed the pocket mobile echocardiography outcomes to be significantly equivalent to the transthoracic echocardiography outcomes with no discernible differences in image quality between pocket mobile echocardiography and transthoracic echocardiography (P = 7.22 × 10(-7)). All outcomes remain significant after correcting for multiple testing using the false discovery rate. CONCLUSIONS: The results from rapid bedside pocket mobile echocardiography examinations performed by experienced cardiology fellows compared favorably with those from formal transthoracic echocardiography studies. For hospitalized patients, this finding could shift the burden of performing and interpreting the echocardiogram to the examining physician and reduce the number and cost associated with formal echocardiography studies.

Left Atrial Diastolic Dysfunction And Pulmonary Venous Hypertension In Atrial Fibrillation: Clinical, Hemodynamic And Echocardiographic Characteristics.

BACKGROUND: Left ventricular diastolic dysfunction has been well described; diastolic abnormalities of the LA are less frequently recognized and poorly understood. OBJECTIVE: The purpose of this study was to investigate the clinical, hemodynamic and echocardiographic features of left atrial (LA) diastolic dysfunction. METHODS: Patients with atrial fibrillation (AF), severe LA enlargement, and pulmonary venous hypertension (PVH, Group 1) were compared to patients with pulmonary arterial hypertension (PAH), normal LA size and sinus rhythm (Group 2). All underwent right heart catheterization and transthoracic echo to evaluate hemodynamics and LA function. Mitral regurgitation was evaluated by transesophageal echocardiography. LA diastolic function was measured by comparing filling fraction, pulmonary venous flow and compliance. RESULTS: Right atrial, pulmonary artery systolic and mean pressures were similar. Mean wedge pressure were increased in Group 1, 20.8±2.6 versus 9.7±2.8 mm of Hg (p<0.0001). The most striking hemodynamic difference was large V wave in Group 1 without significant mitral regurgitation. LA filling fraction was abnormal in Group 1, 11.4%±8.5 compared to Group 2, 111.5%±44 (p<0.0001). LA compliance was 0.39±0.27 ml/m2/mmHg in Group 1 versus 6.8±4.54 ml/m2/mmHg in Group 2 (p=0.001). There was a strong negative correlation between the V wave and LA filling fraction (r= 0.756, p<0.001). The ratio of the height of the transmitral E wave divided by the S/D ratio (the LA diastolic dysfunction index) correlated very strongly with the V wave (r=0.907, p<0.001). CONCLUSION: LA diastolic dysfunction is present in some patients with long standing AF and PVH. LA diastolic dysfunction, in addition to left ventricular diastolic dysfunction, may contribute to the syndrome of heart failure with preserved left ventricular systolic function.

Is pocket mobile echocardiography the next-generation stethoscope? A cross-sectional comparison of rapidly acquired images with standard transthoracic echocardiography.

BACKGROUND: A pocket mobile echocardiography (PME) device is commercially available for clinical use, but public data documenting its accuracy compared with standard transthoracic echocardiography (TTE) are not available. OBJECTIVE: To compare the accuracy of rapidly acquired PME images with those acquired by standard TTE. DESIGN: Cross-sectional study. At the time of referral for TTE, ultrasonographers acquired PME images first in 5 minutes or less. Ultrasonographers were not blinded to the clinical indication for imaging or to the PME image results when obtaining standard TTE images. Two experienced echocardiographers and 2 cardiology fellows who were blinded to the indication for the study and TTE results but not to the device source interpreted the PME images. SETTING: Scripps Clinic Torrey Pines and Scripps Green Hospital, La Jolla, California. PATIENTS: Convenience sample of 97 patients consecutively referred for echocardiography. MEASUREMENTS: Visualizability and accuracy (the sum of proportions of true-positive and true-negative readings and observer variability) for ejection fraction, wall-motion abnormalities, left ventricular end-diastolic dimension, inferior vena cava size, aortic and mitral valve pathology, and pericardial effusion. RESULTS: Physician-readers could visualize some but not all echocardiographic measurements obtained with the PME device in every patient (highest proportions were for ejection fraction and left ventricular end-diastolic dimension [95% each]; the lowest proportion was for inferior vena cava size [75%]). Accuracy also varied by measurement (aortic valve was 96% [highest] and inferior vena cava size was 78% [lowest]) and decreased when nonvisualizability was accounted for (aortic valve was 91% and inferior vena cava size was 58%). Observer agreement was fair to moderate for some measurements among less-experienced readers. LIMITATION: The study was conducted at a single setting, there was no formal estimate of accuracy given the small convenience sample of patients, and few abnormal echocardiographic measurements occurred. CONCLUSION: The rapid acquisition of images by skilled ultrasonographers who use PME yields accurate assessments of ejection fraction and some but not all cardiac structures in many patients. Further testing of the device in larger patient cohorts with diverse cardiac abnormalities and with untrained clinicians obtaining and interpreting images is required before wide dissemination of its use can be recommended. PRIMARY FUNDING SOURCE: National Institutes of Health.

Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and predictors.

BACKGROUND: There have been no studies of atrial diastolic function after catheter ablation of atrial fibrillation (AF). We encountered a few patients with symptomatic left atrial (LA) diastolic dysfunction and associated pulmonary hypertension (PH) that developed after catheter ablation for atrial fibrillation. Similar findings were described in patients after cardiac surgery and were referred to as the "stiff left atrial syndrome." OBJECTIVE: The purpose of this study was to prospectively quantify the incidence of patients developing PH associated with diastolic hemodynamic abnormalities of the LA after radiofrequency ablation of AF and to identify the possible predictors. METHODS: Between January 2009 and July 2010, data on 1,380 consecutive patients were prospectively collected. Before ablation and at follow-up, all patients had an echocardiogram to assess for the presence of PH. Patients with no echocardiographic evidence of PH but complaining of unexplained dyspnea with LA diastolic abnormalities were evaluated with right heart catheterization (RHC). Patients were included in the analysis if they developed new or worsening PH postablation with evidence of LA diastolic dysfunction by RHC or direct LA pressure measurement. All patients were evaluated for pulmonary vein stenosis and excluded if this condition was identified. RESULTS: The mean age was 62 ± 11 (75% male), and nonparoxysmal AF was the predominant arrhythmia (71%). New or worsening PH with associated LA diastolic abnormalities was detected in 19 (1.4%) patients after ablation. The prevalence of PH did not differ between AF types (P = .612). Compared with patients who did not develop PH, LA scarring (P <.001), diabetes (P = .026), and obstructive sleep apnea (OSA; P = .006) were more frequently observed among those who developed PH. In a multivariable logistic model, preprocedure LA size ≤45 mm (odds ratio [OR] = 6.13; P = .033), mean LA pressure (OR 1.14; P = .025), severe LA scarring (OR = 4.4; P = .046), diabetes mellitus (OR = 9.5; P = .004), and OSA (OR = 6.2; P = .009) were independently associated with the development of PH postablation. CONCLUSIONS: After radiofrequency catheter ablation of atrial fibrillation (RFCAF), PH with LA diastolic dysfunction or the so-called stiff LA syndrome is a rare but potentially significant complication of AF ablation. Severe LA scarring, LA ≤45 mm, diabetes mellitus, OSA, and high LA pressure are clinical variables that predict the development of this syndrome. The main clinical findings include dyspnea, congestive heart failure, PH, and large V waves on pulmonary capillary wedge pressure (PCWP) or LA pressure tracings in the absence of mitral regurgitation.

The Biomedical Resource Ontology (BRO) to enable resource discovery in clinical and translational research.

The biomedical research community relies on a diverse set of resources, both within their own institutions and at other research centers. In addition, an increasing number of shared electronic resources have been developed. Without effective means to locate and query these resources, it is challenging, if not impossible, for investigators to be aware of the myriad resources available, or to effectively perform resource discovery when the need arises. In this paper, we describe the development and use of the Biomedical Resource Ontology (BRO) to enable semantic annotation and discovery of biomedical resources. We also describe the Resource Discovery System (RDS) which is a federated, inter-institutional pilot project that uses the BRO to facilitate resource discovery on the Internet. Through the RDS framework and its associated Biositemaps infrastructure, the BRO facilitates semantic search and discovery of biomedical resources, breaking down barriers and streamlining scientific research that will improve human health.