The effect of tablet computer-based telemonitoring added to an established telephone disease management program on heart failure hospitalizations: The Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) III Randomized Controlled Trial.

BACKGROUND: Mobile health applications are becoming increasingly common. Prior work has demonstrated reduced heart failure (HF) hospitalizations with HF disease management programs; however, few of these programs have used tablet computer-based technology. METHODS: Participants with a diagnosis of HF and at least 1 high risk feature for hospitalization were randomized to either an established telephone-based disease management program or the same disease management program with the addition of remote monitoring of weight, blood pressure, heart rate and symptoms via a tablet computer for 90 days. The primary endpoint was the number of days hospitalized for HF assessed at 90 days. RESULTS: From August 2014 to April 2019, 212 participants from 3 hospitals in Massachusetts were randomized 3:1 to telemonitoring-based HF disease management (n = 159) or telephone-based HF disease management (n = 53) with 98% of individuals in both study groups completing the 90 days of follow-up. There was no significant difference in the number of days hospitalized for HF between the telemonitoring disease management group (0.88 ± 3.28 days per patient-90 days) and the telephone-based disease management group (1.00 ± 2.97 days per patient-90 days); incidence rate ratio 0.82 (95% confidence interval, 0.43-1.58; P = .442). CONCLUSIONS: The addition of tablet-based telemonitoring to an established HF telephone-based disease management program did not reduce HF hospitalizations; however, study power was limited.

The Cardiac Amyloidosis Registry Study (CARS): Rationale, Design and Methodology.

BACKGROUND: CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. METHODS AND RESULTS: This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CONCLUSIONS: CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition.

Emerging Therapies for Transthyretin Amyloidosis.

PURPOSE OF REVIEW: This review provides an overview of the available therapies for treating neuropathic and/or cardiac manifestations of transthyretin amyloidosis (ATTR), as well as investigational therapeutic agents in ongoing clinical trials. We discuss additional emergent approaches towards thwarting this life-threatening disease that until recently was considered virtually untreatable. RECENT FINDINGS: Advances in noninvasive diagnostic methods for detecting ATTR have facilitated easier diagnosis and detection at an earlier stage of disease when therapeutic interventions are likely to be more effective. There are now several ATTR-directed treatments that are clinically available, as well as investigational agents that are being studied in clinical trials. Therapeutic strategies include tetramer stabilization, gene silencing, and fibril disruption. ATTR has been historically underdiagnosed. With advances in diagnostic methods and the advent of disease-modifying treatments, early diagnosis and initiation of treatment is revolutionizing management of this disease.

Disseminated mucormycosis masquerading as rejection early after orthotopic heart transplantation.

Mucorales organisms are an uncommon cause of invasive fungal infections after solid organ transplantation but are associated with great morbidity and mortality. We report a fatal case of disseminated Cunninghamella infection early after heart transplantation. The patient developed graft dysfunction and elevated markers of myocyte injury and autopsy revealed fulminant fungal myocarditis. This case highlights the need for a high index of suspicion in immunocompromised patients who are not improving with standard antimicrobial therapy.

Acute Hemodynamic Effects of Intra-aortic Balloon Counterpulsation Pumps in Advanced Heart Failure.

BACKGROUND: The utility of intra-aortic balloon counterpulsation pumps (IABPs) in low cardiac output states is unknown and no studies have explored the impact of IABP therapy on ventricular workload in patients with advanced heart failure (HF). For these reasons, we explored the acute hemodynamic effects of IABP therapy in patients with advanced HF. METHODS: We prospectively studied 10 consecutive patients with stage D HF referred for IABP placement before left ventricular assist device (LVAD) surgery and compared with 5 control patients with preserved left ventricular (LV) ejection fraction (EF) who did not receive IABP therapy. Hemodynamics were recorded using LV conductance and pulmonary artery catheters. Cardiac index (CI)-responder and CI-nonresponder status was assigned a priori as being "equal to or above" or below the median of the IABP effect on CI, respectively, within 24 hours after IABP activation. RESULTS: Compared with controls, patients with advanced HF had lower LVEF, lower LV end-systolic pressure, lower LV stroke work, and higher LV end-diastolic pressures and volumes before IABP activation. IABP activation reduced LV stroke work primarily by reducing end-systolic pressure. IABP therapy increased CI by a median of 20% as well as increased diastolic pressure time index and the myocardial oxygen supply:demand ratio. Compared with CI-nonresponders, CI-responders had higher systemic vascular resistance, lower right heart filling pressures, and a trend toward lower left heart filling pressures with improved indices of right heart function. Compared with CI-nonresponders, the diastolic pressure time index was increased among CI-responders. CONCLUSIONS: IABP therapy may be effective at reducing LV stroke work, increasing CI, and favorably altering the myocardial oxygen supply:demand ratio in patients with advanced HF, especially among patients with low right heart filling pressures and high systemic vascular resistance.

Preoperative three-dimensional echocardiography to assess risk of right ventricular failure after left ventricular assist device surgery.

BACKGROUND: Right ventricular failure (RVF) is associated with significant morbidity after left ventricular assist device (LVAD) surgery. Hemodynamic, clinical, and 2-dimensional echocardiographic variables poorly discriminate patients at risk of RVF. We examined the utility of 3-dimensional echocardiography (3DE) right ventricular (RV) volumetric assessment to identify patients at risk for RVF. METHODS AND RESULTS: RVF was defined as the need for inotropic infusion for >14 days after LVAD surgery or the need for biventricular assist device support. Preoperative RV volumes and ejection fraction (EF) were measured, blinded to clinical data, from transthoracic 3DE full volume data sets in 26 patients. Baseline variables and 3DE RV indices were compared between patients with and without RVF. Twenty-four patients received continuous-flow LVADs, and 2 required biventricular support devices. Ten patients required prolonged inotropes after LVAD placement. Baseline characteristics associated with RVF included higher right atrial pressure, higher right atrial pressure to pulmonary capillary wedge pressure ratio, and lower cardiac index and RV stroke work index (RVSWI). Echocardiographic indices associated with RVF included 3DE indexed RV end-diastolic and end-systolic volumes (RVEDVI and RVESVI) and RV ejection fraction (RVEF). The relationship between 3DE quantification of RV volumes and the development of RVF was independent from RVSWI: RVEDVI: odds ratio (OR) 1.16, 95% confidence interval (CI) 1.00-1.33 (P = .04); RVESVI: OR 1.14, 95% CI 1.01-1.28 (P = .03). CONCLUSIONS: Quantitative 3DE is a promising method for pre-LVAD RV assessment. RV volumes assessed by 3DE are predictive of RVF in LVAD recipients independently from hemodynamic correlates of RV function.

Left Ventricular Ejection Time Derived From the Common Carotid Artery Doppler Waveform: Association With Left Ventricular Ejection Fraction and Prediction of Heart Failure.

OBJECTIVES: Left ventricular ejection time (LVET) is measured from blood pressure tracings as the interval from end diastole to the dicrotic notch and shows associations with left ventricular ejection fraction (LVEF) and heart failure. LVET can be measured on common carotid artery Doppler waveforms. We therefore studied the possible associations of common carotid artery LVET with LVEF measured by echocardiography and heart failure. METHODS: We performed a retrospective study of 110 patients who had transthoracic echocardiography and carotid Doppler evaluations within 1 day of each other. LVEF was determined by the biplane modified Simpson method. LVET was measured from left common carotid artery Doppler tracings. Linear regression was used to evaluate associations between LVET and LVEF. We also used logistic regression with LVEF of less than 40% as a cut point for heart failure to generate a receiver operating characteristic curve, estimate the area under the curve, and calculate sensitivity and specificity. RESULTS: LVET was associated with LVEF (P < .0001). The area under the curve of LVET for heart failure was 0.81 (95% confidence interval [CI], 0.72-0.87), and the sensitivity and specificity were 76.9% (95% CI, 65.4%-88.4%) and 65.5% (95% CI, 53.4%-77.8%), respectively, for LVET of 321 milliseconds. CONCLUSIONS: LVET measured on common carotid artery Doppler tracings decreases with LVEF and is strongly associated with prevalent heart failure. Based on what is known of blood pressure-measured LVET, common carotid artery Doppler waveform-derived LVET could be used to serially monitor cardiac function.

Association of common carotid artery Doppler-determined dicrotic notch velocity with the left ventricular ejection fraction.

OBJECTIVES: The appearance of the dicrotic notch on blood pressure tracings is associated with impaired cardiac function. Common carotid artery waveforms have similar fiduciary markers, yet they have not been related to cardiac function. We studied associations of common carotid artery dicrotic notch velocities with the left ventricular ejection fraction (LVEF) determined by echocardiography. METHODS: We conducted a retrospective study of 37 patients who had cardiac echocardiography and carotid Doppler evaluations within 1 day of each other. The LVEF was determined by the biplane modified Simpson rule. Doppler parameters were measured from tracings of the left common carotid artery 4 cm from the flow divider. Linear regression and stepwise multivariable linear regression models were used to evaluate any association between the LVEF and the following variables: age, sex, peak systolic velocity (PSV), end-diastolic velocity (EDV), dicrotic notch velocity, rise time (EDV to PSV), resistive index, and cardiac cycle length. RESULTS: The dicrotic notch velocity was the only variable associated with the LVEF (P = .028) in a bivariate analyses. A backward selection stepwise multivariable equation predicting the LVEF had the dicrotic notch (P = .001) and resistive index (P = .01) as significant predictors, whereas the cardiac cycle length (P = .08) and PSV (P = .08) were borderline not significant. Model goodness of fit was R(2) = 0.37 (P = .004). CONCLUSIONS: Dicrotic notch velocities measured from common carotid artery Doppler waveforms are associated with the LVEF and might offer some clinical value in selected cases.

The syndrome of degenerative calcific aortic stenosis: prevalence of multiple pathophysiologic disorders in association with valvular stenosis and their implications.

BACKGROUND: We hypothesized that degenerative calcific aortic stenosis (DCAS) is a syndrome influenced by factors beyond aortic valve stenosis (AS). The aim of this study was to assess how frequently DCAS is complicated by increased vascular load, systolic and/or diastolic left ventricular (LV) dysfunction, and comorbid disorders. METHODS: In 215 consecutive patients > 60 years of age with severe and moderate AS, we analyzed systemic arterial compliance, global hemodynamic load, LV ejection fraction (EF), the presence of diastolic dysfunction, and other valvular or systemic disorders. RESULTS: A total of 164 patients had severe AS and 51 had moderate AS. In patients with severe AS, the prevalence of increased vascular load was 42%; LV systolic and diastolic dysfunction was present in 27% and 42%; other valve diseases in 23%; and comorbid disorders in 82%. In the moderate AS group, abnormal vascular load was found in 52%; LV systolic and diastolic dysfunction was prevalent in 26% and 31%; other valve diseases in 17%; and comorbid disorders in 78% patients. More than half the patients in both groups had symptoms. In both severe and moderate AS groups, the prevalence of increased vascular load and systolic dysfunction was higher in the symptomatic group. CONCLUSION: Considerable number of patients with DCAS have abnormal vascular load, abnormal LV function, and significant coexisting disorders. These could influence the total pathophysiologic burden on the heart and symptom expression. Thus, DCAS should not be considered just as valvular stenosis, but a syndrome of DCAS because of the diagnostic, prognostic, and therapeutic implications of various factors associated with it.

Left ventricular stroke volume index following transcatheter aortic valve replacement is an early predictor of 1-year survival.

BACKGROUND: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. HYPOTHESIS: Steady-state (30-day) LVSVI after TAVR is associated with 1-year mortality. METHODS: A single-center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30-day post-TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre-TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. RESULTS: This analysis focuses on 238 patients treated with TAVR. The 1-year mortality rate was 9% and 124 (52%) patients had normal flow post-TAVR. Of those with pre-TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30-day normal flow was associated with lower 1-year mortality when compared to low flow (4% vs. 14%, p = .007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02-11.63 [per 1 ml/m2 decrease], p = .046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new-onset low flow (12%) (p = .01). CONCLUSIONS: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1-year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short-term imaging marker might represent a novel therapeutic target.

Automated Detection of Aortic Stenosis Using Machine Learning.

BACKGROUND: Aortic stenosis (AS) is a degenerative valve condition that is underdiagnosed and undertreated. Detection of AS using limited two-dimensional echocardiography could enable screening and improve appropriate referral and treatment of this condition. The aim of this study was to develop methods for automated detection of AS from limited imaging data sets. METHODS: Convolutional neural networks were trained, validated, and tested using limited two-dimensional transthoracic echocardiographic data sets. Networks were developed to accomplish two sequential tasks: (1) view identification and (2) study-level grade of AS. Balanced accuracy and area under the receiver operator curve (AUROC) were the performance metrics used. RESULTS: Annotated images from 577 patients were included. Neural networks were trained on data from 338 patients (average n = 10,253 labeled images), validated on 119 patients (average n = 3,505 labeled images), and performance was assessed on a test set of 120 patients (average n = 3,511 labeled images). Fully automated screening for AS was achieved with an AUROC of 0.96. Networks can distinguish no significant (no, mild, mild to moderate) AS from significant (moderate or severe) AS with an AUROC of 0.86 and between early (mild or mild to moderate AS) and significant (moderate or severe) AS with an AUROC of 0.75. External validation of these networks in a cohort of 8,502 outpatient transthoracic echocardiograms showed that screening for AS can be achieved using parasternal long-axis imaging only with an AUROC of 0.91. CONCLUSION: Fully automated detection of AS using limited two-dimensional data sets is achievable using modern neural networks. These methods lay the groundwork for a novel method for screening for AS.

The Emerging Significance of Amyloid Deposits in the Ligamentum Flavum of Spinal Stenosis Patients: A Review.

Spinal stenosis is one of the most common neurosurgical diseases and a leading cause of pain and disability. Wild-type transthyretin amyloid (ATTRwt) has been found in the ligamentum flavum (LF) of a significant subset of patients with spinal stenosis who undergo decompression surgery. Histologic and biochemical analyses of LF specimens from spinal stenosis patients, normally discarded as waste, have the potential to help elucidate the underlying pathophysiology of spinal stenosis and possibly allow for medical treatment of stenosis and screening for other systemic diseases. In the present review, we discuss the utility of analyzing LF specimens after spinal stenosis surgery for ATTRwt deposits. Screening for ATTRwt amyloidosis cardiomyopathy through LF specimens has led to the early diagnosis and treatment of cardiac amyloidosis in several patients, with more expected to benefit from this process. Emerging evidence in the literature also point to ATTRwt as a contributor to a previously unrecognized subtype of spinal stenosis in patients who might, in the future, benefit from medical therapy. In the present report, we review the current literature regarding the early detection of ATTRwt cardiomyopathy via LF screening and the possible contribution of ATTRwt deposits in the LF to spinal stenosis development.

Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS).

BACKGROUND: TRACS sought to describe the clinical outcomes and disease progression of transthyretin (TTR) cardiac amyloidosis (ATTR) in an observational study. Clinical course is largely determined by disease type with ATTR categorized as wild-type (ATTRwt) or genetic-variant protein (ATTRm). Prospective data are lacking in the most common TTR mutation, V122I, present in approximately 3.5% of African Americans. METHODS: Patients with ATTRwt (n = 18) and V122I ATTRm (n = 11) were longitudinally assessed every 6 months for up to 2 years by functional class assessments, biochemical markers, and echocardiography. RESULTS: At baseline, no differences in clinical characteristics, biomarkers, or echocardiographic parameters were noted between patients with ATTRwt and patients with ATTRm. After 15.5 ± 8 months, there were 11 deaths and 1 cardiac transplant, with higher mortality (73% vs 22%, P = .03) and cardiovascular hospitalization (64% vs 28%, P = .02) among patients with ATTRm. The median survival from diagnosis was 25.6 months for ATTRm vs 43.0 months for ATTRwt (P = .04). Univariate predictors of mortality included disease duration, heart rate ≥ 70 beats/min, baseline stroke volume, left ventricular ejection fraction <50%, and ATTRm status. For each 6-month increment, the mean 6-minute walk distance declined by 25.8 m, N-terminal pro b-type natriuretic peptide increased by 1,816 pg/mL, and left ventricular ejection fraction fell by 3.2%, for the entire cohort. CONCLUSIONS: In this prospective study, disease progression, morbidity, and mortality were observed in ATTR cardiomyopathy, particularly due to V122I, over a short duration. Given the prevalence of this mutation, further study of V122I in at-risk African American patients is warranted.

The pulmonary artery pulsatility index identifies severe right ventricular dysfunction in acute inferior myocardial infarction.

BACKGROUND: Right ventricular dysfunction (RVD) is a major cause of morbidity and mortality in the setting of acute inferior wall myocardial infarction (IWMI), and early detection may improve clinical outcomes. We defined a novel hemodynamic index, the pulmonary artery pulsatility index (PAPi), and explored whether the PAPi correlates with severe RVD in acute IWMI. METHODS: From 2008 to 2010, we identified 20 patients presenting with angiographically confirmed proximal right coronary artery occlusion and suspected RVD (sRVD) as defined by hemodynamic instability, profound bradycardia, or ST-elevation in lead V4R. Two controls groups were studied (1) 50 patients with nonobstructive coronary artery disease (Non-CAD) and (2) 14 patients presenting with acute coronary syndrome requiring left coronary stenting (ACS). Hemodynamic indices analyzed at the time of catheterization included: (1) the right atrial to pulmonary capillary wedge pressure ratio (RA:PCWP), (2) right ventricular stroke work (RVSW), and (3) the PAPi. Qualitative echocardiographic scores of RV systolic function were determined by two blinded investigators within 24 hr of catheterization. RESULTS: Among subjects with sRVD, 7 (35%) received a percutaneous RV support device (pRVSD) for medically refractory RV failure and 4 (20%) died prior to hospital discharge. Compared to Non-CAD and ACS controls, subjects with sRVD had a significantly lower PAPi (4.32 ± 3.04 vs. 5.52 ± 4.40 vs. 1.11 ± 0.57, respectively, P < 0.01) and a higher RA:PCWP ratio (0.48 ± 0.24 vs. 0.51 ± 0.26 vs. 0.81 ± 0.30, respectively, P < 0.05). Both the PAPi and RA:PCWP ratios correlated significantly with RVSW and qualitative echocardiographic grading. The PAPi demonstrated the highest sensitivity (88.9%) and specificity (98.3%) for predicting in-hospital mortality and/or requirement of a pRVSD. Using ROC curve derived cut-points, a PAPi ≤ 0.9 provided 100.0% sensitivity and 98.3% specificity (C-statistic: 0.998) for predicting these outcomes, exceeding the predictive value of the RA:PCWP ratio or RVSW. CONCLUSIONS: The PAPi is a simple, invasive hemodynamic measure that may help identify high-risk patients with acute IWMI with severe RVD. Earlier identification of this high-risk population may improve clinical outcomes.

Three-dimensional echocardiographic analysis of right atrial volume in normal and abnormal hearts: comparison of biplane and multiplane methods.

BACKGROUND: Although right atrial size has clinical and prognostic importance, few data exist regarding the optimal three-dimensional echocardiography (3DE) method for assessing right atrial volume (RAV). While measuring RAV in multiple planes may improve the accuracy, it also increases analysis time. The purpose of this study was to determine the minimum number of planes required for optimal assessment of RAV, using eight-plane 3DE measurements as a reference standard. METHODS: 3DE was performed in 70 subjects (35 normal and 35 abnormal). 3DE RAV was obtained from three methods by tracing right atrial endocardial borders at ventricular end-systole in two orthogonal planes (two-plane), four equiangular planes (four-plane), and eight equiangular planes (eight-plane) in each subject. The time required for analysis was recorded for each method. RESULTS: Based on eight-plane RAV, mean RAV was 41 ± 13 mL in the normal group, and 82 ± 35 mL in the abnormal group. The average time for two-plane, four-plane, and eight-plane analysis was 69 ± 29, 118 ± 29, and 203 ± 37 s, respectively (P < 0.001 for comparisons between all groups). Four-plane approach had close agreement with eight-plane (2.6% underestimation for total group), while two-plane measurement underestimated RAV by an average of 19% for the total group, compared to eight-plane. CONCLUSION: Four-plane measurement of RAV shows good agreement with eight-plane measurement, while reducing the time required for analysis. Compared to eight-plane analysis, biplane measurement of RAV can result in underestimation of RAV, particularly in abnormal subjects with right atrial enlargement and remodeling.

Three-dimensional speckle-tracking echocardiography: methodological aspects and clinical potential.

Speckle-tracking echocardiography (STE) is an advanced echocardiographic technique that allows a novel approach to the assessment of cardiac physiology through the study of myocardial mechanics. In its three-dimensional (3D) modality, it overcomes the drawbacks inherent to other echocardiographic techniques, namely two-dimensional echocardiography and tissue Doppler imaging. Several research studies and software improvements have led 3D-STE to become a promising tool for accurate evaluation of global and regional cardiac function. This article addresses the image acquisition, analytical methods, and parameters of myocardial mechanics that could be derived from 3D-STE. This systematic guidance may help to establish its usefulness in the global and regional evaluation of cardiac function, and to facilitate its clinical application.

The use of PYP scan for evaluation of ATTR cardiac amyloidosis at a tertiary medical centre.

Cardiac transthyretin amyloidosis (ATTR) is an often underdiagnosed disease that can lead to significant morbidity and mortality for patients. In recent years, technetium-99m pyrophosphate scintigraphy (PYP) imaging has become a standard of care diagnostic tool to help clinicians identify this disease. With newly emerging therapies for ATTR cardiomyopathy, it is critical to identify patients who are eligible for therapy as early as possible. At our institution, we sought to describe the frequency of PYP scanning and how it has impacted the management of a patient suspected to have amyloid cardiomyopathy. Between 1 January 2017 and 31 December 2020, we identified 273 patients who completed PYP scanning for evaluation of cardiac amyloidosis at Tufts Medical Center, a tertiary care centre. We reviewed pertinent clinical data for all study subjects. A PYP scan was considered positive when the heart to contralateral lung ratio was greater than or equal to 1.5, with a visual grade of 2 or 3, and confirmation with single-photon emission computerised tomography (SPECT) imaging. In total there were 55 positive, 202 negative, and 16 equivocal PYP scans. Endomyocardial biopsies were rarely performed following PYP results. Of the seven patients with a positive PYP scan who underwent biopsy, five were positive for ATTR amyloid; of the patients with a negative scan who were biopsied, none were positive for ATTR amyloidosis and two were positive for amyloid light-chain (AL) amyloidosis. The biomarkers troponin I, B-type naturietic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), as well as the interventricular septal end-diastolic thickness (IVSd) seen on echocardiogram, were all found to be statistically higher in the PYP positive cohort than in the PYP negative cohort using Mann-Whitney U statistical analysis. In total, 27 out of the 55 patients with a positive PYP scan underwent therapy specific for cardiac amyloid. In conclusion, this study reinforces the clinical significance of the PYP scan in the diagnosis and management of cardiac amyloidosis. A positive scan allowed physicians to implement early amyloid-directed treatment while a negative scan encouraged physicians to pursue an alternative diagnosis.

Accuracy of echocardiographic estimations of right heart pressures in adult heart transplant recipients.

BACKGROUND: Accurate assessment of right atrial pressure (RAP) and pulmonary artery systolic pressure (PASP) is critical in the management of heart transplant recipients. The accuracy of echocardiography in estimating these pressures has been debated. OBJECTIVE: To assess the correlation and agreement between echocardiographic estimations of right heart pressures with those of respective invasive hemodynamic measurements by right heart catheterization (RHC) in adult heart transplant recipients. METHODS: This is a prospective evaluation of 84 unique measurements from heart transplant recipients who underwent RHC followed by standard echocardiographic evaluation within 159 ± 64 min with no intervening medication changes. The relationship between noninvasive pressure estimations and invasive hemodynamic measurements was examined. RESULTS: Mean RAP was 7 ± 5 mmHg and mean PASP was 33 ± 8 mmHg by RHC. There was no significant correlation between echocardiographic estimation of RAP and invasive RAP (Spearman's rho = -0.05, p = .7), and no significant agreement between these two variables (weighted kappa = -0.1). There was a modest correlation between echocardiographic estimation of PASP and invasive PASP (r = .39, p = .002). Bland-Altman analysis showed a mean bias of 2.1 ± 9 mmHg (limits of agreement = -15 to 20 mmHg). CONCLUSION: In heart transplant recipients, there is no significant correlation or agreement between echocardiographic RAP estimation and invasively determined RAP. Noninvasive PASP estimation correlates significantly but modestly with invasively measured PASP. Further refinement of echocardiographic methods for assessment of RAP is warranted in this unique patient population.

Analysis of lumbar spine stenosis specimens for identification of amyloid.

BACKGROUND: Lumbar spinal stenosis (LSS) is a common reason for spine surgery in which ligamentum flavum is resected. Transthyretin (TTR) amyloid is an often unrecognized and potentially modifiable mechanism for LSS that can also cause TTR cardiac amyloidosis. Accordingly, older adult patients undergoing lumbar spine (LS) surgery were evaluated for amyloid and if present, the precursor protein, as well as comprehensive characterization of the clinical phenotype. METHODS: A prospective, cohort study in 2 academic medical centers enrolled 47 subjects (age 69 ± 7 years, 53% male) undergoing clinically indicated LS decompression. The presence of amyloid was evaluated by Congo Red staining and in those with amyloid, precursor protein was determined by laser capture microdissection coupled to mass spectrometry (LCM-MS). The phenotype was assessed by disease-specific questionnaires (Swiss Spinal Stenosis Questionnaire and Kansas City Cardiomyopathy Questionnaire) and the 36-question short-form health survey, as well as biochemical measures (TTR, retinol-binding protein, and TTR stability). Cardiac testing included technetium-99m-pyrophosphate scintigraphy, electrocardiograms, echocardiograms, and cardiac biomarkers as well as measures of functional capacity. RESULTS: Amyloid was detected in 16 samples (34% of participants) and was more common in those aged ≥ 75 years of age (66.7%) compared with those <75 years (22.3%, p < 0.05). LCM-MS demonstrated TTR as the precursor protein in 62.5% of participants with amyloid while 37.5% had an indeterminant type of amyloid. Demographic, clinical, quality-of-life measures, electrocardiographic, echocardiographic, and biochemical measures did not differ between those with and without amyloid. Among those with TTR amyloid (n = 10), one subject had cardiac involvement by scintigraphy. CONCLUSIONS: Amyloid is detected in more than a third of older adults undergoing LSS. Amyloid is more common with advancing age and is particularly common in those >75 years old. No demographic, clinical, biochemical, or cardiac parameter distinguished those with and without amyloid. In more than half of subjects with LS amyloid, the precursor protein was TTR indicating the importance of pathological assessment.

Echocardiographic characterization of left ventricular apical hypoplasia accompanied by a patent ductus arteriosus.

Left ventricular (LV) apical hypoplasia is an unusual, recently identified cardiomyopathy, whose clinical course is uncertain. In this report, we describe a case of this cardiomyopathy occurring in an asymptomatic 50-year-old male with a remote history of a surgically corrected patent ductus arteriosus (PDA), primarily using transthoracic echocardiography (TTE) to illustrate the imaging characteristics. This patient had been referred to our institution for an abnormal electrocardiogram, and TTE subsequently (Figure 1) revealed a dilated left ventricle with moderately to severely reduced function; LV ejection fraction was 30% by two- and three-dimensional quantification. The left ventricle had a spherical appearance with a thin-walled, truncated, and akinetic distal LV. The right ventricle appeared elongated and was noted to wrap around the distal left ventricle, but right ventricular systolic function was normal. There were no significant valvular abnormalities, and no evidence of residual PDA flow. Subsequent cardiac magnetic resonance (CMR) imaging confirmed these findings (Figure 1). The TTE and CMR findings seen in this patient are consistent with LV apical hypoplasia. Until now, this cardiomyopathy has been described only as an isolated congenital anomaly primarily using CMR and cardiac computed tomography. To our knowledge, this is the first reported case of LV apical hypoplasia in conjunction with another congenital cardiac abnormality, and the findings demonstrate that the distinctive appearance of this cardiomyopathy can be easily identified with echocardiography. As more cases are recognized and patients are followed over time, the natural history and optimal treatment for this cardiomyopathy may be further elucidated.