Infiltrative Cardiomyopathy Research Articles

Biventricular Strain Imaging with Cardiac MRI in Genotyped and Histology Validated Amyloid Cardiomyopathy.

Cardiac amyloidosis (CA) is a common and potentially fatal infiltrative cardiomyopathy. Contrast-enhanced cardiac MRI (CMR) is used as a diagnostic tool. However, utility of CMR for the comprehensive analysis of biventricular strains and strain rates is not reported as extensively as echocardiography. In addition, RV strain analysis using CMR has not been described previously.Objectives:We sought to study the global and regional indices of biventricular strain and strain rates in endomyocardial biopsy (EMB)-proven, genotyped cases of CA.Methods:A database of 80 EMBs was curated from 2012 to 2019 based on histology. A total of 19 EMBs positive for CA were subjected to further tissue-characterization with histology, and compared with four normal biopsy specimens. Samples were genotyped for ATTR- or AL-subtypes. Five patients, with both echocardiography and contrast-enhanced CMR performed 72-h apart, were subjected to comprehensive analysis of biventricular strain and strain-rates.Results:Histology confirmed that the selected samples were indeed positive for cardiac amyloid. Echocardiography showed reduced global and regional left-ventricular (LV) longitudinal strain indices. CMR with tissue-characterization of LV showed global reductions in circumferential, radial and longitudinal strains and strain-rates, following a general trend with the echocardiographic findings. The basal right-ventricular (RV) segments had reduced circumferential strains with no changes in longitudinal strain.Conclusions:In addition to providing a clinical diagnosis of CA based on contrast clearance-dynamics, CMR can be a potent tool for accurate functional assessment of global and regional changes in strain and strain-rates involving both LV and RV. Further studies are warranted to validate and curate the strain imaging capacity of CMR in CA.

Utility of Cardiac Magnetic Resonance Imaging in the Diagnosis, Prognosis, and Treatment of Infiltrative Cardiomyopathies.

Diagnosis of infiltrative cardiomyopathies can be challenging despite differences in clinical manifestations due to overlapping cardiac manifestations. We review the salient findings by cardiac magnetic resonance imaging that aids in diagnosis, as well the potential implications for prognosis and treatment. Cardiac magnetic resonance imaging has added substantially to our understanding of various infiltrative cardiomyopathies, and the addition of late gadolinium enhancement imaging and parametric mapping has yielded additional insights regarding potential diagnoses, prognosis, and therapy. Cardiac magnetic resonance imaging should be employed in the setting of suspected hypertrophic or infiltrative cardiomyopathies to aid in diagnosis. In the setting of cardiac amyloidosis and Fabry disease, there is data to suggest that cardiac magnetic resonance imaging is useful for risk stratification as well as for monitoring response to therapy.

Cardiac amyloidosis in non-transplant cardiac surgery.

Cardiac amyloidosis is a rare infiltrative cardiomyopathy that portends a poor prognosis. There is a growing recognition of co-existent aortic valve stenosis and transthyretin cardiac amyloidosis, with some studies suggesting that dual pathology may be associated increased risk of complication and mortality during surgical intervention. This review aims to evaluate the available literature on non-transplant cardiac surgical interventions in patients with cardiac amyloidosis, with particular focus on diagnosis, high surgical risk and areas of uncertainty that require further research.

Reversible Catecholamine Induced Cardiomyopathy

Background: Pheochromocytomas and paragangliomas (PPGL) are rare neuro-endocrine tumors associated with a myriad of poor outcomes as a result of long-term exposure to catecholamines. Although paragangliomas are less commonly associated with increased catecholamine production than adrenal pheochromocytomas, there have been a few reports of catecholamine-induced cardiomyopathy in patients diagnosed with PPGL. We report a case of a PPGL associated with hypercoagulability and cardiomyopathy. Clinical Case: 42-year-old man with uncontrolled hypertension presented to the emergency department with abdominal pain. On CT imaging, he was found to have hepatic lesions, aortocaval lymph node concerning for metastatic disease, left renal infarct, and a left ventricular thrombus. Soon after his admission, he developed acute ataxia, gaze palsies and left hemiparalysis. CTA of the head showed a basilar artery thrombus [FJ1] which was treated with emergent thrombectomy. In addition patient had absent distal pulse of the right foot[FJ2], and found to have thrombus of the popliteal artery, which was treated with thrombectomy. Further workup with abdominal MRI showed retroperitoneal mass[FJ3] and multiple hepatic lesions concerning for metastatic extra-adrenal neuroendocrine tumor. Plasma normetanephrine was 4.5 nmol/L (ULN 0.89), plasma metanephrine 0.3 nmol/L (ULN 0.49) Chromogranin A was 387 ng/ml (ULN 160). Ga-68 DOTATE scan was consistent with an extra adrenal paraganglioma with less prominent radiotracer activity in hepatic lesion concerning for dedifferentiated metastatic disease. In addition, echocardiogram showed reduced LV ejection fraction of 24% with global hypokinesis, and confirmed the LV thrombus. Cardiac MRI showed infiltrative nonischemic cardiomyopathy and mild dilation of left ventricle, as well as patchy delayed enhancement in the basal and inferoseptal walls suggestive of myocarditis. Treatment included rivaroxaban[FJ4], lisinopril, doxazosin, furosemide, and carvedilol. Several months after discharge, his EF improved to 48%. Hepatic lesions concerning for dediffertiated tumor vs unrelated malignancy was biopsied[FJ5] and consistent with neuroendocrine tumor. Future plan for his PPGL include revaluation for resection of retroperitoneal mass or DOTA Lutathera therapy. Conclusions: This case highlights a young man who was incidentally found to have metastatic paraganglioma with catecholamine-induced cardiomyopathy. The patient was asymptomatic until he developed significant heart failure. Cardiomyopathy in this setting is thought to be secondary to uncontrolled hypertension, as well as sympathetic overdrive from overstimulation of norepinephrine. We present the case to highlight the management challenges in a patient with PPGL with significant cardiovascular compromise and limited therapeutic options.

High Rate of Systolic Heart Failure in Patients with Hereditary Transthyretin Cardiac Amyloid

Purpose Hereditary Transthyretin Cardiac Amyloidosis (hATTR- CM) is an infiltrative cardiomyopathy that is usually associated with significant ventricular hypertrophy and restrictive diastolic dysfunction. Recent studies have demonstrated that patients with the V122Ile hATTR-CM variant present with worse functional status at diagnosis compared to wild-type and other hereditary variants. Therefore, we sought to assess the prevalence of systolic heart failure and associated clinical characteristics at the time of diagnosis of V122Ile hATTR-CM patients in our single, tertiary care center. Methods 69 patients were diagnosed with V122Ile hATTR-CM between 2013 - 2020 by genetic testing in combination with technetium pyrophosphate scanning or endomyocardial biopsy. Demographic and diagnostic data were collected by retrospective chart review and patients with systolic heart failure, defined as EF ≤ 40%, were identified. All data is reported as mean ± standard error or percentage of whole. Results Among our cohort of 69 patients with V122Ile hATTR-CM, 46 (67%) were found to have systolic heart failure with a LVEF of 26% ± 10.1, IVS thickness of 17.4 mm ± 4.1, and LV Mass Index was 166.2 g/m2 ± 61.2. Troponin I and BNP biomarkers averaged 0.26 ± 0.61 and 885 ± 561, respectively. The most prominent extra-cardiac manifestations among the systolic heart failure group were bilateral carpal tunnel syndrome in 25 (54%) patients, lumbar stenosis in 11 (24%), and polyneuropathy in 9 (20%). A significant delay in diagnosis was seen with an average time of 19 months from time of presentation to ATTR diagnosis. Average survival time after diagnosis was 2.5 ± 1.8 years and 6 (16%) patients underwent successful orthotopic heart transplant. 33% of patients with systolic heart failure were found to have primary prevention ICDs. Conclusion In a cohort of 69 V122Ile hATTR-CM patients, 67% were found to have systolic heart failure at the time of initial diagnosis. A significant delay was noted in time to diagnosis, which is consistent with the existing literature. Despite the delay in diagnosis and depressed LVEF at presentation, average survival remained > 2 years. Delayed diagnosis remains a critical problem for hATTR-CM patients.

The Importance of Multimodality Imaging in the Diagnosis and Management of Patients with Infiltrative Cardiomyopathies: An Update.

Infiltrative cardiomyopathies (ICMs) comprise a broad spectrum of inherited and acquired conditions (mainly amyloidosis, sarcoidosis, and hemochromatosis), where the progressive buildup of abnormal substances within the myocardium results in left ventricular hypertrophy and manifests as restrictive physiology. Noninvasive multimodality imaging has gradually eliminated endomyocardial biopsy from the diagnostic workup of infiltrative cardiac deposition diseases. However, even with modern imaging techniques’ widespread availability, these pathologies persist in being largely under- or misdiagnosed. Considering the advent of novel, revolutionary pharmacotherapies for cardiac amyloidosis, the archetypal example of ICM, a standardized diagnostic approach is warranted. Therefore, this review aims to emphasize the importance of contemporary cardiac imaging in identifying specific ICM and improving outcomes via the prompt initiation of a targeted treatment.

Epicardial adipose tissue modulates arrhythmogenesis in right ventricle outflow tract cardiomyocytes.

Ventricular arrhythmia (VA) frequently occurs in fatty infiltrative cardiomyopathy or epicardial adipose tissue (EAT) abundant hearts. Right ventricular outflow tract (RVOT), commonly covered with EAT, is vital for VA genesis. This study explored whether EAT contributes to RVOT arrhythmogenesis. Conventional microelectrodes and whole-cell patch clamp were used to record electrical activity and ionic currents in rabbit RVOT tissue preparation or isolated single cardiomyocytes with or without (control) connected EAT. Epicardial adipose tissue-connected (N = 6) RVOT had more portions of fibrosis than did control (N = 5) RVOT (160.3 ± 23.2 vs. 91.9 ± 13.4 μm2/mm2, P < 0.05). Epicardial adipose tissue-connected RVOT cardiomyocytes (n = 18) had lower negative resting membrane potential (-68 ± 1 vs. -73 ± 2 mV, P < 0.05); smaller action potential (AP) amplitude (108 ± 4 vs. 135 ± 6 mV, P < 0.005); and longer 90%, 50%, and 20% of AP duration repolarization (361 ± 18 vs. 309 ± 9 ms, P < 0.05; 310 ± 17 vs. 256 ± 13 ms, P < 0.05; and 182 ± 19 vs. 114 ± 24 ms, P < 0.05, respectively) than did control (n = 13) RVOT cardiomyocytes. Moreover, compared with control RVOT cardiomyocytes, EAT-connected RVOT cardiomyocytes had larger transient outward potassium currents, similar delayed rectifier potassium currents, smaller L-type calcium currents, and inward rectifier potassium currents. After ajmaline (10 μM, a sodium channel blocker) superfusion, high VA inducibility was observed through rapid pacing in EAT-connected RVOT but not in control RVOT. Epicardial adipose tissue exerts distinctive electrophysiological effects on RVOT with a propensity towards VA induction, which might play a role in lipotoxicity pathogenesis-related ventricular arrhythmogenesis.

Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. Most common CA types are light chain amyloidosis (AL) caused by monoclonal immunoglobulin light chains and transthyretin amyloidosis (ATTR) caused by either mutated or wild-type transthyretin aggregates. Previously considered a rare disease, CA is increasingly recognized among patients who may be misdiagnosed as undifferentiated heart failure with preserved ejection fraction (HFPEF), paradoxical low-flow/low-gradient aortic stenosis, or otherwise unexplained left ventricular hypertrophy. Progress in diagnosis has been due to the refinement of cardiac echocardiographic techniques (speckle tracking imaging) and magnetic resonance (T1 mapping) and mostly due to the advent of bone scintigraphy that has enabled noninvasive diagnosis of ATTR, limiting the need for endomyocardial biopsy. Importantly, proper management of CA starts from early recognition of suspected cases among high prevalence populations, followed by advanced diagnostic evaluation to confirm diagnosis and typing, preferentially in experienced amyloidosis centers. Differentiating ATTR from other types of amyloidosis, especially AL, is critical. Emerging targeted ATTR therapies offer the potential to improve outcomes of these patients previously treated only palliatively.

A Retrospective Audit of Positive 99mTc-Pyrophosphate (PYP) Studies to Identify the Frequency of Extracardiac Manifestations of Amyloidosis

Amyloidosis is a systemic or localised disease that is caused by the deposition of anomalous fibrillar proteins. Deposits of amyloid in the heart results in an infiltrative cardiomyopathy, known as cardiac amyloidosis. A heart to contralateral chest ratio of >1.5 in a 99mTc-pyrophosphate (PYP) which has shown to be 97% sensitive and 100% specific for identifying TTR amyloidosis. There can be extracardiac manifestations of systemic amyloidosis that are rarely elucidated in clinical practice.

Global Left Ventricular Myocardial Work Efficiency in Heart Failure Patients with Cardiac Amyloidosis: Pathophysiological Implications and Role in Differential Diagnosis.

Introduction:Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies.Aims:This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers.Materials and Methods:The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive 99mTc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module.Results:Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (Β = −0.55; P < 0.0001), global longitudinal strain (Β =0.35; P < 0.008), and regional relative strain ratio (Β = −0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55–0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: a GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%.Conclusions:The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA.

CMR-derived ECVs vary with myocardial region and associate with the regional wall thickness

This study was designed to identify whether the position and size of the region of interest (ROI) influence extracellular volume fraction (ECV) measurements. Patients with localized (n = 203) or infiltrative (n = 215) cardiomyopathies and 36 normal controls were enrolled in this study. ECV measurements at 4 different regions, including the anterior, septal, posterior and lateral wall regions, were measured, and all groups were compared. Regional ECV was correlated with the corresponding regional wall thickness. The diagnostic power to differentiate the myocardial abnormalities was evaluated for each myocardial region. ECVs measured using five different ROI sizes within each myocardial region were compared. Our results showed that ECVs varied among the myocardial regions, and this variation was significantly associated with regional wall thicknesses. For the detection of myocardial abnormalities, regional ECV revealed similar results as ECV derived from the whole region except for the anterior region. No significant difference was found in the ECVs measured using the five different ROI sizes. In conclusion, CMR-derived ECVs vary with myocardial region, and this variation is significantly associated with the regional wall thickness. In contrast, the measured size of the ROI has less of an effect on the ECV.

A case report of an infiltrative cardiomyopathy in everyday practice: a specific cause that cannot be missed in the elderly.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a commonly misdiagnosed cardiac condition due to low disease awareness and perceived rarity, which frequently results in incorrect management and poor outcomes. Early and prompt diagnosis has become critical with emerging therapies that improve patient survival.Case summary A 68-year-old woman presented to a tertiary care centre with acute decompensated heart failure following recurrent hospitalizations for the same issue over the past several months. Transthoracic echocardiography revealed severe concentric left ventricular hypertrophy with grade III diastolic dysfunction. However, QRS voltage by 12-lead electrocardiogram (ECG) was discordant with the degree of left ventricular hypertrophy seen by echocardiography, and the patient had recurrent non-sustained ventricular tachycardia that necessitated implantable cardioverter-defibrillator implantation a few months prior. After aggressive diuresis, the patient completed cardiac magnetic resonance imaging that raised concern for cardiac amyloidosis. Subsequent serum and urine protein electrophoresis with associated immunofixation were within normal limits. Finally, ATTR-CM was confirmed by technetium-99m pyrophosphate scintigraphy with plans to initiate tafamidis after genetic testing.Discussion Patients >60 years of age with diastolic heart failure phenotypically similar to hypertrophic cardiomyopathy and/or hypertensive heart disease should always be evaluated for ATTR-CM. Features that increase suspicion include discordance between left ventricular wall thickness and ECG voltage, and signs/symptoms of a primary peripheral and autonomic neuropathy. Useful non-invasive diagnostic testing has also made the diagnosis of ATTR-CM inexpensive and possible without the need for an endomyocardial biopsy. Unfortunately, this patient’s diagnosis of ATTR-CM came late in her disease course, which delayed the onset of definitive therapy.

Abstract 16136: Underutilization of Appropriate Testing for Transthyretin Amyloidosis Despite Suspicious Clinical &amp; Echocardiographic Findings

Introduction: Both hereditary (hATTR) and wild-type (wtATTR) transthyretin amyloidosis are under-recognized causes of cardiomyopathy (CM) and heart failure. Certain findings on Transthoracic Echocardiography (TTE) and cardiac Magnetic Resonance Imaging (cMRI) are suggestive but not diagnostic of ATTR. Although biopsy historically has been the gold standard for diagnosis, patients can be diagnosed with the highly sensitive and specific technetium-99m pyrophosphate scan (Tc-99m PYP). Genetic testing is recommended to confirm hATTR in patients diagnosed with ATTR cardiac amyloidosis. Despite growing awareness of this condition, many cases remain undiagnosed. This study evaluated if patients with TTEs concerning for infiltrative CM received appropriate diagnostic testing for ATTR-CM. Methods: Our echocardiography registry was queried from January 2011 to March 2020 for patients with our echo lab’s embedded infiltrative CM code. Data on demographics, comorbidities, TTE variables, cMRI results, PYP scans, genetic testing and biopsy results were retrieved from electronic medical records. Thorough manual chart review excluded other causes of CM. Data was expressed as mean ± SD and n (%). Results: We retrieved 510 patients (mean age 64 ± 16 years; 43% female) with TTEs suspicious for infiltrative CM revealing a mean interventricular septal diameter (IVSd) of 1.6 ± 0.3 cm. Only 67 (13%) patients underwent cMRI with 11 (16%) suggestive of cardiac amyloidosis. Of the patients with suspicious TTEs, 16 (3.1%) had PYP scans and 24 (4.7%) had tissue biopsy, with positive results in 7 (44%) and 11 (46%), respectively. Genetic testing in 31 (6%) patients revealed known hATTR mutations in 2 (6.5%) patients. Cardiac amyloidosis was diagnosed in 23 (4.5%) with 11 ATTR (2 hATTR), 5 amyloid light chain, and 7 unknown subtype. Conclusion: Despite clinical and TTE findings suspicious for ATTR-CM, many patients did not undergo appropriate confirmatory testing (see Figure 1).

Abstract 12812: The Use of Hemodynamics Does Not Aide in Correctly Identifying the Etiology of Cardiomyopathy in Patients Receiving Advanced Therapy

Introduction: There is limited evidence demonstrating the benefit of hemodynamics in diagnosing the etiology of cardiomyopathy in patients referred for advanced therapies such as left ventricular assist device (LVAD) or orthotropic heart transplantation (OHT). Hypothesis: In patients with end stage heart failure, invasive hemodynamic measures differ between patients with different etiologies of cardiomyopathy. Methods: Hemodynamic and echocardiography data from 119 patients undergoing LVAD (n=85, Male 76%, Age 63 ± 12 years) or OHT (n=34, Male 70%, Age 60 ± 11 years) at a single center was reviewed. The follow invasive hemodynamic measurements were recorded and compared (central venous pressure (CVP), Pulmonary Artery Pulsatility Index (PAPI), peripheral vascular resistance (PVR), transpulmonary gradient, mean pulmonary artery pressure, cardiac index, and pulmonary diastolic pressure decoupling) were compared between groups. Results: Between patients with dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and those with missed diagnosis, there were no significant differences between CVP, PAPI, PVR, transpulmonary gradient, mean PA pressure, cardiac index, or decoupling (Table 1). Left ventricular end diastolic diameter (LVEDD) on echocardiography was significantly larger in patients with DCM when compared to those with ischemic cardiomyopathy as well as infiltrative cardiomyopathies (6.65±1.04mm, 6.24±0.77mm, and 5.14±1.25mm, respectively p&lt;0.0001). Conclusions: Hemodynamic measures in patients with stage D cardiomyopathy did not differ according to the etiology of the underlying cardiomyopathy. . The similarity in hemodynamic profiles amongst different cardiomyopathy subtypes likely reflects end stage disease. LVEDD performed better than hemodynamics to help differentiate cardiomyopathy etiologies, and in addition were helpful in identifying cases where the diagnosis was incorrect.

Abstract 14455: Hidden in Plain Sight: An Elusive Cause of Cardiogenic Shock

A 54-year-old man with chronic obstructive pulmonary disease (COPD) presented with three days of chest pain, dyspnea on exertion, and orthopnea. Physical examination revealed jugular venous distention and lower extremity edema. Cardiac biomarkers were elevated. The differential diagnosis for the clinical presentation included: acute coronary syndrome, and type II myocardial infarction or myocardial injury due to acute decompensated heart failure. External records demonstrated recurrent admissions for similar signs and symptoms, with negative coronary angiogram. Shortly after admission, the patient developed acute cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. Echocardiogram revealed biventricular failure and a possible mitral valve vegetation. The differential diagnosis was refined to include myocarditis (infectious and noninfectious causes), bacterial versus marantic endocarditis, and infiltrative cardiomyopathies. Transesophageal echocardiography revealed mass-like, bileaflet thickening of the mitral valve, not consistent with true vegetation. Infectious, rheumatologic, and hypercoagulable workups were negative. Given the lack of a unifying diagnosis, a right ventricular (RV) endomyocardial biopsy was pursued. This revealed myocardial necrosis and fibrosis, and a mural thrombus with extensive eosinophils. The primary data was then revisited, which revealed history of peripheral eosinophilia that was intermittently suppressed by steroids given for COPD. Cardiac magnetic resonance imaging (MRI) demonstrated diffuse biventricular subendocardial late gadolinium enhancement and RV thrombi. Evaluation for underlying causes of eosinophilia was negative leading to the diagnosis of Loeffler’s endocarditis due to idiopathic hypereosinophilic syndrome. This case demonstrates: (1) the important role of cardiac MRI in the evaluation of both unexplained myocardial injury and new cardiomyopathy, (2) a rare case of Loeffler’s endocarditis requiring mechanical circulatory support, and (3) the consequences of both availability bias and failure to fully “unpack” the primary diagnostic data, which rendered the true etiology of the patient’s cardiogenic shock “hidden in plain sight.”

Abstract 16558: The Burden of Arrhythmia in Cardiac Amyloidosis Hospitalizations: Perspective From a Nationwide Study

Introduction: Cardiac amyloidosis (CA) is a significantly underdiagnosed cause of infiltrative and restrictive cardiomyopathy, which leads to rapidly progressive heart failure associated with poor outcomes. Hypothesis: There is a paucity of data on the incidence and outcomes of arrhythmia among CA hospitalizations. Methods: Nationwide Inpatient Sample from 2016 to 2017 was used for the present analysis. CA hospitalizations with concurrent arrhythmia were identified by using appropriate ICD-10 CM codes, and it was compared with CA hospitalizations without arrhythmia. The primary outcome was all-cause in-hospital mortality, and secondary outcomes were the length of stay and total hospital cost. The adjusted odds ratio was calculated by multivariable regression analysis after adjusting for baseline characteristics and comorbidities. Results: A total of 5030 hospitalizations with CA were identified, of which 1570 had associated arrhythmia. CA hospitalizations with arrhythmia had higher mortality compared to without arrhythmia (150 (10.82%) vs. 215 (6.21%), P=0.012) (Table 1). Length of stay (9.74 days vs. 8.20 days, P=0.02) and total cost of hospitalization (avg. $ 112840 vs. $88638, P=0.02) were significantly higher in CA hospitalizations with concomitant arrhythmia (Table 1). Among arrhythmia, atrial fibrillation was the most common (89.38%) (Figure 1). Adjusted odds of in-hospital mortality due to any arrhythmia (aOR (adjusted odds ratio) = 1.83, CI (confidence interval) = 1.14 - 2.92, P=0.012) or atrial fibrillation (aOR= 1.73, CI= 1.075-2.277, P= 0.02) were significantly higher in CA hospitalization (Table 2). Conclusions: CA hospitalizations with arrhythmia had a higher adjusted odds of in-hospital mortality as compared to without arrhythmia. Additionally, CA hospitalization with arrhythmia had a longer length of stay, and cost of care. Among all arrhythmia, atrial fibrillation was the most common.

Abstract 15864: Measured versus Estimated Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction

Introduction: Obesity is common in heart failure with preserved ejection fraction (HFpEF) and dietary weight loss can improve functional capacity, but sarcopenia and frailty are also frequently present. Little evidence is available regarding resting metabolic rate (RMR) or how commonly used equations to estimate RMR compare to measured RMR in HFpEF. This information is vital for counseling patients on individual caloric needs. Hypothesis: Commonly used estimation equations do not accurately reflect measured RMR in patients with HFpEF. Methods: Resting metabolic rate (RMR) was measured with a metabolic cart for consecutive patients with HFpEF (EF ≥50%) referred for right heart catheterization at the University of Michigan from 2011-2015. Patients with congenital, infiltrative, hypertrophic, or restrictive cardiomyopathy were excluded. The RMR was calculated using the Weir formula: RMR= 1440*[3.94 VO 2 (l/min) + 1.11*VCO 2 (l/min)] kcal/day. Measured RMR and estimations of RMR using the Harris Benedict Equation (HBE), Mifflin-St Jeor Equation (MSJE), and World Health Organization (WHO) equation were compared using paired t-tests and Bland-Altman plots. Results: Patients (n=43) were aged (mean ± SD) 62 ± 11.6 years, 53% female, and BMI 34.9 ± 11. Mean measured RMR from Weir equation was 1514 ± 479 kcal/day. Estimated RMR by HBE was 1784 ± 530, MSJE was 1685 ± 457, and WHO equation was 1816.8 ± 485 kcal/day. All estimations significantly overestimated RMR when compared to the Weir method (&gt;10% difference and p&lt;0.01 for all; Figure A-C). The MSJE had the closest range of agreement to the measured RMR. Conclusions: Estimations of resting metabolic rate in patients with HFpEF demonstrated a fixed bias towards overestimation when compared to measured RMR by metabolic cart. Given HFpEF populations are often obese and are counseled routinely on weight loss, understanding the implicit bias of equations estimating RMR is vital when providing nutritional and dietary counseling.

A multi-modal diagnostic model improves detection of cardiac amyloidosis among patients with diagnostic confirmation by cardiac biopsy

Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed. We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard. Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression. The overall cohort was characterized by elevated BNP (median 727 ng/mL), increased left ventricular wall thickness (IWT; median 1.7 cm), and reduced voltage-to-mass ratio (median 0.06 mm/[g/m2]). One hundred and thirteen patients (46%) had either light chain (n = 53) or transthyretin (n = 60) amyloidosis by cardiac biopsy. A prediction model including age, relative wall thickness, left atrial pressure by E/e', and low limb lead voltage (<0.5 mV) showed good discrimination for cardiac amyloidosis with an optimism-corrected c-index of 0.87 (95% CI 0.83-0.92). The diagnostic accuracy of this model (79% sensitivity, 84% specificity) surpassed that of traditional screening parameters, such as IWT in the absence of left ventricular hypertrophy on ECG (98% sensitivity, 20% specificity) and IWT with low limb lead voltage (49% sensitivity, 91% specificity). Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.

Negative bone scintigraphy in wild-type transthyretin cardiac amyloidosis

BackgroundAmyloidosis is a rare systemic disease due to the extracellular tissue deposition of a fibrillar-shaped misfolded protein, called amyloid. Only two types of proteins commonly affect the heart leading to an infiltrative cardiomyopathy: immunoglobulin light chain and transthyretin (TTR) cardiac amyloidosis (CA). Despite the promising role of emerging imaging modalities, such as strain echocardiography, cardiac magnetic resonance and bone scintigraphy, its diagnosis is still often missed or delayed due to their inherent limitations and to a nonspecific clinical scenario with frequent concomitance of cardiac comorbidities. The gold standard for a definite diagnosis still remains endomyocardial biopsy, but in rare cases Congo Red staining could provide false negative results, as in our case, requiring immunoelectron microscopy.Case presentationA middle-aged male adult presented to the emergency department for relapse of heart failure. Echocardiography and cardiac magnetic resonance, along with the history of bilateral carpal tunnel syndrome, were suspicious for TTR-CA. The diagnosis, however, was hampered by concomitant cardiac comorbidities and conflicting results of imaging modalities. In fact bone scintigraphy was negative, as well as Congo Red Staining on myocardial tissue samples obtained by endomyocardial biopsy. Given the high clinical suspicion, immunoelectron microscopy was performed, showing TTR amyloid fibrils deposits, that confirmed the diagnosis. A genetic analysis excluded and hereditary form. The patient was then referred to a specialist center for specific treatment.ConclusionsThis is a rare case of a TTR-CA with a negative Bone Scintigraphy and Congo red staining, which demonstrated that CA is frequently misdiagnosed because of the low specific clinical manifestations and the results of imaging modalities that sometimes could be misleading, with subsequent delayed diagnosis and correct treatment.

Comparing outcomes for infiltrative and restrictive cardiomyopathies under the new heart transplant allocation system

The new heart transplantation (HT) allocation policy was introduced on 10/18/2018. Using the UNOS registry, we examined early outcomes following HT for restrictive cardiomyopathy, hypertrophic cardiomyopathy, cardiac sarcoidosis, or cardiac amyloidosis compared to the old system. Those listed who had an event (transplant, death, or waitlist removal) prior to 10/17/2018 were in Era 1, and those listed on or after 10/18/2018 were in Era 2. The primary endpoint was death on the waitlist or delisting due to clinical deterioration. A total of 1232 HT candidates were included, 855 (69.4%) in Era 1 and 377 (30.6%) in Era 2. In Era 2, there was a significant increase in the use of temporary mechanical circulatory support and a reduction in the primary endpoint, (20.9 events per 100 PY (Era 1) vs. 18.6 events per 100 PY (Era 2), OR 1.98, p=.005). Median waitlist time decreased (91 vs. 58days, p<.001), and transplantation rate increased (119.0 to 204.7 transplants/100 PY for Era 1 vs Era 2). Under the new policy, there has been a decrease in waitlist time and waitlist mortality/delisting due to clinical deterioration, and an increase in transplantation rates for patients with infiltrative, hypertrophic, and restrictive cardiomyopathies without any effect on post-transplant 6-month survival.