Cardiac Amyloidosis: A Review of Current Imaging Techniques

Systemic amyloidosis is a rare, heterogenous group of diseases characterized by extracellular infiltration and deposition of amyloid fibrils. Cardiac amyloidosis (CA) occurs when these fibrils deposit within the myocardium. Untreated, this inevitably leads to progressive heart failure and fatality. Historically, treatment has remained supportive, however, there are now targeted disease-modifying therapeutics available to patients with CA. Advances in echocardiography, cardiac magnetic resonance (CMR) and repurposed bone scintigraphy have led to a surge in diagnoses of CA and diagnosis at an earlier stage of the disease natural history. CMR has inherent advantages in tissue characterization which has allowed us to better understand the pathological disease process behind CA. Combined with specialist assessment and repurposed bone scintigraphy, diagnosis of CA can be made without the need for invasive histology in a significant proportion of patients. With existing targeted therapeutics, and novel agents being developed, understanding these imaging modalities is crucial to achieving early diagnosis for patients with CA. This will allow for early treatment intervention, accurate monitoring of disease course over time, and thereby improve the length and quality of life of patients with a disease that historically had an extremely poor prognosis. In this review, we discuss key radiological features of CA, focusing on the two most common types; immunoglobulin light chain (AL) and transthyretin (ATTR) CA. We highlight recent advances in imaging techniques particularly in respect of their clinical application and utility in diagnosis of CA as well as for tracking disease change over time.

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Prevalence and outcomes of cardiac amyloidosis in all-comer referrals for bone scintigraphy

European Heart Journal ◽

10.1093/eurheartj/ehab724.0280 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

C Nitsche ◽

K M Mascherbauer ◽

T W Wollenweber ◽

M K Koschutnik ◽

C D Dona ◽

...

Keyword(s):

Heart Failure ◽

Bone Scintigraphy ◽

Cardiac Amyloidosis ◽

Cox Regression ◽

Significant Proportion ◽

Tracer Uptake ◽

Adverse Outcomes ◽

Study Endpoint ◽

Outcome Analysis ◽

Kaplan Meier

Abstract Objectives Cardiac amyloidosis (CA) is increasingly identified as a cause of heart failure due to diagnostic advances and enhanced disease awareness. Screening ascertainments have unveiled a significant proportion of (coexisting) CA for various cardiac conditions, but the true prevalence of CA in the general population as well as prognostic implications remain unknown. Methods Consecutive all-comer referrals for 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy between January 2010 and August 2020 were included retrospectively. CA was defined as positive cardiac tracer uptake (Perugini grade 0: negative; grades 1 to 3: increasingly positive). Owing to the study design, CA subtype (transthyretin vs. light chain) was not assessed. Indications for DPD, laboratory, and clinical data were retrieved from medical records. Mortality was captured from the Austrian death registry. Combined hospitalization for heart failure (HHF) and all-cause death was defined as study endpoint. Outcome analysis was performed using Kaplan Meier estimates and multivariate Cox regression. Results 17202 scans from 11549 subjects (61.2±16.1 y/o, 62.9% female, 73.7% cancer patients) were analyzed. Follow-up scans for patients with >1 test yielded identical Perugini grades in all cases. Prevalence of CA for the overall population was 5.5% (n=638/11549; grade 1: 4.0%, grade 2/3: 1.5%), increased with age (<60 y/o: 2.5%, 60–70 y/o: 5.4%, 70–80 y/o: 7.6%, >80 y/o: 14.2%, p<0.001, Figure), and was higher in men vs. women (7.4% vs. 4.4%, p<0.001). Also, CA was more prevalent in cardiac (19.1%, n=207/1081) vs. non-cardiac referrals (4.1%, n=431/10468; p<0.001). Across all age groups of non-cardiac referrals, CA patients more often had atrial fibrillation and cardiomyopathy, and displayed worse renal function (p for all<0.05). Following DPD, 3490 patients (30.2%) had reached the study endpoint (84 HHF, 3313 death, 93 both) after 5.9±3.3 years. By Kaplan Meier estimates, the presence of CA among all-comers predicted adverse outcomes (log-rank, p<0.001, Figure). After adjustment for age and cancer, CA remained significantly associated with outcomes by multivariate Cox regression (hazard ratio [HR]: 1.30, 95% confidence interval [CI] 1.14–1.48, p<0.001). This effect was consistent across subgroups of cardiac (HR: 1.41, 95% CI 1.06–1.89, p=0.018) and non-cardiac referrals (HR: 1.20, 95% CI 1.03–1.39, p=0.018). Outcomes were similar in grade 1 vs. 2/3 CA patients (p>0.05). Conclusion Cardiac tracer uptake is present in 1 in 20 patients referred for bone scintigraphy, and independently predicts prognosis – even in this population with significantly reduced life expectancy due to the high rate of malignancy. With novel CA-specific drugs available – especially for transthyretin CA – diagnosis of CA is even more crucial to improve patient outcomes. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Pfizer Cardiac Tracer Uptake in DPD Referrals

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Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads

Medicina ◽

10.3390/medicina57070660 ◽

2021 ◽

Vol 57 (7) ◽

pp. 660

Author(s):

Csilla-Andrea Eötvös ◽

Roxana-Daiana Lazar ◽

Iulia-Georgiana Zehan ◽

Erna-Brigitta Lévay-Hail ◽

Giorgia Pastiu ◽

...

Keyword(s):

Left Ventricular Hypertrophy ◽

Cardiac Amyloidosis ◽

Ventricular Hypertrophy ◽

Low Voltage ◽

Disease Process ◽

Left Ventricular ◽

Clinical Suspicion ◽

Immunoglobulin Light Chain ◽

Different Types

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.

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Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

Journal of Clinical Medicine ◽

10.3390/jcm10061214 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1214

Author(s):

Ji Tu ◽

Jose Vargas Castillo ◽

Abhirup Das ◽

Ashish D. Diwan

Keyword(s):

Cervical Myelopathy ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Imaging Techniques ◽

Disease Process ◽

Classification Systems ◽

Molecular Features ◽

Formidable Challenge ◽

Long Term Treatment ◽

Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

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Heritability of Longitudinal Measures of Body Mass Index and Lipid and Lipoprotein Levels in Aging Twins

Twin Research and Human Genetics ◽

10.1375/twin.10.5.703 ◽

2007 ◽

Vol 10 (5) ◽

pp. 703-711 ◽

Cited By ~ 52

Author(s):

Ellen L. Goode ◽

Stacey S. Cherny ◽

Joe C. Christian ◽

Gail P. Jarvik ◽

Mariza de Andrade

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Genetic Factors ◽

Significant Proportion ◽

Lipoprotein Cholesterol ◽

Equation Modeling ◽

Shared Environment ◽

Significant Contributor ◽

Age Related ◽

Over Time

AbstractBody-mass index (BMI), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels are known to be highly heritable. We evaluated the genetic and environmental relationships of these measures over time in an analysis of twin pairs. Monozygotic (235 pairs) and dizygotic (260 pairs) male twins were participants in the National Heart Lung and Blood Institute Veteran Twin Study, and were followed with three clinical exams from mean age 48 years to mean age 63 years. Structural equation modeling (SEM) with adjustment forAPOEgenotype (a significant contributor to TC and LDL-C) was used to assess longitudinal patterns of heritability. Results indicated a contribution of genetic factors to BMI, TC, LDL-C, HLD-C, and TG. Modest increases over time were observed in the heritability of BMI (from 0.48 to 0.61), TC (from 0.46 to 0.57), LDL-C (from 0.49 to 0.64), and HDL-C (from 0.50 to 0.62), but this trend was not present for TG. There was a corresponding decrease in shared environmental influences over time for these traits, although shared environment was a significant contributor only for HDL-C. Moreover, we observed that genetic influences for all measures were significantly correlated over time, and we found no evidence of age-specific genetic effects. In summary, longitudinal analyses of twin data indicate that genetic factors do not account for a significant proportion of the variation in age-related changes of BMI or lipid and lipoprotein levels.

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Serial Analysis of the Gut and Respiratory Microbiome in Cystic Fibrosis in Infancy: Interaction between Intestinal and Respiratory Tracts and Impact of Nutritional Exposures

mBio ◽

10.1128/mbio.00251-12 ◽

2012 ◽

Vol 3 (4) ◽

Cited By ~ 172

Author(s):

J. C. Madan ◽

D. C. Koestler ◽

B. A. Stanton ◽

L. Davidson ◽

L. A. Moulton ◽

...

Keyword(s):

Cystic Fibrosis ◽

Respiratory Tract ◽

Microbial Communities ◽

Effective Means ◽

Significant Proportion ◽

Gut Colonization ◽

Pulmonary Damage ◽

Chronic Colonization ◽

High Degree ◽

Over Time

ABSTRACT Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, with evidence of more rapidly acquired diversity in the respiratory tract. There was a high degree of concordance between the bacteria that were increasing or decreasing over time in both compartments; in particular, a significant proportion (14/16 genera) increasing in the gut were also increasing in the respiratory tract. For 7 genera, gut colonization presages their appearance in the respiratory tract. Clustering analysis of respiratory samples indicated profiles of bacteria associated with breast-feeding, and for gut samples, introduction of solid foods even after adjustment for the time at which the sample was collected. Furthermore, changes in diet also result in altered respiratory microflora, suggesting a link between nutrition and development of microbial communities in the respiratory tract. Our findings suggest that nutritional factors and gut colonization patterns are determinants of the microbial development of respiratory tract microbiota in infants with CF and present opportunities for early intervention in CF with altered dietary or probiotic strategies. IMPORTANCE While efforts have been focused on assessing the microbiome of pediatric and adult cystic fibrosis (CF) patients to understand how chronic colonization by these microbes contributes to pulmonary damage, little is known regarding the earliest development of respiratory and gut microflora in infants with CF. Our findings suggest that colonization of the respiratory tract by microbes is presaged by colonization of the gut and demonstrated a role of nutrition in development of the respiratory microflora. Thus, targeted dietary or probiotic strategies may be an effective means to change the course of the colonization of the CF lung and thereby improve patient outcomes.

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Abstract P35: The Trend of Stroke Rehabilitation Utilization Between 2014- 2019 in a Community Based Study

Stroke ◽

10.1161/str.52.suppl_1.p35 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Daniel Uhm ◽

Esther Olasoji ◽

Alexis N Simpkins ◽

Carolyn Geis ◽

Keyword(s):

Clinical Practice ◽

Trend Analysis ◽

Significant Proportion ◽

Inpatient Rehabilitation ◽

Outpatient Rehabilitation ◽

Rehabilitation Services ◽

Institutional Review ◽

Ischemic Attack ◽

Over Time

Introduction: Stroke is the leading cause of long-term disability in adults, resulting in significant impairments in motor, sensory, and/ or cognitive that often requires continued rehabilitation services, which vary from intensive acute inpatient rehabilitation to outpatient rehabilitation services. Efforts to reduce disability have advanced rapidly over the past several years. Our data analysis was undertaken to assess whether recent changes in clinical practice have impacted the proportion of stroke patients receiving inpatient versus outpatient rehabilitation over time between 2014-2019 at our institution, which serves a diverse mix of rural, suburban, and urban populations. Methods: Our Institutional Review Board approved retrospective stroke database, including adult patients discharged to receive rehabilitation services data from 2014-2019, was used for analysis. Cochran-Armitage trend analysis was used to assess for differences type of rehabilitation services used over time and regression analysis was used to identify clinical factors associated with discharge type over time. Results: A total of 3467 patients were included in the analysis, 50% woman, 1% Asian, 20% Black, 75% White, 4% undetermined race, 17% intracerebral hemorrhage, 65% ischemic stroke, 11% subarachnoid hemorrhage, 3% transient ischemic attack, 3% other cerebrovascular disease. In this community population, 65% were discharged to inpatient rehab. Trend analysis demonstrated a significant increase in the proportion of patients being discharged home with rehab services, p<.0001. In comparison to those discharged home, patients discharged to rehab were older (odds ratio (OR) 1.02, confidence interval (CI) 1.02-1.03), with a higher NIHSS (OR 1.16, CI 1.14-1.18), discharged in 2014 (OR 1.72, CI 1.23-2.39) or 2016 (OR 1.46, CI 1.05-2.05) versus 2019. There was no association with race, gender, or discharge in 2015, 2017, or 2018. Discussion: Our findings demonstrate the community impact of recent changes in clinical practice guidelines for stroke. The increasing trend of home discharges is encouraging, but the significant proportion of those still not discharged home suggests there is still more work to be done to reduce stroke associated disability in adults.

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Abstract 3851: Temporal Distribution of Stroke Volumes and Clinical-Diffusion Mismatch in Patients with Proximal Arterial Occlusions

Stroke ◽

10.1161/str.43.suppl_1.a3851 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Raul G Nogueira ◽

David S Liebeskind ◽

Leticia M Souza ◽

Qing Hao ◽

Karen Furie ◽

...

Keyword(s):

Linear Regression ◽

Infarct Volume ◽

Linear Regression Analysis ◽

Significant Proportion ◽

Arterial Occlusion ◽

Reperfusion Therapy ◽

Poor Correlation ◽

Lesion Volume ◽

Collateral Flow ◽

Over Time

Background and Purpose: Previous studies have demonstrated that the benefit of reperfusion therapy declines over time. The Clinical-Diffusion Mismatch (CDM) model has been suggested as surrogate for salvable tissue in acute ischemic stroke (AIS) patients. We sought to describe the temporal behavior profile of infarct volumes and CDM in patients suffering AIS due to proximal arterial occlusion (PAO). Methods: We performed a retrospective analysis of consecutive AIS patients admitted to two large academic institutions fulfilling the following criteria: (1) Baseline NIHSS ≥8; (2) PAO defined as MCA-M1, intracranial ICA, or tandem cervical + ICA/MCA-M1 occlusion on admission CTA/MRA; and (3) MRI-DWI performed ≤8 hours from time of stroke onset/last seen well (TSO). CDM was defined as baseline NIHSS ≥8 and DWI volume ≤25cc (as proposed by Davalos et al). Linear regression analysis was performed to define the changes on DWI lesion volume on presentation over time. The observed TSO to MRI were broken down into quartiles to look for any differences in the distribution of the baseline variables over time. Results: A total of 132 consecutive patients were identified (mean age, 66±16.8 years; 57% females; mean baseline NIHSS 17.5±5.3; occlusion site: MCA-M1, 64%; intracranial-ICA, 29%; tandem, 5%, mean TSO to DWI, 269.5±105.48 minutes). The mean DWI stroke volume on presentation was 46.7±54.8 cc (range, 0.19-436.1) and 63 (46.7%) patients had CDM. There was no significant changes in age, gender, baseline NIHSS, or occlusion site amongst the different time quartiles. Median infarct volume (cc) increased (quartile #1=8.5; #2=30.1; #3=38.5; #4=29.4) and the chances of having a CDM decreased (p<0.0001) across the different time quartiles. However, there was an overall poor correlation between DWI lesion volume on presentation and TSO to MRI (R-square=0.031, Figure ) and a significant proportion of the patients still had a CDM at later time epochs (#1=91.1%[20/22]; #2=47.8%[11/23]; #3=34.4%[21/61]; #4=42.3%[11/26]). Conclusions: Although infarct volume increases and the amount of penumbral tissue decreases over time, many patients with PAO will still have salvable penumbra at the later time epochs. This reflects individual differences in anatomic and physiological characteristics including the strength of collateral flow and highlights that selected patients may benefit from reperfusion therapy even at the later time windows. Figure : Relationship between Baseline DWI Volume (cc) and Time (minutes). Line is best fitted linear regression model.

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Segmentation analysis in the volumetric measurement and tissue characterization of MS lesions over time

Journal of Neuroimmunology ◽

10.1016/0165-5728(95)98985-k ◽

1995 ◽

Vol 56-63 ◽

pp. 40-40

Author(s):

CF Gonzalez ◽

S. Vlnltski ◽

S. Shehagiri ◽

F.D. Lublin ◽

R.L. Knobler

Keyword(s):

Tissue Characterization ◽

Volumetric Measurement ◽

Segmentation Analysis ◽

Over Time

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Determinants of progression of nicotine dependence symptoms in adolescent waterpipe smokers

Tobacco Control ◽

10.1136/tobaccocontrol-2018-054244 ◽

2018 ◽

Vol 28 (3) ◽

pp. 254-260 ◽

Cited By ~ 11

Author(s):

Raed Bahelah ◽

Kenneth D Ward ◽

Ziyad Ben Taleb ◽

Joseph R DiFranza ◽

Thomas Eissenberg ◽

...

Keyword(s):

Physical Activity ◽

Nicotine Dependence ◽

School Performance ◽

Psychological Factors ◽

Significant Proportion ◽

Self Esteem ◽

Waterpipe Smoking ◽

Waterpipe Cafés ◽

Over Time

IntroductionWaterpipe smoking continues to pose significant challenges to tobacco control efforts and many adolescent waterpipe smokers experience symptoms of nicotine dependence (ND). This study examined the predictors of progression of ND symptoms in adolescent waterpipe smokers.MethodsWe assembled a cohort of Lebanese adolescents enrolled in eighth and ninth grades at baseline, and surveyed them every 6 months over the next 24 months. Progression of ND symptoms was defined as an increase over time in the number of items endorsed on the Hooked on Nicotine Checklist. Predictors included individual (eg, psychological factors, attitudes towards waterpipe, school performance, physical activity) and socioenvironmental (eg, smoking among parents, siblings and close friends; the café environment) attributes.ResultsAmong 264 adolescent waterpipe smokers (baseline mean age=14.6 years, 50.4% females), 105 (39.7%) progressed on ND symptoms during follow-up. Predictors of progression were higher baseline stress (OR 1.11, 95% CI 1.03 to 1.19) and higher self-esteem (OR 1.14, 95% CI 1.05 to 1.24). Reporting difficulty refraining from smoking waterpipe while in a restaurant was the strongest predictor of progression (OR 4.04, 95% CI 1.44 to 11.34). Having a mother with ≥12 years of education protected against progression of ND (OR 0.46, 95% CI 0.21 to 0.99).ConclusionsA significant proportion of adolescent waterpipe smokers progressed on ND. Venue-based policies such as limiting youth access to waterpipe cafés are warranted.

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Bone scintigraphy imaging of cardiac amyloidosis

World Journal of Nuclear Medicine ◽

10.4103/wjnm.wjnm_9_19 ◽

2019 ◽

Vol 18 (3) ◽

pp. 314 ◽

Cited By ~ 3

Author(s):

IssaMenge Kuria ◽

SamuelNguku Gitau ◽

KhalidBashir Makhdomi

Keyword(s):

Bone Scintigraphy ◽

Cardiac Amyloidosis

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