Presence Of Cardiac Amyloidosis Research Articles

Association of cardiac amyloidosis with periprocedural complications in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis

Abstract Introduction Cardiac amyloidosis (CA) has been frequently observed in patients with aortic stenosis (AS). While transcatheter aortic valve replacement (TAVR) may be an option, the association of CA with risk of periprocedural complications has not been well evaluated. Purpose This study aimed to evaluate the association of CA with periprocedural complications after TAVR in patients with severe AS. Methods A literature search was performed for studies evaluating patients with severe AS undergoing AVR, comparing periprocedural safety endpoints for patients with and without CA. The primary endpoints were vascular complications and bradyarrhythmias post-TAVR requiring permanent pacemaker (PPM) implantation. Secondary endpoints included periprocedural acute kidney injury (AKI), cerebrovascular accidents (CVA), and major bleeding events. Endpoints were defined using the Valve Academic Research Consortium-2 criteria. The search was not restricted to time or publication status. Results 6 studies with 1,138 patients with severe AS (150 with CA, 988 without CA) met inclusion criteria. Mean age was 82 years, 52.4% were men, all except 1 study assessed only patients with ATTR CA. Echocardiographic mean aortic valve parameters included valve area of 0.718 cm2, mean gradient of 40.8, and peak velocity of 4.13 m/s. The mean left ventricular ejection fraction was 55.2%. The presence of CA was not associated with an increased risk of periprocedural vascular complications (OR 0.69, 95% CI 0.25-1.88; p=0.47). While a trend toward higher risk of periprocedural PPM implantation was observed in patients with CA, this finding did not reach statistical significance (OR 1.51; 95% CI 0.77-2.94; p=0.23). The presence of CA was not associated with increased risk of periprocedural AKI, CVA, or major bleeding (OR 1.3, 95% CI 0.32-5.3; p=0.72, OR 0.65, 95% CI 0.17-2.41; p=0.52; OR 0.55, 95% CI 0.16-1.87; p=0.34). Conclusion In the context of patients with severe AS undergoing TAVR, the presence of cardiac amyloidosis did not increase the risk of periprocedural complications, including vascular complications, AKI, CVA, or major bleeding. Although a trend toward a higher risk of bradyarrhythmias requiring PPM implantation was noted in patients with CA, further studies are warranted to confirm this observation. Overall, these findings contribute valuable insight into the safety profile of TAVR in the patients with CA.Figure 1Figure 2

How Often Does Apical Sparing of Longitudinal Strain Indicate the Presence of Cardiac Amyloidosis?

Echocardiographic diagnosis of cardiac amyloidosis (CA) is frequently suggested by the presence of a left ventricular (LV) apical sparing pattern (ASP) on longitudinal strain (LS) assessment, the so-called "cherry on top" pattern, defined by strain magnitude preserved exclusively at the apex. However, it is unclear how frequently this strain pattern truly represents CA. This study aimed to evaluate the predictive value of ASP in the diagnosis of CA. We retrospectively identified consecutive adult patients who had the following studies performed within an 18-month period: (1) transthoracic echocardiogram and (2) either (a) cardiac magnetic resonance imaging, (b) Technetium-Pyrophosphate (PYP) imaging, or (c) endomyocardial biopsy. LS was retrospectively measured in the apical 4-, 3-, and 2-chamber views in patients who had adequate noncontrast images (n=466). An apical sparing ratio (ASR) was calculated as (average apical strain)/[(average basal strain)+(average midventricular strain)]. Patients with ASR ≥1 were evaluated for the presence/absence of CA, using established criteria. Basic LV parameters were also measured. A total of 33 patients (7.1%) had ASP. Nine of these patients (27%) had "confirmed" CA, 2 (6.1%) "highly probable" CA, 1 (3.0%) "possible" CA, and 21 (64%) no evidence of CA. When comparing patients with and without confirmed CA, there were no significant differences in ASR, average global LS, ejection fraction, or LV mass. Patients with confirmed CA were older (76 ± 9 vs 59 ± 18years, p=0.01) and had thicker posterior wall (15 ± 3 vs 11 ± 3mm, p=0.004) with a trend toward thicker septal wall (15 ± 2 vs 12 ± 4mm, p=0.05). In conclusion, the presence of ASP on LS represents confirmed or highly probable CA in only 1/3 of patients and is more likely to indicate true CA in older patients with increased LV wall thickness. Although a larger, prospective study is needed to confirm these findings, 1/3 should be considered as a large diagnostic yield that justifies further testing, given the poor outcomes associated with CA diagnosis.

Transthyretin cardiac amyloidosis: a review of the nuclear imaging findings with emphasis on the radiotracers mechanisms.

Cardiac amyloidosis is a protein deposition disease characterized by the infiltration of the myocardium and coronary arteries resulting in a progressive thickening of both ventricles, interatrial septum and atrioventricular valves, eventually leading to organ failure. It is a disease hard to diagnose, due to the lack of diagnostic investigations. However, development of new and more accurate examinations is undergoing. Endomyocardial biopsy is the gold standard investigation for this disease, but it has its limitations (invasive and not widely available). Other investigations may be able to detect the presence of cardiac amyloidosis but cannot specify the type involved. To that end, nuclear medicine through bone scanning offers a simple, non-invasive solution to detect, differentiate and diagnose transthyretin cardiac amyloidosis (ATTR) from other types of cardiac amyloidosis. In order to demonstrate the importance of bone scanning we will present a few methods of image processing based on literature and a personalized method, followed by a few important examples of positive cases. The aim of this review was to present the current methods of ATTR detection with emphasis on nuclear medicine bone scanning and its important place in the decision algorithm of the cardiologist for a personalized approach to this pathology.

Ruling in or out the presence of cardiac amyloidosis based on cut-off values using T1-mapping – caution is required regarding the control group

Abstract Background Cardiac amyloidosis (CA) is an infiltrative disease that is characterized by accumulation of amyloid deposits in the interstitium of the myocardium. In contrast, hypertrophic cardiomyopathy (HCM) is caused by a disorganized arrangement of myocyte hypertrophy as well as expanded extracellular matrix, composed of interstitial and replacement fibrosis. Purpose A diagnostic algorithm based on (native) T1-mapping using cardiovascular magnetic resonance (CMR) was suggested in a recent study for the diagnosis of CA: A native T1 <1,036ms was mentioned to have a 98% negative predictive value (NPV) for ruling out CA whereas a native T1 >1,164ms showed a 98% positive predictive value (PPV) for the presence of CA. In the present study, we critically addressed the calculation of such cut-off values considering possible differences in the composition of the control group. Methods N=30 patients with CA, N=20 patients with HCM and N=15 healthy controls without relevant cardiac disease underwent dedicated CMR studies on a 1.5-T MR scanner. The CMR protocol comprised standard sequences for cine-imaging, native and post-contrast MOLLI-based T1-mapping and late-gadolinium-enhancement (LGE). ECV measurements were based on pre- and post-contrast T1-mapping images. Results Native T1 and ECV were significantly increased in CA compared to HCM and receiver operating characteristic (ROC) analyses revealed an area-under-the-curve (AUC) = 0.984 for native T1 (p<0.001) and AUC = 0.985 for ECV (p<0.001) regarding the diagnosis of CA). When CA patients were compared to HCM patients (excluding healthy controls), a native T1 <1,036ms or an ECV <33% were associated with a 99% NPV for ruling out CA whereas a native T1 ≥1,082ms or an ECV ≥41% were associated with a 99% PPV for diagnosis of CA. However, when CA patients were compared to healthy controls (excluding HCM patients), a native T1 <1,025ms or an ECV <34% were associated with a 99% NPV for ruling out CA whereas a native T1 ≥1,025ms or an ECV ≥34% were associated with a 99% PPV for diagnosis of CA since there was no overlap in native T1 and ECV values between CA patients and healthy controls. Conclusion Cut-off values for native T1 or ECV derived from ROC analyses (in a specific group of study patients) for ruling in or out the presence of CA are – amongst others - determined by the native T1 and ECV values of the respective “control group”. A different composition of the control group (e.g. HCM patients vs. healthy volunteers) will result in different cut-off values. Hence, previously suggested cut-off values obtained in single center studies need to be considered carefully – with a special attention to the control group of the underlying study – and should not be transferred to other centers carelessly. Funding Acknowledgement Type of funding source: None

Diagnosis of Cardiac Amyloidosis: Clinical and Echocardiographic Features

This review is geared to address the various forms of amyloidosis which have cardiac involvement and discuss the echocardiographic findings that may be present in patients with cardiac amyloidosis. The use of echocardiography has revolutionized the diagnosis of cardiac amyloidosis. The diagnosis is often first suspected due to characteristic echocardiographic findings. Although no single finding is pathognomonic, there are a constellation of features that point to the diagnosis including increased left and right ventricular wall thickness, thickened cardiac valves and atrial walls, and a pericardial effusion. Alterations in diastolic function with evidence of elevated filling pressures are common. The use of myocardial strain imaging has allowed for earlier detection of cardiac amyloidosis and has revealed a distinctive pattern, sometimes suggesting the diagnosis when more classic findings are subtle or absent. Multiple echocardiographic findings have been found to be prognostic in cardiac amyloid. Using current techniques, functional measures such as myocardial strain and stroke volume index are more powerful predictors of outcome than myocardial thickness. While other imaging modalities are complementary including cardiac magnetic resonance imaging and nuclear medicine scintigraphy techniques using bone tracers, echocardiography remains a mainstay in the diagnosis and follow-up of patients with cardiac amyloidosis. Echocardiography is a critical tool in the evaluation of the patient with heart failure, as well as those with unexplained chest pain and arrhythmias. Key findings on an echocardiogram can help alert the clinician to the presence of cardiac amyloidosis. The degree of cardiac dysfunction in a patient with systemic amyloidosis correlates with prognosis. Recognition of subtle echocardiographic findings may allow for earlier and more aggressive treatment to improve overall mortality in patients with cardiac amyloidosis.

The Incidence of Atrial Fibrillation Among Patients with AL Amyloidosis Undergoing High Dose Melphalan and Stem Cell Transplantation (HDM/SCT): Experience at a Single Institution

BackgroundHigh dose melphalan and autologous stem cell transplantation (HDM/SCT) can induce hematologic responses and prolong survival in selected patients with AL amyloidosis. However, cardiac toxicity associated with HDM/SCT remains an ongoing concern in patients with AL amyloidosis. Atrial fibrillation (AF) may complicate SCT 4-10% of the time (Olivieri et al. 1998, Hidalgo et al. 2004). The development of AF in the SCT period can be challenging to manage. Studies identifying risk factors for the development of AF in amyloidosis are limited (Abhishek et al. 2013).ObjectiveWe sought to determine the incidence of atrial fibrillation in patients with AL amyloidosis undergoing SCT.Patients and methodsWe retrospectively analyzed charts of 91 consecutive patients undergoing HDM/SCT for AL amyloidosis between January 2011 and May 2015. The peri-transplant period was defined from the first day of stem cell mobilization until the time to engraftment. For all patients, medical records were reviewed for age, gender, prior history of AF, baseline troponin I, brain natriuretic peptide (BNP), baseline echocardiography, dose of Melphalan, ventricular rate at the time of AF event, hemodynamic stability (based on blood pressure), AF management and the return to normal sinus rhythm (NSR).ResultsNinety-one patients with AL Amyloidosis underwent HDM/SCT from January 2011 to May 2015. Overall, twelve patients (13.1%) developed AF during SCT period, at a median of D+9 (range, D-10 to D+21). Baseline characteristics of these patients are listed in Table 1. Patient characteristics and AF management are listed in Table 2.Of note, there were three patients who had a history of PAF who did not develop AF during the peri-transplant period.ConclusionAF occurred in 13.1% of patients with AL amyloidosis undergoing HDM/SCT in the peri-transplant period, a rate higher than previously reported in other patient populations. Four of seven patients with a history of supraventricular tachyarrhythmia (SVT) developed AF during the peri-transplant period, making prior SVT a potential risk factor. The presence of cardiac amyloidosis, even in early stages, in combination with high dose Melphalan, may also predispose this group of patients to supraventricular arrhythmias. The identification of risk factors for developing AF in patients with AL amyloidosis may enable the use of preventative action in the future.Table 1Patient Characteristics at BaselineN = 12 (%)Median Age, years (range)59.5 (40-68)Gender Male Female6 (50) 6 (50)Organ Involvement Cardiac only Renal only Pulmonary only Cardiac and renal3 (25.0) 4 (33.3) 1 (8.3) 4 (33.3)History of AfibPrior anticoagulation Prior rate control4 (33.3) 2/4 (50.0) 4/4 (100.0)Median BNP, pg/mL (range)59.5 (17-558)Median Troponin, ng/mL (range)0.0385 (0.006 - 0.446)Median TSH*, IU/mL (range)1.56 ( 0.24-5.39)Cardiac Echo IVSD**, mm (range) Presence of diastolic dysfunction Diastolic Dysfunction, grade (range) LVEF***, % (range) Left atrial size****, mm (range)11.5 ( 8.0-17.0)8 (66.6) 1.0 ( 0.0-3.0)61.6 ( 44-71)36.5 ( 23-43)Median PR interval on EKG in ms, (range)183 (132-230)Dose of Melphalan140mg/m2 200mg/m24(33.3) 8(66.6)*TSH: Thyroid stimulating hormone**IVSD: Interventricular septal diastolic thickness (normal < 10mm for women and < 11mm for men)***LVEF: Left ventricular ejection fraction**** Left atrial size in parasternal long axis view (normal < 40mm)Table 2Patient Characteristics at Time of AF EventN = 12 (%)Median Day to event as it relates to stem cell infusion, (range)D+9 (D-10 to D+21)Median Ventricular Rate, beats per minute (range)130 (83-159)Hemodynamic Stability Stable Unstable5(41.6) 7(58.3)Treatment of rate/rhythm Beta blocker alone Calcium channel blocker Amiodarone and beta blocker No specific intervention5(41.7) 0 (0.0) 3(33.3) 4(33.3)Anticoagulation Yes No3(33.3) 9(75.0) DisclosuresNo relevant conflicts of interest to declare.

962Comparison of Myocardium and Blood Pool Null Points as determined by a Breathhold Single Slice Multiphase Inversion Recovery Acquisition Predicts the Presence of Cardiac Amyloidosis

962Comparison of Myocardium and Blood Pool Null Points as determined by a Breathhold Single Slice Multiphase Inversion Recovery Acquisition Predicts the Presence of Cardiac Amyloidosis

How to treat patients with systemic amyloid light chain amyloidosis? Comparison of high-dose melphalan, low-dose chemotherapy and no chemotherapy in patients with or without cardiac amyloidosis

High-dose melphalan and autologous stem cell transplantation (HDM) is an effective treatment for systemic amyloid light chain (AL) amyloidosis but the eligibility criteria exclude many patients with this disorder. The aim of this study was to determine appropriate treatment strategies for systemic AL amyloidosis according to each patient's clinical condition in Japan. Historical cohort study. Fifty-three patients with systemic AL amyloidosis (those with malignancies were excluded) were treated in our hospital with HDM (15 patients), melphalan + prednisolone (MP) (17 patients), vincristine + adriamycin + dexamethasone (VAD) (11 patients), or supportive treatment (no chemotherapy, 10 patients). We compared the survival rates among these treatment groups. Mean survival was significantly longer in the HDM group than in the other three groups (P<0.01, log-rank test). This trend remained the same when patients were divided into those with and without cardiac amyloid involvement. Furthermore, in patients with heart involvement, survival in the VAD therapy group was significantly inferior to that in the MP therapy group (P<0.01 by log-rank test). Significant factors related to the survival rate included the presence or absence of heart involvement and treatment modality. HDM should be considered the treatment of choice in eligible patients with systemic AL amyloidosis even in the presence of cardiac amyloidosis. If HDM is not eligible, indications for VAD therapy should be carefully evaluated in patients with cardiac amyloidosis.

Diagnostic and Prognostic Utility of Cardiovascular Magnetic Resonance Imaging in Light-Chain Cardiac Amyloidosis

Although the presence of abnormal late gadolinium enhancement (LGE) in cardiac amyloidosis has been well established, its prognostic implication and utility to identify cardiac involvement in patients with systemic amyloidosis is unknown. The aim of this study was to assess the diagnostic and prognostic significance of cardiovascular magnetic resonance imaging in patients with amyloid light-chain amyloidosis but unknown cardiac involvement. Cardiovascular magnetic resonance imaging with LGE was performed in 28 patients with systemic amyloidosis. The presence of cardiac amyloidosis was determined by separate clinical evaluation. The performance of LGE for the prediction of cardiac amyloidosis and prognostic implications of LGE were determined. LGE was observed in 19 patients (68%). The sensitivity, specificity, positive predictive value, and negative predictive value of LGE for the identification of clinical cardiac involvement were 86%, 86%, 95%, and 67%, respectively. During a median follow-up period of 29 months, there were 5 deaths (82% survival). LGE itself did not predict survival (p = 0.62). LGE volume was positively correlated with serum level of B-type natriuretic peptide (BNP; R = 0.64, p < or =0.001), and in multivariate analysis, LGE volume proved the strongest independent predictor of BNP. BNP was correlated with New York Heart Association class (p = 0.03). Reduced right ventricular end-diastolic volume (p <0.01) and stroke volume (p = 0.02) were associated with mortality. In conclusion, in patients with systemic amyloidosis, LGE is highly sensitive and specific for the identification of cardiac involvement but does not predict survival. LGE is strongly correlated with heart failure severity as assessed by BNP.

Diagnosis and Management of the Cardiac Amyloidoses

Cardiac amyloidosis is a manifestation of one of several systemic diseases known as the amyloidoses.1,2 This uncommon disease is probably underdiagnosed, and even when a diagnosis of amyloidosis of the heart is made, the fact that there are several types of amyloid, each with its unique features and treatment, is often unrecognized. This can lead to errors in management and in the information conveyed to the patient. The purpose of this review is to familiarize the reader with the clinical features of amyloidosis and to address the approach to the patient with this disease, focusing on the various types of amyloidosis, their prognosis and treatment. The common feature of this group of diseases is the extracellular deposition of a proteinaceous material that, when stained with Congo red, demonstrates apple-green birefringence under polarized light and that has a distinct color when stained with sulfated Alcian blue (Figure 1). Viewed with electron microscopy, the amyloid deposits are seen to be composed of a β-sheet fibrillar material (Figure 2). These nonbranching fibrils have a diameter3 of 7.5 to 10 nm and are the result of protein misfolding.4,5 Cardiac involvement in amyloidosis may be the predominant feature or may be found on investigation of a patient presenting with another major organ involvement. The presence of cardiac amyloidosis and its relative predominance varies with the type of amyloidosis. Thus, senile systemic amyloidosis and some forms of transthyretin amyloidosis invariably affect the heart, whereas cardiac involvement ranges from absent to severe in amyloidosis derived from a light-chain precursor (AL amyloidosis). Secondary amyloidosis almost never affects the heart in any clinically significant manner.6 The specific composition of the fibrils differs in the different types of amyloid7 and are outlined in the Table. Both on the basis of common usage and for …