Citations

Aims Prognostication and treatment selection for cardiac amyloidosis requires accurate amyloid typing. The aim of this study was to investigate the utility of histomorphology for predicting type. Methods and results Autopsy cases with cardiac amyloidosis (1998–2010) were typed by the use of mass spectrometry‐based proteomics. Deposition patterns were correlated with amyloid type. Among 108 decedents (mean age 75 years; 69% men), 107 had a single type, including transthyretin (ATTR) (60 cases), amyloid light chain (AL) (32 λ; 12 κ), amyloid A (AA) (two), and apolipoprotein AIV (AApoAIV) (one). Interstitial deposition was more extensive in AL amyloidosis cases than in ATTR cases [odds ratio (OR) 6.8, P = 0.0004]. Histomorphological patterns of interstitial deposition were mixed in 61% of AL amyloidosis cases and in 61% of ATTR cases, but diffuse pericellular deposits favoured AL amyloidosis (OR 10.7, P = 0.0001), nodular deposits favoured ATTR (OR 3.1, P = 0.0229), and discrete pericellular deposits tended to partially favour ATTR (OR 1.7, P = 0.1970). Arterial and venous deposits each favoured AL amyloidosis (OR ranging from 9.3 to 192.0, P‐value ranging from 0.0022 to <0.0001), and were severe in AL amyloidosis. Endocardial deposits favoured AL amyloidosis (OR 46.3, P < 0.0001) and were also more severe in AL amyloidosis. Conclusions The extent and distribution of cardiac amyloidosis strongly correlate with amyloid type, suggesting fundamental differences in the pathobiology of deposition. The tendency for mixed patterns to occur limits the practicality and accuracy of using histopathology for amyloid typing.

The use of soluble cardiac biomarkers such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and troponin has revolutionized prognostication for patients with AL amyloidosis. Soluble ST2 (sST2) and galectin‐3 have also been reported to have prognostic value in other cardiac patient populations. We identified 502 patients with AL amyloidosis, who provided a research sample and consent to review their medical records between 1/1/2006‐12/31/2010 within 90 days of their diagnosis. Samples were assayed for sST2 and galectin‐3. Within this AL amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7 months). Receiver operating curve analyses were done to detect the best cut‐points for sST2 and galectin‐3 to predict both 1‐ and 5‐year OS. The respective cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin‐3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6 ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin‐3 were prognostic, upon multivariate analysis, only sST2 was independent of troponin, NT‐proBNP, serum immunoglobulin free light chain, and blood pressure. Not only did sST2 add to previously reported prognostication systems, but a novel prognostication 5‐point system including sST2 was possible. The addition of sST2 – but not galectin‐3 – to existing prognostication systems for patients with AL amyloidosis strengthens the ability to predict for death. Am. J. Hematol. 90:524–528, 2015. © 2015 Wiley Periodicals, Inc.

Objective: To compare the safety and effectiveness of video-assisted thoracic surgery (VATS) versus conventional median sternotomy (open) in the repair of secundum atrial septal defect (ASD) or patent foramen ovale (PFO). Design: Among 415 consecutive patients undergoing open or VATS ASD/PFO closure between 1993 and October 2012, 153 patients were compared using 2:1 frequency matching (n = 102 open vs 51 VATS). Matching variables include age, gender, body surface area, past medical history of neurologic events, and need of patch closure. Median age was 43 years (3-71 years), and 67% were female. Results: There were no early deaths in either group. There were no conversions to open sternotomy. Although mean cross-clamp time (14.5 ± 7.6 vs 26.3 ± 13.2 minutes, P < .001) and bypass time (31.7 ± 13.8 vs 60.9 ± 20.9 minutes, P < .001) were longer in the VATS group, patients who underwent VATS had shorter postoperative ventilation time (7.5 ± 6.4 vs 4.4 ± 2.8 hours, P = .03) with 62.7% extubated in the operating room, along with shorter intensive care unit stay (26.7 ± 10.8 vs 19.1 ± 9.9 hours, P < .001) and hospital stay (5.2 ± 1.9 vs 3.5 ± 0.9 days, P < .001). At early follow-up (mean 1.5 years, maximum 4.2 years), there was no difference in need for reintervention. Of the 27 patients who underwent VATS ASD/PFO closure for a neurologic event, none had a recurrence. Conclusion: The use of VATS provides a safe, equally effective alternative to conventional sternotomy for ASD/PFO closure, using a less invasive approach.

Objectives To define whether the high sensitivity cardiac troponin T (hs-cTnT) assay in patients with immunoglobulin light chain amyloidosis (AL) improves risk prediction. Background Cardiac involvement is the major cause of death in patients with AL amyloidosis. Risk stratification is facilitated by cardiac biomarkers such as cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods Stored serum from patients with newly diagnosed AL was used to measure hs-cTnT, cTnT, and NT-proBNP. Survival modelling was performed. Results The direct numeric result from hs-cTnT measurement cannot merely be substituted for a cTnT measurement in the Mayo AL staging system. The performance of the receiver operator curve derived an hs-cTnT cut-point of 54 ng/L which improves on the value of 35 ng/L validated with the prior iteration of the assay. An alternate staging option using hs-cTnT alone—using the two thresholds 14 ng/L and 54 ng/L—performs as well as either the original Mayo AL staging system or other systems incorporating hs-cTnT. On multivariate analysis, an hs-cTnT alone staging system was independent of period of diagnosis, type of therapy, and NT-proBNP value, the last of which dropped out of the model. Alternate models were explored, but none performed better than the original system or the new hs-cTnT system. Thus, hs-cTnT can be used alone for the staging of disease prognosis. Conclusions A survival model based on hs-cTnT improves the prognostic staging of patients with AL amyloidosis, relegating NT-proBNP to a measure of cardiac response.

ICD in Cardiac AmyloidosisBackgroundCardiac amyloidosis (CA) is associated with increased risk of sudden cardiac arrest. Although ICD therapy improves survival in patients with cardiomyopathy due to other etiologies, the benefit of ICD therapy in patients with CA is unclear in large part due to limited data on the precise mechanism of sudden cardiac arrest and selection of patients with cardiac amyloidosis for ICD therapy.ObjectiveThe objective was to determine the benefit of ICD therapy in cardiac amyloidosis.MethodsWe reviewed all ICD implant indications, procedures, and therapies, of CA patients evaluated at Mayo Clinic between 2000 and 2009.ResultsA total of 53 patients with CA (33 AL, 10 senile, 9 familial, and 1 AA) who underwent ICD implantation were included. Indication for ICD implantation was for primary prevention of sudden cardiac arrest in 41 (77%) patients and secondary prevention in 12 (23%) patients. The rate of appropriate ICD shocks was 32% in the first year and was observed almost exclusively in AL amyloidosis patients, occurring in 15 patients (12 AL amyloidosis, 2 senile, 1 AA). Appropriate ICD shocks were more frequent in patients with prior sudden cardiac arrest or sustained ventricular arrhythmias (secondary prevention indication), and less frequent in patients who presented with decreased ejection fraction or syncope.ConclusionsA high rate of appropriate ICD shocks was observed especially in patients with AL‐type amyloidosis. However, appropriate ICD therapy did not translate into overall survival benefit, suggesting that selection of patients with CA who might be candidates for ICD is imprecise.

Tetralogy of Fallot (TOF) is a cyanotic congenital heart defect typically diagnosed in infancy and treated with early surgical correction. We report a patient with TOF diagnosed at age 78. Successful surgical repair was performed at age 83, the oldest reported age of surgical correction of this condition. Despite a complicated surgical and postoperative course, the patient is doing well almost four years later.