Relation of Body Mass Index to Transthyretin Cardiac Amyloidosis Particularly in Black and Hispanic Patients (from the SCAN-MP Study).

Heart failure with preserved ejection fraction is a heterogeneous clinical syndrome that includes distinct subtypes with different pathophysiologies, genetics, and treatment. Distinguishing heart failure with preserved ejection fraction caused by transthyretin cardiac amyloidosis (ATTR-CA) is critical given its specific treatment. We analyzed a single-center retrospective cohort to determine the association of body mass index (BMI) with a composite of either ATTR-CA or the valine-to-isoleucine substitution (Val122Ile) variant genotype (ATTR-CA+Val122Ile). These BMI differences were prospectively evaluated in the multicenter Screening for Cardiac Amyloidosis using nuclear imaging for Minority Populations (SCAN-MP) study of Black and Hispanic patients with heart failure. The association of BMI with ATTR-CA+Val122Ile was compared by Wilcoxon rank sum analysis and combined with age, gender, and maximum left ventricle wall thickness in multivariable logistic regression. In the retrospective analysis (n = 469), ATTR-CA+Val122Ile was identified in n = 198 (40%), who had a lower median BMI (25.8 kg/m2, interquartile range [IQR] 23.4 to 28.9) than other patients (27.1 kg/m2, IQR 23.9 to 32.0) (p <0.001). In multivariable logistic regression, BMI <30 kg/m2 (odds ratio 2.6, 95% confidence interval 1.5 to 4.5) remained independently associated with ATTR-CA+Val122Ile with a greater association in Black and Hispanic patients (odds ratio 5.8, 95% confidence interval 1.7 to 19.6). In SCAN-MP (n = 201), 17 (8%) had either ATTR-CA (n = 10) or were Val122Ile carriers (n = 7) with negative pyrophosphate scans. BMI was lower (25.4 kg/m2 [IQR 24.3 to 28.2]) in ATTR-CA+Val122Ile patients than in non-amyloid patients (32.7 kg/m2 [28.3 to 38.6]) (p <0.001), a finding that persisted in multivariable analysis (p = 0.002). In conclusion, lower BMI is associated with ATTR-CA+Val122Ile in heart failure with increased left ventricle wall thickness, particularly in Black and Hispanic patients, and may aid in the identification of those benefiting from ATTR-CA evaluation.

False positive technetium-99m pyrophosphate scintigraphy in a patient with cardiac amyloidosis light chain: Case report.

INTRODUCTION: Patients with cardiac amyloidosis light chain (AL) present with negative Tc-99m pyrophosphate (PYP) scintigraphy (absent or mild heart uptake). On the contrary, patients with cardiac amyloidosis transthyretin (ATTR) present with positive Tc-99m PYP scanning (intensive heart uptake). We present a false positive Tc-99m PYP scintigraphy (grade 2, the heart-to-contralateral ratio is 1.65) in a patient with AL. PATIENT CONCERNS: A 42-year-old Chinese man complained of effort intolerance, chest discomfort, and short of breath progressively over 1 year. New York Heart Association Class III. Physical examination showed legs swelling. Laboratory revealed elevated brain natriuretic peptide of 23,031 ng/mL (0-88) and Troponin-T of 273.4 ng/mL (0-14). DIAGNOSIS: Cardiac amyloidosis light chain. Evidences: free light chains (FLCs): decreased serum free kappa/lambda ratio of 0.043 (0.31-1.56). Immunofixation electrophoresis: a positive lambda light chain monoclonal protein. Cardiac biopsy: HE: Ambiguity Congo red strain. Myocardial immunofluorescence: positive lambda light chain. Myocardial immunohistochemistry: positive lambda light chain, negative kappa light chain, and TTR. INTERVENTIONS: Furosemide 40 mg qd, torasemide 20 mg qd, spirolactone 20 mg qd, potassium chloride 10 mL per 500 mL urine, atorvastatin calcium tablet 20 mg qd, aspirin enteric-coated tablets 100 mg qd during the 2-weeks in-hospital. OUTCOMES: The patient died 2 months later after discharge. CONCLUSION: False positive Tc-99m PYP scintigraphy may rarely presented in patients with cardiac amyloidosis light chain. So, the clonal plasma cell process based on the FLCs and immunofixation is a base to rule out AL cardiac amyloidosis when we interpret a positive Tc-99m PYP scintigraphy.

Admission Cardiac Diagnostic Testing with Electrocardiography and Troponin Measurement Prognosticates Increased 30-Day Mortality in COVID-19.

Background Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID-19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs-cTnT), were abstracted. At 30 days follow-up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST-T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non-life-threatening rhythms (P<0.001). Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST-T wave changes, and initial hs-cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs-cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality. Conclusions Myocardial injury with hs-cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID-19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.

Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution.

OBJECTIVES: This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. BACKGROUND: 99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics. METHODS: Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed. RESULTS: Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans. CONCLUSIONS: Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.

Repeat Revascularization for Severe Recurrent Coronary Artery Disease in a Young Woman With Takayasu Arteritis.

A young woman with Takayasu arteritis presented with an acute coronary syndrome with ostial left main coronary artery stenosis. She underwent urgent coronary artery bypass surgery but developed recurrent symptoms 6 months later owing to graft failure. She was treated with percutaneous coronary intervention with resolution of her symptoms. (Level of Difficulty: Beginner.).

Cardiac Tumors: Clinical Presentation, Diagnosis, and Management.

OPINION STATEMENT: Cardiac masses and tumors are a heterogenous group of disorders and include primary tumors (both benign and malignant), metastatic disease, and numerous masquerades such as thrombus. Clinical presentation ranges from incidental discovery on imaging tests ordered for other reasons to life-threatening presentations such as cardiac tamponade, arrhythmia, obstruction, and systemic embolization. Of the available imaging modalities, cardiac MRI is generally the most useful for assessment and helps to delineate the relevant anatomy. Due to the technical difficulties and risk of biopsy of cardiac masses, a presumptive diagnosis is typically made using imaging techniques with surgery serving both a diagnostic and curative role. Because these conditions can vary widely in their management, we recommend early involvement of a multidisciplinary group which should include a cardiologist, cardiac surgeon, and oncologist.

More than an anticoagulant: Do heparins have direct anti-inflammatory effects?

The heparins, well-known for their anticoagulant properties, may also have anti-inflammatory effects that could contribute to their effectiveness in the treatment of venous thromboembolism and other vascular diseases. This review focuses on the inflammatory pathophysiology that underlies the development of thrombosis and the putative effects of heparin on these pathways. We present evidence supporting the use of heparin for other indications, including autoimmune disease, malignancy, and disseminated intravascular coagulation. These considerations highlight the need for further research to elucidate the mechanisms of the possible pleiotropic effects of the heparins, with a view to advancing treatments based upon heparin derivatives.

Warfarin and Vascular Calcification.

The vitamin K antagonist, warfarin, is the most commonly prescribed oral anticoagulant. Use of warfarin is associated with an increase in systemic calcification, including in the coronary and peripheral vasculature. This increase in vascular calcification is due to inhibition of the enzyme matrix gamma-carboxyglutamate Gla protein (MGP). MGP is a vitamin K-dependent protein that ordinarily prevents systemic calcification by scavenging calcium phosphate in the tissues. Warfarin-induced systemic calcification can result in adverse clinical effects. In this review article, we highlight some of the key translational and clinical studies that associate warfarin with vascular calcification.

A retrospective comparison of skin and renal direct immunofluorescence findings in patients with glomerulonephritis in adult Henoch-Schönlein purpura.

BACKGROUND: Henoch-Sch¨onlein purpura (HSP) is a vasculitis tha tcan affect the skin and kidneys. It is characterized by immunoglobulin(Ig) A-predominant deposition in small blood vessels. To our knowledge, there has been no comparison of direct immunofluorescence (DIF) findings in skin and kidney biopsy specimens. METHODS: We retrospectively studied 21 adults with HSP who had IgA deposition in the skin and kidneys. The skin and kidney DIF findings were compared and tested for an association with the progression of renal disease. RESULTS: Mean age of the patients was 51.4 years. Follow-up data were available for 19 patients, of whom 5 had progression to chronic kidney disease or renal failure. Concordance between DIF findings onskin and renal biopsies was 100% for IgA, 80% for C3, 80% for IgG,71% for IgM and 53% for fibrinogen. A worse renal outcome was associated with renal IgG deposition (p=0.04). A trend for worse renal outcome was found with renal fibrinogen and skin IgM deposition(p=0.10 and 0.14, respectively). CONCLUSIONS: In this retrospective study of adult HSP, theconcordance between DIF findings in skin and kidney specimens was low-moderate. Further study is required to elucidate the mechanisms responsible for these differences in Ig deposition.

Histopathology and correlates of systemic disease in adult Henoch-Schönlein purpura: a retrospective study of microscopic and clinical findings in 68 patients at Mayo Clinic.

BACKGROUND: The histopathology of Henoch-Schönlein purpura (HSP) is well defined, but specific markers have not been correlated with systemic involvement. OBJECTIVE: We sought to evaluate whether histopathologic markers were associated with renal or other systemic involvement in adult HSP. METHODS: We retrospectively reviewed clinical information and pathology slides of 68 adult patients with HSP seen at Mayo Clinic between 1992 and 2011. RESULTS: Of the 68 patients, mean age was 45.8 years and 41 (60%) of the patients were male. Renal involvement was observed in 30 patients (44%), gastrointestinal tract in 27 (40%), joint in 32 (47%), and any systemic signs in 52 (76%). Patients who were older than 40 years and had leukocytoclastic vasculitis with an absence of eosinophils on skin biopsy specimen had higher rates of renal involvement than those who did not have both of these features (75% vs 27%; P < .001). Patients with skin biopsy specimens showing leukocytoclastic vasculitis and an absence of histiocytes had higher rates of gastrointestinal tract involvement (P = .03). Age of 40 years or younger was associated with increased risk for gastrointestinal tract involvement and a nonsignificant trend for joint involvement (P = .004 and P = .06, respectively). LIMITATIONS: This study is retrospective, and the causative factors of HSP were unable to be determined in many patients. CONCLUSION: Patients older than 40 years with HSP who had an absence of eosinophils on skin biopsy specimen had a nearly 3-times increased risk of renal involvement compared with patients who did not have both features.

Correlates of systemic disease in adult Henoch-Schönlein purpura: a retrospective study of direct immunofluorescence and skin lesion distribution in 87 patients at Mayo Clinic.

BACKGROUND: Detection of IgM in lesional skin of adult patients with Henoch-Schönlein purpura via direct immunofluorescence (DIF) has been associated with the presence of renal disease. OBJECTIVE: We sought to examine whether DIF findings of skin biopsy specimens and distribution of skin lesions were associated with the presence of systemic disease, including renal, gastrointestinal tract, and joint involvement. METHODS: We performed a retrospective review of adult patients with Henoch-Schönlein purpura seen at Mayo Clinic between 1992 and 2011. RESULTS: Of the 87 patients (mean age, 46.1 years), 51 (59%) were male. A total of 39 patients (45%) had renal disease; 32 (37%), gastrointestinal tract involvement; 39 (45%), joint involvement; and 65 (75%), some systemic involvement. In all, 61 patients (70%) had cutaneous lesions above the waist. The DIF findings showed the presence of IgA in all 87 patients (100%). In addition, findings were positive for IgM in 32 patients (37%); IgG in 3 patients (3%); C3 in 75 patients (87%); and fibrinogen in 78 patients (92%). IgM was not found to be significantly associated with renal disease (P = .10); however, absence of fibrinogen was correlated with presence of renal involvement (P = .04). No other correlations were detected between DIF findings and systemic disease. Lesions above the waist were not significantly associated with renal (P = .12) or any (P = .76) systemic involvement. LIMITATIONS: This study is retrospective. CONCLUSIONS: Neither IgM in lesional skin nor distribution of skin lesions above the waist was a reliable indicator of renal or systemic disease in adults with Henoch-Schönlein purpura.