Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis.

BACKGROUND: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS: A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36). CONCLUSIONS: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.

Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients.

OBJECTIVES: The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid. BACKGROUND: AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV). METHODS: Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition. RESULTS: A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECVCT accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm. CONCLUSIONS: ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well.

DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker.

OBJECTIVES: To assess whether single-photon emission computed tomography (SPECT/CT) quantification of bone scintigraphy would improve diagnostic accuracy and offer a means of quantifying amyloid burden. BACKGROUND: Transthyretin-related cardiac amyloidosis is common and can be diagnosed noninvasively using bone scintigraphy; interpretation, however, relies on planar images. SPECT/CT imaging offers 3-dimensional visualization. METHODS: This was a single-center, retrospective analysis of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans reported using the Perugini grading system (0 = negative; 1 to 3 = increasingly positive). Conventional planar quantification techniques (heart/contralateral lung, and heart/whole-body retention ratios) were performed. Heart, adjacent vertebra, paraspinal muscle and liver peak standardized uptake values (SUVpeak) were recorded from SPECT/CT acquisitions. An SUV retention index was also calculated: (cardiac SUVpeak/vertebral SUVpeak) × paraspinal muscle SUVpeak. In a subgroup of patients, SPECT/CT quantification was compared with myocardial extracellular volume quantification by CT imaging (ECVCT). RESULTS: A total of 100 DPD scans were analyzed (patient age 84 ± 9 years; 52% male): 40 were Perugini grade 0, 12 were grade 1, 41 were grade 2, and 7 were grade 3. Cardiac SUVpeak increased from grade 0 to grade 2; however, it plateaued between grades 2 and 3 (p < 0.001). Paraspinal muscle SUVpeak increased with grade (p < 0.001), whereas vertebral SUVpeak decreased (p < 0.001). The composite parameter of SUV retention index overcame the plateauing of the cardiac SUVpeak and increased across all grades (p < 0.001). Cardiac SUVpeak correlated well (r2 = 0.73; p < 0.001) with ECVCT. Both the cardiac SUVpeak and SUV retention index had excellent diagnostic accuracy (area under the curve [AUC]: 0.999). The heart to contralateral lung ratio performed the best of the planar quantification techniques (AUC: 0.987). CONCLUSIONS: SPECT/CT quantification in DPD scintigraphy is possible and outperforms planar quantification techniques. Differentiation of Perugini grade 2 or 3 is confounded by soft tissue uptake, which can be overcome by a composite SUV retention index. This index can help in the diagnosis of cardiac amyloidosis and may offer a means of monitoring response to therapy.

Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation.

AIMS: Cardiac amyloidosis is common in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI). We hypothesized that patients with dual aortic stenosis and cardiac amyloid pathology (AS-amyloid) would have different baseline characteristics, periprocedural and mortality outcomes. METHODS AND RESULTS: Patients aged ≥75 with severe AS referred for TAVI at two sites underwent blinded bone scintigraphy prior to intervention (Perugini Grade 0 negative, 1-3 increasingly positive). Baseline assessment included echocardiography, electrocardiogram (ECG), blood tests, 6-min walk test, and health questionnaire, with periprocedural complications and mortality follow-up. Two hundred patients were recruited (aged 85 ± 5 years, 50% male). AS-amyloid was found in 26 (13%): 8 Grade 1, 18 Grade 2. AS-amyloid patients were older (88 ± 5 vs. 85 ± 5 years, P = 0.001), with reduced quality of life (EQ-5D-5L 50 vs. 65, P = 0.04). Left ventricular wall thickness was higher (14 mm vs. 13 mm, P = 0.02), ECG voltages lower (Sokolow-Lyon 1.9 ± 0.7 vs. 2.5 ± 0.9 mV, P = 0.03) with lower voltage/mass ratio (0.017 vs. 0.025 mV/g/m2, P = 0.03). High-sensitivity troponin T and N-terminal pro-brain natriuretic peptide were higher (41 vs. 21 ng/L, P < 0.001; 3702 vs. 1254 ng/L, P = 0.001). Gender, comorbidities, 6-min walk distance, AS severity, prevalence of disproportionate hypertrophy, and post-TAVI complication rates (38% vs. 35%, P = 0.82) were the same. At a median follow-up of 19 (10-27) months, there was no mortality difference (P = 0.71). Transcatheter aortic valve implantation significantly improved outcome in the overall population (P < 0.001) and in those with AS-amyloid (P = 0.03). CONCLUSIONS: AS-amyloid is common and differs from lone AS. Transcatheter aortic valve implantation significantly improved outcome in AS-amyloid, while periprocedural complications and mortality were similar to lone AS, suggesting that TAVI should not be denied to patients with AS-amyloid.

Patterns of solid particle embolization during transcatheter aortic valve implantation and correlation with aortic valve calcification.

OBJECTIVES: To evaluate solid embolization during transcatheter aortic valve implantation (TAVI) and correlate this with aortic valve calcification. BACKGROUND: There is a known stroke risk with TAVI, thought partly to be due to dislodgement of native aortic valve particles during implantation. However, to date there is little evidence that aortic valve calcification actually impacts embolic risk. METHODS: Transcranial Doppler (TCD) was performed on consecutive suitable patients undergoing TAVI, using hardware and software enabling differentiation between solid and gaseous emboli. Data was analyzed by time points during the TAVI procedure. These results were correlated with aortic valve calcification. RESULTS: TCD was successfully performed on 63 patients. The median number of solid emboli was 76.0. The most common time point for solid embolization was during valve positioning. Forty-five of these patients had an appropriate CT scan which could be analyzed for an Agatston calcium score. The mean scores in the aortic valve and aortic root were 3382.4 and 754.9. There were significant correlations between the total number of solid emboli and valve calcium score (P = 0.033) and solid emboli during valve positioning and valve calcium score (P = 0.035). There was no relationship between gaseous emboli and valve calcium score. CONCLUSIONS: TAVI is associated with significant solid particle embolization, with the most common time point being during valve positioning. Solid embolization correlates with aortic valve calcium score, suggesting that valve calcification is a factor in embolic risk. This should be taken into consideration along with other clinical factors when assessing embolic risk.

Neointima and neoatherosclerotic characteristics in bare metal and first- and second-generation drug-eluting stents in patients admitted with cardiovascular events attributed to stent failure: an optical coherence tomography study.

AIMS: The aim of this study was to assess neoatherosclerotic plaque morphology in bare metal (BMS) and first- and second-generation drug-eluting stents (DES) in patients presenting with an event attributed to stent failure. METHODS AND RESULTS: Thirty-five patients (11 implanted with BMS, 13 with a first-generation and 11 with a second-generation DES) admitted with an event due to stent failure who had neoatherosclerotic lesions on optical coherence tomography were included in the analysis. The lumen and stent borders were detected and the lipid and calcific tissue were identified in the neointima and their burden was estimated. The neointima attenuation and backscatter indices were computed and compared between the different stent types. Although there were no differences in the neointima burden, the BMS group exhibited thinner fibrous caps (p<0.001), and a numerically increased incidence of lipid-rich plaques (p=0.052) and macrophage accumulation (p=0.012). Neointima discontinuities (p=0.009) and thrombus (p=0.032) were seen more often in first-generation DES. In all stent types, neoatherosclerosis had focal manifestations. In neoatherosclerotic lesions the attenuation and backscatter indices were increased in BMS (p=0.031 and p=0.018, respectively) compared to DES; however, there were no differences between stents in the attenuation indices in subsegments located distally to neoatherosclerotic lesions which had low values in all stent types. CONCLUSIONS: Although there are differences in lipid burden and neointima characteristics in different stent types, in all stents neoatherosclerosis has focal manifestations indicating that, irrespective of the stent type, focal triggers are involved in the generation of vulnerable neolesions.

Lesson of the month 1: Pericardial mass and cardiac tamponade associated with Mycoplasma pneumoniae.

Mycoplasma pneumoniae primarily causes respiratory tract infections. Extrapulmonary manifestations are seen in 20-25% of cases. Cardiac involvement is rarely reported. We present a unique case of a pericardial mass and cardiac tamponade associated with a Mycoplasma pneumoniae pneumonia. This required emergency pericardial fenestration. The patient improved dramatically postoperatively on antibiotics and there was no recurrence of the pericardial effusion on follow up. This case highlights the often forgotten invasive properties of a common respiratory tract pathogen and emphasises the need to consider this easily treatable entity in the differential diagnosis of idiopathic pericardial effusions.

Tetrahydrobiopterin.

The endothelium plays a pivotal role in vascular physiology through a variety of factors, foremost of which is nitric oxide (NO). However, the biochemical mechanisms leading to reduced NO availability and subsequent endothelial dysfunction are not clearly understood. Tetrahydrobiopterin (BH(4)) is an essential cofactor for endothelial NO synthase. Recent preclinical and clinical studies in patients with cardiovascular risk and disease support the central role of reduced BH(4) availability in decreased NO production. This has led to BH(4) supplementation emerging as a possible therapy for conditions characterized by endothelial dysfunction (eg, hypertension, hypercholesterolemia, diabetes, and vascular disease states), and those caused by smoking and aging. Recent advances in drug formulation of BH(4) now offer the potential for better clinical understanding of endothelial function in human health and disease.