Prevalence of cardiac amyloidosis in patients with unexplained left ventricle hypertrophy

Background Amyloid cardiomyopathy (CA) it is more frequently diagnosed due to rapidly developing imaging modalities. Misfolding of transthyretin (TTR) is the source of two distinct forms of amyloidosis (ATTR): acquired wild-type (ATTRwt) and hereditary (ATTRm). Types of TTR gene variants display genetic and ethnic variability. The aim of this prospective study was to assess the prevalence and types of pathogenic genetic variants associated with ATTRm amyloidosis in patients with unexplained left ventricle (LV) hypertrophy. Methods We evaluated prospectively 101 consecutive patients (37 (37%) females, age: 69.7±13.6 y.o.) in years 2016–2021. Analysis included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT) with 3,3-disphono-1,2-propanodicarboxylic acid (DPD), and in selected cases cardiac or soft tissue biopsy. Patients with DPD cardiac uptake in SPECT or positive histopathology or family history of ATTR were subjected to genetic testing by an amplicon-based next-generation TTR sequencing approach. Results Enrolled patients presented with marked LV hypertrophy with maximum wall thickness of 18.9±4 mm. Based on performed tests 34 patients (33.7%) were diagnosed with amyloidosis, including 17 cases of light-chain amyloidosis (AL), 16 of ATTR, and 1 case of other type of amyloidosis. Overall, patients with CA presented with mean 2.6±0.9 NYHA class. In TTE there was LV maximum wall thickness of 19.5±4 mm and LV mass value index value of 182±48 g/m2, decreased global longitudinal strain value (GLS, −14.1±5%) and advanced diastolic dysfunction (EA 2.2±1.1, E/E' 22±9). Overall, there were 8 cases of ATTRwt and eight patients were diagnosed ATTRm. There were detected following types of TTR variants - c.302C>T p.(Ala101Val) in a single male patient, c.325G>A p.(Glu109Lys) in a single male patient and c.157T>C p.(Phe53Leu) in six patients. Overall, 10 patients with ATTR presented with polyneuropathy, additionally six had diagnosed carpal tunnel syndrome. All patients with ATTRm had positive family history for CA. Conclusions In patients with unexpected LV hypertrophy evaluated in a cardiology referral center a high number of patients may suffer from underlying CA. Types of detected TTR gene variants associated with CA included most often Phe53Leu, and rare variants Ala101Val, Glu109Lys. FUNDunding Acknowledgement Type of funding sources: None.

Hyperechogenic intimal lesions and wall thickness of the temporal and facial arteries in elderly patients with arterial occlusions of the eye

ObjectiveTo determine the association of arteriosclerosis, characterised by hyperechogenic intimal lesions (HIL), with wall thickness of the temporal and facial arteries in elderly patients with ocular arterial occlusions.MethodsPatients suffering from non-arteritic ocular perfusion disorders were included. High-resolution compression sonography (18 MHz) images of the temporal arteries (frontal and parietal branch at the upper margin of the auricle) and facial arteries (at the crossing point of the artery over the mandible) were analysed for the presence of HIL (grade 0: absent; grade 1: moderate; grade 2: severe). Characteristics of patients with and without evidence of HIL >grade 1 were compared.ResultsIn total, 330 cranial artery segments of 55 patients were analysed. HIL ≥grade 1 was present in 13.0% of all artery segments and in 38.1% of all patients. Patients with HIL ≥grade 1 in at least one arterial segment displayed significantly increased maximum wall thickness of the temporal arteries (0.62±0.23 mm vs 0.50±0.13 mm; p<0.01) and facial arteries (0.71±0.20 mm vs 0.54±0.19 mm; p=0.01). Patients with at least one temporal or facial artery segment with HIL were older, more often male and more frequently suffered from diabetes mellitus.ConclusionThe presence of HIL goes along with a significantly increased wall thickness of the temporal and facial arteries. These findings should be considered when interpreting the results of sonography of the cranial arteries in the diagnostic workup of suspected giant cell arteritis.

Disparate trends of atherosclerotic plaque evolution in stroke patients under 18-month follow-up: a 3D whole-brain magnetic resonance vessel wall imaging study

Purpose The trend of atherosclerotic plaque feature evolution is unclear in stroke patients with and without recurrence. We aimed to use three-dimensional whole-brain magnetic resonance vessel wall imaging to quantify the morphological changes of causative lesions during medical therapy in patients with symptomatic intracranial atherosclerotic disease. Methods Patients with acute ischemic stroke attributed to intracranial atherosclerotic disease were retrospectively enrolled if they underwent both baseline and follow-up magnetic resonance vessel wall imaging. The morphological features of the causative plaque, including plaque volume, peak normalized wall index, maximum wall thickness, degree of stenosis, pre-contrast plaque-wall contrast ratio, and post-contrast plaque enhancement ratio, were quantified and compared between the non-recurrent and recurrent groups (defined as the recurrence of a vascular event within 18 months of stroke). Results Twenty-nine patients were included in the final analysis. No significant differences were found in plaque features in the baseline scan between the non-recurrent ( n = 22) and recurrent groups ( n = 7). The changes in maximum wall thickness (–13.32% vs. 8.93%, P = 0.026), plaque-wall contrast ratio (–0.82% vs. 3.42%, P = 0.005) and plaque enhancement ratio (–11.03% vs. 9.75%, P = 0.019) were significantly different between the non-recurrent and recurrent groups. Univariable logistic regression showed that the increase in plaque-wall contrast ratio (odds ratio 3.22, 95% confidence interval 1.55–9.98, P = 0.003) was related to stroke recurrence. Conclusion Morphological changes of plaque features on magnetic resonance vessel wall imaging demonstrated distinct trends in symptomatic intracranial atherosclerotic disease patients with and without stroke recurrence.

Diagnostic yield of genetic testing in a heterogeneous cohort of 1376 HCM patients

Background Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to evaluate the diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM, referred for genetic testing from multiple centers around the world. Methods A retrospective review of patients with a suspected clinical diagnosis of HCM referred for genetic testing at Blueprint Genetics was undertaken. The analysis included syndromic, myopathic and metabolic etiologies. Genetic test results and variant classifications were extracted from the database. Variants classified as pathogenic (P) or likely pathogenic (LP) were considered diagnostic. Results A total of 1376 samples were analyzed. Three hundred and sixty-nine tests were diagnostic (26.8%); 373 P or LP variants were identified. Only one copy number variant was identified. The majority of diagnostic variants involved genes encoding the sarcomere (85.0%) followed by 4.3% of diagnostic variants identified in the RASopathy genes. Two percent of diagnostic variants were in genes associated with a cardiomyopathy other than HCM or an inherited arrhythmia. Clinical variables that increased the likelihood of identifying a diagnostic variant included: an earlier age at diagnosis (p < 0.0001), a higher maximum wall thickness (MWT) (p < 0.0001), a positive family history (p < 0.0001), the absence of hypertension (p = 0.0002), and the presence of an implantable cardioverter-defibrillator (ICD) (p = 0.0004). Conclusion The diagnostic yield of genetic testing in this heterogeneous cohort of patients with a clinical suspicion of HCM is lower than what has been reported in well-characterized patient cohorts. We report the highest yield of diagnostic variants in the RASopathy genes identified in a laboratory cohort of HCM patients to date. The spectrum of genes implicated in this unselected cohort highlights the importance of pre-and post-test counseling when offering genetic testing to the broad HCM population.

Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes

Background It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. Methods In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. Results One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. Conclusions Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. Trial Registration NCT01475747, registered on November 21, 2011.

Three-dimensional volume-strain loops may reflect fibrosis in hypertrophic cardiomyopathy

Background Combined plotting of deformation parameters against other indices [e.g. arterial pressure, left ventricular (LV) volume] might offer additional information about different diseases. Especially in hypertrophic cardiomyopathy (HCM) this approach might offer new insights into the various phenotypic and pathophysiologic features of this entity. Purpose Aim of this study was i) to apply strain-volume loops in HCM based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops and phenotypic features of HCM (including thickness, obstruction and fibrosis). Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build a strain–volume loop. Peak of radial, longitudinal, and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), and strain to end-diastolic volume (EDV) ratio (Rs/V, Ls/V, Cs/V) were computed for the analysis (panel A). Additionally, burden of fibrosis (percentage of LV mass) was defined by LGE extent (&gt;5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO&gt;30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning strain-volume loops the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Among typical HCM characteristics tested (LV mass, LVOTO and LGE), only LV mass presented significant correlations with LsSl (r=−0.41, p&lt;0.01). Interestingly, HCM patients with smaller LVMI and without LGE presented steeper and narrower (difference between systolic and diastolic strain for the same volume) longitudinal strain-volume loops compared to patients with larger LVMIs and fibrosis (panel B). Conclusions Strain-volume loop is an innovative application of 3D deformation imaging in HCM. According to this new non-invasive method, increase of LVMI in HCM is accompanied by less longitudinal contribution to stroke volume, whereas better systolic-diastolic coupling may exclude the presence of underlying fibrosis. Funding Acknowledgement Type of funding source: None

Speckle tracking deformation imaging to detect regional fibrosis in hypertrophic cardiomyopathy: a comparison between 2D and 3D echo modalities

Aims We aimed at directly comparing three-dimensional (3D) and two-dimensional (2D) deformation parameters in hypertrophic hearts and depict which may best reflect underlying fibrosis in hypertrophic cardiomyopathy (HCM), defined by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). Methods and results We included 40 HCM [54.1 ± 14.3 years, 82.5% male, maximum wall thickness (MWT) 19.3 ± 4.8 mm] and 15 hypertensive (HTN) patients showing myocardial hypertrophy (58.1 ± 15.6 years, 80% male, MWT 12.8 ± 1.4 mm) who have consecutively undergone 2D-, 3D-speckle tracking echocardiography and LGE CMR. Deformation parameters (2D and 3D) presented overall poor to moderate correlations, with 3D_longitudinal strain (LS) and 3D_circumferential strain (CS) values being constantly higher compared to 2D derivatives. By regression analysis, hypertrophy substrate (HCM vs. hypertension) and hypertrophy magnitude were the parameters to influence 2D–3D LS and CS strain correlations (R2 = 0.66, P &lt; 0.001 and R2 = 0.5, P = 0.001 accordingly). Among segmental deformation indices, 2D_LS showed the best area under the curve [AUC = 0.78, 95% confidence intervals (CI) (0.75–0.81), P &lt; 0.0005] to detect fibrosis, with 3D deformation parameters showing similar AUC (0.65) and 3D_LS presenting the highest specificity [93.1%, 95% CI (90.6–95.1)]. Conclusions In hypertrophic hearts, 2D and 3D deformation parameters are not interchangeable, showing modest correlations. Thickness, substrate, and tracking algorithm calculating assumptions seem to induce this variability. Nevertheless, among HCM patients 2D_peak segmental longitudinal strain remains the best strain parameter for tissue characterization and fibrosis detection.

Abstract WMP48: 3D MR Vessel Wall Imaging Reveals Plaque-Specific Responses to Medical Therapy in Patients With Symptomatic Intracranial Atherosclerotic Disease: Initial Experience

Introduction: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke worldwide and carries a high rate of recurrence. Follow-up of symptomatic ICAD routinely relies on assessment of lumen stenosis. Magnetic resonance vessel wall imaging (MR-VWI) has recently demonstrated the potential to reliably quantify plaque features. This work presents our experience in using serial MR-VWI to quantify the morphological changes of culprit lesions in response to medical therapy in patients with symptomatic ICAD. Methods: Twenty-four patients (4 females; age 46.75±14.05 years) with acute ischemic stroke secondary to ICAD underwent baseline (1-44 days after onset) and follow-up (3-15 months after baseline) 3D whole-brain MR-VWI, which was used to acquire pre- and post-contrast images. Quantitative plaque features, including plaque volume, peak normalized wall index (pNWI), maximum wall thickness, stenosis degree, pre-contrast plaque-wall contrast ratio (CR), and post-contrast plaque enhancement ratio (ER), were derived from both baseline and follow-up MR-VWI scans. Patients with 18-month clinical follow-up were divided into progression and non-progression groups depending on whether major vascular events (stroke, TIA, death) occurred. Results: Seventeen patients were categorized into the non-progression group and 4 into the progression group. Maximum wall thickness (P=0.047), CR (P=0.020) and ER (P=0.012) showed significant decreases in the non-progression group. In the progression group, all 4 patients showed an increase in pNWI, stenosis degree and CR; plaque volume, maximum wall thickness and ER increased in three patients. Typical cases are shown in Figure. Conclusions: Quantitative assessment of lesion-specific responses to medical therapy is clinically feasible with serial MR-VWI. The changes of plaque over time may be useful for ischemic stroke risk stratification with implications for ICAD medical management.

Study on optimization of thermal spinning process of accumulator shell

In view of the shortcomings of the existing hot spinning process technology of the accumulator shell, a method for optimizing the multi-spinning process parameters is proposed. The Johnson-Cook constitutive model of the accumulator shell material – 34CrMo4 alloy steel − was established with its parameters obtained experimentally. The finite element simulation was carried out for the hot spinning and closing process. Based on which, three parameters with the greatest influence on the spinning formation were studied: spinning temperature, spindle speed and friction coefficient. Combined with the central composite test, the response surface model and the mapping relationship between the three parameters and the maximum mises stress as well as the maximum wall thickness increment of the shell were established. The Pareto optimized solution set was obtained through multi-objective optimization. Under the condition of not affecting product quality, the optimized solution with low spinning temperature and high spindle speed is selected to reduce energy loss and improve work efficiency. The results indicate that the optimized process is experimentally verified to reduce the process temperature by nearly 30 °C, and the efficiency is increased by 25%.