Lipoprotein(a) and aortic valve stenosis: A casual or causal association?

AimsThis review aims to provide an update of available methods for imaging calcification activity and potential therapeutic options.Data SynthesisAortic valve calcification represents the most common heart valve condition requiring treatment among adults in Western societies. No medical therapies are proven to be effective in treating symptoms or reducing disease progression. Therefore, surgical or transcatheter aortic valve replacement remains the only available treatment option. Elevated circulating concentrations of lipoprotein(a) is strongly associated with degenerative aortic stenosis. This relationship was first observed in prospective observational studies, and the causal relationship was confirmed in genetic studies.ConclusionsNew therapeutic targets have been identified and new imaging techniques could be used to test the effectiveness of new agents and further clarify the pathophysiology of AVS. No therapy that specifically lowers Lp (a) levels has been approved for clinical use.     

Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum

BackgroundTraditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm² were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable.ResultsIn total, 613 patients were initially recruited, with a mean ± standard deviation AVA of 0.72 ± 0.17 cm². Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n = 1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46–3.26; P < 0.001).ConclusionsArtificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.     

Male osteoporosis-what are the causes,diagnostic challenges,and management

Osteoporosis is underrecognized and undertreated in men, even though up to 25% of fractures in patients over the age of 50 years occur in men. Men develop osteoporosis with normal aging and accumulation of comorbidities that cause bone loss. Secondary causes of bone loss may be found in up to 60% of men with osteoporosis. Mortality in men who experience major fragility fracture is greater than in women. Diagnosis of osteoporosis in men is similar to women, based on low-trauma or fragility fractures, and/or bone mineral density dual-energy X-ray absorptiometry (DXA) T-scores at or below ?2.5. Because most clinical trials with osteoporosis drugs in men were based on bone density endpoints, not fracture reduction, the antifracture efficacy of approved treatments in men is not as well documented as that in women. Men at a high risk of fracture should be offered treatment to reduce future fractures.     

Association between dietary fiber intake and risk of incident aortic stenosis

Background and aimsAlthough aortic stenosis is the most common valvular heart disease requiring intervention in Europe, the role that diet plays in development of the disease is largely unknown. The pathophysiology of aortic stenosis is however similar to other cardiovascular diseases that fiber intake has been associated with. The aim of this study was consequently to investigate the association between dietary fiber intake as well as the main food sources of fiber, i.e. fruit and vegetables and whole grains, and risk of incident aortic stenosis.Methods and resultsThe Malmö Diet and Cancer Study is a Swedish prospective population-based cohort study with baseline data collection performed between year 1991–1996. Dietary habits were recorded through seven-day food diaries, 168-item diet questionnaires, and interviews, and data on incident aortic stenosis was collected through national registers. Among the 26,063 participants, 672 cases were ascertained during a mean follow-up period of 20 years. Cox regression was used to estimate the association between dietary intakes and incident aortic stenosis. No associations were found between incident aortic stenosis and intake of dietary fiber (HR for the highest vs lowest quintile: 0.93; 95% CI: 0.72–1.24), fruit and vegetables (HR: 0.98; 95% CI: 0.76–1.28), or whole grains (HR: 1.00; 95% CI: 0.79–1.26) in the main model.ConclusionThe findings of this study do not indicate that consumption of dietary fiber or fiber rich foods are associated with incident aortic stenosis.     

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

ObjectivesThis 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.MethodsPatients 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.ResultsOver 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.ConclusionsUse 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.     

High-sensitivity cardiac troponins: sex-specific values in clinical practice. Precision or confusion?

Cardiac troponins are pivotal in the evaluation of patients who suffer from acute chest pain, and the introduction of the high-sensitivity cardiac troponins (hs-cTn) has shown that there are differences between male and female patients. Recent recommendations from experts point out that an appropriate evaluation must take into account the patients’ sex, but there is no clear evidence of the implementation of this recommendation in the clinical practice, and the matter has sparked controversy. If the same cutoff value is used for both sexes, myocardial infarction in men might be overdiagnosed, especially in the elderly, who have relatively higher values, and might be underdiagnosed in most women. The International Federation of Clinical Chemistry and Laboratory Medicine Task Force on Clinical Applications of Cardiac Bio-Markers (IFCCLM, TF-CB) 2018 and the Fourth Universal Definition of Acute Myocardial Infarction support the overall and sex-specific 99^th percentile Upper Reference Limit (URL) cutoff value, but based on the definition of hs-cTn assays, the Limit of Detection (LoD) may be considered a starting point for an assessment method that does not differentiate between the levels of hs-cTn in male and female patients suspected of suffering from acute coronary syndrome (ACS). In this paper, we discuss the evidence and a novel strategy based on hs-cTn for rapidly ruling out myocardial infarction in low-risk patients who suffer from acute chest pain.     

Watchful waiting care or early intervention in asymptomatic severe aortic stenosis: Where we are

Central illustration. Patient-centred benefit versus risk analysis of early aortic valve replacement (AVR) for asymptomatic severe aortic stenosis. AKI: acute kidney injury; PM: pacemaker; PPM: patient prosthesis mismatch.

     

Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis

BackgroundOlder 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).ObjectivesThis study identified clinical characteristics and outcomes of AS-CA compared with lone AS.MethodsPatients 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.ResultsA 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).ConclusionsConcomitant 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.     

[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain,Transthyretin Amyloidosis,and Mimicking Conditions

ObjectivesThis study aimed to test the diagnostic value of [18F]–florbetaben positron emission tomography (PET) in patients with suspicion of CA.BackgroundDiagnosis of cardiac involvement in immunoglobulin light-chain–derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy.MethodsForty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection.ResultsVisual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUV_mean) in patients with AL, sustained over the whole acquisition period (early SUV_mean: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUV_mean: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUV_mean: 2.55; IQR: 1.80 to 2.97; vs. delayed SUV_mean: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUV_mean: 3.50; IQR: 1.60 to 3.37; vs. delayed SUV_mean: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume.ConclusionsDelayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38)     

Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis

ObjectivesThe aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation.BackgroundDiagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations.MethodsA total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini’s method.ResultsAmong 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings.ConclusionsThe sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.     

Outcomes After Transcatheter Aortic Valve Replacement in Bicuspid Versus Tricuspid Anatomy: A Systematic Review and Meta-Analysis

ObjectivesThe aim of this study was to compare the feasibility, safety, and clinical outcomes of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) stenosis.BackgroundAt present, limited observational data exist supporting TAVR in the context of bicuspid anatomy.MethodsPrimary endpoints were 1-year survival and device success. Secondary endpoints included moderate to severe paravalvular leak (PVL) and a composite endpoint of periprocedural complications; incidence rates of individual procedural endpoints were also explored individually.ResultsIn the main analysis, 17 studies and 181,433 patients undergoing TAVR were included, of whom 6,669 (0.27%) had BAV. A secondary analysis of 7,071 matched subjects with similar baseline characteristics was also performed. Device success and 1-year survival rates were similar between subjects with BAV and those with TAV (97% vs 94% [P = 0.55] and 91.3% vs 90.8% [P = 0.22], respectively). In patients with BAV, a trend toward a higher risk for periprocedural complications was observed in our main analysis (risk ratio [RR]: 1.12; 95% CI: 0.99-1.27; P = 0.07) but not in the matched population secondary analysis (RR: 1.00; 95% CI: 0.81-1.24; P = 0.99). The risk for moderate to severe PVL was higher in subjects with BAV (RR: 1.42; 95% CI: 1.29-1.58; P < 0.0001) as well as the incidence of cerebral ischemic events (2.4% vs 1.6%; P = 0.015) and of annular rupture (0.3% vs 0.02%; P = 0.014) in matched subjects.ConclusionsTAVR is a feasible option among selected patients with BAV anatomy, but the higher rates of moderate to severe PVL, annular rupture, and cerebral ischemic events observed in the BAV group warrant caution and further evidence.     

Prevalence of general and abdominal obesity and its relationship with opium,total opiate drugs,and chronic smoking: Fasa cohort study

Background and aimsObesity and drug use are two major global issues today. This study aimed to evaluate the relationship between alcohol and tobacco use with general and central obesity.MethodsThe data of the longitudinal population-based study were collected from the basis of the Fasa Cohort Study (FACS). Participants were 10141 people with 35–70 years old. Data were analyzed by SPSS 20 software. Binary logistic regression (BLR) was used for modelling. A significance level (α) less than 0.05% was considered for hypothesis testing.ResultsOf the total participants (N = 10104), 54.8% (n = 5539) were women. The prevalence of central obesity in terms of waist circumference (WC), waist to hip ratio (WHR), and waist to height ratio (WHtR) were calculated 48.20% (N = 4871), 79.50% (N = 8032), and 83.30% (N = 8314). The Odds Ratio (OR) adjusted of Abnormal body mass index (BMI) for Opium and chronic smoking were 0.54 (CI: 0.47–0.63) and 0.47 (CI:0.40–0.56). OR adjusted Abnormal WC for opium and chronic smoking were calculated 0.65 (CI: 0.53–0.80) and 0.57 (CI:0.46–0.72), respectively. Three variables of opium (OR = 0.54, CI: 0.46–0.64), total opiate drugs (OR = 1.46, CI:1.16–1.83) and chronic smoking (OR = 0.58, CI: 0.48–0.70) remained in the modeling for Abnormal WHR. Which were statistically significant.ConclusionSignificant and inverse relationships were found between obesity and opium, total opiate drugs, and chronic smoking.