The Association of Mitral Annular Calcification With Cardiovascular and Noncardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.

Mitral annular calcification (MAC) may be a potential marker of biologic aging. However, the association of MAC with noncardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and noncardiovascular mortality, is not well-studied in a multiracial cohort. We used data from 6,814 participants (mean age: 62.2 ± 10.2 years, 52.9% women) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with noncontrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed the cross-sectional association of MAC with BMD and walking pace. Furthermore, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. In addition, we assessed the association of MAC with cardiovascular and noncardiovascular mortality using competing risks regression. The prevalence of MAC was 9.5% and was higher in women (10.7%) than in men (8.0%). MAC was associated with low BMD (coefficient -0.04, 95% confidence interval [CI] -0.06 to -0.02), with significant interaction by gender (p-interaction = 0.035). MAC was, however, not associated with impaired walking pace (odds ratio 1.09, 95% CI 0.89 to 1.33). Compared with participants without MAC, those with MAC had an increased risk of incident renal failure, albeit nonsignificant (hazard ratio [HR] 1.18, 95% CI 0.95 to 1.45), and a significantly higher hazards of dementia (HR 1.36, 95% CI 1.10 to 1.70). IN addition, participants with MAC had a substantially higher risk of all-cause (HR 1.47, 95% CI 1.29 to 1.69), cardiovascular (subdistribution HR 1.39, 95% CI 1.04 to 1.87), and noncardiovascular mortality (subdistribution HR 1.35, 95% CI 1.14 to 1.60) than those without MAC. MAC ≥100 versus <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and noncardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia and all-cause, cardiovascular, and noncardiovascular mortality in this multiracial cohort. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of noncardiovascular outcomes and death from other causes.

Interruption of the tricuspid regurgitant jet: A possible consequence of reflected waves.

Reflected pressure waves can impact central aortic pressure, and can cause notching of the pulmonic valve Doppler signal. However, reflected waves in the venous system usually do not achieve a high enough velocity to alter Doppler flow patterns. Herein we report a case of systolic notching of the tricuspid regurgitant signal that likely resulted from reflected venous waves.

Normal Ranges of Right Atrial Strain: A Systematic Review and Meta-Analysis.

BACKGROUND: Standard measures for the clinical assessment of right atrial (RA) function are lacking. OBJECTIVES: In this systematic review and meta-analysis, the authors sought to report a reference range for RA deformation parameters in healthy subjects and to identify factors that contribute to reported variations. METHODS: The authors conducted a comprehensive search of MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; Embase; Scopus; and the Cochrane Central Register of Controlled Trials from database inception through October 2021. Studies were included if they reported RA strain or strain rate (SR) using 2-dimensional speckle-tracking echocardiography in healthy volunteers or apparently healthy control patients. Data were extracted by 1 reviewer and then reviewed by 2 independent reviewers. Conflicts were resolved through consensus. Data were combined using the method developed by Siegel and adjusted using the restricted maximum likelihood random-effects model. The normal range was defined as the 95% CI of the mean. Heterogeneity was assessed by the Cochran Q-statistic and the inconsistency index (I2). The quality of the included studies and publication bias were assessed. Effects of clinical variables were sought in a metaregression. RESULTS: The search identified 4,111 subjects from 21 studies. The average RA reservoir strain was 44% (95% CI: 25%-63%), contractile strain was 17% (95% CI: 2%-32%), and conduit strain was 18% (95% CI: 7%-28%), with significant between-study heterogeneity and inconsistency. The systolic SR was 2.1 s-1 (95% CI: 0.9-3.4 s-1), early-diastolic SR was -2.0 s-1 (95% CI: -3.3 to -0.8 s-1), and late-diastolic SR was -1.9 s-1 (95% CI: -2.4 to -1.3 s-1), with nonsignificant heterogeneity and inconsistency. Ranges remained wide in healthy volunteers. The metaregression identified only age as significantly associated with systolic SR and no other significant determinants of variation among normal ranges of strain. CONCLUSIONS: There are wide reference ranges for RA deformation, and these may limit the utility of this test in clinical practice.

Systolic Anterior Motion of the Mitral Valve in the Presence of Annular Calcification.

BACKGROUND: Mitral annular calcification (MAC) has been reported as a possible cause of systolic anterior motion (SAM) of the mitral valve and dynamic left ventricular outflow tract (LVOT) obstruction. While morphologic features predisposing to SAM in other clinical settings have been described, patients with MAC+SAM have not been systematically investigated. We hypothesized that bulky calcium deposits in the mitral annulus could displace the valve toward the septum, thus promoting development of SAM. METHODS: We studied 30 patients with severe MAC who had SAM with septal contact. Three comparator groups (matched for age and sex) were developed: 30 controls without MAC or SAM, 30 with severe MAC but no SAM, and 30 with SAM but no MAC. RESULTS: Significant differences were found across groups for mitral valve coaptation point-septal distance (CSD), anterior mitral leaflet (AML) length, left ventricular diastolic dimension, and ejection fraction. Comparing all MAC subjects (n = 60) with controls, CSD was less (20.5 ± 4.1 vs 23.2 ± 3.7 mm, P = .003) and ejection fraction was higher (67.7% ± 7.8% vs 60.9% ± 6.4%, P < .0001) in MAC patients. Within MAC subjects AML was longer (21.9 ± 3.0 vs 17.4 ± 2.2 mm, P < .0001) and CSD was smaller (18.0 ± 2.7 vs 23.1 ± 3.6 mm, P < .0001) when SAM was present despite similar height of the calcium bar in the 2 MAC groups (12.4 ± 2.9 vs 11.1 ± 3.1 mm, P = .11). Regression analysis confirmed AML length and CSD as independent predictors of SAM. MAC+SAM patients also had more echocardiographic risk factors for SAM (acute aortomitral angle, small LVOT, long AML, small CSD, and presence of a septal bump) than MAC/no-SAM patients (3.4 ± 0.9 vs 1.8 ± 1.0, P < .0001). CONCLUSIONS: Bulky MAC appears to contribute to dynamic LVOT obstruction when it accumulates in such a way that the mitral valve is displaced anteriorly toward the septum. However, other features are also associated with SAM in these patients, particularly a long AML. A combination of morphologic features and favorable hemodynamics may be needed for SAM to develop in patients with severe MAC.

NAFLD in Cardiovascular Diseases: A Contributor or Comorbidity?

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.

Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

Simultaneous transcatheter tricuspid and mitral valve-in-valve replacement for the treatment of degenerated bioprosthetic valves.

Transcatheter valve-in-valve replacement has become a viable option for patients with degenerated bioprosthetic valves at high risk for redo surgery. We report a case of a patient who had degenerated mitral and tricuspid bioprosthesis causing severe tricuspid and mitral regurgitation. We performed simultaneous mitral and tricuspid valve-in-valve replacement via a transfemoral approach. Although the data on performing both valve-in-valve procedures are limited, this case demonstrated that these procedures can be safely done as a single procedure.

Obstructive sleep apnea in patients with acute aortic dissection.

BACKGROUND: Obstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the aortic wall. Thus, OSA may increase the risk for aortic dissection (AD). METHODS: This study enrolled 40 subjects with acute AD from four institutions; 37 completed the modified Berlin Questionnaire and 31 underwent attended overnight polysomnography. Aortic diameter was measured on a computed tomography scan at seven locations from the sinotubular junction to the diaphragm. RESULTS: Twenty-seven subjects had type A dissection; 13 had type B. In those who had polysomnography apnea-hypopnea index (AHI) ranged from 0.7 to 89. Prevalence of OSA (AHI ≥ 5) was 61%. Nocturnal presentation (10 p.m.-7 a.m.) did not differ by presence/absence of OSA. The modified Berlin Questionnaire was not predictive of the presence of OSA. Among type A subjects with polysomnography (n = 23), aortic diameters at all locations were greater in the OSA group though differences were not statistically significant. Summating aortic diameters at the seven locations also yielded a numerically larger mean value in the OSA group versus the non-OSA group. CONCLUSIONS: In this sample of patients with acute dissection, OSA was prevalent but was not associated with a nocturnal presentation. The presence of underlying OSA may be associated with larger aortic diameters at the time of dissection compared to patients without OSA. Though differences did not meet statistical significance the current series is limited by small numbers.

Validation of aortic valve calcium quantification thresholds measured by computed tomography in Asian patients with calcific aortic stenosis.

AIMS: Sex-specific thresholds of aortic valve calcification (AVC) have been proposed and validated in Caucasians. Thus, we aimed to validate their accuracy in Asians. METHODS AND RESULTS: Patients with calcific aortic stenosis (AS) from seven international centres were included. Exclusion criteria were ≥moderate aortic/mitral regurgitation and bicuspid valve. Optimal AVC and AVC-density sex-specific thresholds for severe AS were obtained in concordant grading and normal flow patients (CG/NF). We included 1263 patients [728 (57%) Asians, 573 (45%) women, 837 (66%) with CG/NF]. Mean gradient was 48 (26-64) mmHg and peak aortic velocity 4.5 (3.4-5.1) m/s. Optimal AVC thresholds were: 2145 Agatston Units (AU) in men and 1301 AU in women for Asians; and 1885 AU in men and 1129 AU in women for Caucasians. Overall, accuracy (% correctly classified) was high and comparable either using optimal or guidelines' thresholds (2000 AU in men, 1200 AU in women). However, accuracy was lower in Asian women vs. Caucasian women (76-78% vs. 94-95%; P < 0.001). Accuracy of AVC-density (476 AU/cm2 in men and 292 AU/cm2 in women) was comparable to absolute AVC in Caucasians (91% vs. 91%, respectively, P = 0.74), but higher than absolute AVC in Asians (87% vs. 81%, P < 0.001). There was no interaction between AVC/AVC-density and ethnicity (all P > 0.41) with regards to AS haemodynamic severity. CONCLUSION: AVC thresholds defining severe AS are comparable in Asian and Caucasian populations, and similar to those proposed in the guidelines. However, accuracy of AVC to identify severe AS in Asians (especially women) is sub-optimal. Therefore, the use of AVC-density is preferable in Asians.

Aortic valve stenosis and cancer: a common and complex association.

Introduction. The prevalence of aortic valve stenosis (AS) and malignancy are both high, especially in elderly people and in developed countries. These two conditions frequently coexist and share the same risk factors as atherosclerotic disease.Area covered. The progression of calcified AS may be accelerated by both cardiovascular risk factors and cancer treatments, such as radiotherapy. The standard treatment for symptomatic severe AS is surgical aortic valve replacement; however, in cancer patients, transcatheter implantation may be preferred as they are often at high-risk for cardiac surgery. In patients with AS and cancer, physicians may face difficult treatment decisions.To date, there is limited information on the impact of malignancy on outcomes in patients with severe AS; hence, there is no established treatment policy.Expert Opinion. Treating clinicians must integrate complex information about the severity of valve disease and expected cardiac outcomes with information regarding the cancer prognosis and the need for specific treatment, including surgery. Other comorbidities, age and frailty also contribute to decision-making about whether, when, and how to perform aortic valve replacement.

Energy loss associated with in-vitro modeling of mitral annular calcification.

INTRODUCTION: Study aims were to compare hemodynamics and viscous energy dissipation (VED) in 3D printed mitral valves-one replicating a normal valve and the other a valve with severe mitral annular calcification (MAC). Patients with severe MAC develop transmitral gradients, without the commissural fusion typifying rheumatic mitral stenosis (MS), and may have symptoms similar to classical MS. A proposed mechanism relates to VED due to disturbed blood flow through the diseased valve into the ventricle. METHODS: A silicone model of a normal mitral valve (MV) was created using a transesophageal echocardiography dataset. 3D printed calcium phantoms were incorporated into a second valve model to replicate severe MAC. The synthetic MVs were tested in a left heart duplicator under rest and exercise conditions. Fine particles were suspended in a water/glycerol blood analogue for particle image velocimetry calculation of VED. RESULTS: Catheter mean transmitral gradients were slightly higher in the MAC valve compared to the normal MV, both at rest (3.2 vs. 1.3 mm Hg) and with exercise (5.9 vs. 5.0 mm Hg); Doppler gradients were 2.7 vs. 2.1 mm Hg at rest and 9.9 vs 8.2 mm Hg with exercise. VED was similar between the two valves at rest. During exercise, VED increased to a greater extent for the MAC valve (240%) versus the normal valve (127%). CONCLUSION: MAC MS is associated with slightly increased transmitral gradients but markedly increased VED during exercise. These energy losses may contribute to the exercise intolerance and exertional dyspnea present in MAC patients.

Unrecognized pulmonary arterial hypertension in hospitalized patients.

Pulmonary hypertension (PH) is an underdiagnosed and potentially fatal condition. The utility of screening for PH in hospitalized patients undergoing echocardiography is unknown. The goal of this study was to determine the prevalence of undiagnosed pulmonary hypertension (PH) and probable pulmonary arterial hypertension (PAH) in hospitalized patients undergoing echocardiography for any indication. All hospitalized patients undergoing echocardiography were identified and echocardiographs reviewed prospectively for the presence of a tricuspid regurgitant (TR) jet. Electronic medical records (EMR) of patients with a TR jet ≥ 3 m/s were reviewed for identifiable causes of pulmonary hypertension. Patients with no identifiable cause were classified as presumptive World Health Organization (WHO) Group 1 PH (also known as PAH). These PAH patients were compared to other PH patients for baseline demographic characteristics and comorbidities as well as 30-day readmission and mortality. The admitting physicians of patients classified as PH were advised to consider further evaluation including right heart catheterization. We reviewed 4417 consecutive echocardiograms and identified 448 with a TR jet ≥ 3 m/s. Of these 448 patients with PH, 47 were identified as "presumptive PAH" and the other 401 as having PH belonging to WHO Groups 2-5. Presumptive PAH represented 1% of screened echocardiograms and 10.5% of those identified to have an elevated TR jet. Of the patients identified as presumptive PAH, 8 underwent further evaluation including a right heart catheterization, where 5 were confirmed to have PAH. Kaplan-Meier analysis revealed 30-day readmission was higher among those classified as PAH. Our data shows that pulmonary hypertension, as defined by TR jet ≥ 3 m/s, is frequently encountered in hospitalized patients undergoing echocardiography for any reason. A careful review of echocardiogram findings and clinical history suggested 10.5% of those with PH (and 1% of all screened patients) may meet the criteria for PAH. Considering PH is a fatal condition which is frequently missed, a hospital screening program seems feasible.

Aortic stenosis calcium scoring in a racially mixed sample.

Aortic stenosis (AS) is common and increasing in prevalence as the population ages. Using computed tomography (CT) to quantify aortic valve calcification (AVC) it has been reported that men have greater degrees of calcification than women among subjects with severe AS. These data, however, were derived in largely Caucasian populations and have not been verified in non-Caucasian subjects. This retrospective study identified 137 patients with severe AS who underwent valve replacement and had CT scans within 6 months prior to surgery. AVC scores were compared between men and women, both in the entire sample and in racial subgroups. 52% of subjects were male and 62.8% were non-Caucasian. Mean AVC score for the entire cohort was 3062.08±2097.87 with a range of 428-13,089. Gender differences in aortic valve calcification were found to be statistically significant with an average AVC score of 3646±2422 in men and 2433±1453 in women (p=0.001). On multivariate analysis, gender remained significantly associated with AVC score both in the entire sample (p=0.014) and in the non-Caucasian subgroup (p=0.008). Mean AVA was significantly greater in males than females but this difference disappeared when AVA was indexed to BSA (p=0.719). AVA was not different between racial groups (p=0.369). In this research we observed that among subjects with severe AS men have higher AVC scores than women regardless of racial background. This is consistent with previous studies in predominantly Caucasian populations.

Dialysis access as a source of infective endocarditis in dialysis patients.

The incidence of Infective Endocarditis (IE) is higher in dialysis patients compared to the general population. A major risk factor for IE in this group stems from bacterial invasion during repeated vascular access. Previous studies have shown increased risk of bacteremia in patients with indwelling dialysis catheters compared to permanent vascular access. However, association between the development of IE and the type of dialysis access is unclear. We aimed to examine the associated types of intravascular access and route of infection in dialysis patients who were admitted with infective endocarditis at our center. All patients admitted to Albert Einstein Medical Center in Philadelphia with a diagnosis of infective endocarditis who were on chronic hemodialysis were identified from the hospital database for the period of 1/1/07 to 12/31/18. Modified Duke criteria was used to confirm the diagnosis of infective endocarditis. A total of 96 cases were identified. Of those, 57 patients had an indwelling dialysis catheter while the other 39 had permanent dialysis access. In 82% of patients with dialysis catheters, their dialysis access site was identified as the primary source of infection compared to 30% in those with permanent dialysis access (p<0.001). The number of dialysis catheters placed in the preceding 6 months was strongly associated with endocarditis resulting from the dialysis access site (OR = 3.202, p=0.025). Dialysis catheters are more likely to serve as the source of infection in dialysis patients developing IE compared to permanent dialysis access. Increased awareness of risk of IE associated with dialysis catheters is warranted.

Color Doppler Splay: A Clue to the Presence of Significant Mitral Regurgitation.

BACKGROUND: The authors describe a previously unreported Doppler signal associated with mitral regurgitation (MR) as imaged using transthoracic echocardiography. Horizontal "splay" of the color Doppler signal along the atrial surface of the valve may indicate significant regurgitation when the MR jet otherwise appears benign. METHODS: Splay was defined as a nonphysiologic arc of color centered at the point at which the MR jet emerges into the left atrium. The authors present a series of 10 cases of clinically significant MR (moderately severe or severe as defined by transesophageal echocardiography) that were misclassified on transthoracic echocardiography as less than moderate. The splay signal was present on at least one standard transthoracic view in each case. To better characterize the splay signal, two groups were created from existing clinically driven transthoracic echocardiograms: 100 consecutive patients with severe MR and 100 with mild MR. RESULTS: Splay was present in the majority of severe MR cases (81%) regardless of vendor machine, ejection fraction, or MR etiology. Splay was particularly prevalent among patients with wall-hugging jets (28 of 30 [93%]). In patients with mild MR, splay was present less often (16%), on fewer frames per clip, and had smaller dimensions compared with severe MR. Color scale did not differ between subjects with and those without splay, but color gain was higher when splay was present (P = .04). Machine settings were further explored in a single subject with prominent splay: increasing transducer frequency reduced splay, while increasing color gain increased it. CONCLUSIONS: The authors describe a new transthoracic echocardiographic sign of MR. Horizontal splay may be a clue to the presence of severe MR when the main body of the jet is out of the imaging plane. Splay is likely generated as a side-lobe artifact due to a high-flux regurgitant jet.

Exercise behavior of degenerative mitral stenosis.

Mitral annular calcification (MAC) is increasingly encountered, particularly among the elderly and those with chronic kidney disease, and is often associated with a transvalvular gradient. In contrast to rheumatic mitral stenosis relatively little is known about mitral stenosis due to MAC. We aimed to clarify whether exercise limitation in this group is primarily due to valvular obstruction or ventricular dysfunction resulting from multiple comorbidities. 20 patients with severe MAC (bulky calcium deposits which restricted leaflet motion) were submitted to supine bicycle exercise, measuring Doppler and echocardiographic parameters at baseline and during exercise. They were compared 1:1 to subjects matched for age, sex, and left ventricular wall thickness. At baseline MAC subjects had higher mean mitral valve gradients (MVG) than comparison subjects (7.5 ± 3.8 vs 1.6 ± 0.8 mm Hg, p < 0.0001), along with larger indexed left atrial volumes (54.4 ± 14.9 vs 34.0 ± 11.7 mL, p < 0.0001) and reduced left atrial strains (reservoir, conduit, and booster pump). With exercise MAC subjects reached higher levels of MVG (17.3 ± 8.4 vs 5.5 ± 2.5 mm Hg, p < 0.0001), and pulmonary artery systolic pressure (estimated from tricuspid regurgitant jet [TR] velocity) and displayed a moderate correlation between ΔMVG and ΔTR velocity (r2 = 0.57). MAC subjects whose exercise MVG was ≥ 15 mm Hg all had a peak pulmonary artery systolic pressure > 60 mm Hg. MAC subjects also had relative chronotropic incompetence. Patients with severe MAC and a transvalvular gradient experience large increases in MVG and pulmonary pressure with exercise, similar to what has been described in rheumatic mitral stenosis. MAC may be an under-recognized cause of dyspnea and exercise intolerance in older patients.