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

Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the association of MAC with non-cardiovascular measures, including bone mineral density (BMD), incident renal failure, dementia, and non-cardiovascular 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%-females) without cardiovascular disease at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC was assessed with non-contrast cardiac computed tomography at study baseline. Using multivariable-adjusted linear and logistic regression, we assessed cross-sectional association of MAC with BMD and walking pace. Also, using Cox proportional hazards, we evaluated the association of MAC with incident renal failure, dementia, and all-cause mortality. Additionally, we assessed the association of MAC with cardiovascular and non-cardiovascular 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%CI: -0.06 - -0.02) with significant interaction by sex (p-interaction:0.035). MAC was, however, not associated with impaired walking pace (odds ratio:1.09; 95%CI:0.89-1.33). Compared to individuals without MAC, those with MAC had an increased risk of incident renal failure albeit nonsignificant (hazard ratio [HR]:1.18; 95%CI:0.95-1.45) but a significantly higher hazards of dementia (HR:1.36; 95%CI:1.10-1.70). Additionally, persons with MAC had a substantially higher risk of all-cause (HR:1.47; 95%CI:1.29-1.69), cardiovascular (sub-distribution HR:1.39; 95%CI:1.04-1.87), and non-cardiovascular mortality (sub-distribution HR:1.35; 95%CI:1.14-1.60), compared to those without MAC. MAC≥100 vs <100 was significantly associated with reduced BMD, incident renal failure, dementia, all-cause, cardiovascular, and non-cardiovascular mortality. In conclusion, MAC was associated with reduced BMD and dementia, as well as all-cause, cardiovascular, and non-cardiovascular 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 non-cardiovascular outcomes and death from other causes.

Gender, racial and ethnic disparities in acute coronary syndromes with coronary in-stent restenosis.

Background: Coronary in-stent restenosis (ISR) is a major clinical challenge of contemporary percutaneous revascularization and portends adverse cardiovascular outcomes. Objectives: We aimed to evaluate gender, race, and ethnicity related outcomes in acute coronary syndromes (ACS) with ISR. Methods: Primary hospitalizations for ACS and ISR in the National Inpatient Sample database from 2016 to 2019 were included. Patients were stratified by gender, race, and ethnicity. The primary end points were all cause in-hospital mortality and coronary revascularization defined as composite of percutaneous coronary intervention (PCI), balloon angioplasty and/or coronary artery bypass grafting (CABG). Results: During the study period, a nationally weighted total of 97,680 patients with ACS and ISR were included. There was substantial variation in comorbidities, with greatest burden among Black and Hispanic women. All-cause in-hospital mortality was 2.4 % in the study cohort, but significantly higher in women (2.1 % vs. 2.1 %; aOR: 1.282, 95 % CI: 1.174-1.4; p < 0.001) and revascularization rates were significantly lower in women (77 % vs 80.2 %; aOR: 0.891, 95 % CI: 0.862-0.921; p < 0.001). Compared to White men, all women except Hispanic women, had significantly higher likelihood of in-hospital mortality, while White women, Black men and women, and Hispanic men had lower odds of revascularization. Conclusions: There are significant gender, racial, and ethnic related differences in revascularization practices and clinical outcomes in patients with ACS and ISR with an adverse impact on women, racial and ethnic minorities in the U.S.

Cardiovascular outcomes of sodium-glucose Co-transporter 2 inhibitors use after myocardial infarction: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients who had acute myocardial infarction are at high risk of negative cardiac outcomes and previous SGLT2i landmark trials excluded these patients. It therefore remains unclear if SGLT2i is safe and confers beneficial cardiovascular outcomes after acute myocardial infarction. METHODS: We systematically reviewed randomized controlled trials that evaluated the outcomes of adding SGLT2i to conventional post-myocardial infarction care. Random-effects model meta-analysis via RevMan 5.4 was done on data extracted from pooled 11,204 patients. RESULTS: SGLT2i use after acute myocardial infarction was significantly associated with reduced heart failure hospitalization (OR: 0.77, 95%CI: 0.62-0.96, p=0.02), but was not associated with a reduction in all-cause mortality (OR: 1.05, 95%CI: 0.77-1.43, p=0.75), cardiac-related death (OR: 1.04, 95%CI: 0.83-1.30, p=0.76), or major adverse cardiac events (OR: 0.90, 95%CI: 0.77-1.05, p=0.18). CONCLUSION: SGLT2 inhibitor therapy after acute myocardial infarction is safe and is associated with a reduced risk of heart failure hospitalization, but not with all-cause mortality.

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.

Invasive hemodynamic parameters in patients with hepatorenal syndrome.

Background: Hepatorenal syndrome (HRS), a form of kidney dysfunction frequent in cirrhotic patients, is characterized by low filling pressures and impaired kidney perfusion due to peripheral vasodilation and reduced effective circulatory volume. Cardiorenal syndrome (CRS), driven by renal venous hypertension and elevated filling pressures, is a separate cause of kidney dysfunction in cirrhotic patients. The two entities, however, have similar clinical phenotypes. To date, limited invasive hemodynamic data are available to help distinguish the primary forces behind worsened kidney function in cirrhotic patients. Objective: Our aim was to analyze invasive hemodynamic profiles and kidney outcomes in patients with cirrhosis who met criteria for HRS. Methods: We conducted a single center retrospective study among cirrhotic patients with worsening kidney function admitted for liver transplant evaluation between 2010 and 2020. All met accepted criteria for HRS and underwent concurrent right heart catheterization (RHC). Results: 127 subjects were included. 79 had right atrial pressure >10 mmHg, 79 had wedge pressure >15 mmHg, and 68 had both. All patients with elevated wedge pressure were switched from volume loading to diuretics resulting in significant reductions between admission and post diuresis creatinine values (2.0 [IQR 1.5-2.8] vs 1.5 [IQR 1.2-2.2]; p = 0.003). Conclusion: 62% of patients diagnosed with HRS by clinical criteria have elevated filling pressures. Improvement of renal function after diuresis suggests the presence of CRS physiology in these patients. Invasive hemodynamic data profiling can lead to meaningful change in management of cirrhotic patients with worsened kidney function, guiding appropriate therapies based on filling pressures.

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.

Computed Tomography Aortic Valve Calcium Scoring in Patients With Bicuspid Aortic Valve Stenosis.

Background: Sex-specific thresholds of computed tomography (CT)-derived aortic valve calcification (AVC) or AVC density (AVCd) to identify severe aortic stenosis (AS) have been established in populations that consisted mainly of Caucasians with a tricuspid aortic valve. The objective of this study was to evaluate the accuracy (i.e., sensitivity and specificity) of previously established thresholds to identify severe AS in patients with bicuspid aortic valve (BAV) and according to ethnicity: Caucasian vs. Asian. Methods: We built a multicenter registry of echocardiographic and CT data collected in BAV patients with at least mild AS and preserved left ventricular ejection fraction from 7 different centers. Anatomic severity of AS obtained by CT-derived AVC and AVCd was compared to hemodynamic severity of AS obtained by echocardiography. Results: Among 485 BAV patients (60% men, 73% Asians), the best thresholds of AVC and AVCd to identify severe AS in BAV patients were 2315 arbitrary units (AU) (sensitivity [Se]/specificity [Spe] = 82/78%) in men, 1103 AU (Se/Spe = 80/82%) in women, and 561 AU/cm2 (Se/Spe = 86/91%) in men, and 301 AU/cm2 (Se/Spe = 83/82%) in women, respectively. According to ethnicity, thresholds for severe AS in Caucasian patients were, respectively, in men and women: 2208 AU (Se/Spe = 83/83%) and 1230 AU (Se/Spe = 87/82%) for AVC and 474 AU/cm2 (Se/Spe = 88/83%) and 358 AU/cm2 (Se/Spe = 80/82%) for AVCd. In Asian patients, they were 2582 AU (Se/Spe = 76/78%) and 924 AU (Se/Spe = 84/80%) for AVC and 640 AU/cm2 (Se/Spe = 82/89%) and 255 AU/cm2 (Se/Spe = 86/80%) for AVCd. Conclusions: The optimal thresholds to identify hemodynamically severe AS in BAV patients are similar in Caucasians but appear to be higher in Asian men, compared with thresholds previously reported in tricuspid aortic valve patients. Nonetheless, the thresholds currently proposed in the guidelines have good accuracy and can be applied in BAV patients to confirm AS severity.

Platypnea-orthodeoxia syndrome in patent foramen ovale and fenestrated atrial septal aneurysm with normal right atrial pressure: what is the culprit?

A 76-year-old Korean woman presented with intermittent episodes of exertional hypoxia at the rehabilitation facility after a recent admission for ischaemic stroke. Clinical and diagnostic investigation confirmed the presence of platypnea-orthodeoxia syndrome (POS). Transoesophageal echocardiogram revealed a patent foramen ovale and hyperdynamic interatrial septum with right-to-left intracardiac shunt. Further diagnostic workup did not reveal right atrial hypertension, cirrhosis, pulmonary hypertension or any other extracardiac causes of right-to-left shunt. Positional preferential blood flow from inferior vena cava to the left atrium due to counterclockwise displacement of interatrial septum with age and posture was postulated to explain the atrial right-to-left shunt and the resultant POS. Closure was performed using a cribriform amplatzer occluder which improved her symptoms.

Cardiovascular Calcification as a Marker of Increased Cardiovascular Risk and a Surrogate for Subclinical Atherosclerosis: Role of Echocardiography.

The risk prediction of future cardiovascular events is mainly based on conventional risk factor assessment by validated algorithms, such as the Framingham Risk Score, the Pooled Cohort Equations and the European SCORE Risk Charts. The identification of subclinical atherosclerosis has emerged as a promising tool to refine the individual cardiovascular risk identified by these models, to prognostic stratify asymptomatic individuals and to implement preventive strategies. Several imaging modalities have been proposed for the identification of subclinical organ damage, the main ones being coronary artery calcification scanning by cardiac computed tomography and the two-dimensional ultrasound evaluation of carotid arteries. In this context, echocardiography offers an assessment of cardiac calcifications at different sites, such as the mitral apparatus (including annulus, leaflets and papillary muscles), aortic valve and ascending aorta, findings that are associated with the clinical manifestation of atherosclerotic disease and are predictive of future cardiovascular events. The aim of this paper is to summarize the available evidence on clinical implications of cardiac calcification, review studies that propose semiquantitative ultrasound assessments of cardiac calcifications and evaluate the potential of ultrasound calcium scores for risk stratification and prevention of clinical events.

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.