Circulating Plasma Proteins in Aortic Stenosis: Associations With Severity, Myocardial Response, and Clinical Outcomes.

BACKGROUND: Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients. METHODS AND RESULTS: Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow-up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher-risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III-IV, or all-cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT-proBNP (N-terminal pro-B-type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor-3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >-15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area <1 cm2, E/e' >15, and left atrial reservoir strain <20% were associated with higher levels of NT-proBNP. Of 14 proteins associated with the primary end point, phospholipase-C, C-X-C motif chemokine-9, and interleukin-10 receptor subunit ß demonstrated the highest hazard ratios after adjusting for clinical factors (q<0.05). CONCLUSIONS: Plasma proteins involved in inflammation and immune regulation were differentially expressed in patients with aortic stenosis with reduced left ventricular global longitudinal strain, and associated with adverse clinical outcomes. Their incorporation into aortic stenosis risk stratification warrants further assessment.

An updated analysis on myocarditis and pericarditis cases reported following mRNA SARS-CoV-2 vaccination in Singapore.

INTRODUCTION: Messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been associated with myocarditis/pericarditis, especially in young males. We evaluated the risk of myocarditis/pericarditis following mRNA vaccines by brand, age, sex and dose number in Singapore. METHODS: Adverse event reports of myocarditis/pericarditis following mRNA vaccines received by the Health Sciences Authority from 30 December 2020 to 25 July 2022 were included, with a data lock on 30 September 2022. Case adjudication was done by an independent panel of cardiologists using the US Centers for Disease Control and Prevention case definition. Reporting rates were compared with expected rates using historical data from 2018 to 2020. RESULTS: Of the 152 adjudicated cases, males comprised 75.0%. The median age was 30 years. Most cases occurred after Dose 2 (49.3%). The median time to onset was 2 days. Reporting rates were highest in males aged 12-17 years for both primary series (11.5 [95% confidence interval [CI] 6.7-18.4] per 100,000 doses, post-Dose 2) and following booster doses (7.1 [95% CI 3.0-13.9] per 100,000 doses). In children aged 5-11 years, myocarditis remained very rare (0.2 per 100,000 doses). The reporting rates for Booster 1 were generally similar or lower than those for Dose 2. CONCLUSIONS: The risk of myocarditis/pericarditis with mRNA vaccines was highest in adolescent males following Dose 2, and this was higher than historically observed background rates. Most cases were clinically mild. The risk of myocarditis should be weighed against the benefits of receiving an mRNA vaccine, keeping in mind that SARS-CoV-2 infections carry substantial risks of myocarditis/pericarditis, as well as the evolving landscape of the disease.

Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients.

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se. We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6-71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2-4; range 2-27) during a median of 4.0 years (IQR: 2.3-6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0-62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI95: 1.87-1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 1.70-1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age (p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group.

An Updated Meta-Analysis on the Clinical Outcomes of Percutaneous Left Atrial Appendage Closure Versus Direct Oral Anticoagulation in Patients With Atrial Fibrillation.

The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA2DS2-VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed.

Prognostic Value of Left Atrial Strain in Aortic Stenosis: A Competing Risk Analysis.

BACKGROUND: The role of left atrial (LA) strain as an imaging biomarker in aortic stenosis is not well established. The aim of this study was to investigate the prognostic performance of phasic LA strain in relation to clinical and echocardiographic variables and N-terminal pro-B-type natriuretic peptide in asymptomatic and minimally symptomatic patients with moderate to severe aortic stenosis and left ventricular ejection fraction > 50%. METHODS: LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured using speckle-tracking echocardiography. The primary outcome was a composite of all-cause mortality, heart failure hospitalization, progression to New York Heart Association functional class III or IV, acute coronary syndrome, or syncope. Secondary outcomes 1 and 2 comprised the same end points but excluded acute coronary syndrome and additionally syncope, respectively. The prognostic performance of phasic LA strain cutoffs was evaluated in competing risk analyses, aortic valve replacement being the competing risk. RESULTS: Among 173 patients (mean age, 69 ± 11 years; mean peak transaortic velocity, 4.0 ± 0.8 m/sec), median LASr, LAScd, and LASct were 27% (interquartile range [IQR], 22%-32%), 12% (IQR, 8%-15%), and 16% (IQR, 13%-18%), respectively. Over a median of 2.7 years (IQR, 1.4-4.6 years), the primary outcome and secondary outcomes 1 and 2 occurred in 66 (38%), 62 (36%), and 59 (34%) patients, respectively. LASr < 20%, LAScd < 6%, and LASct < 12% were identified as optimal cutoffs of the primary outcome. In competing risk analyses, progressing from echocardiographic to echocardiographic-clinical and combined models incorporating N-terminal pro-B-type natriuretic peptide, LA strain parameters outperformed other key echocardiographic variables and significantly predicted clinical outcomes. LASr < 20% was associated with the primary outcome and secondary outcome 1, LAScd < 6% with all clinical outcomes, and LASct < 12% with secondary outcome 2. LAScd < 6% had the highest specificity (95%) and positive predictive value (82%) for the primary outcome, and competing risk models incorporating LAScd < 6% had the best discriminative value. CONCLUSIONS: In well-compensated patients with moderate to severe aortic stenosis and preserved left ventricular ejection fractions, LA strain was superior to other echocardiographic indices and incremental to N-terminal pro-B-type natriuretic peptide for risk stratification. LAScd < 6%, LASr < 20%, and LASct < 12% identified patients at higher risk for adverse outcomes.

Factors Affecting Rate of Progression of Aortic Stenosis and Its Impact on Outcomes.

The rate of aortic stenosis (AS) progression in patients with moderate AS is unclear. This study examined the risk factors of progression from moderate to severe AS and its impact on clinical outcomes. A total of 954 patients with moderate AS (valve area >1.0 and ≤1.5 cm²) and follow-up echocardiograms were included. AS progressed to severe (valve area <1.0 cm1) in 589 patients (61.7%) over a median follow-up of 2.46 (interquartile range [IQR] 1.29 to 3.91) years. Of those who progressed to severe AS, patients were subdivided into Slow (n = 294, over 3.91 [IQR 3.11 to 5.10] years) versus Fast (n = 295, over 1.29 [IQR 0.85 to 1.85] years) Progressors, according to the median time between the 2 echocardiograms. The correlates of fast AS progression and its impact on cumulative survival and freedom from valve intervention were evaluated. On multivariate analysis, age, thickened left ventricle posterior wall, severe renal impairment, and aortic valve area were significantly associated with fast AS progression. Over a median follow-up of 6.34 (IQR 4.05 to 9.55) years, 228 patients (38.7%) died. Despite similar aortic valve intervention rates, Fast Progressors had worse 5-year survival (61.2% vs 81.9%, log-rank p <0.001) and event-free (valve intervention and all-cause mortality) survival rates (16.2% vs 55.9%, log-rank p <0.001). On multivariable Cox analysis, shorter progression to severe AS (in years) was independently associated with increased risk of all-cause mortality (hazard ratio 1.26, 95% confidence interval 1.16 to 1.37, p <0.001), or combined aortic valve intervention and death (hazard ratio 1.46, 95% confidence interval 1.38 to 1.55, p <0.001). In conclusion, fast progression from moderate to severe AS is associated with worse outcomes.

Prognostic implications of left ventricular diastolic dysfunction in moderate aortic stenosis.

OBJECTIVE: To investigate the prognostic impact of left ventricular (LV) diastolic dysfunction in patients with moderate aortic stenosis (AS) and preserved LV systolic function. METHODS: Patients with a first diagnosis of moderate AS (aortic valve area >1.0 and ≤1.5 cm2) and preserved LV systolic function (LV ejection fraction ≥50%) were identified. LV diastolic function was evaluated using echocardiographic criteria according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as all-cause mortality and a composite of all-cause mortality and aortic valve replacement (AVR). RESULTS: Of 1247 patients (age 74±10 years, 47% men), 535 (43%) had LV diastolic dysfunction at baseline. Patients with LV diastolic dysfunction showed significantly higher mortality rates at 1-year, 3-year and 5-year follow-up (13%, 30% and 41%, respectively) when compared with patients with normal LV diastolic function (6%, 17% and 29%, respectively) (p<0.001). On multivariable analysis, LV diastolic dysfunction was independently associated with all-cause mortality (HR 1.368; 95% CI 1.085 to 1.725; p=0.008) and the composite endpoint of all-cause mortality and AVR (HR 1.241; 95% CI 1.035 to 1.488; p=0.020). CONCLUSIONS: LV diastolic dysfunction is independently associated with all-cause mortality and the composite endpoint of all-cause mortality and AVR in patients with moderate AS and preserved LV systolic function. Assessment of LV diastolic function therefore contributes significantly to the risk stratification of patients with moderate AS. Future clinical trials are needed to investigate whether patients with moderate AS and LV diastolic dysfunction may benefit from earlier valve intervention.

Novel predictive role for mid-regional proadrenomedullin in moderate to severe aortic stenosis.

OBJECTIVE: We investigated the prognostic significance of selected known and novel circulating biomarkers in aortic stenosis (AS). METHODS: N-terminal pro-BNP (NT-proBNP), high-sensitivity troponin-T (hsTnT), growth differentiation factor-15 (GDF-15), suppression of tumorigenicity-2 (ST2), mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) were measured in patients with moderate to severe AS, New York Heart Association (NYHA) class I-II and left ventricular ejection fraction ≥50%, recruited consecutively across five centres from 2011 to 2018. Their ability to predict both primary (all-cause mortality, heart failure hospitalisation or progression to NYHA class III-IV) and secondary (additionally incorporating syncope and acute coronary syndrome) outcomes was determined by competing risk analyses. RESULTS: Among 173 patients with AS (age 69±11 years, 55% male, peak transaortic velocity (Vmax) 4.0±0.8 m/s), the primary and secondary outcomes occurred in 59 (34%) and 66 (38%), respectively. With aortic valve replacement as a competing risk, the primary outcome was determined consistently by the comorbidity index and each selected biomarker except ST2 (p<0.05), independent of NYHA class, Vmax, LV-global longitudinal strain and serum creatinine. MR-proADM had the highest discriminative value for both primary (subdistribution HR (SHR) 11.3, 95% CI 3.9 to 32.7) and secondary outcomes (SHR 12.6, 95% CI 4.7 to 33.5). Prognostic assessment of dual-biomarker combinations identified MR-proADM plus either hsTnT or NT-proBNP as the best predictive model for both clinical outcomes. Paired biomarker models were not superior to those including MR-proADM as the sole circulating biomarker. CONCLUSION: MR-proADM most powerfully portended worse prognosis and should be further assessed as possibly the biomarker of choice for risk stratification in AS.

Pericarditis and myocarditis after COVID-19 mRNA vaccination in a nationwide setting.

INTRODUCTION: Despite reports suggesting an association between COVID-19 mRNA vaccination and pericarditis and myocarditis, detailed nationwide population-based data are sparsely available. We describe the incidence of pericarditis and myocarditis by age categories and sex after COVID-19 mRNA vaccination from a nationwide mass vaccination programme in Singapore. METHODS: The incidence of adjudicated cases of pericarditis and myocarditis following COVID-19 mRNA vaccination that were reported to the vaccine safety committee between January to July 2021 was compared with the background incidence of myocarditis in Singapore. RESULTS: As of end July 2021, a total of 34 cases were reported (9 pericarditis only, 14 myocarditis only, and 11 concomitant pericarditis and myocarditis) with 7,183,889 doses of COVID-19 mRNA vaccine administered. Of the 9 cases of pericarditis only, all were male except one. The highest incidence of pericarditis was in males aged 12-19 years with an incidence of 1.11 cases per 100,000 doses. Of the 25 cases of myocarditis, 80% (20 cases) were male and the median age was 23 years (range 12-55 years) with 16 cases after the second dose. A higher-than-expected number of cases were seen in males aged 12-19 and 20-29 years, with incidence rates of 3.72 and 0.98 case per 100,000 doses, respectively. CONCLUSION: Data from the national registry in Singapore indicate an increased incidence of pericarditis and myocarditis in younger men after COVID-19 mRNA vaccination.

Echocardiographic Global Longitudinal Strain Is Associated With Myocardial Fibrosis and Predicts Outcomes in Aortic Stenosis.

Aims: Left ventricular ejection fraction is the conventional measure used to guide heart failure management, regardless of underlying etiology. Left ventricular global longitudinal strain (LV-GLS) by speckle tracking echocardiography (STE) is a more sensitive measure of intrinsic myocardial function. We aim to establish LV-GLS as a marker of replacement myocardial fibrosis on cardiovascular magnetic resonance (CMR) and validate the prognostic value of LV-GLS thresholds associated with fibrosis. Methods and results: LV-GLS thresholds of replacement fibrosis were established in the derivation cohort: 151 patients (57 ± 10 years; 58% males) with hypertension who underwent STE to measure LV-GLS and CMR. Prognostic value of the thresholds was validated in a separate outcome cohort: 261 patients with moderate-severe aortic stenosis (AS; 71 ± 12 years; 58% males; NYHA functional class I-II) and preserved LVEF ≥50%. Primary outcome was a composite of cardiovascular mortality, heart failure hospitalization, and myocardial infarction. In the derivation cohort, LV-GLS demonstrated good discrimination (c-statistics 0.74 [0.66-0.83]; P < 0.001) and calibration (Hosmer-Lemeshow χ2 = 6.37; P = 0.605) for replacement fibrosis. In the outcome cohort, 47 events occurred over 16 [3.3, 42.2] months. Patients with LV-GLS > -15.0% (corresponding to 95% specificity to rule-in myocardial fibrosis) had the worst outcomes compared to patients with LV-GLS < -21.0% (corresponding to 95% sensitivity to rule-out myocardial fibrosis) and those between -21.0 and -15.0% (log-rank P < 0.001). LV-GLS offered independent prognostic value over clinical variables, AS severity and echocardiographic LV mass and E/e'. Conclusion: LV-GLS thresholds associated with replacement myocardial fibrosis is a novel approach to risk-stratify patients with AS and preserved LVEF.

Predicting premature termination of exercise during Bruce protocol stress echocardiography.

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool. METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001). CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

Discordant severity criteria in patients with moderate aortic stenosis: prognostic implications.

BACKGROUND: The criteria to define the grade of aortic stenosis (AS)-aortic valve area (AVA) and mean gradient (MG) or peak jet velocity-do not always coincide into one grade. Although in severe AS, this discrepancy is well characterised, in moderate AS, the phenomenon of discordant grading has not been investigated and its prognostic implications are unknown. OBJECTIVES: To investigate the occurrence of discordant grading in patients with moderate AS (defined by an AVA between 1.0 cm² and 1.5 cm² but with an MG <20 mm Hg) and how these patients compare with those with concordant grading moderate AS (AVA between 1.0 cm² and 1.5 cm² and MG ≥20 mm Hg) in terms of clinical outcomes. METHODS: From an ongoing registry of patients with AS, patients with moderate AS based on AVA were selected and classified into discordant or concordant grading (MG <20 mm Hg or ≥20 mm Hg, respectively). The clinical endpoint was all-cause mortality. RESULTS: Of 790 patients with moderate AS, 150 (19.0%) had discordant grading, moderate AS. Patients with discordant grading were older, had higher prevalence of previous myocardial infarction and left ventricular (LV) hypertrophy, larger LV end-diastolic and end-systolic volume index, higher LV filling pressure and lower LV ejection fraction and stroke volume index as compared with their counterparts. After a median follow-up of 4.9 years (IQR 3.0-8.2), patients with discordant grading had lower aortic valve replacement rates (26.7% vs 44.1%, p<0.001) and higher mortality rates (60.0% vs 43.1%, p<0.001) as compared with patients with concordant grading. Discordant grading moderate AS, combined with low LV ejection fraction, presented the higher risk of mortality (HR 2.78 (2.00-3.87), p<0.001). CONCLUSION: Discordant-grading moderate AS is not uncommon and, when combined with low LV ejection fraction, is associated with high risk of mortality.

Prognostic Implications of Associated Cardiac Abnormalities Detected on Echocardiography in Patients With Moderate Aortic Stenosis.

OBJECTIVES: This study aimed to evaluate the prevalence and prognostic value of the extent of extra-aortic valvular cardiac abnormalities in a large multicenter registry of patients with moderate AS. BACKGROUND: The prognostic significance of a new classification system that incorporates the extent of cardiac injury (beyond the aortic valve) has been proposed in patients with severe aortic stenosis (AS). Whether this can be applied to patients with moderate AS is unclear. METHODS: Based on the echocardiographic findings at the time of diagnosis of moderate AS (aortic valve area between 1.0 and 1.5 cm2 and dimensionless velocity index ratio of ≥0.25), a total of 1,245 patients were included and analyzed retrospectively. They were recategorized into 5 groups according to the extent of extra-aortic valvular cardiac abnormalities: none (Group 0), involving the left ventricle (Group 1), the left atrial or mitral valve (Group 2), the pulmonary artery vasculature or tricuspid valve (Group 3), or the right ventricle (Group 4). Patients were followed for all-cause mortality and combined endpoint (all-cause mortality, stroke, heart failure, or myocardial infarction). RESULTS: The distribution of patients according to the proposed classification was 13.1%, 26.8%, 42.6%, 10.6%, and 6.9% in Groups 0, 1, 2, 3, and 4, respectively. During a median follow-up of 4.3 (2.4 to 6.9) years, 564 (45.3%) patients died. There was a significant higher mortality rates with increasing extent of extra-aortic valvular cardiac abnormalities (log-rank p < 0.001). On multivariable analysis, the presence of extra-aortic valvular cardiac abnormalities remained independently associated with all-cause mortality and combined outcome, adjusted for aortic valve replacement as a time-dependent covariable. In particular, Group 2 and above were independently associated with all-cause mortality. CONCLUSIONS: In patients with moderate AS, the presence of extra-aortic valvular cardiac abnormalities is associated with poor outcome.

Clinical presentation of cardiac myxoma in a Singapore national cardiac centre.

INTRODUCTION: Cardiac myxoma is the most common cardiac tumour. In this study, we summarise our 17-year experience with the clinical presentation of cardiac myxoma at National Heart Centre Singapore, Singapore. METHODS: Between January 2000 and December 2016, retrospective data was reviewed for all consecutive patients who underwent surgical resection of cardiac myxoma. Patients' clinical characteristics were reviewed and described. RESULTS: A total of 67 (18 male, 49 female; mean age 53.1 ± 13.5 years) patients underwent cardiac myxoma resection. There were 19 (28.4%) patients with asymptomatic cardiac myxoma. There were no significant differences in gender; body habitus and myxoma size; and haemoglobin, white blood cell or platelet counts between patients with symptomatic and asymptomatic myxoma. However, the number of asymptomatic cardiac myxomas seemed to follow an increasing trend from 19.4% (period 2000-2008) to 36.1% (period 2009-2016), suggestive of an 'era effect'. CONCLUSION: In our study, a majority of patients were women, with a wide age range of 18-78 years. The diagnosis of asymptomatic cardiac myxoma was present in 28.4% of patients, with an increasing trend for incidence over the years. This is possibly due to increased opportunistic screening (with electrocardiography and clinical examination) as well as higher usage of medical imaging.

Diastolic function and its association with diabetes, hypertension and age in an outpatient population with normal stress echocardiography findings.

BACKGROUND: Diastolic dysfunction can be caused by hypertension or diabetes mellitus, and it is also often found with increasing age. In a given patient, the cause of diastolic dysfunction is therefore not always obvious. We sought to study the interplay of these risk factors for diastolic dysfunction in an outpatient population with a low likelihood of ischemic heart disease. METHODS: Consecutive patients referred for stress echocardiography were included retrospectively. Exclusion criteria included pathological stress response, atrial arrhythmia, left ventricular ejection fraction < 55%, and more than mild valvular disease. Standard diastolic parameters were recorded in all patients. In a subset of patients, mechanistic analysis of early filling was performed using the parameterized diastolic filling (PDF) method. RESULTS: We included 726 patients (median [interquartile range] age 56 (44-65) years, 57% male). The prevalence of diabetes and hypertension was 43 and 49%, respectively. In multiple linear regression modeling, the presence of diabetes, hypertension, sex and increasing age explained a moderate amount of the variance in e' velocities, E/A ratio and E/e' (R2 = 0.31-0.48, p < 0.001), and a low amount of the variance in left atrial volume index (LAVI) and the PDF parameters (n = 446, R2 = 0.05-0.17, p < 0.001). Sex was only related to LAVI and E/e' for the conventional parameters (beta - 0.94, p = 0.04, and beta - 0.91, p < 0.001, respectively). CONCLUSIONS: Diabetes, hypertension, increasing age, and to a lesser extent sex, explain a moderate amount of the variance in conventional diastolic parameters related to myocardial tissue velocities and E/A ratio in a healthy outpatient population. The effect of these risk factors was substantially less pronounced on left atrial volume index and the PDF parameters.

Incremental value of left ventricular global longitudinal strain in a newly proposed staging classification based on cardiac damage in patients with severe aortic stenosis.

AIMS: Cardiac damage in severe aortic stenosis (AS) can be classified according to a recently proposed staging classification. The present study investigated the incremental prognostic value of left ventricular (LV) global longitudinal strain (GLS) over stages of cardiac damage in patients with severe AS. METHODS AND RESULTS: From an ongoing registry, a total of 616 severe symptomatic AS patients with available LV GLS by speckle tracking echocardiography were selected and retrospectively analysed. Patients were categorized according to cardiac damage on echocardiography: Stage 0 (no damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (tricuspid valve or pulmonary artery vasculature damage), or Stage 4 (right ventricular damage). LV GLS was divided by quintiles and assigned to the different stages. The endpoint was all-cause mortality. Over a median follow-up of 44 [24-89] months, 234 (38%) patients died. LV GLS was associated with all-cause mortality independent of stage of cardiac damage. After incorporation of LV GLS by quintiles into the staging classification, Stages 2-4 were independently associated with outcome. LV GLS showed incremental prognostic value over clinical characteristics and stages of cardiac damage. CONCLUSION: In this large single-centre cohort of severe AS patients, incorporation of LV GLS by quintiles in a novel proposed staging classification resulted in refinement of risk stratification by identifying patients with more advanced cardiac damage. LV GLS was shown to provide incremental prognostic value over the originally proposed staging classification.

E/e' in relation to outcomes in ST-elevation myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a high-risk condition especially when filling pressure is raised, and earlier reports have suggested that E/e' is associated with poor outcome. However, whether E/e' predicts risk better than LVEF, which is the current standard of practice, is not known. We investigated this question in the largest and most rigorous study of MI patients so far. METHODS AND RESULTS: We studied 660 patients with ST-elevation MI (STEMI) treated with primary percutaneous coronary intervention and related E/e' to short-term mortality (in-hospital death), as well as long-term events at 2 years comprising (a) a composite of MI, stroke, heart failure, and death, and (b) death alone. Short-term models were adjusted for age, sex, and LVEF. Long-term models were adjusted for age, sex, diabetes, revascularization procedure, history of MI, hypertension, renal function, drugs on discharge, and LVEF. Elevated E/e'> 15 indicated higher risk of short-term events (n = 19:7.0% (95% confidence interval 3.4-10.8%) vs. 1.0% (0.3 - 2.3%); adjusted odds ratio 3.7 (1.3-10.5)). While elevated E/e' was also associated with long-term outcomes (n = 103 composite events: 15.9% (11.9% - 21.4%) vs 6.8% (5.2% - 8.7%), P < .001; n = 38 death events: 6.0% (3.9% - 9.5%) vs 2.0% (1.3% - 3.2%), P = .001), E/e' was rendered nonsignificant for long-term outcomes by multivariable adjustment (p = ns for both). LVEF, on the contrary, was a highly significant predictor in the adjusted long-term model. CONCLUSION: E/e' is associated with poor outcome in STEMI, but LVEF is a stronger predictor of long-term risk.

Successful MitraClip for severe rheumatic mitral regurgitation: a case report.

BACKGROUND: Anatomical exclusion criteria for the MitraClip procedure have included rheumatic heart disease (RHD) involving the mitral valve. This was primarily because RHD is typically associated with mitral stenosis (MS). CASE SUMMARY: We report the case of an 85-year-old male who had recurrent heart failure admissions from severe rheumatic mitral regurgitation (MR). This was successfully treated with the MitraClip system. DISCUSSION: Our case demonstrated the possibility of rheumatic MR being treated by the MitraClip system in appropriately selected patients. Careful examination of the mechanism of MR to determine suitability for MitraClip must be done as well as exclusion of significant MS.