Role of Cardiac Energetics in Aortic Stenosis Disease Progression: Identifying the High-risk Metabolic Phenotype.

BACKGROUND: Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability. METHODS: We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging. RESULTS: Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21-1.71] versus Q1, 1.64 [1.53-1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18-1.70]; P=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86-1.98] versus Q1, 1.03 [0.81-1.56]; P=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (r=0.219; P=0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (r=-0.20; P=0.04) but also strongly associated with myocardial fibrosis (r=-0.24; P=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS. CONCLUSIONS: A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression.

Predictors and clinical implications of residual mitral regurgitation following left ventricular assist device therapy.

BACKGROUND: Correction of mitral regurgitation (MR) at the time of left ventricular assist device (LVAD) implantation remains controversial. There is conflicting evidence regarding the clinical impact of residual MR, and studies have not examined whether MR aetiology or right heart function impacts the likelihood of residual MR. METHODS: This is a retrospective single-centre study of 155 consecutive patients with LVAD implantation from January 2011 to March 2020. Exclusion criteria were no MR pre-LVAD (n=8), inaccessible echocardiography (n=9), duplicate records (n=10) and concomitant mitral valve repair (n=1). Statistical analysis was performed using STATA V.16 and SPSS V.24. RESULTS: Carpentier IIIb MR aetiology was associated with more severe MR pre-LVAD (severe 18/27 (67%) vs non-severe 32/91 (35%), p=0.004) and a higher likelihood of residual MR (8/11 (72%) vs 30/74 (41%), p=0.045). Of 95 patients with significant MR pre-LVAD, 15 (16%) had persistent significant MR, which was associated with higher mortality (p=0.006), post-LVAD right ventricle (RV) dilatation (10/15 (67%) vs 28/80 (35%), p=0.022) and RV dysfunction (14/15 (93%) vs 35/80 (44%), p<0.001). Aside from ischaemic aetiology, other pre-LVAD parameters that were associated with significant residual MR included left ventricular end-systolic diameter (LVESD) (6.9 cm (5.7-7.2) vs 5.9 cm (5.5-6.5), p=0.043), left atrial volume index (LAVi) (78 mL/m2 (56-88) vs 57 mL/m2 (47-77), p=0.021), posterior leaflet displacement (2.5 cm (2.3-2.9) vs 2.3 cm (1.9-2.7), p=0.042) and basal right ventricular end-diastolic diameter (RVEDD) (5.1±0.8 cm vs 4.5±0.8 cm, p=0.010). CONCLUSION: LVAD therapy improves MR and tricuspid regurgitation severity in the majority, but 14% have persistent significant residual MR, associated with right ventricular dysfunction and higher long-term mortality. This may be predicted pre-LVAD by greater LVESD, RVEDD and LAVi and by ischaemic aetiology.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis.

BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Freeze-dried Platelet-rich Plasma and Stem Cell-conditioned Medium for Therapeutic Use in Horses.

This study investigated platelet-rich plasma (PRP) and adipose stem cell-conditioned medium (ASC-CM) use as a strategy to accelerate tissue healing. Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) were quantified in fresh and freeze-dried PRP and ASC-CM, and a stability test was performed in the freeze-dried samples (90 and 180 days of storage). A cell proliferation test was performed using equine mesenchymal stem cell culture in reconstituted PRP gel mesh after freeze-drying. In vivo PRP, ASC-CM applications, or their association were performed in induced wounds at 15 and 9-day intervals, according to the treatments: saline solution (control), PRP, ASC-CM, or ASC-CM + PRP. Horses were monitored through photographs and wound area measurements on days 5, 7, 15, and 24 after lesion induction. Skin biopsies were obtained on days 15 and 24 of the experiment. PDGF and VEGF quantification did not differ between fresh or freeze-dried treatments, was similar after freeze-drying or 90 days of storage, but showed a significant reduction after 180 days of storage. Comparing all treatments, no differences were observed in the histopathological analyses. For inflammation, fibroplasia, and collagen formation, only the time effect between the first and second biopsies was significant. The cell proliferation test revealed intense multiplication in the PRP gel mesh. Healing time was similar among all treatments. In conclusion, our results showed the possibility to produce and maintain freeze-dried PRP and ASC-CM for 90 days. Further studies are needed to better explore the in vivo therapeutic PRP and ASC-CM effects.

Acute vasodilator response testing in the adult Fontan circulation using non-invasive 4D Flow MRI: a proof-of-principle study.

BACKGROUND: Pulmonary vasodilator therapy in Fontan patients can improve exercise tolerance. We aimed to assess the potential for non-invasive testing of acute vasodilator response using four-dimensional (D) flow MRI during oxygen inhalation. MATERIALS AND METHODS: Six patients with well-functioning Fontan circulations were prospectively recruited and underwent cardiac MRI. Ventricular anatomical imaging and 4D Flow MRI were acquired at baseline and during inhalation of oxygen. Data were compared with six age-matched healthy volunteers with 4D Flow MRI scans acquired at baseline. RESULTS: All six patients tolerated the MRI scan well. The dominant ventricle had a left ventricular morphology in all cases. On 4D Flow MRI assessment, two patients (Patients 2 and 6) showed improved cardiac filling with improved preload during oxygen administration, increased mitral inflow, increased maximum E-wave kinetic energy, and decreased systolic peak kinetic energy. Patient 1 showed improved preload only. Patient 5 showed no change, and patient 3 had equivocal results. Patient 4, however, showed a decrease in preload and cardiac filling/function with oxygen. DISCUSSION: Using oxygen as a pulmonary vasodilator to assess increased pulmonary venous return as a marker for positive acute vasodilator response would provide pre-treatment assessment in a more physiological state - the awake patient. This proof-of-concept study showed that it is well tolerated and has shown changes in some stable patients with a Fontan circulation.

Effectiveness of exhaled nitric oxide for the prediction of non-invasive left atrial pressure in older people: a cross-sectional cohort study.

BACKGROUND: During left-sided heart failure (HF), left atrial and pulmonary venous pressure increase, which may lead to pulmonary congestion. Previous cohort studies, examining participants with symptomatic HF or rheumatic heart disease, suggest a relationship between increased left atrial pressure (LAP) and fractional exhaled nitric oxide (FeNO). AIM: To examine the strength of association between FeNO and echocardiographic assessment of LAP by the E/e' ratio, to determine if FeNO could be used to identify those with elevated LAP. DESIGN & SETTING: This cross-sectional cohort study examined a subset of the OxVALVE cohort aged ≥65 years. Data collection was undertaken in primary care practices in central England. METHOD: Each participant underwent a focused cardiovascular history and clinical examination. Standard transthoracic echocardiographic (TTE) assessment was performed on all participants, with the E/e' ratio calculated to obtain a validated surrogate of LAP. FeNO was measured in 227 participants. RESULTS: FeNO was higher in males compared with females and no different in participants with asthma, chronic obstructive pulmonary disease (COPD), or those using inhaled steroids. Participants with a high E/e' (>14) were older, with a higher proportion of females than males. There was no relationship between E/e' and FeNO, either when measured as a continuous variable or in the group with high E/e'. CONCLUSION: FeNO was not found to be an accurate predictor of elevated LAP in a primary care setting.

Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging.

Pressure overload in aortic stenosis (AS) encompasses both structural and metabolic remodeling and increases the risk of decompensation into heart failure. A major component of metabolic derangement in AS is abnormal cardiac substrate use, with down-regulation of fatty acid oxidation, increased reliance on glucose metabolism, and subsequent myocardial lipid accumulation. These changes are associated with energetic and functional cardiac impairment in AS and can be assessed with the use of cardiac magnetic resonance spectroscopy (MRS). Proton MRS allows the assessment of myocardial triglyceride content and creatine concentration. Phosphorous MRS allows noninvasive in vivo quantification of the phosphocreatine-to-adenosine triphosphate ratio, a measure of cardiac energy status that is reduced in patients with severe AS. This review summarizes the changes to cardiac substrate and high-energy phosphorous metabolism and how they affect cardiac function in AS. The authors focus on the role of MRS to assess these metabolic changes, and potentially guide future (cellular) metabolic therapy in AS.

Left ventricular T1-mapping in diastole versus systole in patients with mitral regurgitation.

Cardiovascular magnetic resonance T1-mapping enables myocardial tissue characterisation, and is capable of quantifying both intracellular and extracellular volume. T1-mapping is conventionally performed in diastole, however, we hypothesised that systolic readout would reduce variability due to a reduction in myocardial blood volume. This study investigated whether T1-mapping in systole alters T1 values compared to diastole and whether reproducibility alters in atrial fibrillation compared to sinus rhythm. We prospectively identified 103 consecutive patients recruited to the Mitral FINDER study who had T1 mapping in systole and diastole. These patients had moderate or severe mitral regurgitation and a high incidence of ventricular dilatation and atrial fibrillation. T1, ECV and goodness-of-fit (R2) values of the T1 times were calculated offline using Circle cvi42 and in house-developed software. Systolic T1 mapping was associated with fewer myocardial segments being affected by artefact compared to diastolic T1 mapping [217/2472 (9%) vs 515/2472 (21%)]. Mean native T1 values were not significantly different when measured in systole and diastole (985 ± 26 ms vs 988 ± 29 respectively; p = 0.061) and mean post-contrast values showed similar good agreement (462 ± 32 ms vs 459 ± 33 respectively, p = 0.052). No clinically significant differences in ECV, native T1 and post-contrast T1 were identified between diastolic and systolic T1 maps in males versus females, or in patients with permanent atrial fibrillation versus sinus rhythm. A statistically significant improvement in R2 value was observed with systolic over diastolic T1 mapping in all analysed maps (n = 411) (96.2 ± 1.4% vs 96.0 ± 1.4%; p < 0.001) and in subgroup analyses [Sinus rhythm: 96.1 ± 1.4 vs 96.3 ± 1.4 (n = 327); p < 0.001. AF: 95.5 ± 1.3 vs 95.9 ± 1.2 (n = 80); p < 0.001] [Males: 95.8 ± 1.4 vs 96.1 ± 1.3 (n = 264); p < 0.001; Females: 96.2 ± 1.3 vs 96.4 ± 1.4 (n = 143); p = 0.009]. In conclusion, myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Furthermore, systolic acquisition is less prone to gating artefact in arrhythmia.

Artificial Intelligence for Contrast-Free MRI: Scar Assessment in Myocardial Infarction Using Deep Learning-Based Virtual Native Enhancement.

BACKGROUND: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems. METHODS: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed. RESULTS: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction. CONCLUSIONS: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future.

United Kingdom standards for non-invasive cardiac imaging: recommendations from the Imaging Council of the British Cardiovascular Society.

Heart and circulatory diseases affect more than seven million people in the UK. Non-invasive cardiac imaging is a critical element of contemporary cardiology practice. Progressive improvements in technology over the last 20 years have increased diagnostic accuracy in all modalities and led to the incorporation of non-invasive imaging into many standard cardiac clinical care pathways. Cardiac imaging tests are requested by a variety of healthcare practitioners and performed in a range of settings from the most advanced hospitals to local health centres. Imaging is used to detect the presence and consequences of cardiovascular disease, as well as to monitor the response to therapies. The previous UK national imaging strategy statement which brought together all of the non-invasive imaging modalities was published in 2010. The purpose of this document is to collate contemporary standards developed by the modality-specific professional organisations which make up the British Cardiovascular Society Imaging Council, bringing together common and essential recommendations. The development process has been inclusive and iterative. Imaging societies (representing both cardiology and radiology) reviewed and agreed on the initial structure. The final document therefore represents a position, which has been generated inclusively, presents rigorous standards, is applicable to clinical practice and deliverable. This document will be of value to a variety of healthcare professionals including imaging departments, the National Health Service or other organisations, regulatory bodies, commissioners and other purchasers of services, and service users, i.e., patients, and their relatives.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

COVID-19 and Adverse Social Determinants of Health.

This introduction to the Special Issue (SI) on COVID-19 and adverse social determinants of health (SDoH) provides theoretical and empirical context for featured articles. Existing disparities and inequities are highlighted and emerging research on disparities resulting from these and the COVID-19 pandemic are briefly reviewed. General disparities and inequities resulting from the COVID-19 pandemic are briefly conceptualized through the SDoH. Critical factors outlined by the SDoH framework parallel those discussed by the Centers for Disease Control and Prevention as well as those in a conceptual framework article also feature in this SI. Some of these consist of racism, exclusion, blocked opportunity, and socioeconomic status (SES), among others. Furthermore, we discuss broader social inequities, namely growing income and wealth inequality that undermine the health and wellbeing of the general population and ethnic minority groups in particular. Big Event theory is offered as an additional conceptual framework that can illuminate potential downstream negative impacts of the pandemic. Having provided summaries of featured articles in this SI, we make a call for researchers to engage in further theoretical and empirical work to identify the most critical SDOH to further the field of public health as well as related fields and inform policy.

A Longitudinal Study of Mitral Regurgitation Detected after Acute Myocardial Infarction.

BACKGROUND: Mitral regurgitation (MR) is common following myocardial infarction (MI). However, the subsequent trajectory of MR, and its impact on long-term outcomes are not well understood. This study aimed to examine the change in MR severity and associated clinical outcomes following MI. METHODS: Records of patients admitted to a single centre between 2016 and 2017 with acute MI treated by percutaneous coronary intervention (PCI) were retrospectively examined. RESULTS: 294/1000 consecutive patients had MR on baseline (pre-discharge) transthoracic echocardiography (TTE), of whom 126 (mean age: 70.9 ± 11.4 years) had at least one follow-up TTE. At baseline, most patients had mild MR (n = 94; 75%), with n = 30 (24%) moderate and n = 2 (2%) severe MR. Significant improvement in MR was observed at the first follow-up TTE (median 9 months from baseline; interquartile range: 3-23), with 36% having reduced severity, compared to 10% having increased MR severity (p < 0.001). Predictors of worsening MR included older age (mean: 75.2 vs. 66.7 years; p = 0.003) and lower creatinine clearance (mean: 60 vs. 81 mL/min, p = 0.015). Change in MR severity was significantly associated with prognosis: 16% with improving MR reached the composite endpoint of death or heart failure hospitalisation at 5 years, versus 44% (p = 0.004) with no change, and 59% (p < 0.001) with worsening MR. CONCLUSIONS: Of patients with follow-up TTE after MI, MR severity improved from baseline in approximately one-third, was stable in around half, with the remainder having worsening MR. Patients with persistent or worsening MR had worse clinical outcomes than those with improving MR.

Influence of the products of biomass combustion processes on air quality and cancer risk assessment in rural environmental (Spain).

Polycyclic aromatic hydrocarbons (PAHs) associated with atmospheric particles represent a significant risk to human health. This issue is even more relevant in environments where biomass combustion processes are considered as the major potential emission sources, such as the rural ecosystem. This study aimed to assess the levels of PM10-bound PAHs in several rural locations, their distribution along a year and how weather variables could influence them. Also, we focused on the emission sources and the comparison of the PAH mixtures to assess similitude among the sampling points. PM10-bound PAHs levels were monitored at three rural locations (north, center, and south) of Spain between April 2017 and February 2018. The study revealed that there were substantial differences regarding the levels of ΣPAHs, being higher in the central zone (IS; 65.4 mg/m3), then in the south (VA; 35.8 ng/m3) and finally in the north (NA; 20.9 ng/m3). IS and VA showed a similar distribution of emission sources, and temperature and wind speed seemed to influence negatively over the levels of PAHs likely. At both locations, PAH levels ran parallel throughout the year, with maximum levels during cold seasons and a greater presence of high molecular weight PAHs; however, the levels of PAHs and the most representative PAHs differed. On the other hand, NA was characterized for having another distribution of emission sources, which determined other representative PAHs, higher levels during spring, and a similar presence of high/medium/low molecular weight. Finally, the levels of ambient air PAHs represented an acceptable risk to people.

The characteristics of mitral regurgitation: Data from patients admitted following acute myocardial infarction.

Data were collected on patients admitted to the Queen Elizabeth Hospital Birmingham with type-1 myocardial infarction during 2016 and 2017 inclusively, who were treated by percutaneous intervention and had pre-discharge transthoracic echocardiography. The data were obtained from prospectively maintained hospital databases and records. Echocardiography was performed and reported contemporaneously by accredited echocardiographers. The purpose was to understand the prevalence and characteristics of mitral regurgitation (MR) after acute MI, including patients with ST-elevation (STEMI) and non-ST elevation MI (NSTEMI). MR was observed in 294/1000 patients with the following relative severities: mild = 76%, moderate = 21%, severe = 3% [1]. MR was graded by multiparametric quantification including proximal isolvelocity surface area (PISA), vena contracta (VC), effective regurgitant orifice area (EROA) and regurgitant volume (RVol). Amongst all patients with MR (n=294), PISA was performed in 89/294 (30%), VC 75/294 (26%), EROA in 53/294 (18%) and RVol in 26/294 (9%). Amongst patients with moderate or severe MR (n=70), PISA was performed in 57/70 (81%), VC in 55/70 (79%), EROA in 46/70 (66%) and RVol in 25/70 (36%). Characteristics of MR following acute MI were also assessed including frequency of reported leaflet thickness (259/294 = 88%) and mitral annular calcification (102/294 = 35%). Furthermore, the effect of MI on pre-existing MR was investigated and patients with pre-existing MR who continue to have MR after acute MI were found to have progression of MR by one grade in approximately 25% of cases. Finally, using Cox proportional hazards univariate analysis, significant factors associated with mortality in patients with MR post-MI include age (HR 1.065; 95% CI 1.035-1.096; p<0.001), creatinine clearance, (HR 0.981; 95% CI 0.971-0.991; p<0.001), left ventricular ejection fraction (LVEF) (HR 0.966; 95% CI 0.948-0.984; p<0.001), indexed left ventricular end-diastolic volume (LVEDVi) (HR 1.016; 95% CI 1.003-1.029; p=0.018), indexed left ventricular end-systolic volume (LVESVi) (HR 1.021; 95% CI 1.008-1.034; p=0.001), indexed left atrial volume (HR 1.026; 95% CI 1.012-1.039; p<0.001), and those with intermediate likelihood of pulmonary hypertension (pHTN) (HR 2.223; 95% CI 1.126-4.390; p=0.021); or high likelihood of pHTN (HR 5.626; 95% CI 2.189-14.461; p<0.001). Age and LVEF were found to be independent predictors of mortality on multivariate analysis [1].

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Mitral Regurgitation Following Acute Myocardial Infarction Treated by Percutaneous Coronary Intervention-Prevalence, Risk factors, and Predictors of Outcome.

Mitral regurgitation (MR) following acute myocardial infarction (AMI) worsens prognosis and reports of prevalence vary significantly. The objective was to determine prevalence, risk factors, and outcomes related to MR following AMI. We identified 1000 consecutive patients admitted with AMI in 2016/17 treated by percutaneous coronary intervention with pre-discharge transthoracic echocardiography. MR was observed in 294 of 1000 (29%), graded as mild (n = 224 [76%]), moderate (n = 61 [21%]) and severe (n = 9 [3%]). Compared with patients without MR, patients with MR were older (70 ± 12 vs 63 ± 13 years; p <0.001), with worse left ventricular ejection fraction (LVEF) (52 ± 15% vs 55 ± 11%; p <0.001) and creatinine clearance (69 ± 33 ml/min vs 90 ± 39 ml/min; p <0.001). They also had higher rates of hypertension (64% vs 55%; p = 0.012), heart failure (3.4% vs 1.1%; p = 0.014), previous MI (28% vs 20%; p = 0.005) and severe flow-limitation in the circumflex (50% vs 33%; p <0.001) or right coronary artery (51% vs 42%; p = 0.014). Prevalence and severity of MR were unaffected by AMI subtype. Revascularization later than 72 hours from symptom-onset was associated with increased likelihood of MR (33% vs 25%; p = 0.036) in patients with non-ST elevation myocardial infarction (NSTEMI). After a mean of 3.2 years, 56 of 288 (19%) patients with untreated MR died. Age and LVEF independently predicted mortality. The presence of even mild MR was associated with increased mortality (p = 0.029), despite accounting for confounders. In conclusion, MR is observed in over one-quarter of patients after AMI and associated with lower survival, even when mild. Prevalence and severity are independent of MI subtype, but MR was more common with delayed revascularization following NSTEMI.

Survival of people with valvular heart disease in a large, English community-based cohort study.

OBJECTIVE: Valvular heart disease (VHD) is present in half the population aged >65 years but is usually mild and of uncertain importance. We investigated the association between VHD and its phenotypes with all-cause and cause-specific mortality. METHODS: The OxVALVE (Oxford Valvular Heart Disease) population cohort study screened 4009 participants aged >65 years to establish the presence and severity of VHD. We linked data to a national mortality registry and undertook detailed outcome analysis. RESULTS: Mortality data were available for 3511 participants, of whom 361 (10.3%) died (median 6.49 years follow-up). Most had some form of valve abnormality (n=2645, 70.2%). In adjusted analyses, neither mild VHD (prevalence 44.9%) nor clinically significant VHD (moderate or severe stenosis or regurgitation; 5.2%) was associated with increased all-cause mortality (HR 1.20, 95% CI 0.96 to 1.51 and HR 1.47, 95% CI 0.94 to 2.31, respectively). Conversely, advanced aortic sclerosis (prevalence 2.25%) and advanced mitral annular calcification (MAC, 1.31%) were associated with an increased risk of death (HR 2.05, 95% CI 1.28 to 3.30 and HR 2.51, 95% CI 1.41 to 4.49, respectively). Mortality was highest for people with both clinically significant VHD and advanced aortic sclerosis or MAC (HR 4.38, 95% CI 1.99 to 9.67). CONCLUSIONS: Advanced aortic sclerosis or MAC is associated with a worse outcome, particularly for patients with significant VHD, but also in the absence of other VHD. Older patients with mild VHD can be reassured about their prognosis. The absence of an association between significant VHD and mortality may reflect its relatively low prevalence in our cohort.