Advanced Diastolic Dysfunction Research Articles

Impact of microvascular resistance reserve on post-STEMI cardiac remodelling and diastolic function

Abstract Background Coronary microvascular dysfunction (CMD) is a common sequelae of ST-segment elevation myocardial infarction (STEMI), preventing adequate recovery of left ventricular (LV) perfusion. The interferences of con-commitment epicardial stenosis or hyperemic hemodynamic alterations limit traditional physiologic metrics. The microvascular resistance reserve (MRR) was developed to overcome these shortcomings. Purpose We aim to investigate the association between post-STEMI MRR, and the ensuing left ventricle (LV) diastolic dysfunction, and functional remodeling. Methods In this prospective, observational study, we enrolled STEMI patients with multivessel disease who successfully underwent primary percutaneous coronary intervention (PCI). At three months post-PCI, all patients received complete revascularization followed by coronary physiology assessment using the bolus thermodilution method to measure the fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). MRR was calculated using the formula: MRR = (CFR/FFR) × (Pa rest/Pa hyper), where Pa rest and Pa hyper represent resting and hyperemic aortic pressure, respectively(1). CMD was defined as an MRR < 3.0 based on Boerhout et al(2). Diastolic dysfunction was defined according to the ASE 2016 guidelines. Functional LV remodelling (FLVR) was categorized according to Chimed et al(3). The relationship between CMD and the stages of FLVR and diastolic dysfunction was scrutinized over a 12-month follow-up period. Results We enrolled 210 patients, of whom 125 (59.5%) were men with a median age of 65 (IQR: 58–76). At the 3-month follow-up, the MRR was 3.46 (IQR 3.00, 3.92), with 56 (26.7%) patients having CMD (MRR<3.0). MRR is significantly correlated with the change of LVEF between primary PCI and 12 months (r=0.48, p<0.001, Fig1A). CMD patients have lower LVEF at 12 months (50.00% vs. 40.00%; p < 0.001) and demonstrated significantly less recovery in LV systolic function (-10.00% vs. 8.00%; p < 0.001, Fig 1B, 1C). CMD patients had a higher prevalence of grade 2 or 3 LV diastolic dysfunction (65.38% vs. 3.95%; p < 0.001, Fig 2A) and a higher incidence of advanced FLVR (Groups 3 and 4) compared to those without CMD (30.77% vs. vs. 10.53%; p < 0.001, Fig 2B). In multivariable logistic regression analysis, MRR was independently associated with LV diastolic dysfunction (0.17, 95%CI 0.08-0.33, p<0.001). Conclusions The novel parameter MRR is significantly related to LVEF recovery in STEMI patients and is an independent predictor for advanced LV diastolic dysfunction and FLVR. CMD patients, as diagnosed with MRR, showed a higher prevalence of advanced FLVR and diastolic dysfunction. These results suggest that MRR is a useful parameter for the identification and management of CMD in STEMI patients.

ASSESSMENT OF LEFT VENTRICULAR FUNCTION AFTER CORONARY ARTERY BYPASS GRAFTING

Coronary artery bypass grafting (CABG) is a commonly performed surgical intervention for coronary artery disease (CAD), aiming to restore blood flow to the myocardium and improve cardiac function. Left ventricular (LV) systolic function is a crucial determinant of postoperative outcomes in CABG patients, yet the predictors of adverse outcomes remain incompletely understood. Objective: This study aimed to evaluate left ventricular function outcomes following CABG and identify predictors of mortality among CABG patients. Methods: A prospective cohort study was conducted at, Ch. Pervaiz Elahi Institute Of Cardiology (CPEIC), Multan, Pakistan, from December 2022 to December 2023. The study included 96 patients undergoing CABG surgery. Preoperative data collection encompassed demographic information, medical history, and baseline clinical characteristics. Left ventricular function was assessed using echocardiography preoperatively and postoperatively. Statistical analysis involved descriptive statistics, univariate analysis, and univariate regression. Results: The study cohort comprised 96 participants, with a mean age of 56.1 years (±12.2) and a male predominance (67.7%). Prevalent comorbidities included diabetes mellitus (78.1%) and hypertension (79.2%). LV systolic dysfunction (30.2%) and old ischemic heart disease (72.9%) were common preexisting conditions. Intraoperative variables included perioperative inotropes (5.2%) and emergent surgeries (3.1%). Postoperative complications included reoperation for bleeding (5.2%) and deterioration of LV ejection fraction (34.4%). The mortality rate was 5.2%. Postoperatively, the mean LVEF increased significantly from 32.00% (±5.219) to 37.00% (±9.801) in isolated CABG patients. Conclusion: This study confirms the significant improvement in LV systolic function following CABG and underscores the high benefit of CABG in patients with reduced EF. However, diabetes mellitus, advanced diastolic dysfunction, and the insertion of IABP were identified as significant predictors of adverse outcomes. Identifying patients with these risk predictors could provide complementary prognostic information and help optimise care, monitoring, and follow-up to improve their expected poor outcomes.

Conduit Flow Compensates for Impaired Left Atrial Passive and Booster Functions in Advanced Diastolic Dysfunction.

Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction. We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110). The early passive filling progressively decreased with worsening diastolic function (P<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (P=0.021) and declines with more advanced diastolic function (P<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (P<0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow. An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.

The Contemporary Role of Speckle Tracking Echocardiography in Cirrhotic Cardiomyopathy.

Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association-in the majority of studies-with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis.

Sarcoidosis Associated Pulmonary Hypertension.

In patients with sarcoidosis, the development of pulmonary hypertension is associated with significant morbidity and mortality. The global prevalence of sarcoidosis-associated pulmonary hypertension (SAPH) reportedly ranges between 2.9% and 20% of sarcoidosis patients. Multiple factors may contribute to the development of SAPH, including advanced parenchymal lung disease, severe systolic and/or diastolic left ventricular dysfunction, veno-occlusive or thromboembolic disease, as well as extrinsic factors such as pulmonary vascular compression from enlarged lymph nodes, anemia, and liver disease. Early diagnosis of SAPH is important but rarely achieved primarily due to insufficiently accurate screening strategies, which rely entirely on non-invasive tests and clinical assessment. The definitive diagnosis of SAPH requires right heart catheterization (RHC), with transthoracic echocardiography as the recommended gatekeeper to RHC according to current guidelines. A 6-min walk test (6MWT) had the greatest prognostic value in SAPH patients based on recent registry outcomes, while advanced lung disease determined using a reduced DLCO (<35% predicted) was associated with reduced transplant-free survival in pre-capillary SAPH. Clinical management involves the identification and treatment of the underlying mechanism. Pulmonary vasodilators are useful in several scenarios, especially when a pulmonary vascular phenotype predominates. End-stage SAPH may warrant consideration for lung transplantation, which remains a high-risk option. Multi-centered randomized controlled trials are required to develop existing therapies further and improve the prognosis of SAPH patients.

Which Diastolic Pressure Should Be Used to Assess Diastolic Function?

Although high left ventricular filling pressures [left ventricular (LV) end-diastolic pressure or pulmonary capillary wedge pressure (PCWP)] are widely taken as surrogates for LV diastolic dysfunction, the actual distending pressure that governs LV diastolic stretch is transmural pressure difference (∆PTM). Clinically, preferring ∆PTM over PCWP may improve diagnostic and therapeutic decision-making. We aimed to compare the clinical implications of diastolic function characterization based on PCWP or ∆PTM. We retrospectively screened our hospital database for adult patients with a clinical diagnosis of heart failure who underwent right heart catheterization. Echocardiographic diastolic dysfunction was graded according to the current guidelines. LV end-diastolic properties were assessed with construction of complete end-diastolic pressure-volume relationship (EDPVR) curves using the single-beat method. Survival status was checked via the electronic national health-care system. A total of 693 cases were identified in our database; the final study population comprised 621 cases. ∆PTM-based, but not PCWP-based, EDPVR diastolic stiffness constants were significantly predictive of advanced diastolic dysfunction. PCWP-based diastolic stiffness constants were not able to predict 5-year mortality, whereas ∆PTM-based EDPVR stiffness constants and volumes all turned out to have significant predictive power for 5-year mortality. Left ventricular diastolic function assessment can be improved using ∆PTM instead of PCWP. As ∆PTM ultimately linked to right-sided functions, this approach emphasizes the limitations of taking LV diastolic function as an isolated phenomenon and underlines the need for a complete hemodynamic assessment involving the right heart in therapeutic and prognostic decision-making processes.

MR 4D flow–derived left atrial acceleration factor for differentiating advanced left ventricular diastolic dysfunction

ObjectivesThe magnetic resonance (MR) 4D flow imaging–derived left atrial (LA) acceleration factor α was recently introduced as a means to non-invasively estimate LA pressure. We aimed to investigate the association of α with the severity of left ventricular (LV) diastolic dysfunction using echocardiography as the reference method.MethodsEchocardiographic assessment of LV diastolic function and 3-T cardiac MR 4D flow imaging were prospectively performed in 94 subjects (44 male/50 female; mean age, 62 ± 12 years). LA early diastolic peak outflow velocity (vE), systolic peak inflow velocity (vS), and early diastolic peak inflow velocity (vD) were evaluated from 4D flow data. α was calculated from α = vE / [(vS + vD) / 2]. Mean parameter values were compared by t-test; diagnostic performance of α in predicting diastolic (dys)function was investigated by receiver operating characteristic curve analysis.ResultsMean α values were 1.17 ± 0.14, 1.20 ± 0.08, 1.33 ± 0.15, 1.77 ± 0.18, and 2.79 ± 0.69 for grade 0 (n = 51), indeterminate (n = 9), grade I (n = 13), grade II (n = 13), and grade III (n = 8) LV diastolic (dys)function, respectively. α differed between subjects with non-advanced (grade < II) and advanced (grade ≥ II) diastolic dysfunction (1.20 ± 0.15 vs. 2.16 ± 0.66, p < 0.001). The area under the curve (AUC) for detection of advanced diastolic dysfunction was 0.998 (95% CI: 0.958–1.000), yielding sensitivity of 100% (95% CI: 84–100%) and specificity of 99% (95% CI: 93–100%) at cut-off α ≥ 1.58. The AUC for differentiating grade III diastolic dysfunction was also 0.998 (95% CI: 0.976–1.000) at cut-off α ≥ 2.14.ConclusionThe 4D flow–derived LA acceleration factor α allows grade II and grade III diastolic dysfunction to be distinguished from non-advanced grades as well as from each other.Clinical relevance statementAs a single continuous parameter, the 4D flow–derived LA acceleration factor α shows potential to simplify the multi-parametric imaging algorithm for diagnosis of advanced LV diastolic dysfunction, thereby identifying patients at increased risk for cardiovascular events.Key Points• Detection of advanced diastolic dysfunction is typically performed using a complex, multi-parametric approach.• The 4D flow–derived left atrial acceleration factor α alone allows accurate detection of advanced left ventricular diastolic dysfunction.• As a single continuous parameter, the left atrial acceleration factor α could simplify the diagnosis of advanced diastolic dysfunction.

Abstract 14176: Cardiac Structure and Function in Relation to Health-Related Quality of Life in Heart Failure Patients With Preserved Ejection Fraction: Results From the PARAGON-HF Study

Background: Health-related quality of life (HRQL) is reduced in patients with heart failure with preserved ejection fraction (HFpEF). However, the extent to which HRQL outcomes are related to cardiac structure and function in patients with HFpEF is not well understood. Methods: We examined the association between baseline echocardiographic measures and longitudinal Kansas City Cardiomyopathy Questionnaire (KCCQ) measures in patients with HFpEF in the PARAGON-HF trial using longitudinal regression models adjusted for age, sex, baseline KCCQ score, randomization, and other important clinical confounders. Results: Among 1,094 patients with baseline KCCQ data at randomization and a baseline echocardiogram within 6 months of enrollment, the mean age was 74 years and 53% were women. Over 3 years, 78% completed KCCQ measures at baseline, 12, 24, and 36 months. Missing values for non-survivors (n=116) were imputed as zero to avoid survival bias. Posterior wall thickness, septal E/e’, and right ventricular (RV) end diastolic area were negatively associated with the KCCQ Overall Summary Score, and a similar pattern of associations was observed for the KCCQ Clinical Summary Score (Table). Pulmonary artery systolic pressure was additionally negatively associated with the KCCQ Total Symptom Score. Notably, left ventricular (LV) size, septal wall thickness, LV ejection fraction, LV strain, and left atrial size were not significantly associated with longitudinal changes in KCCQ. Conclusion: In patients with HFpEF, increased LV posterior wall thickness, elevated LV filling pressure, elevated pulmonary pressure, and RV enlargement - together suggestive of more advanced diastolic dysfunction - are associated with a decline in KCCQ scores and may influence future worsening of quality of life.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

Paradoxical increase in global longitudinal strain by handgrip exercise despite left ventricular diastolic dysfunction.

Although global longitudinal strain (GLS) is recognized as a sensitive marker of intrinsic left ventricular (LV) dysfunction, its afterload dependency has also been pointed. We hypothesized that decrease in GLS during handgrip exercise could be more sensitive marker of intrinsic myocardial dysfunction. Handgrip exercise-stress echocardiography was performed in 90 cardiovascular disease patients with preserved LV ejection fraction. LV diastolic function was graded according to the guidelines. Diastolic wall stress (DWS) and ratio of left atrial (LA) volume index to late-diastolic mitral annular velocity (LAVI/a') were measured at rest as LV stiffness. As well, LA strains were measured to assess LA function. GLS was expressed as absolute value and significant changes in GLS by handgrip exercise was defined as changes over prespecified mean absolute test-retest variability (2.65%). While mean value of GLS did not change by the exercise, substantial patients showed significant changes in GLS: decreased (group I, n=28), unchanged (group II, n=34), and increased (group III, n=28). Unexpectedly, patients in group I did not show any clinical and echocardiographic characteristics, while those in group III were characterized by elevated natriuretic peptide levels, blunted heart rate response to handgrip exercise, and advanced LV diastolic dysfunction. Multivariable analyses revealed that DWS, left atrial booster strain, and grade II or more diastolic dysfunction determined the increase in GLS even after adjustment for elevated natriuretic peptides and the changes in heart rate by the exercise. In contrast to our hypothesis, paradoxical increase in GLS by handgrip exercise could be associated with advanced LV diastolic dysfunction in cardiovascular patients with preserved LV ejection fraction. Our findings suggest that HG exercise for heart failure patients does not enhance the afterload straightforward, resulting in variable changes of GLS according to the individual conditions.

Parameters of intra-cardiac hemodynamics in women with essential hypertension and heart failure, carriers of different polymorphic variants of the galectin-3 gene (LGALS-3, rs 2274273)

Annotation. The study aims to improve the prediction and diagnostics of cardiac remodeling, specifically left ventricular myocardial hypertrophy (LVH) in essential hypertension and the development of chronic heart failure (CHF) in carriers of polymorphic variants of the galectin-3 gene (LGALS-3, rs2274273). 180 postmenopausal women, on average aged 58.51±0.45, residents of the Podillya region of Ukraine, were examined. The main group consisted of 113 women with EH, of which 62 had EH II, and 51 had EH III with CHF II A stage. The control group included 67 women without signs of cardiovascular pathology. General clinical examination, enzyme immunoassay method for determining the level of galectin-3 in blood plasma, genotyping of the LGALS3 gene (rs2274273) using polymerase chain reaction, and ultrasound of the heart were performed. Compliance of the frequency distribution of genotypes in the studied populations to the Hardy-Weinberg equilibrium was checked using the MedCalc Software Ltd. Odds ratio calculator. https://www.medcalc.org/calc/odds_ratio.php and calculated the odds ratio (OR) of developing left ventricular myocardial hypertrophy (LVH) and chronic heart failure (CHF). OR = 1 was considered as no association, OR&gt;1 – as a positive association (increased risk of pathology), and OR&lt;1 – as a negative association (reduced risk of pathology). The results were considered reliable at p&lt;0.05. Statistical processing of the obtained results was performed using the SPSS statistical program package, STATISTICA v. 10.0. The reliability of the difference in percentages of quantitative values between groups was calculated according to the χ2 criterion. In postmenopausal women, residents of the Podillya region of Ukraine, without signs of cardiovascular pathology, the following frequency distribution of galectin-3 gene genotype variants (rs2274273) was found: GA – 49.25%, GG – 40.30%, AA – 10.45%, which corresponds to the Hardy-Weinberg equilibrium. The specified ratio does not reliably differ from that in women with EH of different stages. Therefore, the galectin-3 gene polymorphism (rs2274273) is not associated with the risk of EH: OR =0.88; 95% CI 0.47 – 1.63; z statistic 0.417; χ2 =0.1744, p=0.6763. Analysis of the structural and functional parameters of the myocardium in carriers of the A allele shows more pronounced remodeling of the myocardium with eccentric LVH, a more advanced diastolic dysfunction (DD), and lower left ventricular ejection fraction than in GG homozygotes (LVEF 47.63±0.49% vs. 50.61±0.63%, p&lt;0.05). Therefore, the GG genotype of the galectin-3 gene (rs2274273) is a marker of limited changes in the structure of the myocardium in EH.

PO-05-016 GRADE 1 DIASTOLIC DYSFUNCTION PREDICTS MICRA AV ATRIO-VENTRICULAR SYNCHRONOUS PACING

The Micra AV (Medtronic) is a leadless ventricular pacemaker offering atrioventricular synchronous pacing relying on the detection of mechanical atrial contraction using an accelerometer. We have previously reported that diastolic dysfunction improves atrial tracking with this device. The purpose of this study was to evaluate the relationship between grade 1 diastolic dysfunction and atrioventricular synchronous pacing in patients with a Micra leadless pacemaker. The effect of heart rate on atrial tracking was also assessed. We performed a retrospective cohort review of all patients who underwent AV Micra placement within Northwell Health over a one-year period. Contemporaneous echocardiograms of 186 patients as well as device report rate histograms documenting atrial tracking at 10 bpm heart rate intervals were obtained. The percentage of total pacing performed with atrioventricular synchrony was assessed. 75 (40.3%) patients had normal diastolic function, 71 (38.2%) patients had grade 1 diastolic dysfunction, and 40 (21.5%) patients had advanced (grade 2 or 3) diastolic dysfunction. The rate of synchronous pacing was significantly higher in patients with grade 1 diastolic dysfunction compared with patients with advanced diastolic dysfunction (72.6% vs. 50.5%, P<0.001) or normal diastolic function (72.6% vs. 59.5%, P<0.01). Average time spent in atrial tracking modes was highest between heart rates of 70-80 (51%) and 80-90 (52.7%), followed by 60 – 70 (47%), 50-60 (46%), and 90-100 (43%). Atrial tracking was poor at heart rates of 40-50 (21%) and 100-110 (22%). Tracking at heart rates above 110 was rare (<5%). In this analysis, grade 1 diastolic function was associated with better atrial tracking in the Micra AV leadless pacemaker relative to normal or advanced diastolic function. Ventricular filling becomes more dependent on atrial contraction in patients with early diastolic dysfunction relative to patients with normal diastolic function. In advanced diastolic dysfunction, the atrial contribution to filling diminishes. This property of grade 1 diastolic dysfunction may allow the Micra AV to more accurately track atrial activity. Tracking based on heart rate appears to be most effective between heart rates of 70 and 90, decreasing at higher and lower rates. With this in mind, the Micra AV may be better suited to older patients who tend to be less active and are more likely to have impaired myocardial relaxation.

Diastolic Dysfunction Criteria and Heart failure Readmission in Patients with Heart Failure and Reduced Ejection Fraction

Background: Advanced diastolic dysfunction (DDys) correlates with elevated LV filling pressures and predicts heart failure readmission (HF-R). As grade 2-3 DDys has predictive value for HF-R, and requires 2 of 3 criteria (left atrial volume index &gt;34 ml/m2, E/e’&gt;14, or tricuspid regurgitation velocity &gt;2.8 m/s), we hypothesized that all 3 criteria would predict greater HF risk than any 2 criteria. Methods: In this single-center retrospective study that included 380 patients in sinus rhythm with HF and reduced ejection, we recorded patient characteristics, Doppler-echo, and HF-R with follow-up to 2167 days (median=1423 days; interquartile range=992-1821 days). Results: For grade 1 DDys (223 patients), any single criteria resulted in greater HF-R as compared to 0 criteria (HR=2.52, (1.56-3.88) p&lt;0.0001) with an AUC (area under curve)=0.637, p&lt;0.001. For grade 2 DDys (94 patients), there was greater HF-R for all 3 (vs. 0 criteria: HR=4.0 (2.90-8.36), p&lt;0.0001). There was greater HF-R for 3 vs any 2 criteria (HR=1.81, (1.10-3.39), p=0.0222). For all 3 criteria, there was moderate predictability for HF-R (AUC=0.706, p&lt;0.0001) which was more predictive than any 2 criteria (AUC difference 0.057, (0.011-0.10), p=0.009). For grade 3 DDys (63 patients), E/A&gt;2+2-3 criteria identified a subgroup with the greatest risk of HF-R (HR=5.03 (4.62-22.72), p&lt;0.0001) compared with 0 DDys criteria with moderate predictability for 2-3 criteria (AUC=0.726, p&lt;0.0001) exceeding E/A&gt;2+0-1 criteria (AUC difference=0.120, (0.061-0.182), p&lt;0.001). Conclusion: Increasing the number of abnormal criteria increased the risk and predictive value of HF-R for grade 1-3 DDys in patients with HF with reduced ejection fraction.

Diastolic Dysfunction Criteria and Heart failure Readmission in Patients with Heart Failure and Reduced Ejection Fraction

Background: Advanced diastolic dysfunction (DDys) correlates with elevated LV filling pressures and predicts heart failure readmission (HF-R). As grade 2-3 DDys has predictive value for HF-R, and requires 2 of 3 criteria (left atrial volume index &gt;34 ml/m2, E/e’&gt;14, or tricuspid regurgitation velocity &gt;2.8 m/s), we hypothesized that all 3 criteria would predict greater HF risk than any 2 criteria. Methods: In this single-center retrospective study that included 380 patients in sinus rhythm with HF and reduced ejection, we recorded patient characteristics, Doppler-echo, and HF-R with follow-up to 2167 days (median=1423 days; interquartile range=992-1821 days). Results: For grade 1 DDys (223 patients), any single criteria resulted in greater HF-R as compared to 0 criteria (HR=2.52, (1.56-3.88) p&lt;0.0001) with an AUC (area under curve)=0.637, p&lt;0.001. For grade 2 DDys (94 patients), there was greater HF-R for all 3 (vs. 0 criteria: HR=4.0 (2.90-8.36), p&lt;0.0001). There was greater HF-R for 3 vs any 2 criteria (HR=1.81, (1.10-3.39), p=0.0222). For all 3 criteria, there was moderate predictability for HF-R (AUC=0.706, p&lt;0.0001) which was more predictive than any 2 criteria (AUC difference 0.057, (0.011-0.10), p=0.009). For grade 3 DDys (63 patients), E/A&gt;2+2-3 criteria identified a subgroup with the greatest risk of HF-R (HR=5.03 (4.62-22.72), p&lt;0.0001) compared with 0 DDys criteria with moderate predictability for 2-3 criteria (AUC=0.726, p&lt;0.0001) exceeding E/A&gt;2+0-1 criteria (AUC difference=0.120, (0.061-0.182), p&lt;0.001). Conclusion: Increasing the number of abnormal criteria increased the risk and predictive value of HF-R for grade 1-3 DDys in patients with HF with reduced ejection fraction.

Systemic proinflammatory−profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome

BackgroundPrevious studies have mainly focused more on how diabetes affects the valve than the myocardium in aortic stenosis (AS). In the pressure-overloaded heart, myocardial fibrosis is an important driver of the progression from compensated hypertrophy to heart failure. Using comprehensive noninvasive imaging and plasma proteomics, we investigated whether and how diabetes aggravates the remodeling of the myocardium and its relation with prognosis in AS patients.MethodsSevere AS patients were enrolled in two prospective cohorts for imaging and biomarker analysis. The imaging cohort (n = 253) underwent echocardiography and cardiac magnetic resonance, and the biomarker cohort (n = 100) blood sampling with multiplex proximity extension assay for 92 proteomic biomarkers. The composite outcome of hospitalization for heart failure admissions and death was assessed in the imaging cohort.ResultsDiabetic patients were older (70.4 ± 6.8 versus 66.7 ± 10.1 years) with more advanced ventricular diastolic dysfunction and increased replacement and diffuse interstitial fibrosis (late gadolinium enhancement % 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p = 0.009; extracellular volume fraction % 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p = 0.025) in the imaging cohort. Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) were significantly elevated and that pathways related to inflammatory response and extracellular matrix components were enriched in diabetic AS patients. During follow-up (median 6.3 years), there were 53 unexpected heart failure admissions or death in the imaging cohort. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and aortic valve replacement (HR 1.88, 95% CI 1.06−3.31, p = 0.030).ConclusionsPlasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory−profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.

The Additive Effect of Left Ventricular Filling Pressure and Renal Function on Long-Term Prognosis of High-Risk Patients Undergoing Coronary Angiography

Introduction: Impaired relaxation is the earliest manifestation of ischemic cascade. Risk factors and renal function abnormalities are associated with coronary disease and diastolic dysfunction as well. We aimed to study the association of noninvasive assessment of left ventricular filling pressures and renal function with mortality in high-risk patients undergoing coronary angiography. Patients and Methods: An observational prospective study of 564 consecutive patients undergoing coronary angiography was conducted. The median follow-up was 2,293 days. Patients were categorized into 2 groups according to presence of significant diastolic dysfunction: group 1, 382 patients, with normal and group 2, 182 patients, with elevated filling pressure. Renal insufficiency was determined as calculated glomerular filtration rate <60 mL/min. Patients demographic, clinical, echocardiography, laboratory, and angiographic data were prospectively collected. Results: Fifty-three percent of patients underwent angiography due to acute coronary syndrome (ACS), 85.5% had coronary artery disease, 53.4% had reduced (<50%) left ventricular ejection fraction (LVEF), and 47.4% had abnormal renal function. The mortality during the follow-up period was 30.0%. Patients with elevated filling pressure had significantly higher mortality (50.5% vs. 20.2%, p < 0.0001). Impaired renal failure as well, was associated with higher mortality (48% vs. 15%, p < 0.001). The association remained significant in subgroups of patients with and without ACS and reduced and preserved LVEF. In Cox regression model which combined elevated filling pressure, renal insufficiency, age, diabetes mellitus, hypertension, presence of atrial fibrillation, LVEF, and anemia, elevated filling pressure and renal function impairment were independently associated with higher mortality (HR: 3.717, CI: 1.623–8.475, p < 0.0001 and HR: 0.972, CI: 0.958–0.985, p = 0.0001, respectively). There was an incremental prognostic value of elevated filling pressures and renal function impairment on mortality. Conclusions: Advanced diastolic dysfunction and impaired renal function are signals toward worse outcomes and are associated with mortality in high-risk patients undergoing coronary angiography.

The Mitral L-wave: A Marker of Advanced Diastolic Dysfunction.

The Mitral L-wave: A Marker of Advanced Diastolic Dysfunction.

Hypertrophic cardiomyopathy and atrial fibrillation: the Cardiomyopathy/Myocarditis registry of the EURObservational Research Programme of the European Society of Cardiology

Abstract Background Current guidelines for AF management underline a complex approach to detecting and treating atrial fibrillation (AF). Hypertrophic cardiomyopathy (HCM) is commonly associated with AF. Purpose To assess the clinical characteristic and prognosis in patients with HCM and AF. Methods and results Overall, 1739 adult patients with HCM (711/40.9% female; median age at diagnosis: 55.5 years) were enrolled in the EURObservational Research Programme – Cardiomyopathy/Myocarditis Long-Term Registry. Baseline clinical characteristics and adverse cardiovascular endpoints at 1-year follow-up were analysed. Results At baseline, AF was found in 478 (27.5%) subjects (paroxysmal: 54.7%, persistent: 17.6%, permanent: 27.7%). Newly diagnosed AF was identified during 1-year follow-up in 48 (2.8%) subjects with HCM. The presence of AF was associated with higher age (59.6±13.8 vs 50.8±16.1, p&amp;lt;0.001); BMI (27.7±5.1 vs 26.6±4.6 kg/m2, p&amp;lt;0.001); more advanced NYHA class (NYHA I/II and III/IV: 75.1 and 24.9 vs 86.2 and 13.8%, p&amp;lt;0.001); more frequent history of diabetes (14.6 vs 8.4%, p&amp;lt;0.001); arterial hypertension 43.4 vs 34.6%, p&amp;lt;0.001); renal impairment (15.4 vs 6.35%, p&amp;lt;0.001); and history of sustained VT (10.8 vs 6.35%, p&amp;lt;0.001). AF patients were characterized by lower left ventricular ejection fraction (LV EF) (59±12 vs 63±11%, P&amp;lt;0.001), left atrium (LA) dilatation (48.9±9.1 vs 42.4±7.7%, p&amp;lt;0.001), increased pulmonary artery systolic pressure (37.8±13.7 vs 29.6±12.6 mmHg, p&amp;lt;0.001), distribution of LV hypertrophy (p=0.032) and more advanced LV diastolic dysfunction (p&amp;lt;0.001). On multivariate logistic regression analysis, independent predictors of AF in the HCM population were: age at enrolment (OR 1.068, P&amp;lt;0.001); LVEF (OR 0.978, p&amp;lt;0.001); and LA diameter (OR 1.094, p&amp;lt;0.001). Oral anticoagulation (OAC) was administered in 69.5% of patients with AF (vitamin K antagonist: 48.5%; direct OAC: 21%). ICD was implanted in 26.8% in AF and 16.9% in non-AF subjects (p&amp;lt;0.001). PVI was performed in 9.9% of AF patients only. The annual incidence of stroke/TIA was higher in AF than in the non-AF population (2.64 vs 0.85%, p=0.009). There was a trend towards increased death from any cause in the AF population (3.39 vs 1.74%, p=0.05). There were no differences in SCD-risk score between AF and non-AF subjects. Conclusion The study reveals a high prevalence of AF in patients with HCM that corresponds with more advanced symptoms, increased prevalence of comorbidities, structural and functional heart remodelling along with inadequate anticoagulation and a significant increase in the risk of stroke. The clinical characteristics of HCM-AF patients indicate that the ESC recommended complex AF approach “CC To ABC” is appropriate in this population. Funding Acknowledgement Type of funding sources: None.

Systemic proinflammatory-profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome

Abstract Background It is unclear whether and how diabetes mellitus may aggravate myocardial fibrosis and remodeling in the pressure-overloaded heart. We investigated the impact of diabetes on the prognosis of aortic stenosis (AS) patients and its underlying mechanisms using comprehensive noninvasive imaging studies and plasma proteomics. Methods Severe AS patients undergoing both echocardiography and cardiovascular magnetic resonance (CMR) (n=253 of which 66 had diabetes) comprised the imaging cohort. The degree of replacement and diffuse interstitial fibrosis by late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) was quantified using CMR. Plasma samples were analyzed with the multiplex proximity extension assay for 92 proteomic biomarkers in a separate biomarker cohort of severe AS patients (n=100 of which 27 had diabetes). Results In the imaging cohort, diabetic patients were older (70.4±6.8 vs. 66.7±10.1 years) and had a higher prevalence of ischemic heart disease (28.8% vs. 9.1%), with more advanced ventricular diastolic dysfunction. On CMR, diabetic patients had increased replacement and diffuse interstitial fibrosis (LGE% 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p=0.009; ECV% 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p=0.025) (Figure 1). Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) are significantly elevated in diabetic AS patients (Figure 2). Pathway over-representation analyses of the plasma proteomics with Gene Ontology terms indicated that pathways related to inflammatory response and extracellular matrix components were enriched, suggesting that diabetes is associated with systemic effects that evoke proinflammatory and profibrotic response to the pressure-overloaded myocardium. During follow-up (median 6.3 years [IQR 5.2–7.2]) of the imaging cohort, 232 patients received aortic valve replacement (AVR) with 53 unexpected heart failure admissions or death. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and AVR (hazard ratio 1.88, 95% confidence interval 1.06–3.31, p=0.030). Conclusion Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory and profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea

Comparison Between Echocardiography and Cardiac Computed Tomography in the Evaluation of Diastolic Dysfunction and Prediction of Heart Failure

Recent data indicate that left atrial (LA) function assessment by cardiac computed tomography (CT) is closely related to diastolic dysfunction (DD). Therefore, we aimed to perform a direct comparison between CT and echocardiography for diagnosis of advanced DD and prediction of future heart failure or cardiovascular death. We identified 340 patients who had both spiral cardiac CT and a proximate echocardiogram. LA total emptying fraction (LATEF), a measure of global LA function, was automatically calculated from CT data, as a surrogate for diastolic function and was compared with echocardiographic grades of diastolic function. The area under the receiver operating characteristic curve for LATEF to differentiate between advanced DD (grades 2 and 3) and all other grades was 0.84 (0.79 to 0.88). Over a median of 4 years, 69 events (admissions for heart failure and cardiovascular deaths) occurred. By multivariate Cox analysis, LATEF &lt;40% provided incremental prognostic information after adjustments for advanced DD by echocardiography (hazard ratio 2.15, 95% confidence interval 1.13 to 3.94). There was a significant interaction (p=0.03) between LATEF and echocardiography-based diastolic grades. Stratified analyses within the diastolic function groups revealed that LATEF &lt;40% was equivalent to echocardiography in predicting events in the subgroup with advanced DD by echocardiography (p=0.20) but was associated with a significantly higher event rates in patients with normal filling pressures (p=0.0001) or indeterminate diastolic function (p=0.04) by echocardiography. In conclusion, LA function derived from CT can accurately detect advanced DD diagnosed by echocardiography and has additive value to echocardiography-derived DD.