Diastolic Dysfunction Grade Research Articles

Peak atrial longitudinal strain to replace atrial volume in diastolic function grading: associations with long-term outcomes in a community-based sample with normal left ventricular ejection fraction

Abstract Background Diastolic dysfunction (DD) often precedes symptomatic heart failure and is a predictor of adverse outcomes; thus, accurate assessment and grading are crucial for early interventions. Current guidelines recommend combining multiple echocardiographic parameters, including left atrial volume index (LAVi), for diagnosing DD in patients with normal left ventricular ejection fraction (LVEF). Recently, peak atrial longitudinal strain (PALS) emerged as a more sensitive marker of left atrial function, although its added value in the grading of DD and associated adverse outcomes is scarcely explored. Purpose We aimed to investigate the impact of replacing LAVi with PALS on DD grading by its associations with long-term all-cause mortality in a low-risk, community-based sample. Methods We retrospectively identified 1319 volunteers from a population-based screening program (mean age 53.8±14.9 years, 59.1% female) with LVEF>50%. Subjects underwent echocardiography to measure mitral annular early diastolic velocities (e’), the ratio between mitral inflow early diastolic velocity (E) and e' (E/e'), tricuspid regurgitation peak velocity, LAVi, and PALS by speckle tracking. Diastolic function was initially classified according to the 2016 ASE/EACVI guidelines into normal, indeterminate, and DD groups and then reclassified by replacing LAVi>34 ml/m² with a standard PALS cut-off of <24%. The primary endpoint was all-cause mortality. Results During the median follow-up time of 11 years, 135 (10,2%) subjects met the primary endpoint. According to guideline definitions, 59 subjects were diagnosed with DD, 128 were indeterminate, and 1132 showed normal function. Kaplan-Meier analysis (Figure 1) showed significant differences in mortality between normal versus indeterminate and DD groups (log-rank p<0.001), with a three-fold (HR [95% CI]: 3.363 [1.802 - 6.274], and nearly five-fold increased risk (HR [95% CI]: 4.935 [1.919 - 12.690], respectively. Notably, no significant difference was observed between the outcomes of the indeterminate and DD groups. When subjects were reclassified using PALS instead of LAVi, 35 had DD, 75 were indeterminate, and 1209 had normal function. This classification resulted in different outcomes between groups (Figure 2, log-rank p=0.003). Compared to the normal, the indeterminate group exhibited a two-fold increase in mortality risk (HR: 2.277 [95% CI: 1.038-4.997]), while the DD group had a ten-fold increased risk (HR: 10.180 [95% CI: 2.870-36.130]). DD was associated with a nearly five-fold increase in mortality risk (HR: 4.724 [95% CI: 2.177-10.250]) compared to the indeterminate group. Conclusions In a community-based sample with normal LVEF, replacing LAVi with PALS in diastolic function classification separated groups with significant differences in their long-term all-cause mortality. This adjustment also reduced the size of the indeterminate group and refined its mortality risk.Figure 1Figure 2

Prognostic implications of microvascular resistance reserve in symptomatic patients with intermediate coronary stenosis

Abstract Background Microvascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). Objective To evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. Methods The current study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiologic assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR)≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR≤3.0. Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. Results Among the total patients, 172 patients (31.4%) had FFR≤0.80 and 200 patients (36.6%) had CMD defined by MRR≤3.0. MRR showed no significant correlation with FFR (R=-0.031, P=0.469), however, it was significantly correlated with index of microcirculatory resistance (R=-0.353, P<0.001), NT-proBNP (R=-0.296, P<0.001), left ventricular filling pressure (E/e’) (R=-0.224, P<0.001), and diastolic dysfunction grade (P<0.001). During median follow-up of 3.3 years (interquartile range from 2.0 to 4.5 years), MRR was significantly associated with MACE risk (HR 1.23 per-1 decrease, 95% CI 1.12-1.36, P<0.001). CMD defined by MRR≤3.0 was associated with an increased MACE risk in both FFR>0.80 (41.0% vs. 26.0%; HRadj 1.59, 95% CI 1.07-2.35, P=0.021) and FFR≤0.80 (34.7% vs. 14.8%; HRadj 2.32, 95% CI 1.12-4.82, P=0.024) groups. Conclusion Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as with increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk of a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis.

Left atrial morpho-functional parameters and their correlation with other phenotypic and functional characteristics of hypertrophic cardiomyopathy

Abstract Background Left atrial (LA) volume index (LAVI), LA reservoir strain (LARS) and total atrial conduction time (TACT) (estimated by tissue Doppler imaging) are morphological and functional parameters reflecting LA structural and electrical remodeling, connected to atrial fibrillation development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), correlation of the above-mentioned parameters with other disease characteristics is not fully investigated. Purpose Aim of this study was to estimate the prevalence of atrial myopathy characteristics such as increased LAVI, impaired LARS and elongated TACT in a cohort of HCM patients without AF history and investigate their correlation with other phenotypic and functional characteristics of the disease such as left ventricular (LV) hypertrophy magnitude, fibrosis extent and diastolic dysfunction grade. Methods We included 100 HCM patients (54±21 years, 75% male, maximum wall thickness 19±3.4mm) without history of atrial fibrillation who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT and LARS measurement is shown on left panel. Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices. Results All HCM patients had preserved EF (60±7.5%), while 28 (28%) presented outflow tract obstruction and 10 (10%) diastolic dysfunction stage≥2. LGE was observed in 64 patients (64%) occupying 8±5% of left ventricular (LV) mass. Mean TACT was 140±22 msec, with LAVI being 32±16 mL/m2 and LARS 26±14%. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r=0.54, p<0.0005 and r=0.44, p=0.002 respectively, right upper panel), while E/E’ (r=-0.44, p=0.003) and fibrosis extent (r=0.36, p=0.02) were the strongest predictors of LARS and LAVI values respectively (right lower panel). Conclusions Atrial myopathy parameters seem to correlate with various morphological and functional characteristics of HCM. Atrial electro-mechanical delay assessed through TDI based TACT correlates significantly with LVMI, whereas LARS and LAVI are strong regressors of elasticity properties, partially expressed through diastolic function and underlying fibrosis.

Prognostic implications and alterations in left atrial deformation following transcatheter aortic valve implantation for severe aortic stenosis

Abstract Background Left atrial reservoir strain (LARS) as a single parameter estimate of left ventricular (LV) diastolic dysfunction (DD), may provide important prognostic insights into patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Purpose To evaluate the prognostic implications of pre- and post TAVI LARS-defined DD (LARS-DD) grade in patients undergoing TAVI for severe AS and its association with new-onset atrial fibrillation. Methods Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS ≥24%), grade 2 (LARS ≥19 to <24%) and grade 3 (LARS <19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements, no history of atrial fibrillation and with clinical/ECG follow-up following the post-TAVI follow-up echocardiogram were evaluated for the occurrence of new-onset atrial fibrillation. Results A total of 601 patients (median age 81 [76-85] years, 53% male) undergoing TAVI for severe AS were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26 to 58) months, a total of 258 (43%) patients died (Figure 1). In a comprehensive multivariable Cox regression model adjusted for age, sex, EuroSCORE II, New York Heart Association class III to IV symptoms, LV ejection fraction, atrial fibrillation, LA volume index and LV stroke volume index, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one grade increase above LARS-DD grade 0/1, 95% CI 1.07 to 1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated (Figure 2). On multivariable Fine and Gray regression analyses adjusting for age and LA volume index, post-TAVI LARS (SDHR 1.14 per 1% <20%, 95% CI 1.05 to 1.23, P=0.0009), rather than pre-TAVI LARS (SDHR 1.00 per 1% <20%, 95% CI 0.91 to 1.11, P=0.93) was associated with the occurrence of new-onset atrial fibrillation. Conclusions Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS and may enhance risk stratification. In addition, post-TAVI LARS, but not pre-TAVI LARS, was closely related to the occurrence of new-onset atrial fibrillation, likely better reflecting intrinsic LA dysfunction.Figure 1:All-Cause MortalityFigure 2:New-Onset Atrial Fibrillation

Cardiac structure and function in patients with chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is common and strongly associated with cardiovascular disease, but the pathophysiology has not been fully elucidated. Purpose We aimed to investigate cardiac structure and function in patients with COPD compared to a matched general population. Methods In a prospective cohort study, 796 patients with COPD were included and matched 1:2 on age and sex with controls from a general population study. All participants underwent an examination program including echocardiography. Standardized linear regression coefficients were used to compare cardiac structure and function in patients with COPD vs. controls. Impaired left ventricular (LV) function was defined as a left ventricular ejection fraction (LVEF) <50%, or global longitudinal strain (GLS) <16% (numerical). Impaired right ventricular (RV) function was defined as tricuspid annular plane systolic excursion (TAPSE) <1.7 cm. Diastolic dysfunction was defined as having at least two of the following parameters: E/e’ >14, septal e’ velocity <7cm/s, or lateral e’ velocity <10 cm/s, left atrial volume index (LAVi) >34 mL/m2, or tricuspid regurgitation velocity (TRV) >2.8 m/s. Logistic regression was used to assess associations between having COPD and systolic and diastolic dysfunction. Results Mean age was 70.2 ± 8.3 years and 52% were females. COPD patients had a mean forced expiratory volume in 1 second (FEV1) of 49.4 ± 18.8% predicted. At baseline, 43% of the patients with COPD had hypertension and 10% had diabetes (DM). Additionally, 57% with COPD had cardiovascular disease at baseline, including 12% with ischemic heart disease (IHD), 15% with atrial fibrillation (AF), 6% with heart failure, and 5% with a previous ischemic stroke. Patients with COPD had impaired measures of cardiac structure and function including a lower GLS (COPD vs. controls: 16.3 vs. 19.2%), lower TAPSE (2.3 vs. 2.6 cm), larger LAVi (29.0 vs. 24.7 mL/m2), and higher TRV (2.7 vs. 2.3 m/s), p for all associations <0.001. (See figure). Patients with COPD had a significantly higher prevalence of impaired LV systolic function (OR for GLS <16%: 8.18, 95% CI(6.04; 11.1), p <0.001), impaired RV systolic function (OR for TAPSE <1.7 cm: 2.77, 95% CI(1.63; 4.69), p <0.001), and LV diastolic dysfunction (OR for diastolic dysfunction grade I or higher: 4.00, 95% CI(3.12; 5.13), p <0.001) after adjustment for age, sex, hypertension, smoking, DM, IHD, AF, and lower density lipoprotein. (See figure). Conclusion Patients with COPD had significantly impaired LV and RV systolic function as well as impaired diastolic function compared with individuals from the general population. These findings underscore the importance of recognizing and addressing cardiovascular comorbidities in COPD.

Left atrioventricular coupling index: association with diastolic dysfunction and prognostic implications in heart failure patients

Abstract Background Left atrioventricular coupling index (LACI), an index coupling left atrial (LA) to left ventricular (LV) volume at end-diastole (Figure 1), showed to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. Purpose The present study aimed to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). Methods We retrospectively analyzed 1158 stable HF patients (mean age 66±12 years, 75% men) on optimal medical therapy (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (endpoint: all-cause death/HF-hospitalization) was assessed by Cox regression and spline curve analyses. Results were validated in an external cohort of 242 HF patients. Results In the derivation cohort, the median LACI value was 0.29 (IQR:0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. While prevalence of grade-1 DD (ASE/EACVI classification) progressively decreased across LACI tertiles, the prevalence of grade-3 DD significantly increased (8%,23%, and 46% respectively, P<0.0001). A cut-off value ³0.26 identified moderate-to-severe DD with an area-under the-curve of 0.75. During follow-up (median 28 months, IQR:11-53), 407 (35%) patients reached the endpoint. On multivariable analysis, LACI was independently associated with outcomes (HR for 1-unit-increase 2.34; 95%CI 1.35-4.03; P=0.002 – Figure 2), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<0.0001). The prognostic value of LACI was consistent in the external validation cohort. Conclusions LACI is associated with DD severity and is an independent predictor of outcomes in HF patients.How to assess LACIPrognostic value of LACI in HF

The Agreement Between Transthoracic and Transesophageal Echocardiography in the Assessment of Right Ventricular Diastolic Dysfunction Grades in Adult Patients Undergoing Cardiac Surgery: A Prospective Observational Study.

Introduction The importance of right ventricular (RV) diastolic function in cardiac surgery cannot be overstated, as it significantly affects prognosis and long-term outcomes. Conventionally, RV diastolic dysfunction (RVDD) is assessed and graded using criteria from either the American Society of Echocardiography (ASE) or the British Society of Echocardiography (BSE), with measurements done by transthoracic echocardiography (TTE). However, during cardiac surgery, perioperative echocardiographic evaluation is done predominantly by transesophageal echocardiography (TEE). This study aimed to assess the agreement between TTE and TEE in grading RVDD using both ASE and BSE criteria. Methods Key two-dimensional (2D) and Doppler parameters were measured in 81 patients undergoing cardiac surgery by both TTE and TEE after anesthesia induction within 10 minutes of each other, under similar hemodynamic, anesthetic, and ventilatory conditions. RVDD gradings were done separately by TTE and TEE with both ASE and BSE criteria using the measured values of the key parameters by TTE and TEE, respectively. RVDD gradings derived from TTE were compared with those derived from TEE. The tricuspid inflow Doppler and tricuspid annular tissue Doppler parameters were measured in TEE in both mid-esophageal RV inflow-outflow (MERVIO) and deep transgastric RV inflow-outflow (DTGRVIO) views. Gradings were done separately for both views of TEE by using the Doppler values measured in the respective views (TEE-MERVIO and TEE-DTGRVIO). The TTE-derived RVDD grades were compared with those derived by both TEE-MERVIO and TEE-DTGRVIO. Weighted κ values were used to assess observed agreement beyond chance. Inter-rater reliability of the RVDD grades derived by both TTE and TEE (both views) was also checked. Individual 2D and Doppler parameters were compared between TTE and TEE in terms of Bland-Altman limits of agreement. Results As per ASE criteria, disagreement of RVDD by ≥1 grade was seen in 43 (53.1%) patients and by 2 grades in eight (9%)patients when comparing TTE and TEE-MERVIO, yielding a weighted κ of 0.14 (p=0.123). Disagreement by ≥1 grade was observed in 32 (39.5%) patients and by 2 grades in 10 (12.3%) patients when comparing TTE and TEE-DTGRVIO, yielding a weighted κ of 0.3 (p=0.002). Using the BSE Criteria, disagreement of RVDD grades occurred in nine (11.1%) patients when comparing TTE and TEE-MERVIO, yielding an unweighted κ of 0.25 (p=0.295). Disagreement occurred in 12 (14.8%) patients when comparing TTE and TEE-DTGRVIO, yielding an unweighted κ of 0.260 (p=0.187). There was almost perfect agreement between independent raters regarding both TTE- and TEE-derived RVDD grades per the ASE criteria, and substantial to almost perfect agreement per BSE criteria. Bland-Altman analysis of paired data between the TTE- and TEE-measured values of individual 2D and Doppler parameters showed wide limits of agreement. Conclusions This study revealed, at best, only fair agreement between TTE and TEE in grading RVDD. The measured 2D and Doppler echocardiographic parameters showed wide limits of agreement between TTE and TEE. We recommend further researchto develop a TEE-based algorithm for grading RVDD, and to evaluate the prognostic effectiveness of perioperative TEE for predicting adverse clinical outcomes associated with RVDD.

Clinical impact of diastolic dysfunction and atrial fibrillation before and after initiating hemodialysis in patients with end-stage kidney disease

Background Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD). Methods A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication. Results The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes. Conclusions The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.

Relationship of left ventricular diastolic dysfunction with quality of life in heart failure patients with reduced ejection fraction (HFrEF).

Heart failure is a complex clinical manifestation due to diastolic dysfunction and systolic dysfunction of the left ventricle (LV). Diastolic dysfunction of the LV plays an important role in worsening the quality of life (QoL) in heart failure patients. The aim of this study was to assess the relationship between the severity or grade of LV diastolic dysfunction and QoL in heart failure with reduced ejection fraction (HFrEF) patients. A retrospective cohort study was conducted at the Cardiac Center of H. Adam Malik Hospital, Medan, Indonesia, from January 2022 to December 2022. This study included inpatients and outpatients aged above 18 years who were diagnosed with HFrEF, identified by echocardiography with an ejection fraction of ≤40%. Echocardiography was performed to evaluate left ventricular diastolic dysfunction, and QoL was assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) 6-12 months after the severity of LV diastolic dysfunction was confirmed. The MLHFQ was classified into good and poor QoL. The severity of LV diastolic function was measured using the E/A ratio, mean E/e' ratio, tricuspid regurgitation velocity (TR Vmax), and left atrial volume index (LAVI), and was classified into grades I, II, and III. The relationships between the severity of diastolic dysfunction and other factors with QoL were measured using Chi-squared, Fisher's exact test, or Mann-Whitney test, as appropriate. A total of 96 patients were included in the study, of which 56 (58.3%) patients had grade I, 12 (12.5%) had grade II, and 28 (29.2%) patients had grade III of LV diastolic dysfunction. There were 77 (80.2%) and 19 (19.8%) patients with good and poor QoL, respectively. This study revealed a significant relationship between the severity of LV diastolic dysfunction and QoL in HFrEF patients with p=0.040. In conclusion, the degree of LV diastolic dysfunction is related to the QoL of HFrEF patients and therefore better comprehensive management strategies should be considered in HFrEF cases to address the impact of LV diastolic dysfunction on QoL.

Predicting cardiovascular events in out-of-hospital patients presenting with atypical chest pain and complete left bundle branch block: role of CTA and echocardiographic Global Longitudinal Strain.

Out-of-hospital patients presenting with atypical chest pain and complete left bundle branch block (LBBB) have to be stratified for the presence of coronary artery disease and the risk of developing heart failure (HF). We investigated the prognostic role of coronary CT-angiography (CTA) and echocardiographic global longitudinal strain (GLS) in those patients in a mid-term follow-up. Out-of-hospital patients with LBBB underwent echocardiography and a 64-slice CT angiography were evaluated retrospectively. Development of HF or a cardiovascular death were the events scheduled. Seventy-eight patients (32 female; mean age: 66.0 ± 10.4 years were enrolled. During a follow-up of 33 months (IQR: 17-77), one patient (1.5%) experienced a cardiovascular death, 14 patients (17.9%) required urgent outpatient visits due to acute decompensated HF (12 hospitalizations). Echocardiography showed a slightly reduced left ventricular ejection fraction (LVEF) (50.0% ± 9.8%) and GLS within the normal range (-16.2% ± 4.1%). CTA analysis showed coronary stenosis > 50% in 28 patients (35.9%). A high Agatston score (> 100) was observed in 29.5%. Notably, 25 patients (32.1%) were diagnosed with left main coronary artery disease and 15 patients (16.7%) underwent revascularization during the follow up. Significant associations were observed between events and LVEF (P = 0.001), diastolic dysfunction grade ≥ 2 (P = 0.02), GLS (P < 0.001), multiple coronary stenosis (P = 0.04) and Agatston score (P = 0.05). Multivariate analysis confirmed the relationships with LVEF (R2 = 0.89, P < 0.001), diastolic dysfunction (R2 = 3.30, P = 0.04), GLS (R2 = 1.43, P < 0.001), and Agatston score (R2 = 1.01, P = 0.05). In patients with complete LBBB, CTA and GLS identified those at a high risk of development HF.

Prognostic Implications and Alterations in Left Atrial Deformation Following Transcatheter Aortic Valve Implantation.

To evaluate the prognostic implications of left atrial reservoir strain-defined diastolic dysfunction (LARS-DD) grade in patients undergoing TAVI for severe aortic stenosis (AS) and to determine if post-TAVI LARS was more closely associated with new-onset atrial fibrillation than pre-TAVI LARS. Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS≥24%), grade 2 (LARS≥19 to <24%) and grade 3 (LARS<19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements and no history of atrial fibrillation were evaluated for the occurrence of new-onset atrial fibrillation. A total of 601 patients (median age 81 [76-85] years, 53% male) were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26-58) months, a total of 258 (43%) patients died. In a comprehensive multivariable Cox regression model, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one-grade increase, 95%CI 1.07-1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated. Post-TAVI LARS (SDHR 1.14 per 1%<20%, 95%CI 1.05-1.23, P=0.0009), but not pre-TAVI LARS (P=0.93) was independently associated with new-onset atrial fibrillation. Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS. Post-TAVI LARS was closely related to the occurrence of new-onset atrial fibrillation.

Left Atrial Strain for assessment of left ventricle diastolic dysfunction in acute coronary syndrome patients.

Patients with acute coronary syndrome (ACS) have a high incidence of Left ventricle diastolic dysfunction (DD). Latest algorithms for the assessment of DD lay on 2D parameters and describe a grading to quantify its severity. However, there persists a "gray zone" of values in which DD remains indeterminate. to analyze the diagnostic value of Left atrium strain (LAS) for categorization of LV DD and assessment of LV filling pressures in ACS patients. Cross-sectional study that prospectively evaluated 105 patients presenting ACS with preserved LV ejection fraction (LVEF). Patients were divided in 4 groups according to the DD grade. Mean values of LAS, corresponding to three phases of atrial function: reservoir (LASr), conduit (LAScd) and contraction (LASct), were obtained by speckle-tracking echocardiography. Mean age was 60±10 years, with a gender ratio of 6.14. LASr and LASct were significantly lower according to DD severity (p combined=0.021, p combined=0.034; respectively). E/e' ratio was negatively correlated to LASr (r= - 0.251; p= 0.022) and LASct (r= -0.197; p=0.077). Left atrial volume index (LAVI) was also negatively correlated to LASr (r= -0.294, p= 0.006) and LASct (r= -0.3049, p=0.005). Peak tricuspid regurgitation was negatively correlated to LASr (r=-0.323, p=0.017) and LASct (r=-0.319, p=0.020). Patients presenting elevated LV filling pressures had lower LASr and LASct (p=0.049, p=0.022, respectively) compared to patients witn normal LV filling pressures. ROC curve analysis showed that a LASr < 22% (Se= 75%, Sp= 73%) and a LASct < 13% (Se= 71%, Sp=58%) can increase the likelihood of DD grade II or III by 4.6 (OR= 4.6; 95% CI: 1.31-16.2; p=0.016) and 3.7 (OR= 3.7; 95% CI: 1.06-13.1; p= 0.047), respectively. LAS is a valuable tool, which can be used to categorize DD in ACS patients.

Study of P wave dispersion in patients with paroxysmal atrial fibrillation and its role in prediction of atrial fibrillation recurrence

BackgroundIt has been known that increased P wave duration and P wave dispersion reflect prolongation of intra-atrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses, which are well-known electrophysiologic characteristics in patients with atrial arrhythmias and especially paroxysmal atrial fibrillation. The objective of this study was assessment of P wave dispersion value in cases with paroxysmal atrial fibrillation and its role in predicting recurrence.ResultsForty-eight patients with documented paroxysmal AF were subjected to clinical evaluation, electrocardiogram and routine Doppler echocardiogram. We found that a statistically significant association was detected between P wave dispersion and older age, diabetic and hypertensive cases with positive correlation also detected with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Mean corrected P wave dispersion and corrected QT interval were higher among cases using sotalol, ca channel blockers, among cases using nitrates and among cases with Morris index > 0.04. Higher mean value of corrected QT was associated with biphasic P v1 shape. Old age, female sex, P wave dispersion and QT wave dispersion are statistically significant predictors of PAF recurrence.ConclusionP wave dispersion in patients with paroxysmal atrial fibrillation was strongly correlated to older age, diabetic and hypertensive patients and also with left atrial dimension (LAD), left ventricle size and diastolic dysfunction grade. Also, mean corrected P wave dispersion can predict atrial fibrillation recurrence in patients with Morris index > 0.04, old age, female sex, and QT wave dispersion.

Left Atrioventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure

Left atrioventricular coupling index (LACI), an index coupling left atrial to left ventricular (LV) volume at end-diastole, has been shown to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The aims of the present study were to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). A total of 1,158 patients with HF in stable condition, on optimal medical therapy, were retrospectively analyzed (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (end point: all-cause death or HF hospitalization) was assessed using Cox regression. Results were validated in an external cohort of 242 patients with HF. In the derivation cohort, the median LACI value was 0.29 (interquartile range, 0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. Although the prevalence of grade 1 DD (American Society of Echocardiography/European Association of Cardiovascular Imaging classification) progressively decreased across LACI tertiles, the prevalence of grade 3 DD significantly increased (8%, 23%, and 46%, respectively; P<.0001). A cutoff value of ≥0.26 identified moderate to severe DD with an area under the curve of 0.75. During follow-up (median, 28months; interquartile range, 11-53 months), 407 patients (35%) reached the end point. On multivariable analysis, LACI was independently associated with outcomes (hazard ratio for a 1-SD increase, 1.16; 95% CI, 1.06-1.28; P=.002), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<.0001). The prognostic value of LACI was consistent in the external validation cohort. LACI is associated with DD severity and is an independent predictor of outcomes in patients with HF.

Heart Rate at Rest and Incident Atrial Fibrillation in Patients With Diastolic Dysfunction

Diastolic dysfunction (DD) is associated with incident atrial fibrillation (AF). The influence of resting heart rate (RHR) on incident AF in patients with DD has not been investigated. The goal of this study is to assess the influence of RHR on incident AF in patients with DD. Patients from a large health system with no prior history of AF, a left ventricular ejection fraction ≥50% and documented DD on echocardiography were divided into quartiles (<66, 66-76, 77-91, >91 bpm) based on RHR. Incident AF was estimated using AF hospitalization during follow-up. Hazard ratios (HR) for AF hospitalization and all-cause death were calculated with a Cox proportional hazards model. A total of 19,046 patients were analyzed. Over a median follow-up of 42.2 months, 742 (3.9%) patients were hospitalized for AF. Both slower and faster RHR were associated with increased risk of AF hospitalization (HR 1.40, CI: 1.14-1.71, p = 0.001, HR 1.23, CI: 0.99-1.53, p = 0.06 and HR 1.72, CI: 1.38-2.14, p<0.001, for quartiles 1, 2, and 4, respectively), suggesting a J-shaped relationship. Progressive increase in all-cause death was noted with faster RHR (HR1.19 per quartile increase, CI: 1.16-1.22, p<0.001). These results persisted after adjustment for age, cardiovascular comorbidities, grade of DD and beta blocker use. In conclusion, this large, real-world analysis indicates increased risk of incident AF with slower and faster RHR in patients with DD. Randomized trials are needed to evaluate the potential of RHR modification to mitigate the risk of incident AF.

Prognostic Implications of Microvascular Resistance Reserve in Symptomatic Patients With Intermediate Coronary Stenosis

BackgroundMicrovascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). ObjectivesThe aim of this study was to evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. MethodsThe present study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiological assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR) ≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR ≤3.0. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. ResultsAmong the study group, 172 patients (31.4%) had FFR ≤0.80, and 200 patients (36.6%) had CMD defined by MRR ≤3.0. MRR showed no significant correlation with FFR (R = −0.031; P = 0.469), but it was significantly correlated with the index of microcirculatory resistance (R = −0.353; P < 0.001), N-terminal pro–B-type natriuretic peptide (R = −0.296; P < 0.001), left ventricular filling pressure (E/e′ ratio) (R = −0.224; P < 0.001), and diastolic dysfunction grade (P < 0.001). During a median follow-up period of 3.3 years (Q1-Q3: 2.0-4.5 years), MRR was significantly associated with MACE risk (HR: 1.23 per 1-U decrease; 95% CI: 1.12-1.36; P < 0.001). CMD defined by MRR ≤3.0 was associated with an increased MACE risk for both FFR >0.80 (41.0% vs 26.0%; adjusted HR: 1.59; 95% CI: 1.07-2.35; P = 0.021) and FFR ≤0.80 (34.7% vs 14.8%; adjusted HR: 2.32; 95% CI: 1.12-4.82; P = 0.024). ConclusionsDecreased MRR was associated with the presence of cardiac diastolic dysfunction as well as increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk for a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis. (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function [DIAST-CMD]; NCT05058833)

Patient Outcomes by Ventricular Systolic and Diastolic Function.

Left ventricular dysfunction is characterized by systolic and diastolic parameters, leading to heart failure (HF) with reduced or preserved ejection fraction (EF), respectively. The goal of this study is to examine the impact of left ventricular systolic and diastolic dysfunction (DD) on patient outcomes. Two cohorts were used in this analysis: Cohort A included 136 455 patients with EF ≥50%, stratified by the presence and grade of DD. Cohort B included 16 850 patients with EF <50%, stratified by EF quartiles. Patients were followed to the end points of all-cause death and cardiovascular, HF, or cardiac arrest hospitalizations. Over a median follow-up of 3.42 years, 23 946 (16%) patients died and 31 113 (20%), 13 305 (9%), and 1269 (1%) were hospitalized for cardiovascular, HF, or cardiac arrest causes, respectively. With adjustment for comorbidities, the risk of all-cause mortality and of cardiovascular and HF hospitalizations increased steadily with increasing grade of DD in patients with normal EF, and even more so in patients with worsening EF. The risk of hospitalization for cardiac arrest in patients with grade III DD, however, was comparable to that of patients with EF <25% (hazard ratio, 1.00 [95% CI, 0.98-1.01]) and worse than that of patients in better EF quartiles. Although systolic dysfunction is associated with a greater risk of overall death and HF hospitalizations than DD, the risk of cardiac arrest in patients with grade II and III DD is comparable to that of patients with moderate and severe systolic dysfunction, respectively. Future studies are needed to examine treatment strategies than can improve these outcomes.

Diastology in the intensive care unit: Challenges for the assessment and future directions.

Myocardial dysfunction is common in patients admitted to the intensive care unit (ICU). Septic disease frequently results in cardiac dysfunction, and sepsis represents the most common cause of admission and death in the ICU. The association between left ventricular (LV) systolic dysfunction and mortality is not clear for critically ill patients. Conversely, LV diastolic dysfunction (DD) seems increasingly recognized as a factor associated with poor outcomes, not only in sepsis but also more generally in critically ill patients. Despite recent attempts to simplify the diagnosis and grading of DD, this remains relatively complex, with the need to use several echocardiographic parameters. Furthermore, the current guidelines have several intrinsic limitations when applied to the ICU setting. In this manuscript, we discuss the challenges in DD classification when applied to critically ill patients, the importance of left atrial pressure estimates for the management of patients in ICU, and whether the study of cardiac dysfunction spectrum during critical illness may benefit from the integration of left ventricular and left atrial strain data to improve diagnostic accuracy and implications for the treatment and prognosis.

Artificial intelligence-enabled ECG for left ventricular diastolic function and filling pressure

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645–1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298–1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.

Multiparametric Monitoring of Disease Progression in Contemporary Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy Initiating Tafamidis Treatment.

Recently, a disease modifying therapy has become available for transthyretin amyloid cardiomyopathy (ATTR-CM). A validated monitoring concept of treatment is lacking, but a current expert consensus recommends three clinical domains (clinical, biomarker and ECG/imaging) assessed by several measurable features to define disease progression. We retrospectively analyzed data of wild-type ATTR-CM patients initiating tafamidis therapy assessed within our local routine protocol at baseline and 6-months follow-up with respect to the frequency of values beyond the proposed thresholds defining disease progression. Additionally, associations of cardiac magnetic resonance (CMR) tomography with clinical domains were examined within a subgroup. Sixty-two ATTR-CM patients were included (88.7% male, mean age 79 years). In total, 16.1% of patients had progress in the clinical and functional domain, 33.9% in the biomarker domain and 43.5% in the imaging/electrocardiography (ECG) domain, with the latter driven by deterioration of the diastolic dysfunction grade and global longitudinal strain. In total, 35.5% of patients showed progress in none, 35.5% in one, 29.0% in two and no patient in three domains, the latter indicating overall disease progression. A subgroup analysis of twenty-two patients with available baseline and follow-up CMR data revealed an increase in CMR-based extracellular volume by more than 5% in 18.2% of patients, with no significant correlation with progress in one of the clinical domains. We provide first frequency estimates of the markers of disease progression according to a recent expert consensus statement, which might help refine the multiparametric monitoring concept in patients with ATTR-CM.