Longitudinal Assessment of Left Atrial Remodeling in Patients With Chronic Severe Aortic Regurgitation.

BACKGROUND: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. OBJECTIVES: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. METHODS: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. RESULTS: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. CONCLUSIONS: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters.

Prognostic Power of Quantitative Assessment of Functional Mitral Regurgitation and Myocardial Scar Quantification by Cardiac Magnetic Resonance.

BACKGROUND: The severity classification of functional mitral regurgitation (FMR) remains controversial despite adverse prognosis and rapidly evolving interventions. Furthermore, it is unclear if quantitative assessment with cardiac magnetic resonance can provide incremental risk stratification for patients with ischemic cardiomyopathy (ICM) or non-ICM (NICM) in terms of FMR and late gadolinium enhancement (LGE). We evaluated the impact of quantitative cardiac magnetic resonance parameters on event-free survival separately for ICM and NICM, to assess prognostic FMR thresholds and interactions with LGE quantification. METHODS: Patients (n=1414) undergoing cardiac magnetic resonance for cardiomyopathy (ejection fraction<50%) assessment from April 1, 2001 to December 31, 2017 were evaluated. The primary end point was all-cause death, heart transplant, or left ventricular assist device implantation during follow-up. Multivariable Cox analyses were conducted to determine the impact of FMR, LGE, and their interactions with event-free survival. RESULTS: There were 510 primary end points, 395/782 (50.5%) in ICM and 114/632 (18.0%) in NICM. Mitral regurgitation-fraction per 5% increase was independently associated with the primary end point, hazards ratios (95% CIs) of 1.04 (1.01-1.07; P=0.034) in ICM and 1.09 (1.02-1.16; P=0.011) in NICM. Optimal mitral regurgitation-fraction threshold for moderate and severe FMR were ≥20% and ≥35%, respectively, in both ICM and NICM, based on the prediction of the primary outcome. Similarly, optimal LGE thresholds were ≥5% in ICM and ≥2% in NICM. Mitral regurgitation-fraction×LGE emerged as a significant interaction for the primary end point in ICM (P=0.006), but not in NICM (P=0.971). CONCLUSIONS: Mitral regurgitation-fraction and LGE are key quantitative cardiac magnetic resonance biomarkers with differential associations with adverse outcomes in ICM and NICM. Optimal prognostic thresholds may provide important clinical risk prognostication and may further facilitate the ability to derive selection criteria to guide therapeutic decision-making.

Quantitative Echocardiographic Assessment and Optimal Criteria for Early Intervention in Asymptomatic Tricuspid Regurgitation.

BACKGROUND: Significant tricuspid regurgitation (TR) is associated with poor outcome and high operative mortality resulting from late presentation. Yet, the optimal timing for intervention is unknown. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of echocardiographic parameters to inform early intervention in asymptomatic TR. METHODS: Using the Cleveland Clinic echocardiography database 2004 to 2018, the authors identified a consecutive cohort of asymptomatic patients with moderate to severe (3+) or severe (4+) TR. Quantitative TR and right heart parameters were retrospectively determined, and their prognostic utility for all-cause mortality was assessed. RESULTS: In 325 asymptomatic patients (mean age: 67.9 years; 79.4% female) with at least 3+ TR, there were 132 deaths (40.6%), with a median survival time of 9.9 years (95% CI: 7.9-12.7 years). By contrast, the median survival time in an age- and sex-matched cohort of symptomatic TR patients was 4.4 years (95% CI: 2.8-5.9 years). Among all the echocardiographic parameters evaluated, right ventricle free wall strain (RVFWS) and tricuspid regurgitant volume (RVol) were the strongest predictors of mortality in asymptomatic TR. The optimal discriminatory thresholds for these parameters were RVFWS <-19% and RVol >45 mL. The 5-year survival rates by number of risk factors (RF) were 93% (95% CI: 86%-96%), 65% (95% CI: 55%-74%), and 38% (95% CI: 26%-49%) for no RF, 1 RF, and both RFs, respectively. Compared with symptomatic TR, mortality was lower for asymptomatic TR with no RF (HR: 0.10; 95% CI: 0.04-0.29) or 1 RF (HR: 0.29; 95% CI: 0.14-0.58), but similar for asymptomatic TR with both RFs (HR: 1.11; 95% CI: 0.56-2.19). CONCLUSIONS: RVFWS and RVol are key prognostic markers that can be serially monitored to inform optimal timing of intervention for severe asymptomatic TR.

Left Ventricular Longitudinal Strain in Characterization and Outcome Assessment of Mixed Aortic Valve Disease Phenotypes.

OBJECTIVES: The aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD. BACKGROUND: Little is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes. METHODS: This observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality. RESULTS: Mean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was -14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear. CONCLUSIONS: LV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD.

Reclassification of coronary heart disease risk in a primary prevention setting: traditional risk factor assessment vs. coronary artery calcium scoring.

BACKGROUND: In a primary prevention screening program of asymptomatic middle-aged subjects, we sought to assess the degree of risk-reclassification provided by traditional risk assessment vs. coronary artery calcification scoring (CACS). METHODS: A total of 1,806 consecutive asymptomatic subjects (age 55 years, 76% men), who underwent comprehensive screening in a primary prevention clinic between 3/2016 and 9/2017 were included. Standard risk factors, C-reactive protein (CRP) and CAC scoring were performed. % 10-year coronary heart disease (CHD) risk was calculated using Reynolds Risk Score (RRS), atherosclerotic cardiovascular disease (ASCVD) score and multiethnic study on subclinical atherosclerosis (MESA) CACS were calculated. % 10-year CHD risk for all scores was categorized as follows: <1%, 1-5%, 6-10% and >10%. RESULTS: Mean CRP, RRS, ASCVD and MESA-CACS were 2.1±4.2, 3.7±4, 4.9±6, 4.9±5; 54% had CAC of 0, while 21% had CAC >75th percentile. There was a significant, but modest correlation between MESA-CAC score and (I) RRS (r=0.62) and (II) ASCVD scores (r=0.65, both P<0.001). Compared to MESA-CAC, for RRS, (I) 188 (10%) patients had a downgrade in risk and (II) 538 (30%) patients had an upgrade in risk (40% reclassification of risk). Similarly, compared to MESA-CAC, for ASCVD score, (I) 412 (23%) patients had a downgrade in risk and (II) 329 (18%) patients had a downgrade in risk (41% reclassification of risk). CONCLUSIONS: In a primary prevention screening program of asymptomatic middle-aged patients, RRS overestimates and ASCVHD underestimates 10-year CHD risk vs. MESA-CACS. Addition of CACS results in significant risk reclassification.

Impact of abnormal longitudinal rotation on the assessment of right ventricular systolic function in patients with severe pulmonary hypertension.

BACKGROUND: Assessment of right ventricular (RV) function plays an important role in patients with cardiopulmonary disease, and current guidelines recommend parameters including tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic excursion velocity (RVS') to assess RV longitudinal function. We assessed the hypothesis that the previously undescribed motion of RV longitudinal rotation (RVLR) is an independent predictor of both TAPSE and RVS'. METHODS: We assessed a series of 100 consecutive patients with pulmonary hypertension (PH) undergoing echocardiography. Patients with left ventricular (LV) dilation and dysfunction were excluded. Standard RV parameters were determined using established guidelines, while RVLR and right ventricular global longitudinal strain (RVGLS) measurements were performed using 2-dimensional (2D) speckle tracking technique. RESULTS: Mean peak RVLR measured -4.2±3.7 degrees. By convention, negative values implied clockwise motion. In a multiple linear regression model, TAPSE could be predicted from a combination of RVLR and RVGLS (R=0.56, P<0.001). A similar relationship was found for RVS' which could also be predicted from a combination of RVLR and RVGLS (R=0.52, P<0.001). While no association was found between RVLR and RV size, estimated RV systolic pressure (RVSP) or the presence of a pericardial effusion, a mild correlation was noted between RVLR and QRS duration (R=0.25, P=0.01). CONCLUSIONS: RVLR is an independent predictor of TAPSE and RVS'. Awareness of this motion should be considered in the interpretation of TAPSE and RVS' values as markers of RV systolic function, as abnormal RVLR may account for exaggerated values, particularly in patients with PH and RV dysfunction.

Recognized Obstructive Sleep Apnea is Associated With Improved In-Hospital Outcomes After ST Elevation Myocardial Infarction.

BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for many cardiovascular conditions such as coronary artery disease, myocardial infarction, systemic hypertension, pulmonary hypertension, and stroke. However, the association of OSA with outcomes in patients hospitalized for ST-elevation myocardial infarction remains controversial. METHODS AND RESULTS: We used the nation-wide inpatient sample between 2003 and 2011 to identify patients with a primary discharge diagnosis of ST-elevation myocardial infarction and then used the International Classification of Diseases, Clinical Modification code 327.23 to identify a group of patients with OSA. The primary outcome of interest was in-hospital mortality, and secondary outcomes were in-hospital cardiac arrest, length of stay and hospital charges. Our cohort included 1 850 625 patients with ST-elevation myocardial infarction, of which 1.3% (24 623) had documented OSA. OSA patients were younger and more likely to be male, smokers, and have chronic pulmonary disease, depression, hypertension, known history of coronary artery disease, dyslipidemia, obesity, and renal failure (P<0.001 for all). Patients with OSA had significantly decreased in-hospital mortality (adjusted odds ratio, 0.78 [95% CI, 0.73-0.84]), longer hospital stay (5.00±4.68 versus 4.85±5.96 days), and incurred greater hospital charges ($79 460.12±70 621.91 versus $62 889.91±69 124.15). There was no difference in incidence of in-hospital cardiac arrest (adjusted odds ratio, 0.93 [95% CI, 0.84-1.03]) between these 2 groups. CONCLUSION: ST-elevation myocardial infarction patients with recognized OSA had significantly decreased mortality compared with patients without OSA. Although patients with OSA had longer hospital stays and incurred greater hospital charges, there was no difference in incidence of in-hospital cardiac arrest.

Erratum: Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension.

[This corrects the article on p. 398 in vol. 45, PMID: 26413108.].

Relationship between Right Ventricular Longitudinal Strain, Invasive Hemodynamics, and Functional Assessment in Pulmonary Arterial Hypertension.

BACKGROUND AND OBJECTIVES: Right ventricular longitudinal strain (RVLS) is a new parameter of RV function. We evaluated the relationship of RVLS by speckle-tracking echocardiography with functional and invasive parameters in pulmonary arterial hypertension (PAH) patients. SUBJECTS AND METHODS: Thirty four patients with World Health Organization group 1 PAH (29 females, mean age 45±13 years old). RVLS were analyzed with velocity vector imaging. RESULTS: Patients with advanced symptoms {New York Heart Association (NYHA) functional class III/IV} had impaired RVLS in global RV (RVLSglobal, -17±5 vs. -12±3%, p<0.01) and RV free wall (RVLSFW, -19±5 vs. -14±4%, p<0.01 to NYHA class I/II). Baseline RVLSglobal and RVLSFW showed significant correlation with 6-minute walking distance (r=-0.54 and r=-0.57, p<0.01 respectively) and logarithmic transformation of brain natriuretic peptide concentration (r=0.65 and r=0.65, p<0.01, respectively). These revealed significant correlations with cardiac index (r=-0.50 and r=-0.47, p<0.01, respectively) and pulmonary vascular resistance (PVR, r=0.45 and r=0.45, p=0.01, respectively). During a median follow-up of 33 months, 25 patients (74%) had follow-up examinations. Mean pulmonary arterial pressure (mPAP, 54±13 to 46±16 mmHg, p=0.03) and PVR (11±5 to 6±2 wood units, p<0.01) were significantly decreased with pulmonary vasodilator treatment. RVLSglobal (-12±5 to -16±5%, p<0.01) and RVLSFW (-14±5 to -18±5%, p<0.01) were significantly improved. The decrease of mPAP was significantly correlated with improvement of RVLSglobal (r=0.45, p<0.01) and RVLSFW (r=0.43, p<0.01). The PVR change demonstrated significant correlation with improvement of RVLSglobal (r=0.40, p<0.01). CONCLUSION: RVLS correlates with functional and invasive hemodynamic parameters in PAH patients. Decrease of mPAP and PVR as a result of treatment was associated with improvement of RVLS.

Assessment of Right Ventricular Longitudinal Strain in Patients with Ischemic Cardiomyopathy: Head-to-Head Comparison between Two-Dimensional Speckle-Based Strain and Velocity Vector Imaging Using Volumetric Assessment by Cardiac Magnetic Resonance as a "Gold Standard".

BACKGROUND: Longitudinal strain of right ventricle (RV) can be used to determine RV systolic function. This study compared RV longitudinal strain values of two different speckle tracking software technologies, velocity vector imaging (VVI) and two-dimensional speckle tracking echocardiography (2DSTE), and longitudinal strain by cardiac magnetic resonance (CMR). METHODS: We studied 36 patients (28 men, 63 ± 11 years) with ischemic cardiomyopathy (ICM) who underwent echocardiography with GE machines and CMR. Longitudinal strain of RV analyzed with 2DSTE and VVI in same DICOM files. Longitudinal RV strain analyzed with 2DSTE and VVI in same raw data. These values were compared with RVEF and longitudinal strain by CMR. RESULTS: VVI strain showed significant correlations with RVEF by CMR (global RV: r = -0.56, P < 0.01, free wall: r = -0.52, P < 0.01, and septum: r = -0.49, P < 0.01). 2DSTE strain also revealed significant correlations (global RV: r = -0.40, P = 0.02, and septum: r = -0.35, P = 0.04). 2DSTE strain had significant bias with wide limits of agreement in global RV and septum compared with CMR strain. 2DSTE strain had significantly lower intra-observer variability than VVI (P = 0.03) or CMR strain (P = 0.04) in RV-free wall. CONCLUSIONS: RV longitudinal strains by VVI and 2SDTE demonstrated relatively good correlations with RVEF and longitudinal strain by CMR. However, when compared to CMR-derived strain, 2DSTE-derived strain underestimates longitudinal strain of RV septum and of global right ventricle. 2DSTE strain had significantly lower intra-observer variability compared with VVI or CMR strain analysis.

Significance of aortic valve calcification in patients with low-gradient low-flow aortic stenosis.

BACKGROUND: Assessment of patients with aortic stenosis (AS) and impaired left ventricular function remains challenging. Aortic valve calcium (AVC) scoring with computed tomography (CT) and fluoroscopy has been proposed as means of diagnosing and predicting outcomes in patients with severe AS. HYPOTHESIS: Severity of aortic valve calcification correlates with the diagnosis of true severe AS and outcomes in patients with low-gradient low-flow AS. METHODS: Echocardiography and CT database records from January 1, 2000 to September 26, 2009 were reviewed. Patients with aortic valve area (AVA)<1.0 cm2 who had ejection fraction (EF)≤25% and mean valvular gradient≤25 mmHg with concurrent noncontrast CT scans were included. AVC was evaluated using CT and fluoroscopy. Mortality and aortic valve replacement (AVR) were established using the Social Security Death Index and medical records. The role of surgery in outcomes was evaluated. RESULTS: Fifty-one patients who met the above criteria were included. Mean age was 75.1±9.6 years, and 15 patients were female. Mean EF was 21%±4.6% with AVA of 0.7±0.1 cm2. The peak and mean gradients were 35.5±10.6 and 19.0±5.1 mmHg, respectively. Median aortic valve calcium score was 2027 Agatston units. Mean follow-up was 908 days. Patients with calcium scores above the median value were found to have increased mortality (P=0.02). The benefit of surgery on survival was more pronounced in patients with higher valvular scores (P=0.001). Fluoroscopy scoring led to similar findings, where increased AVC predicted worse outcomes (P=0.04). CONCLUSIONS: In patients with low-gradient low-flow AS, higher valvular calcium score predicts worse long-term mortality. AVR is associated with improved survival in patients with higher valve scores.

Integration of 3D imaging data in the assessment of aortic stenosis: impact on classification of disease severity.

BACKGROUND: In patients with aortic stenosis (AS), precise assessment of severity is critical for treatment decisions. Estimation of aortic valve area (AVA) with transthoracic echocardiographic (TTE)-continuity equation (CE) assumes a circular left ventricular outflow tract (LVOT). We evaluated incremental utility of 3D multidetector computed tomography (MDCT) over TTE assessment of AS severity. METHODS AND RESULTS: We included 51 patients (age, 81±8 years; 61% men; mean gradient, 42 ± 12 mm Hg) with calcific AS who underwent evaluation for treatment options. TTE parameters included systolic LVOT diameter (D) and continuous and pulsed wave (CW and PW) velocity-time integrals (VTI) through the LVOT and mean transaortic gradient. MDCT parameters included systolic LVOT area, ratio of maximal to minimal LVOT diameter (eccentricity index), and aortic planimetry (AVA(p)). TTE-CE AVA [(D(2)×0.786×VTIpw)/VTIcw] and dimensionless index (DI) [VTIpw/VTIcw] were calculated. Corrected AVA was calculated by substituting MDCT LVOT area into CE. The majority (96%) of patients had eccentric LVOT. LVOT area, measured on MDCT, was higher than on TTE (3.84 ± 0.8 cm(2) versus 3.03 ± 0.5 cm(2), P<0.01). TTE-AVA was smaller than AVA(p) and corrected AVA (0.67 ± 0.1cm(2), 0.82 ± 0.3 cm(2), and 0.86 ± 0.3 cm(2), P<0.01). Using TTE measurements alone, 73% of patients had congruence for severe AS (DI ≤0.25 and CE AVA <0.8 cm(2)), which increased to 92% using corrected CE. CONCLUSIONS: In patients with suspected severe AS, incorporation of MDCT-LVOT area into CE improves congruence for AS severity.