Ventricular Volume Index Research Articles

Cardiac-MRI Predicts Clinical Worsening and Mortality in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

ObjectivesThis meta-analysis evaluates assessment of pulmonary arterial hypertension (PAH), with a focus on clinical worsening and mortality. BackgroundCardiac magnetic resonance (CMR) has prognostic value in the assessment of patients with PAH. However, there are limited data on the prediction of clinical worsening, an important composite endpoint used in PAH therapy trials. MethodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science databases were searched in May 2020. All CMR studies assessing clinical worsening and the prognosis of patients with PAH were included. Pooled hazard ratios of univariate regression analyses for CMR measurements, for prediction of clinical worsening and mortality, were calculated. ResultsTwenty-two studies with 1,938 participants were included in the meta-analysis. There were 18 clinical worsening events and 8 deaths per 100 patient-years. The pooled hazard ratios show that every 1% decrease in right ventricular (RV) ejection fraction is associated with a 4.9% increase in the risk of clinical worsening over 22 months of follow-up and a 2.1% increase in the risk of death over 54 months. For every 1 ml/m2 increase in RV end-systolic volume index or RV end-diastolic volume index, the risk of clinical worsening increases by 1.3% and 1%, respectively, and the risk of mortality increases by 0.9% and 0.6%. Every 1 ml/m2 decrease in left ventricular stroke volume index or left ventricular end-diastolic volume index increased the risk of death by 2.5% and 1.8%. Left ventricular parameters were not associated with clinical worsening. ConclusionsThis review confirms CMR as a powerful prognostic marker in PAH in a large cohort of patients. In addition to confirming previous observations that RV function and RV and left ventricular volumes predict mortality, RV function and volumes also predict clinical worsening. This study provides a strong rationale for considering CMR as a clinically relevant endpoint for trials of PAH therapies.

Swollen heart in COVID-19 patients who progress to critical illness: a perspective from echo-cardiologists.

AimsCardiac complications are common and associated with mortality in critically ill patients with COVID‐19; however, the diagnostic and prognostic implications of critical care echocardiography (CCE) have not been studied.Methods and resultsA cohort of 43 patients with COVID‐19 who were in the intensive care unit (ICU) underwent bedside CCE during their disease course. Demographic, clinical, and survival data were collected. The echocardiographic analyses revealed high frequencies of pericardial effusion (90.7%), increased left ventricular mass index (60.5%), elevated relative wall thickness (76.7%), and reduced left ventricular stroke volume index (LVSVi; 53.5%) and cardiac index (51.2%). Twenty‐two (51.2%) patients died in the ICU. In multivariate Cox regression, the strongest predictor of in‐ICU death was decreased cardiac index [hazard ratio (HR), 0.67, 95% confidence interval (CI), 0.45–0.98; P = 0.041], after adjusting for male sex, shock status, high‐sensitivity cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide. Negative associations with mortality were observed for LVSVi (HR, 0.91, 95% CI 0.85–0.96; P = 0.002), tricuspid annular plane systolic excursion (HR, 0.74, 95% CI 0.64–0.84; P < 0.001), and S′ (HR, 0.78, 95% CI 0.69–0.88; P < 0.001). Kaplan–Meier analyses indicated that reductions in LVSVi, cardiac index, TAPSE, and S′ were associated with a shorter survival time.ConclusionsPericardial effusion and increased ventricular mass in COVID‐19 might indicate a swollen heart. Both left and right heart dysfunction and a reduced cardiac index may lead to an increased risk of mortality. Clinicians should pay special attention to cardiac haemodynamic disorders in critical patients with COVID‐19.

High Intensity Resistance Exercise Training vs. High Intensity (Endurance) Interval Training to Fight Cardiometabolic Risk Factors in Overweight Men 30-50 Years Old.

Cardiovascular and cardiometabolic diseases are leading causes of death worldwide. Exercise favorably affects this problem, however only few invest (enough) time to favorably influence cardiometabolic risk-factors and cardiac morphology/performance. Time-effective, high-intensity, low-volume exercise protocols might increase people's commitment to exercise. To date, most research has focused on high-intensity interval training (HIIT), the endurance type of HIT, while corresponding HIT-resistance training protocols (HIT-RT) are rarely evaluated. In this study we compared the effect of HIIT vs. HIT-RT, predominately on cardiometabolic and cardiac parameters in untrained, overweight-obese, middle-aged men. Eligible, untrained men aged 30–50 years old in full-time employment were extracted from two joint exercise studies that randomly assigned participants to a HIIT, HIT-RT or corresponding control group. HIIT predominately consisted of interval training 90 s−12 min, (2–4 sessions/week), HIT-RT (2–3 sessions/week) was applied as a single set resistance training to muscular failure. Core intervention length of both protocols was 16 weeks. Main inclusion criteria were overweight-obese status (BMI 25–35 kg/m2) and full employment (occupational working time: ≥38.5 h/week). Primary study-endpoint was the Metabolic Syndrome (MetS) Z-Score, secondary study-endpoints were ventricular stroke volume index (SVI) and myocardial mass index (MMI) as determined by Magnetic Resonance Imaging. The Intention to treat (ITT) principle was applied to analyze the summarized data set. Twenty-seven eligible men of the HIT-RT and 30 men of the HIIT group were included in the ITT. Both interventions significantly (p < 0.001) improve the MetS Z-Score, however the effect of HIIT was superior (p = 0.049). In parallel, HIT-RT and HIIT significantly affect SVI and MMI, with the effect of HIIT being much more pronounced (p < 0.001). Although HIIT endurance exercise was superior in favorably affecting cardiometabolic risk and particularly cardiac performance, both exercise methods positively affect cardiometabolic risk factors in this overweight to obese, middle-aged cohort of males with low time resources. Thus, the main practical application of our finding might be that in general overweight-obese people can freely choose their preferred exercise type (HIIT-END or HIT-RT) to improve their cardiometabolic health, while investing an amount of time that should be feasible for everybody.Trial Registrations: NCT01406730, NCT01766791.

Paradoxical low-flow phenotype in hospitalized heart failure with preserved ejection fraction

BackgroundLow flow (LF) in heart failure with preserved ejection fraction (HFpEF) is a paradox but is associated with worse prognosis. Determinants of LF in HFpEF have not been clarified but their assessment could corroborate recognition and definition of such a paradoxical condition. MethodsA cohort of 193 patients hospitalized with HFpEF was retrospectively studied and divided in a group with LF (N = 45), defined by a left ventricular (LV) stroke volume index (SVI) < 30 ml/m2, and a group with normal flow (N = 148). A small LV cavity was pre-defined as LV end diastolic diameter index (EDDI) below median values (<25 mm/m2 for males and <26 mm/m2 for females). Right ventricular dysfunction (RVD) was defined as the ratio between tricuspid annular plane systolic excursion and systolic pulmonary artery pressure < 0.36 mm/mmHg. An endpoint of all-cause mortality was evaluated after a median follow-up of 2.4 years. ResultsRVD (OR = 7.4; P < 0.001), atrial fibrillation (AF) during echocardiography (OR = 3.26; P = 0.008), and small LV cavity (OR = 3.81; P = 0.003) were independently associated with LF. After adjusting for age, body mass index, systolic blood pressure, renal function, chronic obstructed pulmonary disease, use of ACE inhibitors/angiotensin receptor blockers, moderate tricuspid regurgitation, RVD), LF was associated with mortality (HR = 3.69; P < 0.001) whereas the combination of the determinants of LF was not. ConclusionParadoxical LF in HFpEF is associated with small LV cavity, AF and RVD. None of the combination of different factors associated with LF could substitute direct assessment of LF status in predicting prognosis in this cohort.

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4±5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1±33.8 vs 165.1±29.1; adjusted P=.007) and wider retinal venular diameter (237.9±42.2 vs 214.9±44.8; adjusted P=.045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β=0.744, P=.031) and for retinal arteriolar diameter and E/e' ratio (adjusted β=-0.158, P=.001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.

Influence of maternal aerobic exercise during pregnancy on fetal cardiac function and outflow

Risk factors for cardiovascular disease, the leading cause of death, have been documented in children as young as 3 years of age. Maternal environment (eg, exercise) influences fetal development and long-term health. Thus, the development of the fetal cardiovascular system during pregnancy is likely a preliminary indicator of cardiac health at birth and a proxy for the future risk of cardiovascular disease throughout life. The purpose of this study was to assess the effects of supervised prenatal aerobic exercise at recommended levels on fetal cardiac function and outflow in the third trimester of pregnancy. We hypothesized that fetuses of aerobically trained women compared with fetuses of nonexercising women would exhibit increased cardiac function and greater cardiac output. Secondary data analyses of a 20-week, randomized controlled exercise intervention trial in pregnant women between 2015 and 2018 in Eastern North Carolina were performed. Eligibility criteria included pregnant women <16 weeks gestation, singleton pregnancy, aged 18-40 years, body mass index of 18.5-34.99 kg/m2, physician clearance letter for exercise participation, reliable transportation, and method of communication. Exclusion criteria included the presence of chronic conditions (eg, type 1 or 2 diabetes mellitus), current medications known to adversely affect fetal growth (eg, antidepressants), alcohol, smoking, or illicit drug use. The patient cohort consisted of 133 eligible pregnant women who were assigned randomly to either an aerobic exercise (n=66) group that participated in 150 minutes of supervised, moderate-intensity (40-59% VO2peak; 12-14 on Borg Rating of Perceived Exertion) aerobic exercise per week or a nonexercising group (n=61) that consisted of 150 minutes per week of light (<40% VO2peak) stretching and relaxation breathing techniques. Between 34 and 36 weeks gestation, a fetal echocardiogram was performed to assess fetal cardiac function, which included fetal heart rate, right- and left-ventricular stroke volume, stroke volume index, cardiac output, cardiac output index, and cardiac outflow that included pulmonary and aortic valve diameters, peak flow velocity, and peak flow velocity-time integral. Fetal activity state (quiet vs active) during the echocardiogram and maternal aerobic capacity served as covariates. Intention-to-treat and per-protocol (participants who attended ≥80% of exercise sessions) analysis of covariance regression models were performed. Of the 127 randomly assigned participants, 66 and 50 participants were included in the intention-to-treat and per-protocol analyses, respectively. Prenatal aerobic exercise significantly increased fetal right-ventricular cardiac measures of right ventricular stroke volume (P=.001) and stroke index via velocity-time integral (P=.003), right ventricular cardiac output (P=.002), cardiac index via velocity-time integral (P=.006), pulmonary artery diameter (P=.02), and pulmonary valve velocity-time integral (P=.03). Only in the intention-to-treat analysis was a significant difference in fetal left ventricular cardiac outflow observed; there was a greater aortic valve peak velocity (P=.04) found among fetuses of aerobically trained pregnant women. No other statistically significant between-group differences were found. The findings of this study demonstrate that participation in prenatal aerobic exercise at recommended levels may improve fetal cardiac function and outflow parameters. Follow-up cardiovascular measures in the postnatal period are needed to determine potential long-term effects on the offspring's cardiac function and outflow.

Prevalence and determinants of elevated D-dimer in patients with hypertrophic cardiomyopathy.

Aim: To evaluate D-dimer levels in patients with hypertrophic cardiomyopathy (HCM). Patients & methods: A total of 346 patients with HCM were recruited. Plasma D-dimer was determined by clinical laboratory of our hospital. Left ventricular mass, stroke volume, cardiac output and cardiac index were assessed with cardiovascular magnetic resonance. Results: A total of 36 (10.4%) patients had elevated D-dimer levels. Age, female patients and statin therapy were independently associated with increasing D-dimer levels, and predictors of elevated D-dimer. Conclusion: Patients with HCM may have higher plasma D-dimer levels than subjects without HCM. D-dimer levels in patients with HCM are influenced by age, sex, atrial fibrillation, statin therapy and diastolic blood pressure.

Cardiac troponin I is associated with non-sustained ventricular tachycardia in patients with hypertrophic obstructive cardiomyopathy.

As highly sensitive and specific markers of myocardial damage, cardiac troponins were demonstrated to correlate with clinical parameters of patients with hypertrophic cardiomyopathy. However, the relationship between cardiac troponins and presence of non-sustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy remains unclear. The aim of our study was to explore the association between serum cardiac troponin I (cTNI) and presence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 309 HOCM patients were enrolled in our study. All participants underwent clinical evaluations, including collections of medical history, blood tests, 24-h Holter monitoring, echocardiography, and cardiac magnetic resonance imaging. There were 53 (17.2%) patients with NSVT and 256 patients without it. Compared to patients without NSVT, serum cTNI (P < 0.001) and plasma NT-proBNP (P = 0.042) were significantly higher in patients with NSVT. Moreover, cTNI and NT-proBNP were positively correlated with left atrial diameter, maximum wall thickness (MWT), left ventricular volume index and left ventricular mass index. In multivariable logistic analysis, log cTNI [odds ratio (OR) = 2.408, 95% confidence interval (CI) 1.108-5.325, P = 0.027], left ventricular end-diastole diameter (OR = 0.922, 95%CI 0.856-0.994, P = 0.034), MWT (OR = 1.131, 95%CI 1.035-1.235, P = 0.006) and left ventricular end-systole volume index (OR = 1.060, 95%CI 1.025-1.096, P = 0.001) were independent determinants of NSVT occurrence after adjustment for potential cofounders. Serum cTNI level was elevated in patients with NSVT. And it was independently associated with NSVT in patients with HOCM. Our results suggest that it may be more reasonable for HOCM patients with elevated serum cTNI to extend the time of Holter monitoring.

Efficacy and Safety of Shengmai Injection for Chronic Heart Failure: A Systematic Review of Randomized Controlled Trials.

Background Shengmai injection (SMI) is made from purified ginseng, Radix Ophiopogonis, and Schisandra chinensis. It has cardiotonic effects and is clinically used for the adjuvant treatment of chronic heart failure (CHF). However, its efficacy and safety are uncertain. The purpose of this study was to systematically evaluate the existing efficacy and safety evidence in randomized controlled trials (RCTs) that studied SMI for the treatment of CHF. Methods PubMed, Embase, Cochrane Library, clinicaltrials.gov, CNKI, Wanfang, VIP, and CBM databases were searched up to September 10, 2019. RCTs that compared basic Western medicine treatment with SMI + basic Western medicine were included. The Cochrane Collaboration Risk of Bias Tool was used to assess the risk of bias in the RCTs. The meta-analysis used the random effects model; the mean difference (MD) and 95% confidence intervals (CIs) were combined using the inverse variance method, and the Mantel–Haenszel method was used to combine the relative risk (RR) and 95% CIs. Heterogeneity was assessed using I2 and Q tests, and the source of heterogeneity was explored by analyzing three preset subgroup hypotheses. Results A total of 20 RCTs were included (n = 1562), with a moderate-to-high risk of bias. The meta-analysis showed that, compared with Western medicine alone, SMI adjuvant therapy significantly improved cardiac function indicators, including left ventricular ejection fraction (MD 6.8%, 95% CI 4.68 to 8.91), stroke volume (MD 9.81 ml, 95% CI 5.67 to 13.96), cardiac output (MD 0.96 L/min, 95% CI 0.66 to 1.25), and cardiac index (MD 0.53 L/min, 95% CI 0.36 to 0.70); heterogeneity was generally high among these outcomes. Compared with the controls, patients receiving SMI adjuvant therapy also had a higher response to treatment (RR 2.89, 95% CI 2.10 to 3.99; I2 = 0%), a greater decrease in brain natriuretic peptide levels (MD −284.66 ng/l, 95% CI −353.73 to −215.59, I2 = 0%), and a greater increase in six‐minute walk test performance (MD 70.67 m, 95% CI 22.92 to 118.42; I2 = 84%). Nine studies reported mild adverse events, such as gastrointestinal reactions, and no serious adverse events were reported. Conclusion Currently, available evidence indicates that SMI, as an adjuvant for basic Western medicine treatment, can improve the cardiac function of patients with CHF with good safety outcomes. Because of the high risk of bias among the included RCTs and the large heterogeneity of partial outcomes, the findings of this study must be verified by high-quality studies with large sample sizes.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in myocardial and skeletal muscles in idiopathic inflammatory cardiomyopathy

BackgroundIdiopathic inflammatory myopathy (IIM) manifest as systematic muscle involvement. Multiparametric cardiovascular magnetic resonance (CMR) could be a useful technique to detect systemic involvement and disease progression in IIM patients. This study aimed to describe the tissue characteristics and dynamic changes in myocardial and skeletal muscles after treatment in IIM patients.MethodsForty-four consecutively recruited IIM patients (49.0 ± 12.0 years; 22 males) underwent 3 T CMR at first diagnosis, and 28 patients underwent follow-up scan after receiving standard treatment for more than 1 year. Thirty age- and sex-matched healthy subjects served as controls. The CMR protocol included: cines, T2-weighted (T2w), late gadolinium enhancement (LGE), T1 and T2 mapping, and extracellular volume (ECV) evaluated for the myocardium, and T1 and T2 mapping and ECV evaluated for skeletal muscles. Correlations between laboratory biomarkers and myocardial and skeletal tissue characteristics were analyzed. Comparisons between baseline and follow-up scans were performed using paired t-tests.ResultsAt baseline, IIM patients showed significantly decreased hematocrit, higher left ventricular (LV) mass index, right ventricular (RV) volume index, myocardial and skeletal native T1, T2 mapping, and ECV than healthy controls. Significant correlations were found among myocardial native T1, T2 mapping, and ECV values and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels, and significant correlations between skeletal T2 mapping and inflammatory biomarkers in IIM patients.During the follow-up, 28 patients underwent repeated CMR scan (median interval, 14.5 months, interquartile range: 13.2–15.5 months). Significant relief from clinical symptoms and decreased inflammatory biomarkers levels were observed. Significant reduction in myocardial native T1, T2, ECV, and skeletal native T1, T2, and ECV were observed during the follow-up assessment.ConclusionsBoth myocardial and skeletal muscles in newly diagnosed IIM patients show distinct characteristics on multiparametric CMR. In addition, significant changes were observed in patients showing clinical remission after effective treatment, which suggests that quantitative T1, T2, and ECV techniques may have potential clinical value in IIM patients.

Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease

AbstractCardiac complications have been well-described in sickle cell disease; however, it has been rare to see improvements in cardiac abnormalities following any interventions. Previous work has shown no significant structural changes after treatment with hydroxyurea. The cardiac effects of red blood cell exchange transfusion (RBCx) and hematopoietic stem cell transplantation (HSCT) have not been well described. We studied 56 patients undergoing HSCT (41 HLA-matched, 15 haploidentical), of whom 32 had RBCx within 3 months before HSCT. Echocardiograms and laboratory parameters were obtained at baseline, and at 3, 6, and 12 months following HSCT. Although hemolytic parameters and anemia improved following RBCx, there was a small increase in left ventricular volume index. Following successful HSCT, however, there were significant improvements in cardiac size, function, and diastolic filling parameters at 3 months followed by continued smaller improvements up to 1 year. There was a significant improvement in N-terminal pro B-type natriuretic peptide levels and a trend toward improvement in 6-minute walk time 1 year after HSCT. The magnitude of cardiac improvement seen following HSCT was comparable to that observed following correction of a volume overload state as seen in pregnancy or after repair of chronic valvular regurgitation. Further studies in sickle cell disease patients will help delineate which cardiac complications and what level of severity should be considered indications for HSCT.

P2445Prognostic values of left ventricular reservoir functional indices measured by three dimensional speckle tracking analysis

Abstract Background Left atrial functional indices measured by two dimensional echocardiography (2DE) have prognostic significance for major cardiovascular events (MACE). Retrospective analysis using propensity score matching to assess the prognostic values of left atrial reservoir function measured by three dimensional speckle tracking analysis (3DSTA) was performed. Methods Two hundred sixty-four patients (Male 60%, 65±15yo) who underwent both clinically indicated 2DE and 3DSTA for various underlying heart diseases from January 4, 2013 to February 28, 2016 were followed to record MACE. Patients with significant mitral valve disease, history of pulmonary vein isolation and persistent atrial fibrillation were excluded. Maximum and minimum left atrial volume (LAVImax and LAVImin), left atrial emptying fraction (LAEmpF), peak global LA area ratio (LAAC), circumferential strain (LACS) and longitudinal strain (LALS) were measured using 3DSTA. Standard indices including peak global LVLS (2DLVLS) and left ventricular ejection fraction (LVEF) and LA volume index were also assessed by 2DE. Cutoff line for LA reservoir functional indices and 2DLVLS was determined using ROC analysis. Average treatment effect for the treated (ATT), Average treatment effect (ATE) for each index were calculated after propensity score matching for clinical indices (age, sex, coronary artery disease, hypertension, diabetes, eGFR &lt;45 ml/min/1.73m2, LVEF &lt;40%) Results During a mean follow-up of 547±435 days, MACE developed in 30 patients (7 cardiac death 6 stroke, 1 nonfatal MI, 22 admission for heart failure). Age, coronary artery disease (CAD), diabetes mellitus (DM), chronic kidney disease (CKD: eGFR&lt; 45ml/min/1.73m2), LVEF, 2DLVLS, LAVImax and LAVImin by 2DE and all LA indices by 3DSTA had significant prognostic value by univariate analysis. LAEmpF and LALS by 3DSTA had higher ATT, ATE and Log rank χ2 than other LA indices and 2DLVLS. The model added LALS or LAEmpF by 3DSTA had higher prognostic value (LALS &lt;10.6%: AUC; 0.82, HR; 5.57 CI: 2.32–14.06, LAEmpF &lt;33.0%: AUC; 0.82, HR; 6.59 CI; 2.60–20.18) than LA volume indices by 2DE and also tended to be better than 2DLVLS (LVLS &lt;6.04%: AUC; 0.77, HR; 5.37 CI; 2.06–13.73). propensity score matching Conclusion LALS and LAEmpF by 3DSTA showed additive prognostic value for MACE.

6098The role of diastolic function in risk stratification of patients with moderate aortic stenosis

Abstract Background Currently data on the risk stratification of patients with moderate aortic stenosis (AS) are very limited. Method Patients diagnosed with moderate AS in 2012 (aortic valve area [AVA]: &gt;1 and ≤1.5cm2) were identified. Patients were stratifying by LV diastolic function (normal vs high filling pressure), left ventricular ejection fraction (LVEF ≥50 vs &lt;50%) and stroke volume index (SVI ≥35 vs &lt;35 ml/m2). High filling pressure was defined as average E/e' ≥14 or septal E/e' ≥11 when atrial fibrillation was present. The prognosis was compared to age- and sex-matched general population. Results 898 patients were included (age 74 years, 58% male, AVA 1.25 cm2). During a median follow-up of 2.9 years, there were 346 deaths. In patients with moderate AS, mortality was higher than expected (P&lt;0.001, Fig 1A). LV high filling pressure, LVEF&lt;50% and SVI&lt;35ml/m2 were present in 416 (55%), 140 (17%) and 81 (9%) patients, respectively. Those with normal filling pressure had similar prognosis when compared to controls (Fig 1C, P=0.35); whereas mortality rates remained higher than reference even when LVEF≥50% or SVI≥35ml/m2 (Fig 1E, 1G, P&lt;0.001). Amongst all groups, mortality rates were the highest in patients with LVEF &lt;50% or SVI &lt;35 ml/m2 (Fig 1D, 1F, P&lt;0.001); mortality ratios were 3.78 (95% CI 3.01–4.67) and 6.91 (95% CI 5.13–9.11), respectively. Noteworthy, high filling pressure allowed further risk stratification when LVEF or SVI was preserved (Fig 2, P&lt;0.001). Figures 1 &amp; 2 Conclusions Patients with moderate AS showed poor survival. A clinical trial examining role of aortic valve replacement would be beneficial not only in patients with reduced LVEF or SVI but also in those with high LV filling pressures.

Assessment of the Left Ventricular-Arterial Coupling: A More Reasonable Method.

To the Editor: We read with great interest the article by Li et al. recently published in Shock(1) which investigated the performance of left ventricular–arterial coupling (VAC) in septic shock patients who are unresponsive to fluid administration. As described in the article (1), the formula for calculating the effective arterial elastance (Ea), left ventricular (LV) end-systolic elastance (Ees), and VAC (defined as Ea/Ees) is shown as follows: Ea = ESP/SV, Ees = ESP/(ESV-V0), and VAC = (ESV-V0)/SV, where V0 was defined as the volume axis intercept of the end-systolic pressure–volume relationship (see the Figure 1 in the article (1), ESP represents end-systolic pressure of ventricular, ESV represents end-systolic volume of ventricular, and SV represents stroke volume). We respectfully disagreed with the method applied in this study for evaluating the VAC because the abovementioned approximated calculations are unreliable and may overestimate the actual value measured by the invasive method. First, to simplify the formula for calculation, the authors made a simple assumption that the V0 is negligible. Indeed, the parameter V0 is, theoretically, near to 0 when the heart load is in the physiologic range (2, 3). However, in some case, particularly in cardiac dysfunction, the V0 is not equal to 0 and should not be neglected. A study by Ky et al. (4) revealed a median V0 of 43 mL (interquartile range: −2.6 mL to 113 mL) for patients with chronic systolic heart failure, and the V0 was positively associated with the New York Heart Association (NYHA) functional class (ρ = 0.31; P < 0.001), indicating that the worse the cardiac function, the greater the V0. In the study by Li et al. (1), we can guess that the patients included in this study had a cardiac dysfunction according to the data regarding the global end-diastolic ventricular volume index (GEDVI) and stroke volume index (SVI), despite a normal cardiac index. Hence, roughly neglecting the V0 in this study would, inevitably, result in an overestimation of the true VAC. Second, the ratio ESP/ESV was used to calculate Ees by Li et al (1); however, this formula was proven as a suboptimal method for estimating Ees in the study by Chen et al. (5). Chen et al. found that the approximately calculated Ees (ESP/ESV) was not well correlated with the invasively measured Ees (y = 0.18x + 0.69; r = 0.56, P < 0.001), and the residuals of the calculated Ees to the invasively measured Ees were significantly different from 0, averaging 2.2 mmHg/mL (5). Meanwhile, a novel method, named the “single-beat” method, was proposed by Chen et al. (5) to estimate Ees; this method was validated as more well correlated with the invasively measured Ees (y = 0.78x + 0.55; r = 0.81, P < 0.0001) compared with the ratio ESP/ESV. Importantly, the “single-beat” method just requires several parameters that can be noninvasively measured by echocardiography; it thus seems to be more reasonable and suitable for evaluating Ees and VAC in critically ill patients. Lastly, the authors (1) used the arterial systolic pressure (ASP) of the femoral artery to represent the LV ESP; this method for assessing LV ESP is also not reasonable. The invasive method using LV catheterization is the “gold-standard” for the assessment of LV ESP; however, it is an unrealistic practice in the intensive care unit at present. Alternatively, the researchers have commonly used the mean aortic pressure (MAP) (3, 6) and 90% of the ASP (7, 8) as surrogate for LV ESP, and the ratio of MAP/SV was confirmed as a robust surrogate for Ea and is interchangeably in any peripheral artery (9). Therefore, this unreasonable approximation for LV ESP used in this study (1) may also lead to an overestimation of Ea and VAC. Overall, the inappropriate method for assessing the Ea, Ees, and VAC will downgrade the credibility of their evidence to some extent.

Estimated Ventricular Size, Asthma Severity, and Exacerbations: The Severe Asthma Research Program III Cohort

Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size. We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression. Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1mL/m2 smaller eETVVI than healthy control subjects (P= .003) and 14.1mL/m2 smaller eETVVI than those with mild/moderate disease (P= .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57%higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P= .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations. In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations. ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov.

Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy.

Aims The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM.Methods and results We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73–0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06–3.68; P = 0.03).Conclusion PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.

Correlation between the left atrial low-voltage area and the cardiac function improvement after catheter ablation for paroxysmal atrial fibrillation.

BackgroundThe impact of the left atrial low‐voltage area (LVA) on the cardiac function improvement following ablation for atrial fibrillation (AF) is unclear.MethodsIn 49 patients with paroxysmal AF who underwent ablation, the left ventricular stroke volume index (SVI) was repeatedly measured using an impedance cardiography until 6 months after ablation. We defined the cardiac function improvement as a 20% increase in the SVI. The LVA (the area with the voltage amplitude of <0.5 mV) was assessed before ablation.ResultsThe reduced baseline SVI (<33 mL/m2) was observed in 18 (37%) patients. The SVI increased following ablation (from 36 ± 5 to 39 ± 6 mL/m2, P < .001). We observed the cardiac function improvement in 14 (29%) patients. The LVA was smaller in patients with the improved cardiac function than in those without (8.3% ± 5.2% vs 14.0% ± 8.5%, P = .026). The multivariate analysis revealed that only the LVA was independently associated with the cardiac function improvement (odds ratio, 0.878; 95% confidence interval: 0.778‐0.991, P = .036). Furthermore, LVAs of the anterior (7.9% ± 7.6% vs 18.2% ± 15.5%, P = .022), septal (12.0 ± 7.3% vs 20.7% ± 13.8%, P = .031), and roof walls (6.9% ± 6.0% vs 16.9% ± 15.2%, P = .022) were smaller in patients with the improved cardiac function than in those without.ConclusionsThe LVA was related to the cardiac function improvement following ablation in patients with paroxysmal AF.

SAT-021 AGING, STRUCTURAL HEART DISEASE, AND SURVIVAL AMONG INCIDENT, MAINTENANCE HEMODIALYSIS PATIENTS

Abnormal echocardiogram (ECHO) findings are common in hemodialysis (HD) patients, and many of these structural heart disease (SHD) characteristics including biventricular dysfunction are strong predictors of mortality. It is uncertain how the effect of aging plays a role in the presence of SHD findings among incident chronic HD patients. Our aim was to determine the prevalence of SHD among incident HD patients in different age cohorts and the impact of these SHD characteristics on survival. We performed a retrospective cohort study including adults (≥18 years old) who initiated HD for at least thirty days and received an ECHO around the time of HD initiation between January 1st, 2001 to December 31st, 2013 with followup until March 31st, 2018. We determined the prevalence of SHD characteristics among four age groups: <55, 55-64, 65-74, and ≥75. SHD was defined by the presence of at least one of the following: ejection fraction (EF) <45%, any right ventricular (RV) dysfunction, diastolic dysfunction, left ventricular hypertrophy (LVH), increased left ventricular (LV) volume index, aortic/mitral valve disease, left atrial enlargement (LAE), and regional wall motion abnormalities (RWMA). We assessed the cumulative incidence of mortality among these age groups while accounting for the competing risk of kidney transplantation. Finally, we determined the association of SHD with mortality by age group using Cox proportional hazards modeling. A total of 654 patients met inclusion criteria during the study period. The patient age distribution was 154 (23%) age <55, 121 (19%) age 55-64, 161 (25%) age 65-74, and 218 (33%) age ≥75. The prevalence of coronary artery disease (range 32% for age <55 vs 72% ≥75) and heart failure (range 35% for age <55 vs 67% ≥75) were more likely with increasing age (trend p-value <0.001 for both). There was no difference in dialysis duration, sex, BMI, or the presence of diabetes. The majority of patients had at least 1 SHD finding ranging from 75% to 93% in those <55 and ≥ 75 years old, respectively. SHD findings were more common with increasing age (Table 1) including EF <45%, RV dysfunction, aortic/mitral valve disease, LAE and RWMA (trend p-value <0.001 for all). There was no difference in the presence of diastolic dysfunction, LVH, or increased LV volume index. The incidence of all-cause mortality was much lower in the youngest vs older age groups (Figure 1).Cox proportional hazards modeling was performed in three age groups <65, 65-74, and ≥75; patients <55 and 55-64 were combined given the relatively low event rate in those age <55 (potentially contributed to by kidney transplantation). RV dysfunction was a significant predictor of mortality in all age groups (Table 2). EF was a significant predictor in patients ≥65 but not those age <65. LVH was unexpectedly associated with decreased mortality in patients <65.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT) SHD is common even in the youngest incident HD patients. In general, the prevalence of SHD abnormalities increases with age except diastolic dysfunction, LVH, or increased LV volume index. RV dysfunction is a strong predictor of mortality among all age groups, while other SHD characteristics including EF and LVH differ in their impact on survival.

A Multi-Trait Approach Identified Genetic Variants Including a Rare Mutation in RGS3 with Impact on Abnormalities of Cardiac Structure/Function

Heart failure is a major cause for premature death. Given the heterogeneity of the heart failure syndrome, identifying genetic determinants of cardiac function and structure may provide greater insights into heart failure. Despite progress in understanding the genetic basis of heart failure through genome wide association studies, the heritability of heart failure is not well understood. Gaining further insights into mechanisms that contribute to heart failure requires systematic approaches that go beyond single trait analysis. We integrated a Bayesian multi-trait approach and a Bayesian networks for the analysis of 10 correlated traits of cardiac structure and function measured across 3387 individuals with whole exome sequence data. While using single-trait based approaches did not find any significant genetic variant, applying the integrative Bayesian multi-trait approach, we identified 3 novel variants located in genes, RGS3, CHD3, and MRPL38 with significant impact on the cardiac traits such as left ventricular volume index, parasternal long axis interventricular septum thickness, and mean left ventricular wall thickness. Among these, the rare variant NC_000009.11:g.116346115C > A (rs144636307) in RGS3 showed pleiotropic effect on left ventricular mass index, left ventricular volume index and maximal left atrial anterior-posterior diameter while RGS3 can inhibit TGF-beta signaling associated with left ventricle dilation and systolic dysfunction.

The relation of left ventricular geometry to left ventricular outflow tract shape and stroke volume index calculations.

Stroke volume (SV) and aortic valve area calculations require the left ventricular (LV) outflow tract (LVOT) or aortic annular area calculations that involve squaring the respective diameters. Area calculation errors became evident with transcatheter aortic valve replacement where areas were underestimated due to an elliptical annulus. We hypothesized that LVOT and annular shape are more elliptical in patients with greater relative LV wall thickness (RWT) leading to underestimation of SV index using 2D Doppler echocardiography. We studied 203 consecutive patients referred to an outpatient noninvasive laboratory for Doppler echocardiograms which included acceptable 3-dimensional images. 3-dimensional assessment of the LVOT at 3-5mm from the valve insertion, at the site of valve insertion, and at the sinus of Valsalva (SOV) was performed with assessment of the minor axis (MN), major axis (MJ), and areas at mid-systole. SV index was calculated from LVOT and annular diameters obtained from 2-dimensional echo and from 3-dimensional LVOT areas. An inverse relation of RWT with MN/MJ at mid-systole for the LVOT (r=0.5812, P<0.0001) and annulus (r=0.6865, P<0.0001) was noted. LVOT and annulus areas were similar among groups at mid-systole. SV index calculated from 2D LVOT dimensions was significantly smaller than using 3D LVOT areas (35.6±8.9 vs 53.6±16.1mL, P<0.0001). There is an inverse relation between MN/MJ and RWT at the LVOT and aortic annulus despite the LVOT and annular areas being similar across most geometries resulting in SV index underestimation calculated using LVOT diameters vs 3D LVOT areas.