Circumferential End-systolic Stress Research Articles

Impaired Left Ventricular Circumferential Midwall Systolic Performance Appears Linked to Depressed Preload, but Not Intrinsic Contractile Dysfunction or Excessive Afterload, in Paradoxical Low-Flow/Low-Gradient Severe Aortic Stenosis.

Paradoxical low-flow/low-gradient aortic stenosis (P-LFLG-AS) occurs in about one-third of patients with severe AS and preserved left ventricular (LV) ejection fraction (EF). Our aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS. We retrospectively analyzed medical records of patients with isolated severe degenerative AS and preserved EF (30 subjects with P-LFLG-AS and 30 patients with normal-flow/high-gradient severe AS (NFHG-AS)), without relevant coexistent diseases (e.g., diabetes, coronary artery disease and chronic kidney disease) or any abnormalities which could account for a low-flow state. Patients with P-LFLG-AS and NFHG-AS did not differ in aortic valve area index and most clinical characteristics. Compared to NFHG-AS, subjects with P-LFLG-AS exhibited smaller LV end-diastolic diameter (LVd) (44 ± 5 vs. 54 ± 5 mm, p < 0.001) (consistent with lower LV preload) with pronounced concentric remodeling, higher valvulo-arterial impedance (3.8 ± 1.1 vs. 2.2 ± 0.5 mmHg per mL/m2, p < 0.001) and diminished systemic arterial compliance (0.45 ± 0.11 vs. 0.76 ± 0.23 mL/m2 per mmHg, p < 0.001), while circumferential end-systolic LV midwall stress (cESS), an estimate of afterload at the LV level, was similar in P-LFLG-AS and NFHG-AS (175 ± 83 vs. 198 ± 69 hPa, p = 0.3). LV midwall fractional shortening (mwFS) was depressed in P-LFLG-AS vs. NFHG-AS (12.3 ± 3.5 vs. 14.7 ± 2.9%, p = 0.006) despite similar EF (61 ± 6 vs. 59 ± 8%, p = 0.4). By multiple regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS upon adjustment for cESS (β ± SEM: −2.35 ± 0.67, p < 0.001); however, the significance was lost after further correction for LVd (β = −1.10 ± 0.85, p = 0.21). In conclusion, the association of P-LFLG-AS with a lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank–Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS.

Interrelation between midwall mechanics and longitudinal strain in newly diagnosed and never-treated hypertensive patients without clinically defined hypertrophy.

In hypertensive patients, an impairment of midwall myocardial mechanics was described in presence of left ventricular (LV) concentric geometry. Under these circumstances, also LV longitudinal dysfunction was found. Our aim was to evaluate longitudinal and circumferential systolic function and correlations between these two functional components in newly diagnosed hypertensive patients without clinically defined LV hypertrophy (LVH). One hundred and thirty-eight newly diagnosed, never-treated hypertensive patients without LVH and a control group of 105 healthy normotensive individuals underwent two-dimensional and speckle tracking echocardiography. Global longitudinal strain (GLS) was derived (in absolute value) and midwall fractional shortening (MFS) computed. In addition, the hypertensive population was divided into two groups according to GLS: normal GLS (≥20%, n = 94) and reduced GLS (<20%, n = 44). Hypertensive patients had lower MFS (P < 0.001) and GLS (P < 0.0001) than healthy controls. By dividing hypertensive patients according to GLS thresholds of normalcy, MFS was lower in patients with GLS less than 20% (P < 0.0001) while no significant difference was found in LV geometry, ejection fraction and diastolic parameters in comparison with patients with GLS at least 20%. In the pooled hypertensive population, GLS resulted positively related to MFS (r = 0.33, P < 0.0001). By a multiple linear regression analysis, after adjusting for female sex, age, BMI, circumferential end-systolic stress, average e', ejection fraction and relative wall thickness, MFS remained independently associated with GLS (β = 0.222, P < 0.005). In newly diagnosed and never-treated hypertensive patients without LVH, an early LV systolic dysfunction is testified by the reduction of both MFS and GLS. These two parameters resulted independently associated after adjusting for several confounders.

Relationship Between Myocardial Energy Expenditure and Postoperative Ejection Fraction in Patients with Severe Mitral Regurgitation

Objective:This prospective study aimed to investigate the myocardial energy metabolism in severe mitral regurgitation (MR) and explore its effect on postoperative differentiation of ejection fraction (EF).Methods:A total of 85 patients with severe MR were prospectively enrolled from October 2018 to June 2019. During the study period, a total of 50 patients underwent mitral valve surgery and 49 patients were finally enrolled due to 1 missing data. Left ventricular function, circumferential end-systolic stress (cESS), and myocardial energy expenditure (MEE) were measured by transthoracic echocardiography preoperatively and 3 months after surgery. Patients were divided into 2 groups according to absolute difference of postoperative differentiation of EF.Results:Nine patients underwent mitral valve repair and 40 underwent prosthetic valve replacement. Patients with reduced EF had higher MEE demonstrated with cESS and MEE. Negative correlation between preoperative EF and N-terminal pro-brain natriuretic peptide (NT-proBNP), cESS, MEEs, and MEEm and positive correlation between preoperative EF and effective regurgitant orifice area were found. Complications occurred in 12 patients during hospitalization. Basal NT-proBNP, left atrium (LA), and cESS were significantly higher in postoperatively decreased EF group. Taking into consideration the covariates of multiple logistic regression analysis, LA and cESS were found to be independent predictors of EF reduction postoperatively.Conclusion:Higher LA and cESS are independent predictors of postoperative EF reduction. Preoperative high end-systolic stress could predict postoperative EF reduction and hence could be helpful for determining the timing of mitral valve surgery. Although MEE was higher in postoperatively decreased EF group, it did not reach statistical significance.

Better Myocardial Function in Aortic Stenosis with Low Left Ventricular Mass: A Mechanism of Protection against Heart Failure Regardless of Stenosis Severity?

About one-tenth to one-third of patients with severe aortic stenosis (AS) do not develop left ventricular hypertrophy (LVH). Intriguingly, the absence of LVH despite severe AS is associated with lower prevalence of heart failure (HF), which challenges the classical notion of LVH as a beneficial compensatory response. Notably, the few studies that have attempted to characterize AS subjects with inadequately low left ventricular (LV) mass relative to LV afterload (i-lowLVM) described better prognosis and enhanced LV performance in AS associated with i-lowLVM, but those reports were limited to severe AS. Our aim was to compare myocardial function between moderate and severe AS with i-lowLVM. We retrospectively analyzed in-hospital records of 225 clinically stable nondiabetic patients with isolated moderate or severe degenerative AS in sinus rhythm, free of coexistent diseases. Subjects with i-lowLVM were compared to those with appropriate or excessive LVM (a/e-LVM), defined on the basis of the ratio of a measured LVM to the LVM predicted from an individual hemodynamic load. Patients with i-lowLVM and a/e-LVM did not differ in aortic valve area, LV end-diastolic diameter (LVd, a measure of LV preload), and circumferential end-systolic LV wall stress (cESS), an estimate of LV afterload. Compared to a/e-LVM, patients with i-lowLVM had increased LV ejection fraction (EF) and especially higher LV midwall fractional shortening (a better index of LV myocardial function than EF in concentric LV geometry) (p < 0.001–0.01), in both moderate and severe AS. LVd and cESS were similar in the four subgroups of the study subjects, i.e., moderate AS with i-lowLVM, moderate AS with a/e-LVM, severe AS with i-lowLVM, and severe AS with a/e-LVM (p > 0.6). Among patients with i-lowLVM, LVM did not differ significantly between moderate and severe AS (p > 0.4), while in those with a/e-LVM, LVM was increased in severe versus moderate AS (p < 0.001). In conclusion, the association of the low-LVM phenotype with better myocardial contractility may already develop in moderate AS. Additionally, cESS appears to be a controlled variable, which is kept constant over AS progression irrespective of LVM category, but even when controlled (by increasing LVM), is not able to prevent deterioration of LV function. Whether improved myocardial performance contributes to favorable prognosis and the preventive effect against HF in AS without LVH, remains to be studied.

P3779NT-proBNP adds incremental predictive information on incident atrial fibrillation in patients with asymptomatic aortic stenosis

Abstract Background Incident atrial fibrillation (AF) marks an adverse shift in the prognosis of patients with aortic stenosis (AS). Identifying risk factors for AF is therefore of paramount importance for timely intervention in patients with AS. In patients without AS, brain natriuretic peptides (BNP) is a well-established biomarker for left ventricular pressure overload on the pathway to heart failure and atrial fibrillation. However, a potential role of NT-proBNP to predict risk of new-onset AF in asymptomatic patients with mild to moderate AS is not well studied. Methods We included 1,434 patients with mild to moderate AS from the SEAS Study (Simvastatin and Ezetimibe in Aortic Stenosis) without AF or clinically overt heart failure at baseline. The primary endpoint for this substudy was time to incident AF, as determined by the first annual in-study 12-lead ECG with AF. Multivariable Cox model were adjusted for other important predictors of incident AF as selected by Bayesian statistics. Fine and Gray competing risk regression was used to evaluate the influence of all-cause mortality on selected predictor variables of incident AF. Results During a median follow-up of 4.3 years (range 0.1–6.9 years), incident AF occurred in 114 (6.1%) patients (13.8 per 1,000 person-years of follow-up), who at baseline were older (69±10 vs. 67±10 years, p&lt;0.001), had larger systolic left atrial diameter (46±24 vs. 34±18 mm, p&lt;0.001) and higher NT-proBNP level (286 [132; 613] vs. 154 [82; 297] pg/ml, p&lt;0.001); but same left ventricular ejection fraction (66±6 mm vs. 67±6, p=0.4). In multivariable Cox regression, adjusted for age, circumferential end-systolic stress, left atrial volume and ECG PR interval, Ln(NT-proBNP) was associated with higher risk of new-onset AF (HR: 1.9 [95% CI: 1.6–2.3], p&lt;0.001). Similar results were found when using Fine and Gray estimates with all-cause mortality (HR: 2.0 [95% CI: 1.7–2.4], p&lt;0.001 (Figure, panel A). NT-proBNP level added incremental predictive information on incident AF over the other important, as selected by Bayesian statistics, predictor variables (C-index 0.81, p&lt;0.001, Figure, panel B). There was no interaction with aortic valve area (p&gt;0.05). Figure 1 Conclusions In patients with asymptomatic aortic stenosis and sinus rhythm at baseline, NT-proBNP levels were significantly higher in patients who subsequently developed AF. NT-proBNP significantly improved prognostic information of incident AF over other important predictor variables. This supports the notion that incident AF is a marker of left ventricular pressure overload and possibly a novel marker of timely intervention with aortic valve replacement.

Low Left Ventricular Mass in Aortic Stenosis: A Distinct Mode of Adaptation to Pressure Overload Associated with Better Contractility?

Introduction About 10-30% of patients with severe aortic stenosis (AS) do not develop left ventricular hypertrophy (LVH). Intriguingly, the absence of LVH does not adversely affect outcome in AS, which challenges the classical notion of LVH as a beneficial compensatory response. Notably, only a few studies have attempted to characterize AS subjects with inadequately low LV mass (low-LVM) relative to afterload. We hypothesized that the low-LVM phenotype may be linked to myocardial function irrespective of AS severity. Aim: To assess relations between LV myocardial function and load in patients with low-LVM and moderate or severe AS. Methods We retrospectively analyzed hospital records of 227 patients with moderate or severe degenerative AS in sinus rhythm. Subjects with low-LVM were compared to those with appropriate or excessive LVM (ae-LVM), defined on the basis of the ratio of a measured LVM to the LVM predicted from an individual hemodynamic load. Circumferential end-systolic LV wall stress (cESS) and valvulo-arterial impedance (Zva), indices of LV afterload, were calculated from echocardiography and blood pressure. Assuming a constant LV wall volume during the cardiac cycle, we also computed LV midwall fractional shortening (mwFS), a better estimate of LV myocardial function than EF in concentric LV geometry. Results Patients with low-LVM and ae-LVM did not differ in aortic valve area, blood pressure, symptomatic status, prevalence of CAD or diabetes, end-diastolic LV diameter (a raw measure of LV preload), as well as Zva and cESS (estimates of LV afterload). Compared to ae-LVM, patients with low-LVM had higher mwFS (by 20−30%) in both moderate AS (p 0.5). Conclusions Subjects with low LVM maintain constant cESS during AS progression, probably due to higher LV contractility than in the majority of AS patients in whom the magnitude of LVH rises gradually over time. Thus, low LVM is associated with enhanced myocardial function, which may reflect a distinct mode of adaptation to chronic pressure overload, occurring already in less than severe AS. Whether better myocardial function contributes to favorable prognosis in AS without LVH, remains to be studied.

Relative Contribution of Afterload and Interstitial Fibrosis to Myocardial Function in Severe Aortic Stenosis

ObjectivesThe present study aimed at investigating the respective contribution of afterload and myocardial fibrosis to pre- and post-operative left ventricular (LV) function by using stress−strain relationships. BackgroundSeparating the effect of myocardial dysfunction and afterload on pump performance has important implications for the prognosis and management of patients with severe aortic stenosis (AS). MethodsA total of 101 patients with isolated severe AS (57% men; mean age 71 years) and 75 healthy control subjects underwent resting 2-dimensional and speckle-tracking echocardiography to measure global circumferential strain (GCS) and global longitudinal strain (GLS), as well as end-systolic wall stress (ESWS). Normal stress−strain relationships were constructed using control subjects’ data and fitted to linear regression. End-systolic stress−strain indexes (the number of SDs from the mean regression line) were used as an afterload-independent index of myocardial function and compared with myocardial fibrosis, measured on transmural myocardial biopsies harvested at the time of surgery. ResultsGCS and GLS were afterload-dependent in both control subjects and patients. The GLS-ESWS relationship of patients was shifted downward compared with control subjects. Patients with reduced pre-operative end-systolic stress−strain indexes exhibited larger degrees of interstitial myocardial fibrosis than patients without (3.8 ± 2.9% vs. 8.3 ± 6.3%, p < 0.001; and 4.9 ± 4.4% vs. 9.5 ± 6.4%; p < 0.001, for GLS and GCS, respectively). By multivariate analysis, pre-operative end-systolic stress−strain indexes were the only predictors of post-operative longitudinal and circumferential end-systolic stress−strain indexes (ß = 0.49 and ß = 0.60, respectively; p < 0.001). ConclusionsMyocardial strains are afterload-dependent. In patients with severe AS, pre-operative stress−strain indexes allow identification of patients with increased myocardial fibrosis and predict the extent of functional recovery after aortic valve replacement.

Depressed systemic arterial compliance and impaired left ventricular midwall performance in aortic stenosis with concomitant type 2 diabetes: a retrospective cross-sectional study

BackgroundDegenerative aortic stenosis (AS), a disease of the elderly, frequently coexists with concomitant diseases, including type 2 diabetes (T2DM) which amplifies the cardiovascular (CV) risk. T2DM affects left ventricular (LV) structure and function via hemodynamic and metabolic factors. In concentric LV geometry, typical for AS, indices of LV midwall mechanics are better estimates of LV function than ejection fraction (EF). Effects of T2DM coexisting with AS on circumferential LV midwall systolic function and large artery properties have not been reported so far. Our aim was to compare characteristics of AS patients with and without T2DM, with a focus on LV midwall systolic function and arterial compliance.MethodsMedical records of 130 electively hospitalized patients with moderate or severe isolated degenerative AS were retrospectively analyzed. Exclusion criteria included clinical instability, atrial fibrillation, coronary artery disease and relevant non-cardiac diseases. From in-hospital echocardiography and blood pressure, we calculated LV midwall fractional shortening (mwFS), circumferential end-systolic LV wall stress (cESS) and valvulo-arterial impedance (Zva), estimates of LV afterload, as well as systemic arterial compliance.ResultsPatients with (n = 50) and without T2DM (n = 80) did not differ in age, AS severity, LV mass and LV diastolic diameter. T2DM patients exhibited elevated cESS (247 ± 105 vs. 209 ± 84 hPa, p = 0.025) and Zva (5.8 ± 2.2 vs. 5.1 ± 1.8 mmHg per mL/m2, p = 0.04), and lower stroke volume index (33 ± 10 vs. 38 ± 12 mL/m2, p = 0.01) and systemic arterial compliance (0.53 ± 0.16 vs. 0.62 ± 0.22 mL/m2 per mmHg, p = 0.01). mwFS (11.9 ± 3.9 vs. 14.1 ± 3.7%, p = 0.001), but not EF (51 ± 14 vs. 54 ± 13%, p = n.s.), was reduced in T2DM. mwFS and cESS were inversely interrelated in patients both with (r = − 0.59, p < 0.001) and without T2DM (r = − 0.53, p < 0.001) By multiple regression, higher cESS (p < 0.001) and T2DM (p = 0.02) were independent predictors of depressed mwFS.ConclusionsIn AS, coexistent T2DM appears associated with reduced systemic arterial compliance and LV dysfunction at the midwall level, corresponding to slightly depressed myocardial contractility.

Left Ventricular Contractility and Wall Stress in Patients With Aortic Stenosis With Preserved or Reduced Ejection Fraction

ObjectivesThis study sought to determine the prevalence of reduced contractility and uncompensated wall stress in patients with aortic stenosis (AS) with preserved or reduced left ventricular ejection fraction (LVEF) and their impact on survival. BackgroundLVEF in AS is determined not only by contractility but also by loading conditions. MethodsPatients with first diagnosis (time 0) of severe AS (aortic valve area [AVA]≤1 cm2) with prior echo study (−3±1 years) were identified. Contractility was evaluated by plotting midwall fractional shortening (mFS) against circumferential end-systolic wall stress (cESS), stratified by LVEF of 60% at time 0. The temporal changes (from −3 years to time 0) and prognostic value of LVEF, contractility, and wall stress were assessed. ResultsOf 445 patients, 290 (65%) had LVEF ≥60% (median: 66% [interquartile range {IQR}: 63% to 69%]) and 155 patients (35%) had LVEF <60% (median: 47% [IQR: 34% to 55%]). Median AVA was 1.27 cm2 (IQR: 1.13 to 1.43 cm2) at −3 years and 0.90 cm2 (IQR: 0.83 to 0.96 cm2) at time 0. Decreased contractility was already present at −3 years (49 [17%] vs. 59 [38%]; LVEF ≥60% vs. <60%; p < 0.001) and became more prevalent at time 0 (69 [24%] vs. 106 [68%]; p < 0.001). Overall, wall stress was well controlled in both groups at −3 years (1 [0%] vs. 12 [8%]; p < 0.001) but deteriorated over time in patients with LVEF <60% (time 0: 0 [0%] vs. 26 [17%]; p < 0.001). During a median follow-up of 3.4 years, LVEF <60%, decreased contractility and high wall stress were associated with worse survival (p < 0.01 for all). Decreased contractility remained incremental to LVEF in patients with LVEF ≥60% (p < 0.01), but less so when LVEF was <60% (p = 0.11). ConclusionsIn patients with severe AS, LVEF <60% is associated with a poor prognosis, being linked with decreased contractility and/or high wall stress. Decreased contractility is also present in a subset of patients with LVEF ≥60% and provides incremental prognostic value. These abnormalities already exist before AVA reaches 1.0 cm2.

Association of Inadequately Low Left Ventricular Mass with Enhanced Myocardial Contractility in Severe Degenerative Aortic Stenosis.

Background: Left ventricular hypertrophy (LVH), traditionally considered an adaptive mechanism that is aimed at the maintenance of LV systolic function, is absent in 10%–35% of patients with severe aortic stenosis (AS). Our aim was to estimate the clinical and hemodynamic characteristics in patients with severe AS and absent LVH, or inadequately low LV mass (i-lowLVM) relative to an individual hemodynamic load. Methods: We retrospectively analyzed in-hospital records of 100 patients with pure severe degenerative AS, preserved LV systolic function and without relevant coexistent diseases, except for well-controlled hypertension or diabetes. Results: Clinical characteristics were similar in patients with and without LVH, as well as those with and without i-lowLVM, except for slightly lower GFR at i-lowLVM. When compared to their counterparts, subjects without LVH or with i-lowLVM had smaller LV cavities, decreased LV wall thicknesses and higher EF. There were no significant differences in stenosis severity and indices of afterload (valvulo-arterial impedance and circumferential end-systolic LV wall stress), according to the presence or absence of either LVH or i-lowLVM. However, LV fractional shortening at the midwall level was elevated only in patients with i-lowLVM, but not in those without LVH, compared to the remainder (15.8 ± 3.3 vs. 12.9 ± 3.2%, p < 0.001 for those with and without i-lowLVM, respectively; 13.7 ± 3.7 vs. 13.8 ± 3.6% for LVH presence and absence, p = 0.9). Conclusions: Inadequately low LVM relative to the individual hemodynamic load could potentially reflect a different mode of the LV response to severe AS, associated with enhanced load-independent LV systolic performance, i.e., better LV contractility. If confirmed in a large series of patients, our small preliminary study may add to the possible mechanisms of a previously reported counterintuitive tendency of a lower, not higher, risk of adverse outcome in patients with low LV mass despite severe AS. Prospective studies are warranted, in order to determine a potential utility of LVM inadequacy in the risk stratification of patients with AS.

Increased myocardial energy expenditure in cardiac syndrome X: More work, more pain

The aim of this study was to assess the myocardial energy expenditure (MEE) in patients with cardiac syndrome X (CSX) and to examine its association with exercise electrocardiogram (ECG) parameters. A total of 99 patients who underwent coronary angiography and who were diagnosed as having normal coronary arteries were included. The patients were divided into 2 groups based on symptoms and exercise ECG parameters: 56 CSX patients and 43 control patients with a negative stress test. MEE was calculated using transthoracic echocardiography-derived parameters: circumferential end-systolic stress, left ventricular ejection time, and stroke volume. In patients with CSX, the MEE at rest was 28% higher in than the control group (89.2±36.3 vs. 69.8±17.2 cal/minute). Correlation analysis revealed a moderately negative correlation between MEE and the Duke treadmill score (DTS) (ß:-0.456; p<0.001). Receiver operating characteristic analysis with a cut-off value of 74.6 cal/minute for MEE had a sensitivity of 78.1% and a specificity of 75.3% for the prediction of CSX (area under the curve: 0.872; p<0.001). An extra 1 calorie spent per minute at rest increased the likelihood of CSX by about 86% (odds ratio: 1.863). This study demonstrated that MEE was greater in CSX patients compared with a control group. Increased MEE was determined to be an independent predictor of CSX. DTS was inversely correlated with MEE. Increased MEE may have a crucial role in CSX pathophysiology.

Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction

In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFrEF population.

Left Ventricular Function Assessed by One-Point Carotid Wave Intensity in Newly Diagnosed Untreated Hypertensive Patients.

To investigate whether newly diagnosed untreated hypertensive patients show higher left ventricular (LV) contractility, as assessed by traditional echocardiographic indices and carotid wave intensity (WI) parameters, including amplitude of the peak during early (W1 ) and late systole (W2 ). A total of 145 untreated hypertensive patients were compared with 145 age- and sex-matched normotensive subjects. They underwent comprehensive echocardiography and WI analysis. WI analysis was performed at the level of the common carotid artery. The diameter changes were the difference between the displacement of the anterior and posterior walls, with the cursors set to track the media-adventitia boundaries 2 cm proximal to the carotid bulb and calibrated by systolic and diastolic BP. Peak acceleration was derived from blood flow velocity measured by Doppler sonography with the range-gate positioned at the center of the vessel diameter. WI was based on the calculation of (dP/dt)×(dU/dt), where dP/dt and dU/dt were the derivatives of BP (P) and velocity (U) with respect to time. One-point pulse wave velocity (PWVβ) and the interval between the R wave on ECG and the first peak of WI (R-W1 ), using a high definition echo-tracking system implemented in the ultrasound machine (Aloka), were also derived. After adjustment for body weight, heart rate, and physical activity, the two groups had similar general characteristics and diastolic function. However, hypertensives showed significantly higher LV mass, LV ejection fraction (LVEF), circumferential and LV end-systolic stress, and one-point PWV as well as W1 (13.646 ± 7.368 vs 9.308 ± 4.675 mmHg m/s3 , P =.001) and W2 (4.289 ± 2.017 vs 2.995 ± 1.868 mmHg m/s3 , P =.001). Hypertensives were divided into tertiles according to LVEF: W1 (11.934 ± 5.836 vs 11.576 ± 5.857 vs 17.227 ± 8.889 mmHg m/s3 , P <.0001) was higher in the highest LVEF tertile along with relative wall thickness, midwall fractional shortening, endocardial fractional shortening, and R-W1 . Newly diagnosed hypertensives show increased LVM and LV contractility, including carotid WI parameters and R-W1 values, as compared with normotensive subjects, but no differences in LV diastolic function.

Cardiac and arterial elastance and myocardial wall stress in children with pectus excavatum.

Pectus excavatum (PE) is one of the most common skeletal deformities of childhood. The study was undertaken to assess cardiac functions in children with PE. Echocardiography was performed on 32 children with PE and 40 age-matched healthy controls. The following parameters were monitored: meridional left ventricular (LV) wall stress (WSM), arterial elastance (Ea), LV elastance at end-systole derived by single beat (Ees(sb)), LV circumferential end-systolic wall stress (ESWSc), midwall shortening fraction (SFmid), predicted midwall fiber shortening for a measured fiber stress (midwall VCFc), myocardial fiber stress (MFS), LV end-systolic dimension (LVES), LV end-diastolic dimension (LVED) and end-systolic blood pressure (Pes), LV wall thickness at end-systole (hes). To assess the severity of PE, Haller index (HI) was calculated by computed tomography of the thorax. SFmid, ESWSc, midwall VCFc and MFS were lower in PE children than in controls. The degree to which the parameters SFmid, ESWSc, midwall VCFc and MFS were altered in PE children was 14.9, 27.5, 20.3 and 20.3%, respectively. The minimum HI value of children with PE was 2.00, the maximum value was 4.93 and the arithmetic mean was 2.62 ± 0.56. Of the 32 children, 14 (43.75%) demonstrated mild deformity, 15 (46.88%) showed moderate and only 3 (9.37%) had severe deformity. In children with PE, there was no statistically significant correlation between the cardiac data (ESWSc, midwall VCFc, MFS, Ea, Ees(sb), LVES, LVED, Pes, hes) and HI. We found ESWSc, MFS, midwall VCFc and SFmid to be lower in children with PE than in controls. We concluded that the myocardial contractility and afterload is affected in children with PE.

Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction in Patients with Rheumatoid Arthritis without Overt Cardiac Disease

Background Patients with rheumatoid arthritis have an increased risk for cardiovascular disease. Because of accelerated atherosclerosis and changes in left ventricular (LV) geometry, circumferential and longitudinal (CL 95% CI, 1.01–1.06; P = .04) and concentric LV geometry (odds ratio, 2.76; 95% CI, 1.07–7.15; P = .03). By multiple logistic regression analysis, rheumatoid arthritis emerged as an independent predictor of combined CL 95% CI, 1.06–6.25). The relationship between sc-MS and S′ was statistically significant in the subgroup of 142 patients without combined CL r 2 = 0.19, P It appears clear that, starting from the same 198 patients included in the database, different sub-groups of patients were selected and analyzed in the two papers (they had different echocardiographic characteristics) and, consequently, different factors emerged by the statistical analyses as covariates associated with the different phenotypes of LVSD considered. Importantly, both papers E and J had a very long gestation because all reviewers for the different journals found several and important issues that merited to be addressed: a lot of changes were proposed and much additional information was required, particularly by the reviewers of paper E. Considering this context, it emerges that although paper E was written well before paper J, the two manuscripts were accepted at the same time (we received the letters of acceptance within a couple of weeks). Thus, the uncertainty about the fate of both manuscripts made it very difficult (if not impossible) to cite either of them in the other one and, afterward, we just did not think about this point anymore. Of note, the idea to combine in the analysis longitudinal function came therefore well after the starting process of revision of the paper E and was, in some way inspired by a reviewer's comment. That is why we did not put both findings in the same paper. We think that our explanations provide the broad audience of your journal a perspective of transparency and our respect for the readers' right to understand how the work described in the paper J relates to other work by our research group. Giovanni Cioffi On behalf of all co-authors Ombretta Viapiana, Federica Ognibeni, Andrea Dalbeni, Davide Gatti, Carmine Mazzone, Giorgio Faganello, Andrea Di Lenarda, Silvano Adami, and Maurizio Rossini

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

BackgroundTissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk.MethodsTwo hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise.ResultsExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S’) was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S’, higher LV circumferential end-systolic stress and LASF.ConclusionsIn asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Fatigue as Presenting Symptom and a High Burden of Premature Ventricular Contractions Are Independently Associated With Increased Ventricular Wall Stress in Patients With Normal Left Ventricular Function.

High idiopathic premature ventricular contractions (PVC) burden has been associated with PVC-induced cardiomyopathy. Patients may be symptomatic before left ventricular (LV) dysfunction develops. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and circumferential end-systolic wall stress (cESS) on echocardiography are markers for increased ventricular wall stress. This study aimed to evaluate the relation between presenting symptoms, PVC burden, and increased ventricular wall stress in patients with frequent PVCs and preserved LV function. Eighty-three patients (41 men; 49±15 years) with idiopathic PVCs and normal LV function referred for PVC ablation were included. Type of symptoms (palpitations, fatigue, and [near-]syncope), PVC burden on 24-hour Holter, NT-proBNP levels, and cESS on echocardiography were assessed before and 3 months after ablation. Sustained successful ablation was defined as ≥80% PVC burden reduction during follow-up. Patients were symptomatic for 24 months (Q1-Q3, 16-60); 73% reported palpitations, 47% fatigue, and 30% (near-)syncope. Baseline PVC burden was 23±13%, median NT-proBNP 92 pg/mL (Q1-Q3 50-156), and cESS 143±35 kdyne/cm(2). Fatigue was associated with higher baseline NT-proBNP and cESS (P<0.001, P=0.011, respectively). After sustained successful ablation, achieved in 81%, NT-proBNP and cESS decreased significantly (P<0.001 and P=0.036, respectively). Fatigue was independently associated with a significantly larger reduction in NT-proBNP. In patients with nonsuccessful ablation, NT-proBNP and cESS remained unchanged. In patients with frequent PVCs and preserved LV function, fatigue was associated with higher baseline NT-proBNP and cESS, and with a significantly larger reduction in NT-proBNP after sustained successful ablation. These findings support a link between fatigue and PVC-induced increased ventricular wall stress, despite preserved LV function.

Association between Left Ventricular Postsystolic Shortening and Diastolic Relaxation in Asymptomatic Patients with Systemic Hypertension.

Few data have existed on myocardial postsystolic shortening (PSS) accounting for left ventricular (LV) diastolic dysfunction in systemic hypertension. We examined this relationship, along with clinical and other cardiac parameters, in asymptomatic patients with hypertension. We analyzed 104 patients on pharmacological treatment for hypertension who had no signs or symptoms of heart failure for conventional and speckle tracking echocardiography. The sum of the postsystolic index for multiple LV segments (total PSI) and global longitudinal strain (GLS) was computed and used as measures for global PSS and myocardial systolic function, respectively. The tissue Doppler e' and the speckle tracking-derived global strain rate during early diastole (e'sr) were obtained as indicators of LV relaxation. The circumferential end-systolic stress was also determined noninvasively and substituted for a measure of myocardial afterload. Main variables that correlated with the e' and e'sr were shown to be age, LV mass index, left atrial volume index, GLS, and the total PSI. Multivariate analysis including gender, circumferential end-systolic stress, and the use of calcium channel blockers as possible covariates revealed that age (β=-0.29, P=0.002), total PSI (β=-0.26, P=0.008), and LV mass index (β=-0.25, P=0.017) were significant independent determinants of e' and that age (β=-0.34, P<0.001) and GLS (β=-0.28, P=0.006) were of e'sr. Our findings indicate that while depending on the degree of GLS, PSS may affect diastolic relaxation in patients with asymptomatic, but treated, hypertensive patients.

Coronary slow flow phenomenon: Not only low in flow rate but also in myocardial energy expenditure

Background and aimCoronary slow flow phenomenon (CSFP) is a miscellaneous clinical entity leading to angina-like symptoms, and electrocardiographic and scintigraphic evidence of ischemia. The impact of this syndrome on myocardial performance has not been comprehensively evaluated. In this study, we sought to evaluate the myocardial energy expenditure (MEE) in patients with CSFP and its relationship with exercise capacity. Methods and resultsA total of 64 patients (64.1% male, mean age 53.2 ± 10.3 years) with CSFP and 64 patients (60.9% male, mean age 52.2 ± 10.9 years) with normal coronary artery as control group were included. MEE was calculated by a validated formula that uses transthoracic echocardiography (TTE) parameters, including left ventricular circumferential end-systolic stress, stroke volume, and ejection timeCSFP patients had significantly lower MEE (0.79 cal/systole ± 0.15 vs. 0.91 cal/systole ± 0.09, p < 0.001). In correlation analysis, MEE had a significant negative correlation with mean corrected TIMI frame count (mTFC) (β = −0.523; p < 0.001) and positive correlations with metabolic equivalents (METs) (β = 0.560; p < 0.001), rate pressure product (β = 0.649; p < 0.001), and exercise duration (β = 0.408; p < 0.001). At multivariate analysis, MEE was demonstrated as an independent predictor of CSFP (OR 1.863, CI 95% 1.485–2.338 p < 0.001). ConclusionMyocardial energy consumption, as a calculation obtained from TTE parameters, was reduced in patients with CSFP, and it had a significant relationship with exercise capacity. Considering its significant correlation with exercise capacity, myocardial energy consumption seemed to use evaluation of myocardial performance and functional status in another cardiovascular disease.

Effect of food intake on left ventricular wall stress

ObjectiveLeft ventricular wall stress has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether left ventricular wall stress is affected by food intake in healthy subjects.MethodsTwenty-three healthy subjects aged 25.6 ± 4.5 years were investigated. Meridional end-systolic wall stress (ESS) and circumferential end-systolic wall stress (cESS) were measured before, 30 minutes after, and 110 minutes after a standardised meal.ResultsBoth ESS and cESS decreased significantly (P < 0.001) from fasting values 30 minutes after the meal, and had not returned to baseline after 110 minutes. ESS decreased from 65 ± 16 kdynes/cm2 (fasting) to 44 ± 12 kdynes/cm2 30 minutes after, and to 58 ± 13 kdynes/cm2 110 minutes after eating. cESS decreased from 98 ± 24 kdynes/cm2 to 67 ± 18 kdynes/cm2 30 minutes after, and to 87 ± 19 kdynes/cm2 110 minutes after the meal.ConclusionThis study shows that left ventricular wall stress is affected by food intake in healthy subjects.