Coronary microvascular dysfunction affects left ventricular global longitudinal strain response to dipyridamole stress echocardiography: a pilot study.

The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (- 16.8 ± 2.7 vs. - 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from - 19.1 ± 3.1 to - 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from - 16.8 ± 2.7 to - 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = - 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia.

Left ventricular contractile reserve as a determinant of adverse clinical outcomes: a systematic review.

An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality.

Systolic and diastolic functional reserve of the subpulmonary and systemic right ventricles as assessed by pharmacologic and exercise stress: A systematic review.

We performed a systematic review of the literature on the assessment of subpulmonary and systemic right ventricular (RV) functional reserve during pharmacological and exercise stress in congenital heart patients and patients with pulmonary arterial hypertension (PAH). Literature search was conducted using PubMed, EMBASE, and MEDLINE from their inception up to August 2020. Of 913 records identified, 56 studies with a total of 1730 patients were included. Of the 56 studies, 23 assessed subpulmonary RV functional reserve in repaired tetralogy of Fallot patients, 19 assessed systemic RV reserve in patients with transposition of the great arteries (TGA) after atrial switch and those with congenitally corrected TGA, and 14 assessed subpulmonary RV research in patients with PAH. Pharmacological and exercise stress was used, respectively, in 22 and 34 studies. The main findings were (1) impairment of RV systolic and diastolic functional reserve, (2) associations between impaired functional reserve and worse baseline functional parameters, and (3) prognostic implications of RV systolic functional reserve on clinical outcomes in patients with volume and/or pressure-loaded subpulmonary and systemic right ventricles. Further studies are required to establish the incremental value of incorporating stress studies of RV systolic and diastolic function in the clinical management algorithm of congenital heart patients and patients with PAH.

Myocardial adaptation and exercise performance in patients with pulmonary arterial hypertension assessed with patient-specific computer simulations.

Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole circulation properties in PAH at rest and exercise and determinants of exercise reserve. CMR and right heart catheterization were performed in nine patients with idiopathic PAH, and CMR in 10 healthy controls. CMR during exercise was performed in seven patients with PAH. A full-circulation computer model was developed, and model parameters were optimized at the individual level. Patient-specific simulations were used to analyze the effect of right ventricular (RV) inotropic reserve on exercise performance. Simulations achieved a high consistency with observed data. RV contractile force was increased in patients with PAH (127.1 ± 28.7 kPa vs. 70.5 ± 14.5 kPa, P < 0.001), whereas left ventricular contractile force was reduced (107.5 ± 17.5 kPa vs. 133.9 ± 10.3 kPa, P = 0.002). During exercise, RV contractile force increased by 1.56 ± 0.17, P = 0.001. In silico experiments confirmed RV inotropic reserve as the important limiting factor for cardiac output. Subject-specific computer simulation of myocardial mechanics in PAH is feasible and can be used to evaluate myocardial performance. With this method, we demonstrate marked functional myocardial adaptation to PAH in the resting state, primarily composed of increased contractile force development by RV myofibers, and we show the negative impact of reduced RV inotropic reserve on cardiac output during exercise.NEW & NOTEWORTHY Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea.

BACKGROUND: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear. METHODS AND RESULTS: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm2 vs 2.58 ± 1.14 mm Hg/cm2; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea. CONCLUSIONS: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.

Evaluation of dyspnea of unknown etiology in HIV patients with cardiopulmonary exercise testing and cardiovascular magnetic resonance imaging.

AIM: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. METHODS AND RESULTS: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). CONCLUSION: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

Stress Echocardiography and Strain in Aortic Regurgitation (SESAR protocol): Left ventricular contractile reserve and myocardial work in asymptomatic patients with severe aortic regurgitation.

OBJECTIVES: To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. BACKGROUND: The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision-making of AR asymptomatic patients. METHODS: Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age- and sex-comparable healthy controls. RESULTS: 115 AR patients (male sex 58.2%; 52.3 ± 18.3 years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS-15.8 ± 2.8 vs -21.4 ± 4.4; P < .001). Patients with AR and CR- showed reduced resting LV GLS and MWE and increased B-lines. MWE was closely related to peak effort watts, VO2 , LV E/e', and B-lines, at a multivariable analysis. Both GLS and MWE were strong independent predictors of CR. A resting LV GLS cutoff of -12% differentiated CR+ and CR- (78% sensitivity and 84% specificity). CONCLUSIONS: The lower resting values of LV GLS and MWE in severe AR asymptomatic patients suggest an early subclinical myocardial damage that seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during stress.

Quantitative assessment of contractile reserve of systemic right ventricle in post-Senning children: Incorporating speckle-tracking strain and dobutamine stress echocardiography.

INTRODUCTION: The systemic load on the right ventricle (RV) after Senning atrial switch leads to ventricular dysfunction. Quantitative assessment of RV contractile reserve is mandatory to anticipate the need for anti-fibrotic treatment. We aimed to quantitatively assess RV contractile reserve in Senning children by estimating speckle-based global longitudinal strain (GLS) during dobutamine stress echocardiography (DSE). METHODS: This prospective study compared thirty-one post-Senning children (group I) and thirty controls (group II). In post-Senning children, echocardiographic RV systolic function using one-plane ejection fraction (RVEF), RV fractional area change (RVFAC), tricuspid annulus plane systolic excursion (TAPSE), its Z-score, and RVGLS were recorded at rest and peak DSE. Contractile reserve was defined as improvement >5% in RVEF, >2% in GLS, and/or to near normal TAPSE. RESULTS: RVEF, RVFAC, TAPSE, and TAPSE Z-score were significantly lower in patients than controls [RVEF:40.13 ± 2.93% vs 53.17 ± 3.17% (P < .001*), RVFAC: 21.17 ± 2.37% vs 37.23 ± 2.13% (P < .001*), TAPSE:13.81 ± 1.26 vs 17.45 ± 2.93 mm (P < .001*), TAPSE Z-score: -3.47 ± 0.46 vs -2.09 ± 0.48 (P < .001*)]. Also, RVGLS was significantly impaired in Senning children than controls[ (-11.89 ± 2.31% vs -22.35 ± 6.73% (P < .001*)]. At peak DSE, contractile reserve was not evident as measured by RVEF which increased none significantly to 42.47 ± 2.80% (P = .063). However, RVGLS improved significantly to -15.78 ± 0.93% (P < .001*) and discovered the masked contractile reserve in Senning children. The 19(61.29%) children who showed masked contractile reserve (improvement in RVGLS > 2%) underwent continuation of anti-fibrotic medications. CONCLUSIONS: Despite systemic RV function in post-Senning children was impaired at rest and during DSE, RVGLS was useful in quantitative assessment of masked contractile thus promoted continuing anti-fibrotic treatment.

Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis following transcatheter aortic valve replacement.

OBJECTIVES: The aim of this study was to determine the prognostic value of contractile reserve (CR) at baseline in patients with low-flow, low-gradient severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with severe AS, left ventricular dysfunction, and low transaortic gradient are at high risk for mortality during surgical aortic valve replacement (SAVR). Furthermore, patients without CR have been shown to have perioperative mortality comparable to that of patients treated medically for severe AS. METHODS: We retrospectively analyzed patients who underwent TAVR with a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40 mmHg, LVEF < 50%, and AVA ≤ 1.0 cm2 or AVAi ≤ 0.6 cm2 ) and who had a pre-TAVR dobutamine stress echocardiogram (DSE). Patients were stratified by the presence or absence of CR, defined as an increase in stroke volume ≥ 20% during DSE. RESULTS: From 2008 to 2016, 61 patients with low-gradient severe AS underwent TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30 (49%). There was no significant difference between the two groups in baseline demographics, medical history, access site, or types of valves. All-cause mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P = 0.69). CONCLUSION: In patients with low-flow, low-gradient severe AS undergoing TAVR, the presence or absence of CR does not predict all-cause mortality at 30 days or 1 year.

Left ventricular contractile reserve by stress echocardiography as a predictor of response to cardiac resynchronization therapy in heart failure: a systematic review and meta-analysis.

BACKGROUND: The presence of left ventricular contractile reserve (LVCR) during stress echo (SE) may provide favorable response to cardiac resynchronization therapy (CRT) in heart failure patients. The aim of the study was to perform a meta-analysis of available SE data in this set of patients. METHODS: From a Pubmed and Advance Google Scholar database web based search scan up to December 2016, we initially identified 5906 records. From this initial set, we removed that did not include SE and duplicate studies. We assessed for eligibility 71 full-text articles assessed for eligibility, and 60 of them did not meet the inclusion criteria as follow: 1) heart failure patients with NYHA class III and IV, depressed ejection fraction (EF <35%) and QRS duration ≥120 ms at study entry; 2) SE with assessment of LVCR; 3) Follow-up data. LVCR during SE was identified as reduction in wall motion score index and/or an increase in EF. RESULTS: Eleven studies with 861 patients (mean age 67 ± 9 years, ejection fraction 25 ± 6%) were included in the meta-analysis. The type of stress was either exercise (n = 2) or dobutamine (n = 9), the latter with low-dose (10 mcg) in two, intermediate-dose (20 mcg) in five, and high-dose (40 mcg) protocol in two studies. LVCR was detected in 555 patients (63%) and CRT-response was present in 584 (66%). The overall odds ratio for LVCR to predict a favorable CRT response was 2.06 (95%, CI 1.70-2-43), Z score: 11.055, p < 0.001. CONCLUSION: The presence of LVCR during SE with either dobutamine or exercise is associated with a greater chance of response to CRT. This parameter is now ready to be tested in a prospective multicenter trial to select patients more likely to benefit from CRT.

Galectin-3 and fibulin-1 in systolic heart failure - relation to glucose metabolism and left ventricular contractile reserve.

BACKGROUND: Heart failure (HF) patients with diabetes (DM) have an adverse prognosis and reduced functional capacity, which could be associated with cardiac fibrosis, increased chamber stiffness and reduced left ventricular (LV) contractile reserve. Galectin-3 (Gal-3) and fibulin-1 are circulating biomarkers potentially reflecting cardiac fibrosis. We hypothesize that plasma levels of Gal-3 and fibulin-1 are elevated in HF patients with DM and are associated with reduced LV contractile reserve in these patients. METHODS: A total of 155 patients with HF with reduced ejection fraction underwent a low-dose dobutamine echocardiography and blood sampling for biomarker measurements. Patients were classified according to history of DM and an oral glucose tolerance test (OGTT) as: normal glucose tolerance (NGT) (n = 70), impaired glucose tolerance (IGT) (n = 25) and DM (n = 60). RESULTS: Galectin-3 levels were elevated in DM patients as compared to non-diabetic patients (P = 0.02), while higher fibulin-1 levels were observed in HF patients with IGF and DM (P = 0.07). Reduced LV contractile reserve was associated with increasing Gal-3 levels (ß = -0.19, P = 0.03) although, this association was attenuated after adjustment for estimated glomerular filtration rate (P = 0.66). Fibulin-1 was not associated with LV contractile reserve (P = 0.71). CONCLUSIONS: Galectin-3 and fibulin-1 levels were elevated in HF patients with impaired glucose metabolism. However, reduced LV contractile reserve among HF patients with DM does not to have an independent impact on plasma Gal-3 and fibulin-1 levels.

Contractile reserve and cardiopulmonary exercise parameters in patients with dilated cardiomyopathy, the two dimensions of exercise testing.

BACKGROUND: Left ventricular (LV) contractile reserve assessed using imaging and cardiopulmonary exercise testing (CPX) has been shown to predict outcome in patients with dilated cardiomyopathy (DCM). Few clinical studies have, however, analyzed the relationship between them. METHODS: A cohort of 75 ambulatory patients with DCM underwent stress treadmill echocardiography with CPX. LV contractile reserve was calculated as absolute change (ΔLVEF=LVEFpeak -LVEFrest ) and percent change (%LVEF=[(LVEFpeak -LVEFrest )/LVEFpeak) ]×100) in LVEF, circumferential and longitudinal strain (LS). Exercise capacity was measured as peak oxygen uptake (peak VO2 ) and ventilatory efficiency as the slope of minute ventilation to CO2 production (VE/VCO2 slope). Values of contractile reserve were compared to matched controls. We also explored which metric of ventricular response (absolute or percent change) was less dependent on baseline LV function. RESULTS: Patients with DCM had a mean age, rest and peak LVEF of 44±10 years, 42±10% and 50±12%, respectively. Among parameters of contractile reserve, peak cardiac output was the strongest parameter associated with peak VO2 (r=.63, P<.001). Along with age, sex, and BMI, it explained more than 70% of the variance in peak VO2 . In contrast, LVEF and LS were only weakly related to peak VO2 . With regard to ventilatory efficiency, the strongest parameter that emerged was right atrial volume index (r=.36, P<.001). Percent change in LVEF was more independent of baseline function than absolute change. CONCLUSION: Echocardiographic contractile reserve and CPX provide complementary information. Percent change in contractile reserve was most independent of baseline function, therefore may be preferred when analyzing the ventricular response to exercise.

Myocyte repolarization modulates myocardial function in aging dogs.

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

The effects of exercise on right ventricular contractility and right ventricular-arterial coupling in pulmonary hypertension.

RATIONALE: Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility. OBJECTIVES: To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exercise response in end-systolic elastance (ΔEes), and the effects of exercise on the matching of Ees and RV afterload (Ea) (i.e., RV-arterial coupling; Ees/Ea). In addition, we compared ΔEes with a recently proposed surrogate, the rest-to-exercise change in pulmonary artery pressure (ΔPAP). METHODS: We prospectively included 17 patients with precapillary PH and 7 control subjects without PH who performed a submaximal invasive cardiopulmonary exercise test between January 2013 and July 2014. Ees and Ees/Ea were assessed using single-beat pressure-volume loop analysis. MEASUREMENTS AND MAIN RESULTS: Exercise data in 16 patients with PH and 5 control subjects were of sufficient quality for analysis. Ees significantly increased from rest to exercise in control subjects but not in patients with PH. Ea significantly increased in both groups. As a result, exercise led to a decrease in Ees/Ea in patients with PH, whereas Ees/Ea was unaffected in control subjects (Pinteraction = 0.009). In patients with PH, ΔPAP was not related to ΔEes but significantly correlated to the rest-to-exercise change in heart rate. CONCLUSIONS: In contrast to control subjects, patients with PH were unable to increase Ees during submaximal exercise. Failure to compensate for the further increase in Ea during exercise led to deterioration in Ees/Ea. Furthermore, ΔPAP did not reflect ΔEes but rather the change in heart rate.

Endomyocardial radial strain rate imaging during dobutamine stress echocardiography for the evaluation of contractile reserve in patients with dilated cardiomyopathy.

PURPOSE: Myocardial contractile reserve is associated with clinical prognosis in patients with dilated cardiomyopathy (DCM). We assessed myocardial contractile reserve using tissue Doppler strain rate imaging with dobutamine stress echocardiography in DCM patients. METHODS: Simultaneous echocardiography and left ventricular (LV) catheterization during dobutamine stress were performed in 20 patients with DCM, and echocardiography was performed in 31 control subjects. Dobutamine was infused at a starting dose of 5 µg/kg/min for 5 minutes and then at 10 µg/kg/min. Peak endomyocardial radial strain (ɛ) and systolic strain rate (SRsys ) measured with echocardiography and the maximum first derivative of LV pressure (LV dP/dtmax ) derived from catheterization were used as indices of contractility. Their percentage change from baseline to the dose of 10 µg/kg/min was calculated. RESULTS: The ɛ and SRsys were significantly smaller in DCM patients than in controls. The LV dP/dtmax , ɛ, and SRsys were significantly higher at the dose of 10 µg/kg/min than at baseline. The percentage change in SRsys was significantly correlated with the percentage change in LV dP/dtmax . CONCLUSIONS: Strain rate imaging during dobutamine stress in DCM might prove noninvasively informative for the evaluation of myocardial contractile reserve and provide insight into LV systolic dysfunction. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:555-560, 2016.

Left ventricular restrictive filling pattern and the presence of contractile reserve in patients with low-flow/low-gradient severe aortic stenosis.

OBJECTIVE: We sought to study diastolic function in patients with low-flow/low-gradient aortic stenosis (LF/LGAS) and to clarify the relationship between contractile reserve on dobutamine stress echocardiography (DSE) and the restrictive filling pattern on echocardiography in patients with LF/LGAS. PATIENTS AND METHODS: Thirty patients with LF/LG severe AS were divided into 2 groups. Group I included 14 patients with contractile reserve on DSE. Group II included 16 patients with no contractile reserve on DSE. Diastolic function was studied in all patients using baseline echo Doppler study. RESULTS: No significant difference was found between both groups regarding baseline left ventriculae end-diastolic dimension (LVEDD), ejection fraction (EF), stroke volume, aortic valve area (AVA), mean transaortic pressure gradient, septal thickness or posterior wall thickness, P > 0.05. Transmitral E/A ratio was 1.3 ± 0.5 compared to 2.6 ± 0.7, respectively, deceleration time (DT) was 160 ± 31 compared to 120 ± 15 ms, isovolumic relaxation time (IVRT) was 81 ± 22 compared to 53 ± 18 ms, S/D ratio was 1.2 ± 0.3 compared to 0.8 ± 0.2, respectively, (P < 0.001 for all).Three patients in group I had restrictive pattern of diastolic dysfunction compared to 12 in group II (P < 0.003). DSE data in both groups showed a peak SV of 64 ± 11 mL compared to 50 ± 7 mL (P < 0.005), peak EF was 42 ± 9 compared to 34 ± 11% (P < 0.03). Peak stress mean transaortic pressure gradient was 39 ± 9 compared to 22 ± 10 mmHg, respectively, P < 001. CONCLUSION: Restrictive filling pattern of diastolic dysfunction on baseline echo Doppler study may predict lack of contractile reserve in patients with LF/LG severe AS.

Dynamic relationship of left-ventricular dyssynchrony and contractile reserve in patients undergoing cardiac resynchronization therapy.

AIMS: Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction (LVEF) and the response to cardiac resynchronization therapy (CRT). Using apical rocking (ApRock) as surrogate dyssynchrony parameter, we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular (LV) dyssynchrony and LVEF and their potential pathophysiological interdependence. METHODS AND RESULTS: Fifty-eight guideline-selected CRT candidates were prospectively enrolled for low-dose DSE. Dyssynchrony was quantified by the amplitude of ApRock. An LVEF increase during stress of >5% was regarded significant. Scar burden was assessed by magnetic resonance imaging. Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death. ApRock during DSE predicted CRT response (AUC 0.88, 95% CI 0.77-0.99, P < 0.001) and correlated inversely with changes in EF (r = -0.6, P < 0.001). Left-ventricular ejection fraction changes during DSE were not associated with CRT response (P = 0.082). Linear regression analysis revealed an inverse association of LVEF changes during DSE with both, total scar burden (B = -2.67, 95CI -3.77 to -1.56, P < 0.001) and the DSE-induced change in ApRock amplitude (B = -1.23, 95% CI -1.53 to -0.94, P < 0.001). Kaplan-Meier analysis revealed that DSE-induced increase in ApRock, but not LVEF, was associated with improved long-term survival. CONCLUSION: During low-dose DSE in CRT candidates with baseline dyssynchrony, myocardial contractile reserve predominantly results in more dyssynchrony, but less in an increase in LVEF. Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT.

Left ventricular contractile reserve in asymptomatic primary mitral regurgitation.

AIMS: There are very few data regarding the assessment and prognostic value of left ventricular contractile reserve (LVCR) in asymptomatic patients with primary mitral regurgitation (MR). We aimed to quantify LVCR and to evaluate its usefulness for risk stratification in asymptomatic patients with primary MR. METHODS AND RESULTS: Comprehensive resting and exercise (EX) transthoracic echocardiography, including two-dimensional speckle tracking quantification, were performed in 115 consecutive asymptomatic patients with ≥ moderate degenerative MR and no LV dysfunction/dilatation. Left ventricular contractile reserve was defined as an EX-induced increase in LV ejection fraction (LVCR(LVEF)) ≥ 4% or in LV global longitudinal strain (LVCR(GLS)) ≥ 2%. LVCR(LVEF) was present in 54 patients (47%) and LVCR(GLS) in 58 (50%). The brain natriuretic peptide (BNP) level was significantly correlated with EX-induced changes in GLS (r = 0.45, P < 0.0001), but not in LVEF (r = 0.09, P = 0.31). Patients with no LVCR(GLS) had significant lower 3-year cardiac event-free survival (42 ± 8 vs. 69 ± 7%, P = 0.0008). In contrast, there was no significant difference in outcome regarding to the presence or absence of LVCR(LVEF) (60 ± 7 vs. 51 ± 8%, P = 0.40). The multivariable Cox proportional hazard model showed that the absence of LVCR(GLS) was a strong independent predictor of cardiac events (HR = 2.27, 95% CI: 1.05-4.76, P = 0.037), even after adjustment for Ex-echo variables and BNP level. The association between LVCR(GLS) and outcome remained significant (HR = 1.6, 95% CI: 1.1-2.3, P = 0.01) after further adjustment for the resting echocardiographic parameters included in the ESC Guidelines. CONCLUSION: In asymptomatic primary MR, LVCR seems to be better assessed using EX-induced changes in LV myocardial longitudinal function rather than in LVEF. In patients with preserved LV function, the absence of LVCR is independently associated with two-fold increase in risk of cardiac events. Left ventricular contractile reserve may be useful to improve risk stratification and clinical decision-making in these patients.

ABCDEG Stress Echocardiography in Aortic Stenosis.

Rest and stress echocardiography (SE) plays a pivotal role in the evaluation of valvular heart disease. The use of SE is recommended in valvular heart disease when there is a mismatch between resting transthoracic echocardiography findings and symptoms. In aortic stenosis (AS), rest echocardiographic analysis is a stepwise approach that begins with the evaluation of aortic valve morphology and proceeds to the measurement of the transvalvular aortic gradient and aortic valve area (AVA) using continuity equations or planimetry. The presence of the following three criteria suggests severe AS: AVA < 1.0 cm2, a peak velocity > 4.0 m/s, or a mean gradient > 40 mmHg. However, in approximately one in three cases, we can observe a discordant AVA < 1 cm2 with a peak velocity < 4.0 m/s or a mean gradient <40 mmHg. This is due to reduced transvalvular flow associated with LV systolic dysfunction (LVEF < 50%) defined as "classical" low-flow low-gradient (LFLG) AS or normal LVEF "paradoxical" LFLG AS. SE has an established role in evaluating LV contractile reserve (CR) patients with reduced LVEF. In classical LFLG AS, LV CR distinguished pseudo-severe AS from truly severe AS. Some observational data suggest that long-term prognosis in asymptomatic severe AS may not be as favorable as previously thought, offering a window of opportunity for intervention prior to the onset of symptoms. Therefore, guidelines recommend evaluating asymptomatic AS with exercise stress in physically active patients, particularly those younger than 70 years, and symptomatic classical LFLG severe AS with low-dose dobutamine SE. A comprehensive SE assessment includes evaluating valve function (gradients), the global systolic function of the LV, and pulmonary congestion. This assessment integrates considerations of blood pressure response, chronotropic reserve, and symptoms. StressEcho 2030 is a prospective, large-scale study that employs a comprehensive protocol (ABCDEG) to analyze the clinical and echocardiographic phenotypes of AS, capturing various vulnerability sources which support stress echo-driven treatment strategies.

Role of the right ventricular contractile reserve during low-load exercise in predicting heart failure readmission.

BACKGROUND: Exercise intolerance in patients with heart failure (HF) increases HF-associated readmission, and right ventricular (RV) contractile reserve assessed by low-load exercise stress echocardiography (ESE) is associated with exercise intolerance. This study investigated the impact of RV contractile reserve evaluated by low-load ESE on HF readmission. METHODS: We prospectively examined 81 consecutive patients hospitalized for HF who underwent low-load ESE under a stabilized HF condition between May 2018 and September 2020. We performed a 25-W low-load ESE and defined RV contractile reserve as the increment in RV systolic velocity (RV s'). The primary outcome was hospital readmission. Incremental values of the change in RV s' over a readmission risk (RR) score were analyzed using the receiver operating characteristic (ROC) area under the curve; internal validation using bootstrapping was performed. The association between RV contractile reserve and HF readmission was illustrated with the Kaplan-Meier curve. RESULTS: Eighteen (22 %) patients were readmitted due to worsening HF during the observation period (median 15.6 months). The cut-off value of 0.68 cm/s for the change in RV s' to predict HF readmission with the ROC curve analysis indicated good sensitivity (100 %) and specificity (76.2 %). The discriminatory ability for HF readmission was significantly improved by adding the change in RV s' to the RR score (p = 0.006), and the c-statistic using the bootstrap method was 0.92. The cumulative survival rate free of HF readmission was significantly lower in patients with reduced-RV contractile reserve (log-rank test, p < 0.001). CONCLUSIONS: The change in RV s' during low-load exercise had an incremental prognostic value for predicting HF readmission. The results demonstrated the loss of RV contractile reserve assessed by low-load ESE was associated with HF readmission.