Ventricular Ejection Fraction Response Research Articles

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT

BackgroundLeft bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. ObjectivesThis study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. MethodsWe analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. ResultsThere were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. ConclusionsRemodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Retraining an Artificial Intelligence Algorithm to Calculate Left Ventricular Ejection Fraction in Pediatrics

Identifying patients with low left ventricular ejection fraction (LVEF) and monitoring LVEF responses to treatment are important clinical goals. Can a deep-learning algorithm predict pediatric LVEF within clinically acceptable error? The study authors wanted to fine-tune an adult deep-learning algorithm to calculate LVEF in pediatric patients. A priori, their objective was to refine the algorithm to perform LVEF calculation with a mean absolute error (MAE) ≤5%. A quaternary pediatric hospital PARTICIPANTS: A convenience sample (n=321) of echocardiograms from newborns to 18 years old with normal cardiac anatomy or hemodynamically insignificant anomalies. Echocardiograms were chosen from a group of healthy controls with known normal LVEF (n=267) and a dilated cardiomyopathy patient group with reduced LVEF (n=54). The artificial intelligence model EchoNet-Dynamic was tested on this data set and then retrained, tested, and further validated to improve LVEF calculation. The gold standard value was LVEF calculated by clinical experts. In a random subset of subjects (n=40) not analyzed prior to selection of the final model, EchoNet-Dynamic calculated LVEF with a MAE of 8.39%, R2=0.47 without, and MAE 4.47%, R2=0.87 with fine-tuning. Bland-Altman analysis suggested that the model slightly underestimates LVEF (bias=-2.42%). The 95% limits of agreement between actual and calculated values were -12.32% to 7.47%. The fine-tuned model calculates LVEF in a range of pediatric patients within clinically acceptable error. Potential advantages include reducing operator error in LVEF calculation and supporting independent LVEF assessment by inexperienced users.

Left atrial strain predicts cardiovascular response to exercise in young adults with suboptimal blood pressure.

To investigate the left ventricular response to exercise in young adults with hypertension, and identify whether this response can be predicted from changes in left atrial function at rest. A total of 127 adults aged 18-40years who completed clinical blood pressure assessment and echocardiography phenotyping at rest and during cardiopulmonary exercise testing, were included. Measurements were compared between participants with suboptimal blood pressure ≥120/80mm Hg (n=68) and optimal blood pressure <120/80mm Hg (n=59). Left ventricular systolic function during exercise was obtained from an apical four chamber view, while resting left atrial function was assessed from apical four and two chamber views. Participants with suboptimal blood pressure had higher left ventricular mass (p = 0.031) and reduced mitral E velocity (p = 0.02) at rest but no other cardiac differences. During exercise, their rise in left ventricular ejection fraction was reduced (p = 0.001) and they had higher left ventricular end diastolic and systolic volumes (p = 0.001 and p = 0.001, respectively). Resting cardiac size predicted left ventricular volumes during exercise but only left atrial booster pump function predicted the left ventricular ejection fraction response ( = .29, p = 0.011). This association persisted after adjustment for age, sex, body mass index, and mean arterial pressure. Young adults with suboptimal blood pressure have a reduced left ventricular systolic response to exercise, which can be predicted by their left atrial booster pump function at rest. Echocardiographic measures of left atrial function may provide an early marker of functionally relevant, subclinical, cardiac remodelling in young adults with hypertension.

Erratum to: Left atrial fibrosis predicts left ventricular ejection fraction response after atrial fibrillation ablation in heart failure patients: the Fibrosis-HF Study.

Erratum to: Left atrial fibrosis predicts left ventricular ejection fraction response after atrial fibrillation ablation in heart failure patients: the Fibrosis-HF Study.

Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose.

AimsIn the PARADIGM‐heart failure trial, sacubitril‐valsartan demonstrated a reduction in heart failure admissions and reduced all‐cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear.This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population.Methods and resultsThis is a retrospective single‐centre review of patients switched from angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers to sacubitril‐valsartan between May 2016 and August 2018. Baseline and follow‐up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril‐valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values.To date, a total of 322 patients (75% male patients) have been switched to sacubitril‐valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril‐valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD.ConclusionsSacubitril‐valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril‐valsartan.

Predicting response to cardiac resynchronization therapy: Use of strict left bundle branch block criteria.

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). CRT efficacy is greater in left bundle branch block (LBBB). This study aimed to determine if strict LBBB criteria predict an improved QRS duration and left ventricular ejection fraction (LVEF) response after CRT. HFrEF patients who received a CRT device at a single quaternary center were included. Patients were divided into three groups based on baseline QRS morphology. Group 1 consisted of patients with strict LBBB. Group 2 had conventional LBBB, and group 3 had non-LBBB morphology. Outcomes assessed included change in QRS duration after CRT, change in LVEF, and all-cause mortality. In 231 patients, 56% of patients were in group 1, 29% were in group 2, and 15% were in group 3. Patients with strict LBBB had a significant reduction in QRS duration (-20.9±12.4ms) compared to conventional LBBB (6.7±19.4ms; P<0.0001) and non-LBBB (3.9±29.3ms; P<0.0001). Patients with strict LBBB had a significant increase in LVEF (19.5±10.2) compared to conventional LBBB (5.3±12.6; P<0.0001) and non-LBBB (-1.3±10.9; P<0.0001). There was moderate negative correlation between changes in QRS duration and LVEF (correlation coefficient=-0.63, P<0.0001). Strict LBBB criteria were associated with a significant reduction in mortality compared to conventional LBBB (odds ratio 0.49, 95% confidence interval 0.24 to 0.99; P=0.046). Strict LBBB predicted a reduction in QRS duration and an increase in LVEF compared to conventional LBBB and non-LBBB morphology in patients with HFrEF who received CRT.

Exercise cardiac magnetic resonance imaging: a feasibility study and meta-analysis.

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.

Prognostic value of myocardial perfusion imaging performed pre-renal transplantation: post-transplantation follow-up and outcomes.

Noninvasive stress testing is commonly performed as part of pre-renal transplantation (RT) evaluation. We evaluated the prognostic value of myocardial perfusion imaging (MPI)-myocardial perfusion, left ventricular ejection fraction (LVEF) and heart rate response (HRR)-post-RT. Consecutive RT recipients were identified at our institution. MPI was considered abnormal when there was a perfusion defect or reduced ejection fraction. HRR to vasodilator stress was calculated as percentage change from baseline. The primary outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI) and coronary revascularization (CR) post-RT; all-cause mortality was the secondary endpoint. Among 1189 RT recipients, 819 (69%) underwent MPI. Of those, 182 (22%) had abnormal MPI, and 31 (4%) underwent CR pre-RT. During a median follow-up of 56months post-RT, the annual CV event and mortality rates for patients who had no MPI, normal MPI and abnormal MPI were 1.5%, 3.1% and 4.3% (p < 0.001), and 1.8%, 2.6% and 3.6% (p = 0.016), respectively. After multivariate adjustment, compared to patients without MPI, the hazard ratios (HRs) for CV events for normal and abnormal MPI were 1.47 ([0.93-2.33], p = 0.1) and 1.78 ([1.03-3.06], p = 0.04). Blunted HRR was an independent predictor of CV events (HR = 1.73 [1.04-2.86], p = 0.034) and all-cause death (HR = 2.26 [1.28-3.98], p = 0.005) after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR pre-RT had annual mortality rates similar to those with no or normal MPI (1.9% vs. 1.7-2.6%, p = 0.2), while those who did not undergo CR had higher annual mortality (4% vs. 1.7-2.6%, p = 0.003). One in five RT recipients who underwent screening MPI had an abnormal study, an independent predictor of CV events. A blunted HRR to vasodilator stress was associated with increased risk of CV events and death, even after adjusting for abnormal MPI. Patients with abnormal MPI who underwent CR were at low risk of mortality following RT. MPI is a useful tool to aid in risk stratification pre-RT.

Exercise cardiac MRI unmasks right ventricular dysfunction in acute hypoxia and chronic pulmonary arterial hypertension.

Coupling of right ventricular (RV) contractility to afterload is maintained at rest in the early stages of pulmonary arterial hypertension (PAH), but exercise may unmask depleted contractile reserves. We assessed whether elevated afterload reduces RV contractile reserve despite compensated resting function using noninvasive exercise imaging. Fourteen patients with PAH (mean age: 39.1 yr, 10 women and 4 men) and 34 healthy control subjects (mean ageL 35.6 yr, 17 women and 17 men) completed real-time cardiac magnetic resonance imaging during submaximal exercise breathing room air. Control subjects were then also exercised during acute normobaric hypoxia (fraction of inspired O2: 12%). RV contractile reserve was assessed by the effect of exercise on ejection fraction. In control subjects, the increase in RV ejection fraction on exercise was less during hypoxia (P = 0.017), but the response of left ventricular ejection fraction to exercise did not change. Patients with PAH had an impaired RV reserve, with half demonstrating a fall in RV ejection fraction on exercise despite comparable resting function to controls (PAH: rest 53.6 ± 4.3% vs. exercise 51.4 ± 10.7%; controls: rest 57.1 ± 5.2% vs. exercise 69.6 ± 6.1%, P < 0.0001). In control subjects, the increase in stroke volume index on exercise was driven by reduced RV end-systolic volume, whereas patients with PAH did not augment the stroke volume index, with increases in both end-diastolic and end-systolic volumes. From baseline hemodynamic and exercise capacity variables, only the minute ventilation-to-CO2 output ratio was an independent predictor of RV functional reserve (P = 0.021). In conclusion, noninvasive cardiac imaging during exercise unmasks depleted RV contractile reserves in healthy adults under hypoxic conditions and patients with PAH under normoxic conditions despite preserved ejection fraction at rest.NEW & NOTEWORTHY Right ventricular (RV) reserve was assessed using real-time cardiac magnetic resonance imaging in patients with pulmonary arterial hypertension and in healthy control subjects under normobaric hypoxia, which has been previously associated with acute pulmonary hypertension. Hypoxia caused a mild reduction in RV reserve, whereas chronic pulmonary arterial hypertension was associated with a marked reduction in RV reserve.

Feasibility of Using Multiplane Stress Imaging to Add Measurement of LV Ejection Fraction Response to Exercise to Regional Wall Motion Scoring During Stress Echo

Multiplane 4D imaging probes not only increase accuracy of stress echo by reducing image acquisition time whilst maintaining orthogonal triplane views, but also have the potential to add a biplane ejection fraction (LVEF) measurement to the standard regional wall motion scoring. Methods: We prospectively studied 67 consecutive patients undergoing a treadmill stress echocardiogram using a Bruce protocol. Multiplane images of the left ventricle were obtained at rest and post exercise using a GE Vivid 9 scanner and a 4D multiplane probe. All studies were performed by a single senior sonographer. The time taken to obtain the images post exercise was recorded and the LVEF measured off line using EchoPac™ BT12 software and Simpson's biplane method. Results: We included 67 patients (52 male, 15 female) over 12 months, ranging in age from 28 to 85 years, (63 ± 11 years, mean ± SD). The patients’ sizes varied with BSA ranging from 1.53–2.38 m2 (mean 1.92m2). Images suitable for standard regional wall motion scoring were obtained in 95%, within 35 ± 9 seconds, and the LVEF was measurable in 100% of these patients. Conclusion: Left ventricular ejection fraction response to exercise could be measured using multiplane 4D imaging in all patients with suitable stress echo images. Whilst the clinical utility of this will depend on the context in which it is used the results do suggest that it is feasible to incorporate this into standard stress echo protocols and may add important information to regional wall motion scoring.

0251: Prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive Algerian patients without coronary artery disease

We sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive Algerian patients with normal resting echocardiography and absence of coronary artery disease. From our database of patients (military hospitals of Algeria) referred for treadmill exercise echocardiography, we identified 91 hypertensive patients with preserved resting left ventricular ejection fraction (>50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 38 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 53 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. Patients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95% CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). In hypertensive Algerian patients patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.

New-onset left bundle branch block–associated idiopathic nonischemic cardiomyopathy and left ventricular ejection fraction response to guideline-directed therapies: The NEOLITH study

Left ventricular ejection fraction (LVEF) response to guideline-directed medical therapy (GDMT) and to early cardiac resynchronization therapy (CRT) in new-onset idiopathic nonischemic cardiomyopathy (NICM) and left bundle branch block (LBBB) is not well described. CRT is recommended if LVEF remains ≤35% after at least 3 months of GDMT. The purpose of this study was to describe LVEF response to GDMT at 3 months and to early CRT in new-onset LBBB-associated idiopathic NICM. A retrospective cohort study was performed in subjects with new-onset idiopathic NICM, LVEF ≤35%, and LBBB or narrow (<120 ms) QRS complex morphology. LVEF response between groups was evaluated with log-binomial and linear regression. LVEF response within groups was evaluated using the paired Student t test. In 102 subjects (70 with narrow QRS complex and 32 with LBBB), post-GDMT LVEF was >35% in 39 narrow QRS complex subjects (56%) and 2 LBBB subjects (6%) (P < .0001). The absolute difference between post-GDMT LVEF and initial LVEF was greater in the narrow QRS complex group (16.1% ± 14.6% vs. 3.3% ± 10.7%; P < .0001). Narrow QRS complex, referenced to LBBB, was significantly associated with post-GDMT LVEF >35% (relative risk 10.30; 95% confidence interval 2.63-40.27; P = .0008) and absolute difference between post-GDMT LVEF and initial LVEF (β = 16.296; standard error = 2.977; P < .0001) in final multivariable analyses. CRT super-response, defined as post-CRT LVEF ≥50%, was observed in 8 of LBBB subjects (35%) who received CRT. GDMT did not significantly improve LVEF in new-onset LBBB-associated idiopathic NICM at 3 months. Most remained candidates for CRT, and a high percentage were super-responders. Optimal timing for CRT implantation requires further investigation.

Valor pronóstico de la disfunción ventricular izquierda inducida por el ejercicio en pacientes hipertensos sin enfermedad arterial coronaria

Introduction and objectivesWe sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. MethodsFrom our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. ResultsPatients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). ConclusionsIn hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.Full English text available from: www.revespcardiol.org/en

Prognostic Value of Exercise-induced Left Ventricular Systolic Dysfunction in Hypertensive Patients Without Coronary Artery Disease

Introduction and objectivesWe sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. MethodsFrom our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. ResultsPatients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). ConclusionsIn hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.

Effect of β Adrenoreceptor Antagonism on Left Ventricular Ejection Fraction in Hispanic Subjects with Chronic Heart Failure: A Multi-Ethnic Comparison

Background: Hispanics, the fastest growing and third largest ethnic group in the US, have been conspicuously absent from most of inter-ethnic analyses. The aim of this study is to examine the response of left ventricular ejection fraction (LVEF) to beta blocker (BB) therapy among different ethnic groups and Hispanic heart failure (HF) patients. Methods: 76 Hispanic, 65 African Americans, and 46 Caucasian patients with LVEF ≤ 40% from any etiology were selected from the HF Clinic. LVEF was recorded at baseline and after one year of BB therapy.

Deletion of Inducible Nitric Oxide Synthase Provides Cardioprotection in Mice With 2-Kidney, 1-Clip Hypertension

Inducible NO synthase (iNOS) has been implicated in the pathogenesis of hypertension and target organ damage. We hypothesized that induction of iNOS contributes to left ventricular (LV) hypertrophy and dysfunction in mice with 2-kidney, 1-clip hypertension. Deletion of iNOS diminishes oxidative stress, thereby attenuating LV hypertrophy and enhancing cardiac performance. 2-Kidney, 1-clip hypertension was induced in mice lacking iNOS and wild-type controls (C57BL/6J). Sham-clipped mice served as controls. Systolic blood pressure was measured weekly by tail cuff. Left ventricular ejection fraction (by echocardiography) and cardiac response (maximum and minimum dP/dt, as well as an indicator of isovolumic contraction) to isoproterenol (50 ng per mouse, i.v.) were studied at the end of the experiment. 4-Hydroxy-2-nonenal (a byproduct of lipid peroxidation and an indicator of oxidative stress) was measured by immunohistochemical staining. gp91(phox), endothelial NO synthase, and iNOS protein expression were determined by Western blot. We found that systolic blood pressure, LV weight, myocyte cross-sectional area, interstitial collagen fraction, ejection fraction, and cardiac response to isoproterenol did not differ between strains with sham clipping. 2-Kidney, 1-clip hypertension increased systolic blood pressure, LV weight, myocyte cross-sectional area, and interstitial collagen fraction similarly in both strains. However, in mice lacking iNOS, maximum and minimum dP/dt, as well as an indicator of isovolumic contraction, markedly increased in response to isoproterenol, associated with decreased cardiac 4-hydroxy-2-nonenal expression and urinary nitrate/nitrite. We concluded that deletion of iNOS does not seem to play a significant role in preventing 2-kidney, 1-clip hypertension-induced hypertension and cardiac hypertrophy; however, it does enhance preservation of cardiac function, probably because of a reduction of iNOS-induced oxidative stress.

39.26

39.26

Synergistic polymorphisms of β1 and α2C-adrenergic receptors and the influence on left ventricular ejection fraction response to β-blocker therapy in heart failure

The Arg389Gly polymorphism (Arg389Gly) in the beta1-adrenergic receptor gene (ADRB1) has been associated with improvement in left-ventricular remodeling with beta-blocker treatment. One study of risk for heart failure suggested a synergistic effect of ADRB1 Arg389Gly with the insertion/deletion polymorphism in the alpha2C-adrenergic receptor gene (ADRA2C). We tested whether the ADRA2C insertion/deletion polymorphism was associated with beta-blocker response in heart failure, either alone or in combination with the ADRB1Arg389Gly polymorphism. Fifty-four beta-blocker naive heart failure patients underwent echocardiography before and after 5-6 months of metoprolol CR/XL therapy. Multivariant linear regression modeling was performed to assess the impact of genotypes and other variables on changes in left-ventricular function in response to metoprolol therapy. Deletion carriers had a significantly greater negative chronotropic response. Predictors of the end of study ejection fraction were baseline ejection fraction, deletion carrier status and Arg389Arg genotype. Patients with Arg389Arg/Del-carrier status showed the greatest ejection fraction increase with metoprolol CR/XL. Adjusting for baseline ejection fraction, final S-metoprolol plasma concentration and race, final ejection fraction in patients with this genotype combination was significantly higher than all other genotype combination groups. ADRB1 and ADRA2C polymorphisms synergistically influence the ejection fraction response to beta-blocker therapy of heart failure patients.

The role of left ventricular long axis contraction in patients with asymptomatic non-ischemic mitral valve regurgitation and normal systolic function

Background Several indices have been proposed in order to better evaluate chronic mitral regurgitation, however, none of them is unique, thus underlying the diagnostic deficiency. We aimed to investigate the role of long axis contraction in both ventricles in patients with non-ischemic asymptomatic mitral regurgitation (MR). Methods Eighty-nine patients (40 men, mean age 59.9 ± 13.5 years) with non-ischemic asymptomatic MR along with 50 healthy controls were studied. An echocardiographic, including tissue Doppler imaging study, an exercise radionuclide cineangiography and a cardiac catheterization were also performed. Results Fifty of 89 patients (56.2%) had a normal response of left ventricular (LV) ejection fraction on exercise. LV end-diastolic diameter and volume index were significantly higher in patients with an impaired LV response. Moreover, systolic wave maximal velocity and systolic wave slope both at the lateral wall and at the inter-ventricular septum were significantly lower in patients with an impaired LV response. Systolic wave maximal velocity at the lateral wall was the index that best predicted LV response to exercise; while a cutoff value of 9.5 cm/s predicted an impaired LV response with a sensitivity of 96% and a specificity of 100%. MR as defined by the width of vena contracta, was mild/moderate in 78% of patients with a systolic wave maximal velocity at the lateral wall > 9.5 cm/s and severe in 69.2% of patients with a velocity < 9.5 cm/s. Conclusion In patients with asymptomatic non-ischemic MR, the evaluation of LV long axis contraction at rest can unmask a subnormal LV functional status.

Relation between contractile reserve and improvement in left ventricular function with beta-blocker therapy in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Beta blockers improve left ventricular (LV) ejection fraction but patient responses are heterogenous. We investigated the role of contractile reserve (CR) in predicting β-blocker response in ischemic and nonischemic cardiomyopathy. Resting and low-dose dobutamine echocardiograms were recorded in 32 patients with heart failure (LV ejection fraction ≤35%), 18 with ischemic cardiomyopathy (IC), and 14 with idiopathic dilated cardiomyopathy (IDC). A segment was defined as CR positive (CR+) or negative (CR−) based on response to dobutamine. Patients were then classified as CR+ or CR− based on number of improved segments (IC group) or ejection fraction improvement (IDC group) in response to dobutamine. During follow-up (2, 6, and 14 months after β-blocker initiation), response was measured by the percent of segments showing improved contractility from baseline, ejection fraction, and wall motion score index. In the IC group, the percent of improved segments was greater at 2 and 6 months in CR+ versus CR− (70% vs 15% and 39% vs 17%, p <0.05), whereas it was greater at all periods in the patients with IDC (36% vs 9% at 2 months, 50% vs 19% at 6 months, and 63% vs 42% at 14 months, p <0.05). Findings for ejection fraction and wall motion score index were similar. Therefore, time course and magnitude of improvement in LV function in patients with heart failure receiving β blockers are related to CR status. CR predicts a greater early response in IC, whereas it predicts a greater response at all time periods in IDC. However, even patients without CR showed improvement in LV function at 14 months.