Exercise Left Ventricular Ejection Fraction Research Articles

Abstract 14867: Examining Effects of a Physical Activity Intervention on Exercise Capacity and Cardiovascular Function Among Patients With Lymphoma and Breast Cancer Undergoing Treatment

Introduction. Patients receiving serial outpatient infusion treatment for lymphoma or breast cancer (BC) with potentially cardio-toxic chemotherapeutic regimens may experience declines in left ventricular ejection fraction (LVEF) and exercise capacity. This study sought to determine if a physical activity intervention (PAI) administered during cancer treatment could attenuate deterioration of exercise capacity and LVEF. Methods. Across two NCI funded cancer centers, we randomized (2:1) 34 participants to a home-based PAI or healthy living education intervention (HLI) within 6 weeks of initiating curative therapies for stage I-IV Hodgkin’s, non-Hodgkin’s lymphoma, or stage I-III BC (NCT01719562). Training programs were tailored by treatment and functional status and adapted for remote delivery during COVID-19. Exercise capacity was determined via cardiopulmonary exercise test (peak VO 2 [ml/kg/min]) and LVEF (%) was determined by magnetic resonance imaging at baseline, 3, and 6 months. Separate linear mixed-effects regression models controlling for baseline values examined changes in peak VO 2 and LVEF by time and treatment group. Results. Demographics were similar between the two arms (PAI vs. HLI, 52.4 [16.3] vs. 56.8 [12.7] years of age [SD]; 69% vs. 75% white; and 57.7% vs. 50% female). Peak VO 2 increased at 3 (+1.15 ml/kg/min [CI: -1.46 - 3.77]) and 6 months (+3.88 ml/kg/min [CI: 0.79 - 6.96]) in the PAI arm, while the HLI arm increased slightly at 3- (+0.67 ml/kg/min [CI: -5.14 - 6.48]) but not 6 months (-0.83 ml/kg/min [CI: -5.99 - 4.33]). LVEF declined slightly at 3 months in the PAI (-2.29% [CI: -4.83 - 0.25]) but not HLI arm (3.05.% [CI: -2.49 - 8.60]), while at 6 months, the PAI arm had returned to baseline LVEF (-0.58% [CI: -4.30 - 3.14]) and the HLI arm declined slightly (-1.76% [CI: -7.23 - 3.71]). Conclusions. This pilot RCT suggests the importance and utility of home-based physical activity during cancer treatment in protecting against expected declines in exercise capacity and LVEF. These results highlight the need for larger randomized trials that examine the effects of lifestyle interventions administered during treatment to improve quality of life and to support long term cardiovascular health in cancer survivors.

Limited usefulness of resting hemodynamic assessments in predicting exercise capacity in hypertensive patients.

Reliable assessments of reduced exercise capacity based on resting tests are one of the major challenges in clinical practice. The aim of this study was to evaluate the relationship between hemodynamic parameters obtained via resting tests (echocardiography and impedance cardiography (ICG)) and objective parameters of exercise capacity assessed via cardiopulmonary exercise testing and exercise ICG in patients with controlled arterial hypertension (AH). The left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function parameters (e', E/A, E/e'), cardiac output (CO), stroke volume (SV), and systemic vascular resistance index were evaluated for any correlations with selected parameters of exercise capacity, such as peak oxygen uptake (VO2) and peak CO in 93 people with AH (mean age 54 years, 47 women). Statistically relevant correlations occurred between indices of exercise capacity (peak VO2; peak CO) and only the following hemodynamic parameters: diastolic blood pressure (R = 0.23, p = 0.026; R = 0.24, p = 0.021; respectively), e' (R = 0.32, p = 0.002; R = 0.24, p = 0.027), E/e' (R = 0.35, p < 0.001; ns), E/A (R = 0.23, p = 0.030; R = 0.21, p = 0.047), SV at rest (ns; R = 0.24, p = 0.019), and CO at rest (ns; R = 0.21, borderline p = 0.052). No significant correlations between the exercise capacity parameters and either LVEF or GLS were observed. No hemodynamic parameter proved to be an independent correlate of either peak VO2 or peak CO. The association between hemodynamic parameters at rest and parameters of exercise capacity was weak and limited to selected parameters of diastolic function. Exercise capacity assessment in patients with AH based on resting tests alone is insufficiently reliable and should be supplemented with exercise tests.

Early Effects of Sacubitril/Valsartan on Exercise Tolerance in Patients with Heart Failure with Reduced Ejection Fraction.

Background. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. Methods. We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy. Results. At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3–14.9 months) systolic blood pressure decreased from 117 ± 14 to 101 ± 12 mmHg (p < 0.0001), left ventricular ejection fraction (LVEF) increased from 27 ± 6 to 29.7 ± 7% (p < 0.0001), peak oxygen consumption (VO2) improved from 14.6 ± 3.3 (% of predicted = 53.8 ± 14.1) to 17.2 ± 4.7 mL/kg/min (% of predicted = 64.7 ± 17.8) (p < 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO2 Slope) decreased from 34.1 ± 6.3 to 31.7 ± 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 ± 2.6 to 12.6 ± 3.5 mL/kg/min (p = 0.007), oxygen pulse increased from 11.5 ± 3.0 to 13.4 ± 4.3 mL/kg/min (p < 0.0001), and ∆VO2/∆Work increased from 9.2 ± 1.5 to 10.1 ± 1.8 mL/min/watt (p = 0.0002). Conclusion. Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.

Exercise left ventricular ejection fraction predicts events in right bundle branch block

ABSTRACT Objective Interpretation of the electrocardiogram (ECG) during exercise is not easy in patients with right bundle branch block (RBBB). Also, the value of exercise echocardiography (ExE) for predicting outcome in them has not been addressed. We sought to assess its prognostic value in patients with RBBB and known/suspected coronary disease. Design Retrospective analysis of data on 703 patients with RBBB who were submitted to a clinically-indicated ExE. The end points were overall mortality and combined myocardial infarction and cardiovascular mortality. Results During follow-up (4.1 ± 4.5 years) there were 130 deaths and 108 combined events. Independent predictors of combined events were history of coronary artery disease (hazard ratio [HR] = 2.37, 95% Confidence Interval [CI] = 1.24–4.52, p = 0.009) resting wall motion score index (HR = 2.14, 95% CI = 1.12–4.10, p = 0.02), metabolic equivalents (HR = 0.89, 95% CI = 0.93–0.97, p = 0.007), Δ in double product with exercise (HR = 0.96, 95% CI = 0.92–1.00, p = 0.036) and Δ in left ventricular ejection fraction (LVEF) with exercise (HR = 0.97, 95% CI = 0.94–0.99, p = 0.01). Neither positive clinical nor ECG exercise testing was predictive. Combined event rates were 3.3% in patients with ΔLVEF > 5%, 4.7% in those with ΔLVEF between 1–5% and 8.2% in those with no increase (Δ < 1%). Conclusions A decrease in LVEF during exercise is predictive of serious events in patients with RBBB.

Stress Echocardiography in Regurgitant Valve Disease

Because of its wide availability, low cost, versatility, and clinical use, stress echocardiography has become increasingly recognized as a valuable tool in the assessment of patients with regurgitant valvular heart disease. Exercise testing is favored compared with pharmacological stress testing for risk stratification in asymptomatic patients and can identify what might otherwise be considered as a moderate valve disease. It has been shown to provide insights into exertional symptoms disproportionate to resting hemodynamics in these patients and to facilitate individual risk stratification. Aggravation of valvular regurgitation severity, exercise-induced pulmonary hypertension (PHT), impaired left ventricular (LV) contractile reserve, inducible ischemia, dynamic LV dyssynchrony, and altered exercise capacity, together with the development of symptoms during exercise echocardiography, provide the clinician with straightforward prognostic information, therefore enabling a more accurate definition of the optimal timing of intervention in patients with valvular regurgitation.1,2 In contrast, dobutamine stress echocardiography has little value in cases of valvular regurgitation. Dobutamine infusion is almost systematically associated with a decrease in the severity of regurgitation; however, it might be of interest in the detection of LV contractile reserve and inducible ischemia. The most common form of exercise used in conjunction with echocardiography is immediate postexercise imaging on a treadmill or upright bicycle ergometer. However, semisupine exercise testing on an appropriate tilted table allows continuous echocardiographic monitoring, which represents an advantageous tool for quantifying changes in valvular regurgitation severity, LV function, and pulmonary pressure (Table). This exercise stress echocardiography modality (ie, per-exercise echocardiography) is the most used in Europe, and we strongly suggest this approach in the setting of valvular heart disease to detect evanescent changes. A symptom-limited graded exercise test is recommended, and ≥80% of the age-predicted upper heart rate should be reached in the absence of symptoms. The test is adapted to the clinical conditions …

154 Patients receiving standard pacemaker generator replacements frequently have impaired left ventricular function and exercise intolerance, related to the percentage of right ventricular pacing

<h3>Background</h3> Right ventricular (RV) pacing is an accepted treatment for symptomatic bradycardia. However, long-term RV pacing is increasingly recognised to be detrimental to left ventricular (LV) systolic function. We wanted to establish the prevalence, associated features and predictors of LV systolic dysfunction (LVSD) and outcome in a contemporary group of patients with long–term RV pacemakers. <h3>Methods</h3> We prospectively recruited consecutive patients listed for PGR between 2008 and 2010 at Leeds General Infirmary. We performed echocardiography, exercise testing and recorded indications for pacing, pacing variables and duration of pacing, co-morbidities, current medication and renal function. <h3>Results</h3> Of 399 PGR procedures 342 subjects (86%), 184 men, attended. Non-attendees had similar pacing variables and were of similar age as attendees. Mean age (SE) was 76 (1), and mean duration of pacing was 10 (0.3) years. Comorbidites were common: diabetes mellitus in 11%, previous myocardial infarction in 15%, previous cardiac surgery in 26% and atrial fibrillation (AF) in 26%. Medical therapy included β-blockers in 60% and ACE inhibitors in 70%. Dual chamber devices were implanted in 77% (45% of all patients had rate responsive (RR) pacing programmed). Mean percentage of ventricular pacing (%VP) was 61 (2)%. Mean left ventricular ejection fraction (LVEF) was 49 (1)%, (44% had an LVEF &lt;50%). Mean peak oxygen uptake (pVo₂) (in 107 subjects) was 17 (1) ml/kg/min and mean creatinine was 108 (3) μmol/l. There was an inverse relationship between LVEF and %VP (0.42; p&lt;0.0001), and years since first implanted (p=0.09) but there was no effect on LVEF of age, the presence of AF and the pacing mode. In single chamber devices, RR pacing was associated with higher %VP (p=0.01), and a trend to worse LVEF (p=0.09). These differences were not seen in RR programmed dual chamber devices. There was a negative relationship between pVo₂ and %VP (r=0.21; p&lt;0.03). Even with a short follow-up period of 16 (0.5) months, 23 (7%) patients are dead. Patients dead at the censor date were older at the time of the assessment (p&lt;0.005), had a higher %VP (p&lt;0.03) and worse renal function (p&lt;0.001), but did not have significantly worse LVEF or pVo₂. The presence of a single chamber device was associated with a poorer outcome (p&lt;0.002) despite patients with a single chamber device being of similar age as those with a dual chamber device. <h3>Conclusions</h3> Patients receiving standard pacemaker generator replacements frequently have cardiovascular comorbidities, left ventricular dysfunction and impaired pVo₂ and suffer a high mortality rate. In an unselected population of patients with pacemakers, we have established that the amount of RV pacing is related not only to important surrogate measures of outcome such as exercise tolerance and LVEF but also mortality. Whether an aggressive policy of limiting RV pacing in patients at risk reduces mortality is unknown.

Clinical observation on the treatment of chronic heart failure with Qiliqiangxin capsule

Objective To investigate the influence of Qiliqiangxin capsule on the exercise tolerance in patients with chronic heart failure. Methods 86 patients with chronic heart failure were selected and recruited into a control group and an observation group randomly. The patients in the control group were given angiotensin-converting enzyme inhibitor, diuretic,carvedilol or metoprolol and dixina. The patients in the observation group were given Qiliqiangxin capsule on the basis of the control group. The change of exercise tolerance and left ventricular ejection fraction in all patients were detected after 4 weeks.Results The distance of walking in 6 minutes increased for all patients after 4 weeks' treatment(P＜0.05), while the observation group increased more significantly than the control group(P＜0.05). The left ventricular ejection fraction increased for all patients after therapy 4 weeks (P＜0.05), while the observation group increased more obviously than the control group (P＜0.05). The total excellent rate and effective rate in the observation group were both higher than the control group (P＜0.05). Conclusion Qiliqiangxin capsule can increase the clinic curative effect by increasing the exercise tolerance and improving the heart function of patients with chronic heart failure. Key words: Qiliqiangxin capsule; Heart failure; Walking experiment in 6 minutes

Prognostic value of cardiopulmonary exercise testing in children with heart failure secondary to idiopathic dilated cardiomyopathy in a non‐β‐blocker therapy setting

Peak oxygen consumption and resting left ventricular ejection fraction (LVEF) are independent predictors of survival in adult heart failure (HF) patients. To evaluate these factors in children. We prospectively studied 31 children with NYHA class I to III HF (mean LVEF 26+/-10%; mean age 8.6+/-1.9 years). All had dilated cardiomyopathy and were awaiting heart transplantation. A cardiopulmonary treadmill exercise test was performed and LVEF determined by radionuclide ventriculography. During a median follow-up of 1282 days, 20 children reached at least one end-point (death or heart transplantation). Clinical data from the 11 children without events and the 20 children with events are as follows: NYHA class 1+/-0 vs. 2+/-0.9 (p<0.01); SBP 118+/-17 vs. 102+/-16 (p=0.01); DBP 70+/-10 vs. 61+/-10 (p=0.02); heart rate 165+/-22 vs. 148+/-22 (NS); double-product 19+/-4 vs. 15+/-4 (p=0.01); end-tidal carbon dioxide tension (PetCO2) 35+/-5 vs. 30+/-6 (NS); oxygen consumption (VO2) 22+/-5.4 vs. 18.3+/-5.7 (NS); exercise time 19+/-4 vs. 13+/-6 (p<0.003), and LVEF 31+/-8 vs. 22+/-10 (p=0.02). These variables all correlated with prognosis on univariate analysis. In multivariate analysis, only decreasing exercise time and LVEF were predictive of events during follow-up (p<0.001 and 0.04). These findings suggest that reduction in LVEF and exercise tolerance in children with heart failure is predictive of functional status.

Impairment in Walking Capacity and Myocardial Function in the Elderly: Is There a Role for Nonpharmacologic Therapy with Nutritional Amino Acid Supplements?

Elderly persons have reduced muscular mass, with consequent deterioration of their daily activities and reduced quality of life. This is more pronounced in elderly patients affected by chronic diseases such as chronic heart failure (CHF). It has been demonstrated that oral amino acid (AA) supplementation improves muscle protein metabolism. A recent study shows that use of oral supplements with a special mixture of AAs for 12 weeks increases (1) 6-minute walk distance (from 212.5 +/- 34 m to 268.8 +/- 34.9 m; p <0.001), (2) maximal isometric muscular strength (from 14.6 +/- 2.2 kg to 20.2 +/- 2 kg; p <0.001), and (3) peak exercise left ventricular ejection fraction (LVEF 0.55 + 0.4 vs 0.67 + 0.7) (0.558 vs 0.67 +/- 0.7; p <0.01). In a pilot observational study, we studied elderly patients with CHF who were clinically stable on standard therapy (age range, 68-76 years; New York Heart Association (NYHA) class II-III; LVEF <0.40; normal body mass index and arm muscle measurements; peak oxygen consumption <15 mL/kg per min). After basal assessment of (1) cardiac function (by 2-dimensional echocardiography), (2) 6-minute walk test, and (3) blood variables, an AA mixture (4 g x 2 die) was orally administered to the patients for 12 weeks in conjunction with standard therapies and a controlled diet. The AA supplements increased 6-minute walk distance significantly (201 +/- 12 m vs 226 +/- 9 m; p < 0.05). Interestingly, urea values were unchanged (31.3 +/- 10.5 mg/dL vs 32.4 +/- 8.1 mg/dL; p = NS). Our results suggest the potential role of a nonpharmacologic therapy with nutrients (ie, AAs) in an attempt to improve muscular metabolism and function in elderly subjects and in hypercatabolic syndromes such as CHF.

Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: Insights from echocardiography and exercise cardiac performance evaluation

Objectives Left ventricular (LV) diastolic dysfunction is considered the earliest manifestation of diabetic cardiomyopathy. Whether LV abnormalities identified at rest by echocardiography predict peak exercise LV performance in uncomplicated type 1 diabetes mellitus (DM1) is largely unknown. Research design and methods We evaluated LV size, mass, and functions and peak exercise LV performance in 25 subjects with uncomplicated DM1 (median disease duration 13.5 years, 1–30 years) and in 56 non-DM subjects (24 hypertensive (HT) and 32 normotensive (NT)). Overt coronary heart disease, significant microangiopathy and central autonomic neuropathy were minimized by exclusion criteria. Peak exercise LV stroke index (SVi), cardiac index (COi), LV ejection fraction (EF), LV end-diastolic and end-systolic volumes were assessed noninvasively. No subject was on cardiovascular medications at the time of evaluation. Results In our study, DM1 did not show LV hypertrophy or impaired LV systolic function at rest. Prevalence of diastolic dysfunction was 8% among DM1, 18% among NT and 50% among HT. Pre-exercise heart rate, SVi, COi, and peak exercise blood pressure (BP) and heart rate were comparable among the three groups, but peak exercise LV EF, SVi and COi were lower in DM1 than in HT and NT independent to covariates ( p < 0.05). In separate analyses, DM1 predicted lower peak exercise SVi ( B = −6.2) and COi ( B = −1.6, both p < 0.05) independently. Within DM1, glycated haemoglobin (HbA1c) and disease duration did not predict peak exercise LV systolic function. Conclusions Our study suggests that uncomplicated DM1 may be associated with subnormal LV contractility reserve, which might not be predicted by LV dysfunction evaluated at rest.

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)

Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.

Left ventricular function during arm exercise: influence of leg cycling and lower body positive pressure

The purpose of this study was to characterize left ventricular (LV) diastolic filling and systolic performance during graded arm exercise and to examine the effects of lower body positive pressure (LBPP) or concomitant leg exercise as means to enhance LV preload in aerobically trained individuals. Subjects were eight men with a mean age (+/-SE) of 26.8 +/- 1.2 yr. Peak exercise testing was first performed for both legs [maximal oxygen uptake (Vo(2)) = 4.21 +/- 0.19 l/min] and arms (2.56 +/- 0.16 l/min). On a separate occasion, LV filling and ejection parameters were acquired using non-imaging scintography using in vivo red blood cell labeling with technetium 99(m) first during leg exercise performed in succession for 2 min at increasing grades to peak effort. Graded arm exercise (at 30, 60, 80, and 100% peak Vo(2)) was performed during three randomly assigned conditions: control (no intervention), with concurrent leg cycling (at a constant 15% leg maximal Vo(2)) or with 60 mmHg of LBPP using an Anti G suit. Peak leg exercise LV ejection fraction was higher than arm exercise (60.9 +/- 1.7% vs. 55.9 +/- 2.7%; P < 0.05) as was peak LV end-diastolic volume was reported as % of resting value (110.3 +/- 4.4% vs. 97 +/- 3.7%; P < 0.05) and peak filling rate (end-diastolic volume/s; 6.4 +/- 0.28% vs. 5.2 +/- 0.25%). Concomitant use of either low-intensity leg exercise or LBPP during arm exercise failed to significantly increase LV filling or ejection parameters. These observations suggest that perturbations in preload fail to overcome the inherent hemodynamic conditions present during arm exercise that attenuate LV performance.

Outcomes of Patients With Reduced Exercise Capacity at Time of Exercise Echocardiography

Objective To characterize the prognostic implications of exercise echocardiography in patients who have reduced exercise capacity at the time of testing. Patients and Methods We examined the outcomes of 941 patients at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1995, who had reduced exercise capacity on exercise echocardiography (women, <5 metabolic equivalents; men, <7 metabolic equivalents) and evaluated the potential association between clinical, electrocardiographic, and echocardiographic variables and outcomes for patients with normal vs abnormal exercise echocardiograms. We used variables of independent prognostic value to estimate cardiac risk. Results For patients with normal exercise echocardiograms (n=282), the rate of cardiac death or nonfatal myocardial infarction was 0.9% per person-year of follow-up, and previous coronary revascularization was the only predictor of the time to cardiac event. For patients with abnormal exercise echocardiograms (n=659), the cardiac event rate was 4.4%. Independent predictors of outcome were exercise left ventricular (LV) ejection fraction (risk ratio, 1.44 per 10% decrement; 95% confidence interval, 1.2-1.7; P<.001) and an increase or no change in LV end-systolic size in response to exercise (risk ratio, 2.22; 95% confidence interval, 1.2-4.1; P=.01). Conclusion Exercise echocardiographic findings have important prognostic implications for patients who have reduced exercise capacity on testing. Echocardiographic descriptors of LV systolic function and dysfunction obtained immediately after exercise can be used to stratify cardiac risk of patients who do not achieve a level of exercise ordinarily considered to be of “diagnostic” value. To characterize the prognostic implications of exercise echocardiography in patients who have reduced exercise capacity at the time of testing. We examined the outcomes of 941 patients at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1995, who had reduced exercise capacity on exercise echocardiography (women, <5 metabolic equivalents; men, <7 metabolic equivalents) and evaluated the potential association between clinical, electrocardiographic, and echocardiographic variables and outcomes for patients with normal vs abnormal exercise echocardiograms. We used variables of independent prognostic value to estimate cardiac risk. For patients with normal exercise echocardiograms (n=282), the rate of cardiac death or nonfatal myocardial infarction was 0.9% per person-year of follow-up, and previous coronary revascularization was the only predictor of the time to cardiac event. For patients with abnormal exercise echocardiograms (n=659), the cardiac event rate was 4.4%. Independent predictors of outcome were exercise left ventricular (LV) ejection fraction (risk ratio, 1.44 per 10% decrement; 95% confidence interval, 1.2-1.7; P<.001) and an increase or no change in LV end-systolic size in response to exercise (risk ratio, 2.22; 95% confidence interval, 1.2-4.1; P=.01). Exercise echocardiographic findings have important prognostic implications for patients who have reduced exercise capacity on testing. Echocardiographic descriptors of LV systolic function and dysfunction obtained immediately after exercise can be used to stratify cardiac risk of patients who do not achieve a level of exercise ordinarily considered to be of “diagnostic” value.

Effects of oral amino acid supplementation on myocardial function in patients with type 2 diabetes mellitus

Background Diabetes mellitus is associated with an increased rate of cardiac amino acid catabolism that could interfere with cardiac function. Methods We assessed the effects of an oral amino acids mixture (AAM) on myocardial function in patients with type 2 diabetes mellitus (DM2). We studied 65 consecutive patients with DM2 who had normal resting left ventricular ejection fraction (LVEF) and did not have obstructive coronary artery disease (CAD). After baseline evaluations, patients were randomized to receive, in a single-blinded fashion, AAM (12 grams/day) or placebo for 12 weeks, after which, treatment was crossed over for another similar period. At baseline and at the end of each treatment, 2-dimensional ecocardiography at rest and during isometric exercise (handgrip) was performed, as were biochemical assays. Twenty adults, matched for age, sex, and body mass index served as control subjects. Results At baseline and during AAM or placebo treatment, resting left ventricular dimensions and LVEF in patients with DM2 did not differ from those of control subjects. In patients with DM2, at baseline and during placebo treatment, peak handgrip LVEF decreased significantly in comparison with the resting value (63% ± 9% vs 56% ± 9%, P <.001; and 62% ± 6% vs 55% ± 8%, P <.001). During AAM treatment, peak handgrip LVEF did not differ from resting value (66% ± 11% vs 64% ± 9%, P = not significant). Thus, exercise LVEF was higher during AAM treatment than both baseline and placebo treatment (66% ± 11% vs 56% ± 9% and vs 55% ± 8%, P <.001). In contrast to placebo treatment, after the AAM supply, a decreased glycated hemoglobin level was observed (7.0% ± 1.3% vs 7.6% ± 1.8%, P <.05). Conclusions Myocardial dysfunction is easily inducible with isometric exercise in patients with DM2 who have normal resting LV function and do not have CAD. An increased amino acid supply prevents this phenomenon and improves metabolic control.

Outcomes of Patients With Reduced Exercise Capacity at Time of Exercise Echocardiography

To characterize the prognostic implications of exercise echocardiography in patients who have reduced exercise capacity at the time of testing. We examined the outcomes of 941 patients at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and December 31, 1995, who had reduced exercise capacity on exercise echocardiography (women, <5 metabolic equivalents; men, <7 metabolic equivalents) and evaluated the potential association between clinical, electrocardiographic, and echocardiographic variables and outcomes for patients with normal vs abnormal exercise echocardiograms. We used variables of independent prognostic value to estimate cardiac risk. For patients with normal exercise echocardiograms (n=282), the rate of cardiac death or nonfatal myocardial infarction was 09% per person-year of follow-up, and previous coronary revascularization was the only predictor of the time to cardiac event. For patients with abnormal exercise echocardiograms (n=659), the cardiac event rate was 4.4%. Independent predictors of outcome were exercise left ventricular (LV) ejection fraction (risk ratio, 1.44 per 10% decrement; 95% confidence interval, 1.2-1.7; P<.001) and an increase or no change in LV end-systolic size in response to exercise (risk ratio, 2.22; 95% confidence interval, 1.2-4.1; P=.01). Exercise echocardiographic findings have important prognostic implications for patients who have reduced exercise capacity on testing. Echocardiographic descriptors of LV systolic function and dysfunction obtained immediately after exercise can be used to stratify cardiac risk of patients who do not achieve a level of exercise ordinarily considered to be of "diagnostic" value.

The background of the MERIT-HF trial.

In the not so distant past, the idea of using beta-blockers as a primary therapy for congestive heart failure to improve symptoms and prognosis seemed paradoxical. The cardiac community reacted with skepticism when, in 1975, the pioneering report of Waagstein et al. appeared in the British Heart Journal. Since then numerous groups have investigated the effects of beta-adrenoceptor antagonists in patients with congestive heart failure. Unfortunately, the results of these trials have sometimes contradicted one another. Exercise tolerance and left ventricular ejection fraction improved in the trials with a duration of treatment of longer than 3 months, but no benefit was observed when beta-blockers were administered for only 1 month. Now, in the year 2000 we have proof for the concept that beta-blockade improves symptoms and prolongs life in heart failure. Three large placebo-controlled clinical trials with more than 9000 patients have shown that carvedilol, bisoprolol and metoprolol significantly reduce morbidity and mortality in heart failure. These agents, therefore, are clearly indicated in the majority of patients with mild to moderate heart failure.

76. Serial assessment of rest and exercise left ventricular ejection fraction (LVEF) post-cardiomyoplasty

s: Abstracts of the 30th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine

A STUDY OF THE EFFICACY AND SAFETY OF IRBESARTAN IN COMBINATION WITH CONVENTIONAL THERAPY, INCLUDING ACE INHIBITORS, IN HEART FAILURE

SUMMARYBecause heart failure therapy with angiotensin‐converting enzyme (ACE) inhibitors may not be optimal, owing to persistent levels of angiotensin II occurring through incomplete blockade and alternate pathways, the benefit of adding irbesartan, an angiotensin receptor antagonist, to conventional therapy, including ACE inhibitors, was examined. In this multicentre, randomised, double‐blind, placebo‐controlled study, 109 patients with heart failure (New York Heart Association functional class II and III) and left ventricular ejection fraction (LVEF) ≤40% received stable doses of ACE inhibitors and diuretics before and throughout the study. Irbesartan was titrated as tolerated to 150 mg once daily in all patients. Exercise tolerance time (ETT), LVEF and clinical status were assessed at baseline and after 12 weeks. Compared with placebo, irbesartan in combination with conventional therapy, including ACE inhibitors, produced favourable trends in ETT and LVEF and was well tolerated in patients with mild to moderate heart failure. (Int J Clin Pract 2000; 54(1): 11‐18)

Thallium-201 right lung/heart ratio during exercise in patients with coronary artery disease: relation to thallium-201 myocardial single-photon emission tomography, rest and exercise left ventricular function and coronary angiography.

The aim of this study was to correlate lung thallium-201 uptake on exercise with 201Tl single-photon emission tomography (SPET) myocardial perfusion imaging, rest and exercise equilibrium radionuclide angiographic and coronary angiographic findings in patients with coronary artery disease (CAD) using a simple, reproducible lung/heart (L/H) ratio that would be easy to use in clinical practice. L/H ratio was defined on the anterior planar image obtained during exercise 201Tl SPET acquisition as the mean counts per pixel in an entire right lung field region of interest divided by the mean counts per pixel in the hottest myocardial wall region of interest. We studied 103 patients. Fifty-nine patients (group I) with <5% likelihood of CAD were used as a reference group. In 44 CAD patients (group II), L/H ratio was compared with 201Tl SPET, radionuclide angiographic and coronary angiographic variables. The group I L/H ratio of 0.35+/-0.05 (mean +/-1 SD) was significantly lower (P<0.001) than the group II L/H ratio of 0. 45+/-0.10. An L/H ratio >0.45 (mean + 2 SD in group I) was considered abnormal. In group II, L/H ratio showed a significant correlation with stress and rest 201Tl perfusion defect size (r = 0. 39 and r = 0.42, P<0.01, respectively), but not with extent of ischaemic myocardium. The mean L/H ratio was 0.41+/-0.10 in patients with one-vessel disease (n = 15), 0.46+/-0.08 in those with two-vessel disease (n = 17) and 0.47+/-0.12 in those with three-vessel disease (n = 12), but no significant difference was found between the three subgroups. L/H ratio showed a significant inverse relation with rest and exercise left ventricular ejection fraction (r = -0.37 and r = -0.50, P<0.05 and P<0.001, respectively). Using stepwise multiple regression analysis, exercise left ventricular ejection fraction and previous history of hypertension were the sole two variables independently predictive of the L/H ratio. In conclusion, although lung thallium uptake is usually found to correlate with extent and severity of CAD, increased L/H ratio should primarily be considered as a marker of exercise-induced left ventricular systolic and perhaps diastolic dysfunction, probably independent of the underlying cardiac disease.

Twelve-year outcome of patients with an abnormal exercise radionuclide left ventricular angiogram and angiographically insignificant coronary artery disease

This study examines the long-term prognosis of patients with an abnormal exercise radionuclide angiogram in the absence of significant angiographic coronary artery disease (CAD). In general, patients without significant CAD have an excellent prognosis, but the long-term outcome for the subset of patients with an “ischemic” exercise test is not known. In this study, 161 patients with normal coronary arteries or insignificant CAD (<50% left main and <70% left anterior descending, left circumflex, or right), resting left ventricular (LV) ejection fraction ≥0.50, and an abnormal exercise radionuclide angiogram (LV ejection fraction that decreased with exercise or peak exercise LV ejection fraction <0.60) were followed for a median duration of 11.3 years. The mean Δ LV ejection fraction was −0.07, 98 patients (61%) had a decrease in LV ejection fraction of ≥5 units, and 40 patients (25%) had peak exercise LV ejection fraction <0.50. During follow-up there were 19 deaths (only 1 of which was cardiac), 7 nonfatal myocardial infarctions, and 9 revascularization procedures. At 12 years, overall survival was 88%, better than the expected survival for the age- and sex-matched general population. Survival free of cardiac death or myocardial infarction was 94% and survival free of any cardiac event including revascularization was 88%. Thus, patients with an abnormal exercise radionuclide angiogram but without significant CAD have an excellent long-term prognosis.