Treadmill Exercise Duration Research Articles

Zibotentan in microvascular angina: a randomized, placebo-controlled, crossover trial

Abstract Background/Introduction Microvascular angina is a chronic condition characterized by abnormal myocardial blood flow leading to ischemic symptoms. Endothelin-1, a peptide secreted by endothelial cells, is a highly potent constrictor of the human coronary arterioles. Microvascular angina is associated with elevated circulating concentrations of endothelin-1, and prolonged exposure to ‘excess’ endothelin causes vasoconstriction and vascular remodelling. The chronic elevation of circulating endothelin-1 in microvascular angina may be influenced by genetic factors. Purpose Zibotentan, the most selective antagonist of the endothelin A receptor with no off-target binding to the endothelin B receptor, was evaluated in oncology trials and did not improve survival. We identified zibotentan as a potential disease-modifying therapy for patients suffering from microvascular angina. We hypothesized that zibotentan 10 mg daily for 12 weeks in addition to background medical therapy could be an efficacious and safe treatment for patients with microvascular angina. We further hypothesized that the SNP regulator of EDN1 gene expression, rs9349379 (G allele), could be a novel theragnostic biomarker. Methods The trial involved a prospective, multicentre, randomized, double-blind, placebo-controlled, sequential crossover design to assess the effects of zibotentan 10 mg or matched placebo, once daily for 12 weeks. The primary outcome was treadmill exercise duration (seconds) using the Bruce protocol. The secondary outcomes included exercise test parameters, health status questionnaires, safety (frequency and severity of severe adverse events (SAEs) and adverse events), feasibility (withdrawal rate), and biomarkers of efficacy (pharmacokinetics, pharmacodynamics). Results The study found no significant difference in exercise duration with zibotentan (-4.26 seconds; 95% CI: -19.60 to 11.06; P=0.5871). There was no effect on the secondary outcomes. However, for exploratory (mechanistic) outcomes, zibotentan increased plasma big endothelin-1, endothelin-1, and global myocardial blood flow, while reducing hemoglobin, diastolic, and systolic blood pressure (all p<0.001). Adverse events were more common during the zibotentan period (60.2%) compared to placebo (14.4%, p<0.001). Conclusion(s) In conclusion, daily administration of 10 mg zibotentan for 12 weeks did not enhance exercise duration and was commonly associated with adverse effects related to fluid retention. Further trials exploring lower zibotentan doses in combination with agents to mitigate fluid retention, and longer treatment durations, are warranted.

Zibotentan in Microvascular Angina: A Randomized, Placebo-Controlled, Crossover Trial.

Background: Microvascular angina is associated with dysregulation of the endothelin system and impairments in myocardial blood flow, exercise capacity, and health-related quality of life. The G allele of the noncoding single nucleotide polymorphism RS9349379 enhances expression of the endothelin-1 gene (EDN1) in human vascular cells, potentially increasing circulating concentrations of Endothelin-1 (ET-1). Whether zibotentan, an oral ET-A receptor selective antagonist, is efficacious and safe for the treatment of microvascular angina is unknown. Methods: Patients with microvascular angina were enrolled in this double-blind, placebo-controlled, sequential crossover trial of zibotentan (10 mg daily for 12 weeks). The trial population was enriched to ensure a G allele frequency of 50% for the RS9349379 single nucleotide polymorphism. Participants and investigators were blinded to genotype. The primary outcome was treadmill exercise duration (seconds) using the Bruce protocol. The primary analysis estimated the mean within-participant difference in exercise duration after treatment with zibotentan versus placebo. Results: A total of 118 participants (mean ±SD; years of age 63.5 [9.2 ]; 71 [60.2% ] females; 25 [21.2% ] with diabetes) were randomized. Among 103 participants with complete data, the mean exercise duration with zibotentan treatment compared with placebo was not different (between-treatment difference, -4.26 seconds [95 ] CI, -19.60 to 11.06] P=0.5871). Secondary outcomes showed no improvement with zibotentan. Zibotentan reduced blood pressure and increased plasma concentrations of ET-1. Adverse events were more common with zibotentan (60.2%) compared with placebo (14.4%; P<0.001). Conclusions: Among patients with microvascular angina, short-term treatment with a relatively high dose (10 mg daily) of zibotentan was not beneficial. Target-related adverse effects were common.

Outcome indicators in clinical trials on traditional Chinese medicine treatment of microvascular angina

This study reviewed the current status of the use of outcome indicators in randomized controlled trial(RCT) on traditional Chinese medicine(TCM) treatment of microvascular angina(MVA) and analyzed the existing problems and possible solutions, aiming to provide a basis for the design of high-quality RCT and the establishment of core outcome sets for MVA. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries were searched for the RCT on TCM treatment of MVA according to pre-defined criteria. The Cochrane's risk of bias assessment tool was used to evaluate the methodological quality of the included RCT and the use of outcome indicators was summarized. A total of 69 RCTs were included, from which 100 outcome indicators were extracted, with the frequency of 430. The extracted outcome indicators belonged to 8 domains: response rate, symptoms and signs, physical and chemical examinations, TCM efficacy, safety, quality of life, economic evaluation, and long-term prognosis. The indicators of physical and chemical examinations were the most(70 indicators with the frequency of 211), followed by those of response rate(7 indicators with the frequency of 73) and symptoms and signs(7 indicators with the frequency of 54). The outcome indicators with higher frequency were adverse reactions, angina attack frequency, clinical efficacy, endothelin-1, total duration of treadmill exercise, and hypersensitive C-reactive protein. The RCT on TCM treatment of MVA had the following problems: irregular reporting of adverse reactions, diverse indicators with low frequency, lack of attention to the application of endpoint indicators, insufficient use of TCM differentiation and efficacy indicators, non-standard evaluation criteria and failure to reflect the basic characteristics of TCM. A unified MVA syndrome differentiation standard should be established, on the basis of which an MVA treatment efficacy evaluation system and core outcome indicator set that highlights the characteristics of TCM with patient-reported outcomes as the starting point should be established to improve the clinical research and research value.

Association between Cardiorespiratory Fitness and Bronchiectasis at CT: A Long-term Population-based Study of Healthy Young Adults Aged 18-30 Years in the CARDIA Study.

Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespiratory fitness and bronchiectasis. Materials and Methods This was a secondary analysis of a prospective observational study: the Coronary Artery Risk Development in Young Adults cohort (from 1985-1986 [year 0] to 2015-2016 [year 30]). During a 30-year period, healthy participants (age at enrollment 18-30 years) underwent treadmill exercise testing at year 0 and year 20 visits. Cardiorespiratory fitness was determined according to the treadmill exercise duration. The 20-year difference in cardiorespiratory fitness was used as the fitness measurement. At year 25, chest CT was performed to assess bronchiectasis and was used as the primary outcome. Multivariable logistic models were performed to determine the association between cardiorespiratory fitness changes and bronchiectasis. Results Of 2177 selected participants (at year 0: mean age, 25 years ± 4 [standard deviation]; 1224 women), 209 (9.6%) had bronchiectasis at year 25. After adjusting for age, race-sex group, study site, body mass index, pack-years smoked, history of tuberculosis, pneumonia, asthma and myocardial infarction, peak lung function, and cardiorespiratory fitness at baseline, preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT at year 25 (per 1-minute-longer treadmill duration from year 0 to year 20: odds ratio [OR], 0.88; 95% CI: 0.80, 0.98; P = .02). A consistent strong association was found when cough and phlegm were included in bronchiectasis (OR, 0.72; 95% CI: 0.59, 0.87; P < .001). Conclusion In a long-term follow-up, the preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.

Resting Heart Rate and Risk of Cancer Mortality.

Increased resting heart rate (RHR) is a predictor of mortality. RHR is influenced by cardiorespiratory fitness (CRF). Little is known about the combined associations of RHR and CRF on cancer mortality. 50,108 men and women (mean age 43.8 years) were examined between 1974 and 2002 at the Cooper Clinic in Dallas, Texas. RHR was measured by electrocardiogram and categorized as <60, 60-69, 70-79, or ≥80 beats/minute. CRF was quantified by maximal treadmill test and dichotomized as unfit and fit corresponding to the lower 20% and the upper 80%, respectively, of the age- and sex-specific distribution of treadmill exercise duration. The National Death Index was used to ascertain vital status. Cox regression was used to compute HRs and 95% confidence intervals (CI) for cancer mortality across RHR categories. During a mean follow-up of 15.0 ± 8.6 years, 1,090 cancer deaths occurred. Compared with RHR <60 beats/minute, individuals with RHR ≥80 beats/minute had a 35% increased risk of overall cancer mortality (HR, 1.35; 95% CI, 1.06-1.71) after adjusting for confounders, including CRF. Compared with "fit and RHR <80 beats/minute", HRs (95% CI) for cancer mortality were 1.41 (1.20-1.66), 1.51 (1.11-2.04), and 1.78 (1.30-2.43) in "unfit and RHR <80," "fit and RHR ≥80," and "unfit and RHR ≥80 beats/minute," respectively. RHR ≥80 beats/minute is associated with an increased risk of overall cancer mortality. High CRF may help lower the risk of cancer mortality among those with high RHR. RHR along with CRF may provide informative data about an individual's cancer mortality risk.

Relationship of Stress Test Findings to Anatomic or Functional Extent of Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve.

Background In the United States, functional stress testing is the primary imaging modality for patients with stable symptoms suspected to represent coronary artery disease (CAD). Coronary computed tomography angiography (CTA) is excellent at identifying anatomic coronary artery disease (CAD). The application of computational fluid dynamics to coronary CTA allows fractional flow reserve (FFR) to be calculated noninvasively (FFRCT). The relationship of noninvasive stress testing to coronary CTA and FFRCT in real-world clinical practice has not been studied. Methods We evaluated 206 consecutive patients at Loyola University Chicago with suspected CAD who underwent noninvasive stress testing followed by coronary CTA and FFRCT when indicated. Patients were categorized by stress test results (positive, negative, indeterminate, and equivocal). Duke treadmill score (DTS), METS, exercise duration, and chest pain with exercise were analyzed. Lesions ≥ 50%stenosis were considered positive by coronary CTA. FFRCT < 0.80 was considered diagnostic of ischemia. Results Two hundred and six patients had paired noninvasive stress test and coronary CTA/FFRCT results. The median time from stress test to coronary CTA was 49 days. Average patient age was 60.3 years, and 42% were male. Of the 206 stress tests, 75% were exercise (70% echocardiographic, 26% nuclear, and 4% EKG). There were no associations of stress test results with CAD > 50% or FFRCT < 0.80 (p = 0.927 and p = 0.910, respectively). Of those with a positive stress test, only 30% (3/10) had CAD > 50% and only 50% (5/10) had FFRCT < 0.80. Chest pain with exercise did not correlate with CAD > 50% or FFRCT < 0.80 (p = 0.66 and p = 0.12, respectively). There were no significant correlations between METS, DTS, or exercise duration and FFRCT (r = 0.093, p = 0.274; r = 0.012, p = 0.883; and r = 0.034, p = 0.680; respectively). Conclusion Noninvasive stress testing, functional capacity, chest pain with exercise, and DTS are not associated with anatomic or functional CAD using a diagnostic strategy of coronary CTA and FFRCT.

Rationale and design of the Medical Research Council's Precision Medicine with Zibotentan in Microvascular Angina (PRIZE) trial

BackgroundMicrovascular angina is caused by cardiac small vessel disease, and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina.MethodsWe will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan.The PRIZE trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo.ConclusionPRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial.

Abstract MP08: Higher Fitness Level and Favorable Hemodynamic Responses to Submaximal Exercise Test in Young Adults are Associated With Lower Risk of Chronic Kidney Disease in Later Life: The Framingham Heart Study

Introduction: Studies have demonstrated that higher cardiorespiratory fitness (CRF) and a favorable heart rate (HR) and blood pressure (BP) response to submaximal exercise, including during the recovery period, are associated with lower cardiovascular disease (CVD) risk. However, there are limited studies examining the association of CRF and hemodynamic response to exercise test with incidence of chronic kidney disease (CKD). Hypothesis: We hypothesized that high CRF and a favorable HR and BP response to submaximal exercise test and during recovery will be associated with lower risk of CKD prospectively. Methods: We evaluated 3,535 Framingham Offspring Study participants (mean age 43.5 yrs, 52.1% women) without CKD, who completed a submaximal exercise test between 1979-1983. CKD incidence was defined as eGFR &lt;60ml/min/1.73m 2 on follow-up. Multivariable-adjusted Cox regression models with discrete time intervals were used to relate CRF and hemodynamic responses to exercise test at baseline with the incidence of CKD on follow-up. Results: At baseline, 23% of participants had chronotropic incompetence and 19.6% had impaired HR recovery after exercise (Δ HR 1 &lt; 12 bpm). On follow-up (median 25.7 years), 801 individuals (22.8%; 434 women) developed CKD. Participants in the second and third tertile of CRF (defined based on age and sex-specific treadmill exercise duration) had lower risk of CKD compared to those in the first tertile of CRF ( Table ). Participants with chronotropic incompetence, higher peak SBP during exercise and impaired HR recovery had higher risk of CKD, compared to those with chronotropic competence, lower peak SBP during exercise, and normal HR recovery post-exercise ( Table ). Conclusions: Higher CRF and favorable HR and BP responses to exercise test in young adulthood may be a marker of lower risk of CKD in later life. The biological mechanisms underlying the observed association warrant further investigation.

Validation of the Seattle angina questionnaire in women with ischemic heart disease

BackgroundAlthough the Seattle Angina Questionnaire (SAQ) has been widely used to assess disease-specific health status in patients with ischemic heart disease, it was originally developed in a predominantly male population and its validity in women has been questioned. MethodsUsing data from 8892 men and 4013 women across 2 multicenter trials and 5 registries, we assessed the construct validity, test–retest reliability, responsiveness to clinical change, and predictive validity of the SAQ Summary Score (SS) and its 5 subdomains (Physical Limitation (PL), Anginal Stability (AS), Angina Frequency (AF), Treatment Satisfaction (TS), and Quality of Life (QoL)) separately in men and women. ResultsComparable correlations of the SAQ SS with Canadian Cardiovascular Society class was demonstrated in both men and women (−0.48 for men, −0.46 for women). Similar correlations between the SAQ PL scale with treadmill exercise duration and Short Form-12 (SF-12) Physical Component Summary were observed in women and men (0.34–0.63 and 0.40–0.63, respectively). SAQ AS scores were significantly lower for both men and women with acute syndromes compared with 1 month later. The SAQ AF scale was strongly correlated with daily angina diaries (0.62 for men and 0.66 for women). The SAQ QoL scores were moderately correlated with the EQ5D visual analog scale and SF-12 general health question in men (0.43–0.50) and women (0.33–0.39). All SAQ scales demonstrated excellent reliability (intraclass correlation ≥0.78) in both men and women with stable CAD and were very sensitive to change after percutaneous coronary intervention (≥15-point difference in scores, standardized response mean ≥ 0.67). The SAQ SS was similarly predictive of 1-year mortality and cardiac re-hospitalizations for both men and women. ConclusionThe SAQ demonstrates similar psychometric properties in men and women with CAD. These findings provide evidence for validity of the SAQ in assessing women with IHD.

Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.

Effect on VLa4 of Reduced Exercise Periods During Conditioning of Horses

IntroductionOne week of reduced workload between 3 periods of 2 weeks of conditioning (CP) 5 times/fortnight at VLa10 for two bouts of 5 minutes allowed for a continuous increase of VLa4, but the extent was smaller than in another study with the same conditioning program but for the recovery week (VLa4, VLa10: horse's speed, which produced a blood lactate concentration of 4 and 10 mmol/l).MethodsSix Purebred Arabians were submitted to the same conditioning protocol of the studies mentioned above except for increasing the duration of treadmill exercise in each CP by 2.5 minutes (2 x 10 minutes in the third CP). A standardized exercise test (SET) was performed at the beginning of CP to determine VLa4 and VLa10, and repeated after the week with reduced workload after each CP. Exercise speed was individually adapted to the new VLa10 for every CP. The effects of conditioning on VLa4 were examined using repeated measures analysis of variance. Significant results were analyzed further with Fisher's test.ResultsMean VLa4 increased after the first CP (P&lt;0.001), fell between first and second CP (P&lt;0.001) and remained at this level after the third CP (P&gt;0.05).ConclusionsThis conditioning program did not allow for VLa4 increases of the magnitude observed in other studies with the same exercise protocols but without the week with reduced workload and increases in exercise duration. It is possible that the decline of VLa4 of the horses after the first CP was due to overtraining (simultaneous increase of speed and duration of exercise). The effect of recovery from training needs further studies.Ethical Animal ResearchAll procedures were approved by the Bioethical Committee of the University of La Plata, Argentina. Sources of funding: Verein zur Förderung der Forschung im Pferdesport, Germany. Competing interests: none.

Integrated treadmill stress testing and MR relaxometry (T1, T2, T2*): response in healthy calf muscles

Background Peripheral arterial disease (PAD) is accompanied by a complex lower limb pathophysiology resulting in reduced functional capacity and quality of life. We aim to characterize the exercise recovery kinetics in the calf muscle of healthy volunteers by combining treadmill exercise and magnetic resonance (MR) relaxometry (T1, T2 and T2*), and to investigate their relation with age and treadmill exercise duration.

Atrial Fibrillation reduces the Functional REServe of the Heart by a fifth: A pilot FRESH-AF study

The advent of catheter ablation has reignited the controversy about whether rhythm or rate control should be the preferred mode of therapy for atrial fibrillation (AF) [1]. It is well known that compared to sinus rhythm (SR), AF is associated with increased mortality and morbidity including stroke, heart failure, and impaired quality of life. Furthermore, patients may experience adverse effects from drug treatment that may negate thebeneficial effects ofmaintaining SR [2].What is still unknown is inwhatways and by howmuch overall cardiac function is impairedwhen the atrial “kick” in SR is lost after the onset of AF. To fill this gap in knowledge, it is essential to assess cardiac functionnot onlyat rest but also during maximal stress, and not merely piecemeal aspects of cardiac function. This can be achieved by conducting full cardiopulmonary exercise testing (CPX) in combination with non-invasive evaluation of central haemodynamics [3]. Thiswouldprovide a quantitative assessment of aerobic physical exercise capacity represented by peak O2 consumption (VO2max), together with peak cardiac power output (CPOmax) which measures the overall cardiac dysfunction [4], and is by far the strongest predictor of prognosis in heart failure patients [5]. As metabolic and circulatory demands increase during severe exercise, patients with AF have lower cardiovascular reserve. Previous studies have shown that VO2max improved by 5–13% after restoration of SR in patients with AF [6], buthowmuchcardiac functional gain is achieved thereby is still unknown. We therefore measured changes in CPOmax after successful DC cardioversion (DCCv) in patients with optimally rate-controlled AF. In so doing, we tested the hypothesis that the cardiac pumping capability of patients in AF is diminished by about a fifth. Twelve unselected ambulatory patients (10 males, age: 57.5 ± 13.7 (mean ± SD) years) with symptomatic persistent AF recruited from outpatient clinics underwent full CPX with measurements of non-invasive haemodynamics before and after successful DCCv. The aetiologies (including overlaps) of their AF were ischaemic heart disease (17%), hypertension (25%), LV dysfunction (42%), valve disease (25%), lone AF (25%), and obesity (BMI N 35, 25%). None of the patients had previous catheter ablation, or any contraindication to undergomaximal exercise, such as significant outflow obstruction, haemodynamically serious structural heart disease, uncontrolled ventricular tachyarrhythmia, uncontrolled hypertension, limiting symptoms of ischaemic heart disease, inability or deemed unsafe to exercise on treadmill, contraindications to electrical cardioversion or full anticoagulation, or inability to provide full informed consent. Standardexerciseparametersweremeasuredaspartof an incremental cardiopulmonary exercise test performed on a Trackmaster TMX425 treadmill (Full Vision, Kansas, USA) using the Bruce or modified Bruce protocol, as previously described [3]. Rates of oxygen consumption (VO2) and other gaseous exchanges were recorded breath-by-breath using the Medgraphics Ultima CardiO2 analytic system (Medgraphics, Minnesota, USA). Using the CO2-rebreathing technique (indirect Fick), cardiac output were measured at rest and during peak exercise. Mean arterial pressure was calculated from the equation, MAP=DBP+ 0.412 ∗ (SBP− DBP) [7]. CPOmax in watts is the product of peak cardiac output (COmax in l.min−1)multiplied by theMAP inmm Hg at peak exercisemultiplied by a conversion factor (2.22 × 10−3) [8]. A paired sample t-test was used to assess the change in cardiac reserve variables pre and post DCCv. This study was approved by the National Research Ethics Service Committee for Yorkshire & Humber in Leeds East. After successful cardioversion, subjectively all patients claimed to feel better and more energetic and, as shown in Table 1, objectively their treadmill exercise duration increased by 19.3% (P b 0.05), coupled with an improvement in peak O2 consumption by 16.5% (P b 0.01). Their resting ventricular rate decreased from 83.1 ±20.3 to 66.9 ± 20.5 min− 1 (P b 0.05), while peak exercise HR decreased from 163 ± 42 to 128 ± 18 min−1 to (P b 0.05). Secondarily, these negative chronotropic effects led to heightened stroke volume at peak exercise by 46% (P b 0.0001), thereby raising the peak cardiac output by 16.5% (P b 0.0001). Due to a concomitantly greater

Abstract 316: Favorable Long Term Rates of Revascularization and Myocardial Infarction with Optimal Medical Therapy: No Effect of Second Opinion Status for Invasive Management

Long-term outcomes of patients (pts) with stable coronary artery disease (CAD) are needed to properly assess the efficacy of Optimal Medical Therapy (OMT). Whether pts who seek a second opinion (SO) regarding OMT are at higher risk by virtue of the first opinion for invasive management is unknown. As part of a prospective cohort study of OMT in pts with stable CAD without prior coronary artery bypass graft (CABG), we ascertained opinion status at entry and the end-points of myocardial infarction (MI) and revascularization (revasc) as of 2005. Out of 693 pts, opinion status was available in 646 pts; of these, 118 were SO for invasive evaluation and management. Management decisions were based on history, physical examination, and non-invasive data; coronary anatomy was available in only 50% of the SO cohort. During follow up, the decision to intervene depended on stability of symptoms, LV function, and treadmill exercise duration. Revasc was defined as percutaneous coronary intervention (PCI) or CABG. MI was defined as meeting two of the three WHO criteria or a typical pattern of MI on a myocardial perfusion study or 2-D Echocardiography. Assessment of clinical predictors of each endpoint used stepwise multivariate Cox modeling with 0.15 as level of entry and 0.8 as level of removal. Variables significant at the 0.05 level in a univariate model as well as SO status were included. Results: The mean age of the cohort was 67.3 years, and the majority of pts (53.9%) had class 1 or 2 angina. During mean follow-up time of 6.9 years there were a total of 252 revascularization events and 114 MIs, of which 11 were fatal. SO patients were younger with a mean age of 63.9 years. Coronary anatomy was available in 39% of the entire cohort, and 50% of the SO group. The strongest predictor of MI or revasc in Cox models was a change in clinical stability of CAD. For Revasc, other predictors were BMI, total cholesterol, diastolic BP, and angina at entry; for MI, other predictors were resting ejection fraction and treadmill duration. SO status was not a predictor of either event. Conclusions: Long term rates of revasc and MI in pts with stable CAD managed with OMT were low, and comparable to the medical arms of the COURAGE and BARI2D trials. Our study extends those results to a longer follow up period. SO status per se was not a predictor of either revasc or MI, suggesting that pts with a previous recommendation for invasive management who sought a SO did not represent a higher risk sub-group.

Prognostic Value of Late Heart Rate Recovery After Treadmill Exercise

Recovery from exercise can be divided into an early, rapid period and a late, slower period. Although early heart rate (HR) recovery 1 minute after treadmill exercise independently predicts survival, the prognostic value of late HR recovery has not been well studied. The aim of this study was to evaluate the independent prognostic value of late HR recovery for all-cause mortality. A total of 2,082 patients referred to the nuclear cardiology laboratory of an urban academic medical center for treadmill exercise with imaging from August 1998 to December 2003 were followed for all-cause mortality. During 9.9 ± 1.5 years of follow-up, 196 deaths (9%) occurred. To avoid overlap with early HR recovery or the baseline HR, late HR recovery was defined as the percentage of the cycle length change between rest and peak exercise that had been recovered after 5 minutes. Lower values represent impaired recovery, by analogy with 1-minute HR recovery. Impaired late HR recovery was a significant univariate predictor of all-cause mortality (hazard ratio 0.28 per percentage, 95% confidence interval 0.17 to 0.46, p <0.001). It significantly improved a nested, multivariate model (change in chi-square 8.66, p = 0.003), including 1-minute HR recovery, with independent prognostic value (adjusted hazard ratio 0.58, 95% confidence interval 0.41 to 0.84, p = 0.004). In conclusion, late HR recovery after treadmill exercise stress adds prognostic value for all-cause mortality to a multivariate model including early, 1-minute HR recovery.

A COMPARATIVE STUDY OF EFFICACY AND TOLERABILITY OF ANTIANGINAL DRUGS OF DIFFERENT GROUPS — NITROVASODILATATOR (ISOSORBIDE-5-MONONITRATE SUSTAINED RELEASE) AND BETA-BLOCKER WITH VASODILATING ACTION (NEBIVOLOL) — IN PATIENTS WITH STABLE ANGINA

Aim. To compare the efficacy and safety of the slow-release isosorbide-5-mononitrate and of the nebivolol in patients with stable angina. Material and Methods. Patients (n=19) with ischemic heart disease (stable angina) were enrolled into randomized, double-blind, placebo-controlled, crossover study. They alternatively received nebivolol 5 mg QD or slow-release isosorbide-5-mononitrate 50 mg QD. The drug efficacy was assessed by changes in symptoms, angina attack number , sublingual nitroglycerin need, and treadmill test duration. Results. Patients treated with isosorbide-5-mononitrate shown significant increase in heart rate (HR) at rest in all time check-points in comparison with patients receiving placebo. HR significantly decreased 2 hours after nebivolol intake both single one and after 30 days of treatment (p&lt;0.001). Duration of treadmill exercise significantly increased (vs placebo) 2 hours after a single intake of both isosorbide-5-mononitrate (454.3±37.1 vs 310.6±13.3 s; p &lt;0.001) and nebivolol (428.6±33.3 vs 310.6±13.3 s; p&lt;0.01). In one month of treatment isosorbide- 5-mononitrate and nebivolol reduced a number of angina episodes vs placebo (5.6±2.1 and 4.3±1.4, respectively , vs 8.6±2.4 episodes per month; p&lt;0.05), the need for nitroglycerin (5.5±2.6 and 3.1±1.2, respectively , vs 6.7±2.2 sublingual tablets/month; p&gt;0.05). No significant differences of these indicators were found between studied drugs. Conclusion. Nebivolol 5 mg daily is not inferior to slow-release isosorbide-5-mononitrate 50 mg daily in antianginal efficacy , significantly reduces HR, and much less causes headache and other side effects.

Post Exercise Carbohydrate And Fat Oxidation Rates In Women With Different Levels Of Body Fat

PURPOSE: Substrate oxidation during and after exercise may be affected by the level of body fat. We investigated the effects of prior exercise on post-exercise carbohydrate (CHO) and fat (FAT) oxidation rates in women of high (>25%, HF) and low (<25%, LF) body fat percentage. METHODS: 14 healthy, physically active young (18-23 y) females were categorized by body composition into a high fat >25% (HF, n=8) or low fat <25% (LF, n=6) group. Air displacement plethysmography was used to determine percent body fat (% fat), fat-free mass (FFM), and fat mass (FM), and a graded exercise test was used to determine maximal aerobic power (VO2max). HF women were 30.9±3.7% fat; LF women were 21.6±2.6% fat. Following a 10 h fast, subjects completed 2 treatment sessions (30 min and 60 min duration) of treadmill exercise at 55% of VO2max. For 2 h post-exercise, expired gases were analyzed to determine FAT and CHO oxidation rates, which were normalized to mg/kg FFM/min. A group x treatment x time ANOVA was used to determine significant differences with p<0.05. RESULTS: There was no significant difference between groups for VO2max (HF 63.6±11.8 ml/kg FFM/min and LF 62.2±5.9 ml/kg FFM/min). There were no significant differences between groups or within the 2 h post-exercise period following the 30 min session. A significant group effect was observed following the 60 min exercise session with HF women displaying lower CHO and higher FAT oxidation rates (mg/kg FFM/min) during the 2 h post-exercise period.Table: No caption provided.CONCLUSIONS: In women of similar fitness levels, the percentage of body fat may play a role in determining post-exercise substrate oxidation rates during exercise of longer duration (e.g. 60 min vs 30 min).

Response to “Obesity and Treadmill Exercise Duration in Hazmat Candidates”

Response to “Obesity and Treadmill Exercise Duration in Hazmat Candidates”

Obesity and Treadmill Exercise Duration in Hazmat Candidates

Obesity and Treadmill Exercise Duration in Hazmat Candidates

Safety, Acceptance, and Physiologic Effects of Sauna Bathing in People With Chronic Heart Failure: A Pilot Report

Basford JR, Oh JK, Allison TG, Sheffield CG, Manahan BG, Hodge DO, Tajik AJ, Rodeheffer RJ, Tei C. Safety, acceptance and physiologic effects of sauna bathing in people with chronic heart failure: a pilot report. Objectives To perform a pilot study and make a preliminary assessment of the safety and acceptance of supervised sauna bathing at moderate temperatures in people with chronic heart failure (CHF). Secondary measures included its impact on exercise tolerance and neuroendocrine concentrations. Design Randomized, controlled, cross-over trial. Setting Physical medicine and rehabilitation clinic. Participants Six men and 3 women (age, 62–87y) with New York Heart Association Class III and IV CHF. Interventions Subjects were randomized into 2 groups and told to maintain their normal medication and activity regimens. One group then began a 3-times-a-week, 4-week sauna bathing program at 60±1°C while the other continued with their usual activities and medications. Assignments were then reversed. Sessions were 15 minutes in length but were prolonged an additional 5 minutes for oral temperature increases less than 1.0°C. Main Outcome Measures Patient acceptance, Minnesota Living With Heart Failure Questionnaire (MLWHFQ) scores; treadmill exercise duration and plasma adrenaline, noradrenalin, aldosterone, atrial naturectic factor, adrenomedulin, and endothelin. Results Sauna bathing was well tolerated and no adverse effects were reported. Improvements in MLWHFQ scores and treadmill endurance did not achieve statistical significance on a between-group basis but were more marked after the sauna than during the control phase. Neuroendocrine concentrations showed no clear effect of sauna treatment with a between-group statistically significant difference ( P=.049) found only in the case of noradrenalin's 24% decrease. Conclusions Sauna bathing under the moderate and supervised conditions of this study appears to be well tolerated and may be safe for people with CHF. More research is needed to further evaluate the safety and potential benefits of this approach.