Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Disease management using home-based cardiac rehabilitation for patients with heart failure.

Home-based cardiac rehabilitation (HBCR) is expected to address the low participation rate in cardiac rehabilitation; however, it is not covered by insurance in Japan, and the optimal method for monitoring a patient's condition during exercise has not been determined. Patients hospitalized for heart failure often deteriorate soon after discharge and require appropriate disease monitoring. In this report, we describe cases in which real-time monitoring of exercise intensity, electrocardiography, and video chat during HBCR was useful in the management of heart failure. Furthermore, the use of HBCR enabled frequent disease monitoring, even during the coronavirus disease 2019 pandemic, and timely medicine adjustment. Learning objective: Clinicians cannot perform radiography, blood tests, or physical examinations at home during home-based cardiac rehabilitation (HBCR). Therefore, it is particularly important to reconsider the appropriate monitoring indicators for HBCR and apply them to disease management. Our cases suggest that real-time monitoring of the following three indicators is useful for disease management using HBCR: (1) exercise intensity, (2) electrocardiography, and (3) shortness of breath.

Predictors of Improvement in Exercise Capacity After Cardiac Rehabilitation Differ Between Octogenarian and Young-Old Patients With Acute Myocardial Infarction.

BACKGROUND: Whether the magnitude and predictors of improvement in exercise capacity after cardiac rehabilitation (CR) are the same between young-old (YO) and octogenarian (OCT) patients with acute myocardial infarction (AMI) is unknown.Methods and Results: We studied 284 YO (age range 65-69 years; mean [±SD] 67±1 years) and 65 OCT (age range ≥80 years; mean [±SD] 83±2 years) patients who participated in a post-AMI CR program. After 3 months of CR, peak oxygen uptake (PV̇O2) measured during cardiopulmonary exercise testing improved significantly in both age groups (P<0.01), although the percentage increase in PV̇O2(%∆PV̇O2) was significantly smaller in the OCT than YO group (5.4±13.7% vs. 10.0±12.8%; P<0.01). Multiple regression analysis demonstrated that independent predictors of %∆PV̇O2were the number of outpatient CR (OPCR) sessions attended (P=0.015), left ventricular ejection fraction (P=0.028), and baseline PV̇O2(P=0.0007) in the YO group; and the number of sessions attended (P=0.018), atrial fibrillation (P=0.042), and the presence of nutritional risk (Geriatric Nutritional Risk Index ≤98; P=0.036) in the OCT group. CONCLUSIONS: The predictors of improvement in exercise capacity after CR differed between the YO and OCT patients with AMI. To obtain a greater improvement in PV̇O2in CR, frequent OPCR session attendance may be necessary in both groups; in addition, particularly in OCT patients, better nutritional status may be important.

Association of adherence to a 3 month cardiac rehabilitation with long-term clinical outcomes in heart failure patients.

AIMS: Although comprehensive cardiac rehabilitation (CCR) is recommended for patients with heart failure (HF), participants often show low adherence. The aim of this study was to evaluate the association of CCR completion and response with long-term clinical outcomes. METHODS AND RESULTS: We screened 824 HF patients who participated in a 3 month CCR programme and underwent baseline assessment, including cardiopulmonary exercise testing (CPX). After excluding 52 participants who experienced all-cause death or HF hospitalization within 180 days, long-term outcomes were compared between those who attended 3 month follow-up assessment including CPX (completers) and those who did not (non-completers). We also compared the prognostic value of the changes in peak oxygen uptake (VO2 ) vs. quadriceps muscle strength (QMS) during the 3 month CCR programme. Among the 772 study patients, there were no significant differences in baseline characteristics, including left ventricular ejection fraction, B-type natriuretic peptide levels, and peak VO2 , between the completers (n = 561) and non-completers (n = 211), except for a higher age (63.2 ± 14.2 vs. 59.4 ± 16.2 years; P = 0.0015) and proportion of females (27% vs. 17%; P = 0.0030) among the completers. During a median follow-up of 55.4 months, the completers had lower rates of the composite of all-cause death or HF hospitalization (34.4% vs. 44.6%; P = 0.0015) and all-cause death (16.9% vs. 24.6%; P = 0.0037) than the non-completers. After adjustment for prognostic baseline characteristics, including age and sex, CCR completion was associated with 34% and 44% reductions in the composite outcome and all-cause death, respectively. Among the completers, peak VO2 and QMS increased significantly (8.9 ± 15.8% and 10.5 ± 17.9%, respectively) over 3 months. Patients who had an increase in peak VO2  ≥ 6.3% (median value) during the CCR programme had significantly lower rates of the composite outcome (27.0% vs. 33.8%; P = 0.048) and all-cause mortality (10.0% vs. 17.4%; P = 0.0069) than those who did not. No statistically significant difference was observed in the composite outcome (30.5% vs. 30.4%; P = 0.76) or all-cause mortality (13.0% vs. 14.4%; P = 0.39) between those with and without an increase in QMS ≥8.3% (median value). CONCLUSIONS: In HF patients who participated in a 3 month CCR programme, its completion was associated with lower risks of subsequent HF hospitalization and death. Within the group of patients who completed the programme, the improvement in exercise capacity, but not in skeletal muscle strength, over the 3-month period was associated with better outcomes. These findings highlight the importance of the post-CCR follow-up assessment, including CPX, to identify a patient's adherence and response to the CCR programme.

Sex-related Differences in Exercise Capacity Trends and Determinants after Cardiac Rehabilitation in Patients with Acute Myocardial Infarction.

OBJECTIVE: This study aimed to investigate whether longitudinal changes in exercise capacity in patients with acute myocardial infarction (AMI) differ by sex and clarified what contributed to these differences. METHODS: We retrospectively examined the differences in each variable between men and women in 156 patients with AMI (mean age: 65 ± 12 years; 82.0% male) who participated in a 3-month cardiac rehabilitation (CR) program and could be followed-up for exercise capacity 12-months after AMI onset. Sex-related differences in the change in peak oxygen uptake (peak VO2) at baseline, 3-months, and 12-months after AMI were analyzed. RESULTS: Male patients with AMI were younger and had higher body mass index and employment rate than women. The attendance of the CR program was higher in women (men vs. women; 10 [3-15] vs. 14 [11-24] sessions, p = 0.0002). Women showed a significant lower %change in peak VO2 after 12 months (men vs. women; 7.8% [-0.49% to 14.6%] vs. 1.3% [-5.7% to 7.5%], p = 0.013). In multiple linear regression analysis, age (ß = -0.76, 95% confidence interval [CI] = -1.0 to -0.50, p <0.0001) and female sex (ß = -6.3, 95% CI = -9.1 to -3.5, p <0.0001) were negative independent predictors of change in peak VO2 over 12 months, while CR attendance (ß = 0.21, 95% CI = 0.0032-0.42, p = 0.047) and recommended exercise habit after the CR program (ß = 2.1, 95% CI = 0.095-4.1, p = 0.040) were positive independent predictors of change in peak VO2 over 12 months. CONCLUSION: In female patients, exercise capacity improved during the CR program but decreased to AMI onset levels after 12 months.

Depressive symptoms interfere with the improvement in exercise capacity by cardiac rehabilitation after left ventricular assist device implantation.

BACKGROUND: Although depressive symptoms are associated with an increased risk of readmission after left ventricular assist device (LVAD) implantation, it is unclear whether they affect the efficacy of exercise-based cardiac rehabilitation (EBCR). This study aimed to investigate the effect of depressive symptoms on EBCR efficacy. METHODS: We analyzed 48 patients who participated in EBCR after LVAD implantation (mean age 45 ± 12 years; 60% male). Patients were classified into two groups using the Zung Self-Rating Depression Scale (SDS): depressive group (SDS ≥40, n = 27) and non-depressive group (SDS <40, n = 21). We examined changes in peak oxygen uptake (VO2 ), knee extensor muscular strength (KEMS), and quality of life (QOL) during EBCR using analysis of covariance. RESULTS: Although baseline characteristics were similar between the two groups, the non-depressive group was less likely to receive diuretics (22% vs. 52%, p = 0.030). Peak VO2 , KEMS, and QOL significantly increased over time in both groups (all p < 0.05). The depressive group had a significantly lower change in peak VO2 than the non-depressive group (2.7 vs. 1.6 ml/kg/min; mean difference: -1.1 ml/kg/min, 95% confidence interval [CI]: -0.045 to -2.17; p = 0.041, d = 0.59). There was no between-group difference regarding the change in KEMS or QOL. Adjusting for the baseline value, a significant difference between groups was observed only in peak VO2 (p = 0.045). CONCLUSIONS: Although EBCR significantly improved exercise capacity after LVAD implantation, depressive symptoms interfered with this improvement. Further studies are needed to determine whether psychological interventions for depression, in addition to EBCR, would improve the response to EBCR after LVAD implantation.

Mid-Right Coronary Artery Spasm Diagnosed by an Ergometrine Provocation Test Through a Saphenous Vein Graft.

Although coronary artery spasm is a cause of acute coronary syndrome (ACS), demonstration of its possible cause in patients with a history of coronary artery bypass grafting remains challenging. We report a case of ACS that successfully provoked coronary artery spasm by pharmacological testing through a saphenous vein graft. (Level of Difficulty: Beginner.).

Exercise-Based Cardiac Rehabilitation Improves Exercise Capacity Regardless of the Response to Cardiac Resynchronization Therapy in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND: In patients with chronic heart failure with reduced ejection fraction (HFrEF), cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) and exercise-based cardiac rehabilitation (ECR) enhances exercise capacity. This study examined the relationship between the 2 responses.Methods and Results:Sixty-four consecutive HFrEF patients who participated in a 3-month ECR program after CRT were investigated. Patients were categorized according to a median improvement in peak oxygen uptake (PV̇O2) after ECR of 7% as either good (n=32; mean percentage change in PV̇O2[%∆PV̇O2]=23.2%) or poor (n=32; mean %∆PV̇O2=2.5%) responders. There was no significant difference in baseline characteristics between the good and poor responders, except for PV̇O2(51% vs. 59%, respectively; P=0.01). The proportion of good CRT responders was similar between the good and poor responders (%∆LVEF ≥10%; 53% vs. 47%, respectively; P=NS). Overall, there was no significant correlation between %∆LVEF after CRT and %∆PV̇O2after ECR. Notably, among poor CRT responders (n=32), the prevalence of atrial fibrillation (0% vs. 29%; P<0.03) and baseline PV̇O2(48% vs. 57%; P<0.05) were significantly lower among those with a good (n=15) than poor (n=17) response to ECR. CONCLUSIONS: In patients with HFrEF, good ECR and CRT responses are unrelated. A good PV̇O2response to ECR can be achieved even in poor CRT responders, particularly in those with a sinus rhythm or low baseline PV̇O2.

COVID-19 pandemic is associated with mechanical complications in patients with ST-elevation myocardial infarction.

OBJECTIVE: Although there are regional reports that the COVID-19 pandemic is associated with a reduction in acute myocardial infarction presentations and primary percutaneous coronary intervention (PCI) procedures, little is known about the impact of the COVID-19 pandemic on mechanical complications resulting from ST-segment elevation myocardial infarction (STEMI) and mortality. METHODS: This single-centre retrospective cohort study analysed presentations, incidence of mechanical complications, and mortality in patients with STEMI before and after a state of emergency was declared due to the COVID-19 pandemic by the Japanese government on 7 April 2020. RESULTS: We analysed 359 patients with STEMI hospitalised before the declaration and 63 patients hospitalised after the declaration. The proportion of patients with late presentation was significantly higher after the declaration than before (25.4% vs 14.2%, p=0.03). The incidence of late presentation was significantly higher during the COVID-19 pandemic than before (incidence rate ratio (IRR), 2.41; 95% CI, 1.37 to 4.05; p=0.001, even after adjusting for month (IRR, 2.61; 95% CI, 1.33 to 5.13; p<0.01). Primary PCI was performed significantly less often after the declaration than before (68.3% vs 82.5%, p=0.009). The mechanical complication resulting from STEMI occurred in 13 of 359 (3.6%) patients before the declaration and 9 of 63 (14.3%) patients after the declaration (p<0.001). However, the incidence of in-hospital death (before, 6.2% vs after, 6.4%, p=0.95) was comparable. CONCLUSIONS: Following the COVID-19 pandemic, an increased incidence of mechanical complications resulting from STEMI was observed. Instructing people to stay at home, without effectively educating them to immediately seek medical attention when suffering symptoms of a heart attack, may worsen outcomes in patients with STEMI.

Cardiac rehabilitation program improves exercise capacity in heart transplantation recipients regardless of marginal donor factors.

Cardiac rehabilitation (CR) is recommended to improve exercise capacity after heart transplantation (HTx); however, the effects of marginal donor factors are unclear. Forty-one recipients participated in a 3-month CR program early after HTx (mean age 39 ± 14 years; 88% male). Patients were divided into marginal (≥ 2 marginal donor factors; n = 24) and control groups (< 2 marginal donor factors; n = 17). We examined donor and recipient factors related to change in peak oxygen uptake (peak VO2) during the CR program using multiple linear regression analysis. Baseline characteristics were similar between groups, although the mean age was higher in the marginal group (43 ± 13 vs. 34 ± 14 years, p = 0.043). Peak VO2 and knee extensor muscular strength (KEMS) improved significantly in both groups (p < 0.05), but there were no observed inter-group differences. Multiple analysis revealed change in KEMS (ß = 0.52, 95% CI = 0.023-1.01) as an independent predictor of change in peak VO2 after adjustment for recipients' age, sex, and CR attendance frequency (adjusted R2 = 0.25, p = 0.0084), whereas marginal donor factors were not a predictor (p = 0.76). The CR program improved exercise capacity in HTx recipients regardless of marginal donor factors, suggesting that recipients of marginal donor hearts should be referred to CR programs.

Effects of exercise training on physical activity in heart failure patients treated with cardiac resynchronization therapy devices or implantable cardioverter defibrillators.

OBJECTIVE: This study elucidated the effects of exercise training on physical activity, 6-min walk distance, and all-cause hospitalization rates in patients with chronic heart failure, and evaluated factors contributing to changes in physical activity. DESIGN: Prospective cohort observational study. PATIENTS AND METHODS: Patients (n =62) who completed an exercise training programme after implantable cardioverter-defibrillator or cardiac resynchronization therapy treatment between May 2017 and May 2018 were included. Patients exercised for 20-50 min 3-5 times weekly for 3 months and were assigned to the active (≥ 10 min/day) or non-active (< 10 min/day) group based on changes in walking times between baseline and 3 months, as assessed by the International Physical Activity Questionnaire. RESULTS: The 6-min walk distance improved in both groups with exercise training. Physical activity level did not increase in some patients, despite improvements in exercise tolerance. Depression improved significantly in the active group, but no correlation was found with physical activity. Factors contributing to physical activity changes were not identified. The all-cause hospitalization rate was lower in the active group during follow-up (mean 10.5 months). CONCLUSION: Exercise training effectively increased 6-min walk distance regardless of physical activity. Non-active patients experienced increased all-cause hospitalizations. Increasing physical activity improves patient outcomes.

Combination of Peak Exercise Systolic Blood Pressure and Left Atrial Diameter as a Novel Non-Spirometry Prognostic Predictor Comparable to Peak Oxygen Uptake for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Although peak oxygen uptake (pV̇O2) is a well-established powerful prognostic predictor in heart failure (HF) patients, implementation of cardiopulmonary exercise testing (CPX) is limited by its complex analysis. We aimed to develop a new bivariate predictor obtained without respiratory gas measurement, comparable to pV̇O2.Methods and Results:We studied 560 consecutive HF patients with ejection fraction (EF) <45% who underwent CPX. During a median follow-up of 49.0 months, the composite of all-cause death or HF hospitalization occurred in 228 patients (40.7%) and all-cause death in 111 (19.8%). pV̇O2was the strongest single predictor of the composite outcome (chi-square, 99.3). Among the bivariate non-spirometry parameters, the ratio of systolic blood pressure at peak exercise to left atrial diameter (pSBP/LAD) was the strongest predictor (chi-square, 112.4). Patients with pSBP/LAD <2.8 mmHg/mm, compared with those with pSBP/LAD ≥2.8 mmHg/mm, had a hazard ratio of 3.84 (95% confidence interval, 2.95-5.04) for the composite outcome and 3.66 (2.50-5.37) for all-cause death. In the subgroup with pV̇O2<14 mL/kg/min (n=149), where pV̇O2had no further predictive value, pSBP was the strongest single predictor, and the predictive power of pSBP/LAD was more enhanced. CONCLUSIONS: pSBP/LAD was a new powerful predictor of HF hospitalization and death, comparable to pV̇O2, in HF with reduced EF. Because of its simplicity and high availability, this index has the potential for more widespread use than pV̇O2.

Efficacy of Cardiac Rehabilitation in Heart Failure Patients With Low Body Mass Index.

BACKGROUND: Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as <18.5 kg/m2and normal BMI, as 18.5≤BMI<25 kg/m2. All patients underwent cardiopulmonary exercise testing and muscle strength testing at the beginning and end of the 3-month CR program. After CR, a significantly greater proportion of HF patients with low BMI had a positive change in peak V̇O2than in the normal BMI group (91% vs. 70%; P=0.010). Average percent change in peak V̇O2was significantly greater in patients with low vs. normal BMI (17.1±2.8% vs. 7.8±1.5%; P<0.001). In addition, on multivariable logistic regression, low BMI was an independent predictor of a positive change in peak V̇O2after CR (OR, 3.97; 95% CI: 1.10-14.31; P=0.035). CONCLUSIONS: CR has a greater effect in patients with low than normal BMI, and low BMI is an independent predictor of a positive change in peak V̇O2. Thus, CR should be strongly recommended for HF patients with low BMI.

Effect of Exercise Training in Heart Failure Patients Without Echocardiographic Response to Cardiac Resynchronization Therapy.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment of heart failure (HF) with ventricular dyssynchrony, but not all patients respond to a similar extent. We investigated the efficacy and safety of exercise training (ET) in patients without response to CRT. Methods and Results: Thirty-four patients who participated in a 3-month ET program and underwent cardiopulmonary exercise testing at baseline and after the program were divided into 17 responders and 17 non-responders based on echocardiographic response criteria: either an increase in ejection fraction (EF) ≥10% or a reduction in left ventricular (LV) end-systolic volume ≥10%. Baseline characteristics including peak oxygen uptake (V̇O2) and isometric knee extensor muscle strength (IKEMS) were similar in both groups, but non-responders had lower EF and larger LV. During the ET program, neither group had exercise-related adverse event including life-threatening ventricular arrhythmia. Peak V̇O2 and IKEMS were significantly improved in both groups and there was no significant difference in change in peak V̇O2 or IKEMS between responders and non-responders. On multiple regression analysis, change in IKEMS was an independent predictor of change in peak V̇O2, whereas the response to CRT was not. Conclusions: In HF patients undergoing CRT implantation, ET safely improved exercise capacity regardless of response to CRT, suggesting that even advanced HF patients without response to CRT can possibly benefit from ET.

Successful Transcatheter Atrial Septal Defect Closure Prior to Coronary Artery Bypass Grafting Using Anti-Congestive Therapies and Intraaortic Balloon Pumping in a Patient with Severe Ischemic Cardiomyopathy and Triple-Vessel Coronary Artery Disease.

In patients with an atrial septal defect (ASD) and left ventricular (LV) dysfunction associated with coronary artery disease (CAD), to avoid the development of acute left heart failure (HF) and an increase in myocardial oxygen consumption following ASD closure, it is conceivable that coronary artery revascularization should be performed prior to ASD closure. We report the case of a 67-year-old man with a large secundum ASD and LV ejection fraction of 15.6% resulting from severe ischemic cardiomyopathy and triple-vessel CAD, both of which contributed to biventricular HF characterized by high left-to-right shunt (Qp:Qs of 7.1:1) and low systemic cardiac output. After evaluating his hemodynamics and biventricular function with cardiac catheterization and cardiovascular magnetic resonance imaging, we successfully conducted an inverse, stepwise strategy of transcatheter ASD closure using anti-congestive therapies, intraaortic balloon pumping, and subsequent balloon occlusion testing, followed by on-pump beating-heart coronary artery bypass grafting.

Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. METHODS/DESIGN: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. DISCUSSION: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

Predictors of improvements in exercise capacity during cardiac rehabilitation in the recovery phase after coronary artery bypass graft surgery versus acute myocardial infarction.

This study aimed to elucidate the predictors of improvements in exercise capacity during cardiac rehabilitation (CR) in the recovery phase after coronary artery bypass graft surgery (CABG) versus acute myocardial infarction (AMI). We studied 152 patients (91 after AMI and 61 after CABG) who participated in a 3-month CR program. All patients underwent a cardiopulmonary exercise test, blood tests, maximal quadriceps isometric strength (QIS) measurement, and bioelectrical impedance body composition measurement at the beginning and end of the 3-month CR program. At baseline, the percentage of predicted peak oxygen uptake (%pred-PVO2), maximal QIS, and hemoglobin (Hb) were significantly lower, while C-reactive protein (CRP) was significantly higher, in the CABG than the AMI group. After the 3-month CR, %change in PVO2 (%ΔPVO2) was significantly greater in the CABG than the AMI group (18 ± 15% vs 11 ± 12%, P < 0.01). At univariate analysis, baseline plasma brain natriuretic peptide (BNP), %change in maximal QIS after CR (%Δ maximal QIS), and change in plasma hemoglobin (ΔHb) significantly correlated with %ΔPVO2 in the CABG group, whereas only baseline %pred-PVO2 did so in the AMI group. Multiple regression analysis revealed that the same factors were independent and significant predictors of %ΔPVO2 in the CABG and AMI groups. The predictors of improvements in exercise capacity after CR differed between patients after CABG or AMI. Specifically, in CABG patients both enhancing QIS and correcting anemia may contribute to greater improvements in exercise capacity after CR, while a more effective CR program should be designed for CABG patients with high baseline BNP.

Cholinesterase levels predict exercise capacity in cardiac recipients early after transplantation.

PURPOSE: Although cardiac rehabilitation is recommended for patients early after heart transplantation (HTx), adequate exercise effect cannot always be obtained, partly because in patients with chronic heart failure, exercise capacity is reduced due to malnutrition while waiting for HTx. This study aimed to investigate the relationships between exercise capacity and clinical variables, including nutritional indicators, early after HTx. PATIENTS AND METHODS: Forty-three HTx recipients were studied. The mean age at HTx was 38 ± 14 years, and 86% were male. We assessed the relationships between peak oxygen uptake (VO2 ) and clinical variables, including plasma B-type natriuretic peptide (BNP), isometric knee extensor muscle strength (KEMS), and nutritional indicators within 1 week of their respective discharges. RESULTS: Peak VO2 correlated positively with isometric KEMS (r = .63, P < .0001) and negatively with BNP level (r = -.37, P = .015). Of the nutritional indicators, only cholinesterase levels had a significant relationship with peak VO2 (r = .34, P = .028), whereas the Geriatric Nutritional Risk Index and the Controlling Nutritional Status scores did not. In multiple linear regression analysis, cholinesterase levels and isometric KEMS were independent predictors of peak VO2 . CONCLUSION: Cholinesterase levels predicted exercise capacity early after HTx.

Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction.

Aims: There are limited data about the optimal anti-thrombotic therapy for preventing embolism while minimizing bleeding events in patients with first acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). Methods and results: Among 2301 consecutive patients with AMI hospitalized between 2001 and 2014, we studied 1850 patients with first AMI who discharged alive to investigate clinical characteristics, incidence of systemic embolism (SE), and association between anticoagulation and embolic or bleeding events. Left ventricular thrombus was diagnosed by echocardiography, left ventriculography, or cardiac magnetic resonance imaging in 92 (5.0%) patients (62 ± 12 years). During a median follow-up period of 5.4 years (interquartile range 2.1-9.1 years), SE occurred in 15 of 92 patients with LVT (16.3%) and 51 of 1758 patients without LVT (2.9%), respectively. Kaplan-Meier analysis showed a significantly higher incidence of SE in the LVT group (log-rank test, P < 0.001). Multivariate analysis showed that LVT was an independent predictor of SE. Among the LVT patients treated with vitamin K antagonists (n = 84), we compared the patients with therapeutic range (TTR) ≥50% (n = 34) and those with TTR <50% (n = 50). Only one embolic event developed in the TTR ≥50% group and nine embolic events developed in the TTR <50% group (2.9% vs. 19%, P = 0.036). There was no difference in major bleeding events (TTR ≥50%; 9% vs. TTR <50%; 8%, P = 0.89). Conclusion: Appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first AMI complicated by LV thrombus.

Improvement in Exercise Capacity by Exercise Training Associated With Favorable Clinical Outcomes in Advanced Heart Failure With High B-Type Natriuretic Peptide Level.

BACKGROUND: The efficacy of exercise training (ET) programs and its relationship with long-term clinical outcomes in advanced heart failure (HF) patients with high levels of B-type natriuretic peptide (BNP) remain uncertain.Methods and Results:We studied 340 consecutive HF patients with ejection fraction (EF) <45% who completed a 3-month ET program. Patients with BNP ≥200 pg/mL (High-BNP, n=170) had more advanced HF characteristics, including lower EF (25.0±8.6% vs. 28.1±8.0%, P=0.0008), than those with BNP <200 pg/mL. In the High-BNP patients, peak oxygen uptake (V̇O2) was significantly increased by 8.3±16.2% during the ET program, and changes in peak V̇O2inversely correlated with changes in BNP (R=-0.453, P<0.0001) and changes in ventilatory efficiency (V̇E/V̇CO2slope) (R=-0.439, P<0.0001). During a median follow-up of 46 months, patients in the upper tertile of changes in peak V̇O2(≥13.0%), compared with those in the lower tertile (<1.0%), had lower rates of the composite of all-cause death or HF hospitalization (37.9% vs. 54.4%, P=0.036) and all-cause death (8.6% vs. 24.6%, P=0.056). In the multivariate analysis, change in peak V̇O2was a significant independent predictor of the composite outcome and all-cause death. CONCLUSIONS: Even among advanced HF patients with high BNP level, an ET program significantly improved exercise capacity, and a greater improvement in exercise capacity was associated with greater decreases in BNP level and V̇E/V̇CO2slope and more favorable long-term clinical outcomes.