Determinants of Peak Oxygen Uptake at Each Stage of Renal Dysfunction in Patients with Heart Disease.

Background: Identifying the causes of low peak oxygen uptake (peak V̇ O 2 ) in heart disease patients with renal dysfunction is necessary for prognostic improvement strategies. The purpose of this study was to verify the determinants of peak V̇ O 2 for each stage of renal function in heart disease patients, focusing on end-tidal oxygen partial pressure ( PETO 2 ). Methods: Two hundred fifty heart disease patients who underwent cardiopulmonary exercise testing (CPET) in our institution were consecutively enrolled. Patients were divided into three groups by their estimated glomerular filtration rate (eGFR): < 45, 45-59 and ≥ 60 mL/min/1.73 m 2 . Patient characteristics and CPET parameters including Δ 2 (rest-anaerobic threshold) were compared between the groups. The relationship between Δ PETO PETO 2 and peak V̇ O 2 was also investigated for each group. Results: In total, 201 patients were analyzed. Δ PETO 2 decreased with the deterioration of renal function (eGFR < 45, 0.1 mmHg vs. eGFR 45-59, 2.4 mmHg vs. eGFR ≥ 60, 5.2 mmHg, p < 0.001). In the eGFR < 45 group, left ventricular ejection fraction (LVEF) and hemoglobin (Hb) were significantly associated with peak V̇ O 2 ß = 0.518, p < 0.001 and ß = 0.567, p < 0.001, respectively), whereas Δ PETO 2 was not. In the eGFR 45-59 group, age, Hb, and Δ PETO 2 showed a significant association with peak V̇ O 2 ( ß = -0.354, p = 0.006; ß = 0.258, p = 0.007; ß = 0.501, p < 0.001; respectively). In the univariate analysis, eGFR 45-59 group showed the highest coefficient of determination of Δ PETO 2 to peak V̇ O 2 ( R 2 = 0.247, p < 0.001). Conclusions: The determinants of peak V̇ O 2 in heart disease patients depended on the stage of renal function. The determinants of peak V̇ O 2 in patients with eGFR < 45 were LVEF and Hb, while Δ PETO 2 was the strongest predictor of peak V̇ O 2 in patients with eGFR 45-59.

Older phase 2 cardiac rehabilitation patients engaged in gardening maintained physical function during the COVID-19 pandemic.

This study aimed to clarify the effects of gardening on hemodynamic response, rating of perceived exertion (RPE) during exercise, and body weight in patients in whom phase 2 cardiac rehabilitation (CR) was interrupted due to the Coronavirus disease 2019 (COVID-19) pandemic. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. Patients under the age of 65 were excluded. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the gardener group and the non-gardener group. Forty-one patients were enrolled in the final analysis. After CR interruption, the gardener group did not show any significant difference in all items, whereas the non-gardener group experienced significant increase in HR (Peak) (p = 0.004) and worsening of the Borg scale scores for both dyspnea and lower extremity fatigue (p = 0.039 and p = 0.009, respectively). Older phase 2 CR patients engaged in gardening did not show any deterioration in hemodynamic response or RPE during exercise, despite CR interruption and refraining from going outside. Gardening may be recommended as one of the activities that can maintain or improve physical function in older phase 2 CR patients during the COVID-19 pandemic.

Relationship of end-tidal oxygen partial pressure to the determinants of anaerobic threshold in post-myocardial infarction patients.

The anaerobic threshold (AT), obtained during cardiopulmonary exercise testing (CPET), is an important prognostic measure and can be used to develop an exercise prescription in patients after a myocardial infarction (post-MI). The purpose of this study was to examine the central and peripheral determinants of AT in post-MI patients end-tidal oxygen partial pressure (PETO2) measures. We performed cardiopulmonary exercise testing (CPET) on 148 consecutively enrolled post-MI patients to determine PETO2 measured at the AT (AT PETO2) and ΔPETO2 (difference between resting PETO2 and AT PETO2). We subsequently investigated the relationship between these measures of PETO2 and the individual AT for each patient. Multivariate linear regression analysis indicated that AT PETO2 and ΔPETO2 were independently and significantly associated with the AT (ß = -0.344, p < 0.001 and ß = 0.228, p < 0.001, respectively). Furthermore, the independent factors of AT PETO2 were left ventricular ejection fraction (p = 0.005), resting ventilatory equivalent for carbon dioxide (p = 0.002), and resting dead-space gas volume to tidal volume ratio (p < 0.001). However, the independent factors for ΔPETO2 were history of diabetes (p = 0.047), estimated glomerular filtration rate (p = 0.001), and resting systolic blood pressure (p = 0.017). These findings suggested that AT PETO2 was associated with central determinants; whereas, and ΔPETO2 was associated with peripheral determinants, The AT PETO2 and ΔPETO2 provide variable insight regarding the cause of exercise intolerance and can be used to determine appropriate therapies.

Impact of the COVID-19 pandemic on phase 2 cardiac rehabilitation patients in Japan.

This study aimed to clarify the effects of the interruption of cardiac rehabilitation (CR) and refraining from going outside due to the COVID-19 pandemic on hemodynamic response and rating of perceived exertion (RPE) during exercise including differences by age in phase 2 CR outpatients. Among 76 outpatients participating in consecutive phase 2 CR in both periods from March to April and June to July 2020, which were before and after CR interruption, respectively, at Sanda City Hospital were enrolled. The inclusion criterion was outpatients whose CR was interrupted due to COVID-19. We compared the data of hemodynamic response and RPE during exercise on the last day before interruption and the first day after interruption when aerobic exercise was performed at the same exercise intensity in the < 75 years group and ≥ 75 years group. Fifty-three patients were enrolled in the final analysis. Post-CR interruption, peak heart rate increased significantly (p = 0.009) in the < 75 years group, whereas in the ≥ 75 years group, weight and body mass index decreased significantly (p = 0.009, 0.011, respectively) and Borg scale scores for both dyspnea and lower extremities fatigue worsened significantly (both, p < 0.001). CR interruption and refraining from going outside due to the COVID-19 pandemic affected the hemodynamic response, RPE during exercise and body weight in phase 2 CR outpatients. In particular, patients aged ≥ 75 years appeared to be placed at an increased risk of frailty.

Impact of worsening renal function on peak oxygen uptake in patients with acute myocardial infarction.

AIM: Worsening renal function (WRF) induced by acute myocardial infarction (AMI) is a strong predictor of cardiovascular events and mortality. Peak oxygen uptake may contribute to prognosis in AMI patients with WRF, however, the impact of WRF on peak oxygen uptake is unclear. METHODS: Among 154 patients with AMI who underwent emergency percutaneous coronary intervention and participated in phase II cardiac rehabilitation, those who underwent cardiopulmonary exercise testing were consecutively enrolled. WRF was defined as a ≥20% decrease in estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]) from admission to that at cardiopulmonary exercise testing. The association of WRF with peak oxygen uptake was evaluated by multivariate regression analysis. The non-WRF group was divided into two subgroups according to eGFR <60/≥60 at cardiopulmonary exercise testing, and eGFR at cardiopulmonary exercise testing and peak oxygen uptake of all three groups were compared. RESULTS: Ninety-four patients were enrolled in the final analysis. Multiple linear regression analysis showed that WRF was associated with peak oxygen uptake (p = .003). Comparing the non-WRF group with eGFR at cardiopulmonary exercise testing <60 and the WRF group, although eGFR at cardiopulmonary exercise testing was similar (p = 1.000), peak oxygen uptake in the WRF group was significantly lower (p = .026). CONCLUSION: WRF, not eGFR at cardiopulmonary exercise testing was significantly associated with peak oxygen uptake in patients with AMI. This result suggests that when considering the relationship between renal function and peak oxygen uptake, WRF must be taken into account.

Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis.

RATIONALE: Vascular endothelial growth factor (VEGF), a major proangiogenic agent, exerts its proangiogenic action by binding to VEGF receptor 2 (VEGFR2), the activity of which is regulated by direct interactions with other cell surface proteins, including integrin α(V)ß(3). However, how the interaction between VEGFR2 and integrin α(V)ß(3) is regulated is not clear. OBJECTIVE: To investigate whether Necl-5/poliovirus receptor, an immunoglobulin-like molecule that is known to bind integrin α(V)ß(3), regulates the interaction between VEGFR2 and integrin α(V)ß(3), and to clarify the role of Necl-5 in the VEGF-induced angiogenesis. METHODS AND RESULTS: Necl-5-knockout mice displayed no obvious defect in vascular development; however, recovery of blood flow after hindlimb ischemia and the VEGF-induced neovascularization in implanted Matrigel plugs were impaired in Necl-5-knockout mice. To clarify the mechanism of the regulation of angiogenesis by Necl-5, we investigated the roles of Necl-5 in the VEGF-induced angiogenic responses in vitro. Knockdown of Necl-5 by siRNAs in human umbilical vein endothelial cells (HUVECs) inhibited the VEGF-induced capillary-like network formation on Matrigel, migration, and proliferation, and conversely, enhanced apoptosis. Coimmunoprecipitation assays showed the interaction of Necl-5 with VEGFR2, and knockdown of Necl-5 prevented the VEGF-induced interaction of integrin α(V)ß(3) with VEGFR2. Knockdown of Necl-5 suppressed the VEGFR2-mediated activation of downstream proangiogenic and survival signals, including Rap1, Akt, and endothelial nitric oxide synthase. CONCLUSIONS: These results demonstrate the critical role of Necl-5 in angiogenesis and suggest that Necl-5 may regulate the VEGF-induced angiogenesis by controlling the interaction of VEGFR2 with integrin α(v)ß(3), and the VEGFR2-mediated Rap1-Akt signaling pathway.

Nectin-like molecule-5 regulates intimal thickening after carotid artery ligation in mice.

OBJECTIVE: Intimal thickening is considered to result from the dedifferentiation of medial smooth muscle cells (SMCs) from a contractile to a synthetic phenotype, and their subsequent migration and proliferation. It is unknown whether nectin-like molecule (Necl)-5, which is overexpressed in cancer cells, is involved in intimal thickening. APPROACH AND RESULTS: Necl-5 was upregulated in mouse carotid artery after ligation. Compared with wild-type mice, intimal thickening after carotid artery ligation was milder in Necl-5 knockout mice. In vitro, the expression levels of SMC differentiation markers were higher, whereas the expression level of an SMC dedifferentiation marker was lower, in Necl-5 knockout mouse aortic SMCs (MASMCs) compared with wild-type MASMCs. The migration, proliferation, and extracellular signal-regulated kinase activity in response to serum were decreased in Necl-5 knockout MASMCs compared with wild-type MASMCs. In wild-type MASMCs, inhibition of extracellular signal-regulated kinase activity increased the expression levels of SMC differentiation markers and decreased their migration and proliferation in response to serum. CONCLUSIONS: The present findings indicate that Necl-5 plays a role in the formation of intimal thickening after carotid artery ligation by regulating dedifferentiation, migration, and proliferation of SMCs in an extracellular signal-regulated kinase-dependent manner. Our results suggest that Necl-5 may represent a potential therapeutic target to limit intimal thickening after vascular injury.

Detection of severe stenosis and total occlusion in the left anterior descending coronary artery with transthoracic Doppler echocardiography in the emergency room.

BACKGROUND: The noninvasive measurement of coronary flow velocity in the left anterior descending artery (LAD) has recently been realized by using the transthoracic Doppler echocardiography (TTDE). A couple of investigations demonstrated that the diastolic-to-systolic peak velocity ratio (DSVR) by TTDE is a simple and noninvasive method for the detection of severe stenosis in the elective settings. However, the usefulness of DSVR by TTDE in the emergency settings has not been evaluated. OBJECTIVE: The purpose of this study was to assess the clinical feasibility to document the LAD flow by TTDE in emergency patients who complained of chest pain. METHODS: We studied 49 consecutive patients with acute coronary syndrome who were going to undergo emergency coronary angiography (CAG) for the anatomical diagnosis and the facilitated percutaneous coronary intervention (PCI). Prior to CAG, we recorded the LAD flow by TTDE and measured the diastolic peak velocity (DVp), systolic peak velocity (SVp), and their ratio, DSVR (DVp/SVp) of LAD flow. RESULTS: By CAG, the culprit lesions actually resided in the proximal LAD in 36 patients. Among the 36 patients, we detected the Doppler LAD flow in 29. Five out of 7 patients who were unable to detect the LAD flow revealed total occlusions by CAG. DSVR of the LAD is significantly lower in 17 patients who showed severe stenoses (>90%) than those in the rest of 12 patients who did not show such critical stenoses (1.44 +/- 0.16 vs 2.10 +/- 0.26, P < 0.0001). CONCLUSION: In the emergency settings, a noninvasive assessment of the LAD flow by TTDE accurately estimates the critical stenotic lesions of the LAD.

Increased Heart Rate during Walk Test Predicts Chronic-Phase Worsening of Renal Function in Patients with Acute Myocardial Infarction and Normal Kidney Function.

Chronic-phase worsening renal function (WRF) in patients with acute myocardial infarction (AMI) has been associated with poor prognosis. However, there is no consensus on either the method of prevention or the cause. The aim of this study was to determine factors predictive of chronic-phase WRF from the viewpoint of circulatory dynamics response to exercise during hospitalization of AMI patients without renal dysfunction on admission. We studied 186 consecutively AMI patients who underwent the 200-m walk test. Chronic-phase WRF was defined as a 20% decrease in estimated glomerular filtration rate (eGFR) from baseline to 8-10 months after AMI onset. Heart rate (HR) and systolic blood pressure recorded during the 200-m walk test were evaluated as circulatory dynamics responses. In total, 94 patients were enrolled. Multiple linear regression analysis showed that ΔHR (peak-rest) associated significantly with ΔeGFR (ß = 0.427, p = 0.018). The receiver operating characteristic curve of ΔHR to predict chronic-phase WRF showed an area under the curve of 0.77, with a cut-off value of 22.0 bpm having a 95% sensitivity and 55% specificity. Among circulatory dynamics responses during exercise in the acute phase after AMI, ΔHR was an independent predictor of chronic-phase WRF.

Transthoracic Doppler echocardiographic assessment of left anterior descending coronary artery and intramyocardial artery predicts left ventricular remodeling and wall-motion recovery after acute myocardial infarction.

BACKGROUND: Previous studies reported that a coronary flow velocity (FV) pattern with a rapid diastolic deceleration time (DDT) immediately after percutaneous coronary intervention implies advanced microvascular damage in patients who have experienced an acute myocardial infarction (AMI). METHODS: Using transthoracic echocardiography, we recorded the coronary FV in the left anterior descending coronary artery (LAD) and the FV in the intramyocardial artery 2 days after successful percutaneous coronary intervention in 24 patients who had experienced an anterior AMI. We measured the DDT of the LAD and the intramyocardial artery. DDT of the LAD and the intramyocardial artery was detected in the anteroseptal lesion, the wall motion of which revealed severe hypokinesis or akinesis. We performed echocardiography during both the acute phase and 6 months after the AMI. RESULTS: Patients were divided into two groups (group A: DDT of the LAD < or = 600 milliseconds [n = 10], group B: DDT of the LAD > or = 600 milliseconds [n = 14]). DDT of the LAD and the intramyocardial artery was significantly shorter for group A than group B (373 +/- 223 vs 786 +/- 105 milliseconds, P < .0001). In the acute phase, there were no significant differences in left ventricular (LV) wall-motion score index (WMSI), LV end-diastolic volume (EDV), or ejection fraction (WMSI: 2.38 +/- 0.24 vs 2.08 +/- 0.58, P = .20; LV EDV: 160 +/- 41 vs 154 +/- 34 mL; ejection fraction: 45 +/- 11 vs 46 +/- 5%). However, WMSI and LV EDV in group A were significantly greater than in group B (WMSI: 2.47 +/- 0.16 vs 1.84 +/- 0.57, P = .01; LV EDV: 198 +/- 28 vs 132 +/- 37 mL, P = .0004) and the ejection fraction in group A was significantly lower than in group B (38 +/- 9 vs 55 +/- 10%, P = .001) during the chronic phase. CONCLUSIONS: In patients who had experienced an anterior AMI, we could predict wall-motion recovery of the infarcted area by using the coronary FV of the LAD and FV of the intramyocardial artery.