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Beneficial Effects of Positive Airway Pressure Therapy for Sleep-Disordered Breathing in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction
S156 Journal of Cardiac Failure Vol. 21 No. 10S October 2015
Workshops Workshop 1 WS1-3 Characteristics of Patients with HFpEF Followed up after a Reperfused First STEMI: The Risk/Benefit of the Administration of Diuretics NORIAKI IWAHASHI1, TOSHIAKI EBINA1, SATOSHI UMEMURA2, KAZUO KIMURA1 1 Yokohama City University Medical center, Division of Cardiology; 2Yokohama City University Hospital Background: Acute myocardial infarction (AMI) is one of the main causes of heart failure with preserved ejection fraction (HFpEF). We explored the characteristics of patients with HFpEF who had undergone successful reperfusion of ST elevation AMI (STEMI). Methods: A total of 503 patients who had a first STEMI and who underwent reperfusion therapy within 12 hours after onset and had a preserved EF (EFO40%) were followed up. Among these patients, 71 were admitted because of heart failure or cardiac arrest in the last five years. Echocardiography was obtained within 2 weeks (2-21 days) after onset. Conventional 2D parameters and transmitral flow velocity were examined. BNP and creatinine were obtained at discharge. Results: In univariate analysis, age, hypertension, administration of diuretics, creatinine, BNP, LVEF, LVMI, and E/A were all associated with the progression of HFpEF. Multiple logistic regression analysis showed that administration of diuretics (OR511.5, 95% CI-2.3 - -0.63), p50.0006) was the strongest predictor, followed by BNP (OR510.2, p50.001) and E/A (OR55.5, p50.01). The patients who were administered with diuretics had a high BNP (3756342 pg/mL) and E/A (1.0860.67). Conclusions: The administration of diuretics after STEMI even after a successful reperfusion therapy is an important indicator of HFpEF. Patients with a high BNP and E/A after administration of diuretics show a high risk of developing HFpEF after STEMI.
WS1-5 Beneficial Effects of Positive Airway Pressure Therapy for Sleep-Disordered Breathing in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction AKIOMI YOSHIHISA, YUKI KANNO, TAKESHI SHIMIZU, YAMAUCHI HIROYUKI, TAKAMASA SATO, SATOSHI SUZUKI, MASAYOSHI OIKAWA, ATSUSHI KOBAYASHI, SHU-ICHI SAITOH, YASUCHIKA TAKEISHI Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan Backgrounds: Right heart dysfunction is associated with poor prognosis in heart failure with preserved left ventricular ejection fraction (HFpEF). It remains unclear whether sleep-disordered breathing (SDB) treatment using positive airway pressure (PAP) improves right heart and pulmonary function and exercise capacity and reduces mortality rates of HFpEF patients. Methods: Consecutive 109 patients with HFpEF (LVEFO50%) and moderate-severe SDB (apnea hypopnea indexO15/h) treated with optimal medications were divided into two groups: 31 patients with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right ventricular fractional area change (RV-FAC), tricuspid valve regurgitation pressure gradient (TR-PG), tricuspid valve E/e, forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), percentage of vital capacity, and peak VO2 were determined before and 6 months later. All-cause mortality was followed up for average 916 days. Results: All parameters improved in the PAP group (RV-FAC: 36.0 to 46.5%; TRPG: 31.1 to 22.4mmHg; tricuspid valve E/e: 7.8 to 5.1; FEV1/FVC: 83.9 to 89.8%; percentage of vital capacity: 83.5 to 89.9%; peak VO2: 16.6 to 19.6 ml/kg/ min; p!0.05, respectively), but not in the non-PAP group. Importantly, all-cause mortality was significantly lower in the PAP group than in the non-PAP group (0% vs. 12.8%, log-rank p50.014). Conclusions: PAP improves right heart and pulmonary function and exercise capacity and may reduce all-cause mortality in patients with HFpEF and SDB.
Workshop 2 WS2-2 The PLGF/Flt-1 Signaling Pathway Can be a Novel Mechanism for CardioRenal Syndrome AYAKO SENO, YUKIJI TAKEDA, MASARU MATSUI, YASUKI NAKADA, HITOSHI NAKAGAWA, KENJI ONOUE, HIROYUKI KAWATA, RIKA KAWAKAMI, SHIRO UEMURA, YOSHIHIKO SAITO The First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan Background: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease, which is called cardio-renal syndrome (CRS), however, its underling molecular mechanism is not fully understood. In our previous data, sFlt-1, an endogenous inhibitor of PLGF (placental growth factor), can be a key molecule of
CRS. sFlt-1 production was decreased with the progression of renal diseases, and sFlt-1 deficiency results in progression of atherosclerosis using double knock-out mice (sFlt-1 / ApoE / ) by relative activation of atherogenic PLGF signal. In this study, we examined the role of PLGF/Flt-1 system in heart failure using sFlt-1 / mice which mimic the CKD condition. Methods and Results: Soluble Flt-1 deficient mice and WT were subjected to transverse aortic constriction (TAC). Almost half of sFlt-1 / died within 1 week after TAC. LV wall thickeness was significantly increased and cardiac function was impared in sFlt-1 / compared to WT by echocardiography. Histological analysis showed that cardiac fibrosis and macrophage infiltration were significantly increased in sFlt-1 / compared to WT. An antiPLGF neutralizing antibody (aPLGF) prevented pressure-overloaded cardiac hypertrophy and dysfunction after TAC in sFlt1 / . Furthermore, aPLGF prevented not only macrophage accumulation but cardiac fibrosis in sFlt-1 / . Moreover, recombinant sFlt-1 protein administration prevented the deterioration of cardiac hypertrophy and dysfunction following pressure overload in sFlt-1 / . Conclusion: The present study clarified the novel mechanism of PLGF/Flt-1 for CRS.
WS2-3 Intra-renal Doppler Profile in Chronic Heart Failure: A Link with Central Venous Pressure and Renal Function YOSHIHIRO SEO, MASAYOSHI YAMAMOTO, SEIKA SAI, TOMOKO MACHINO, TOMOKO ISHIZU, KAZUTAKA AONUMA Cardiovascular Division, University of Tsukuba Background: Cardio-renal syndrome is a key pathophysiology of congestive heart failure (CHF). We sought to investigate intra-renal Doppler (IRD) profile in patients with chronic heart failure (CHF). Methods: We performed right-sided heart catheterization and IRD studies in 84 patients with CHF. In IRD studies, resistance index (RI) of interlobar arteries and interlobar venous flow (VF) pattern were assessed. In addition, 38 normal control subjects were studied to determine the normal IRD profiles. Results: From control data, RIS 0.7 were abnormal range, and a discontinuous VF pattern was abnormal. In CHF patients with RI S 0.7, hemoglobin and eGFR were significantly lower, and SCr, BUN, Log10 BNP, PCWP, and right atrial pressure (RAP) were significantly higher than patients with RI!0.7. Meanwhile, in patients with discontinuous VF pattern, patients with monophasic pattern had significantly higher RAP accompanied with higher SCr and BUN compared to continuous and discontinuous biphasic pattern (RAP: continuous, 5.163.3; biphasic, 8.163.1; monophasic,16.967.4 mmHg, p!0.001). In contrast, cardiac index did not differ between patients with RI S 0.7 and RI!0.7, and between continuous and discontinuous VF patterns. Conclusion: IRD profile was associated with central venous pressure in both artery and venous sides. The observations suggest IRD profile may be useful in assessing renal congestion related with heart failure.
WS2-4 The Role of Liver in the Context of Metabolism in Congestive Heart Failure TAKAO KATO, AKIRA KAWAMOTO, TETSUO SHIOI, TAKESHI KIMURA Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Liver plays a central role in systemic metabolic regulation and little is known about the roles in congestive heart failure (CHF). First, we analyzed Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11 weeks and CHF at 17-19 weeks of age. In CHF rats, body weight and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. The mRNA and content of tumor necrosis factor-alpha and interleukin-1beta were increased, liver incorporated more glucose, the mRNA related to gluconeogenesis was decreased, the mRNA related to lipogenesis was increased, and the triglyceride content of the liver was increased, when the body is losing weight and peripheral tissues need more substrates to maintain tissue homeostasis. Second, in order to clarify the effect of pulmonary hypertension on the liver, we examined the relationships among nutritional status and markers of congestion in 8 stable pulmonary arterial hypertension patients with the mean estimated systolic pulmonary artery pressure of 82.7 (SD, 15.7) mmHg. A close relationship between pulmonary hypertension with IVC dilatation, poor nutritional status, elevated liver enzymes, and low body mass index was observed. In conclusion, liver was associated with poor nutritional status, one of prognostic factors, in CHF through abnormal metabolism, inflammatory responses, and congestion.
WS2-5 Heart Failure is a Dysfunction of Brain Renin Angiotensin-Neuron-Glial Interaction TAKUYA KISHI Collaborative Research Institute of Innovation for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan No one doubt that one of the major notably abnormalities in heart failure is inadequate sympathoexcitation, and that sympathetic nerve activity is determined by brain.
Workshops Workshop 1 WS1-3 Characteristics of Patients with HFpEF Followed up after a Reperfused First STEMI: The Risk/Benefit of the Administration of Diuretics NORIAKI IWAHASHI1, TOSHIAKI EBINA1, SATOSHI UMEMURA2, KAZUO KIMURA1 1 Yokohama City University Medical center, Division of Cardiology; 2Yokohama City University Hospital Background: Acute myocardial infarction (AMI) is one of the main causes of heart failure with preserved ejection fraction (HFpEF). We explored the characteristics of patients with HFpEF who had undergone successful reperfusion of ST elevation AMI (STEMI). Methods: A total of 503 patients who had a first STEMI and who underwent reperfusion therapy within 12 hours after onset and had a preserved EF (EFO40%) were followed up. Among these patients, 71 were admitted because of heart failure or cardiac arrest in the last five years. Echocardiography was obtained within 2 weeks (2-21 days) after onset. Conventional 2D parameters and transmitral flow velocity were examined. BNP and creatinine were obtained at discharge. Results: In univariate analysis, age, hypertension, administration of diuretics, creatinine, BNP, LVEF, LVMI, and E/A were all associated with the progression of HFpEF. Multiple logistic regression analysis showed that administration of diuretics (OR511.5, 95% CI-2.3 - -0.63), p50.0006) was the strongest predictor, followed by BNP (OR510.2, p50.001) and E/A (OR55.5, p50.01). The patients who were administered with diuretics had a high BNP (3756342 pg/mL) and E/A (1.0860.67). Conclusions: The administration of diuretics after STEMI even after a successful reperfusion therapy is an important indicator of HFpEF. Patients with a high BNP and E/A after administration of diuretics show a high risk of developing HFpEF after STEMI.
WS1-5 Beneficial Effects of Positive Airway Pressure Therapy for Sleep-Disordered Breathing in Heart Failure Patients with Preserved Left Ventricular Ejection Fraction AKIOMI YOSHIHISA, YUKI KANNO, TAKESHI SHIMIZU, YAMAUCHI HIROYUKI, TAKAMASA SATO, SATOSHI SUZUKI, MASAYOSHI OIKAWA, ATSUSHI KOBAYASHI, SHU-ICHI SAITOH, YASUCHIKA TAKEISHI Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan Backgrounds: Right heart dysfunction is associated with poor prognosis in heart failure with preserved left ventricular ejection fraction (HFpEF). It remains unclear whether sleep-disordered breathing (SDB) treatment using positive airway pressure (PAP) improves right heart and pulmonary function and exercise capacity and reduces mortality rates of HFpEF patients. Methods: Consecutive 109 patients with HFpEF (LVEFO50%) and moderate-severe SDB (apnea hypopnea indexO15/h) treated with optimal medications were divided into two groups: 31 patients with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right ventricular fractional area change (RV-FAC), tricuspid valve regurgitation pressure gradient (TR-PG), tricuspid valve E/e, forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), percentage of vital capacity, and peak VO2 were determined before and 6 months later. All-cause mortality was followed up for average 916 days. Results: All parameters improved in the PAP group (RV-FAC: 36.0 to 46.5%; TRPG: 31.1 to 22.4mmHg; tricuspid valve E/e: 7.8 to 5.1; FEV1/FVC: 83.9 to 89.8%; percentage of vital capacity: 83.5 to 89.9%; peak VO2: 16.6 to 19.6 ml/kg/ min; p!0.05, respectively), but not in the non-PAP group. Importantly, all-cause mortality was significantly lower in the PAP group than in the non-PAP group (0% vs. 12.8%, log-rank p50.014). Conclusions: PAP improves right heart and pulmonary function and exercise capacity and may reduce all-cause mortality in patients with HFpEF and SDB.
Workshop 2 WS2-2 The PLGF/Flt-1 Signaling Pathway Can be a Novel Mechanism for CardioRenal Syndrome AYAKO SENO, YUKIJI TAKEDA, MASARU MATSUI, YASUKI NAKADA, HITOSHI NAKAGAWA, KENJI ONOUE, HIROYUKI KAWATA, RIKA KAWAKAMI, SHIRO UEMURA, YOSHIHIKO SAITO The First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan Background: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease, which is called cardio-renal syndrome (CRS), however, its underling molecular mechanism is not fully understood. In our previous data, sFlt-1, an endogenous inhibitor of PLGF (placental growth factor), can be a key molecule of
CRS. sFlt-1 production was decreased with the progression of renal diseases, and sFlt-1 deficiency results in progression of atherosclerosis using double knock-out mice (sFlt-1 / ApoE / ) by relative activation of atherogenic PLGF signal. In this study, we examined the role of PLGF/Flt-1 system in heart failure using sFlt-1 / mice which mimic the CKD condition. Methods and Results: Soluble Flt-1 deficient mice and WT were subjected to transverse aortic constriction (TAC). Almost half of sFlt-1 / died within 1 week after TAC. LV wall thickeness was significantly increased and cardiac function was impared in sFlt-1 / compared to WT by echocardiography. Histological analysis showed that cardiac fibrosis and macrophage infiltration were significantly increased in sFlt-1 / compared to WT. An antiPLGF neutralizing antibody (aPLGF) prevented pressure-overloaded cardiac hypertrophy and dysfunction after TAC in sFlt1 / . Furthermore, aPLGF prevented not only macrophage accumulation but cardiac fibrosis in sFlt-1 / . Moreover, recombinant sFlt-1 protein administration prevented the deterioration of cardiac hypertrophy and dysfunction following pressure overload in sFlt-1 / . Conclusion: The present study clarified the novel mechanism of PLGF/Flt-1 for CRS.
WS2-3 Intra-renal Doppler Profile in Chronic Heart Failure: A Link with Central Venous Pressure and Renal Function YOSHIHIRO SEO, MASAYOSHI YAMAMOTO, SEIKA SAI, TOMOKO MACHINO, TOMOKO ISHIZU, KAZUTAKA AONUMA Cardiovascular Division, University of Tsukuba Background: Cardio-renal syndrome is a key pathophysiology of congestive heart failure (CHF). We sought to investigate intra-renal Doppler (IRD) profile in patients with chronic heart failure (CHF). Methods: We performed right-sided heart catheterization and IRD studies in 84 patients with CHF. In IRD studies, resistance index (RI) of interlobar arteries and interlobar venous flow (VF) pattern were assessed. In addition, 38 normal control subjects were studied to determine the normal IRD profiles. Results: From control data, RIS 0.7 were abnormal range, and a discontinuous VF pattern was abnormal. In CHF patients with RI S 0.7, hemoglobin and eGFR were significantly lower, and SCr, BUN, Log10 BNP, PCWP, and right atrial pressure (RAP) were significantly higher than patients with RI!0.7. Meanwhile, in patients with discontinuous VF pattern, patients with monophasic pattern had significantly higher RAP accompanied with higher SCr and BUN compared to continuous and discontinuous biphasic pattern (RAP: continuous, 5.163.3; biphasic, 8.163.1; monophasic,16.967.4 mmHg, p!0.001). In contrast, cardiac index did not differ between patients with RI S 0.7 and RI!0.7, and between continuous and discontinuous VF patterns. Conclusion: IRD profile was associated with central venous pressure in both artery and venous sides. The observations suggest IRD profile may be useful in assessing renal congestion related with heart failure.
WS2-4 The Role of Liver in the Context of Metabolism in Congestive Heart Failure TAKAO KATO, AKIRA KAWAMOTO, TETSUO SHIOI, TAKESHI KIMURA Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Liver plays a central role in systemic metabolic regulation and little is known about the roles in congestive heart failure (CHF). First, we analyzed Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11 weeks and CHF at 17-19 weeks of age. In CHF rats, body weight and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. The mRNA and content of tumor necrosis factor-alpha and interleukin-1beta were increased, liver incorporated more glucose, the mRNA related to gluconeogenesis was decreased, the mRNA related to lipogenesis was increased, and the triglyceride content of the liver was increased, when the body is losing weight and peripheral tissues need more substrates to maintain tissue homeostasis. Second, in order to clarify the effect of pulmonary hypertension on the liver, we examined the relationships among nutritional status and markers of congestion in 8 stable pulmonary arterial hypertension patients with the mean estimated systolic pulmonary artery pressure of 82.7 (SD, 15.7) mmHg. A close relationship between pulmonary hypertension with IVC dilatation, poor nutritional status, elevated liver enzymes, and low body mass index was observed. In conclusion, liver was associated with poor nutritional status, one of prognostic factors, in CHF through abnormal metabolism, inflammatory responses, and congestion.
WS2-5 Heart Failure is a Dysfunction of Brain Renin Angiotensin-Neuron-Glial Interaction TAKUYA KISHI Collaborative Research Institute of Innovation for Cardiovascular Diseases, Kyushu University Center for Disruptive Cardiovascular Medicine, Fukuoka, Japan No one doubt that one of the major notably abnormalities in heart failure is inadequate sympathoexcitation, and that sympathetic nerve activity is determined by brain.