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Prognostic Impact of Increased Heart Rate on Heart Failure with Preserved Ejection Fraction
The 16th Annual Scientific Meeting
YIA-CL-1 Subcutaneous Tissue Biopsy is a Useful Diagnostic and Prognostic Tool for Cardiac Amyloidosis YASUHIRO IZUMIYA, SEIJI TAKASHIO, MEGUMI YAMAMURO, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Cardiac involvement in systemic amyloidosis causes detrimental prognosis, therefore early detection and classification are important to develop appropriate therapeutic strategies. Subcutaneous tissue biopsy is a useful screening for systemic amyloidosis; however, its diagnostic and prognostic value in patients with cardiac amyloidosis remains elusive. Methods: We retrospectively analyzed 14 consecutive patients with cardiac amyloidosis who underwent subcutaneous tissue biopsy. Results: Amyloid deposition was observed in 11 patients (79%). Histopathological analysis demonstrated that acquired monoclonal immunoglobulin light-chain amyloidosis could be predicted when the degree of amyloid deposition was greater in blood vessels than adipose tissue compare to senile systemic amyloidosis and familial amyloidosis (60% vs. 0%; p50.03). During the follow-up period (median 297 days, range 3-761 days), 7 patients died or were admitted to the hospital due to worsening heart failure. Among them, 6 patients (86%) were positive for amyloid deposition in blood vessels. The incidence of death and composite outcome, including heart failure hospitalization and death, was significantly higher in patients positive for amyloid deposition in blood vessels than in those without (p50.03, p50.006; respectively). Conclusions: Amyloid subtype could be diagnosed by analyzing the degree of amyloid deposition in blood vessels and adipose tissue using subcutaneous tissue biopsy samples in patients with cardiac amyloidosis. Amyloid deposition in blood vessels suggests poor prognosis of these patients.
YIA-CL-2 Preoperative Levels of Bilirubin or Creatinine Adjusted by Age can Predict Their Reversibility After Implantation of Left Ventricular Assist Device TERUHIKO IMAMURA1, KOICHIRO KINUGAWA2, TARO SHIGA1, TOSHIRO INABA1, HISATAKA MAKI1, MASARU HATANO1, ATSUSHI YAO1, SHUNEI KYO2, MINORU ONO3, RYOZO NAGAI4 1 Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 3Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 4Jichi Medical University, Tochigi, Japan Background: To predict a reversibility of end-organ function after LVAD implantation is difficult in patients with decompensated state, but is indispensable to determining the eligibility for transplant listing. Methods and Results: Preoperative data were obtained from 69 patients with LVAD (18 continuous-flow, 51 pulsatile). Persistent hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or creatinine (Cre) more than 1.5 mg/dL at 6 months after LVAD implantation. TB score or Cre score was calculated: 0.15 Age + 1.1 (preoperative TB) or 0.2 Age + 3.6 (preoperative Cre), in which coefficients were determined on the basis of odds ratios for persistent hepatic or renal dysfunction, respectively. ROC analyses showed good predictabilities for persistent end-organ dysfunction (AUCs: 0.794 for the TB score and 0.839 for the Cre score). Using the combination of both scores, 6 months’ mortality by multiple organ failure was significantly stratified into 3 groups: the low (5.6%, the TB score !11.0 with any Cre score), intermediate (22.2%, the TB score O11.0 but the Cre score !14.1), and high (83.3%, the TB score O11.0 and the Cre score O14.1) risk strata. Conclusions: Reversibility of end-organ function with LVAD can be predicted by our new risk scoring system, which is beneficial in stratifying the likelihood of transplant listing during bridge to candidacy.
YIA-CL-3 Cardiac Troponin T Release is Increased by Coronary Microvascular Dysfunction in Patients with Nonischemic Heart Failure SEIJI TAKASHIO, MEGUMI YAMAMURO, YASUHIRO IZUMIYA, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Background: Cardiac troponin T (cTnT) is established as a specific biomarker of ongoing myocardial damage and predicts adverse outcome in patients with heart failure (HF). However, the mechanisms of underlying cTnT release remain unclear. It is reported that coronary microvascular dysfunction is potential cause for elevated cTnT release. Therefore, we evaluated the association between coronary microvascular dysfunction and cTnT release from failing myocardium by novel highly sensitive assay. Methods and Results: We studied 45 nonischemic HF patients (mean age: 62615 y.o, Male: 69 %, ejection fraction: 42.5611.5 %). Coronary flow reserve (CFR) was calculated by using a intracoronary Doppler guidewire (FloWire, Volcano, Rancho Cordova, CA, U.S.A.) and CFR ! 2.0 was considered existing coronary microvascular dysfunction. Serum cTnT levels sampled from aortic root (Ao) and coronary sinus (CS) simultaneously during cardiac catheterization were measured. cTnT extracted from heart was describe as the differences between Cs and Ao of cTnT levels (d cTnT). CFR ! 2.0 was observed in 14 patients (31%). d cTnT levels of
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CFR ! 2.0 patients were significantly higher than those of CFR O and 5 2.0 patients (6.767.5 ng/L vs. 2.261.8 ng/L; p50.047). Conclusions: cTnT release into coronary circulation was increased by existing coronary microvascular dysfunction in nonischemic HF patients. Coronary microvascular dysfunction is considered one of the causes for elevated cTnT.
YIA-CL-4 Prognostic Impact of Increased Heart Rate on Heart Failure with Preserved Ejection Fraction TSUYOSHI TAKADA1, YASUHIKO SAKATA2, SATOSHI MIYATA2, JUN TAKAHASHI1, KOTARO NOCHIOKA1, MASANOBU MIURA1, HIROAKI SHIMOKAWA1 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Department of Evidenced-Based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Since heart failure (HF) with preserved ejection fraction (HFpEF) is generally complicated with diastolic dysfunction, it is anticipated that heart rate (HR) control is crucial for the management of HFpEF as compared with HF with reduced EF (HFrEF). Thus, we examined the influence of HR control on cardiovascular (CV) mortality in patients with HFpEF and those with HFrEF. Methods: Among the 10,219 patients in our cohort, as named CHART-2 Study, we enrolled 2,978 patients with Stage C/D HF and sinus rhythm (mean age 67.8 years, 69.0% male). CV mortality during the median follow-up period of 3.1 years was compared among the following 4 groups; G1 (n51121, HR!71bpm, EF$50%), G2 (n5853, HR$71bpm, EF$50%), G3 (n5491, HR!71bpm, EF!50%), and G4 (n5513, HR$71bpm, EF!50%). Results: G2 had a significantly higher CV mortality than G1 (6.0 vs. 3.6%, P50.009), whereas G3 and G4 had similar CV mortality (10.0 vs. 9.9%, P50.740). A Cox regression analysis revealed that G2 was associated with significantly higher CV mortality than G1 (hazard ratio 1.79, P50.008), whereas G3 showed comparable prognosis to G4 (hazard ratio 0.85, P50.418). Conclusions: These results indicate that increased HR is associated with worse prognosis in patients with HFpEF but not in those with HFrEF, suggesting that HR could be a therapeutic target for HEpEF but not for HFrEF.
YIA-CL-5 Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free Survival after Acute Myocardial Infarction MASAHIKO HARA1, YASUHIKO SAKATA1,2, SEN MATSUMOTO1, MASAYA USAMI1, SHINICHIRO SUNA1, DAISAKU NAKATANI1, ISSEI KOMURO1 1 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan, 2Department of Cardiovascular Medicine and Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. Methods and Results: We evaluated whether serum DHA and EPA levels were associated with HF-free survival, and HF hospitalization rates after AMI. We enrolled 712 AMI patients and divided them into 3 groups (Low, Middle, and High) according to the tertile values of DHA or EPA serum levels. Impact of serum n-3 PUFA levels was assessed using propensity-score-stratified Cox regression analysis. Although both DHA and EPA Low groups showed statistically significant worse HF-free survival as compared to other groups (HR 1.68, p50.0358 in DHA and HR 1.69, p50.0280 in EPA), only EPA Low group had a higher risk of HF hospitalization (HR 2.40, p50.0097). Unfavorable impacts of low DHA or EPA levels were generally common in all subgroups; however, impact of low serum EPA on HF hospitalization was particularly prominent in male patients, and those with low high-density lipoprotein cholesterol or without statin. Conclusions: Low levels of serum n-3 PUFA were associated with lower HF-free survival in patients with AMI.
YIA-CO-1 Effect of Exercise Training on Nitric Oxide Synthasesin the Cardiovasculature and Kidney of Rats with Chronic Heart Failure DAISUKE ITO1, OSAMU ITO1, NOBUYOSHI MORI1, CHIHIRO SUDA1, KIYOTAKA HAO2, PENG-YU CAO1, YOSHIKAZU MUROYA1, KENTA TAKASHIMA1, HIROAKI SHIMOKAWA2, MASAHIRO KOHZUKI1 1 Department of Internal Medicine and Rehabilitation Science, Tohoku University, Sendai, Japan, 2Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan Aims: Exercise training has beneficial effects in patients with heart disease, and is known to upregulate endothelial nitric oxide synthase (eNOS) in cardiovasculature. However, the effects of exercise training on nitric oxide synthase (NOS) in the kidney with heart disease have not been reported. Thus, the aim of the present study is to examine whether exercise training upregulates the NOS in the kidney and
YIA-CL-1 Subcutaneous Tissue Biopsy is a Useful Diagnostic and Prognostic Tool for Cardiac Amyloidosis YASUHIRO IZUMIYA, SEIJI TAKASHIO, MEGUMI YAMAMURO, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Cardiac involvement in systemic amyloidosis causes detrimental prognosis, therefore early detection and classification are important to develop appropriate therapeutic strategies. Subcutaneous tissue biopsy is a useful screening for systemic amyloidosis; however, its diagnostic and prognostic value in patients with cardiac amyloidosis remains elusive. Methods: We retrospectively analyzed 14 consecutive patients with cardiac amyloidosis who underwent subcutaneous tissue biopsy. Results: Amyloid deposition was observed in 11 patients (79%). Histopathological analysis demonstrated that acquired monoclonal immunoglobulin light-chain amyloidosis could be predicted when the degree of amyloid deposition was greater in blood vessels than adipose tissue compare to senile systemic amyloidosis and familial amyloidosis (60% vs. 0%; p50.03). During the follow-up period (median 297 days, range 3-761 days), 7 patients died or were admitted to the hospital due to worsening heart failure. Among them, 6 patients (86%) were positive for amyloid deposition in blood vessels. The incidence of death and composite outcome, including heart failure hospitalization and death, was significantly higher in patients positive for amyloid deposition in blood vessels than in those without (p50.03, p50.006; respectively). Conclusions: Amyloid subtype could be diagnosed by analyzing the degree of amyloid deposition in blood vessels and adipose tissue using subcutaneous tissue biopsy samples in patients with cardiac amyloidosis. Amyloid deposition in blood vessels suggests poor prognosis of these patients.
YIA-CL-2 Preoperative Levels of Bilirubin or Creatinine Adjusted by Age can Predict Their Reversibility After Implantation of Left Ventricular Assist Device TERUHIKO IMAMURA1, KOICHIRO KINUGAWA2, TARO SHIGA1, TOSHIRO INABA1, HISATAKA MAKI1, MASARU HATANO1, ATSUSHI YAO1, SHUNEI KYO2, MINORU ONO3, RYOZO NAGAI4 1 Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 2Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 3Department of Cardiothoracic Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, 4Jichi Medical University, Tochigi, Japan Background: To predict a reversibility of end-organ function after LVAD implantation is difficult in patients with decompensated state, but is indispensable to determining the eligibility for transplant listing. Methods and Results: Preoperative data were obtained from 69 patients with LVAD (18 continuous-flow, 51 pulsatile). Persistent hepatic or renal dysfunction was defined as levels of total bilirubin (TB) or creatinine (Cre) more than 1.5 mg/dL at 6 months after LVAD implantation. TB score or Cre score was calculated: 0.15 Age + 1.1 (preoperative TB) or 0.2 Age + 3.6 (preoperative Cre), in which coefficients were determined on the basis of odds ratios for persistent hepatic or renal dysfunction, respectively. ROC analyses showed good predictabilities for persistent end-organ dysfunction (AUCs: 0.794 for the TB score and 0.839 for the Cre score). Using the combination of both scores, 6 months’ mortality by multiple organ failure was significantly stratified into 3 groups: the low (5.6%, the TB score !11.0 with any Cre score), intermediate (22.2%, the TB score O11.0 but the Cre score !14.1), and high (83.3%, the TB score O11.0 and the Cre score O14.1) risk strata. Conclusions: Reversibility of end-organ function with LVAD can be predicted by our new risk scoring system, which is beneficial in stratifying the likelihood of transplant listing during bridge to candidacy.
YIA-CL-3 Cardiac Troponin T Release is Increased by Coronary Microvascular Dysfunction in Patients with Nonischemic Heart Failure SEIJI TAKASHIO, MEGUMI YAMAMURO, YASUHIRO IZUMIYA, SUNAO KOJIMA, HISAO OGAWA Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan Background: Cardiac troponin T (cTnT) is established as a specific biomarker of ongoing myocardial damage and predicts adverse outcome in patients with heart failure (HF). However, the mechanisms of underlying cTnT release remain unclear. It is reported that coronary microvascular dysfunction is potential cause for elevated cTnT release. Therefore, we evaluated the association between coronary microvascular dysfunction and cTnT release from failing myocardium by novel highly sensitive assay. Methods and Results: We studied 45 nonischemic HF patients (mean age: 62615 y.o, Male: 69 %, ejection fraction: 42.5611.5 %). Coronary flow reserve (CFR) was calculated by using a intracoronary Doppler guidewire (FloWire, Volcano, Rancho Cordova, CA, U.S.A.) and CFR ! 2.0 was considered existing coronary microvascular dysfunction. Serum cTnT levels sampled from aortic root (Ao) and coronary sinus (CS) simultaneously during cardiac catheterization were measured. cTnT extracted from heart was describe as the differences between Cs and Ao of cTnT levels (d cTnT). CFR ! 2.0 was observed in 14 patients (31%). d cTnT levels of
JHFS
S147
CFR ! 2.0 patients were significantly higher than those of CFR O and 5 2.0 patients (6.767.5 ng/L vs. 2.261.8 ng/L; p50.047). Conclusions: cTnT release into coronary circulation was increased by existing coronary microvascular dysfunction in nonischemic HF patients. Coronary microvascular dysfunction is considered one of the causes for elevated cTnT.
YIA-CL-4 Prognostic Impact of Increased Heart Rate on Heart Failure with Preserved Ejection Fraction TSUYOSHI TAKADA1, YASUHIKO SAKATA2, SATOSHI MIYATA2, JUN TAKAHASHI1, KOTARO NOCHIOKA1, MASANOBU MIURA1, HIROAKI SHIMOKAWA1 1 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Department of Evidenced-Based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Since heart failure (HF) with preserved ejection fraction (HFpEF) is generally complicated with diastolic dysfunction, it is anticipated that heart rate (HR) control is crucial for the management of HFpEF as compared with HF with reduced EF (HFrEF). Thus, we examined the influence of HR control on cardiovascular (CV) mortality in patients with HFpEF and those with HFrEF. Methods: Among the 10,219 patients in our cohort, as named CHART-2 Study, we enrolled 2,978 patients with Stage C/D HF and sinus rhythm (mean age 67.8 years, 69.0% male). CV mortality during the median follow-up period of 3.1 years was compared among the following 4 groups; G1 (n51121, HR!71bpm, EF$50%), G2 (n5853, HR$71bpm, EF$50%), G3 (n5491, HR!71bpm, EF!50%), and G4 (n5513, HR$71bpm, EF!50%). Results: G2 had a significantly higher CV mortality than G1 (6.0 vs. 3.6%, P50.009), whereas G3 and G4 had similar CV mortality (10.0 vs. 9.9%, P50.740). A Cox regression analysis revealed that G2 was associated with significantly higher CV mortality than G1 (hazard ratio 1.79, P50.008), whereas G3 showed comparable prognosis to G4 (hazard ratio 0.85, P50.418). Conclusions: These results indicate that increased HR is associated with worse prognosis in patients with HFpEF but not in those with HFrEF, suggesting that HR could be a therapeutic target for HEpEF but not for HFrEF.
YIA-CL-5 Low Levels of Serum N-3 Polyunsaturated Fatty Acids are Associated with Lower Heart Failure Free Survival after Acute Myocardial Infarction MASAHIKO HARA1, YASUHIKO SAKATA1,2, SEN MATSUMOTO1, MASAYA USAMI1, SHINICHIRO SUNA1, DAISAKU NAKATANI1, ISSEI KOMURO1 1 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan, 2Department of Cardiovascular Medicine and Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. Methods and Results: We evaluated whether serum DHA and EPA levels were associated with HF-free survival, and HF hospitalization rates after AMI. We enrolled 712 AMI patients and divided them into 3 groups (Low, Middle, and High) according to the tertile values of DHA or EPA serum levels. Impact of serum n-3 PUFA levels was assessed using propensity-score-stratified Cox regression analysis. Although both DHA and EPA Low groups showed statistically significant worse HF-free survival as compared to other groups (HR 1.68, p50.0358 in DHA and HR 1.69, p50.0280 in EPA), only EPA Low group had a higher risk of HF hospitalization (HR 2.40, p50.0097). Unfavorable impacts of low DHA or EPA levels were generally common in all subgroups; however, impact of low serum EPA on HF hospitalization was particularly prominent in male patients, and those with low high-density lipoprotein cholesterol or without statin. Conclusions: Low levels of serum n-3 PUFA were associated with lower HF-free survival in patients with AMI.
YIA-CO-1 Effect of Exercise Training on Nitric Oxide Synthasesin the Cardiovasculature and Kidney of Rats with Chronic Heart Failure DAISUKE ITO1, OSAMU ITO1, NOBUYOSHI MORI1, CHIHIRO SUDA1, KIYOTAKA HAO2, PENG-YU CAO1, YOSHIKAZU MUROYA1, KENTA TAKASHIMA1, HIROAKI SHIMOKAWA2, MASAHIRO KOHZUKI1 1 Department of Internal Medicine and Rehabilitation Science, Tohoku University, Sendai, Japan, 2Department of Cardiovascular Medicine, Tohoku University, Sendai, Japan Aims: Exercise training has beneficial effects in patients with heart disease, and is known to upregulate endothelial nitric oxide synthase (eNOS) in cardiovasculature. However, the effects of exercise training on nitric oxide synthase (NOS) in the kidney with heart disease have not been reported. Thus, the aim of the present study is to examine whether exercise training upregulates the NOS in the kidney and