Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-ß Signaling Pathway.

BACKGROUND: Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process. METHODS AND RESULTS: In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7(-/-)) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7(-/-) mice. In vitro, Sirt7(-/-) mouse-derived or Sirt7 siRNA-treated cardiac fibroblasts showed reduced transforming growth factor-ß signal activation and low expression levels of fibrosis-related genes compared with wild-type mice-derived or control siRNA-treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-ß receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process. CONCLUSION: Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.

Akt1-mediated fast/glycolytic skeletal muscle growth attenuates renal damage in experimental kidney disease.

Muscle wasting is frequently observed in patients with kidney disease, and low muscle strength is associated with poor outcomes in these patients. However, little is known about the effects of skeletal muscle growth per se on kidney diseases. In this study, we utilized a skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse model that promotes the growth of functional skeletal muscle independent of exercise to investigate the effects of muscle growth on kidney diseases. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 TG and wild-type (WT) control mice. The expression of atrogin-1, an atrophy-inducing gene in skeletal muscle, was upregulated 7 days after UUO in WT mice but not in Akt1 TG mice. UUO-induced renal interstitial fibrosis, tubular injury, apoptosis, and increased expression of inflammatory, fibrosis-related, and adhesion molecule genes were significantly diminished in Akt1 TG mice compared with WT mice. An increase in the activating phosphorylation of eNOS in the kidney accompanied the attenuation of renal damage by myogenic Akt1 activation. Treatment with the NOS inhibitor L-NAME abolished the protective effect of skeletal muscle Akt activation on obstructive kidney disease. In conclusion, Akt1-mediated muscle growth reduces renal damage in a model of obstructive kidney disease. This improvement appears to be mediated by an increase in eNOS signaling in the kidney. Our data support the concept that loss of muscle mass during kidney disease can contribute to renal failure, and maintaining muscle mass may improve clinical outcome.

Circulating thrombospondin-2 reflects disease severity and predicts outcome of heart failure with reduced ejection fraction.

BACKGROUND: Thrombospondin-2 (TSP-2) is a matricellular protein found in human serum. Deletion of TSP-2 causes age-dependent dilated cardiomyopathy. We hypothesized that TSP-2 is a useful biomarker in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Serum TSP-2 was measured in 101 patients with HFrEF, and mortality and cardiovascular events were followed. Serum TSP-2 in the HFrEF group was significantly higher than in the non-HF group (n=17). Mean NYHA functional class was significantly higher in the high TSP-2 group (>median) than the low TSP-2 group (2.26 vs. 1.76, P=0.004). Circulating TSP-2 level was significantly associated with that of B-type natriuretic peptide (BNP; r=0.40, P<0.0001) on multivariate linear regression analysis. On Kaplan-Meier curve analysis the high TSP-2 group had a lower event-free rate than the low TSP-2 group (log-rank test, P=0.03). Multivariate Cox hazard analysis identified hemoglobin (hazard ratio [HR], 0.66; 95% confidence interval [CI]: 0.53-0.82, P<0.0001), and TSP-2 (ln[TSP-2]; HR, 3.34; 95% CI: 1.03-10.85, P=0.045) as independent predictors of adverse outcome. The area under the curve for 1-year events increased when TSP-2 was added to Framingham risk score (FRS; alone, 0.60) or BNP (alone, 0.69; FRS+TSP-2, 0.75; BNP+TSP-2, 0.76). CONCLUSIONS: TSP-2 is a potentially useful biomarker for assessment of disease severity and prognosis in HFrEF.

Growth differentiation factor 15 can distinguish between hypertrophic cardiomyopathy and hypertensive hearts.

To distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on a morphological examination is often challenging. Growth differentiation factor 15 (GDF-15) is a novel diagnostic and prognostic biomarker for several cardiovascular diseases. In patients with LVH, GDF-15 promises to be a useful biomarker to distinguish between HCM and H-LVH. We evaluated 93 patients with H-LVH, 28 with HCM, and 28 disease control individuals. Serum GDF-15 concentrations were measured with an enzyme-linked immunosorbent assay. Circulating GDF-15 levels were significantly higher in patients with H-LVH than with HCM (P = 0.003). On the other hand, values for plasma B-type natriuretic peptide (BNP) levels were significantly lower in patients with H-LVH than with HCM (P = 0.004). Serum GDF-15 and plasma BNP levels positively correlated in patients with H-LVH but not with HCM. Multivariate logistic regression analysis revealed GDF-15 (odds ratio 12.06, confidence interval 1.85-78.77, P < 0.01) as an independent predictor of H-LVH among patients with LVH. In receiver-operating characteristic analysis, GDF-15 achieved an area under the curve of 0.70 for the identification of H-LVH. We found that GDF-15 might be a useful biomarker for discriminating HCM from H-LVH. Understanding serum GDF-15 values may have clinical utility for patients with LVH because the therapeutic strategies for treating HCM and H-LVH differ.

Subclinical leaflet thrombus in patients with severe aortic stenosis and atrial fibrillation -ENRICH-AF TAVI study.

Subclinical leaflet thrombosis (SLT) can be one of the causes of transcatheter heart valve (THV) failure after transcatheter aortic valve implantation (TAVI). We sought to clarify the formation process of SLT and thrombogenicity during the perioperative period of TAVI. This multicenter, prospective, single-arm interventional study enrolled 26 patients treated with edoxaban for atrial fibrillation and who underwent TAVI for severe aortic stenosis between September 2018 and September 2022. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI in 18 patients and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD) (n = 11). SLT was observed in 16.7% (3/18) at 1 week, but decreased to 5.9% (1/17) at 3 months after TAVI. Patients with SLT at 1 week had a significantly decreased maximal leaflet thickness compared to those without SLT. Thrombogenicity assessed by T-TAS decreased markedly at 1 week and tended to increase at 3 months. The stagnation volume assessed by CFD was positively associated with a higher maximum leaflet thickness. This study showed the course of leaflet thrombus formation and visualization of stagnation in neo-sinus of THV in the acute phase after TAVI.

Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via endothelial nitric oxide synthase-dependent mechanism.

Obesity-related diseases are associated with vascular dysfunction and impaired revascularization. Omentin is a fat-derived secreted protein, which is down-regulated in association with obese complications. Here, we investigated whether omentin modulates endothelial cell function and revascularization processes in vitro and in vivo. Systemic delivery of an adenoviral vector expressing omentin (Ad-omentin) enhanced blood flow recovery and capillary density in ischemic limbs of wild-type mice in vivo, which were accompanied by increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In cultured human umbilical vein endothelial cells (HUVECs), a physiological concentration of recombinant omentin protein increased differentiation into vascular-like structures and decreased apoptotic activity under conditions of serum starvation. Treatment with omentin protein stimulated the phosphorylation of Akt and eNOS in HUVECs. Inhibition of Akt signaling by treatment with dominant-negative Akt or LY294002 blocked the stimulatory effects of omentin on differentiation and survival of HUVECs and reversed omentin-stimulated eNOS phosphorylation. Pretreatment with the NOS inhibitor also reduced the omentin-induced increase in HUVEC differentiation and survival. Omentin protein also stimulated the phosphorylation of AMP-activated protein kinase in HUVECs. Transduction with dominant-negative AMP-activated protein kinase diminished omentin-induced phosphorylation of Akt and omentin-stimulated increase in HUVEC differentiation and survival. Of importance, in contrast to wild-type mice, systemic administration of Ad-omentin did not affect blood flow in ischemic muscle in eNOS-deficient mice in vivo. These data indicate that omentin promotes endothelial cell function and revascularization in response to ischemia through its ability to stimulate an Akt-eNOS signaling pathway.

Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb.

OBJECTIVE: Whole-body periodic acceleration (WBPA) has been developed as a passive exercise technique to improve endothelial function by increasing shear stress through repetitive movements in spinal axis direction. We investigated the effects of WBPA on blood flow recovery in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease. METHODS AND RESULTS: After unilateral femoral artery excision, mice were assigned to either the WBPA (n=15) or the control (n=13) group. WBPA was applied at 150 cpm for 45 minutes under anesthesia once a day. WBPA significantly increased blood flow recovery after ischemic surgery, as determined by laser Doppler perfusion imaging. Sections of ischemic adductor muscle stained with anti-CD31 antibody showed a significant increase in capillary density in WBPA mice compared with control mice. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in skeletal muscle. The proangiogenic effect of WBPA on ischemic limb was blunted in eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on revascularization are eNOS dependent. Quantitative real-time polymerase chain reaction analysis showed significant increases in angiogenic growth factor expression in ischemic hindlimb by WBPA. Facilitated blood flow recovery was observed in a mouse model of diabetes despite there being no changes in glucose tolerance and insulin sensitivity. Furthermore, both a single session and 7-day repeated sessions of WBPA significantly improved blood flow in the lower extremity of patients with peripheral arterial disease. CONCLUSIONS: WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of proangiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable noninvasive intervention to facilitate therapeutic angiogenesis.

Endovascular Treatment of Long Superficial Femoral Artery-Chronic Total Occlusions Using the Gogo Catheter With IVUS Via a Popliteal Puncture Method Is Effective, Safe, and Useful.

OBJECTIVES: We aimed to investigate the usefulness of inserting a 6Fr sheath guided by duplex ultrasonography via a popliteal artery puncture. We also aimed to demonstrate endoluminal tracking using a retrograde approach using the Gogo catheter with intravascular ultrasound (IVUS). BACKGROUND: The bidirectional approach is useful for increasing the success rate of the procedure for long superficial femoral artery-chronic total occlusions (SFA-CTOs). However, this procedure becomes somewhat complicated. Since the proximal blood vessel diameter is clearly larger than the distal end of the CTO and the body surface duplex guide can also be used in the proximal part, it is easier to introduce a retrograde guidewire (GW) into the proximal end. METHODS: We performed endovascular treatment for long SFA-CTOs with a Gogo catheter + IVUS guide in 31 consecutive cases (male 20/female 11; mean age, 75.6 ± 7.6) from May 2017 to November 2018. We advanced the IVUS until the true lumen could be confirmed and advanced the Gogo catheter toward the IVUS for reinforcement. We attempted to approach the long CTO by repeating this procedure. We named this procedure the GIP method (GIP: Gogo catheter with IVUS via a popliteal puncture). Hemostasis of the popliteal artery was achieved using a commercially available compression hemostatic kit (Tometa-kun, XEMEX, Japan). RESULTS: Successful revascularization was achieved in all cases (in 2 cases, a femoral artery puncture was added, and a bidirectional approach was used, and in 1 case, a CROSSER system was used). On average, the fluoroscopy time was 42.2 ± 30.4 minutes, radiation dose 93.7 ± 78.7 mGy, and amount of contrast medium used 15.0 ± 9.6 mL. The procedure time was defined as from the start of the popliteal artery puncture to the time the GW passed through the CTO lesion, including the posture transformation time from prone to the supine position. The procedure time was 42.1 ± 40.2 minutes. There were no major adverse events or other major complications, such as a distal embolism, rupture of the CTO lesion, arteriovenous fistula, or major hematoma requiring a transfusion or surgical treatment. Only 2 small hematomas occurred at the popliteal artery puncture site. The patients were treated conservatively and were discharged as usual. CONCLUSIONS: Endovascular treatment of long SFA-CTOs via the popliteal approach was effective and safe. Using the GIP method to address long SFA-CTOs is recommended.

[A case of glioblastoma misdiagnosed initially due to positive finding of anti-glutamate receptor antibody].

A 53-year-old man was admitted to our hospital after suffering four attacks with loss of consciousness and/or topographic agnosia. Three months after the first attack, the cerebrospinal fluid analysis showed no abnormal findings. IgG-autoantibodies and IgM-autoantibodies against glutamate receptor epsilon2 (GluRepsilon2) were detected in cerebrospinal fluid and serum respectively. At that time, we diagnosed him as having limbic encephalopathy. Brain MRI revealed a high intensity lesion on T2-weighted and FLAIR images in the medial regions of the bilateral temporal lobes and splenium. A diffusion-weighted image revealed high intensity lesions which were also weakly enhanced by Gd-DTPA in the deep white matter beside the posterior horns. The patient then developed numbness in the right hand. The cerebralspinal fluid analysis, four months after the onset of the disease, exhibited slight pleocytosis and elevated protein. IgG-autoantibodies against GluRepsilon2 were detected in the serum. The lesions beside the posterior horns were ring-like enhanced more strongly. Brain biopsy led to a diagnosis of glioblastoma. We suggest that patients with autoantibodies against GluRepsilon2 should be carefully diagnosed with limbic encephalopathy associated with autoimmune mechanisms even if radiological findings are typical of the disease.

A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline.

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.

Growth differentiation factor-15 is a useful prognostic marker in patients with heart failure with preserved ejection fraction.

BACKGROUND: Circulating growth differentiation factor 15 (GDF-15) levels correlate with heart mass and fibrosis; however, little is known about its value in predicting the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We measured serum GDF-15 levels in 149 consecutive patients with left ventricular diastolic dysfunction (LVDD) and normal LV ejection fraction (>50%) and followed them for cardiovascular events. LVDD was defined according to the European Society of Cardiology guidelines. RESULTS: The New York Heart Association functional class and circulating B-type natriuretic peptide (BNP) levels were significantly higher in the high-GDF-15 group (n = 75; greater than or equal to the median value [3694 pg/mL]) than in the low-GDF-15 group (n = 74). Patients were divided into HFpEF and LVDD groups according to the presence or absence of HF. Serum GDF-15 levels were significantly higher in the HFpEF group (n = 73) than in the LVDD group (n = 76) (median, 4215 [interquartile range, 3382-5287] vs 3091 [interquartile range, 2487-4217 pg/mL]; P < 0.0001). Kaplan-Meier curve analysis showed a significantly higher probability of cardiovascular events in the high-GDF-15 group than in the low-GDF-15 group for data of all patients (log-rank test P = 0.006) and data of patients in the HFpEF group only (P = 0.014). Multivariate Cox hazard analysis identified age (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.87-0.98; P = 0.008), atrial fibrillation (HR, 7.95; 95% CI, 1.98-31.85, P = 0.003), lnBNP (HR, 3.37; 95% CI, 1.73-6.55; P < 0.0001), and GDF-15 (ln[GDF-15]) (HR, 4.74; 95% CI, 1.26-17.88, P = 0.022) as independent predictors of primary end points. CONCLUSIONS: GDF-15 is a potentially useful prognostic biomarker in patients with HFpEF.

Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling.

Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 µg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production.

Simultaneous pressure recording in mid-ventricular obstructive hypertrophic cardiomyopathy.

A 70-year-old man was diagnosed with mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHCM) with apical aneurysm and paradoxic jet flow. At cardiac catheterization, pressure study showed that there was a markedly high pressure-gradient of 90 mmHg between the apex and the base in systole. Apical pressure was 350 mmHg after premature ventricular contraction. The apical aneurysm was already dilated and spherical in late systole; the absence of active relaxation was considered to be the cause of the paradoxic jet flow. In this report, we suggest the pathogenesis of left ventricular apical aneurysm and paradoxic jet flow in MVOHCM.

Marked decrease in BNP levels in 2 related patients with reversible dilated cardiomyopathy.

Two male patients, one in his thirties and the other in his fifties, were admitted to different hospitals for congestive heart failure (CHF). In both patients, laboratory findings indicated high plasma B-type natriuretic peptide (BNP) levels (266.0 and 902.7 pg/mL, respectively) and echocardiography showed large left ventricular diastolic dimensions (LVDd) (67 and 73 mm, respectively) and low ejection fractions (EF) (26% and 18%, respectively). Coronary arteriography revealed no organic stenosis in either patient. Following treatment, plasma BNP levels decreased to below the limit of measurement (4 pg/mL) in both patients and echocardiography revealed improved LVDd (61 and 52 mm, respectively) and EF (41% and 45%, respectively). Because these patients are related, genetic factors might have affected low plasma BNP levels. Moreover, these results suggest that marked decrease in plasma BNP during follow up may be an indicator of preserved neurohormonal and organ systems.

Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction.

BACKGROUND: It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling following myocardial infarction. In contrast, little is known about the effects of increasing skeletal muscle mass, typically achieved through resistance training, on this process. Here, we utilized transgenic (TG) mice that can induce the growth of functional skeletal muscle by switching Akt1 signaling in muscle fibers to assess the impact of glycolytic muscle growth on post-myocardial infarction cardiac remodeling. METHODS AND RESULTS: Male-noninduced TG mice and their nontransgenic littermates (control) were subjected to left anterior coronary artery ligation. Two days after surgery, mice were provided doxycycline in their drinking water to activate Akt1 transgene expression in a skeletal muscle-specific manner. Myogenic Akt1 activation led to diminished left ventricular dilation and reduced contractile dysfunction compared with control mice. Improved cardiac function in Akt1 TG mice was coupled to diminished myocyte hypertrophy, decreased interstitial fibrosis, and increased capillary density. ELISA and protein array analyses demonstrated that serum levels of proangiogenic growth factors were upregulated in Akt1 TG mice compared with control mice. Cardiac eNOS was activated in Akt1 TG mice after myocardial infarction. The protective effect of skeletal muscle Akt activation on cardiac remodeling and systolic function was abolished by treatment with the eNOS inhibitor l-NAME. CONCLUSIONS: Akt1-mediated skeletal muscle growth attenuates cardiac remodeling after myocardial infarction and is associated with an increased capillary density in the heart. This improvement appears to be mediated by skeletal muscle to cardiac communication, leading to activation of eNOS-signaling in the heart.

Obscured meshwork structure after treatment for heart failure: a case study.

An 87-year-old man with heart failure was admitted to our hospital. A transthoracic echocardiography showed diffuse mild left ventricular (LV) hypokinesis and LV noncompaction at the apex. A three-dimensional transthoracic echocardiography confirmed a trabecular meshwork. After treatment for heart failure, LV end-systolic dimension decreased and trabeculae seemed to converge and became obscure in end-systole. This is a rare case suggesting mechanism of obscured LV noncompaction after treatment for heart failure.

Prominent isovolumic relaxation flow in a patient with cardiac tamponade.

We present herein the case of a 72-year-old man who presented with orthopnea and was diagnosed with cardiac tamponade due to carcinomatous pericarditis. Pulsed Doppler echocardiogram showed prominent isovolumic relaxation flow (IVRF) directed from the cardiac base toward the apex. Such flow is rare in pericardial effusion and may be due to enhanced early diastolic untwisting, sphericalization of apex, and restriction of wall motion by epicardial fibrous tissue. We describe herein a rare case of prominent IVRF with interesting underlying mechanisms.

Triphasic mitral inflow in acute coronary syndrome: A case study.

An 86-year-old woman was referred to our hospital for the management of rapid onset of chest pain. Blood analysis showed increased levels of cardiac enzymes and B-type natriuretic peptide. An electrocardiogram showed poor R wave in precordial leads and a QS wave in lead V4. A chest roentgenogram showed mild pulmonary congestion. An echocardiogram showed hypokinesis of the broad anterior wall of the left ventricle (LV). A pulsed Doppler echocardiogram of mitral inflow revealed an abnormal relaxation pattern. After increasing the preload by leg elevation, an intermittent triphasic mitral inflow pattern emerged. The patient underwent emergent cardiac catheterization for acute coronary syndrome (ACS). A pressure study after leg elevation disclosed an elevation in LV diastolic pressure and a "dip-up-down pattern." The patient underwent percutaneous coronary intervention of the left anterior descending artery. This case showed that a triphasic mitral inflow pattern is observed not only in hypertrophic diastolic heart failure but also in ACS. The triphasic pattern may be observed in the case of low LV distensibility and markedly increased preload. This is the first case report describing triphasic mitral inflow in ACS and demonstrating the pathophysiology of a triphasic mitral inflow pattern.