CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

Effectiveness of high flow-volume intermittent hemodiafiltration during and after intervention to prevent contrast-induced nephropathy in patients with advanced chronic kidney disease: A pilot study.

OBJECTIVES: We analyzed the effect of high flow-volume intermittent hemodiafiltration (HF-IHDF) on patients with advanced chronic kidney disease (CKD) undergoing procedures requiring administration of contrast medium. BACKGROUND: There is no effective method for preventing contrast-induced nephropathy (CIN), especially in patients with advanced CKD. We established HF-IHDF as a renal protective therapy with a filtration flow rate up to 5 times greater than standard continuous HDF. In this study, we tested whether HF-IHDF could prevent CIN in patients with advanced CKD more effectively than saline hydration only. METHODS: We retrospectively analyzed the incidence of CIN and clinical outcomes up to 1 year after performance of a procedure in 76 patients with advanced CKD. HF-IHDF was performed from just before the procedure until 2.5 hr after it. Hydration with 0.9% saline was also administered. RESULTS: The incidence of CIN was significantly lower in the HF-IHDF group than the saline group 2-3 days (0%, 0/76 patients vs. 9.3%, 5/54 patients; p < .05) and 1 month (3.9%, 3/76 patients vs. 14.8%, 8/54 patients; p < .05) after intervention. No difference between the two groups was detected in the proportion of patients requiring permanent hemodialysis within 1 year after intervention or the 1 year mortality rate. However, the number of patients free from progression of renal dysfunction after 1 year of follow-up was significantly higher in the HF-IHDF group (86.8%, 66/76 patients vs. 64.8%, 35/54 patients; p < .01). CONCLUSIONS: HF-IHDF during and after interventional procedure requiring administration of contrast medium may prevent CIN in patients with advanced CKD.

Modification of treatment strategy after FFR measurement: CVIT-DEFER registry.

The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in daily practice. The CVIT-DEFER registry is a prospective multicenter registry enrolling consecutive patients with angiographically intermediate coronary stenosis for whom FFR measurement is clinically indicated. The treatment strategy determined from angiographic findings alone and the strategy selected after FFR measurement were compared. Data on the treatment strategy were obtained for 3093 subjects. The average age of these subjects was 69.5 ± 10.2 years and 73.8 % were men. The majority had stable coronary artery disease, including 60.4 % with stable angina pectoris. The treatment strategy based on angiographic findings was medical management in 34.5 %, percutaneous coronary intervention (PCI) in 63.5 %, and coronary artery bypass grafting in 2.1 %. The FFR was ≤0.8 in 1566 lesions (42.2 %). After FFR measurement, medical treatment was changed to revascularization in 19.7 %, while PCI was switched to medical treatment in 57.4 % at the lesion level. As a result, reclassification of the treatment strategy at the patient level was done in 39.0 % of the patients. Revascularization was frequently switched to medical treatment after FFR measurement. These findings support the clinical utility of employing FFR data to guide selection of PCI.

Prevalence of visual-functional mismatch regarding coronary artery stenosis in the CVIT-DEFER registry.

The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clinically relevant coronary artery stenosis. However, mismatch in assessing the severity of coronary stenosis between coronary angiography and the FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)-DEFER registry is a prospective multicenter registry study that has enrolled 3,228 consecutive patients among 3,804 patients with angiographically moderate coronary artery lesions in whom FFR analysis was clinically indicated. The demographic and angiographic parameters associated with an FFR ≤0.8 were analyzed, and the incidence of discrepancy between the angiographic severity of coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609 (42.9%) lesions were categorized as showing 50% stenosis, 1,882 lesions (50.2%) as 75% stenosis, and 257 lesions (6.9%) as 90% stenosis. Angiographic-FFR "mismatch," which was defined as visual stenosis ≥75% with FFR >0.80, was found in 43.4% of lesions, while reverse angiographic mismatch (visual stenosis <75% with FFR ≤0.8) was found in 23.2%. The independent predictors for "angiographic-FFR mismatch" were the presence of percutaneous coronary intervention (PCI) history, one-vessel disease, non-left anterior descending artery (LAD) location, non-diffuse lesion, non-ostial lesion, and non-tandem lesion. Conversely, "reverse angiographic mismatch" was independently associated with the multivessel disease, LAD location, and diffuse lesion. The FFR is not only influenced by luminal stenosis but also by coronary artery morphology and the amount of jeopardized myocardium. Angiographic-FFR mismatch is frequent in patients with moderate coronary stenosis, which suggests the clinical importance of using physiological assessment to guide PCI.

Current treatment of ST elevation acute myocardial infarction in Japan: door-to-balloon time and total ischemic time from the J-AMI registry.

The door-to-balloon time and total ischemic time are important predictors of the outcome in patients with ST elevation myocardial infarction (STEMI) receiving primary angioplasty, but the current situation in Japan is unknown. The Japan Acute Myocardial Infarction registry is a prospective observational study of 2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time from symptom onset to hospital arrival, door-to-balloon time, and in-hospital outcome were assessed. Data were compared between patients treated during regular hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the treated cases. The median symptom onset-to-door time (25th and 75th percentiles) was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and mean procedural time was 98 ± 51 min. The on-call catheterization team performed 48.5 % of the procedures. There was no significant difference of door-to-balloon time between the patients treated after hours and those treated during regular hours. The cardiac mortality rate was 3.2 %, and it increased with longer door-to-balloon times (P = 0.03). The relationship between total ischemic time and cardiac mortality showed 2 peaks, with a trough at 5 h. Median door-to-balloon time was <90 min and was not longer in after hours cases. These findings suggest that Japanese institutions can provide primary angioplasty within an acceptable time frame.

Current antiplatelet therapy for Japanese patients with ST elevation acute myocardial infarction: J-AMI registry.

Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk of bleeding. Recent studies have revealed that bleeding complications are relatively frequent in patients with acute coronary syndromes. Our aim was to describe the current status of antiplatelet therapy for Japanese patients with acute myocardial infarction (AMI). The Japan AMI (J-AMI) registry is a prospective observational study that has enrolled 2,030 consecutive patients with stent thrombosis elevation myocardial infarction (STEMI) admitted to 213 participating Japanese institutions. Current antiplatelet therapy for STEMI was assessed, and the occurrence of bleeding complications (based on GUSTO bleeding criteria) and stent thrombosis was also evaluated. Additionally, the clinical course after bleeding episodes was investigated. Percutaneous coronary intervention (PCI) was done in 97.2% of the patients, using a drug-eluting stent in 30% and a bare metal stent in 63% of PCI cases. A 300-mg loading dose of clopidogrel followed by its administration at 75 mg/day with aspirin was the current standard treatment for Japanese STEMI patients. In-hospital bleeding complications occurred in 1.9%, especially in patients with severe clinical features or a history of cerebrovascular disease. Moderate to severe bleeding complications were associated with 10 deaths. The in-hospital stent thrombosis (ST) rate was 1.47 %, and loading with clopidogrel prior to PCI was significantly less frequent in patients who developed ST (P < 0.001). In conclusion, the J-AMI registry revealed that severe symptoms of STEMI increased the risk of bleeding, while delay of clopidogrel loading was associated with ST. These findings suggest the need for treatment based on risk stratification to improve the balance between the beneficial and adverse effects of antiplatelet therapy in Japanese STEMI patients.

Continuous administration of nicorandil decreases QT dispersion during the chronic phase of acute myocardial infarction.

We previously reported that continuous intravenous (IV) administration of nicorandil (NIC) inhibits QT dispersion (QTd). However, no prior study has evaluated the efficacy of NIC when administered orally to acute myocardial infarction (AMI) patients following continuous IV administration. Thirty patients with anteroseptal infarction in whom revascularization was performed successfully within 6 hours of AMI onset were included in the study and assigned to one of 3 groups: group A (continuous IV administration of NIC), group B (continuous IV and oral administration of NIC), and group C (no treatment with NIC). After 24 hours, QTd in groups A and B was significantly decreased compared to QTd in group C (P < 0.01) (group A, 58.1; group B, 58.2; and group C, 81.3). The QTd obtained 3 months later was significantly shorter in group B subjects who were orally administered NIC, and QTd before percutaneous coronary intervention (PCI) was restored in group A, in which no NIC had been administered orally [group A, 66.7; group B, 54.1; and group C, 73.9; P < 0.05 (group A versus group B) and P < 0.01 (group B versus group C)]. The effects were evaluated by comparing different routes of administration. Continuous IV and subsequent oral administration of NIC inhibited prolongation of QTd, suggesting that these effects may prevent the occurrence of cardiac events during both the acute and chronic phases of AMI.

SOCS1/JAB likely mediates the protective effect of cardiotrophin-1 against lipopolysaccharide-induced left ventricular dysfunction in vivo.

BACKGROUND: Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of cytokine signaling whose expression is induced in the rat heart by cardiotrophin-1 (CT-1). Sepsis-induced myocardial depression results from the expression of inducible nitric oxide synthase (iNOS) evoked by inflammatory cytokines. METHODS AND RESULTS: The effect of CT-1 on lipopolysaccharide (LPS)-induced cardiac dysfunction was examined in a rat model of sepsis. In the absence of CT-1, LPS (1 mg/kg ip) elicited a reduction of systolic function and dilation of the ventricular cavity within 3-6 h after administration. These physiological effects were accompanied by increased ventricular phosphorylation of signal transducers and activators of transcription (STAT) 1 and STAT3, activation of nuclear factor-kappaB and expression of iNOS mRNA. Notably, administration of CT-1 (20 microg/kg iv) immediately prior to LPS significantly inhibited all of these LPS-induced changes. To determine whether SOCS1 expression in cardiomyocytes is sufficient to inhibit LPS- and cytokine-induced expression of iNOS mRNA, the effects of forced expression of SOCS1 in cultured neonatal cardiomyocytes were investigated using an adenovirus-mediated transfection system. Forced expression of SOCS1 significantly inhibited iNOS transcription induced by LPS, tumor necrosis factor-alpha or interferon-gamma. CONCLUSIONS: CT-1-mediated expression of SOCS1 in cardiomyocytes may be a useful target for preventing sepsis-induced myocardial depression.

Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A.

Myocardial hypertrophy and extended cardiac fibrosis are independent risk factors for congestive heart failure and sudden cardiac death. Before age 50, men are at greater risk for cardiovascular disease than age-matched women. In the current studies, we found that cardiac hypertrophy and fibrosis were significantly more pronounced in males compared with females of guanylyl cyclase-A knockout (GC-A KO) mice at 16 wk of age. These gender-related differences were not seen in wild-type mice. In the further studies, either castration (at 10 wk of age) or flutamide, an androgen receptor antagonist, markedly attenuated cardiac hypertrophy and fibrosis in male GC-A KO mice without blood pressure change. In contrast, ovariectomy (at 10 wk of age) had little effect. Also, chronic testosterone infusion increased cardiac mass and fibrosis in ovariectomized GC-A mice. None of the treatments affected cardiac mass or the extent of fibrosis in wild-type mice. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, TGF-beta1, TGF-beta3, angiotensinogen, and angiotensin converting enzyme in the ventricles of male GC-A KO mice was substantially decreased by castration. The gender differences were virtually abolished by targeted deletion of the angiotensin II type 1A receptor gene (AT1A). Neither castration nor testosterone administration induced any change in the cardiac phenotypes of double-KO mice for GC-A and AT1A. Thus, we suggest that androgens contribute to gender-related differences in cardiac hypertrophy and fibrosis by a mechanism involving AT1A receptors and GC-A.

Fibronectin signaling stimulates BNP gene transcription by inhibiting neuron-restrictive silencer element-dependent repression.

OBJECTIVE: Brain natriuretic peptide (BNP) is a cardiac hormone mainly synthesized in ventricles and its expression is markedly increased in ventricular hypertrophy that involves the accumulation of extracellular matrix proteins, such as fibronectin (Fn). We recently reported that Fn signaling stimulated BNP secretion accompanied by hypertrophic responses in vitro. METHODS: To elucidate the regulatory mechanism for BNP gene transcription, we examined cis-acting elements downstream of Fn signaling in rat ventricular myocytes transfected with either the -1812 human BNP-luciferase reporter gene (-1812hBNP/Luc) or one of several truncated forms. RESULTS: A strong cis-repressor element was identified between -552 and -522 in myocytes plated on uncoated dishes. This region contains a neuron-restrictive silencer element (NRSE)-like element (NRSE(BNP)) that is 90% homologous with the NRSE consensus sequence. Neuron-restrictive silencer factor (NRSF) is known to bind to NRSE and to silence transcription of genes containing NRSE. Deletion of NRSE(BNP) and dominant negative NRSF markedly increased the reporter activity in transfected cells, suggesting that the NRSE/NRSF system silences basal BNP gene transcription. When myocytes were cultured on Fn-coated dishes, the reporter activity of -1812hBNP/Luc was increased by approximately 600% compared with that on uncoated dishes. Interestingly, truncation from -552 to -522 reduced the Fn-inducible reporter activity. Moreover, deletion of NRSE(BNP) and dominant negative NRSF also inhibited the Fn-inducible reporter activity. Electrophoretic mobility shift assays showed that Fn signaling inhibited the binding activity of NRSF to NRSE(BNP). CONCLUSION: These results suggest that Fn-induced BNP up-regulation in rat ventricular myocytes is due to inhibition of NRSE(BNP)-dependent repression of BNP gene transcription.