Valuable Predictors for Non-measurability of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography.

Background The fractional flow reserve (FFR) derived from coronary computed tomography (CT) angiography (FFRCT) is a variable tool for coronary disease diagnosis that non-invasively provides the value of FFR. It can add physiological information to coronary CT angiography (CCTA) and reduce unnecessary invasive coronary angiography (CAG). However, it cannot be analyzed in some cases, which is also called "non-measurability." While FFRCT has become globally widespread, the current data on non-measurability are lacking. This study aimed to determine the rate of non-measurability and identify predictors thereof in routine clinical settings to explore potential approaches to reduce the non-measurability rate. Methods and results This retrospective observational single-center study included consecutive patients who underwent FFRCTanalysis in Japan. The mean age of the overall population was 71.3 ± 10.6, and an FFRCTof ≤0.8 was seen in 47.6% of patients with a measurable FFRCT. Of the 307 enrolled patients, FFRCT analysis was not feasible in 21 cases (6.8%). Heart rate (HR) at a CT scan and coronary calcium scores (CCS) were significantly higher in patients with non-measurability than those in patients whose FFRCT was appropriately analyzed (HR: 69.6±8.9 bpm vs. 61.0±11.1 bpm; p < 0.01; CCS; 931.2 (290.8, 1451.3) vs. 322.9 (100.7, 850.0); p < 0.01). Multiple logistic regression showed that HR was an independent predictor for non-measurability (odds ratio: 1.05; 95% confidential interval: 1.02, 1.09; p < 0.01)). Based on the receiver operating characteristic curve analysis, the optimal cut-off value of HR and CCS was 63 bpm (specificity: 67.1%; sensitivity: 76.2%) and 729.2 (specificity: 71.3%; sensitivity: 66.7%). In addition, the combination of two features (HR > 63 bpm and CCS > 729.2) showed a high negative predictive value (99.3%) for FFRCT non-measurability. Conclusions In this study, the rate of FFRCTnon-measurability was 6.8%. Higher HR at a CT scan and CCS were significantly associated with non-measurability, and in cases with both HR and CCS below a specified threshold, the likelihood of ruling out non-measurability could be significantly high. Our findings suggest that reducing the HR to ideally under 63 bpm at the time of the CT scan significantly ensures feasibility. Further study on large-scale cohorts is warranted.

Sodium-Glucose Cotransporter-2 Inhibitors in Heart Failure with Malnutrition, Frailty, Sarcopenia, or Cachexia.

(1) Background: In patients with heart failure (HF) and impaired nutritional status or decreased muscle mass, sodium-glucose cotransporter-2 inhibitors (SGLT2is) may worsen these conditions and result in poor prognosis, especially worsening of frailty. We aimed to investigate the relationship between SGLT2is and clinical outcomes, including frailty-related events, in patients with HF and malnutrition, frailty, sarcopenia, or cachexia. (2) Methods: In this retrospective observational cohort study, a global federated health research network provided data on patients with HF and malnutrition, frailty, sarcopenia, or cachexia from January 2016 to December 2021. We investigated the incidence of the composite endpoint of death or frailty-related events within one year. (3) Results: Among 214,778 patients included in the analysis, 4715 were treated with SGLT2is. After propensity score matching, 4697 patients in the SGLT2is group were matched with 4697 patients in the non-SGLT2is groups. The incidence of the composite endpoint, mortality, and frailty-related events was lower in the SGLT2is group than in the non-SGLT2is group (composite endpoint, 65.6% versus 77.6%, p < 0.001; mortality, 17.4% vs. 35.5%, p < 0.001; frailty-related events, 59.4% vs. 64.3%, p < 0.001). (4) Conclusions: Patients with HF and malnutrition, frailty, sarcopenia, or cachexia had a high incidence of death and frailty-related events. SGLT2is were associated with a lower incidence of these events.

Impact of Dapagliflozin on the Renal Function and Damage in Patients with Heart Failure with a Reduced Ejection Fraction.

Objective Whether or not the initial dip in the glomerular filtration rate (GFR) after the initiation of sodium-glucose co-transporter 2 inhibitors (SGLT2is) is associated with renal tubular injury in patients with heart failure with a reduced ejection fraction (HFrEF) is unclear. We therefore investigated the relationship between changes in the estimated GFR (eGFR) and urine N-acetyl-ß-D-glucosaminidase (uNAG) after the initiation of dapagliflozin in patients with HFrEF. Methods We prospectively investigated 89 patients with HFrEF who were newly started on dapagliflozin 10 mg/day. Changes in the eGFR and uNAG-to-creatinine ratio (uNAG/Cre) were evaluated at 2 weeks and 2 months after the initiation of dapagliflozin. Results The eGFR was decreased at 2 weeks but had not declined further by 2 months. The uNAG/Cre was increased at 2 weeks but had not increased further by 2 months. There was no correlation between the changes in the eGFR and uNAG/Cre (r=-0.022, p=0.853 at 2 weeks and r=0.078, p=0.538 at 2 months). The relative change in the systolic blood pressure, hematocrit, plasma volume, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were correlated with the relative change in the eGFR. In a multiple linear regression analysis, the relative change in the eGFR at 2 weeks was significantly associated with NT-proBNP, and the relative change in the uNAG/Cre was significantly associated with the use of loop diuretics and the relative change in urine osmolality at 2 weeks. Conclusion A transient decrease in the eGFR after the initiation of dapagliflozin in patients with HFrEF was not generally associated with renal tubular injury and might have been the result of hemodynamic alteration.

Safety and Efficacy of Renal Denervation in Patients Taking Antihypertensive Medications.

BACKGROUND: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. OBJECTIVES: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications. METHODS: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis. RESULTS: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients. CONCLUSIONS: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).

Guillain-Barré syndrome after percutaneous coronary intervention and transcatheter aortic valve implantation.

Guillain-Barré syndrome (GBS) usually develops after preceding infection, but cardiac surgery can also occasionally cause GBS. Currently, cardiac catheterizations have already become common therapeutic options for heart diseases, but there have been no reports of GBS occurrence after that. Herein, we present a rare case in which GBS occurred following catheterization. An 85-year-old-man with sudden onset chest pain was rushed to our hospital and diagnosed with ST-elevated myocardial infarction. He underwent emergent percutaneous coronary intervention (PCI) to left anterior descending artery, but he still had exertional chest pain. Echocardiography revealed severe aortic stenosis (AS) and our heart team considered AS was the cause of symptom and decided to perform and transcatheter aortic valve implantation (TAVI), 11 days after the PCI. However, 5 days after the TAVI procedure, he presented with symmetrical muscular weakness of extremities. Cranial magnetic resonance imaging showed no significant lesion. Based on several signs including albuminocytologic dissociation in cerebrospinal fluid examination, demyelinating polyneuropathy in nerve conduction study, positive anti-ganglioside antibody, and the lack of preceding infection, he was diagnosed with GBS triggered by cardiac catheterizations. We administered high-dose intravenous immunoglobulin therapy and his motor strength gradually improved, finally discharged with full motor strength after 7 months rehabilitation. Learning objective: •Cardiac surgery has been already reported as a non-infectious risk factor of Guillain-Barré syndrome (GBS) in previous literatures, and cardiac catheterization such as percutaneous coronary intervention and transcatheter aortic valve implantation, which were relatively less invasive procedure, may be a potential risk factor for GBS occurrence as well.•If a patient complains of progressive, symmetrical neurological symptoms after cardiac catheterization, GBS should be considered as the possible cause, and nerve conduction study and cerebrospinal fluid examination may be helpful for the diagnosis.

Effect of dapagliflozin on ventricular repolarization in patients with heart failure with reduced ejection fraction.

Whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce ventricular arrhythmias and sudden cardiac death is controversial. Ventricular repolarization heterogeneity is associated with ventricular arrhythmias; however, the effect of SGLT2is on ventricular repolarization in patients with heart failure with reduced ejection fraction (HFrEF) has not been fully investigated. We prospectively evaluated 31 HFrEF patients in sinus rhythm who were newly started on dapagliflozin 10 mg/day. Changes in QT interval, corrected QT interval (QTc), QT dispersion (QTD), corrected QTD (QTcD), T peak to T end (TpTe), TpTe/QT ratio, and TpTe/QTc ratio were evaluated at 1-year follow-up. QT interval, QTc interval, QTD, QTcD, TpTe, and TpTe/QTc ratio decreased significantly at 1-year follow-up (427.6 ± 52.6 ms vs. 415.4 ± 35.1 ms; p = 0.047, 437.1 ± 37.3 ms vs. 425.6 ± 22.7 ms; p = 0.019, 54.1 ± 11.8 ms vs. 47.6 ± 14.7 ms; p = 0.003, 56.0 ± 11.2 ms vs. 49.4 ± 12.3 ms; p = 0.004, 98.0 ± 15.6 ms vs. 85.5 ± 20.9 ms; p = 0.018, and 0.225 ± 0.035 vs. 0.202 ± 0.051; p = 0.044, respectively). TpTe/QT ratio did not change significantly (0.231 ± 0.040 vs. 0.208 ± 0.054; p = 0.052). QT interval, QTD, and TpTe were significantly reduced 1 year after dapagliflozin treatment in patients with HFrEF. The beneficial effect of dapagliflozin on the heterogeneity of ventricular repolarization may contribute to the suppression of ventricular arrhythmias.Registry information https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000049428 . Registry number: UMIN000044902.

Impact of coronary bifurcation angle on stent malapposition in a randomized comparison between proximal optimization technique followed by side branch dilatation and kissing balloon inflation.

Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 µm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p < 0.05). In the POT-SBD group, worsening ISA after SBD was prominent at the distal bifurcation. The BA was an independent predictor of major ISA (odds ratio 1.04, 95% confidence interval 1.00-1.07, p < 0.05) with a cut-off value of 59.5° (p < 0.05). However, the cases treated with optimal POT in the short BA (<60°) indicated the lowest incidence of major ISA. In the KBT group, BA had no significant impact. Conclusion: A wide BA has a potential risk for the occurrence of major ISA after POT followed by SBD in coronary bifurcation stenting.

Delayed rupture of the iliac artery after endovascular therapy.

Iliac artery rupture during endovascular therapy (EVT) is a life-threatening complication requiring prompt diagnosis and treatment. However, delayed rupture of the iliac artery after EVT is rare, and its predictive value remains unknown. Herein, we present the case of a 75-year-old woman who developed delayed iliac artery rupture 12 h after balloon angioplasty and placement of a self-expandable stent in the left iliac artery. Hemostasis was achieved with a covered stent graft. However, the patient died of hemorrhagic shock. From the review of previous case reports and the pathological findings of the current case, increased radial force due to overlapping stent and kinking of the iliac artery may be associated with delayed iliac artery rupture. Learning objective: Delayed iliac artery rupture after endovascular therapy is rare but with a poor prognosis. Hemostasis can be achieved using a covered stent; however, the outcome could be fatal. Based on pathological findings and previous case reports, increased radial force at the stent site and kinking of the iliac artery may be associated with delayed iliac artery rupture. Self-expandable stent probably should not be overlapped at the site where kinking is likely to occur, even if long stenting is needed.

Prevalence, characteristics and cardiovascular and non-cardiovascular outcomes in patients with heart failure with supra-normal ejection fraction: Insight from the JROADHF study.

AIMS: We aimed to investigate the characteristics and prognosis of patients with heart failure (HF) with supra-normal ejection fraction (HFsnEF) compared to HF with normal ejection fraction (HFnEF). METHODS AND RESULTS: Among 11 573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1943 patients (16.8%) were classified as HFsnEF (left ventricular ejection fraction [LVEF] >65%), 3277 (28.3%) as HFnEF (50% ≤ LVEF ≤65%), 2024 (17.5%) as HF with mildly reduced ejection fraction (40% ≤ LVEF <50%) and 4329 (37.4%) as HF with reduced ejection fraction (LVEF <40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96, 95% confidence interval 0.88-1.05, p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction. CONCLUSIONS: Heart failure with supra-normal ejection fraction is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

Anticoagulant management during percutaneous coronary intervention for a patient with antithrombin deficiency.

Previous reports on cardiac intervention in cases with antithrombin deficiency are extremely limited. We report a case of acute coronary syndrome with antithrombin deficiency in a 62-year-old man with multiple histories of thrombosis. He had worsening chest pain, and laboratory data showed an elevated level of troponin T, suggesting acute myocardial infarction. Currently, there is no fixed anticoagulation strategy for coronary intervention in patients with antithrombin deficiency. In this case, we performed coronary intervention with heparin in addition to antithrombin concentrate. The intervention was successfully performed without thrombosis or bleeding complications. Learning objective: Antithrombin deficiency is a rare disorder and data about coronary intervention for cases with antithrombin deficiency are limited. We successfully performed intervention with our anticoagulant management and it would be beneficial for future reference.

Malnutrition, hemodynamics and inflammation in heart failure with reduced, mildly reduced and preserved ejection fraction.

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), malnutrition can be associated with intestinal congestion and systemic inflammation. These relationships have not been fully investigated in HF with mildly reduced EF (HFmrEF) and with preserved EF (HFpEF). We analyzed 420 patients with HF who underwent right heart catheterization. The relationships between hemodynamic parameters, C-reactive protein, and the controlling nutritional (CONUT) score were investigated in HFrEF, HFmrEF and HFpEF. The CONUT score of all patients was 2 [1, 4] (median [interquartile range]), and was not significantly different between the left ventricular EF (LVEF) categories (2 [1, 3] for HFrEF, 2 [1, 3] for HFmrEF, and 3 [1, 4] for HFpEF, p = 0.279). In multivariate linear regression analyses, there was a significant association between CRP and the CONUT score in HFmrEF and HFpEF, while brain natriuretic peptide and right atrial pressure were significantly associated with the CONUT score in HFrEF. Higher CONUT scores predicted a higher incidence of the composite endpoint of death or HF hospitalization within 12 months without an interaction with LVEF (p = 0.980). The CONUT score was an independent predictor of the composite endpoint, death, and HF hospitalization after adjustment for confounders in the multivariate analysis. In conclusion, inflammation was associated with malnutrition in HFmrEF and HFpEF, while congestion was an independent predictor of malnutrition in HFrEF. Malnutrition predicted worse outcomes regardless of LVEF.

Acute Myocarditis in a Patient Following mRNA-1273 SARS-CoV-2 Vaccination.

We herein report a case of acute myocarditis possibly related to the second dose of an mRNA-coronavirus disease 2019 vaccine in a 45-year-old woman with no remarkable medical history. She had a fever for one week following the second dose of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 vaccine. One week later, she presented with chest pain and electrocardiogram changes. Her serum troponin levels were elevated upon admission. Echocardiography showed segmental wall motion abnormalities of the apex, apical portion of the anterior and inferior walls. The findings of cardiac magnetic resonance imaging were consistent with acute myocarditis.

Effect of proximal optimization technique on coronary bifurcation stent failure: Insights from the multicenter randomized PROPOT trial.

OBJECTIVE: We investigated the effect of proximal optimization technique (POT) on coronary bifurcation stent failure (BSF) in cross-over stenting by comparing with the kissing balloon technique (KBT) in a multicenter randomized PROPOT trial. BACKGROUND: POT is recommended due to increased certainty for optimal stent expansion and side branch (SB) wiring. METHODS: We randomized 120 patients treated with crossover stenting into the POT group, which was followed by SB dilation (SBD), and the KBT group. Finally, 52 and 57 patients were analyzed by optical coherence tomography before SBD and at the final procedure, respectively. Composite BSF was defined as a maximal malapposition distance of >400 µm, or malapposed and SB-jailed strut rates of >5.95% and >21.4%, respectively. RESULTS: Composite BSF before SBD in the POT and KBT groups was observed in 29% and 26% of patients, respectively. In the POT group, differences in stent volumetric index between the proximal and distal bifurcation (odds ratio [OR] 60.35, 95% confidential interval [CI] 0.13-0.93, p = 0.036) and between the proximal bifurcation and bifurcation core (OR: 3.68, 95% CI: 1.01-13.40, p = 0.048) were identified as independent risk factors. Composite BSF at final in 27% and 32%, and unplanned additional procedures in 38% and 25% were observed, respectively. Composite BSF before SBD was a risk factor for the former (OR: 6.33, 95% CI: 1.10-36.50, p = 0.039) and the latter (OR: 6.43, 95% CI: 1.25-33.10, p = 0.026) in the POT group. CONCLUSION: POT did not result in a favorable trend in BSF. Insufficient expansion of the bifurcation core after POT was associated with BSF.

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.