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.

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.

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.

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.

Admission Heart Rate Is a Determinant of Effectiveness of Beta-Blockers in Acute Myocardial Infarction Patients.

BACKGROUND: Beta-blockers are standard therapy for acute myocardial infarction (AMI). However, despite current advances in the management of AMI, it remains unclear whether all AMI patients benefit from ß-blockers. We investigated whether admission heart rate (HR) is a determinant of the effectiveness of ß-blockers for AMI patients. Methods and Results: We enrolled 3,283 consecutive AMI patients who were admitted to 28 participating institutions in the Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) study. According to admission HR, we divided patients into 3 groups: bradycardia (HR <60 beats/min, n=444), normocardia (HR 60 to ≤100 beats/min, n=2,013), and tachycardia (HR >100 beats/min, n=342). The primary endpoint was major adverse cardiac events (MACE), including all-cause death, non-fatal MI, non-fatal stroke, heart failure (HF), and urgent revascularization for unstable angina, at 3-year follow-up. Beta-blocker at discharge was significantly associated with a lower risk of MACE in the tachycardia group (23.6% vs. 33.0%; P=0.033), but it did not affect rates of MACE in the normocardia group (17.8% vs. 18.4%; P=0.681). In the bradycardia group, ß-blocker use at discharge was significantly associated with a higher risk of MACE (21.6% vs. 12.7%; P=0.026). Results were consistent for multivariable regression and stepwise multivariable regression. CONCLUSIONS: Admission HR might determine the efficacy of ß-blockers for current AMI patients.

Association of onset-season with characteristics and long-term outcomes in acute myocardial infarction patients: results from the Japanese registry of acute myocardial infarction diagnosed by universal definition (J-MINUET) substudy.

It is known that incidence and short-term mortality rate of acute myocardial infarction (AMI) tend to be higher in the cold season. The aim of our study was to investigate the association of onset-season with patient characteristics and long-term prognosis of AMI. This was a prospective, multicenter, Japanese investigation of 3,283 patients with AMI who were hospitalized within 48 h of symptom onset between July 2012 and March 2014. Patients were divided into 3 seasonal groups according to admission date: cold season group (December-March), hot season group (June-September), and moderate season group (April, May, October, and November). We identified 1356 patients (41.3%) admitted during the cold season, 901 (27.4%) during the hot season, and 1026 (31.3%) during the moderate season. We investigated the seasonal effect on patient characteristics and clinical outcomes. Baseline characteristics of each seasonal group were comparable, with the exception of age, Killip class, and conduction disturbances. The rates of higher Killip class and complete atrioventricular block were significantly higher in the cold season group. The 3-year cumulative survival free from major adverse cardiac events (MACE) rate was the lowest in the cold season (67.1%), showing a significant difference, followed by the moderate (70.0%) and hot seasons (72.9%) (p < 0.01). Initial severity and long-term prognoses were worse in patients admitted during the cold season. Our findings highlight the importance of optimal prevention and follow-up of AMI patients with cold season onset.

Impact of Residual Stenosis on the Angiographic Edge Restenosis of a Second-Generation Drug-Eluting Stent.

Edge restenosis has gained attention as a main cause of restenosis after first-generation drug-eluting stent (DES) implantation. The aim of this study was to assess the incidence of edge restenosis and identify the predictors of edge restenosis after second-generation DES implantation. Data were obtained from several postmarketing surveillance (PMS) studies on a cobalt-chromium everolimus-eluting stent (CoCr-EES; Xience V/PROMUS, Xience Prime, Xience Prime SV, and Xience Expedition SV), a second-generation DES, in Japan. Angiographic analysis was conducted at the baseline and after eight months on the following subsegments: in-stent region, proximal edge, and distal edge. Restenosis was defined as ≥ 50% diameter stenosis (DS) at follow-up. We used multivariate logistic regression (with lesions as a random effect) to compare the instances of restenosis between the proximal and the distal edges. Univariate and multivariate analyses of the risk factors for restenosis were performed for each subsegment. We analyzed 1,966 lesions in 1,687 patients. The restenosis rates at the in-stent region, proximal edge, and distal edge were 4.4%, 3.0%, and 1.1%, respectively. The risk of restenosis at the distal edge was significantly lower than that at the proximal edge, when adjusted for 13 variables. The predictors of restenosis were postprocedural % diameter stenosis (%DS), postprocedural reference diameter, ≥ 45° bending, stent overlap at the proximal edge, and postprocedural %DS at the distal edge. Our analysis of eight-month angiographic outcomes from CoCr-EES PMS demonstrated that postprocedural %DS is a major predictor of edge restenosis. Edge restenosis is more likely attributable to postprocedural angiographic results than to the patient's background.

Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting Stents in Patients on Hemodialysis.

BACKGROUND: Elevated serum phosphorus level is an important risk factor for cardiovascular death in general patients on hemodialysis (HD). However, the effect of serum phosphorus levels on outcomes after drug-eluting stent (DES) implantation in HD patients is unknown.Methods and Results:This was a post-hoc study of the OUCH study series, a series of prospective multicenter registries of HD patients who underwent DES implantation comprising 359 patients from 31 centers in Japan. Patients were categorized into 3 groups according to their preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336 patients treated for de novo lesions were evaluated. Compared with patients with high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels, those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%; P=0.032). Multivariate logistic regression analysis revealed that low serum phosphorus level was an independent negative predictor for major adverse cardiac and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval, 0.12-0.70; P=0.0036). CONCLUSIONS: Lowering of serum phosphorus levels beyond the current recommended range may be considered in HD patients who undergo DES implantation.

Prognostic Impact of Computed Tomography-Derived Abdominal Fat Area on Transcatheter Aortic Valve Implantation.

BACKGROUND: Obesity has previously been identified as an indicator of good prognosis in patients undergoing transcatheter aortic valve implantation (TAVI), an association known as the "obesity paradox". We investigated whether abdominal total fat area (TFA), visceral fat area (VFA), or subcutaneous fat area (SFA) are prognostic indicators of long-term clinical outcome in patients undergoing TAVI. Methods and Results: We retrospectively analyzed 100 consecutive patients who underwent TAVI between December 2013 and April 2017. TFA, VFA, and SFA were measured from routine pre-procedural computed tomography (CT). Patients were divided into 2 groups according to median TFA, VFA, or SFA, and we investigated the association of abdominal fat area with adverse clinical events, including all-cause death and re-hospitalization due to worsening heart failure. At a median follow-up of 665 days, patients with higher SFA had significantly lower incidence of the composite outcome and all-cause death compared with patients with lower SFA (15.0% vs. 37.7%, P=0.025; and 8.9% vs. 23.7%, P=0.047, respectively). In contrast, patients with higher TFA or VFA did not show significant reduction in the incidences of the composite outcome or all-cause mortality. CONCLUSIONS: CT-derived SFA had prognostic value in patients undergoing TAVI.

Pulmonary Tumor Thrombotic Microangiopathy due to Advanced Gastric Cancer with Virchow's Node Metastasis.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication characterized by severe progressive pulmonary hypertension. Antemortem diagnosis is difficult owing to the rapid progression of the condition, especially when the patient has no known malignancies and initially presents with pulmonary hypertension. Here we report a case of PTTM due to occult gastric cancer with metastasis in the left supraclavicular lymph node, also known as Virchow's node. Enlarged Virchow's node is an important indicator of advanced gastric cancer. In patients with progressive pulmonary hypertension of unknown origin, enlarged Virchow's node can be an important indicator for the diagnosis of PTTM.

Impact of Indoxyl Sulfate on Coronary Plaques in Patients on Hemodialysis.

Serum indoxyl sulfate (IS; a uremic toxin) levels, which are significantly higher in patients with chronic kidney disease, including those undergoing hemodialysis, than in the robust, are associated with both cardiovascular disease (CVD) and CVD-related mortality. Furthermore, coronary artery calcium (CAC) is an independent predictor of cardiovascular events in patients undergoing hemodialysis. This study aimed to interpret the association between serum IS levels and coronary plaque burden (CPB) or CAC.A total of 30 consecutive patients on hemodialysis, who underwent 320-row coronary multidetector computed tomography (MDCT) angiography for suspected coronary artery disease, were enrolled in this prospective study. Coronary artery percent atheroma volume (a CPB marker) and percent calcium volume (a CAC marker) assessed using MDCT were evaluated. Furthermore, various oxidative and inflammatory markers typified by serum IS levels at a dialysis-free day were measured. Using these data, we investigated correlation between the inflammatory marker IS and CPB or CAC.Multivariable analysis indicated that serum IS levels were positively correlated with CAC [partial regression coefficient, 2.89; 95% confidence interval (CI), 0.35-5.43; P = 0.03] but not with CPB, even after adjustment for cofounders. Composite cardiovascular events, namely, as all-cause death, non-fatal myocardial infarction, disabling stroke, and hospital admission for other cardiovascular events, were reported to be 50% in all patients (95% CI, 32.1-67.9).In patients undergoing hemodialysis, serum IS levels were significantly associated with CAC but not with CPB.

A High Level of Blood Urea Nitrogen Is a Significant Predictor for In-hospital Mortality in Patients with Acute Myocardial Infarction.

High levels of blood urea nitrogen (BUN) have been demonstrated to significantly predict poor prognosis in patients with acute decompensated heart failure. However, this relationship has not been fully investigated in patients with acute myocardial infarction (AMI). We investigated whether a high level of BUN is a significant predictor for in-hospital mortality and other clinical outcomes in patients with AMI. The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective, observational, multicenter study conducted in 28 institutions, in which 3,283 consecutive AMI patients were enrolled. We excluded 98 patients in whom BUN levels were not recorded at admission and 190 patients who were undergoing hemodialysis. A total of 2,995 patients were retrospectively analyzed. BUN tertiles were 1.5-14.4 mg/dL (tertile 1), 14.5-19.4 mg/dL (tertile 2), and 19.5-240 mg/dL (tertile 3). Increasing tertiles of BUN were associated with stepwise increased risk of in-hospital mortality (2.5, 5.1, and 11%, respectively; P < 0.001). These relationships were also observed after adjusting for reduced estimated glomerular filtration rate (estimated GFR < 60 mL/minute/1.73 m2) or Killip classifications. In multivariable analysis, high levels of BUN significantly predicted in-hospital mortality, after adjusting for creatinine and other known predictors (BUN tertile 3 versus 1, adjusted odds ratio [OR]: 2.59, 95% confidence interval [95% CI]: 1.57-4.25, P < 0.001; BUN tertile 2 versus 1, adjusted OR: 1.60, 95% CI: 0.94-2.73, P = 0.081). A high level of BUN could be a useful predictor of in-hospital mortality in AMI patients.

Association of Dyslipidemia and Sex With Coronary Artery Calcium Assessed by Coronary Computed Tomography Angiography.

Previous studies reporting that statin increases coronary artery calcium (CAC) were conducted exclusively on patients with statin as a prevention, regardless of the presence or absence of dyslipidemia. The impact of sex on CAC has not been fully evaluated. We aimed to determine the association of dyslipidemia and sex with CAC using 320-row multi-detector computed tomography (MDCT).Of the 356 consecutive patients who underwent coronary MDCT, 251 patients were enrolled, after excluding those with prior stenting and/or coronary bypass grafting or images showing motion artifacts. The primary outcome measures were the percent calcium volume (PCV) and percent atheroma volume (PAV) per coronary vessel.Multivariable analyses indicated that PCV was significantly higher in dyslipidemia patients without statins than in the subjects without dyslipidemia [partial regression coefficient (PRC): 2.59, 95% confidence interval (CI): 0.83 to 4.34, P = 0.004]. In contrast, PCV was similar in dyslipidemia patients taking statins and those without dyslipidemia (PRC: -1.09, 95% CI: -2.82 to 0.65, P = 0.22). There was no significant difference in PCV between men and women, although women exhibited a significantly lower PAV (PRC: -2.87, 95% CI: -4.54 to -1.20, P = 0.001).In low-risk patients, these results could be translated into hypotheses, which should be tested in future prospective studies. Furthermore, there was no significant difference in CAC between men and women, but women had lower PAV than men.

Effects of Long-Acting Loop Diuretics in Heart Failure With Reduced Ejection Fraction Patients With Cardiac Resynchronization Therapy.

There have been no reports evaluating the impact of long-acting loop diuretics (LLD) on the outcome of heart failure (HF) and arrhythmia treatment in HF with reduced ejection fraction (HFrEF) patients implanted with a cardiac resynchronization therapy (CRT) device.This was a prospective, single-blind, randomized crossover study. We allocated 21 consecutive CRT implanted patients into 2 groups. The furosemide group received furosemide as a first treatment and azosemide as a second treatment. The azosemide group received this treatment in the reverse order. The first treatment was given to each group for 6 months and the second treatment continued for an additional 6 months. We combined the data of each medication regimen in each group and analyzed it at baseline, 6 months, and 1 year. The primary endpoints were the variation of fluid index and thoracic impedance measured by CRT at 6 months.The baseline characteristics were similar for both groups. The difference in the primary endpoints was not statistically significant between the 2 medication arms (fluid index: -29.6 ± 64.4 versus 16.2 ± 48.2; P = 0.22, thoracic impedance: -0.49 ± 17.8 versus 2.45 ± 12.5; P = 0.56). Likewise, the clinical outcome of HF and the CRT derived parameters in both arms were comparable.HFrEF patients taking LLD after CRT implantation might be comparable to those taking short-acting loop diuretics in the treatment of HF and HF-associated arrhythmias.

Three-Year Clinical Outcomes of Everolimus-Eluting Stents From the Post-Marketing Surveillance Study of Cobalt-Chromium Everolimus-Eluting Stent (XIENCE V/PROMUS) in Japan.

BACKGROUND: The Cobalt-Chromium Everolimus-Eluting Stent (CoCr-EES) Post-marketing Surveillance (PMS) is a prospective multicenter registry designed to evaluate the safety and efficacy of XIENCE V/PROMUS everolimus-eluting stents in routine clinical practice at 47 centers representative of the clinical environment in Japan. METHODS AND RESULTS: We enrolled 2,010 consecutive patients (2,649 lesions) who underwent PCI using CoCr-EES. Clinical outcomes were evaluated for up to 3 years. Clinical follow-up was available in 1,930 patients (96%) at 3 years. Major adverse cardiovascular events (MACE) occurred in 6.8% of patients, including cardiac death (1.7%), myocardial infarction (1.5%), and clinically driven target lesion revascularization (CD-TLR, 4.2%). Late CD-TLR rate was 0.8% from 1 to 2 years, and 0.5% from 2 to 3 years. Definite or probable stent thrombosis occurred in 7 patients (0.3%) up to 1 year. There was no very late definite or probable stent thrombosis from 1 to 3 years. Significant independent predictors for MACE were hemodialysis, prior coronary intervention, triple-vessel coronary artery disease, and age >70 years. CONCLUSIONS: Three-year clinical outcomes from the CoCr-EES PMS demonstrated a low incidence of clinical events. There was no major concern about very late stent thrombosis or late catch-up phenomenon in patients treated with EES in routine clinical practice in Japan.

Consensus statement on renal denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: (1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or (2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

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.

Incidence and predictors for late target lesion revascularization after sirolimus-eluting stent implantation.

BACKGROUND: In long-term follow-up after drug-eluting stents (DES) implantation, late target lesion revascularization (TLR) is occasionally required. However, the incidence and predictors for late TLR with DES have not been fully investigated. METHODS AND RESULTS: Between August 2004 and March 2005, 249 consecutive patients underwent percutaneous coronary intervention with sirolimus-eluting stents (SES) at our institution. Angiographic follow-up data were obtained in 228 patients (91.6%) with 274 lesions (91.6%) at 8 months. TLR incidence was evaluated up to 5 years. The 5-year clinical follow-up data were obtained in 222 patients (97.4%) with 264 lesions (96.4%). The incidence of early TLR before 1 year was 16.7%, and that of late TLR (1-5 years) was 8.3% (2.1% per year). Multivariate analysis indicated that significant predictors for late TLR were insulin-treated diabetes mellitus (DM) (odds ratio (OR) 10.88, P=0.001), stent fracture (OR 27.24, P=0.012), and age (OR 0.94, P=0.026). No association was observed between late TLR and lesion characteristics, including parameters measured by quantitative coronary angiography other than stent fracture, at baseline, post procedure, and follow-up. CONCLUSIONS: Late TLR after SES implantation occurred in approximately 2.1% of lesions per year after the first year without attenuation up to 5 years. Significant predictors for late TLR were insulin-treated DM, stent fracture and younger age. Careful long-term follow-up after SES implantation might be recommended.