Real-world clinical outcomes of percutaneous transluminal septal myocardial ablation for patients with drug-refractory hypertrophic obstructive cardiomyopathy: results from a retrospective multicenter registry of non-high-volume centers.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a well-established interventional therapy for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) as an alternative to surgical myectomy. Although guidelines recommend that PTSMA should be performed in institutions with extensive experience, it is not centralized to such high-volume centers in real-world clinical practice. Thus, this study aimed to assess the feasibility of PTSMA in non-high-volume centers. We retrospectively examined patients with HOCM who underwent PTSMA between August 2012 and May 2020 at four institutions that experienced fewer than 20 cases of PTSMA procedures. The primary clinical endpoint was a composite of safety (all-cause death, electrical defibrillation for ventricular tachycardia or fibrillation, cardiac tamponade, permanent pacemaker implantation, and repeated interventions) and efficacy endpoints (repeated interventions [PTSMA or surgical myectomy]). Fifty-eight consecutive patients were enrolled. During the 30-day follow-up, no major clinical adverse events were noted except three patients (5.2%) requiring permanent pacemaker implantation for complete atrioventricular block. The percentage of patients with New York Heart Association functional class 1 or 2 significantly increased from 8.6 to 100% (p < 0.001). In the Cox proportional hazard model, left ventricular outflow tract pressure gradient at rest ≥ 30 mmHg (hazard ratio [HR] 6.56; 95% confidence interval [CI] 1.44-29.90; p = 0.015) and mitral regurgitation grade ≥ 3 (HR 10.75; 95% CI 1.81-63.79; p = 0.009) at the 30-day follow-up were associated with a composite of major clinical adverse events. The current study demonstrated that 58 patients who underwent PTSMA in non-high-volume centers had favorable 30-day clinical outcomes, with a primary composite endpoint rate of 5.2%. A prospective study with a larger sample size and longer follow-up is warranted to verify the safety and efficacy of PTSMA in non-high-volume centers.

Estimating Incidence of Acute Heart Failure Syndromes in Japan　- An Analysis From the KUNIUMI Registry.

BACKGROUND: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. CONCLUSIONS: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

BACKGROUND: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). CONCLUSIONS: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Vascular Response Occurring at 3 Months After Everolimus-Eluting Cobalt-Chromium Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction vs. Stable Coronary Artery Disease.

BACKGROUND: Second-generation drug-eluting stents (DES) reduce the incidence of stent thrombosis, even in patients with ST-segment elevated myocardial infarction (STEMI). However, the early local vascular healing after DES implantation in STEMI lesions, which mainly concerns stent thrombosis, is still unclear.Methods and Results:We attempted to determine early local vascular healing 3 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in STEMI lesions relative to stable coronary artery disease (CAD) lesions. This prospective, multicenter study analyzed 96 total lesions (STEMI=49, stable CAD=51) by frequency domain-optical coherence tomography (FD-OCT) performed post-procedure and at the 3-month follow-up. Although CoCr-EES implanted in STEMI were almost entirely covered at 3 months, they had a relatively high incidence of uncovered struts compared with stable CAD (5.5% vs. 1.6%, P<0.001). Intrastent thrombus in the 2 groups was primarily resolved at the 3-month follow-up (STEMI: 91.7%→26.5%, stable CAD: 74.5%→11.8%). Regarding irregular protrusion, complete resolution was observed in stable CAD (21.6%→0%), while a few stents remained in STEMI (79.2%→8.2%). Although there were almost no changes for the serial change of average lumen area in STEMI, there were slight but significant decreases in stable CAD [STEMI 0.08 (-0.44, 0.55) mm2, stable CAD -0.35 (-0.55, 0.11) mm2; P=0.009]. CONCLUSIONS: Although strut coverage after CoCr-EES implantation for STEMI lesions was slightly delayed, the healing process appeared to be acceptable in both STEMI and stable CAD.

Mid-term effect of balloon aortic valvuloplasty on mitral regurgitation in aortic stenosis.

BACKGROUND: Balloon aortic valvuloplasty (BAV) offers an alternative to conventional aortic valve replacement in elderly and frail patients with severe aortic stenosis (AS) for whom there are no other effective options. We aimed to investigate the mid-term effect of BAV on mitral regurgitation (MR) in patients with severe AS. METHODS: Our analysis was based on the data from 83 patients with severe AS (mean age, 86 ± 5 years; female, 68) treated using BAV. Echocardiography was performed before the procedure and at 1 and 3 months after. MR was quantified by measuring the MR jet area, with more-than-moderate MR being clinically significant. RESULTS: Forty patients were classified in this group (MR group). Significant reduction of MR was observed in the MR group at 1 month and 3 months after procedure, with no improvement in patients in the non-MR group. At 3 months, 15 of the 40 patients in the MR group still had significant MR, with the change at 1 month in the left ventricular end-systolic dimension (OR: 1.36; 95% CI: 1.05-1.76; P = 0.022) and MR jet area (OR: 1.95; 95% CI: 1.16-3.29; P = 0.012) being predictive of persisting significant MR at 3 months after BAV. The prevalence of New York Heart Association functional class III or IV decreased at 1 and 3 months after BAV in both groups. CONCLUSIONS: BAV provides a useful therapeutic strategy for elderly patients with severe AS who are not candidates for surgical or transcatheter aortic valve replacement, especially in those with significant MR.

A pharmacodynamics comparison of prasugrel and clopidogrel in patients undergoing hemodialysis.

Platelet reactivity in the presence of clopidogrel is deteriorated in patients undergoing hemodialysis (HD). However, the impact of residual platelet reactivity with prasugrel use in Japanese patients on HD remains unclear. This was a prospective, multi-center, single-arm study conducted to compare platelet reactivity of prasugrel 3.75 mg per day vs. clopidogrel 75 mg per day in patients on chronic HD. We assessed P2Y12 reaction units (PRU) using the VerifyNow® P2Y12 test for all enrolled patients at baseline (clopidogrel treatment) and at 14 days (prasugrel treatment) pre- and post-HD. Clinical outcomes data were obtained on day 14. A total of 38 patients on HD were included in this study. The PRU were significantly higher in patients on clopidogrel than in patients on prasugrel in both phases (pre-HD: clopidogrel 226 ± 80 vs. prasugrel 175 ± 82, p < 0.001) (post-HD: clopidogrel 256 ± 67 vs. prasugrel 210 ± 63, p < 0.001). There were no patients with bleeding or adverse events during the two weeks of prasugrel treatment. Prasugrel 3.75 mg per day, adjusted for Japanese patients, inhibited platelet aggregation better than clopidogrel, even after hemodialysis, which might contribute to the reduced incidence of major adverse event in patients undergoing HD.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

Effect of Ezetimibe on Stabilization and Regression of Intracoronary Plaque　- The ZIPANGU Study.

BACKGROUND: Diminishing yellow color is associated with plaque stabilization. We assessed the hypothesis that a combination of ezetimibe and statin provides more effective plaque stabilization and regression than statin alone as assessed by plaque color.Methods and Results:Stable coronary artery disease patients (n=131) who underwent elective percutaneous coronary intervention and had yellow plaques were randomized to combination therapy (atorvastatin 10-20 mg and ezetimibe 10 mg/day; Group C) or statin monotherapy (atorvastatin 10-20 mg; Group M). Changes in plaque color and plaque volume during 9 months were assessed by angioscopy and intravascular ultrasound. Low-density lipoprotein cholesterol (LDL-C) decreased from 103±28 to 63±18 mg/dL in Group C (P<0.001) and from 100±28 to 75±17 mg/dL in Group M (P<0.001). Yellow color grade decreased significantly in both Group M (2.1±1.1 vs. 1.7±1.0, P=0.005) and Group C (2.2±1.2 vs. 1.8±1.2, P=0.002), but did not differ between the groups. %plaque volume did not change in Group M (48.5±10.2% vs. 48.2±10.4%, P=0.4), but decreased significantly in Group C (50.0±9.8% vs. 49.3±9.8%, P=0.03). CONCLUSIONS: Compared with statin monotherapy, combination therapy with ezetimibe further reduced LDL-C levels. Significant plaque volume reduction was achieved by the combination therapy, but not statin monotherapy; however, plaque stabilization was similarly achieved by both therapies. Furthermore, reduction in plaque volume was dependent on reduction in LDL-C, regardless of whether it was achieved by statin alone or statin plus ezetimibe.

Qualitative and quantitative assessment of stent restenosis by optical coherence tomography: comparison between drug-eluting and bare-metal stents.

BACKGROUND: We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses. METHODS AND RESULTS: One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01). CONCLUSIONS: The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies.

Volume-outcome relationship in balloon aortic valvuloplasty: results of a consecutive, patient-level data analysis from a Japanese nationwide multicentre registry (J-SHD).

OBJECTIVE: Transcatheter balloon aortic valvuloplasty (BAV) remains an important alternative treatment for severe, symptomatic aortic stenosis. With increasing numbers of BAVs being performed, the need for large-scale volume-outcome relationship assessments has become evident. Here, we aimed to explain such relationships by analysing consecutive, patient-level BAV data recorded in a prospective Japanese nationwide multicentre registry. DESIGN: Prospective study. SETTING: Data of 1920 BAVs performed in 200 Japanese hospitals from January 2015 to December 2019. PARTICIPANTS: The mean patient age was 85 years, and 36.9% of procedures involved male patients. METHODS: The efficacy of BAV was assessed by reducing the mean transaortic valve gradient after the procedure. We also assessed in-hospital complication rates, including in-hospital death, bleeding, urgent surgery, distal embolism, vessel rupture and contrast-induced nephropathy. Based on the distribution of case volume (median 20, IQR 10-46), we divided the patients into high-volume (≥20) and low-volume (<20) groups. In-hospital complication risk was assessed with adjustment by logistic regression modelling. RESULTS: Indications for BAV included palliative/destination (44.2%), bridge to transcatheter aortic valve replacement (34.5%), bridge to surgical aortic valve replacement (7.4%) and salvage (9.7%). Reduction of the mean transaortic valve gradient was similar between the high-volume and low-volume groups (20 mm Hg vs 20 mm Hg, p=0.12). The proportion of in-hospital complications during BAV was 4.2%, and the incidence of complications showed no difference between the high-volume and low-volume groups (4.2% vs 4.1%, p=1.00). Rather than hospital volume, salvage procedure was an independent predictor of in-hospital complications (OR, 4.04; 95% CI, 2.03 to 8.06; p<0.001). CONCLUSION: The current study demonstrated that procedural outcomes of BAV were largely independent of its institutional volume.

Recurrent cardiac arrests caused by Kounis syndrome without typical allergic symptoms.

Kounis syndrome is a rare disease in which coronary spasm or acute coronary syndrome is induced by type I allergy. Concurrence of allergic reaction and chest pain are important clues to establish diagnosis. We report a rare case of Kounis syndrome without obvious signs of allergy.A 52-year-old woman experienced abdominal pain followed by ventricular fibrillation (VF) storm. Ten months earlier, the patient underwent subcutaneous implantable cardioverter-defibrillator implantation based on the previous diagnosis of idiopathic VF. In both episodes, the patient was given dental treatment and administered loxoprofen before VF onset. After we performed loxoprofen provocation test, electrocardiogram revealed ST-segment elevation in leads II, III, and aVF. Moreover, the patient developed VF again. An emergency coronary angiography after recovery showed no significant findings. However, myocardial scintigraphy presented a perfusion-metabolism mismatch in the inferior wall. Furthermore, laboratory test results after provocation revealed increased histamine level. Based on these findings, we diagnosed the patient with Kounis syndrome.Kounis syndrome without typical allergic symptoms is challenging to diagnose. Therefore, suspecting the possibility of allergic reactions and detailed history taking are important, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest. Learning objective: Kounis syndrome is a rare coronary disease with vasospasm or plaque rupture, induced by type I allergy. Since Kounis syndrome without typical allergic symptoms is challenging to diagnose, a high index of suspicion is necessary. Detailed history taking can provide important clues to establish diagnosis, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest.

Aetiology of chronic heart failure in patients from a super-aged society: the KUNIUMI registry chronic cohort.

AIMS: With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super-aged society. METHODS AND RESULTS: The KUNIUMI registry chronic cohort is a community-based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P < 0.01). The prevalence of atrial fibrillation, and in particular long-standing persistent atrial fibrillation, increased at 70 years of age (P < 0.01). The proportion of patients with heart failure with preserved ejection fraction increased to ~60% when age was over 75 years. Although ischaemic heart disease accounted for 35.0% of chronic heart failure aetiologies, valvular heart disease was the most common cause of chronic heart failure (49.8%). The major types of valvular heart disease were mitral regurgitation and tricuspid regurgitation (27.2% and 21.7%, respectively), both of which increased significantly with age (P < 0.01). The incidence of aortic valve stenosis increased markedly over the age of 85 years (P < 0.01). Atrial functional mitral regurgitation increased with age and was the major cause of mitral regurgitation in patients aged >75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long-standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P < 0.001, respectively). CONCLUSIONS: The KUNIUMI registry chronic cohort showed a change in heart failure aetiology to valvular heart disease in a super-aged society. Effective and comprehensive countermeasures are required to prepare for the rapid rise in heart failure incidence in a super-aged society.

Atrial tachycardia related to atrial infarction treated with catheter ablation: a case report.

Background: Atrial infarction, usually concurrent with ventricular infarction, is under-recognized. Although most patients with atrial infarction have complicated supraventricular tachyarrhythmias, its mechanism is still unknown. We report a case of atrial tachycardia (AT) related to atrial infarction treated with catheter ablation. Case summary: A 51-year-old man was referred for acute chest pain. Electrocardiography showed a junctional rhythm with ST depression in the precordial leads. Emergency coronary angiography revealed an occluded dominant left circumflex coronary artery (LCX). A drug-eluting stent was deployed; however, the atrial branch from the distal side of the LCX was jailed by the stent and became occluded. On the 7th day, the premature atrial contractions (PACs) became frequent and changed to AT. Owing to its resistance to medication, we performed catheter ablation. The electro-anatomical map revealed counter-clockwise macro-reentrant tachycardia at the tricuspid valve annulus, with low-voltage and fragmented potential (FP) areas at the posterior wall of the right atrium (RA). After terminating the AT through linear ablation for the cavotricuspid isthmus, multiple-focus PACs originating from the FP area in the RA posterior wall were documented. Coronary angiography revealed that these damaged areas were perfused by the atrial branch of the LCX. Defragmentation in the FP area could eliminate PACs. The patient was discharged with sinus rhythm and without any complications. Discussion: We can perform electro-anatomical mapping to identify tachycardia circuit and PACs arising from the FP area in the posterior RA, where the atrial branch was perfusing. Multiple PACs from infarcted myocardium result in tachycardia.

Incidence and natural history of coronary evagination after implanted biodegradable polymer sirolimus-eluting stent.

Aims: The incidence and temporal change in coronary evagination (CE) after first-generation drug-eluting stent implantation is well established, whereas that after biodegradable polymer sirolimus-eluting stent (BP-SES) implantation has not yet been evaluated. The aim of this study is to assess the incidence and natural history of CE after BP-SES implantation. Methods and results: In this multicenter registry, stable coronary lesions treated by Ultimaster BP-SES were evaluated by serial optical frequency domain imaging (OFDI) (at 0-1-12 or 0-3-12 months) and the incidence of CE was assessed. Coronary evagination was defined as the presence of an outward bulge in luminal vessel contour between apposed struts according to the following criteria: (i) evagination depth ≥10% of nominal stent diameter and (ii) evagination length ≥3.0 mm. Optical frequency domain imaging was obtained in 98, 47, 49, and 87 lesions at 0, 1, 3, and 12 months, respectively. Coronary evagination was observed in 20 (42.6%) and 12 (24.5%) lesions at 1 and 3 months, respectively, and all but one CE had resolved at 12 months. At 12 months, the mean CE area was almost zero and the mean malapposed stent area was also decreased. Comparison of the serial OFDI images indicated that CEs originated mostly from acute stent malapposition or coronary dissection behind the implanted stent. Conclusions: In stable lesions, CE was occasionally observed with Ultimaster BP-SES at 1-3 months but mostly resolved within 12 months, without late-acquired stent malapposition. These findings suggest the safety and feasibility of biodegradable polymer coating on DES.

Effect of Ivabradine on Left Ventricular Diastolic Function of Patients With Preserved Ejection Fraction　- Results of the IVA-PEF Study.

Background: The association between heart rate (HR) reductions caused by ivabradine and left ventricular (LV) diastolic function in heart failure with preserved ejection fraction (HFpEF) remains uncertain because of off-label use. Thus, the present study investigated the effect of HR reductions by ivabradine on LV diastolic function in HFpEF patients. Methods and Results: This study enrolled 16 HFpEF patients with HR ≥75 beats/min. After 3 months administration of ivabradine, no significant changes were observed in mitral inflow E and mitral e' annular velocities, B-type natriuretic peptide, or left atrial volume index, but there were significant improvements in global longitudinal strain. Conclusions: Ivabradine did not improve LV diastolic function for HFpEF patients with HR ≥75 beats/min. Because this may be due to some study limitations, further studies should be conducted.

Efficacy of Renin-angiotensin-aldosterone-system inhibitors for heart failure with preserved ejection fraction and left ventricular hypertrophy -from the KUNIUMI Registry Acute Cohort.

BACKGROUND: Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. METHODS: We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. RESULTS: In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors' prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR <30 mL/min/1.73 m2, the outcome was similar between patients with and without RAAS inhibitor prescription. Multivariable Cox regression analysis showed that the prescription of RAAS inhibitors was the only independent predictor of outcome in HFpEF patients with LVH and mild-moderate CKD (HR 0.49; 95% CI 0.25-0.94; p = 0.03). CONCLUSIONS: Our findings showed the importance of HFpEF phenogrouping for identifying effective pharmacological treatments.

Differences in Prognostic Factors among Patients Hospitalized for Heart Failure According to the Age Category: From the KUNIUMI Registry Acute Cohort.

Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p<0.001). A Cox proportional-hazard regression analysis revealed that the presence of atrial fibrillation [hazard ratio (HR): 23.3, 95% confidence interval (CI): 2.36-231.1, p=0.007] was a notable predictive factor for all-cause death in the ≤65 years old group, whereas the Clinical Frailty Scale score (HR: 1.33, 95% CI: 1.16-1.52, p<0.001) and hypoalbuminemia (HR: 0.49, 95% CI: 0.31-0.78, p=0.003) were predictors in the >85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Association of congestion with worsening renal function in acute decompensated heart failure according to age.

AIMS: Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re-hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re-hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high-aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population-based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. METHODS AND RESULTS: We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re-hospitalization after discharge over a mean follow-up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high-aged patients ≥80 years old, but not for those <80 years old if decongested. Multivariable Cox regression analysis showed that both residual congestion at discharge and WRF were the independent predictors of outcomes for high-aged patients, but residual congestion at discharge, not WRF, was the independent predictor of outcomes for older patients. CONCLUSIONS: Association of residual congestion at discharge with WRF for hospitalized ADHF patients can differ according to age. Our findings showed the importance of WRF and residual congestion at discharge for high-aged ADHF patients and of aggressive diuresis to alleviate congestion for older ADHF patients for better management of such patients in a rapidly ageing society.

A serial optical frequency-domain imaging study of early and late vascular responses to bioresorbable-polymer sirolimus-eluting stents for the treatment of acute myocardial infarction and stable coronary artery disease patients: results of the MECHANISM-ULTIMASTER study.

The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

Reverse remodelling induces progressive ventricular resynchronization after cardiac resynchronization therapy 'from vicious to virtuous cycle'.

AIMS: Cardiac resynchronization therapy (CRT) can stop the vicious cycle resulting from dyssynchrony and generates left ventricular (LV) reverse remodelling. Our objective was to assess the time course and the relationship between improvement in LV dyssynchrony and reverse remodelling after CRT. METHODS AND RESULTS: Sixty-four consecutive patients were evaluated before, immediately after, and 3- and 6 months after CRT. We measured LV volumes, ejection fraction (EF), and sphericity index, and dyssynchrony was assessed using speckle-tracking radial strain. Response was defined as a >15% decrease in end-systolic volume (ESV) 6 months after CRT, and event-free survival was followed for 24 months. Responders and non-responders had similar baseline LV volumes and EF. During the first and the following 3 months after CRT, LV volumes gradually decreased (end-diastolic volume: 195±73 to 164±60* to 129±51 mL†, ESV: 141±70 to 110±47* to 82±40 mL†), and sphericity index and EF progressively increased (sphericity index: 1.52±0.20 to 1.75±0.31* to 1.94±0.34†, EF: 28±7 to 34±7* to 38±8%†, *†P<0.001) in responders. No such changes were observed in non-responders. Furthermore, dyssynchrony diminished progressively during the first and the following 3 months after CRT and patients with progressive resynchronization experienced fewer major cardiovascular events than those without (P<0.001). CONCLUSION: CRT can stop the vicious cycle of remodelling and dyssynchrony, and actually, turn it into the virtuous cycle of reverse remodelling and further resynchronization.