Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.

OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.

Histopathologically TMA-like distribution of multiple organ thromboses following the initial dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech): an autopsy case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide. Vaccination is now recommended as one of the effective countermeasures to control the pandemic or prevent the worsening of symptoms. However, its adverse effects have been attracting attention. Here, we report an autopsy case of multiple thromboses after receiving the first dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) in an elderly woman. CASE PRESENTATION: A 72-year-old woman with a history of diffuse large B-cell lymphoma in the stomach and hyperthyroidism received the first dose of the BNT162b2 mRNA vaccine and died 2 days later. The autopsy revealed multiple microthrombi in the heart, brain, liver, kidneys, and adrenal glands. The thrombi were CD61 and CD42b positive and were located in the blood vessels primarily in the pericardial aspect of the myocardium and subcapsular region of the adrenal glands; their diameters were approximately 5-40 µm. Macroscopically, a characteristic myocardial haemorrhage was observed, and the histopathology of the characteristic thrombus distribution, which differed from that of haemolytic uraemic syndrome and disseminated intravascular coagulation, suggested that the underlying pathophysiology may have been similar to that of thrombotic microangiopathy (TMA). CONCLUSION: This is the first report on a post-mortem case of multiple thromboses after the BNT162b2 mRNA vaccine. The component thrombus and characteristic distribution of the thrombi were similar to those of TMA, which differs completely from haemolytic uraemic syndrome or disseminated intravascular coagulation, after vaccination. Although rare, it is important to consider that fatal adverse reactions may occur after vaccination and that it is vital to conduct careful follow-up.

Effect of cutting balloon after rotational atherectomy in severely calcified coronary artery lesions as assessed by optical coherence tomography.

OBJECTIVES: Using optical coherence tomography (OCT), we evaluated the effect of a cutting balloon (CB) compared with a conventional balloon after rotational atherectomy (RA) and before stenting in severely calcified coronary lesions. BACKGROUND: A CB is designed to create discrete incisions to facilitate fracture of severely calcified plaque. METHODS: OCT was performed preintervention (if possible), post-RA, and poststent implantation. RA modification of calcium was defined as a polished, concave, round-shaped surface. Calcium fracture was defined as a break in the calcium plate. The effects of calcium modification and stent expansion between CB (n = 18) versus conventional balloon (n = 23) following RA were compared. RESULTS: Median patient age was 72 years with 24% on hemodialysis. The amount of calcium and the length of RA modification were comparable between the CB and conventional balloon groups. Final poststent OCT showed that the number and thickness of calcium fracture were greater after CB versus conventional balloon, resulting better stent expansion (78.9% [IQR: 72.4-88.1] vs. 66.7% [IQR: 55.0-76.7], p < 0.01). In the multivariable model, after adjusting for the amount of calcium, CB use was an independent predictor of the presence of calcium fracture (odds ratio 30.0; 95% confidence interval 2.7-994.1, p = 0.004) and an independent predictor for greater stent expansion (regression coefficient 7.4; 95% confidence interval 0.5-14.3, p = 0.04). CONCLUSION: In severely calcified lesions calcium fracture was more often associated with RA followed by CB compared with RA followed by conventional balloon predilation before stenting. CB use was also a determinant of greater stent expansion.

Association of Epicardial Adipose Tissue Volume and Total Coronary Plaque Burden in Patients with Coronary Artery Disease.

The relationship between epicardial adipose tissue volume (EATV) and plaque vulnerability in non-culprit coronary lesions is not clearly understood.Fifty-four consecutive patients/158 lesions with suspected coronary artery disease underwent computed tomography (CT) and 40 MHz intravascular ultrasound imaging (iMap-IVUS) in cardiac catheterization. Cross-sectional CT slices were semiautomatically traced from base to apex of the heart. Using a 3D workstation, EATV was measured as the sum of fat areas (-190 to -30 Hounsfield units [HU]). All coronary vessels were imaged using iMap-IVUS before stenting to analyze coronary plaques as fibrotic, lipidic, necrotic, or calcified tissue.Mean EATV was 73.7 ± 24.6 (range: 30.2 to 131.8) mL. Patients were divided into two groups by mean EATV (group H: n = 27, EATV ≥ 73.7 mL; group L: n = 27, EATV < 73.7 mL). Total luminal volume, total vessel volume, and total plaque volume were significantly larger in group H. Fibrotic plaque and lipidic plaque volumes were also significantly larger in group H. There was a significant negative correlation between EATV and fibrous tissue (r = -0.31, P = 0.02) and a significant positive correlation between EATV and necrotic tissue (r = 0.37, P = 0.007). EATV was related to plaque with vulnerability in the right coronary artery (RCA) (r = 0.57, P = 0.04) and the left anterior descending artery (LAD) (r = 0.53, P = 0.02). In conclusion, increased EATV was associated with the total coronary plaque burden and composition, particularly in the RCA and LAD.

Can right ventricular endomyocardial biopsy predict left ventricular fibrosis beforehand in dilated cardiomyopathy?

AIMS: Myocardial fibrosis of the left ventricle (LV) is a prognostic factor in dilated cardiomyopathy (DCM). This study aims to evaluate whether fibrosis of right ventricular (RV) endomyocardial biopsy (EMB) can predict the degree of LV fibrosis beforehand in DCM. METHODS AND RESULTS: Fibrosis extent in 70 RV-EMB specimens of DCM diagnosis was compared with that in the whole cross-sectional LV of excised hearts in the same patients (52 explanted hearts for transplant and 18 autopsied hearts). The median interval between biopsy and excision was 4.1 (0.13-19.3) years. The fibrosis area ratio of the EMBs and excised hearts were evaluated via image analysis. The distribution of cardiovascular magnetic resonance-late gadolinium enhancement (LGE) in the intraventricular septum was classified into four quartile categories. The fibrosis area ratio in RV-EMB correlated significantly with that in the short-axis cut of the LV of excised hearts (r = 0.82, P < 0.0001) and with a diffuse pattern of LGE (r = 0.71, P = 0.003). In a multivariate model, after adjusting for the interval between biopsy performance and heart excision, the fibrosis area ratio in RV-EMB was associated with that in LV-excised heart (regression coefficient, 0.82; 95% confidence interval, 0.68-0.95; P < 0.0001). CONCLUSIONS: The fibrosis observed in RV-EMB positively correlated with the extent of fibrosis in the LV of excised hearts in patients with DCM. The study findings may help predict LV fibrosis, considered a prognostic factor of DCM through relatively accessible biopsy techniques.

Mechanism of Stent Failure in Patients With Eruptive Calcified Nodule Treated With Rotational Atherectomy.

BACKGROUND: Percutaneous coronary intervention (PCI) for lesions with eruptive calcified nodules (CNs) is associated with worse outcomes compared with that for other calcified lesions. We aimed to clarify the relationship between eruptive CNs at index PCI, optical coherence tomography (OCT) findings at the 8-month follow-up, and clinical outcomes using serial OCT. METHODS: This retrospective observational study used data from a prospective, single-centre registry. We conducted consecutive PCI for calcified lesions requiring rotational atherectomy (RA) with OCT guidance. We categorized 51 patients (54 lesions) into those with (16 patients [16 lesions]) and without eruptive CNs (35 patients [38 lesions]). RESULTS: Post-PCI, stent expansion was comparable between the 2 groups, and CN-like protrusion was found in 75% of lesions with eruptive CNs. Follow-up OCT at 8 months revealed in-stent CNs in 54% of treated eruptive CN lesions, whereas lesions without eruptive CNs lacked in-stent CNs. Multivariate linear regression analysis demonstrated that eruptive CN was associated with maximum neointimal tissue (NIT) thickness (regression coefficient 0.303; 95% confidence interval, 0.057-0.549; P = 0.02). Consequently, patients with eruptive CNs exhibited a higher clinically driven target lesion revascularization (TLR) rate than did those without at 1 year (31.3% vs 2.9%, P = 0.009) and 5 years (43.8% vs 11.4%, P = 0.02). TLR primarily occurred in lesions with maximum eruptive CN arc angles > 180°. CONCLUSIONS: Following RA treatment with acceptable stent expansion, eruptive CNs before PCI correlated with greater NIT formation with in-stent CNs, resulting in a higher TLR rate, particularly in lesions with maximum eruptive CN arc angles exceeding 180°.

Difficulties in Carotid Artery Stenting Due to Calcified Nodules: A Case Report.

The feasibility of carotid artery stenting (CAS) for carotid stenosis with severely calcified plaque remains controversial. Understanding the features associated with CAS difficulty in lesions with severe calcification is crucial. Calcified nodules, one of the morphological patterns of calcified plaques, have not been assessed for their association with the feasibility of CAS, even though they are associated with failure of percutaneous coronary intervention (PCI) in coronary arteries. We present a rare case of carotid stenosis with calcified nodules in whom CAS was unsuccessful and who was subsequently successfully treated by carotid endarterectomy (CEA). A 79-year-old man presented with a transient ischemic attack caused by severe stenosis of the right internal carotid artery and opted for CAS. During the procedure, multiple attempts at balloon angioplasty using a 3.5-mm balloon were made, but effective dilation could not be achieved, resulting in recoil. Subsequently, the patient underwent carotid endarterectomy (CEA), and the excised specimen revealed a calcified nodule, a large nodular calcified plaque protruding into the lumen. The patient was discharged with a modified Rankin Scale score of 0 at 19 days after the CEA. The protrusion of this large calcified nodule into the lumen was deemed responsible for the inadequate stent dilation. Although rarely reported in carotid stenosis, calcified nodules might represent a challenging plaque type for CAS treatment.

Fulminant myocarditis with COVID-19 infection having normal C-reactive protein and serial magnetic resonance follow-up.

A 44-year-old woman who was quarantined for 5 days after the diagnosis of coronavirus disease of 2019 (COVID-19) was transferred to our hospital with the complaint of chest pain. The patient was unvaccinated. Electrocardiography revealed ST elevation in the lateral leads. Echocardiographic biventricular dysfunction with oedematous wall thickening was identified. Cardiac enzyme levels were elevated; however, C-reactive protein (CRP) levels, and the coronary angiogram were normal. The patient required mechanical circulatory support to stabilize haemodynamics and was treated with remdesivir, baricitinib, and intravenous methylprednisolone. She recovered after 13 days of mechanical support. Serial cardiac magnetic resonance imaging revealed acute myocardial oedema and subsequent fibrosis. An endomyocardial biopsy on admission showed mild interstitial inflammatory infiltrates with endomyocardial fibrous thickening and mild interstitial fibrosis of the myocardium. Normal CRP levels suggested minor involvement of interleukin (IL)-6, supporting the efficacy of baricitinib.

Morphological characteristics of cardiac myxoma causing embolism: a series of 40 years of experience at a single institute.

Systemic and cerebral embolisms are serious complications of associated with cardiac myxoma. Embolism risk reportedly depends on the gross and histological morphology. This study is aimed at analyzing the morphologic pattern of excised cardiac myxoma as a high-risk embolic cause. Between 1978 and April 2022, 116 surgical specimens of cardiac myxomas were recorded at the pathology department of our hospital. The tumors were classified into three types based on their macroscopic shapes and external morphology-round-smooth, irregular, and villous-to investigate the embolic complications. Of the 116 specimens, 106 macroscopic images of cardiac myxoma (89% were located in the left atrium) were prepared. Round-smooth types were found in 36 (34.0%) patients, irregular types in 32 (30.2%) patients, and the villous types in 38 (35.8%) patients. Multivariable analysis revealed that a villous external appearance was an independent predictor of embolic events (odds ratio: 8.7; 95% confidence interval: 2.4-42.1; p < 0.001). Villous external appearance of cardiac myxoma was associated with the highest risk of distal embolism.

A 5-year survivor of endarterectomy for sclerosing undifferentiated intimal sarcoma of the pulmonary artery: Importance of clinical suspicion and careful histologic evaluation.

We present a diagnostically challenging case of intimal sarcoma of the pulmonary artery (PA) due to the histologic finding of a sclerosing appearance with no appreciable spindle/pleomorphic cell proliferation. Initial endarterectomy specimens were composed of sclerosing extracellular matrix with a few bland cells, some recanalization, and fibrin thrombi, impeding the confirmation of intimal sarcoma as these findings were also consistent with chronic thromboembolic pulmonary hypertension. However, the patient experienced recurrence 5 years later, and the second endarterectomy specimens revealed more firm and solid mass and the proliferation of atypical spindle/pleomorphic cells within a myxomatous matrix in the distal PA, leading to the definitive diagnosis of undifferentiated intimal sarcoma of the PA. The archival specimens from the endarterectomy confirmed intense MDM2 expression by immunohistochemistry, suggesting its role as a potential diagnostic marker for intimal sarcoma. This case highlights that prominent sclerosing extracellular matrix with very few atypical cells should raise the possibility of intimal sarcoma of the PA and that high index of suspicion, generous sampling, and ancillary tests are critical for accurate diagnosis. In this case, the tumor was incidentally removed by endarterectomy, resulting in 5 years of survival.

Early vascular responses to abluminal biodegradable polymer-coated versus circumferential durable polymer-coated newer-generation drug-eluting stents in humans: a pathological study.

BACKGROUND: Recent clinical studies are testing strategies for short (1-3 months) dual antiplatelet therapy following newer-generation drug-eluting stent (DES) placement. However, detailed biological responses to newer-generation DES remain unknown in humans. AIMS: We sought to evaluate early pathologic responses to abluminal biodegradable polymer-coated (BP-) DES compared with circumferential durable polymer-coated (DP-) DES in human autopsy cases. METHODS: The study included 38 coronary lesions with newer-generation DES implanted for <90 days (DP-DES=24, BP-DES=14) in 26 autopsy cases. The degree of strut coverage was defined as follows: grade 0 (bare), grade 1 (with fibrin or tissues/cells without endothelium), grade 2 (with single-layered endothelium), and grade 3 (with endothelium and underlying smooth muscle cell layers). RESULTS:  The duration following implantation was similar in DP- and BP-DES (median=20 vs 17 days). A total of 2,022 struts (DP-DES=1,297, BP-DES=725) were pathologically analysed. Focal grade 2 coverage was observed as early as 5 days after the implantation in both stents. The multilevel mixed-effects ordered logistic regression model demonstrated that BP-DES exhibited greater strut coverage compared with DP-DES (odds ratio [OR]: 3.64, 95% confidence interval [CI]: 1.37-9.67; p=0.009), which remained significant after adjustment for the duration following implantation and underlying tissue characteristics (OR: 2.74, 95% CI: 1.10-6.80; p=0.030). The predictive probability of grade 2 and 3 coverage was comparably limited at 30 days (DP-DES=17.1%, BP-DES=28.7%) and increased at 90 days (DP-DES=76.5%, BP-DES=86.6%). Both stents showed low inflammation and a similar degree of fibrin deposition. CONCLUSIONS: Single-layered endothelial coverage begins in the days after newer-generation DES placement, and BP-DES potentially exhibit faster strut coverage with smooth muscle cell infiltration than DP-DES in humans. Nevertheless, vessel healing remains suboptimal in both stents at 30 days.

Microthrombosis as a cause of fulminant myocarditis-like presentation with COVID-19 proven by endomyocardial biopsy.

Myocardial injury has been reported as a complication of COVID-19. Although several mechanisms have been proposed as its cause, they are mostly based on autopsy studies, We report a 49-year-old male with COVID-19-associated myocardial injury presented like fulminant myocarditis. We performed endomyocardial biopsy on day 2 and we confirmed the presence of microthrombosis histologically. He died on day 5 due to cardiogenic shock.

Histopathological and epigenetic changes in myocardium associated with cancer therapy-related cardiac dysfunction.

AIMS: Cancer therapy-related cardiac dysfunction (CTRCD) is commonly reported, but its histopathology, mechanisms, and risk factors are not known. We aimed to clarify the histopathology and mechanisms of CTRCD to identify risk factors. METHODS AND RESULTS: We performed myocardial histopathological studies on 13 endomyocardial biopsies from CTRCD patients, 35 autopsied cancer cases with or without cardiac dysfunction, and controls without cancer (10 biopsies and 9 autopsies). Cardiotoxicity risk scores were calculated based on medication; and patient-related risk factors, fibrosis, and cardiomyocyte changes were scored; and p53 and H3K27ac histone modification were evaluated by histological score (H-score). In the biopsy cases, all histopathological changes and the p53 evaluation were significantly higher in the CTRCD group than in the controls [p53 H-score; 63 (9.109) vs. 33 (5.099), P < 0.05]. In patients with a short time between drug and disease onset (<4.2 years), fibrosis and p53 positively correlated (r = 0.76, P < 0.05), and in those with late onset disease (>4.2 years), cellular abnormalities and p53 trended to a positive correlation and cardiotoxicity risk scores and p53 positively correlated (r = 0.95, P < 0.05). A year after biopsy, the short-term group had significant recovery of ejection fraction compared with the long-term group (P < 0.05). The CTRCD group had a significantly worse overall survival prognosis than the control group [hazard ratio 7.61 (95% confidence interval 1.30-44.6), P < 0.05]. Autopsy cases with cancer treatment also had a high grade of histopathological changes, with even more severe changes in patients with cardiac dysfunction, and had increased p53 and H3K27ac expression levels, compared with controls. H-scores of p53 and H3K27ac showed a positive correlation in the CTRCD group in biopsy cases (r = 0.62, P < 0.05) and a positive correlation in autopsy cases. CONCLUSIONS: Our results indicate distinct morphological characteristics in myocardial histopathology associated with CTRCD. p53 and H3K27ac histone modification could be sensitive markers of CTRCD and suggest a mechanistic involvement of epigenetic changes.

Safety and efficacy of exercise training after coronary stenting in patients with stable coronary artery disease.

BACKGROUND: Exercise training (ET) after coronary stenting is considered to have a risk of stent thrombosis (ST). The present study investigated whether ET increases the incidence of ST in patients undergoing coronary stenting. METHODS AND RESULTS: The current study was a prospective observational study. We enrolled 3,672 patients who underwent successful coronary stenting. Patients decided whether to participate in exercise and were divided into an ET group (n=1,592) and a control group (n=2,080). The primary endpoint was the incidence of ST. Secondary endpoints were major adverse cardiovascular events (MACE: death, myocardial infarction, and stroke) and unscheduled hospital visits for angina. The incidence of ST and MACE were similar in both groups (1.8% vs. 2.0%, P=0.73, 14.9% vs. 15.0%, P=0.97, respectively). Unscheduled hospital visits were significantly lower in the ET group (20.2% vs. 27.2%, P<0.0001). After adjusting for baselines, the ET group had no significant increase in ST (hazard ratio (HR) 0.86, adjusted P=0.56) and MACE (HR 0.98, adjusted P=0.83). The ET was effective to prevent an unscheduled hospital visits for worsening angina (HR 0.67, adjusted P<0.0001). CONCLUSIONS: Moderate ET after successful coronary stenting does not increase the incidence of ST and MACE, and was effective in reducing unscheduled hospital visits for angina.

Comparison of the damage to aorta wall in aortitis versus noninflammatory degenerative aortic diseases.

BACKGROUND: Not rarely aortitis is firstly identified in thoracic aorta aneurysm/dissection specimens only by histopathology in the absence of clinical evidence of systemic inflammatory disease emphasizing the importance of histology for the diagnosis of aortitis. Regardless of the improvement of the pathological assessment of aortic diseases by the recent consensus statements on surgical pathology of the aorta, histology can be confusing since medial degenerative changes (MDC) can be prominent in a background where inflammation is sometimes limited. This raises the question of the role of aging or other degenerative process versus the role of inflammation in the damage to aorta wall. PATIENTS AND METHODS: In this study, besides inflammation, we evaluated aorta samples from aortitis cases focusing on the histological scoring of MDC. In this retrospective single center study, we retrieved 719 cases of ascending aorta aneurysms or dissections operated on from January 2010 until June 2018. MDC (elastic fiber fragmentation and/or loss, smooth muscle nuclei loss, mucoid extracellular matrix accumulation intralemellar or translamellar) were estimated using a scoring system derived from that of the consensus statement. Noninfectious aortitis group versus age-matched non-inflammatory degenerative aortic disease group were compared. RESULTS: Noninfectious aortitis was pathologically diagnosed in 62 patients (8.6%). Among the 62 noninfectious aortitis patients, 47 patients (75.8%) had aortitis identified pathologically prior to the clinical diagnosis. Higher MDC scores were observed at all aortic sizes in aortitis group versus non-aortitis group, especially for elastic fiber damage and smooth muscle cell loss. CONCLUSIONS: Aortitis is remarkably associated with severe damage to the aorta wall resulting in advanced MDC scores. Inflammatory process is responsible for higher MDC in the aorta wall than aging or other degenerative process.

Impact of histopathological changes in ascending aortic diseases.

AIMS: To better understand relationship between histological medial degenerative changes (MDC), pathological status [thoracic aorta aneurysm (TAA), thoracic aorta dissection (TAD), bicuspid aortic valve (BAV), and non-BAV] and aortic size at imaging. METHODS AND RESULTS: We collected 496 ascending aorta surgical specimens from patients with degenerative aortic diseases (mean age, 61 years) whose imaging data were available, including BAV in 191 (TAD 4%, TAA 96%) and with non-BAV in 305 (TAD 45%, TAA 55%). We analyzed them according to the pathology consensus statement and scored MDC [elastic fiber fragmentation and/or loss (EFFL); smooth muscle nuclei loss (SMNL); mucoid extracellular matrix accumulation (MEMA), intralamellar (I) or translamellar (T)] and measured medial wall thickness on correlation with imaging data and the status (TAA, TAD, BAV, or non-BAV). In TAA subset, EFFL, SMNL and MEMA-T scores were lower in BAV than in non-BAV. In relation to the aortic diameter, EFFL, SMNL and MEMA-T scores were more important in TAD subset than in TAA at the small aortic diameters. Independent predictors of aortic dissection included thicker medial wall (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.4 to 17.6; p < 0.0001) and greater SMNL score (OR, 1.2; 95% CI, 1.1 to 1.3; p = 0.003). CONCLUSIONS: This large cohort study confirms that non-BAV aortas present higher MDC scores than BAV aortas. Higher MDC scores are correlated with increased aortic diameter. TAD can occur not infrequently in smaller aortas associated with high MDC scores. This suggests that risk stratification of aortic dissection based on aorta dimensions is imperfect.

Poor prognosis of heart failure patients with in-hospital worsening renal function and elevated BNP at discharge.

AIMS: Our purpose was to investigate the association between the B-type natriuretic peptide (BNP) level at discharge, the occurrence of worsening renal function (WRF), and long-term outcomes in patients with heart failure (HF). METHODS AND RESULTS: We enrolled hospitalized acute HF patients. We divided patients into four groups on the basis of BNP <250 pg/mL (BNP-) or BNP ≥250 pg/mL (BNP+) at discharge and the occurrence of WRF during admission: BNP-/WRF-, BNP-/WRF+, BNP+/WRF-, and BNP+/WRF+. We evaluated the association between BNP at discharge, WRF, and cardiovascular/all-cause mortality/hospitalization due to HF. Clinical follow-up was completed in 301 patients. At discharge, percentages of the patients with clinical signs of HF were low and similar among four groups. The median follow-up period was 1206 days (interquartile range, 733-1825 days). The composite endpoint of cardiovascular mortality and HF hospitalization was significantly different between the four groups [12.9% (BNP-/WRF-), 22.7% (BNP-/WRF+), 35.8% (BNP+/WRF-), and 55.4% (BNP+/WRF+), P < 0.0001]. All-cause mortality was also different etween the four groups (15.1%, 38.6%, 28.7%, and 39.3%, respectively, P = 0.003). In the multivariate Cox proportional hazards model, the combination of BNP ≥250 pg/mL and WRF showed the highest hazard ratio (HR) for composite endpoint (HR, 5.201; 95% confidence interval, 2.582-11.11; P < 0.0001), and BNP-/WRF+ was associated with increased all-cause mortality (HR, 2.286; 95% confidence interval, 1.089-4.875; P = 0.03). Patients in BNP+/WRF+ had a higher cardiovascular mortality (28.6%), and those in BNP-/WRF+ had a high non-cardiovascular mortality (29.5%). CONCLUSIONS: Heart failure patients with BNP ≥250 pg/mL at discharge and in-hospital occurrence of WRF had the highest risk for the composite endpoint (cardiovascular mortality and HF hospitalization) among groups.

Chronic stent recoil in severely calcified coronary artery lesions. A serial optical coherence tomography study.

Chronic second-generation drug-eluting stent recoil in severely calcified coronary lesions has not been studied. We aimed to evaluate chronic stent recoil by optical coherence tomography (OCT) in severely calcified lesions treated with thin strut stents after rotational atherectomy. In 28 lesions (26 patients with 23% on hemodialysis) treated with everolimus-eluting stents after rotational atherectomy, baseline and 8-month follow-up OCT were compared. Stent recoil was defined as >10% decrease in stent area from baseline to follow-up. Overall, there was no change in minimal stent area (6.0 mm2 [5.0, 8.1] to 6.0 mm2 [4.8, 8.6], p = 0.51) from baseline to follow-up, although neointimal hyperplasia measured 16.3 ± 15.8%. Thirty-six percent of lesions showed stent recoil associated with 6 non-nodular calcifications, 1 calcified nodule, and 3 stent deformations. The overall mean calcium angle with attenuation decreased (54° [29-76] to 31° [19-48], p < 0.0001), and calcium without attenuation increased (28° [21-67] to 64° [34-93], p < 0.0001), but primarily at the location of stent recoil. Furthermore, in the stent recoil segments in 10 recoil lesions, the stent circumference decreased primarily at non-calcium segments rather than at calcium with or without attenuation. One lesion with stent recoil and 2 lesions without stent recoil required repeat revascularization. Thin strut stents can chronically recoil in severely calcified lesions, but this rarely causes restenosis.