Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring　- The NOCTURNE Study.

BACKGROUND: Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled. The ARB/CCB combination therapy (irbesartan 100 mg+amlodipine 5 mg) achieved a significantly greater reduction in nocturnal home systolic BP (primary endpoint) than the ARB/diuretic combination (daily irbesartan 100 mg+trichlormethiazide 1 mg) (-14.4 vs. -10.5 mmHg, P<0.0001), independently of urinary sodium excretion and/or nocturnal BP dipping status. However, the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity (diabetes, chronic kidney disease, and elderly patients). CONCLUSIONS: This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM. The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake, despite the similar impact of the 2 combinations in patients with higher salt sensitivity.

Water intake disorder in a DEND syndrome afflicted patient with R50P mutation.

In this study, we present a case of developmental delay, epilepsy and neonatal diabetes (DEND) syndrome in a young male patient with the R50P mutation located in the Kir6.2 subunit of the ATP-sensitive K(+) (KATP) channel. Whereas most patients with DEND syndrome are resistant to sulfonylurea therapy, our patient was responsive to sulfonylurea, lacked the most common neurological symptoms, such as epilepsy, but refused to drink water. His serum electrolytes and plasma osmolarity were normal but the serum vasopressin level was increased. To investigate the underlying mechanism of his water intake disorder, a 5 µL aliquot of 340 µM KATP channel opener diazoxide or 100 µM KATP channel inhibitor glibenclamide was injected into the third ventricle of the rat brain, and water intake was monitored. Although the injection of glibenclamide had no effect, injection of diazoxide significantly increased water intake by about 1.5 fold without affecting food intake. This result indicates that the KATP channel activity in the brain may have an influence on water intake. Here, we present the first case of a DEND syndrome-afflicted patient with water intake disorder and increased serum vasopressin level, possibly related to altered KATP channel activity.

Lack of CD4⁺CD25⁺FOXP3⁺ regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease.

UNLABELLED: The aim of this study was to investigate changes in CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) throughout the clinical course of Kawasaki disease (KD) and correlations with response to intravenous immunoglobulin (IVIg) therapy. Participants comprised 18 patients who fulfilled the diagnostic criteria for KD and 20 healthy subjects. Expressions of CD25 and FOXP3 among all CD4(+) T cells in peripheral blood mononuclear cells were analyzed by flow cytometry before and 7 and 30 days after IVIg therapy. Before treatment, percentages of CD4(+)CD25(+)FOXP3(+) Tregs among total CD4(+) Tregs were significantly lower among KD patients (4.19 %; range, 0.16-8.11 %) than among healthy subjects (7.32 %; 4.18-13.42 %; P = 0.0001). Both percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs on day 7 after IVIg therapy were significantly increased compared with values before treatment (8.02 % (range, 0.51-12.6 %) vs. 4.19 % (range, 0.16-8.11 %), P = 0.0005; 93.25/ µL (range, 6.67-258.05) vs. 41.85/ µL (range, 0.44-160.62), P < 0.0001, respectively). Moreover, percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs before treatment were significantly lower in the IVIg-resistant group than in the IVIg-sensitive group (0.18 % (range, 0.16-3.34 %) vs. 4.52 % (range, 2.8-8.11 %), P = 0.0022; 0.68/µL (range, 0.44-53.81) vs. 51.66/µL (range, 2.88-160.62), P = 0.0098, respectively). The frequency of CD4(+)CD25(+)FOXP3(+) Tregs in four of the five IVIg-resistant patients at diagnosis was more than 3 standard deviations below that in healthy subjects. Two of these four patients displayed coronary abnormalities, and one of these two patients developed coronary aneurysm. CONCLUSION: Lack of CD4(+)CD25(+)FOXP3(+) Tregs before treatment may predict resistance to IVIg therapy in patients with KD.

Effects of patient movement on measurements of myocardial blood flow and viability in resting ¹5O-water PET studies.

BACKGROUND: Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous ¹5O-water PET. METHODS: Nineteen ¹5O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated. RESULTS: In nine scans, motions during ¹5O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 ± 0.118 to 0.504 ± 0.087 g/mL (P< .05), but no significant change was found in MBF values. CONCLUSIONS: This study demonstrates that IF motion during ¹5O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and ¹5O-water emission scans.

Acute Myocardial Infarction Due to Coronary Occlusion Caused by a Metastatic Cardiac Tumor Arising from Squamous Cell Lung Cancer: An Evaluation with Three-dimensional Transthoracic Echocardiography.

A 60-year-old man developed acute myocardial infarction from the total occlusion of the right coronary artery via metastatic squamous lung cancer and was treated with percutaneous coronary intervention (PCI). Computed tomography and transthoracic echocardiography (TTE) revealed a metastatic tumor, and three-dimensional TTE was useful for determining the size and location of the tumor in relation to the coronary artery. Six months after PCI, the patient died, and an autopsy confirmed extensive metastasis to the heart and nearby vessels as detected by three-dimensional TTE. Although rare, lung cancer metastasis to the heart may directly occlude the coronary artery.

Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders.

Backgrounds: Intramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine. Methods: Healthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions. Results: Eleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = -0.429, p = 0.249; fat infiltration rate, r = -0.194, p = 0.618). The adverse reactions were comparable between groups. Conclusion: The BNT162b2 vaccine is safe and effective in patients with NMDs.

Clinical implication of the brachial-ankle pulse wave velocity for endovascular treatment.

This study aimed to evaluate the clinical implication of the brachial-ankle pulse wave velocity (baPWV) for endovascular treatment (EVT). Eighty-four patients who underwent EVT for aortoiliac and femoropopliteal artery were included. In these patients, 36 (43 %) had an ABI improvement above 0.9 a day after EVT. The baPWV in patients who received re-EVT afterwards was significantly higher than that of patients who did not. The area under the receiver operating characteristic curve for the baPWV for predicting re-EVT was 0.788. The optimal cut-off values of the baPWV for re-EVT, specificity, and sensitivity were 2220 cm/s, 93.1 %, and 57.1 %, respectively.

Dynamic kinking of right coronary artery after the button Bentall procedure.

Postoperative coronary artery complications after Bentall procedures are well recognised but are rare and potentially fatal. There have been only five cases documenting percutaneous coronary intervention (PCI) for right coronary artery (RCA) involvements after button Bentall procedures. We describe a case of postoperative silent myocardial ischaemia in a 72-year-old man who underwent the button Bentall procedure for a right sinus of Valsalva aneurysm. On postoperative day 15, an RCA complication was incidentally detected by follow-up multidetector CT. Coronary angiography showed proximal RCA kinking, which was not an anastomosis but a native coronary artery. The patient underwent a successful PCI with drug-eluting stent implantation. We reviewed six cases consisting of this case and five previous cases treated with PCI. These cases enhance the recognition of potential RCA complications after the button Bentall procedure.

Subepicardial aneurysm with free wall rupture and its successful surgical intervention: a case report.

BACKGROUND: Subepicardial aneurysm (SEA) is an uncommon but potentially fatal complication of acute myocardial infarction (MI) associated with an increased risk of free wall rupture (FWR) leading to sudden death. We describe a rare case of a silent myocardial infarction complicated by SEA and subsequent FWR, resulting in cardiac tamponade. CASE SUMMARY: A 68-year-old man with no previous chest symptoms presented with syncope. Cardiac computed tomography incidentally revealed a small aneurysmal cavity at the inferolateral wall of the left ventricle, which was overlooked on initial transthoracic echocardiography. Coronary angiography demonstrated a narrowed first obtuse marginal branch with coronary slow flow, suggesting that spontaneous recanalization of the occluded obtuse marginal branch induced SEA and subsequent FWR. The patient underwent an emergency left ventricular aneurysm repair. The post-operative course was uneventful, and the patient was discharged from the hospital on post-operative day 20. DISCUSSION: This case emphasizes the importance of prompt detection and surgical intervention for SEA. Subepicardial aneurysm should be suspected in patients with pericardial effusion and suspected MI. Cardiac computed tomography is not only useful in the detection of such cases but also facilitates the development of a successful surgical strategy.

Delayed-onset constrictive pericarditis associated with trauma.

A 59-year-old man presented with exertional dyspnoea and pretibial oedema that had lasted 6 months. He was referred to our hospital with suspected constrictive pericarditis (CP). Several examinations, including CT, echocardiography and cardiac catheterisation, indicated heart failure associated with CP that had been induced by trauma 13 years prior. The CP and heart failure were unresponsive to medical treatment, therefore, a surgical pericardiectomy was performed, which is considered the only definitive treatment. Pathological examination of the resected pericardium revealed a fatty texture and dense fibrous connective tissues, which are associated with old haemorrhage and focal calcification. The patient's symptoms were improved to New York Heart Association Class I, and his peripheral oedema disappeared 6 months after leaving hospital.

Long COVID presenting with intermittent fever after COVID-19 pneumonia.

A 72-year-old man presented to our hospital with a fever. Chest computed tomography showed typical coronavirus disease 2019 (COVID-19) pneumonia. The fever normalized after a few days, and the pneumonia was alleviated. However, the intermittent fever subsequently re-occurred and persisted for over a month. Various tests, including blood tests, culture tests, and image evaluations, were performed. However, the conclusion was that long COVID was the cause of the intermittent fever as an exclusion diagnosis. Many patients suffer from persistent symptoms of COVID-19, but the symptoms and their durations vary. Here we report a case of prolonged fever after COVID-19 pneumonia.

Triplet state spectra and dynamics of peridinin analogs having different extents of pi-electron conjugation.

The Peridinin-Chlorophyll a-Protein (PCP) complex has both an exceptionally efficient light-harvesting ability and a highly effective protective capacity against photodynamic reactions involving singlet oxygen. These functions can be attributed to presence of a substantial amount of the highly-substituted and complex carotenoid, peridinin, in the protein and the facts that the low-lying singlet states of peridinin are higher in energy than those of chlorophyll (Chl) a, but the lowest-lying triplet state of peridinin is below that of Chl a. Thus, singlet energy can be transferred from peridinin to Chl a, but the Chl a triplet state is quenched before it can sensitize the formation of singlet oxygen. The present investigation takes advantage of Chl a as an effective triplet state donor to peridinin and explores the triplet state spectra and dynamics of a systematic series of peridinin analogs having different numbers of conjugated carbon-carbon double bonds. The carotenoids investigated are peridinin, which has a C(37) carbon skeleton and eight conjugated carbon-carbon double bonds, and three synthetic analogs: C(33)-peridinin, having two less double bonds than peridinin, C(35)-peridinin which has one less double bond than peridinin, and C(39)-peridinin which has one more double bond than peridinin. In this study, the behavior of the triplet state spectra and kinetics exhibited by these molecules has been investigated in polar and nonpolar solvents and reveals a substantial effect of both pi-electron conjugated chain length and solvent environment on the spectral lineshapes. However, only a small dependence of these factors is observed on the kinetics of triplet energy transfer from Chl a and on carotenoid triplet state deactivation to the ground state.

Rare pulmonary embolism caused by the combination of bilateral popliteal venous aneurysms and antiphospholipid syndrome.

Popliteal venous aneurysm (PVA) and antiphospholipid syndrome (APS) are under-recognised as potential causes of pulmonary embolism (PE). A 66-year-old woman presented with progressive shortness of breath. A contrast-enhanced CT revealed bilateral PE, a small renal infarction and bilateral PVAs. Direct oral anticoagulant (DOAC) therapy was initiated immediately for venous thrombosis. Given the positivity for serum antiphospholipid antibody (aPL) in an initial blood test, low-dose aspirin was included to prevent further arterial thrombosis. Her symptoms resolved and she was discharged 1 week later. Twelve weeks later, she was diagnosed with APS because of persistent aPL. Surgical resection of the right PVA was performed 1 year later from her hospitalisation. To the best of our knowledge, this is the first case of PE caused by the combination of bilateral PVAs and APS. This report emphasises the importance of careful screening to identify PE causes, and its optimal management.

Correlations Between the Ankle-Brachial Index, Percentage of Mean Arterial Pressure, and Upstroke Time for Endovascular Treatment.

BACKGROUND: The ankle-brachial index (ABI), percentage of mean arterial pressure (%MAP), and upstroke time (UT) are indicators to diagnose lower-extremity peripheral artery disease (PAD). However, the respective relationship between these parameters is unknown. In this study, we analyzed the correlations between ABI, %MAP, and UT and examined their clinical usefulness for endovascular treatment (EVT). METHODS: Sixty-three consecutive subjects who underwent successful EVT for aortoiliac to femoropopliteal artery diseases were analyzed. The ABI, %MAP, and UT were measured using an automated oscillometric device. RESULTS: There were significant correlations between the ABI and %MAP (r = -0.425, P < 0.001), the ABI and UT (r = -0.304, P = 0.017), and %MAP and UT (r = 0.368, P = 0.003). In terms of lesion length, there was a significant difference in %MAP after EVT (focal, 42.6%; short, 44.5%; intermediate, 47.1%; long, 49.1%; P = 0.015). There was minimal %MAP improvement in the case of a long lesion length (focal, -8.83%; short, -5.10%; intermediate, -3.00%; long, -1.50%; P = 0.006). Excessive lesion calcification also hindered %MAP improvement (grade 0, -7.16%; grade 1, -5.52%; grade 2, -4.71%; grade 3, -2.80%; grade 4, -1.00%; P = 0.049). Patients who underwent re-EVT (an average of 10.1 months after initial EVT) had minimal %MAP improvement (-2.76% vs. -5.95%, P = 0.035) at the first outpatient visit (an average of 3.3 weeks after EVT). CONCLUSIONS: In conclusion, the ABI, %MAP, and UT are correlated with each other. If the length of the lesion is long and there is excessive calcification, %MAP improvement is minimal. Moreover, minimal %MAP improvement may be an indicator of future restenosis.

Perioperative Management of Takayasu Arteritis for Cardiac Surgery in a Patient Treated With Tocilizumab.

We describe the case of a young woman with Takayasu arteritis with severe stenosis in the main trunk of the left coronary artery. After administration of prednisolone and tocilizumab to control disease activity, coronary artery bypass grafting was performed. Here, we report the successful perioperative management of this cardiac surgery. (Level of Difficulty: Advanced.).

Patients With Obesity Exhibit a Plateau Pattern of the Right Ventricular Waveform.

BACKGROUND: Ventricular waveforms are characterized by a dip-and-plateau pattern during diastole owing to an abrupt termination of ventricular filling because of pericardial constraint under conditions such as constrictive pericarditis (CP). However, constrictive hemodynamics is not specifically caused by CP. Therefore, this study aimed to evaluate whether patients with obesity exhibited constrictive hemodynamics. METHODS: Overall, 60 consecutive Japanese patients (mean age, 69.5 years; 45% women) who underwent right heart catheterization at the Japan Community Healthcare Organization Osaka Hospital from July 2016 to September 2018 were examined. Two-dimensional echocardiography was used to measure the epicardial adipose tissue (EAT) in the standard parasternal long-axis view during end-diastole. Because patients who underwent open-heart surgery were highly likely to have CP, they were excluded. RESULTS: Among the 60 patients, 11 (18%) exhibited a plateau pattern of the right ventricular waveform and had a mean EAT value of 4.2 mm, which was significantly higher than that of patients without such a pattern (2.1 mm, P < 0.001). Similarly, the mean body mass index (BMI) values were significantly higher in patients with a plateau pattern than in those without it (27.2 vs. 21.8 kg/m2, P < 0.001). EAT was significantly correlated with the BMI (r = 0.72, P < 0.001). In patients with a plateau pattern, the triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher (TG: 150 vs. 100 mg/dL, LDL-C: 121 vs. 95 mg/dL, P < 0.05) and the left atrial diameter (52.8 vs. 44.7 mm, P < 0.01) and left atrial volume index (58.7 vs. 47.6 mL/m2, P < 0.05) were significantly greater than those in the patients without it. The EAT was also significantly correlated with the TG level (r = 0.37, P < 0.01). CONCLUSIONS: Obese patients may present with constrictive hemodynamics, suggesting left ventricular diastolic dysfunction. EAT was significantly correlated with metabolic syndrome components, namely obesity and TG levels.

Hypertensive heart disease associated with methamphetamine abuse.

In Japan, methamphetamine accounts for the majority of illicit drug use and dependence is becoming a critical issue. Methamphetamine abuse induces cardiovascular complications, such as cardiomyopathy and heart failure. However, methamphetamine-associated cardiovascular complications are not common in Japan. We report the case of a young patient with hypertensive heart disease associated with habitual methamphetamine abuse. A 37-year-old man was admitted with congestive heart failure. He was a habitual methamphetamine abuser and developed chronic hypertension after he started methamphetamine abuse. His echocardiogram demonstrated left ventricular concentric hypertrophy with diffuse hypokinesis. An endomyocardial biopsy revealed histological evidence of a hypertensive heart. This case shows that habitual methamphetamine use may cause hypertensive heart disease because of chronic hypertension. .

Effects of cardiac energy efficiency in diastolic heart failure: assessment with positron emission tomography with 11C-acetate.

Diastolic heart failure (DHF) has become a high social burden, and its major underlying cardiovascular disease is hypertensive heart disease. However, the pathogenesis of DHF remains to be clarified. This study aimed to assess the effects of cardiac energy efficiency in DHF patients. (11)C-Acetate positron emission tomography and echocardiography were conducted in 11 DHF Japanese patients and 10 normal volunteers. The myocardial clearance rate of radiolabeled (11)C-acetate was measured to calculate the work metabolic index (WMI), an index of cardiac efficiency. The ratio of peak mitral E wave velocity to peak early diastolic septal myocardial velocity (E/e') was calculated to assess left ventricular (LV) filling pressure. The LV mass index was greater and the mean age was higher in the DHF patients than in the normal volunteers. There was no difference in WMI between the two groups. However, WMI varied widely among the DHF patients and was inversely correlated with E/e' (r=-0.699, p=0.017). In contrast, there was no correlation in the normal volunteers. In conclusion, the inefficiency of energy utilization is not a primary cause of diastolic dysfunction or DHF, and cardiac efficiency may not affect diastolic function in normal hearts. However, the energy-wasting state may induce the elevation of LV filling pressure in DHF patients, which was considered to principally result from the progressive diastolic dysfunction.

Effect of pi-electron conjugation length on the solvent-dependent S(1) lifetime of peridinin.

Peridinin exhibits an anomalous solvent dependence of its S(1) excited state lifetime attributed to the presence of an intramolecular charge transfer (ICT) state. The nature of this state has yet to be elucidated. Ultrafast time-resolved optical spectroscopy has been performed on a synthetic analog, C(35)-peridinin, having one less conjugated double bond than peridinin. The data reveal the lifetime decreases from 1.5 ns in n-hexane to 9.2 ps in methanol, an order of magnitude larger than peridinin. This is the strongest solvent dependence on the lifetime of an S(1) state of a carotenoid yet reported. The data support the view that the S(1) and ICT states are strongly coupled.