Adjunct Acupuncture Improved Respiratory Status and Weaning from Mechanical Ventilation After Severe COVID-19 Pneumonia.

Background: A patient with severe COVID-19 pneumonia had adjunctive acupuncture to improve respiration and facilitate weaning off prolonged mechanical ventilation (MV). Case: A man in his 40s with COVID-19 was in an advanced critical-care center on symptom day 5 for respiratory failure due to pneumonia requiring MV therapy. He received high-dose corticosteroid pulse therapy, antiviral agents, and multiple antibiotics for complicated bacterial pneumonia and bacteremia. Repeated MV weaning attempts failed, although his pneumonia gradually improved. Then, acupuncture 4 times per week was started to improve his respiration and facilitate MV weaning from day 49 of his symptoms' onset. Results: His weaning-related indices improved, including reductions in respiratory rate and Rapid Shallow Breath Index. His O2 saturation increased immediately after each acupuncture treatment. The day after the first acupuncture treatment, his MV support was reduced by changing ventilation mode from synchronized intermittent mandatory ventilation mode to continuous positive airway pressure (CPAP) mode during the day without exacerbation of respiratory status. After 3 days of acupuncture, this patient was on CPAP support alone. MV therapy was discontinued completely after 8 days of acupuncture (6th acupuncture treatment). Conclusions: Acupuncture improved respiration and facilitated MV weaning in a patient with respiratory failure secondary to COVID-19. Adjunctive acupuncture may benefit such patients and others after severe pneumonia. Large cohort studies are needed.

Sitting maneuver to uncover latent left ventricular outflow tract obstruction in patients without hypertrophic cardiomyopathy.

BACKGROUND: Left ventricular outflow tract obstruction [LVOTO; pressure gradient (PG) ≥30 mmHg] is observed in some patients without hypertrophic cardiomyopathy (HCM), and it may develop especially in older patients without HCM (non-HCM). The aim of this study is to investigate if the Valsalva or an upright sitting maneuver can unveil latent LVOTO in patients with non-HCM. METHODS: A total of 33 non-HCM patients with a late peaking or dagger-shaped pulsed Doppler waveform of the LVOT and PG <30 mmHg were included. The Doppler flow velocity of the LVOT was measured at rest, after the Valsalva and a sitting maneuver. Peak PG of ≥30 mmHg after either maneuver was defined as latent LVOTO. The angle between the left ventricular septum and the aorta in the parasternal long-axis view and the apical three-chamber view was measured. RESULTS: Twenty (61 %) of the 33 patients (mean age 74 ±â€¯9 years) were diagnosed with latent LVOTO. Of these, five (25 %) patients were diagnosed after both the Valsalva and sitting maneuver, and 15 (75 %) were diagnosed only after the sitting maneuver. The latent LVOTO group had a significantly smaller angle than the no-LVOTO group between the ventricular septum and the aorta in the parasternal long axis views (107 ±â€¯8° vs. 117 ±â€¯8°, p < 0.01). CONCLUSION: The sitting maneuver is better than the Valsalva maneuver in unveiling latent LVOTO in older, non-HCM patients.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Rationale and Design of the ATLAS-OCT Study.

Even after successful revascularization with primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), subsequent adverse events still occur. Previous studies have suggested potential benefits of intravascular imaging, including optical coherence tomography (OCT). However, the feasibility of OCT-guided primary PCI has not been systematically examined in these patients. The ATLAS-OCT (ST-elevation Acute myocardial infarcTion and cLinicAl outcomeS treated by Optical Coherence Tomography-guided percutaneous coronary intervention) trial was designed to investigate the feasibility of OCT guidance during primary PCI for STEMI in experienced centers with expertise on OCT-guided PCI as a prospective, multicenter registry of consecutive patients with STEMI who underwent a primary PCI. The sites' inclusion criteria are as follows: (1) acute care hospitals providing 24/7 emergency care for STEMI, and (2) institutions where OCT-guided PCI is the first choice for primary PCI in STEMI. All patients with STEMI who underwent primary PCI at participating sites will be consecutively enrolled, irrespective of OCT use during PCI. The primary end point will be the rate of successful OCT imaging during the primary PCI. As an ancillary imaging modality to angiography, OCT provides morphologic information during PCI for the assessment of plaque phenotypes, vessel sizing, and PCI optimization. Major adverse cardiac events, defined as a composite of all-cause death, myocardial infarction, and target vessel revascularization at 1 year, will also be recorded. The ATLAS-OCT study will clarify the feasibility of OCT-guided primary PCI for patients with STEMI and further identify a suitable patient group for OCT-guided primary PCI.

Infective endocarditis with Osler's nodule in a patient with Osler's disease: a case report and review of the literature.

BACKGROUND: Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, induces arteriovenous malformations in visceral organs. Arteriovenous malformations increase the risk of severe infections and are a common complication associated with hemorrhagic telangiectasia. However, cases of endocarditis associated with hemorrhagic telangiectasia are rarely reported. Although hemorrhagic telangiectasia causes erythematous macules on the extremities, these macules are usually painless. We encountered a rare case of infective endocarditis in a patient with Osler-Weber-Rendu disease. CASE PRESENTATION: A 52-year-old Japanese woman who was diagnosed with hemorrhagic telangiectasia 5 years prior presented to our hospital with fever and muscular pain. She had erythematous nodules and tenderness on the finger, heel, and toe, suggestive of Osler's nodes. A physical examination revealed tachycardia with a 3/6 pansystolic murmur. A transesophageal echocardiogram showed vegetations along the atrial side of the mitral valve and mild mitral regurgitation because of prolapse of the anterior commissure. Methicillin-sensitive Staphylococcus aureus was identified in the blood cultures. Detection of distinctive skin lesions, so-called Osler's nodes, was the symptomatic key to early diagnosis, and the patient was treated without surgery. She was discharged with negative blood cultures after a 6-week intravenous antibiotic administration. CONCLUSIONS: Our report highlights the importance of considering the risk of extracerebral infections including endocarditis in hemorrhagic telangiectasia. This rare case effectively demonstrates the importance of proper diagnosis of skin lesions.

The Feasibility of a Newly Developed Local Network System for Cardiac Rehabilitation (the CR-GNet) in Disease Management and Physical Fitness after Acute Coronary Syndrome.

OBJECTIVE: To examine the Cardiac Rehabilitation Gifu Network (CR-GNet) feasibility in managing diseases and assisting patients in attaining physical fitness, and its impact on long-term outcomes after acute coronary syndrome (ACS). METHODS: In this prospective observational study, we enrolled 47 patients with ACS registered in the CR-GNet between February 2016 and September 2019. 37, 29, and 21 patients underwent follow-up assessments for exercise capacity (peak oxygen uptake) at 3 months, 6 months, and 1 year after discharge, respectively. Major adverse cardiac events (MACE) were compared with controls not registered in the CR-GNet. RESULTS: The coronary risk factors, except blood pressure, improved at 3 and 6 months, and 1 year after discharge. These risk factors in each patient significantly reduced from 2.9 at admission to 1.6, 1.4, and 1.9 at 3 months, 6 months, and 1 year after discharge (p<0.05), respectively. Peak oxygen uptake was significantly higher at 3 months (17.5±4.9 ml/kg/min), 6 months (17.9±5.1 ml/kg/min), and 1 year (17.5±5.5 ml/kg/min) after discharge than that at discharge (14.7±3.6 ml/kg/min) (p<0.05). During follow-up, there was no significant difference; MACE did not occur in any patients in the CR-GNet but occurred in controls. CONCLUSION: CR-GNet is a feasible option for the long-term management of ACS patients.

Impact of Autophagy on Prognosis of Patients With Dilated Cardiomyopathy.

BACKGROUND: Autophagy is a cellular process that degrades a cell's own cytoplasmic components for energy provision and to maintain a proper intracellular environment. Left ventricular reverse remodeling (LVRR) promises a better prognosis for patients with dilated cardiomyopathy (DCM). OBJECTIVES: The authors tested the hypothesis that autophagy is involved in LVRR and has prognostic value in the human failing heart. METHODS: Using left ventricular endomyocardial biopsy specimens from 42 patients with DCM (21 LVRR-positive and 21 LVRR-negative) and 7 patients with normal cardiac function (control), the authors performed immunohistochemistry and immunofluorescent labeling of LC3 and cathepsin D and electron microscopic observation in addition to general morphometry under light microscopy. RESULTS: The clinical characteristics of LVRR-positive patients were similar to those of the LVRR-negative patients, except for pulmonary artery pressure and left atrial dimension. Morphometry under light microscopy did not differ among specimens from DCM patients, regardless of their LVRR status. Electron microscopy revealed that autophagic vacuoles (autophagosomes and autolysosomes) and lysosomes were abundant within cardiomyocytes from DCM patients. Moreover, cardiomyocytes from LVRR-positive patients contained significantly more autophagic vacuoles with higher autolysosome ratios and cathepsin D expression levels than cardiomyocytes from LVRR-negative patients. Logistic regression analysis adjusted for age showed that increases in autophagic vacuole number and cathepsin D expression were predictive of LVRR. DCM patients who achieved LVRR experienced fewer cardiovascular events during the follow-up period. CONCLUSIONS: The authors show that autophagy is a useful marker predictive of LVRR in DCM patients. This provides novel pathologic insight into a strategy for treating the failing DCM heart.

Radiofrequency ablation on the right ventricular septum changed a bundle branch block pattern of a ventricular tachycardia: What is the mechanism?

A ventricular tachycardia (VT) with a left bundle branch block (BBB) pattern exhibited the earliest activation (EA) at the left ventricular basal septum near the His bundle with no excellent pace map (PM). Radiofrequency ablation at the right ventricular basal septum (opposite site of the EA site) changed the QRS morphology of VT to a right BBB pattern that matched a PM at the opposite site in the left ventricle. VT ablation was successful at the earliest activation site. The VT should have originated from an intramural origin with preferential pathways to the endocardial breakout sites in the right and left ventricular septum.

Morphological characteristics in diabetic cardiomyopathy associated with autophagy.

Diabetic cardiomyopathy, clinically diagnosed as ventricular dysfunction in the absence of coronary atherosclerosis or hypertension in diabetic patients, is a cardiac muscle-specific disease that increases the risk of heart failure and mortality. Its clinical course is characterized initially by diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure from an uncertain mechanism. Light microscopic features such as interstitial fibrosis, inflammation, and cardiomyocyte hypertrophy are observed in diabetic cardiomyopathy, but are common to failing hearts generally and are not specific to diabetic cardiomyopathy. Electron microscopic studies of biopsy samples from diabetic patients with heart failure have revealed that the essential mechanism underlying diabetic cardiomyopathy involves thickening of the capillary basement membrane, accumulation of lipid droplets, and glycogen as well as increased numbers of autophagic vacuoles within cardiomyocytes. Autophagy is a conserved mechanism that contributes to maintaining intracellular homeostasis by degrading long-lived proteins and damaged organelles and is observed more often in cardiomyocytes within failing hearts. Diabetes mellitus (DM) impairs cardiac metabolism and leads to dysregulation of energy substrates that contribute to cardiac autophagy. However, a "snapshot" showing greater numbers of autophagic vacuoles within cardiomyocytes may indicate that autophagy is activated into phagophore formation or is suppressed due to impairment of the lysosomal degradation step. Recent in vivo studies have shed light on the underlying molecular mechanism governing autophagy and its essential meaning in the diabetic heart. Autophagic responses to diabetic cardiomyopathy differ between diabetic types: they are enhanced in type 1 DM, but are suppressed in type 2 DM. This difference provides important insight into the pathophysiology of diabetic cardiomyopathy. Here, we review recent advances in our understanding of the pathophysiology of diabetic cardiomyopathy, paying particular attention to autophagy in the heart, and discuss the therapeutic potential of interventions modulating autophagy in diabetic cardiomyopathy.

Primary Angiosarcoma in the Right Atrium Diagnosed by a Cardiac Tumor Biopsy Using Intracardiac Echocardiography.

A 47-year-old woman consulted a doctor due to a persistent cough. Computed tomography revealed a 30 mm × 60 mm intracardiac mass in the right atrium. Because of lung metastasis, her respiratory status did not allow a more invasive procedure, such as general anesthesia. Although intracardiac echocardiography (ICE) during percutaneous transcatheter biopsy (PTB) is not covered by medical insurance, we performed PTB under ICE guidance. Pathology and immunohistochemistry revealed primary cardiac angiosarcoma. Primary cardiac angiosarcoma is a rare tumor with a poor prognosis. After seven cycles of chemotherapy, the pulmonary metastasis was clearly improved. The patient is alive 18 months after the first consult, even though the mortality of angiosarcoma is high. ICE during PTB allowed us to choose appropriate chemotherapy and improve her pulmonary metastasis. ICE during PTB reduces the need for a diagnostic open-chest procedure that requires a more invasive approach.

In situ nuclear DNA methylation in dilated cardiomyopathy: an endomyocardial biopsy study.

AIMS: Although distinct DNA methylation patterns have been reported, its localization and roles remain to be defined in heart failure. We investigated the cellular and subcellular localization of DNA methylation and its pathophysiological significance in human failing hearts. METHODS AND RESULTS: Using left ventricular (LV) endomyocardial biopsy specimens from 75 patients with dilated cardiomyopathy (DCM; age: 58 ± 14 years old, %female: 32%) and 20 patients without heart failure (controls; age: 56 ± 17 years old, %female: 45%), we performed immunohistochemistry and immunoelectron microscopy for methylated DNA, 5-methylcytosine (5-mC). We next investigated possible relations of the incidence of 5-mC-positive (%5-mC+ ) cardiomyocytes with clinicopathological parameters. Immunopositivity for 5-mC was detected in the cardiomyocytes and other cell types. The %5-mC+ cardiomyocytes was significantly greater in DCM hearts than in controls (57 ± 13% in DCM vs. 25 ± 12% in controls, P < 0.0001). The localization of 5-mC immunopositivity in cardiomyocyte nuclei coincided well with that of heterochromatin, as confirmed by immunoelectron microscopy. Substantial DNA methylation was also observed in interstitial non-cardiomyocytes, but the incidences did not differ between control and DCM hearts (39 ± 7.9% in DCM vs. 41 ± 10% in controls, P = 0.4099). In DCM patients, the %5-mC+ cardiomyocytes showed a significant inverse correlation with LV functional parameters such as heart rate (r = 0.2391, P = 0.0388), end-diastolic pressure (r = 0.2397, P = 0.0397), and ejection fraction (r = -0.2917, P = 0.0111) and a positive correlation with LV dilatation (volume index at diastole; r = 0.2442, P = 0.0347; and volume index at systole; r = 0.3136, P = 0.0062) and LV hypertrophy (mass index; r = 0.2287, P = 0.0484)-that is, LV remodelling parameters. No significant correlations between DNA methylation and the histological parameters of the biopsies, including cardiomyocyte hypertrophy, fibrosis, and inflammatory cell infiltration, were noted. CONCLUSIONS: The present study revealed increased nuclear DNA methylation in cardiomyocytes, but not other cell types, from DCM hearts, with predominant localization in the heterochromatin. Its significant relations with LV functional and remodelling parameters imply a pathophysiological significance of DNA methylation in heart failure.

Metformin Enhances Autophagy and Provides Cardioprotection in δ-Sarcoglycan Deficiency-Induced Dilated Cardiomyopathy.

BACKGROUND: Metformin is a popular antidiabetic agent that is also used to treat heart failure patients with type 2 diabetes mellitus. Several reports suggest that metformin may also have cardioprotective effects in patients without diabetes mellitus. In the present study, we investigated the possible therapeutic effect of metformin in heart failure and its underlying molecular mechanisms using a δ-sarcoglycan-deficient mouse model of dilated cardiomyopathy. METHODS AND RESULTS: Thirty-two-week-old δ-sarcoglycan-deficient mice exhibiting established cardiomyopathy with extensive left ventricular dilatation and dysfunction were administered saline or metformin (200 mg/kg per day) for 4 weeks using osmotic mini-pumps. Metformin partially reversed the left ventricular dilatation (reverse remodeling) and significantly improved cardiac function. The hearts of metformin-treated mice showed less fibrosis, less cardiomyocyte hypertrophy, and fewer degenerative subcellular changes than saline-treated mice. These effects were accompanied by restored expression of the sarcomeric proteins myosin heavy chain and troponin I, and their transcription factor, GATA-4. Autophagy was enhanced in the hearts from metformin-treated mice, as indicated by increase of myocardial microtubule-associated protein-1 LC-3 (light chain 3)-II levels and LC3-II/-I ratios as well as levels of cathepsin D and ATP. In addition, increased numbers of autophagic vacuoles and lysosomes were accompanied increased AMP-activated protein kinase activity and suppression of mammalian target of rapamycin phosphorylation. Finally, autophagic flux assays using short-term chloroquine treatment revealed that autophagy was activated in δ-sarcoglycan-deficient hearts and was further augmented by metformin treatment. CONCLUSIONS: Metformin is a beneficial pharmacological tool that mitigates heart failure caused by δ-sarcoglycan deficiency in association with enhanced autophagy.

(Pro)renin Receptor Blockade Ameliorates Heart Failure Caused by Chronic Kidney Disease.

BACKGROUND: The (pro)renin receptor [(P)RR)] is involved in the activation of local renin-angiotensin system and subsequent development of cardiovascular disease. We investigated the therapeutic effect of a (P)RR blocker, handle-region peptide (HRP), on chronic kidney disease (CKD)-associated heart failure. METHODS AND RESULTS: CKD was induced in C57BL/6J mice by means of five-sixths nephrectomy. Eight weeks later, cardiac dysfunction and cardiac dilatation with hypertension developed. Mice were then assigned to 1 of the 3 following groups: vehicle, low-dose (0.01 mg·kg-1·d-1) HRP, or high-dose (0.3 mg·kg-1·d-1) HRP for 4 weeks. High-dose HRP treatment reversed left ventricular dilation and significantly improved cardiac dysfunction with ameliorated hypertension compared with the vehicle. The hearts with high-dose HRP treatment showed significant attenuation of cardiac fibrosis, cardiomyocyte hypertrophy, macrophage infiltration, and oxidative DNA damage. This treatment decreased the myocardial expressions of angiotensin (Ang) II, Ang II type 1 receptor, transforming growth factor ß1, extracellular matrix-related proteins, and lipid peroxidation. Autophagy was activated in the cardiomyocyte from nephrectomized mice, but HRP treatment had no effect on cardiomyocyte autophagy. CONCLUSIONS: This study indicates that (P)PR blockade is a beneficial strategy by suppressing cardiac fibrosis and hypertrophy to ameliorate heart failure caused by CKD.

The intestine responds to heart failure by enhanced mitochondrial fusion through glucagon-like peptide-1 signalling.

AIMS: Glucagon-like peptide-1 (GLP-1) is a neuroendocrine hormone secreted by the intestine. Its receptor (GLP-1R) is expressed in various organs, including the heart. However, the dynamics and function of the GLP-1 signal in heart failure remains unclear. We investigated the impact of the cardio-intestinal association on hypertensive heart failure using miglitol, an α-glucosidase inhibitor known to stimulate intestinal GLP-1 production. METHODS AND RESULTS: Dahl salt-sensitive (DS) rats fed a high-salt diet were assigned to miglitol, exendin (9-39) (GLP-1R blocker) and untreated control groups and treated for 11 weeks. Control DS rats showed marked hypertension and cardiac dysfunction with left ventricular dilatation accompanied by elevated plasma GLP-1 levels and increased cardiac GLP-1R expression as compared with age-matched Dahl salt-resistant (DR) rats. Miglitol further increased plasma GLP-1 levels, suppressed adverse cardiac remodelling, and mitigated cardiac dysfunction. In cardiomyocytes from miglitol-treated DS hearts, mitochondrial size was significantly larger with denser cristae than in cardiomyocytes from control DS hearts. The change in mitochondrial morphology reflected enhanced mitochondrial fusion mediated by protein kinase A activation leading to phosphorylation of dynamin-related protein 1, expression of mitofusin-1 and OPA-1, and increased myocardial adenosine triphosphate (ATP) content. GLP-1R blockade with exendin (9-39) exacerbated cardiac dysfunction and led to fragmented mitochondria with disarrayed cristae in cardiomyocytes and reduction of myocardial ATP content. In cultured cardiomyocytes, GLP-1 increased expression of mitochondrial fusion-related proteins and ATP content. When GLP-1 and exendin (9-39) were administered together, their effects cancelled out. CONCLUSIONS: Increased intestinal GLP-1 secretion is an adaptive response to heart failure that is enhanced by miglitol. This could be an effective strategy for treating heart failure through regulation of mitochondrial dynamics.

Microvolt T-wave alternans monitoring in a patient with levofloxacin-induced Torsade de Pointes.

We present the case of a 62-year-old woman with levofloxacin-induced Torsade de Pointes, in whom microvolt T-wave alternans was measured during acute hospitalization and when QT interval was dynamically changing, illustrating a means for monitoring proarrhythmia.