A 46-year-old patient who had undergone right pneumonectomy for pulmonary artery intimal sarcoma presented with hypoxemia. The recurrent sarcoma in the mediastinum revealed external compression to the left pulmonary veins (PVs), leading to obstructive shock and cardiac arrest. Venous artery extracorporeal membrane oxygenation (VA-ECMO) was initiated; however, withdrawal was difficult, and the patient's survival seemed hopeless. However, the patient's condition improved with stenting for the compressed PV; therefore, VA-ECMO was discontinued, and he was discharged on foot. This is the first case report of obstructive shock due to critical PV stenosis caused by compression of a malignant tumor that responded to PV stenting.
Abstract The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1–3) and 1 (IQR 0–2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21–2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641–0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377
Sodium glucose cotransporter 2 inhibitors reduce morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Clinicians may find estimates of the projected long-term benefits of sodium glucose cotransporter 2 inhibitors a helpful addition to clinical trial results when communicating the benefits of this class of drug to patients.To estimate the projected long-term treatment effects of dapagliflozin in patients with HFrEF over the duration of a patient's lifetime.Exploratory analysis was performed of Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF), a phase 3 randomized, placebo-controlled clinical trial conducted at 410 sites in 20 countries. Patients with an ejection fraction less than or equal to 40% in New York Heart Association functional classification II to IV and elevated plasma levels of N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Mean (SD) duration of follow-up was 17.6 (5.2) months.Dapagliflozin, 10 mg, once daily vs placebo in addition to standard therapy.The primary composite outcome was time to first hospitalization for heart failure, urgent heart failure visit requiring intravenous therapy, or cardiovascular death. The trial results were extrapolated to estimate the projected long-term treatment effects of dapagliflozin over the duration of a patient's lifetime for the primary outcome and the secondary outcome of death from any cause.A total of 4744 patients (1109 women [23.4%]; 3635 men [76.6%]) were randomized in DAPA-HF, with a mean (SD) age of 66.3 (10.9) years. The extrapolated mean event-free survival for an individual aged 65 years from a primary composite end point event was 6.2 years for placebo and 8.3 years for dapagliflozin, representing an event-free survival time gain of 2.1 years (95% CI, 0.8-3.3 years; P = .002). When considering death from any cause, mean extrapolated life expectancy for an individual aged 65 years was 9.1 years for placebo and 10.8 years for dapagliflozin, with a gain in survival of 1.7 years (95% CI, 0.1-3.3; P = .03) with dapagliflozin. Similar results were seen when extrapolated across the age range studied. In analyses of subgroups of patients in DAPA-HF, consistent benefits were seen with dapagliflozin on both event-free and overall survival.These findings indicate that dapagliflozin provides clinically meaningful gains in extrapolated event-free and overall survival. These findings may be helpful in communicating the benefits of this treatment to patients with HFrEF.ClinicalTrials.gov Identifier: NCT03036124.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands are widely used in patients with insulin resistance and diabetes. Because coronary artery disease is a major complication for such patients, it is important to determine the effects of PPARgamma activation on arteriosclerosis. Long-term inhibition of endothelial NO synthesis by administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces coronary vascular inflammation (monocyte infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPARgamma ligand) in this rat model to determine whether PPARgamma activation with pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic conditions or by direct effects on the cells participating to the pathogenesis of arteriosclerosis. We found that pioglitazone did not affect metabolic states, systolic blood pressure, or serum NO levels, but did prevent the L-NAME-induced coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local expression of MCP-1 but markedly attenuated increased expression of the MCP-1 receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. PPARgamma activation with pioglitazone prevented coronary arteriosclerosis, possibly by its antiinflammatory effects (downregulation of CCR2 in circulating monocytes). Inhibition of the CCR2-mediated inflammation may represent novel antiinflammatory actions of pioglitazone beyond improvement of metabolic state.
Platypnea-orthodeoxia syndrome is a rare clinical entity characterized by dyspnea and arterial blood deoxygenation in a sitting position. An 89-year-old woman was diagnosed with subacute cerebellar infarction. Her blood oxygen saturation decreased to 88% in a sitting position, resulting in dyspnea. Cardiological thoracic computed tomography revealed an unruptured aortic aneurysm, an enlarged ascending aorta, right atrial compression, and counterclockwise rotation of the heart. An anatomical distortion of the atrial septum induced by these abnormalities directed the atrial venous inflow such that the right-left shunt flow was exacerbated in a sitting position.
This is an editorial comment to "An extremely wide QRS complex tachycardia induced by anamorelin." presented by Shimojo et al.1 in the current issue of Journal of Arrhythmia. Cancer cachexia is a multifocal syndrome in patients with cancer characterized by reduced muscle mass and malnutrition, causing progressive functional disability and reduced quality of life. Conventional nutritional support cannot completely reverse cancer cachexia, and useful pharmacologic therapies for cachexia management are limited. Since 2021, anamorelin has been licensed for production and marketing in Japan as a pharmacologic therapy for cancer cachexia. Anamorelin functions as a ghrelin-like agonist and may stimulate the secretion of growth hormones and appetite by activating the ghrelin receptor, known as growth hormone release promoting factor receptor type 1a (GHS-R1a). Anamorelin is a drug of interest in the field of cancer cachexia, as several randomized controlled trials have demonstrated efficacy in improving total body weight, lean body mass, quality of life, and appetite in patients with refractory cancer compared with placebo.2, 3 In all adverse events or serious adverse events, the investigators reported no significant differences in terms of safety.2, 3 However, this drug exhibited serious side effects, such as conduction disturbance, hyperglycemia, diabetes worsening, and hepatic dysfunction; thus, patient selection and posttreatment monitoring are very important. Anamorelin generally demonstrates an inhibitory effect on the conduction system because of its Na channel-blocking properties. Therefore, electrocardiographic abnormalities, atrioventricular block, tachycardia, and bradycardia may appear after anamorelin administration. Additionally, anamorelin is contraindicated in patients with heart failure, ischemic heart disease, severe conduction disturbance, and moderate-to-severe hepatic dysfunction. It is administered cautiously to those with a history or risk of QT prolongation and those with conduction disturbances. Periodic electrocardiogram (ECG), pulse, and blood pressure measurements are warranted after anamorelin administration. The mechanism behind anamorelin's proarrhythmic effects remains unknown, but weak binding to sodium channels and L-type calcium channels was revealed.4 Decreased sodium current may predispose to sudden cardiac death, as studies on arrhythmia suppression have demonstrated that sodium channel blockers increase the incidence of sudden cardiac death. Sodium channel blockade-induced conduction disturbances may cause reentrant arrhythmias because of excitability gap widening. In the current issue of the Journal of Arrhytumia, Shimojo et al. reported a case of drug-induced wide QRS tachycardia by anamorelin.1 Healthcare provider should understand the risk of conduction disturbances and wide QRS tachycardia, although infrequent, as has been reported in several case reports. Anamorelin has increased blood levels in patients with severe hepatic dysfunction. It has been affected by CYP3A4, a hepatic drug-metabolizing enzyme, and serum concentrations may be increased with drugs that inhibit CYP3A4. Nevertheless, blood concentration alone cannot determine the degree of intoxication, including electrocardiographic abnormalities and proarrhythmias, as factors beyond antiarrhythmic drug concentration, such as electrolytes and genetic factors, also play a role. The appropriate dose was prescribed in all the past wide QRS tachycardia case reports. Some cases may not be predictable because of individual susceptibility to the drug. Some patients respond well to concentrations lower than the general effective blood concentration range, whereas others do not respond even within that range. This is because of the different effective blood sodium channel blocker concentrations required to exert antiarrhythmic effects in individual patients because of genetic differences in myocardial sodium channel function.5 In particular, the SCN5A gene encodes the alpha subunit of the cardiac sodium channel Nav1.5 and is responsible for phase 0 of the cardiac action potential. Six related polymorphisms (haplotypes; Hap) are known in the promoter region of the SCN5A gene. Hap B is unique to Asians, with a prevalence of 24% in the Japanese population. Patients who respond to sodium channel blockers at low doses may have Hap B.5 Hence, Asians might need to be more observant about anamorelin responsiveness, especially regarding ECG changes early in the administration. Finally, anamorelin causes potentially fatal arrhythmias and should be carefully monitored before and after administration. The blockade of sodium and L-type calcium channels mediates the proarrhythmic effects of anamorelin. Sodium channel gene polymorphisms may be associated with pathogenesis in addition to blood levels and dose dependence. Further reports and clarification of the mechanisms are warranted, with the expectation that anamorelin can be used more safely. The authors have nothing to report. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None. None. None. None. None.
It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis.We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis.VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.
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