Formylation Reaction of Amines Using N-Formylcarbazole.

Formamides are useful starting materials for pharmaceutical syntheses. Although various synthetic methods have been documented in this regard, the use of N-formylcarbazole as a formylation reagent for amines has not yet been reported. We report here the first examples of the use of N-formylcarbazole for the formylation of amines. The characteristic reactivity of N-formylcarbazole enables the selective formylation of sterically less hindered aliphatic primary and secondary amines. In contrast, sterically bulkier amines and weakly nucleophilic amines such as anilines are less reactive under the reaction conditions.

A case of left ventricular assist device application for chemotherapy-related cardiomyopathy caused by trastuzumab and anthracycline.

Left ventricular assist device (LVAD) is an established therapy for patients with severe heart failure. Because the incidence of cardiotoxicity owing to anticancer agents is low, it is difficult to predict the recovery prospects when the cause of heart failure is due to anticancer agents. In this context, cancer patients who present with severe symptoms of heart failure and who fail medical therapy for heart failure may pose a dilemma, especially in countries such as Japan where implantable LVADs are not approved for purposes other than bridging to transplant. Recently, we encountered a 32-year-old woman with chemotherapy-related cardiomyopathy that developed after anticancer treatment using trastuzumab and anthracycline. LVAD therapy was the only option to save the young woman. The patient received an extracorporeal LVAD, her cardiac function gradually recovered while on support, and the device was successfully removed.

Does the presence of coronary artery disease affect the outcome of aortic valve replacement?

The purpose of this study is to compare the late outcome of aortic valve replacement with or without preoperative coronary artery disease, and with or without coronary artery bypass. Between 2014 and 2015, 291 patients underwent aortic valve replacement. Average follow-up term was 2.5 ± 2.2 years. The retrospective comparative study was performed between the patients with (n = 115) or without (n = 176) preoperative coronary artery disease (Study 1) and with (n = 93) or without (n = 198) coronary artery bypass grafting (Study 2). Study 1: male patients were more, and diabetes was more in the patients with coronary artery disease. Long-term survival rate was significantly low in the patients with coronary artery disease (p = 0.0002 by log rank test). Freedom from repeat coronary revascularization rate was lower in the patients with coronary artery disease (p = 0.02 by log rank test). Study 2: operation time (419 ± 130 vs 290 ± 101; p = 0.0001) was longer in the patients with coronary artery bypass grafting. Improvement of ejection fraction at follow-up was more in the patients with coronary artery bypass(114 ± 43 vs 104 ± 26%; p = 0.03). Long-term survival rate and freedom from major adverse cardiac event rater were not different with or without coronary artery bypass grafting (p = 0.26 and p = 0.59, respectively, by log rank test). Although prevalence of coronary artery disease inversely affected the long-term outcome of the aortic valve replacement, simultaneous coronary artery bypass did not. Aggressive simultaneous coronary revascularization would be important to improve the long-term outcome of aortic valve replacement.

Is ganglionated plexus ablation effective for treating atrial fibrillation?

PURPOSE: Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. METHODS: A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. RESULTS: Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. CONCLUSION: Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

Endovascular Treatment for Proximal Anastomotic Pseudoaneurysm after Total Arch Replacement in Behcet's Disease.

A 17-year-old patient underwent total arch replacement for aortic arch aneurysm due to vascular Behcet's disease (BD). Follow-up computed tomography, performed 6 months after the operation, demonstrated pseudoaneurysm formation at the proximal anastomotic site. We performed endovascular treatment and used a short stent graft that was originally designed for abdominal aortic aneurysm. To avoid the occlusion of the coronary or brachiocephalic artery (BCA) due to stent graft migration, we used right ventricular rapid pacing and BCA ballooning. Thus, we believe that endovascular treatment can be used for anastomotic complications in the ascending aorta after open surgery for connective tissue disorders including BD.

Thoracic endovascular aortic repair for recurrent stroke due to atheromatic plaque in the proximal descending aorta: a case report.

BACKGROUND: Diastolic retrograde flow in the descending aorta (DAo) may occur in the presence of atherosclerosis and may be overlooked as a mechanism of retrograde embolization in patients with stroke. We performed thoracic endovascular aortic repair (TEVAR) in a patient with recurrent cerebral infarctions for treatment of aortic aneurysm with atheromatic plaque, which was considered as the source of embolism. CASE PRESENTATION: A 56-year-old man with a history of idiopathic thrombocytopenia and hypertension was referred to our hospital with paralysis of the right upper and lower limbs. Multiple cerebral infarctions were found and treated; however, 1 month later, another cerebral infarction developed. A small saccular aortic aneurysm with plaque was found beyond the left subclavian artery, and this site was deemed as the source of embolism. We performed TEVAR to prevent further recurrence of cerebral infarctions. No cerebral infarctions were observed 6 months post-operation. CONCLUSIONS: TEVAR is a useful treatment for not only aortic aneurysm and dissection, but also cerebral infarctions caused by an embolic source proximal to the DAo due to retrograde aortic blood flow.

Selective oxidation of alcohol-d 1 to aldehyde-d 1 using MnO2.

The selective oxidation of alcohol-d 1 to prepare aldehyde-d 1 was newly developed by means of NaBD4 reduction/activated MnO2 oxidation. Various aldehyde-d 1 derivatives including aromatic and unsaturated aldehyde-d 1 can be prepared with a high deuterium incorporation ratio (up to 98% D). Halogens (chloride, bromide, and iodide), alkene, alkyne, ester, nitro, and cyano groups in the substrates are tolerated under the mild conditions.

Pulmonary Embolectomy for Acute Pulmonary Embolism: A Word of Caution.

Pulmonary embolectomy is an effective treatment of acute pulmonary embolism (APE) but not for chronic pulmonary thromboembolism. We described surgical experience of two patients with APE in preexistent unidentified chronic pulmonary thromboembolism. One patient who presented with severe hypoxia but stable hemodynamics underwent successful pulmonary endarterectomy for proximal organized thrombus instead of pulmonary embolectomy. The other patient who required extracorporeal membrane oxygenation for severe hypoxia developed right heart failure because of residual distal organized thrombus after pulmonary embolectomy. Clinical and radiographical presentation of APE in chronic pulmonary thromboembolism mimics APE, and thus, candidates of pulmonary embolectomy should be carefully selected.

Use of a Smart Watch for Early Detection of Paroxysmal Atrial Fibrillation: Validation Study.

BACKGROUND: Wearable devices with photoplethysmography (PPG) technology can be useful for detecting paroxysmal atrial fibrillation (AF), which often goes uncaptured despite being a leading cause of stroke. OBJECTIVE: This study is the first part of a 2-phase study that aimed at developing a method for immediate detection of paroxysmal AF using PPG-integrated wearable devices. In this study, the diagnostic performance of 2 major smart watches, Apple Watch Series 3 and Fitbit (FBT) Charge HR Wireless Activity Wristband, each equipped with a PPG sensor, was compared, and the pulse rate data outputted from those devices were analyzed for precision and accuracy in reference to the heart rate data from electrocardiography (ECG) during AF. METHODS: A total of 40 subjects from patients who underwent cardiac surgery at a single center between September 2017 and March 2018 were monitored for postoperative AF using telemetric ECG and PPG devices. AF was diagnosed using a 12-lead ECG by qualified physicians. Each subject was given a pair of smart watches, Apple Watch and FBT, for simultaneous pulse rate monitoring. The heart rate of all subjects was also recorded on the telemetry system. Time series pulse rate trends and heart rate trends were created and analyzed for trend pattern similarities. Those trend data were then used to determine the accuracy of PPG-based pulse rate measurements in reference to ECG-based heart rate measurements during AF. RESULTS: Of the 20 AF events in group FBT, 6 (30%) showed a moderate or higher correlation (cross-correlation function>0.40) between pulse rate trend patterns and heart rate trend patterns. Of the 16 AF events in group Apple Watch (workout [W] mode), 12 (75%) showed a moderate or higher correlation between the 2 trend patterns. Linear regression analyses also showed a significant correlation between the pulse rates and the heart rates during AF in the subjects with Apple Watch. This correlation was not observed with FBT. The regression formula for Apple Watch W mode and FBT was X=14.203 + 0.841Y and X=58.225 + 0.228Y, respectively (where X denotes the mean of all average pulse rates during AF and Y denotes the mean of all corresponding average heart rates during AF), and the coefficient of determination (R2) was 0.685 and 0.057, respectively (P<.001 and .29, respectively). CONCLUSIONS: In this validation study, the detection precision of AF and measurement accuracy during AF were both better with Apple Watch W mode than with FBT.

The cardioprotective effect of interleukin-11 against ischemia-reperfusion injury in a heart donor model.

BACKGROUND: Previously, we have demonstrated the cardioprotective effect of interleukin (IL)-11 in animal models of acute coronary syndrome. In this study, we sought to evaluate its cardioprotective potential during prolonged hypothermic global ischemia and subsequent reperfusion using a rat heart donor model. METHODS: IL-11 was administered intravenously 10 minutes before harvesting the rat heart. The hearts were preserved in cold (4 °C) Krebs-Henseleit buffer for 6 hours, and then attached to a Langendorff perfusion apparatus and reperfused with an oxygenated Krebs-Henseleit solution containing IL-11. Normal saline was used instead of IL-11 in the control group. Functional recovery of the reperfused heart was observed by using a left ventricular balloon. Myocardial cell injury was quantified by measuring the biomarkers collected from the coronary effluent. Apoptotic cells were identified and counted using the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining technique. RESULTS: IL-11 administration improved myocardial function after 6 hours of cold ischemia. Although there were no significant differences in any of the baseline-measured values between the two groups, left ventricular developed pressure (LVDP) and changes in left ventricular pressures (dP/dt) were significantly higher in the IL-11 group at 120-minute reperfusion. The number of TUNEL-labeled cardiomyocytes was also significantly smaller in the IL-11 group. CONCLUSIONS: The administration of IL-11 showed a significant recovery of cardiac contractile function after 6 hours of cold ischemia. Our data suggest that it may have significant therapeutic potential for maintaining the functional viability of the heart exposed to prolonged hypothermic global ischemia.

Right ventricular papillary muscle approximation for functional tricuspid regurgitation associated with severe leaflet tethering.

Recurrent tricuspid regurgitation (TR) can occur after tricuspid annuloplasty if severe leaflet tethering persists. To reduce the tethering, we applied right ventricular papillary muscle approximation in 7 patients with severe functional TR associated with significant leaflet tethering. Postoperative echocardiogram revealed mild or less TR and a significant reduction in the tethering effect. In conclusion, this adjunctive technique can improve functional TR associated with leaflet tethering.

Recurrence of Left Ventricular Outflow Tract Obstruction Requiring Alcohol Septal Ablation after Transcatheter Aortic Valve Implantation.

Left ventricular outflow tract (LVOT) obstruction is sometimes observed in patients with severe aortic stenosis (AS). It is still controversial how to manage the remaining severe AS, when LVOT obstruction is well-controlled by medical therapy. We report a case with acute recurrence of LVOT obstruction requiring emergent alcohol septal ablation (ASA) after transcatheter aortic valve implantation (TAVI), even in a stable state on beta-blockers. For the ASA procedure, transesophageal echocardiography was useful to clearly observe the perfusion area of the target septal branch by injecting microbubble contrast. Since it took some time to cause the recurrence of LVOT obstruction in this case, careful evaluation should be done after TAVI in high-risk patients for LVOT obstruction before terminating the TAVI procedure.

Long-term consequences of atrial fibrillation after aortic valve replacement.

Background Atrial fibrillation is a common complication after cardiac surgery, but the risk factors and long-term outcome after primary isolated aortic valve replacement remains to be clarified. Methods A single-center retrospective study was conducted on 157 patients who underwent first-time isolated aortic valve replacement between April 1999 and February 2015. Fifty-eight patients developed new-onset atrial fibrillation within 6 months postoperatively, and they were compared with patients who remained in sinus rhythm. Multivariate analyses, which incorporated the propensity score patient matching technique, were conducted to evaluate the long-term outcome of new-onset postoperative atrial fibrillation and identify patients at risk of developing this arrhythmia. Results At a mean follow-up of 52.4 months (range 8.4-200.7 months), mortality was significantly higher in patients who developed atrial fibrillation compared to those who remained in sinus rhythm (2.8%/patient-year vs. 0.2%/patient-year, respectively; p < 0.05). Patients developing atrial fibrillation were also at an independently increased risk of stroke and readmission during follow-up. Risk analysis revealed that advanced age (>70 years) and absence of a postoperative ß-blocker were predictors of atrial fibrillation. Conclusions New-onset atrial fibrillation after first-time isolated aortic valve replacement correlated significantly with late morbidity and mortality. Advanced age and absence of a postoperative ß-blocker may increase the incidence of atrial fibrillation.

A prospective, randomized study of inhaled prostacyclin versus nitric oxide in patients with residual pulmonary hypertension after pulmonary endarterectomy.

OBJECTIVES: Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but postoperative residual hypertension leads to in-hospital mortality. Inhaled epoprostenol sodium (PGI2) and NO are administered for pulmonary hypertension after cardiothoracic surgery. This prospective study provides the first comparative evaluation of the effects of inhaled PGI2 and NO on pulmonary hemodynamics, systemic hemodynamics, and gas exchange in patients developing residual pulmonary hypertension after PEA. METHODS: Thirteen patients were randomized to receive either NO (n = 6) or PGI2 (n = 7) inhalation when pulmonary hypertension persisted after weaning from cardiopulmonary bypass. Hemodynamic and respiratory variables were measured before inhalation of the agent (T0); 30 min (T1), 3 h (T2), and 6 h after inhalation (T3); and the next morning (T4). The NO dose was started at 20 ppm and gradually tapered until extubation, and PGI2 was administered at a dose of 10 ng kg-1 min-1. RESULTS: In both groups, mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) significantly decreased over time until T4 (mean PAP: p < 0.0001; PVR: p = 0.003), while mean systemic arterial blood pressure significantly increased (p = 0.028). There were no significant between-group differences in patient characteristics, cardiac index, left atrial pressure, or ratio of arterial oxygen tension to fraction of inspired oxygen. There were no in-hospital deaths. CONCLUSIONS: Both inhaled PGI2 and NO significantly reduced PAP and PVR without adverse effects on systemic hemodynamics in patients who developed residual pulmonary hypertension after PEA. Inhaled PGI2 can be offered as alternative treatment option for residual pulmonary hypertension.

Perioperative anticoagulation management in antiphospholipid syndrome.

Patients with antiphospholipid syndrome are at increased risk of developing thrombotic and hemorrhagic complications after cardiac surgery, and may have abnormal coagulation tests and develop thrombocytopenia after invasive procedures, which can complicate the perioperative management of anticoagulant therapy. We describe a patient with chronic thromboembolic pulmonary hypertension and antiphospholipid syndrome, who presented with prolonged activated partial thromboplastin and activated clotting times, and developed thrombocytopenia after the catheterization workup. We performed pulmonary endarterectomy and successfully managed anticoagulation by restricting heparin use at the time of surgery and monitoring the heparin effect by measuring heparin concentrations during cardiopulmonary bypass.