Initial results of transcatheter modification of left atrial appendage by obliteration with device in patients with nonvalvular atrial fibrillation: Real-world data from the TERMINATOR registry.

BACKGROUND: Percutaneous left atrial appendage closure (LAAC) has increased for those who need alternative to long-term anticoagulation with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: From September 2019, after initiating WATCHMAN (Boston Scientific, Maple Grove, MN, USA) device implantation, we established Transcatheter Modification of Left Atrial Appendage by Obliteration with Device in Patients from the NVAF (TERMINATOR) registry. Utilizing 729 patients' data until January 2022, we analyzed percutaneous LAAC data regarding this real-world multicenter prospective registry. A total of 729 patients were enrolled. Average age was 74.9 years and 28.5 % were female. Paroxysmal AF was 37.9 % with average CHADS2 3.2, CHA2DS2-VASc 4.7, and HAS-BLED score of 3.4. WATCHMAN implantation was successful in 99.0 %. All-cause deaths were 3.2 %, and 1.2 % cardiovascular or unexplained deaths occurred during follow-up [median 222, interquartile range (IQR: 93-464) days]. Stroke occurred in 2.2 %, and the composite endpoint which included cardiovascular or unexplained death, stroke, and systemic embolism were counted as 3.4 % [median 221, (IQR: 93-464) days]. Major bleeding defined as BARC type 3 or 5 was seen in 3.7 %, and there was 8.6 % of all bleeding events in total [median 219, (IQR: 93-464) days]. CONCLUSIONS: These preliminary data demonstrated percutaneous LAAC with WATCHMAN device might have a potential to reduce stroke and bleeding events for patients with NVAF. Further investigation is mandatory to confirm the long-term results of this strategy using this transcatheter local therapy instead of life-long systemic anticoagulation.

Decreases of ethanolamine plasmalogen and phosphatidylcholine in erythrocyte are a common phenomenon in Alzheimer's, Parkinson's, and coronary artery diseases.

Decreased plasma levels of plasmalogens in neurodegenerative diseases have been watched with interest. We previously reported the decreases of erythrocyte ethanolamine plasmalogen (PlsPE) of blood not only in Alzheimer's disease (AD) and Parkinson's disease (PD), but also in coronary artery disease (CAD). In the present study, by using the same high-performance liquid chromatography (HPLC) method, we investigated the pattern of changes in the phospholipid composition of erythrocyte membrane in AD, PD and CAD compared with healthy individuals. The common patten of changes among them was as follows: The decrease of erythrocyte PlsPE was accompanied by a decrease of phosphatidylcholine although phosphatidylethanolamine remained unchanged. The decreases of PlsPE and phosphatidylcholine were replaced by an increase of sphingomyelin (SM) in the total phospholipids. The dissociated change between PlsPE and phosphatidylethanolamine (PE) may be caused by the differences in molecular structure or in location in the cell membrane. Such special changes provide another piece of biochemical evidence that these different diseases are caused by identical pathological mechanism, suggesting potential biomarkers for these chronic diseases due to aging.

Impaired deformability and association with density distribution of erythrocytes in patients with type 2 diabetes mellitus under treatment.

BACKGROUND: Disturbed microcirculation is related to diabetic complications, and erythrocyte deformability is a critical factor regulating microcirculation. OBJECTIVES: To know the relationship between the impaired deformability and density profile in diabetic erythrocytes. METHODS: We recruited patients with type 2 diabetes (n = 15, diabetic group) and age- and sex-matched non-diabetic subjects (n = 15, control group). Erythrocyte density (ED) profile was obtained by the phthalate ester separation technique. ED distribution was fitted by sigmoidal curve, yielding specific gravity of phthalate ester allowing passage of half erythrocytes population (ED50) and slope factor. Erythrocyte deformability was estimated by our specific filtration technique. RESULTS: Diabetic group showed significantly (p < 0.001) higher HbA1c and fasting blood glucose concentration. Erythrocyte deformability in diabetic group was impaired as compared with that in control group (p < 0.001) and proportional to HbA1c (p = 0.009). However, ED50 and the slope factor in diabetic group did not differ from respective parameters in control group. CONCLUSIONS: This study demonstrated that erythrocyte deformability was impaired in diabetic patients even under treatment. HbA1c up to 7.5% is concluded not to alter the erythrocyte density but to impair the deformability, which might be a warning to clinicians for prevention of diabetic complications.

Hypoalbuminemia for the prediction of venous thromboembolism and treatment of direct oral anticoagulants in metastatic gastric cancer patients.

BACKGROUND: Venous thromboembolism (VTE) is highly associated with advanced gastric cancer (AGC) and is sometimes lethal. Predictors of VTE have not been identified, and the efficacy and safety of direct oral anticoagulants (DOACs) for AGC-associated VTE remain to be clarified. METHODS: A total of 188 AGC patients who started chemotherapy during the period from January 2014 to December 2017 in our institutions were retrospectively examined for the incidence of VTE, risk factors for VTE, and the efficacy and safety of DOAC-based anticoagulant therapy for VTE. RESULTS: Thirty-four patients (18%) were diagnosed with VTE at the start or during the course of chemotherapy (VTE group). More VTE group patients had a history of abdominal surgery and had moderate-severe ascites (32% versus 17%, 32% versus 14%, respectively) than non-VTE group patients (NVTE group). The mean serum albumin concentrations in the VTE group were significantly lower than NVTE group (3.38 mg/dL vs 3.65 mg/dL, respectively). Multivariate analysis showed that hypoalbuminemia was significantly correlated with VTE (P = 0.012). In the VTE group, 29 patients (85%) received anticoagulant therapy, including 24 patients treated with DOACs. No lethal VTE was observed in any patients. Thirteen patients (45%) terminated DOACs because of anemia or bleeding events, of whom eleven developed major bleeding. Median overall survivals of the VTE and NVTE groups were 9.63 months and 11.5 months, respectively (P = 0.262). CONCLUSION: Hypoalbuminemia appears to be a risk factor for AGC-associated VTE. DOACs are effective to AGC-associated VTE, but careful observation of bleeding events is required.

Sick Sinus Syndrome Observed in a Patient with Cholinesterase Deficiency.

A 58-year-old woman complained of general fatigue and was diagnosed with sick sinus syndrome (SSS) by ambulatory electrocardiogram, which demonstrated sinus arrest at midnight and paroxysmal atrial fibrillation (AF) at nighttime. Since her plasma cholinesterase (ChE) activity had been persistently zero, she was diagnosed with ChE deficiency. She refused permanent pacemaker implantation, and treatment with positive chronotropic drugs is ongoing. A novel association of ChE deficiency with SSS is theoretically possible rather than coincident, considering that ChE plays a key role in cholinergic influences on the sinus node leading to sinus bradyarrhythmia and on the atria, causing vagally mediated AF.

Valve Hemodynamics and Clinical Outcomes After Transcatheter Aortic Valve Replacement for a Small Aortic Annulus.

The hemodynamics and outcomes in patients with a small aortic annulus (SAA) after transcatheter aortic valve replacement (TAVR) with a second-generation transcatheter heart valve remain unclear. We investigated whether TAVR with a Sapien XT (Edwards Lifesciences, Irvine, California) influences postprocedural valve hemodynamics and long-term outcome in high-risk SAA patients compared with surgical aortic valve replacement (SAVR).We retrospectively identified 94 SAA patients who underwent aortic valve replacement (TAVR = 35 and SAVR = 59). SAA was defined as an aortic annulus diameter ≤ 20 mm, measured by preprocedural transesophageal echocardiography.The mean age was 80.2 years. The mean Society of Thoracic Surgeons-Predicted Risk of Mortality was 6.8%. The post-procedural peak transvalvular velocity and mean pressure gradient were significantly lower in the TAVR cohort than in the SAVR cohort, whereas the postprocedural aortic valve area was significantly higher in the TAVR cohort. Severe prosthesis-patient mismatch (PPM) occurred less frequently after TAVR than SAVR (TAVR 2.9% versus SAVR 22.0%, P = 0.01). The two-year mortality in SAA patients was similar between the two groups.TAVR with a Sapien XT in SAA patients improved the valve hemodynamics and reduced the incidence of PPM compared with SAVR. TAVR patients had a similar 2-year mortality despite higher risk baseline characteristics. To avoid PPM and the consequent poor outcomes, TAVR can be considered an alternative option to SAVR in high surgical risk patients with SAA.

Comparison of cardiac energetics after transcatheter and surgical aortic valve replacements.

OBJECTIVES: The effect of transcatheter aortic valve replacement (TAVR) on cardiac energetics has not been described. We compared changes in cardiac energetics after TAVR with those after surgical aortic valve replacement (SAVR). METHODS: We retrospectively estimated end-systolic elastance (Ees) and effective arterial elastance (Ea) using blood pressure and left ventricular (LV) volume obtained from echocardiography. LV efficiency [ventriculoarterial coupling (Ea/Ees) and the stroke work to pressure-volume area ratio (SW/PVA)] was calculated. Measurements were taken before, 1 week after and 1 year after bioprosthetic aortic valve replacement (TAVR, n = 56; SAVR, n = 61) in patients with severe aortic stenosis and preserved ejection fraction. RESULTS: Patients with TAVR had a lower aortic valve pressure gradient and larger stroke volume 1 week after the procedure than those with SAVR. Ea was more markedly decreased, and LV efficiency was significantly improved 1 week after TAVR (SW/PVA 68.1% ± 8.4% to 72.0% ± 8.5%, P < 0.001), but LV efficiency was unchanged 1 week after SAVR (SW/PVA 70.1% ± 7.4% to 69.1% ± 8.0%). LV efficiency was improved 1 year after both procedures (SW/PVA 75.5% ± 6.1% in TAVR; 74.7% ± 6.4% in SAVR). CONCLUSIONS: TAVR decreases the transvalvular pressure gradient further without deteriorating stroke volume in the early postoperative period, which is accompanied by early improvement in afterload and LV efficiency compared with SAVR. Improvement in LV efficiency at mid-term follow-up is satisfactory after both procedures.

Effect of QRS Morphology and Duration on Clinical Outcomes After Cardiac Resynchronization Therapy　- Analysis of Japanese Multicenter Registry.

BACKGROUND: QRS duration (QRSd) and morphology are established response predictors of cardiac resynchronization therapy (CRT). However, evidence in Japanese populations is lacking.Methods and Results:We retrospectively analyzed the Japanese multicenter CRT database. We divided patients according to their intrinsic QRSd and morphology, and assessed echocardiographic responses and clinical outcomes. The primary endpoint was a composite of all-cause death or hospitalization because of heart failure. A total of 510 patients were enrolled: 200 (39%) had left bundle branch block (LBBB) and QRSd ≥150 ms; 80 (16%) had LBBB (QRSd: 120-149 ms); 61 (12%) had non-LBBB (NLBBB) (QRSd: ≥150 ms); 54 (11%) had NLBBB (QRSd: 120-149 ms); 115 (23%), narrow (<120 ms). The proportion of echocardiographic responders was higher in LBBB (QRSd ≥150 ms) [74% vs. 51% vs. 38% vs. 52% vs. 50%, LBBB (QRSd ≥150 ms) vs. LBBB (QRSd 120-149 ms) vs. NLBBB (QRSd ≥150 ms) vs. NLBBB (QRSd 120-149 ms) vs. narrow, respectively, P<0.001]. During follow-up (3.2±1.5 years), the incidence of the primary endpoint was lowest in the LBBB group (QRSd ≥150) (28.6% vs. 42.3% vs. 45.9% vs. 55.6% vs. 55.3%, respectively, P<0.001). This difference was still significant after adjusting for other baseline characteristics. CONCLUSIONS: In this Japanese patient population, LBBB intrinsic QRS morphology and prolonged QRSd (≥150 ms) exhibited the best response to CRT.

Impact of preprocedural atrial fibrillation on immediate and long-term outcomes after successful percutaneous mitral valvuloplasty of significant mitral stenosis.

Optimal time to perform percutaneous mitral valvuloplasty (PMV) for patients with significant mitral stenosis (MS) and atrial fibrillation (AF) remains controversial. We sought to identify prognostic factors and evaluate long-term clinical outcomes after PMV of 77 consecutive patients with MS with a mitral valve area (MVA) <1.5 cm2. According to baseline heart rhythm, these patients were divided into sinus rhythm (SR; n = 24) and AF (n = 53) groups. The study endpoint was defined as a composite of all-cause mortality, admission for heart failure, mitral valve surgery, repeated PMV, and major cerebral vascular accident during follow-up. After successful PMV, there was no significant difference between the two groups in post-MVA and post-mitral mean pressure gradient. However, the New York Heart Association Functional Classification post-procedure was worse in the AF group (p < 0.01). In the AF group, event-free survival during follow-up was significantly lower compared with that of the SR group (p = 0.016). Independent predictors of clinical events were AF [hazard ratio (HR), 2.73; 95 % confidence interval (CI), 1.04-9.36; p = 0.03] and pulmonary artery systolic pressure (HR 2.57; 95 % CI 1.18-5.47; p = 0.017). Patients with AF at baseline were significantly associated with worse symptoms and higher event rates after successful PMV compared with those with SR. The clinical benefit of PMV may be considered for patients with MVA <1.5 cm2 before the onset of AF.

Complex regional pain syndrome induced by pacemaker implantation for sick sinus syndrome.

A 53-year-old woman reported burning pain, muscle weakness, and dysesthesia of the left arm 2 months after permanent pacemaker insertion in the ipsilateral side for the treatment of sick sinus syndrome. Complex regional pain syndrome (CRPS) induced by pacemaker implantation was diagnosed. In 2017, her pulse generator became exhausted and was exchanged carefully to avoid exacerbation of CRPS, under the application of local anesthesia and premedication. Six months later, the patient's grip strength in her left hand remained lower relative to that in her right hand. Although rare, the presence of CRPS following device implantation should be remembered.

Manifestation of J wave induced by acetylcholine applied for a coronary spasm provocation test in a patient with aborted sudden cardiac death.

A 51-year-old man with a resuscitation episode was referred to our hospital. Coronary angiography revealed a focal spasm overlapped with organic stenosis where a bare metal stent was implanted. Acetylcholine (ACh) provocation test did not induce chest pain. It revealed no discernible ST-T changes but unmasked a J wave at the end of the QRS complex, which was associated with short-coupled repetitive premature ventricular beats. A J wave reportedly appears immediately before the onset of ventricular fibrillation caused by vasospastic angina. However, a J wave observed newly after a coronary spasm provocation test using ACh without ST-T changes is informative when considering the mechanisms of the J wave.

Duration of reverse remodeling response to cardiac resynchronization therapy: Rates, predictors, and clinical outcomes.

BACKGROUND: A subset of patients undergoing cardiac resynchronization therapy (CRT) for heart failure (HF) with severe left ventricular (LV) dysfunction experience only short-lived LV reverse remodeling. Little is known about the incidence and prognosis of this finding. We sought to identify predictors of a brief response and investigated the prognosis in a retrospective study. METHODS: A total of 528 patients from a Japanese multicenter database with full echocardiography datasets were enrolled. Follow-up was 3.4±1.3years. Based on relative reduction in LV end-systolic volume (LVESV) at 6months, we categorized patients as responders (reduction in LVESV ≥15%) and non-responders (NRs; reduction in LVESV <15%). Based on reduction in LVESV at 1-2years, responders were subdivided into long-lasting responders (reduction in LVESV ≥15%) and brief responders (reduction in LVESV <15%). RESULTS: Of 328 responders, 50 (15%) were brief responders. Predictors of brief response were prior ventricular tachyarrhythmia, a non-left bundle-branch block (LBBB) intrinsic QRS pattern, and prior hospitalization for HF. The risk of all-cause death in brief responders was significantly lower than that in NRs (P=0.034) and tended to be higher than that in long-lasting responders (P=0.080). CONCLUSIONS: Approximately 15% of responders were brief responders. Prior ventricular tachyarrhythmia, a non-LBBB pattern, and HF hospitalization were independent predictors of a brief response. Brief response was significantly associated with decreased risk of all-cause death compared with NRs and had a tendency toward increased risk of all-cause death compared with long-lasting responders.

Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib.

Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment.

Cardiac metastasis of squamous cell carcinoma of the thyroid gland with severe disseminated intravascular coagulation: A case report.

Distant metastasis of primary squamous cell carcinoma (SCC) of the thyroid gland is rare and, to the best of our knowledge, cardiac metastasis has not been reported to date. A 57-year-old man underwent surgery and adjuvant chemoradiotherapy for stage IVA SCC of the thyroid gland. After 3 months, the patient was admitted to the Kyushu University Hospital (Fukuoka, Japan) with subcutaneous hematomas of the left thigh and lower leg, and he was diagnosed with cardiac and mediastinal lymph node metastases of SCC of the thyroid gland with severe disseminated intravascular coagulation (DIC). Echocardiography revealed a mass, 52 mm in greatest diameter, protruding from the interventricular septum towards the right ventricle. Weekly administration of paclitaxel and concurrent irradiation of the cardiac and lymph node metastases were performed. Eighteen days after the initiation of chemoradiotherapy, the DIC and hematomas had significantly improved, and the cardiac metastasis was stable. However, 2 months after admission, the patient developed dyspnea and multiple nodular shadows appeared to be spreading in the subpleura of the lungs bilaterally, which were initially suspected to be pulmonary tumor embolisms. Prednisolone and subsequent administration of lenvatinib were not effective and the patient succumbed to respiratory failure. Severe DIC caused by extremely rare cardiac metastasis of SCC of the thyroid gland was effectively controlled by chemoradiotherapy. However, intensive local control appears to be required for this condition.

Anticoagulation Stability Depends on CHADS2 Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation.

AIM: Although warfarin remains important despite the widespread use of nonvitamin K antagonist oral anticoagulants (NOACs), to date, the reality of warfarin use in the "NOACs era" is unclear. This multicenter observational study aimed to clarify the key factors contributing to warfarin treatment stability. METHODS: The practical use of warfarin, stability of warfarin therapy, and factors contributing to this stability were investigated in community-based hospitals through a real-world study. Clinical data were retrospectively extracted from the medical records of warfarin-treated Japanese patients (age, 71.3±5.5 years) with atrial fibrillation (AF), prosthetic heart valve, or other concerns requiring anticoagulation. Treatment stability was considered as time in therapeutic range of international normalized ratio of prothrombin time (TTR: %). The factors contributing to TTR were investigated, including CHADS2 score components. RESULTS: Mean CHADS2 score was highest (1.38±0.88, p＜0.001), and most CHADS2 score components in addition to hepatorenal dysfunction were factors contributing to the low TTR in patients with AF (n=176). The similarity was found in overall patients who were prescribed warfarin (n= 518). TTR decreased according to the CHADS2 score component accumulation. Gender, dose and prescription interval of warfarin, and co-administration of antiplatelet agents did not correlate with the low TTR. CONCLUSIONS: This retrospective study demonstrated that the CHADS2 score component accumulation and hepatorenal dysfunction are factors significantly contributing to the low TTR, which is indicative of poor warfarin treatment stability, in patients such as those with AF.