Myasthenic Crisis and Concomitant Takotsubo Syndrome Complicated by Shock: A Case Report.

A man in his 80s with myasthenia gravis (MG) developed dysmobility and chest discomfort. An electrocardiogram revealed ST-segment elevation, and coronary angiography revealed Takotsubo syndrome (TTS). He experienced myasthenic crisis that required ventilation and shock that was refractory to vasopressors and required intra-aortic balloon pump (IABP) insertion. He was managed conservatively without MG-specific treatment until his hemodynamics improved. On hospital day 6, he was weaned from IABP. MG is a high-risk condition for TTS, and TTS with MC is associated with high mortality. We successfully managed this case of TTS with MC with intubation and IABP, without MG-specific treatment.

Outcomes and treatment strategy of transcatheter aortic valve replacement with balloon-expandable valve in borderline-size annulus.

BACKGROUND: Candidates for transcatheter aortic valve replacement (TAVR) occasionally have a "borderline-size" aortic annulus between 2 transcatheter heart valve sizes, based on the manufacturer's sizing chart. Data on TAVR outcomes in such patients are limited. METHODS: We retrospectively reviewed 1816 patients who underwent transfemoral-TAVR with balloon-expandable valve (BEV) at our institution between 2016 and 2020. We divided patients into borderline and non-borderline groups based on computed tomography-derived annular measurements and compared outcomes. Furthermore, we analyzed procedural characteristics and compared outcomes between the smaller- and larger-valve strategies in patients with borderline-size annulus. RESULTS: During a median follow-up of 23.3 months, there was no significant difference between the borderline (n = 310, 17.0 %) and non-borderline (n = 1506) groups in mortality (17.3 % vs. 19.5 %; hazard ratio [HR] = 0.86 [95% CI = 0.62-1.20], p = 0.39), major adverse cardiac/cerebrovascular events (MACCE: death/myocardial infarction/stroke, 21.2 % vs. 21.5 %; HR = 0.97 [0.71-1.32], p = 0.85), paravalvular leak (PVL: mild 21.8 % vs. 20.6 %, p = 0.81; moderate 0 % vs. 1.2 %; p = 0.37), or mean gradient (12.9 ± 5.8 vs. 12.6 ± 5.2 mmHg, p = 0.69) at 1 year. There was no significant difference between the larger-(n = 113) and smaller-valve(n = 197) subgroups in mortality (23.7 % vs. 15.2 %; HR = 1.57 [0.89-2.77], p = 0.12), MACCE (28.1 % vs. 18.4 %; HR = 1.52 [0.91-2.54], p = 0.11), mild PVL (13.3 % vs. 25.9 %; p = 0.12), or mean gradient (12.3 ± 4.5 vs. 13.6 ± 5.3 mmHg, p = 0.16); however, the rate of permanent pacemaker implantation (PPI) was higher in the larger-valve subgroup (15.9 % vs. 2.6 %, p < 0.001). CONCLUSION: Borderline-size annulus is not associated with higher risk of adverse outcomes after BEV-TAVR. However, the larger-valve strategy for borderline-size annulus is associated with higher PPI risk, suggesting a greater risk of injury to the conduction system.

Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease　- A 12-Year Nationwide Cohort Analysis.

BACKGROUND: Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown.Methods and Results: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. CONCLUSIONS: This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Body mass index and outcomes in patients with Takotsubo syndrome: a nationwide retrospective cohort study.

BACKGROUND: Takotsubo syndrome (TTS) is a cardiac disorder that mimics acute coronary syndrome at presentation. While previous studies have demonstrated a relationship between body mass index (BMI) and outcomes in acute coronary syndrome, few have examined its relationship with TTS. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 14,551 patients admitted for TTS between 2010-2021. By applying multivariable regressions with restricted cubic splines, we examined the association between BMI and in-hospital mortality after adjusting for potential confounders. RESULTS: Mean BMI was 21.1 kg/m2, classifying patients into severe underweight (<16.0 kg/m2, 7.1%), mild/moderate underweight (16.0-18.4 kg/m2, 18.3%), normal weight (18.5-22.9 kg/m2, 46.8%), overweight (23.0-27.4 kg/m2, 22.2%), and obese (≥27.5 kg/m2, 5.6%) groups. Patients with severe or mild/moderate underweight were older and had a higher prevalence of impaired physical activity, malignancy, chronic pulmonary disease, and pneumonia. In-hospital mortality was the highest (9.4%) in the severe underweight group, followed by the mild/moderate underweight group (5.4%), with the lowest being in the obese group (2.1%). Severe underweight (adjusted odds ratio=2.05 [95% CI=1.54-2.73]) and mild/moderate underweight (1.26 [1.01-1.57]) were significantly associated with higher mortality compared with normal weight, while no significant association was noted with obesity. A nonlinear association between continuous BMI and mortality was observed, with mortality increasing when BMI decreased <20.0 kg/m2 but nearly plateauing in BMI >20 kg/m2. CONCLUSIONS: The present nationwide analysis demonstrated a nonlinear association between BMI and in-hospital mortality of TTS. BMI is an easily available and clinically relevant marker for the risk stratification of TTS.

The degree of permanent pacemaker dependence and clinical outcomes following transcatheter aortic valve implantation: implications for procedural technique.

Aims: Conduction abnormalities necessitating permanent pacemaker (PPM) implantation remain the most frequent complication post-transcatheter aortic valve implantation (TAVI), yet reliance on PPM function varies. We evaluated the association of right-ventricular (RV)-stimulation rate post-TAVI with 1-year major adverse cardiovascular events (MACE) (all-cause mortality and heart failure hospitalization). Methods and results: This retrospective cohort study of patients undergoing TAVI in two high-volume centers included patients with existing PPM pre-TAVI or new PPM post-TAVI. There was a bimodal distribution of RV-stimulation rates stratifying patients into two groups of either low [≤10%: 1.0 (0.0, 3.6)] or high [>10%: 96.0 (54.0, 99.9)] RV-stimulation rate post-TAVI. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated comparing MACE in patients with high vs. low RV-stimulation rates post-TAVI. Of 4659 patients, 408 patients (8.6%) had an existing PPM pre-TAVI and 361 patients (7.7%) underwent PPM implantation post-TAVI. Mean age was 82.3 ± 8.1 years, 39% were women. A high RV-stimulation rate (>10%) development post-TAVI is associated with a two-fold increased risk for MACE [1.97 (1.20, 3.25), P = 0.008]. Valve implantation depth was an independent predictor of high RV-stimulation rate [odds ratio (95% CI): 1.58 (1.21, 2.06), P=<0.001] and itself associated with MACE [1.27 (1.00, 1.59), P = 0.047]. Conclusion: Greater RV-stimulation rates post-TAVI correlate with increased 1-year MACE in patients with new PPM post-TAVI or in those with existing PPM but low RV-stimulation rates pre-TAVI. A shallower valve implantation depth reduces the risk of greater RV-stimulation rates post-TAVI, correlating with improved patient outcomes. These data highlight the importance of a meticulous implant technique even in TAVI recipients with pre-existing PPMs.

MitraCox Score Predicts In-Hospital Mortality in Patients Admitted for Transcatheter Edge-to-Edge Mitral Valve Repair.

As mitral valve transcatheter edge-to-edge repair (M-TEER) is evolving as an effective treatment for high-risk surgical patients with mitral regurgitation, there is a pressing need for cardiologists to optimize resources through risk stratification of in-hospital mortality for this patient population. Although current risk-prediction models have been shown to predict adverse outcomes with reasonable accuracy, models trained using the US nationwide population are lacking. This study aimed to identify clinical, demographic, and procedural features that predict in-hospital mortality, and to derive and validate an in-hospital mortality risk-prediction tool in patients who have undergone M-TEER. A total of 9,373 admissions from the Nationwide Readmissions Database of patients who underwent M-TEER between 2015 and 2018 were used to develop and validate the model. We first performed least absolute shrinkage and selection operator (LASSO) regularization of Cox regression (Coxnet) that is 10-fold cross-validated. The non-zero coefficients were multiplied with the respective values of each observation of the predictors to build the scoring formula. Out of 9,373 admissions, 196 patients (2%) died in-hospital during index admission. In descending order, the top variables that were most predictive of in-hospital mortality were higher age, presence of fluid and electrolyte disturbance, and large metropolitan location of the hospital. The validation C-statistic of the MitraCox score was 0.82. Using X-tile software (Yale School of Medicine, New Haven, Connecticut), 2 cutoffs of the score were determined on the basis of in-hospital mortality and length of stay, and the survival of the population was classified into 3 risk groups: low, intermediate, and high. The scoring system deployed online as a web-based calculator can be accessed at https://kathavs.shinyapps.io/Mitracox_Kapadia/. In conclusion, MitraCox score is easy to calculate and predicts in-hospital mortality depending on length of stay in a dynamic manner.

Incidence, management, and prognostic impact of arrhythmias in patients with Takotsubo syndrome: a nationwide retrospective cohort study.

AIMS: Arrhythmia is a major complication of Takotsubo syndrome (TTS). However, its incidence, management, and prognostic impact remain to be elucidated in a large cohort. METHODS AND RESULTS: We retrospectively identified 16 713 patients hospitalized for TTS between July 2010 and March 2021 from the Japanese Diagnosis Procedure Combination database. Serious arrhythmias were defined as ventricular tachycardia/fibrillation (VT/VF), 2nd-/3rd-degree atrioventricular block (AVB), sick sinus syndrome (SSS), or unspecified arrhythmias requiring device treatment. Patient characteristics and outcomes were compared based on the occurrence of serious arrhythmias. The overall incidence proportion of serious arrhythmias was 6.2% (n = 1036; 449 VT/VF, 283 2nd-/3rd-degree AVB, 133 SSS, 55 multiple arrhythmias, 116 others), which remained stable over 11 years. The arrhythmia group was younger, more often male, and exhibited greater impairment in activities of daily living (ADLs) and consciousness than the non-arrhythmia group. Although crude in-hospital mortality was higher in the arrhythmia group (9.6% vs. 5.0%, P < 0.001), the significant association between arrhythmias and mortality disappeared after adjustment for confounders (odds ratio = 1.15, 95% confidence interval = 0.90-1.49). Meanwhile, age, sex, ADLs, consciousness level, and Charlson comorbidity index were significantly associated with mortality. In the arrhythmia group, 254 (24.5%) patients received pacemakers (18.4%) or defibrillators (6.1%), which were implanted at a median of 8 and 19 days after admission, respectively. CONCLUSION: Arrhythmias are not uncommon in TTS. Patients' background characteristics, rather than arrhythmia itself, may be associated with in-hospital mortality. Given the reversibility of cardiac dysfunction in TTS, there may be unnecessary device implantations for arrhythmias occurring as sequelae to TTS, warranting further investigations.

Same-Day Discharge After Elective Percutaneous Transcatheter Cardiovascular Interventions.

Percutaneous transcatheter interventions have evolved as standard therapies for a variety of cardiovascular diseases, from revascularization for atherosclerotic vascular lesions to the treatment of structural cardiac diseases. Concomitant technological innovations, procedural advancements, and operator experience have contributed to effective therapies with low complication rates, making early hospital discharge safe and common. Same-day discharge presents numerous potential benefits for patients, providers, and health care systems. There are several key elements that are shared across the spectrum of interventional cardiology procedures to create a successful same-day discharge pathway. These include appropriate patient and procedure selection, close postprocedural observation, predischarge assessments specific for each type of procedure, and the existence of a patient support system beyond hospital discharge. This review provides the rationale, available data, and a framework for same-day discharge across the spectrum of coronary, peripheral, and structural cardiovascular interventions.

Comparison of Outcomes Following Transcatheter Aortic Valve Replacement Requiring Peripheral Vascular Intervention or Alternative Access.

Background Peripheral vascular intervention (PVI) is occasionally required to facilitate delivery system insertion or to treat vascular complications during transfemoral transcatheter aortic valve replacement (TF-TAVR). However, the impact of PVI on outcomes is not well understood. Therefore, we aimed to compare outcomes between TF-TAVR with versus without PVI and between TF-TAVR with PVI versus non-TF-TAVR. Methods and Results We retrospectively reviewed 2386 patients who underwent TAVR with a balloon-expandable valve at a single institution from 2016 to 2020. The primary outcomes were death and major adverse cardiac/cerebrovascular event (MACCE), defined as death, myocardial infarction, or stroke. Of 2246 TF-TAVR recipients, 136 (6.1%) required PVI (89% bailout treatment). During follow-up (median 23.0 months), there were no significant differences between TF-TAVR with and without PVI in death (15.4% versus 20.7%; adjusted HR [aHR], 0.96 [95% CI, 0.58-1.58]) or MACCE (16.9% versus 23.0%; aHR, 0.84 [95% CI, 0.52-1.36]). However, compared with non-TF-TAVR (n=140), TF-TAVR with PVI carried significantly lower rates of death (15.4% versus 40.7%; aHR, 0.42 [95% CI, 0.24-0.75]) and MACCE (16.9% versus 45.0%; aHR, 0.40 [95% CI, 0.23-0.68]). Landmark analyses demonstrated lower outcome rates following TF-TAVR with PVI than non-TF-TAVR both within 60 days (death 0.7% versus 5.7%, P=0.019; MACCE 0.7% versus 9.3%; P=0.001) and thereafter (death 15.0% versus 38.9%, P=0.014; MACCE 16.5% versus 41.3%, P=0.013). Conclusions The need for PVI during TF-TAVR is not uncommon, mainly due to the bailout treatment for vascular complications. PVI is not associated with worse outcomes in TF-TAVR recipients. Even when PVI is required, TF-TAVR is associated with better short- and intermediate-term outcomes than non-TF-TAVR.

Impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome: A multicenter registry of the Tokyo Cardiovascular Care Unit Network.

BACKGROUND: Hypoalbuminemia is common in critically ill patients and is associated with poor outcomes. However, the relationship between serum albumin levels and clinical outcomes in patients with takotsubo syndrome remains unclear. We examined the impact of hypoalbuminemia on in-hospital mortality in patients with takotsubo syndrome. METHODS: Using the multicenter registry of the Tokyo Cardiovascular Care Unit Network between January 2017 and December 2020, we identified 631 eligible patients with takotsubo syndrome (median age, 78 years; male proportion, 22 %) and documented serum albumin levels at admission, which were used to allocate patients to hypoalbuminemia (serum albumin <3.5 g/dL) or normal albumin (serum albumin ≥3.5 g/dL) groups. Patient characteristics and in-hospital mortality were compared between the groups. RESULTS: Hypoalbuminemia was detected in 200 (32 %) patients at admission. The hypoalbuminemia group was older and had a higher proportion of men and preceding physical triggers than the normal albumin group. In-hospital all-cause mortality was greater in the hypoalbuminemia group than in the normal albumin group (9.5 % vs. 1.9 %, p < 0.001). Both cardiac (3.0 % vs. 0.5 %, p = 0.015) and non-cardiac (6.5 % vs. 1.4 %, p = 0.002) mortality was greater in the hypoalbuminemia group. In multivariable logistic regression analysis, hypoalbuminemia was independently associated with increased in-hospital mortality, even after adjusting for confounders, including age, sex, and triggering events (odds ratio, 3.23; 95 % confidence interval, 1.31-7.95; p = 0.011). CONCLUSIONS: In patients with takotsubo syndrome, hypoalbuminemia is a common comorbidity and is associated with a substantial risk of in-hospital death. Close monitoring and comprehensive critical care are required in these patients.

Characteristics and short-term outcomes of outpatient and inpatient cardiac catheterizations: A descriptive study using a nationwide claim database in Japan.

BACKGROUND: Most previous studies on outpatient cardiac catheterization have been conducted in Western countries, but Japanese studies are rare. We aimed to describe patient characteristics and short-term clinical outcomes of outpatient cardiac catheterization compared to those of inpatient cardiac catheterization in Japan. METHODS: We conducted a retrospective cohort study using data from the JMDC Claims Database. We identified all adult patients aged ≥18 years who underwent cardiac catheterization between April 2012 and October 2021. We investigated patient characteristics and clinical outcomes (i.e. all-cause mortality, stroke, acute kidney injury, bleeding, vascular complications, percutaneous coronary intervention, and total healthcare costs) within 2, 7, and 30 days between patients who underwent outpatient cardiac catheterization (outpatient group) and those who underwent inpatient cardiac catheterization (inpatient group). RESULTS: Of the 37,002 eligible patients (57.6 % <60 years old, and 80.2 % male), 1853 (5.01 %) underwent outpatient cardiac catheterization. The outpatient group was more likely to be male, have more comorbidities, and be performed at non-university hospitals than the inpatient group. The proportion of patients who underwent right heart catheterization and imaging was lower in the outpatient group. There were no significant differences in 7-day major complications between the two groups (all-cause mortality, 0.0 % versus 0.0 %, p = 0.57; acute kidney injury, 0.0 % versus 0.1 %, p = 0.10, bleeding, 0.5 % versus 0.9 %, p = 0.052; vascular complication, 0.0 % versus 0.1 %, p = 0.23, respectively). The 30-day total healthcare costs were lower in the outpatient group than in the inpatient group (mean 3212 US dollars versus 3955 US dollars, p = 0.003). CONCLUSIONS: Approximately 5 % of cardiac catheterizations were performed in an outpatient setting. Given the low adverse event risk observed in this study, it may be a reasonable option to widen outpatient cardiac catheterization to include potential populations in Japan, warranting further studies.

Three-Year Outcomes of Balloon-Expandable Transcatheter Aortic Valve Implantation According to Annular Size.

Data on the association between annular size and transcatheter aortic valve implantation (TAVI) outcomes beyond 1 year are limited. The present study assessed the association between the aortic annulus size and TAVI clinical and hemodynamic outcomes at 3 years of follow-up. Patients were classified according to the aortic annulus size as having small, intermediate, and large annuli (size <400, 400 to 574, and ≥575 mm2, respectively). The co-primary endpoints were all-cause mortality and heart failure hospitalization. Further, the changes in hemodynamic outcomes over the follow-up period (median 37, interquartile range: 26 to 45 months) were assessed. The present analysis included 850 patients, with 182 patients (21.4%), 538 patients (63.3%), and 130 patients (15.3%) in the small, intermediate, and large-sized aortic annulus groups, respectively. The groups had comparable age and pre-TAVI pressure gradients; however, patients with small annuli had higher Society of Thoracic Surgeons risk scores. Adjusted Cox regression analysis showed that compared to patients with intermediate-sized annuli, patients with small and large annuli had similar all-cause mortality (hazard ratio [HR] = 1.11, 95% confidence interval [CI] 0.72 to 1.69 and HR = 0.74, 95% CI 0.48 to 1.16, respectively) and heart failure hospitalization rates (HR = 0.96, 95% CI 0.55 to 1.69 and HR = 1.26, 95% CI 0.73 to 2.17, respectively). However, patients with small annuli had consistently higher mean and peak pressure gradients and a higher risk of patient-prosthesis mismatch. The risks of moderate-to-severe regurgitation and structural valve deterioration were similar between the three groups. In conclusion, although patients with small annuli had higher transvalvular gradients, there was no significant association between the aortic annulus size and TAVI clinical outcomes at 3 years of follow-up. Future studies should compare the performance of transcatheter valve types in patients with different aortic annulus sizes.

A study of takotsubo syndrome over 9 years at the Tokyo Cardiovascular Care Unit Network Registry.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiovascular disease with clinical manifestations similar to those of acute myocardial infarction (AMI), and TTS sometimes occurs just after catastrophes. Large-scale studies of TTS in Japan are scarce, so we examined data over 9 years from Tokyo metropolitan acute cardiovascular care hospital network registry. METHODS: A total of 1626 patients were diagnosed with TTS between 2010 and 2018 at Tokyo Cardiovascular Care Unit Network facilities, and data from all these patients were analyzed. We investigated annual and monthly captured incidence of TTS, temporal trend of the captured incidence proportion of TTS versus AMI, the occurrence of TTS on the day of the great earthquake, and we elucidated the prognostic factors for in-hospital death. RESULTS: The annual incidence proportion of TTS versus AMI increased from 2.3 % to 4.5 % (p < 0.001) over 9 years. The mean TTS patient age was 74.4 years: the peak incidence of TTS was at 80 to 84 years of age for both male and female; females accounted for 78.5 % of patients. The monthly variation of the incidence of TTS was found (p = 0.009). In 2011, a total of 137 cases of TTS occurred, with as many as 6 occurring on March 11, the day of the Great East Japan Earthquake. There was a definable trigger for TTS in 64 % (physical: 36 %; emotional: 27 %; others: 2 %). All-cause in-hospital mortality was 5.3 % and was higher in males than in females (10.3 % vs 3.9 %; p < 0.001). Non-cardiac causes accounted for 62 % of in-hospital mortality. Factors at presentation that were associated with in-hospital all-cause mortality were male sex, low body mass index, and a high C-reactive protein level. CONCLUSIONS: This study elucidated the clinical features, in-hospital outcomes, and their attributed factors in patients with TTS in real-world clinical practice in Japan.