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 and 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% confidence interval [CI] = 1.54-2.73) and mild/moderate underweight (1.26; 95% CI = 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 >20.0 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.

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 Predictors of Stroke After Transcatheter Aortic Valve Replacement in the Cerebral Protection Device Era.

BACKGROUND: Studies have shown inconclusive results on the effectiveness of cerebral protection devices (CPDs) with transcatheter aortic valve replacement. We aimed to analyze the national statistics on stroke and other outcomes with CPD use. METHODS AND RESULTS: The Nationwide Readmissions Database (2017-2020) was queried to obtain data on patients undergoing transcatheter aortic valve replacement. Outcomes were compared between patients with a CPD and patients without a CPD. Of 271 804 patients undergoing transcatheter aortic valve replacement, CPD was used in 7.3% of patients. In a multivariable logistic regression analysis, CPD use was not associated with lower overall stroke rates (1.6% versus 1.9% without CPD; odds ratio, 0.95 [95% CI, 0.84-1.07]; P=0.364), but it was significantly associated with lower major stroke rates (1.2% versus 1.5% without CPD; odds ratio, 0.85 [95% CI, 0.74-0.98]; P=0.02). Patients with a CPD also had a shorter length of stay, higher routine discharges to home/self-care (74.9% versus 70.6%), and lower mortality rates (0.7% versus 1.3%). The 30-day (9.6% versus 11.7%) and 180-day (24.6% versus 28.2%) readmission rates were significantly lower in the CPD cohort. Among patients who developed stroke, patients with a CPD had more frequent routine discharges. Prior valve surgery was associated with the highest risk of overall and major stroke. CONCLUSIONS: CPD use during transcatheter aortic valve replacement was not independently associated with a lower risk of overall stroke but was associated with a lower risk of major stroke in a multivariable model. Data from future randomized trials that may offset any potential confounders in our study are required to help identify patients who would benefit from the use of these devices.

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.

Time Course of Left Ventricular Strain Assessment via Cardiovascular Magnetic Resonance Myocardial Feature Tracking in Takotsubo Syndrome.

Background: Although takotsubo syndrome (TTS) is characterized by transient systolic dysfunction of the left ventricle (LV), the time course and mechanism of LV function recovery remain elusive. The aim of this study is to evaluate cardiac functional recovery in TTS via serial cardiac magnetic resonance feature tracking (CMR-FT). Methods: In this Japanese multicenter registry, patients with newly diagnosed TTS were prospectively enrolled. In patients who underwent serial cardiovascular magnetic resonance (CMR) imaging at 1 month and 1 year after the onset, CMR-FT was performed to determine the global circumferential strain (GCS), global radial strain (GRS) and global longitudinal strain (GLS). We compared LV ejection fraction, GCS, GRS and GLS at 1 month and 1 year after the onset of TTS. Results: Eighteen patients underwent CMR imaging in one month and one year after the onset in the present study. LV ejection fraction had already normalized at 1 month after the onset, with no significant difference between 1 month and 1 year (55.8 ± 9.2% vs. 58.9 ± 7.3%, p = 0.09). CMR-FT demonstrated significant improvement in GCS from 1 month to 1 year (-16.7 ± 3.4% vs. -18.5 ± 3.2%, p < 0.01), while there was no significant difference in GRS and GLS between 1 month and year (GRS: 59.6 ± 24.2% vs. 59.4 ± 17.3%, p = 0.95, GLS: -12.8 ± 5.9% vs. -13.8 ± 4.9%, p = 0.42). Conclusions: Serial CMR-FT analysis revealed delayed improvement of GCS compared to GRS and GLS despite of rapid recovery of LV ejection fraction. CMR-FT can detect subtle impairment of LV systolic function during the recovery process in patients with 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.

Utilization and outcomes of aortic valve replacements (from the United States readmissions database).

Study objective: Assess the utilization of aortic valve replacements (AVR). Design: Retrospective analysis of the Nationwide Readmissions Database (2016-2018). Setting: Nationwide. Participants: Heart failure patients with concomitant aortic stenosis (CHF + AS cohort) or aortic stenosis with aortic regurgitation (CHF + AS+AR cohort). Interventions: Transcatheter aortic valve implantation (TAVI), surgical aortic valve replacement (SAVR), no-AVR. Main outcome measures: Utilization of treatment interventions. Results: In the CHF + AS cohort, TAVI, SAVR and no-AVR were done in 9.3 %, 10.8 % and 79.9 % of patients respectively. Similarly, majority of CHF + AS+AR patients were managed with no-AVR (53.2 %). Of patients managed with no-AVR in the first six months of each year, only 7.9 % of CHF + AS and 11.8 % of CHF + AS+AR patients underwent AVR in the subsequent six months of the year. No-AVR patients had worse short-term outcomes in comparison to AVR recipients. Conclusion: More studies are needed to understand the timing, indications and utilization of AVR in this population.

Impact of post-procedural length of stay on short-term outcomes and readmissions after TAVR and MitraClip.

Background: Post-procedural hospital length of stay (P-LOS) is an important determinant of cost-related outcomes. In the present study, we aimed to assess the impact of P-LOS on short-term outcomes after transcatheter aortic valve replacement (TAVR) and MitraClip. Methods: We performed a retrospective cohort study, retrieving data from the National Readmissions Database (NRD) for patients who underwent transfemoral TAVR and MitraClip between January 2014 and December 2017. We employed multivariable logistic regression to evaluate the association between P-LOS and 30-day all-cause mortality and readmissions. Results: A total of 65,726 and 7347 patients underwent TAVR and MitraClip, respectively within the study period. After 30 days of discharge, 13.7% and 15.1% of TAVR and MitraClip patients were readmitted for any reason, while 0.5% and 0.9% died within the readmission hospitalization. A longer P-LOS was associated with an increased risk of 30-day all-cause readmission in both TAVR (OR = 1.027, 95% CI [1.023-1.032]) and MitraClip (OR = 1.025, 95%CI [1.012-1.038]) patients. This finding remained true for patients who developed or did not develop complications after both procedures. In terms of 30-day inhospital mortality, a longer P-LOS was associated with a higher risk in TAVR patients (OR = 1.039, 95%CI [1.028-1.049]), but no increased risk in MitraClip patients (OR = 1.014, 95%CI [0.985-1.044]). Other predictors of 30-day readmission after both procedures included heart failure, post-procedural acute kidney injury, and discharge with disability. Conclusion: The current study shows that shorter P-LOS was associated with reduced risk of short-term readmission after both TAVR and MitraClip and reduced short-term mortality after TAVR (mainly in patients who developed post-procedural complications). Shorter P-LOS is a predictor of readmission and sicker patient group. Patients requiring longer LOS should be followed closely to prevent readmission and enhance better outcomes. Future studies evaluating P-LOS impact on long-term and patient-oriented outcomes are needed.