Impact of osteoporotic risk in men undergoing transcatheter aortic valve replacement: a report from the LAPLACE-TAVI registry.

Low body weight and advanced age are among the best predictors of osteoporosis. Osteoporosis Self-Assessment Tool (OST) values are calculated by a simple formula [(body weight in kilograms - age in years) × 0.2] to identify patients at increased risk of osteoporosis. In our recent single-center study, we demonstrated an association between OST and poor outcomes in postmenopausal women after transcatheter aortic valve replacement (TAVR). We aimed to investigate the impact of osteoporotic risk in men with aortic stenosis who underwent TAVR in a large cohort. In this multi-center study, 1,339 men who underwent TAVR between April 2010 and July 2023 were retrospectively analyzed. Women were excluded from the present study. All patients were deemed appropriate for TAVR after a review by a multidisciplinary team. Baseline characteristics of patients were compared by dividing patients into three tertiles, based on the OST value: ≤ - 6.16, - 6.16 to - 4.14, and - 4.14 < for tertiles 1, 2, and 3, respectively. Primary endpoint was all-cause mortality after TAVR. Tertile 1 (patients with the lowest OST values) included older patients with smaller body mass index, lower hemoglobin and albumin levels. In addition, they had greater clinical frailty scale, slower 5-meter walk test, weaker hand grip strength, and more cognitive impairment, indicating increased frailty. They were more severely symptomatic, with lower ejection fractions, smaller aortic valve areas, and more tricuspid regurgitation than were patients in the other two groups. Multivariate analysis revealed that OST tertiles 3 was associated with decreased risk of all-cause mortality (hazard ratio, 0.66; 95% confidence interval, 0.48-0.90), compared with OST tertile 1 as a reference. For OST tertiles 1, 2, and 3, the estimated 1-year survival rates of all-cause mortality post-TAVR were 83.6% ± 1.9%, 91.1% ± 1.4%, and 93.1% ± 1.3%, respectively, (log-rank, p < 0.001).　In conclusions, in men as same as women, osteoporotic risk assessed by OST values was overlapped with increased frailty. The simple OST formula was useful for predicting all-cause mortality in patients undergoing TAVR in large registry datasets.

Left atrial strain time integral evaluated by two-dimensional speckle tracking predicts left atrial appendage dysfunction in patients with acute ischemic stroke.

Cardioembolic stroke is a serious disease with poor prognosis, whose main embolic source is the left atrial appendage (LAA). Left atrial (LA) strain evaluated by the two-dimensional (2D) speckle tracking technique has been proposed. However, the commonly used peak LA strain reflects only LA reservoir function. The LA strain also includes indicators of the other LA functions, such as booster pump function, which reflects active contraction of the LA. This study aimed to investigate whether a newly developed parameter, the left atrial strain time integral (LASTI), can evaluate LAA dysfunction more accurately in patients with acute stroke. We measured LA strain using a 2D speckle tracking method in 168 patients with acute stroke and 20 age-matched control subjects. LASTI was calculated as the area under the LA strain curve in one cardiac cycle. LAA dysfunction was defined as LAA thrombus and/or severe spontaneous echo contrast by transesophageal echocardiography. LASTI was significantly lower in patients with LAA dysfunction than those without. LASTI was a better correlation with LAA blood flow velocity measured by transesophageal echocardiography than peak LA strain. Multivariate logistic regression analysis showed that LASTI was an independent predictor of LAA dysfunction after adjustment for conventional risk factors. LASTI can be a feasible parameter for predicting LAA dysfunction in patients with acute stroke.

Growth Differentiation Factor-15 and Clinical Outcomes in Lower Extremity Artery Disease.

AIM: Lower extremity artery disease (LEAD) is an increasingly common health problem that is associated with high mortality due to thrombotic and bleeding events. Growth differentiation factor-15 (GDF15), a stress-response cytokine belonging to the transforming growth factor-beta superfamily, is associated with cardiovascular disease and its outcomes. The aim of the present study was to examine the effect of serum GDF15 levels on clinical outcomes in patients with LEAD. METHODS: We measured serum GDF15 levels in 200 patients with LEAD before their initial endovascular therapy. The primary endpoint was the all-cause mortality rate. The secondary endpoints, on the other hand, were thrombotic and bleeding events, such as cerebral infarction, acute coronary syndrome, acute limb ischemia, and Bleeding Academic Research Consortium types 3 and 5. RESULTS: The serum GDF15 levels increased with advancing Fontaine class. Kaplan-Meier analysis revealed that the high-GDF15 group (≥ 2,275 pg/mL) had higher rates of all-cause deaths and thrombotic and bleeding events than the low-GDF15 group (＜2,275 pg/mL). Multivariate Cox proportional-hazards regression analysis revealed that GDF15 was an independent predictor of all-cause mortality and thrombotic and bleeding events after adjusting for confounding risk factors. When the ABC-AF-bleeding score was substituted for GDF15, similar results were obtained. CONCLUSION: Serum GDF15 levels were associated with all-cause mortality and thrombotic and bleeding events in patients with LEAD. Serum GDF15 is a potentially useful marker of clinical outcomes, specifically for tracking thrombotic and bleeding events in patients with LEAD.

Hypokalemia, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear.Methods and Results: We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K+<3.5 mmol/L) and hyperkalemia (K+>5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary ß2-microglobulin to creatinine ratio ≥300 µg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors. CONCLUSIONS: Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

A case of a transcatheter valve-in-valve implantation using balloon expandable valve for failed SOLO SMART stentless bioprosthetic valve.

A 74-year-old man who had undergone surgical aortic valve replacement with the SOLO SMART stentless bioprosthetic valve 25 mm (LivaNova PLC, London, UK) and mitral valve replacement with MOSAIC 29 mm (Medtronic, Minneapolis, USA) 4 years previously was diagnosed with congestive heart failure, and transferred to our hospital. Echocardiography revealed severe aortic regurgitation caused by degraded bioprosthetic valve. He required continuous dobutamine administration to maintain hemodynamics. As a result of heart team discussion, we decided to perform transcatheter valve-in-valve implantation (ViV-TAVI) using balloon expandable valve (Sapien 3, Edwards Lifesciences, Irvine, USA). Since SOLO SMART stentless valve was placed to Valsalva sinus at the supra-annular level with continuous sutures, we planned to anchor TAVI valve 4 mm to the left ventricular side from the bottom of the failed stentless valve. Two pigtail catheters were placed at the bottom of the failed stentless valve leaflet to mark the nadir of stentless valve. After ViV-TAVI, the patient no longer required catecholamine administration and was discharged home one month later. This is the first case of ViV-TAVI using balloon expandable valve for failed SOLO SMART stentless bioprosthetic valve in a Japanese patient. Learning objective: Transcatheter valve-in-valve implantation (ViV-TAVI) for stentless valves is known to be technically challenging due to poor fluoroscopic visibility. Because the SOLO SMART stentless bioprosthetic valve is sutured to the wall of the sinus of Valsalva above the annulus, the landing point of transcatheter heart valve is at a native annulus which is lower than the bottom of the SOLO SMART leaflet. We describe the first Japanese case of ViV-TAVI with balloon expandable valve for the SOLO SMART stentless bioprosthetic valve.

Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry.

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36-3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13-2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06-1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36-2.98),1.37 (95% CI: 0.75-2.48), and 1.13 (95% CI: 0.75-2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men.

Improved cerebral blood flow and hippocampal blood flow in stroke-free patients after catheter ablation of atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is a risk factor for reduced cerebral blood flow (CBF) and cognitive dysfunction, even in stroke-free patients. We aimed to test the hypothesis that CBF and hippocampal blood flow (HBF), measured with arterial spin labeling magnetic resonance imaging (MRI), improve after catheter ablation of AF to achieve sinus rhythm (SR). METHODS: A total of 84 stroke-free patients (63.1 ± 9.1 years; paroxysmal AF, n = 50; non-paroxysmal AF, n = 34) undergoing AF catheter ablation were included. MRI studies were done before, 3 months, and 12 months after the procedure with CBF and HBF measurements. RESULTS: Baseline CBF and HBF values in 50 paroxysmal AF patients were used as controls. Baseline CBF was higher in patients with paroxysmal AF than with non-paroxysmal AF (100 ± 32% vs. 86 ± 28%, p = .04). Patients with non-paroxysmal AF had increased CBF 3 months after AF ablation (86 ± 28% to 99 ± 34%, p = .03). Differences in CBF and HBF were greater in the group with AF restored to SR (p < .01). Both CBF and HBF levels at 12 months were unchanged from the 3 months level. Successful rhythm control by catheter ablation was an independent predictor of an increase in CBF > 17.5%. The Mini-Mental State Examination score improved after ablation (p = .02). CONCLUSION: SR restoration with catheter ablation was associated with improved CBF and HBF at 3 months, maintenance of blood flow, and improved cognitive function at 12 months.

Growth Differentiation Factor-15 and Clinical Outcomes in Japanese Patients With Ischemic Heart Disease.

Background: Despite a reduction in the rate of thrombotic events, ischemic heart disease (IHD) remains a key medical problem associated with high major bleeding and mortality in Asian patients with IHD. Growth differentiation factor (GDF)-15, a stress-response cytokine belonging to the transforming growth factor beta superfamily, is reportedly associated with poor clinical outcomes in Western patients with IHD. However, the clinical significance of GDF-15 in Asian patients with IHD has not yet been fully elucidated. Objectives: The aim of the present study was to examine the impact of serum GDF-15 on clinical outcomes in Japanese patients with IHD. Methods: Serum GDF-15 levels were evaluated in 632 consecutive patients with IHD. All patients were followed up for a median period of 2.8 years. The primary endpoint was the all-cause mortality rate. Secondary endpoints were major adverse cardiovascular events (MACE), heart failure (HF)-related rehospitalization, bleeding, and thrombotic events. Results: Serum GDF-15 levels were elevated in acute coronary syndrome, severe coronary artery disease, and the major Japanese version of the high bleeding risk criteria. Multivariate Cox proportional hazards regression analysis demonstrated that GDF-15 was an independent predictor of all-cause mortality, MACE, HF-related rehospitalizations, and bleeding events after adjusting for confounding risk factors but not for thrombotic events. Adding GDF-15 to risk factors significantly improved the net reclassification index and integrated discrimination improvement for all-cause deaths, MACE, HF-related rehospitalization, and bleeding events. Conclusions: Serum GDF-15 could be a feasible marker for major bleeding and adverse clinical outcomes in Japanese patients with IHD.

Impact of estimated plasma volume status on clinical outcomes in patients with lower extremity artery disease who underwent endovascular therapy.

Lower extremity artery disease (LEAD) is an arterial occlusive disease associated with high morbidity and mortality. Estimated plasma volume status (ePVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular diseases. However, the impact of ePVS on the clinical outcomes of patients with LEAD remains unclear. We calculated ePVS using two different formulas, Kaplan-Hakim (KH-ePVS) and Duarte (D-ePVS), in 288 patients (mean age, 73 years; 77% male) with LEAD who underwent the first endovascular therapy (EVT), and prospectively followed them up between 2014 and 2019. All patients were divided into two groups based on the median ePVS values. The primary endpoints were composite events, including all-cause death and major adverse limb events (death/MALE). The median follow-up duration was 672 days. There were 183, 40 and 65 patients in Fontaine classes II, III, and IV, respectively. The median KH-ePVS and D-ePVS was 5.96 and 5.09, respectively. The ePVS significantly increased with advancing Fontaine classes. Kaplan-Meier analysis demonstrated that the high ePVS group had higher rates of death/MALE than the low ePVS group. Multivariate Cox proportional hazard analysis revealed that each ePVS was an independent predictor for death/MALE after adjusting for confounding risk factors. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. ePVS was associated with LEAD severity and clinical outcomes, suggesting that ePVS could be an additional risk factor for death/MALE in patients with LEAD who underwent EVT. We demonstrated that the association between ePVS and the clinical outcomes of patients with LEAD. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. LEAD lower extremity artery disease, MALE major adverse limb events, PVS plasma volume status.

Renal tubular damage and clinical outcome in heart failure with preserved ejection fraction and chronic kidney disease.

AIMS: Despite advances in heart failure (HF) treatment, HF with preserved ejection fraction (HFpEF) remains a health problem with a high mortality rate. HFpEF is composed of diverse phenogroups, of which patients with concomitant renal impairment have worse outcomes. Renal tubular damage (RTD) is associated with the development of HF and chronic kidney disease (CKD). However, the impact of RTD on HF progression in patients with HFpEF and CKD remains unclear. The aim of the present study was to examine whether RTD could predict HF-related events in patients with HFpEF and CKD. METHODS AND RESULTS: We measured RTD markers, such as urinary ß2 -microglobulin to creatinine ratio (UBCR) and N-acetyl-ß-d-glucosamidase (NAG) level, in 319 consecutive patients with HFpEF and CKD who were hospitalized for acute HF (49% females, mean age 76 ± 12). Based on previous reports, high UBCR and high NAG levels were defined as UBCR ≥300 µg/gCr and NAG >14.2 U/gCr, respectively. There were 91 HF-related events, defined as HF hospitalizations or HF deaths, during the median follow-up period of 5.2 years. The prevalence of high UBCR increased with advancing New York Heart Association functional class and albuminuria. Kaplan-Meier analysis demonstrated that patients with high UBCR had more HF-related events than those with normal or low UBCR. Multivariate Cox proportional hazards regression analyses demonstrated that high UBCR, but not high NAG level, was an independent predictor of HF-related events after adjusting for confounding risk factors in patients with HFpEF and CKD (hazard ratio, 2.60; 95% confidence interval, 1.52-4.72; P = 0.0009). UBCR significantly improved the C-statistic, with a significant net reclassification index and integrated discrimination improvement (0.738 vs. 0.684; P = 0.0244). CONCLUSION: RTD, as assessed by a high UBCR, was associated with the severity and clinical outcomes of HFpEF and CKD, indicating that it could be a feasible marker for HF progression.

Discrepancy between invasive and echocardiographic transvalvular gradient after TAVI: Insights from the LAPLACE-TAVI registry.

BACKGROUND: Echocardiography-based transvalvular mean pressure gradient (ECHO-mPG) used to assess the forward valve function and structural valve deterioration could overestimate the true pressure gradient. This study evaluated the discrepancy between invasive and ECHO-mPG after transcatheter aortic valve implantation (TAVI) with respective valve type and size, its impact on a device success criterion, and predictors of a pressure discrepancy. METHODS: We analyzed 645 patients registered in a multicenter TAVI registry (balloon-expandable valve [BEV]: 500; self-expandable valve [SEV]: 145). The invasive transvalvular mPG was measured after valve implantation using two Pigtail catheters (CATH-mPG), while the ECHO-mPG was measured within 48 h after TAVI. Pressure recovery (PR) was calculated using the following formula: ECHO-mPG × effective orifice area (EOA)/ascending aortic area (AoA) × (1 - EOA/AoA). RESULTS: ECHO-mPG was weakly correlated with (r = 0.29, p < 0.0001), and consistently overestimated CATH-mPG in both BEV and SEV, and respective valve sizes. The magnitude of the discrepancy was larger for BEV than SEV (p < 0.001) and smaller valves (p < 0.001). After the correction of PR using the above formula, the pressure discrepancy remained for BEV (p < 0.001) but not SEV (p = 0.10). The proportion of patients with an ECHO-mPG > 20 mmHg decreased from 7.0% to 1.6% after correction (p < 0.0001). Among the baseline and procedural variables, post-procedural ejection fraction, BEV versus SEV, and smaller valves were associated with a larger discrepancy in mPG. CONCLUSIONS: ECHO-mPG could be overestimated after TAVI, especially in patients with a smaller BEV. A higher ejection fraction, BEV, and smaller valves were predictors of a pressure discrepancy between CATH- and ECHO-mPG.

Impact of periprocedural bleeding on mid-term outcome in nonagenarians who underwent transcatheter aortic valve implantation: insights from LAPLACE registry.

Data from several recent studies have demonstrated the safety and efficacy of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) even in nonagenarians. However, the impact of periprocedural bleeding following TAVI on their outcome remains unclear. In the aLliAnce for exPloring cLinical prospects of AortiC valvE disease (LAPLACE) registry, we compared outcomes between the bleeding and no-bleeding groups among 1953 patients < 90 years old (mean age, 83.0 ± 4.6 years old) and 316 nonagenarians (mean age, 91.7 ± 1.9 years old) who underwent TAVI with a median follow-up period of 628 days. The group with any periprocedural bleeding showed a higher 30-day mortality than the no-bleeding group in patients < 90 years old (3.3% vs. 0.5%, p = 0.001) and nonagenarians (7.9% vs. 0.7%, p = 0.001). In patients < 90 years old, severe periprocedural bleeding (n = 85) was associated with a higher mid-term all-cause mortality rate than no severe bleeding (n = 1,868), even after adjusting for covariates (hazard ratio [HR], 1.994; 95% confidence interval [CI] 1.287-2.937; p = 0.002). On the other hand, in nonagenarians, any periprocedural bleeding (n = 38) was associated with a higher mid-term cardiovascular (CV) mortality rate (21.1% vs. 4.3%, log-rank p = 0.014) than no bleeding (n = 278), even after adjusting for covariates (HR, 3.104; 95% CI 1.140-8.449; p = 0.027). In conclusion, any periprocedural bleeding after TAVI was associated with mid-term CV mortality in nonagenarians, whereas severe bleeding was associated with mid-term all-cause mortality in patients < 90 years old.

Midterm Outcomes of Underweight Patients Undergoing Transcatheter Aortic Valve Implantation: Insight From the LAPLACE-TAVR Registry.

Background: Obesity is a major risk factor for cardiovascular disease; however, a paradoxical effect of obesity has been reported in patients with heart failure or myocardial infarction. Although several studies have suggested the same obesity paradox in patients undergoing transcatheter aortic valve replacement (TAVR), they included a limited number of underweight patients. Objectives: This study aimed to clarify the effect of being underweight on TAVR outcomes. Methods: We retrospectively analyzed 1,693 consecutive patients undergoing TAVR between 2010 and 2020. The patients were categorized according to body mass index: underweight (<18.5 kg/m2; n = 242), normal weight (18.5 to 25 kg/m2; n = 1,055), and overweight (>25 kg/m2; n = 396). We compared midterm outcomes after TAVR among the 3 groups; all clinical events were in accordance with the Valve Academic Research Consortium-2 criteria. Results: Underweight patients were more likely to be women and have severe heart failure symptoms, peripheral artery disease, anemia, hypoalbuminemia, and pulmonary dysfunction. They also had lower ejection fractions, smaller aortic valve areas, and higher surgical risk scores. Device failure, life-threatening bleeding, major vascular complications, and 30-day mortality occurred more frequently in underweight patients. The midterm survival rate of the underweight group was inferior to those of the other 2 groups (P < 0.0001; average follow-up, 717 days). In the multivariate analysis, underweight was associated with noncardiovascular mortality (HR: 1.78; 95% CI: 1.16-2.75) but not cardiovascular mortality (HR: 1.28; 95% CI: 0.58-1.88) after TAVR. Conclusions: Underweight patients had a worse midterm prognosis, demonstrating the obesity paradox in this TAVR population. (Outcomes of transcatheter aortic valve implantation in Japanese patients with aortic stenosis: multi-center registry; UMIN000031133).

Growth Differentiation Factor 15 and Clinical Outcomes in Japanese Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is an increasing health problem associated with a high mortality rate. Growth differentiation factor (GDF) 15, a stress response cytokine belonging to the transforming growth factor-ß superfamily, is associated with poor clinical outcomes in a broad spectrum of cardiovascular diseases. However, the prognostic usefulness of GDF15 in Japanese patients with HF remains unclear.Methods and Results: We measured serum concentrations of GDF15 and B-type natriuretic peptide (BNP) in 1,201 patients with HF. All patients were prospectively followed for a median period of 1,309 days. In all, 319 HF-related events and 187 all-cause deaths occurred during the follow-up period. Kaplan-Meier analysis demonstrated that, among GDF15 tertiles, the highest tertile group had the greatest risk of HF-related events and all-cause mortality. Multivariate Cox proportional hazard regression analysis demonstrated that the serum GDF15 concentration was an independent predictor of HF-related events and all-cause deaths after adjusting for confounding risk factors. Serum GDF15 improved the prediction capacity for all-cause deaths and HF-related events with a significant net reclassification index and integrated discrimination improvement. Subgroup analysis in patients with HF with preserved ejection fraction also showed the prognostic usefulness of GDF15. CONCLUSIONS: Serum GDF15 concentrations were associated with HF severity and clinical outcomes, indicating that GDF15 could provide additional clinical information to track the health status of patients with HF.

Prognostic impact of plasma xanthine oxidoreductase activity in patients with heart failure with atrial fibrillation.

BACKGROUND: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme for uric acid (UA) production and plays an important role in generating reactive oxygen species (ROS). Overproduction of ROS is reported to contribute to the pathophysiology of atrial fibrillation (AF), however, the prognostic impact of plasma XOR activity in patients with heart failure (HF) with AF is undetermined. METHODS: We measured plasma XOR activity in 475 HF patients, including those with sinus rhythm (HF-SR, n = 211), and those with AF (HF-AF, n = 264). The type of AF included paroxysmal (n = 128) and persistent (n = 136) AF. All patients were prospectively followed up for a median period of 804 days. RESULTS: HF-AF patients had significantly higher plasma XOR activity and serum UA levels compared with HF-SR patients. Both plasma XOR activity and serum UA levels were higher in patients with persistent AF than in those with SR and with paroxysmal AF. Multivariate linear regression analysis showed that persistent AF was independently associated with increased XOR activity. During the follow-up period, there were 79 major adverse cardiovascular events (MACEs). HF-AF patients with MACEs had higher plasma XOR activity compared with those without MACEs, while there were no significant differences in serum UA levels. Multivariate Cox proportional analysis showed that high XOR activity was an independent risk factor for MACEs after adjustment for confounding factors. Kaplan-Meier analysis revealed that the high XOR activity group had a higher risk of MACEs than the low XOR activity group. The prediction model was significantly improved by the addition of XOR activity to the basic predictors. CONCLUSIONS: HF-AF patients had significantly higher plasma XOR activity compared with HF-SR patients. Plasma XOR activity proved to be a reliable indicator for MACEs in HF-AF patients.

Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry.

Pulmonary hypertension (PH) is a common complication of aortic stenosis (AS). Despite the established association between PH and poor outcomes in patients with AS, the prognostic implication of a change in PH after transcatheter aortic valve implantation (TAVI) has been rarely evaluated. This study analyzed a prospective multi-center TAVI registry database involving six Japanese centers and used the transtricuspid pressure gradient (TRPG) obtained by echocardiography to estimate pulmonary artery systolic pressure. The participants (n = 2056) were first divided into two groups by TRPG before TAVI, a PH (−) group (TRPG < 30 mmHg) (n = 1407, 61.9%) and a PH (+) group (TRPG ≥ 30 mmHg) (n = 649, 28.6%). Next, by TRPG after (4.1 ± 5.3 days) TAVI, the PH (+) group was further subdivided into two groups, Recovered PH (TRPG < 30 mmHg, n = 253) and Persistent PH (TRPG after TAVI ≥ 30 mmHg, n = 396). The median follow-up duration was 1.8 years. The primary and secondary endpoints were the composite and each of cardiovascular (CV) death and heart failure hospitalization, respectively. Unadjusted Kaplan-Meier estimates with log-rank comparisons showed significantly higher cumulative incidences of primary and secondary endpoints in the Persistent PH group compared to other groups. Moreover, adjusted multivariate Cox-proportional hazard analyses showed that a decreased (−10 mmHg) TRPG after TAVI was linearly associated with a reduced risk of the primary endpoint (hazard ratio (HR): 0.76, 95% confidence interval (CI): 0.64−0.90, p = 0.0020). The findings in the present study indicate that the recovery of PH may partly contributes to the prognostic benefit of TAVI procedure in patients with AS and elevated pulmonary artery systolic pressure.

Prognostic Impact of Renal Dysfunction at 1-Year Follow-Up on Clinical Outcomes After Percutaneous Coronary Intervention.

AIMS: Renal dysfunction is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of mid-term changes in renal dysfunction status remains unclear. This study aimed to investigate the impact of mid-term changes in renal dysfunction status on long-term clinical outcomes in CAD patients who underwent percutaneous coronary intervention (PCI). METHODS: We enrolled 382 consecutive patients with CAD who underwent PCI. Renal dysfunction was defined as a reduced estimated glomerular filtration rate (eGFR) of ＜60 mL/min/1.73m2. Renal dysfunction status was evaluated at baseline and 1-year follow-up after PCI. We divided the study population into three groups: persistent renal dysfunction, new-onset renal dysfunction, and no or improved renal dysfunction at 1-year follow-up as compared with on baseline. The endpoints of this study were composite events, including all-cause death, acute coronary syndrome, target vessel revascularization, and stroke. RESULTS: At baseline, renal dysfunction was observed in 77 patients (20%). At the 1-year follow-up, new-onset renal dysfunction was observed in 46 patients (12%), and 59 patients (15%) had persistent renal dysfunction. Kaplan-Meier analysis revealed a significantly higher event rate in patients with persistent renal dysfunction and new-onset renal dysfunction (log-rank test, P=0.0003). In the multivariate Cox proportional hazards analysis, persistent renal dysfunction and new-onset renal dysfunction were independently associated with composite events after adjusting for confounding factors (adjusted hazard ratios 4.08 and 2.64, 95% confidence intervals 1.72-9.57 and 1.03-6.31, P=0.0016, P=0.0045, respectively). CONCLUSION: Persistent and new-onset renal dysfunction at 1-year follow-up were associated with unfavorable outcomes in patients with CAD who underwent PCI.

Association of malnutrition with renal dysfunction and clinical outcome in patients with heart failure.

Malnutrition, glomerular damage (GD), and renal tubular damage (RTD) are common morbidities associated with poor clinical outcomes in heart failure (HF) patients. However, the association between malnutrition and renal dysfunction and its impact on clinical outcomes in HF patients have not yet been fully elucidated. We assessed the nutritional status and renal function of 1061 consecutive HF patients. Malnutrition, GD, and RTD were defined as a controlling nutritional status (CONUT) score of ≥ 5, reduced eGFR or microalbuminuria, and levels of N-acetyl-beta-D-glucosamidase of > 14.2 U/gCr according to previous reports, respectively. Patients with RTD had a higher CONUT score and a lower prognostic nutritional index and geriatric nutritional risk index than those without. Multivariate logistic analysis demonstrated that RTD, but not GD, was significantly associated with malnutrition. There were 360 cardiac events during the median follow-up period of 688 days. Multivariate Cox proportional hazard regression analysis demonstrated that comorbid malnutrition and renal dysfunction, rather than simple malnutrition, were significantly associated with cardiac events in HF patients. We found a close relationship between malnutrition and renal dysfunction in HF patients. Comorbid malnutrition and renal dysfunction were risk factors for cardiac events in HF patients, suggesting the importance of managing and treating these.

Impact of Modified H2FPEF Score on Chronic Limb-Threatening Ischemia in Patients With Lower Extremity Artery Disease Who Underwent Endovascular Therapy.

Background: Lower extremity artery disease (LEAD) is an arterial occlusive disease characterized by an insufficient blood supply to the lower limb arteries. The H2FPEF score, comprising Heavy, Hypertensive, atrial Fibrillation, Pulmonary hypertension, Elder, and Filling pressure, has been developed to identify patients at high risk of heart failure (HF) with preserved ejection fraction. This study assessed the impact of modified H2FPEF scores on chronic limb-threatening ischemia (CLTI) in patients with LEAD. Methods and Results: This study was a prospective observational study. Because the definition of obesity differs by race, we calculated the modified H2FPEF score using a body mass index >25 kg/m2 to define obesity in 293 patients with LEAD who underwent first endovascular therapy. The primary endpoints were newly developed and recurrent CLTI. The secondary endpoint was a composite of events, including mortality and rehospitalization due to worsening HF and/or CLTI. The modified H2FPEF score increased significantly with advancing Fontaine classes. Multivariate Cox proportional hazard analysis revealed that the modified H2FPEF score was an independent predictor of newly developed and recurrent CLTI and composite events. The net reclassification index and integrated discrimination improvement were significantly improved by adding the modified H2FPEF score to the basic predictors. Conclusions: The modified H2FPEF score was associated with LEAD severity and future CLTI development, suggesting that it could be a feasible marker for patients with LEAD.

Left Atrial Filling Time Index (LAFTI) Evaluated by 2D Speckle Tracking Echocardiography Predicts Poor Cardiac Prognosis in Patients with Heart Failure.

Left atrial (LA) dysfunction is known to be a more sensitive prognostic marker than left ventricular (LV) dysfunction in patients with heart failure (HF). Persistent LA overload increases LA stiffness which impairs LA relaxation. The aim of this study was to investigate whether LA filling time is associated with clinical outcomes in patients with HF. Two-dimensional speckle tracking echocardiography (2DSTE) was performed at discharge, to measure LA and LV strain in 179 HF patients admitted to our hospital. The LA filling time index (LAFTI) was defined as the time from onset of the R wave to the peak LA systolic strain divided by the R-R interval. All patients were prospectively followed with cardiac events including cardiac death and rehospitalization for HF. There were 64 cardiac events during a median follow-up period of 451 days. There were no significant differences in heart rate, severity of HF at discharge, etiology of HF, severity of mitral regurgitation, or LV global longitudinal strain between the cardiac event group and no cardiac event group. Patients with cardiac events had significantly higher levels of brain natriuretic peptide (BNP), ratio of the E wave to e' (E/e'), left atrial volume index (LAVI), and lower LAFTI than those without. Kaplan-Meier analysis showed that patients with lower LAFTI were associated with higher cardiac event rates. Multivariate Cox hazard analysis showed that LAFTI was independently associated with the cardiac events after adjustment for confounding factors. In conclusion, LAFTI is a feasible predictor for cardiac events in patients with HF.