HFpEF as systemic disease, insight from a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in HFpEF patients.

Systemic inflammation and reciprocal organ interactions are associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, the clinical value, especially the diagnositc prediction power of inflammation and extra-cardiac organ dysfunction for HfpEF is not explored. In this cross-sectional study, 1808 hospitalized patients from January 2014 to June 2022 in ChiHFpEF cohort were totally enrolled according to inclusion and exclusion criteria. A diagnostic model with markers from routine blood test as well as liver and renal dysfunction for HFpEF was developed using data from ChiHFpEF-cohort by logistic regression and assessed by receiver operating characteristic curve (ROC) and Brier score. Then, the model was validated by the tenfold cross-validation and presented as nomogram and a web-based online risk calculator as well. Multivariate and LASSO regression analysis revealed that age, hemoglobin, neutrophil to lymphocyte ratio, AST/ALT ratio, creatinine, uric acid, atrial fibrillation, and pulmonary hypertension were associated with HFpEF. The predictive model exhibited reasonably accurate discrimination (ROC, 0.753, 95% CI 0.732-0.772) and calibration (Brier score was 0.200). Subsequent internal validation showed good discrimination and calibration (AUC = 0.750, Brier score was 0.202). In additoin to participating in pathophysiology of HFpEF, inflammation and multi-organ interactions have diagnostic prediction value for HFpEF. Screening and optimizing biomarkers of inflammation and multi-organ interactions stand for a new field to improve noninvasive diagnostic tool for HFpEF.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension.Methods and Results: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study.

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

Involvement of pyroptosis pathway in epicardial adipose tissue - myocardium axis in experimental heart failure with preserved ejection fraction.

Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. CONCLUSION: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF.

The Impact of Renal Denervation on the Progression of Heart Failure in a Canine Model Induced by Right Ventricular Rapid Pacing.

Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson's trichrome staining and the expression of transforming growth factor-ß1 (TGF-ß1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin-angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.

The Role of Angle in the Evaluation of Ablation Accuracy in Pulmonary Vein Isolation Navigated by Image Integration.

BACKGROUND: The conventional index for ablation accuracy is to compare the distance between mapping points with and without treatment by using image integration. We attempted to quantitatively evaluate the role of angle as an index in the ablation accuracy in patients with atrial fibrillation (AF). METHODS: A total of 48 patients with AF were included in the present study. Virtual fluoroscopy planes were predicted by pulmonary vein (PV) angiography, and the standard image planes were defined on the basis of the computed tomography images. Ablations were performed, guided by image integration; and the ablation planes were defined by the actual ablation rings. The predicted angle (distance) was defined as the angle (distance) between the fluoroscopy (predicted) plane and image (standard) plane, whereas the actual angle (distance) was defined as the angle (distance) between the ablation (actual) planes and the image (standard) planes. RESULTS: We found that all actual angles were significantly smaller than the predicted angles (P <.05), but only the actual distances in the left PV, right inferior PV, right superior PV, and right PV were significantly smaller; the distances in the left inferior PV and left superior PV were not significantly different (P >.05). CONCLUSION: Our finding indicates that both the angle and the distance can be significantly reduced by navigation with image integration, but that the angle exhibited better sensitivity than the conventional index of distance. We suggest that the angle should be considered as a new index for ablation accuracy.

Ultrasound targeted microbubble destruction promotes angiogenesis and heart function by inducing myocardial microenvironment change.

The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p < 0.01), and the expression of interleukin-1ß (IL-1ß) in the 1.5 W/cm(2) group was increased twofold over the 1.0 W/cm(2) group, whereas the 0.5 W/cm(2) group experienced no significant changes. UTMD at 1.0 W/cm(2) was performed as previously described before mesenchymal stem cell (MSC) transplantation. Myocardial perfusion, angiogenesis and heart function were investigated before and 1 month after MSC transplantation. Coronary angiography and 99mTc-tetrofosmin scintigraphy revealed that myocardial perfusion was markedly improved after UTMD + MSCs treatment (p < 0.05). At echocardiographic analysis, heart function and the wall motion score index were significantly improved by UTMD + MSCs treatment compared with MSCs or UTMD alone and the control. In a canine model of myocardial infarction, therapeutic effects were markedly enhanced by MSC transplantation after the myocardial micro-environmental changes induced by UTMD; therefore, this novel method may be useful as an efficient approach for cellular therapy.

Targeted delivery of bone mesenchymal stem cells by ultrasound destruction of microbubbles promotes kidney recovery in acute kidney injury.

The aim of the present study was to explore whether ultrasound microbubble destruction augments site-targeted engraftment of bone marrow mesenchymal stem cells (BM-MSCs) to kidney tissue and promotes recovery of the kidney in acute kidney injury (AKI) in rats. AKI was induced by the subcutaneous injection of mercuric chloride (HgCl2). Forty Sprague-Dawley (SD) rats were randomly divided into the following groups after the establishment of rat models of AKI (n = 10): (1) Model group alone (control group); (2) 1.0 W/cm² ultrasound (US) + microbubble (MB) (US/MB group); (3) MSCs group; and (4) 1.0 W/cm² US+MB + MSCs group (US/MB + MSCs group). The number of 4',6-diamidino-2-phenylindole (DAPI) labelled MSCs was evaluated by fluorescence microscopy and real-time polymerase chain reaction (RT-PCR) and Western blotting and histological examination were performed 7 days after MSCs transplantation. It was observed via fluorescence microscopy that the number of DAPI-labelled MSCs in the kidney for the US/MB + MSCs group was significantly more than the MSCs group (p < 0.05). The results from RT-PCR revealed that the US/MB and US/MB + MSCs groups markedly increased the level of inter-cellular adhesion molecule 1 (ICAM-1) messenger ribonucleic acid (mRNA) compared with the control group and the MSCs group (p < 0.05). Western blot analysis showed that the expression of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) in the US/MB + MSCs group were markedly increased compared with the all other groups (p < 0.01). The extent of tubular necrosis and dilation was significantly milder in the US/MB + MSCs group (acoustic exposure conditions: 5s at 1 MHz and 1.0 W/cm² with a 5s pause, totalling 60 s) than the all other groups (p < 0.05). Microbubble destruction by 1.0 W/cm² ultrasound can promote both the homing of BM-MSCs to kidney tissue and the recovery of the kidney in AKI in rats.

One-year clinical outcome of a randomized trial of polymer-free paclitaxel-eluting stents versus biodegradable polymer-based rapamycin-eluting stents in patients with coronary heart disease.

BACKGROUND: More widespread use of drug-eluting stents (DES) to treat coronary heart disease (CHD) has recently generated more attention to thrombosis, which was relative to the polymer. Polymer-free and biodegradable polymer-based stents are more frequently studied, but their efficacy on preventing detrimental clinical events is unclear. METHODS AND RESULTS: To assess whether polymer-free paclitaxel-eluting stent (YINYI stent) was noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents (EXCEL stent) in preventing detrimental clinical cardiovascular events, a total of 167 consecutive CHD patients requiring DES implantation were randomly divided into the YINYI group (n = 82) and the EXCEL group (n = 85). The primary end-point was major adverse cardiac events (MACE). The secondary end-points included stent thrombosis events, all-cause mortality, and rehospitalization. The study was designed to test the noninferiority or equivalence of the YINYI stent compared with the EXCEL stent with respect to one-year MACE according to a noninferiority or equivalence margin of 0.1. One-year MACE was 6.10% in the YINYI group versus 5.88% in the EXCEL group. The lower limit of the one-sided 95% confidence interval was -0.0582 (P = 0.002 from the test for noninferiority). The 95% confidence interval for the equivalence test was [-0.0698, 0.0742] (P1 =0.004 and P2 =0.007 from 2 times the 1-sided test for equivalence). There was no statistically significant difference in thrombosis events, all-cause death, and rehospitalization (all P > 0.05). CONCLUSIONS: In this small randomized trial, polymer-free paclitaxel-eluting stents appear to be noninferior or equivalent to biodegradable polymer-based rapamycin-eluting stents.

[Predict value of clinical risk score, thrombolysis in myocardial infarction flow grade and combined clinical risk score plus TIMI flow on outcome evaluation of patients with acute coronary syndrome].

OBJECTIVE: To compare the prognostic value of clinical risk score and thrombolysis in myocardial infarction (TIMI) flow grade alone or combined on outcome of acute coronary syndrome (ACS). METHODS: A total of 206 eligible patients [135 males, mean age (67.57 +/- 9.88) years] were enrolled. The primary endpoints included cardiac death and non-cardiac death. The secondary endpoints included non-fatal stroke, reinfarction, heart failure and recurrent angina. Receiver operating characteristic curve (ROC) established by using different endpoints and clinical risk score, TIMI flow grade or combined risk scores. The prognostic value for different endpoint expressed as the area under the curve (AUC). RESULTS: Eleven patients lost during the (11.41 +/- 5.33) months follow up and data were available for 195 patients, 8 patients reached the primary endpoints, and 17 patients reached the secondary end-points at the end of follow up. The AUC was 0.67 (95% CI = 0.557 approximately 0.786), P = 0.006; 0.68 (95% CI = 0.557 approximately 0.786), P = 0.004 and 0.730 (95% CI = 0.691 approximately 0.815), P < 0.001, respectively for clinical risk score, TIMI flow grade and the combined risk score respectively. There were no significant differences among clinical risk score, TIMI flow grade and combined risk score (all P > 0.05) for AUC and for primary end point and the secondary end point. CONCLUSION: The result from this study suggests that the efficacy of predicting the total events based on clinical risk score, TIMI flow grade and combined risk score was similar.

[Chronic effects on the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation treated with amiodarone, segmental pulmonary vein ablation, or amiodarone plus losartan: a prospective cohort study].

OBJECTIVE: This study was designed to compare clinical efficacy of segmental pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF). METHODS: Patients with lone PAF were treated with amiodarone alone (A, n = 52), segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12 months follow-up period. RESULTS: During follow-up, AF was documented in 24 patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated a significant equally reduction in AF recurrence in SPVI and AL groups (P = 0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A group. The hazard ratio for AF recurrence in patients treated with SPVI and amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46 (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in AL group, P > 0.05). CONCLUSION: The results of this study suggest that the segmental pulmonary vein isolation and amiodarone plus losartan are superior to amiodarone alone for preventing AF recurrence in patients with lone PAF.

Relationship between myocardial ultrasonic integrated backscatter and mitochondria of the myocardium in dogs.

OBJECTIVE: This study aimed to explore the relationship between integrated backscatter (IBS) and mitochondria in arrested myocardium. METHODS: Twelve open-chest dogs were randomly divided into two groups: one group with cardiac arrest in systole and the other with cardiac arrest in diastole. IBS images at parasternal papillary muscle short-axis view were stored at different time frames (0, 30, and 60 min after cardiac arrest). The values of ultrasonic IBS were obtained using the acoustic densitometry technique. After ultrasound examination, tissue samples of corresponding times were harvested and observed under the transmission electron microscope. The microscopic images were analyzed using a computer imaging analysis system to obtain the stereological parameters of mitochondria. The correlation between IBS and the stereological parameters was analyzed. RESULTS: After cardiac arrest, swollen mitochondria with electron-lucent matrix could be observed in some myofibers following the progression of time. The alteration of IBS correlated well with that of mitochondrial stereological parameters, such as volume density (Vv), surface density (Sv), average volume (v), average surface area (s), and specific surface (Rsv, ratio between surface and volume). CONCLUSION: Mitochondria might be an important scatterer in the myocardium for IBS.

[Long-term clinical efficacy of losartan or perindopril combination therapy with low-dose amiodarone in patients with paroxysmal atrial fibrillation].

OBJECTIVE: The purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF). METHODS: One hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF. RESULTS: During the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3. CONCLUSIONS: The results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.

Effect of polydatin on phospholipase A2 in lung tissues in rats with endotoxic shock.

OBJECTIVE: To study the effect of polydatin on phospholipase A(2) in lung tissues in rats with endotoxic shock. METHODS: Thirty-two healthy male Wistar rats were employed in this study. A total of 8 rats received normal saline intravenously (control group), 8 rats received 10 mg/kg of endotoxin (endotoxic shock group), 8 rats received 1 mg/kg of polydatin after endotoxin injection (polydatin treatment group), and 8 rats received 1 mg/kg of polydatin (polydatin prevention group) 30 minutes before endotoxin injection. Mean arterial pressure was measured once half an hour. Lung tissues were collected 6 hours later. Phospholipase A(2) activity was measured with acid titration. The gene expression of secretory phospholipase A(2) type IIA was detected with reverse transcription polymerase chain reaction. Meanwhile, the histological changes of the lungs among four groups were compared through microscopic examination. RESULTS: Phospholipase A(2) activity and the gene expression of secretory phospholipase A(2) type IIA increased after endotoxin injection, but polydatin could inhibit these effects of endotoxin. Obvious morphological evidence could be found in the lung pathological sections and the protective effect of polydatin was most significant in the polydatin prevention group. CONCLUSIONS: Polydatin has prophylactic and therapeutic effects (the former is more distinct than the latter) on acutely injured lungs in rats with endotoxic shock and which suggests that polydatin may be a phospholipase A(2) inhibitor.