Hypertension Heart Failure Research Articles

Clinical Characteristics and Outcomes of Patients with Heart Failure of Hypertensive Etiology: Analysis of Colombian Heart Failure Registry (RECOLFACA)

Introduction: Arterial hypertension represents one of the main comorbidities observed in patients with heart failure (HF) and one of the main risk factors for its development. Despite this, studies assessing this hypertensive etiology are scarce in Latin America. Our objective was to analyze the prevalence of HF of hypertensive etiology and evaluate its prognosis in patients enrolled in the Colombian Heart Failure Registry (RECOLFACA by its Spanish acronym). Methods: RECOLFACA recruited adult patients diagnosed with HF in 60 centers in Colombia between 2017 and 2019. The primary outcome was all-cause mortality. A Cox proportional hazards regression model was used to assess factors associated with primary outcomes in patients with hypertensive HF. A p value <0.05 was considered significant. All statistical tests were two-tailed. Results: Out of the total number of patients evaluated in RECOLFACA (n = 2,514), 804 had a diagnosis of HF with hypertensive etiology (31.9%). These patients were less frequently males and had a significantly older age and lower prevalence of comorbidities than those with HF of other etiologies. Additionally, patients with hypertensive HF had a higher prevalence of HF with preserved ejection fraction (HFpEF) (34.1% vs. 28.3%; p = 0.004). Finally, type 2 diabetes mellitus, chronic obstructive pulmonary disease diagnosis, and NYHA class IV were classified as independent mortality risk factors. Conclusions: Hypertensive HF represents about one-third of the total number of patients with HF in RECOLFACA. Compared with HF of other etiologies, it presents a differential clinical profile – older age and a higher prevalence of HFpEF. RECOLFACA has become a useful tool to characterize patients with HF in Colombia, with which it has been possible to carry out a more specific search and reach the diagnosis of this pathology in our population, and it has served as an example to stimulate registries of patients with HF in other countries in the region.

Analysis of the gut microbiota profile targeted to multiple hypervariable regions of 16S rRNA in a hypertensive heart failure rat model.

The gut microbiota, comprising a diverse community of microorganisms, significantly influences various aspects of health. Changes in the composition of the gut microbiota are implicated in adverse effects on host physiology, contributing to the pathogenesis of cardiovascular diseases, among others pathological conditions. Understanding the role of the gut microbiota in the context of heart failure is particularly important. In this regard, the spontaneously hypertensive heart failure (SHHF) rat is an adequate experimental model since exhibits many features in common with heart failure (HF) in humans. Recent advancements in next-generation sequencing (NGS) have greatly improved microbiome analysis. However, standardization and the adoption of best practices are essential to mitigate experimental variations across studies. This manuscript outlines a straightforward methodology for analyzing gut microbiota composition in SHHF rat fecal samples using 16S rRNA sequencing, emphasizing the relevance of gut microbiota in heart failure.

Nano formulation of Berberine (Brb): Transforming a natural alkaloid into advanced therapeutics

A naturally occurring isoquinoline alkaloid “Berberine” (Brb) is found in various plant species of the genus Berberis, such as Berberis vulgaris, Berberis aristata, Berberis microphylla, and so on. This component has been studied extensively by various researchers and scientists for its diverse therapeutic properties, including anticancer, antiviral, antimicrobial antidiarrheal, and anti-inflammatory effects. One of the most remarkable applications of berberine is its efficacy in managing type-II diabetes, which is attributed to its capability to initiate adenosine monophosphate, glycolysis stimulation, protein kinases activation, inhibit mitochondrial function and thus collectively enhance the lipid and glucose metabolism. Also, Berberine has shown promising outcomes in addressing other health conditions, such as hypertension, cardiac arrhythmias, and congestive heart failure. In spite of its numerous benefits, extensive usage of berberine has been hindered by some challenges such as low bioavailability, limited absorption, and poor water solubility. Nano formulation has emerged as an auspicious approach to overcome these obstacles. This review highlights the advancements of using nano technology to overcome the limitations of berberine (Brb) associated with its absorption, dissolution, and bio-distribution, which are critical for its active application of pharmacology. While previous studies have explored the use of nano-carriers for transfer of drug, this review uniquely underlines an inclusive evaluation of several nanocarrier, together with lipid-based nanoparticles (SLNs, NLCs, micelles, and liposomes), polymeric-based nanoparticles (chitosan, alginate, dextran, and PLGA) and advanced materials (graphene, dendrimers, gold (Au), and silver (Ag) nanoparticles). It emphasizes their specific applications in treating conditions like diabetes, osteoarthritis, microbial infections, and melanoma, with special attention on innovative applications such as thermal therapy with AuNP-Brb and bio-imaging with Brb-based carbon dots. In conclusion, nanotechnology has shown an outstanding result in improving the therapeutic strength and delivery of berberine, more investigation is necessary to interpret these nanoparticle carriers into clinical applications. The detailing of specific therapeutic effects and this breadth of comparison highlight the novelty of this review, which sets a foundation for future research to translate these findings into clinical applications.

Clinical Effectiveness and Safety of Olprinone Combined with Qiliqiangxin Capsule for Severe Pulmonary Arterial Hypertension and Right Heart Failure

Clinical Effectiveness and Safety of Olprinone Combined with Qiliqiangxin Capsule for Severe Pulmonary Arterial Hypertension and Right Heart Failure

Ambulatory blood pressure and risk of heart failure: a mini-review

The aim of this mini-review is to report current knowledge about the association between ambulatory blood pressure and risk of heart failure in hypertension. We conducted a literature search through PubMed, Web of science and Cochrane Library by using terms such as ambulatory blood pressure, 24-hour blood pressure, daytime blood pressure, nighttime blood pressure, hypertension, heart failure. We identified 4 studies including 7891 patients who developed 260 cases of heart failure during the follow-up. The evaluation of published studies indicates that ambulatory blood pressure is superior to clinic blood pressure in predicting the occurrence of heart failure. Particularly, it has been reported that 24-hour blood pressure values, nighttime nondipping blood pressure pattern and ambulatory resistant hypertension are associated with increased risk of heart failure above clinic blood pressure. Nevertheless, there are still few data in the literature on this topic. Therefore, further studies are needed to broaden our knowledge on this matter to improve our therapeutic approach to prevent HF in hypertensive patients.

Safety of prehospital intravenous bolus dose nitroglycerin in patients with acute pulmonary edema: A 4-year review.

Intravenous nitrates are a primary therapy for hypertensive congestive heart failure (CHF) with acute pulmonary edema (APE) in the hospital setting. Historically, sublingual nitrates are the mainstay of emergency medical services (EMS) pharmacologic therapy for these patients. We aimed to evaluate the safety of prehospital bolus dose intravenous nitroglycerin in patients with APE. This is a retrospective evaluation of EMS data between March 15, 2018, and March 15, 2022, where CHF with APE was suspected and bolus-dose intravenous nitroglycerin was administered. Protocol inclusion criteria were hypertension (systolic blood pressure [SBP]>160mmHg) and acute respiratory distress, with a presumption of decompensated CHF with APE. These patients received 1mg intravenous nitroglycerin, with the option to repeat once for ongoing distress if the SBP remained>160mmHg. The primary outcomes were adverse events, defined as hypotension (SBP<90mmHg), syncope, vomiting, or dysrhythmia. The final analysis included 235 patients. In patients receiving intravenous bolus nitroglycerin, the median (interquartile range [IQR]) initial and final EMS SBP values decreased from 198mmHg (180-218) to 168 (148-187), respectively. The median (IQR) pulse decreased from 108 (92-125) to 103 (86-119), and the median oxygen saturation increased from 89% (82-95) to 98% (96-99). Three episodes (1.3%) of asymptomatic hypotension occurred, and none required intervention. This study supports a favorable safety profile for prehospital bolus-dose intravenous nitroglycerin for decompensated CHF with APE. Blood pressure, heart rate, and oxygen saturation improvements are also demonstrated. Further, prospective studies are needed to confirm these findings.

When the responsibility for a crime is shared between several actors. The case of hypertensive heart failure with preserved ejection fraction

When the responsibility for a crime is shared between several actors. The case of hypertensive heart failure with preserved ejection fraction

20(S)-ginsenoside Rh2 inhibits angiotensin-2 mediated cardiac remodeling and inflammation associated with suppression of the JNK/AP-1 pathway

BackgroundEnhanced levels of angiotensin-2 (Ang-II) causes hypertensive heart failure (HHF) through non-hemodynamical and hemodynamical alterations. 20(S)-ginsenoside Rh2 (20(S)-Rh2) is a natural ginseng compound with numerous cardiovascular benefits. This investigation elucidates the influence of 20(S)-Rh2 on Ang-II-induced heart failure and cardiac alterations. MethodsAng-II was administered in C57BL/6 mice for 4 weeks to induce HHF. In the last 2 weeks of treatment, 20(S)-Rh2 was orally administered in mice to assess the potential 20(S)-Rh2 mechanism. Subsequently, RNA sequencing was carried out. ResultsIt was indicated that 20(S)-Rh2 suppresses myocardial fibrosis, hypertrophy, and inflammation, thereby inhibiting cardiac disruption in Ang-II-challenged mice without affecting blood pressure. According to the RNA sequencing data, this cardio-protective effect was linked with the (JNK)/AP 1 pathway. 20(S)-Rh2 alleviated heart tissue and cardiomyocytes inflammation by inhibiting the Ang-II-mediated JNK/AP-1 pathway. Within cardiomyocytes, JNK or AP-1 absence abolished the anti-inflammatory effects of 20(S)-Rh2. ConclusionThis study investigation indicated that 20(S)-Rh2 prevents cardiovascular dysfunction induced by Ang-II induced by decreasing JNK-regulated inflammatory responses, providing evidence for its use as an efficient regimen for HHF.

Contrasting patterns of symptoms compared to mortality in women and men with Congestive Heart Failure (the G-CHF registry)

Abstract Background There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure, especially in low-and middle-income countries. Purpose In this study from the Global Congestive Heart Failure registry, we examined sex differences in risk factors, clinical characteristics, treatments, and the risk of heart failure hospitalization and mortality by country economic status and by left ventricular ejection fraction (LVEF) category. Methods In the prospective Global-Congestive Heart Failure (G-CHF) study, participants with established heart failure were considered for inclusion from 40 high-, middle-, and low-income countries. We recorded information on the demographic characteristics, medical history, and treatments of participants. We report data on heart failure hospitalization and mortality by sex overall, by country economic status, and by LVEF category. Results From December 2016 to July 2022, 23,000 participants were recruited and followed up. The average age of women in the study was 62 years compared to 64 years in men. Fewer women than men had a LVEF ≤40 (51.7% women vs 66.3% men). By contrast, more women than men had an LVEF≥ 50 (33.2% women vs 18.6% men). Hypertensive heart failure was the most common etiology in women (25.5% women vs 16.8% men), and ischemic heart failure was the most common etiology in men (45.6% men vs 26.6% women). Signs and symptoms of heart failure were more common in women than men: 42.6% of women were NYHA functional class III/IV compared to 37.9% of men. Among participants with a LVEF &amp;lt;35, use of implantable cardiac defibrillator (ICD) was lower in women than men in the overall study (8.7% women vs 17.2% men), and within countries categorized by economic status. However, the use of heart failure medicines and cardiac tests did not differ systematically by sex. Differences by sex were not observed in the adjusted risk of heart failure hospitalization overall (women-to-men adjusted hazard ratio 1.0 (95% CI 0.94 to 1.07)). This pattern was consistent within countries categorized by economic status, geographic region, and by LVEF category. Women had a lower adjusted risk of mortality overall (women-to-men adjusted hazard ratio 0.82 (95% CI 0.77 to 0.87), which was consistently observed within countries categories by economic status, geographic region, and LVEF levels. Conclusions There are differences between women and men in heart failure symptoms, underlying causes, ejection fraction categories, and use of an ICD. However, use heart failure medications, cardiac tests, and hospitalization were similar in women and men; but women had a lower risk of death.

Successful treatment of pulmonary hypertension and right heart failure by antibody-based functional blocking of the extra-domain A of fibronectin in a preclinical animal model

Abstract Background Pulmonary Hypertension (PH) as heterogeneous disease group is pathogenetically accompanied by pulmonary vascular and right ventricular tissue remodelling showing similarities between the clinical groups 1 (Pulmonary Arterial Hypertension), 2 (PH associated with left heart disease) and 3 (PH associated with lung disease). Since the remodelling process entails the abundant re-expression of extra-domain A containing fibronectin (ED-A+ Fn), which is virtually absent in healthy adult organs, a potential functional role in PH development and progression has been suggested and recently proven by our group. The human recombinant antibody F8 (IgG) specifically recognises ED-A+ Fn and is capable to block its function at least in vitro. Thus, F8 might serve as a novel therapeutic agent for the treatment or even prevention of PH. Purpose Against that background, the current study was aimed to test the therapeutic efficacy of F8 after systemic administration in a well-established preclinical model of PH in comparison to a non-specific control antibody and a dual endothelin receptor antagonist as standard of care. Methods Induction of PH was realized by subcutaneous injection of Monocrotaline (MCT) in mice. In total, 41 animals were included in the study approach and were divided into the following experimental groups: sham-treated controls (controls; n=7), PH mice without a specific treatment (PH_untreated; n=12), PH mice treated with the dual endothelin receptor antagonist Macitentan (PH_MAC; n=6), PH mice treated with the F8 antibody (PH_F8; n=8) and PH mice treated with an antibody of irrelevant antigen specificity in the murine system (PH_KSF; n=8). Treatment effects were evaluated on the haemodynamic, echocardiographic and microscopic level. Results In comparison to controls, untreated PH mice showed significantly higher right ventricular systolic pressure values (RVPsys, p&amp;lt;0.05) as well as impaired echocardiographic parameters of right ventricular morphology and function, i.e., enlarged basal right ventricular (RVbasal, p=0.016) diameters and reduced tricuspid annular plane systolic excursion values (TAPSE, p=0.008). In the PH_F8 group, haemodynamic and echocardiographic parameters were significantly improved compared to the PH_untreated or the PH_KSF group (p&amp;lt;0.05 for the majority of parameters). Histological evaluation revealed significant lung tissue damage after in the PH_untreated group compared to controls (p=0.008), which were significantly attenuated in the PH_F8 (p=0.04) but not the PH_KSF group (p=n.s.). Conclusion The therapeutic efficacy of the human recombinant F8 antibody specific to ED-A+ Fn has been proven for the first time in vivo in a well-established preclinical model of PH. F8 acts as a disease-modifier by attenuating PH associated lung tissue remodelling resulting in remarkable improvements of pulmonary hemodynamics and echocardiographic parameters of right ventricular load.

Screening for atrial fibrillation by village doctors in rural areas of china: the jiangsu province rural community atrial fibrillation project

Abstract Background No study has systematically investigated the quality of long-term care delivered to the rural elderly with chronic diseases in China. Since atrial fibrillation (AF) is becoming an increasing burden on healthcare systems worldwide. Purpose We conducted an AF screening programme in rural elderly and evaluated healthcare efficiency led by the village doctors in China. Methods This cross-sectional study of the rural population aged ≥65 years was conducted from April to June 2019 in our towns of Jiangsu Province. AF was identified using 12-lead electrocardiography in the first-step (government-led health examination) and single-lead electrocardiography in the second-step (in-house AF screening). Questionnaire surveys were designed for the AF patients and their village doctors, respectively. Results Among the 31,342 registered subjects, 12,630 (40·3%) declined, 7,956 (25·3%) participated in the first-step and 10,756 (34·3%) in the second-step (Figure 1). The overall AF detection rate was 4·3% (810/18,712). Of the 810 patients with AF (mean age 76·1±5·9 years; 51·4% female), 51·5% had education level below primary school, 2·6% could use smartphone applications, and 8·1% lived with their children. Common risk factors were older age, men, hypertension, diabetes, prior stroke, vascular disease, and congestive heart failure. Among the 402 patients who were aware of AF, there were 367 were at high risk of stroke (CHA2DS2-VASc score ≥3 in women or ≥2 in men) and OAC was currently used in only 10·9% (40/367) of these (Figure 2). Only 17·6% (91/516) of patients with known hypertension had a resting blood pressure level &amp;lt;140/90 mmHg, and 6·0% (8/132) of patients with known diabetes had a fasting blood glucose level ≤6·1 mmol/L. Our questionnaire survey for village doctors showed that only 7·3% (9/122) reported having the knowledge or ability for providing integrated care AF management. Conclusions This screening project in rural villages identified AF in 4·3%, but AF management was suboptimal with low use of oral anticoagulation. The current village doctor-dominant rural healthcare system is far from delivering optimal standardized AF management for older patients in rural China. There is a urgent need to support these rural clinics and empower the village doctors in optimising the care of AF patients.The flow chart of this studyThe use of oral anticoagulation

HS135, a novel activin and GDF trap, is highly efficacious in preclinical models of pulmonary hypertension and obesity-associated heart failure with preserved ejection fraction

Abstract Introduction Activins and growth differentiation factors (GDFs) signal via the Activin Type II receptor (ActRII) and are genetically and clinically validated drivers of heart failure (HF), pulmonary hypertension (PH) and obesity. Despite initial clinical success in PH, current inhibitors of Activin mediated signalling (eg, sotatercept, an ActRIIA receptor ectodomain Fc-fusion protein) cannot be dosed to full biological activity. HS135 is a rationally designed ActRII-based fusion protein that acts as a ligand trap for pathological Activins and GDFs while sparing BMP-9 to treat PH and obesity-associated HF. We previously demonstrated that HS135 achieves best-in-class in vitro potency against Activin and GDF targets, which translated into full in vivo target engagement (not observed with ActRIIA-Fc). Here, the differentiated efficacy profile of HS135 was explored in preclinical models of PH and HF with preserved Ejection Fraction (HFpEF). Methods HS135 PH efficacy was assessed using the rat monocrotaline (MCT) and the mouse transaortic constriction (TAC) models, while the murine High Fat Diet (HFD) and L-NAME model was utilized to explore the potential of HS135 in obesity-associated HFpEF. In the MCT model, rats were injected twice weekly for four weeks with HS135 or ActRIIA-Fc starting the day following MCT induction. In the TAC model, mice were injected twice weekly for four weeks with HS135 or ActRIIA-Fc two weeks following surgical intervention to establish TAC. HFpEF was established by feeding mice HFD in combination with L-NAME supplied in drinking water ad libitum for 5 weeks before commencing twice weekly treatment with HS135 or empagliflozin for three weeks. In each case, tissue remodelling in the heart and lungs was assessed by IHC and RNA-seq. In addition, changes in body composition as well as markers of adiposity were evaluated. Results Right ventricles (RV) of MCT treated animals showed a distinct gene expression profile by RNAseq particularly related to pathways of inflammation and energy balance. This profile was only modestly improved by ActRIIA-Fc whereas RVs of HS135-treated animals were nearly indistinguishable by RNAseq from naïve mice. Similarly, in the lung, HS135 was more efficacious than ActRIIA-Fc at improving inflammation markers and rebalancing Activin and BMP signalling. In the TAC and HFD/L-NAME models, HS135 was efficacious at modulating the left ventricle phenotype. Across all models of PH and HF, HS135 led to profound increases in lean mass and a more metabolically favourable muscle gene expression profile. Furthermore, in the HFD / L-NAME model, HS135 was able to improve fat mass and markers of adiposity. Conclusion HS135 best-in-class target engagement profile uniquely improves PH, HF, and metabolism across in vivo models. Collectively, these data support the development of HS135 as a novel agent in cardiopulmonary and cardiometabolic disease, including PH and obesity-associated HF.

Abstract 14993: Empagliflozin Exerts a Sympathoinhibitory Effect and Ameliorates Cardiorenal Injuries in a Rat Model of Hypertensive Heart Failure

Background: SGLT2 inhibitors may have protective effects on cardiac and renal injuries; however, their mechanisms remain unclear. Sympathetic activation has a crucial role in cardio/renal injuries. This study aimed to investigate whether empagliflozin can inhibit cardio/renal injuries through sympathoinhibition in a rat model of hypertensive heart failure. Methods: Male Dahl salt-sensitive rats were divided into low-salt (LS) and high-salt (HS) diet groups from 6 weeks of age. The rats in HS group were assigned to vehicle (HS-VEH) or empagliflozin (HS-EMPA) treatment group at 8 weeks. The effect of empagliflozin on central sympathetic regulation and cardio/renal injuries was assessed at 12 weeks (pre-heart failure phase), while its protective effect on heart failure was evaluated at 15 weeks in another cohort. Results: At 12 weeks , systolic blood pressure was similarly elevated in HS-VEH and HS-EMPA. Plasma norepinephrine levels were increased in HS-VEH compared to LS, and were suppressed in HS-EMPA, which was consistent with the neuronal activity of pre-sympathetic neurons in the brain. Increased left ventricular (LV) weight/body weight, plasma creatinine levels, renal fibrosis, and glomerular sclerosis in HS-VEH were attenuated in HS-EMPA. At 15 weeks , the high salt-induced blood pressure elevation was similar between HS-VEH and HS-EMPA. Although LV hypertrophy did not significantly differ, both decreased echocardiographic LV fractional shortening and increased lung weight observed in HS-VEH were attenuated in HS-EMPA. Elevated plasma creatinine and norepinephrine levels in HS-VEH were also attenuated in HS-EMPA. Conclusion: Empagliflozin inhibits sympathoexcitation and ameliorates cardio/renal injuries without lowering blood pressure in the hypertensive heart failure model. This sympathoinhibitory effect of empagliflozin observed in the pre-heart failure phase might contribute to the attenuation of heart failure progression.

Abstract 14941: Incidence of Cardiac Implantable Electronic Device Infections in End-Stage Kidney Disease Patients on Dialysis

Introduction: Hemodialysis potentially increases the risk of cardiac implantable electronic device (CIED) infection due to transient bacteremia. There is limited available data on the incidence of CIED infections in patients with end-stage kidney disease (ESKD) on hemodialysis. The objective of this research was to study the 1-year incidence of device infection after a new CIED implant in hemodialysis patients. Methods: We conducted a retrospective observational analysis using the United States Renal Data System database. We identified patients aged &gt;18 years with ESKD on hemodialysis who underwent first CIED implant between January 2006 and September 2014. ICD-9 codes were used and we excluded patients with a prosthetic valve. The primary outcome of the study was 1-year incidence of CIED infection. We analyzed the association of device infection with the type of CIED. Results: During the study period, a total of 46,209 patients with ESKD on dialysis received a CIED. After applying the exclusion criteria, 15,077 patients were included in the study. The mean age of the population was 69.9 years; majority were male (56.8%) and white patients (68.5%). Common comorbidities included hypertension (97.7%), dysrhythmia (75.7%), diabetes mellitus (71.1%), and congestive heart failure (67.7%). Of the included patients, 66.5% received a pacemaker (PPM), 33.1% received an implantable cardioverter-defibrillator (ICD), and 0.4% received cardiac resynchronization therapy (CRT-P or CRT-D). The overall 1-year incidence of CIED infection was 3.1%. The incidence of CIED infection was highest among patients with ICDs (4.2%), followed by CRT (3.7%), and PPM (2.5%) (p&lt;0.0001). Conclusions: The 1-year incidence of CIED infections in ESKD patients on hemodialysis was 3.1%, which is significantly higher than the incidence reported in the general population. The highest incidence was observed in those with ICDs. These findings underscore the importance of monitoring and managing CIED infections in this population to improve patient outcomes.

Abstract 14951: Input From Renal Afferent Nerves Contributes to Hypertensive Heart Failure With Preserved Systolic Function Through Baroreflex Impairment and Sympathoexcitation

Introduction: Activation of renal afferent nerves, which can be caused by hypertensive renal damage, increases sympathetic output. The nucleus tractus solitarius (NTS) receives the inputs from baroreflex afferent nerves as well as renal afferent nerves. Baroreflex dysfunction leads to increased left ventricular (LV) end-diastolic pressure even in the heart with preserved systolic function. The GABAergic inhibitory system in the NTS blunts the signals from baroreflex afferent nerves, resulting in increased sympathetic output. Hypothesis: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation mediated by increased GABAergic inhibition in the NTS. Methods and Results: Male Dahl salt-sensitive rats with 8% high-salt diet from 7 weeks of age develop hypertensive HFpEF at 19 weeks. These rats underwent sham surgery (Sham), selective afferent renal denervation (ARDN), or additionally dissection of baroreflex afferent nerves (ARDN+BAROX) at 9 weeks. As controls, rats underwent sham surgery with a low-salt diet. The rats were evaluated at 19 weeks. Systolic blood pressure was similarly elevated in the three groups on high-salt diet. Impaired LV diastolic function assessed by echocardiography and pressure-volume loop analysis in Sham was recovered in ARDN group, while systolic function was preserved in all the group. Decreased baroreflex sensitivity and increased sympathetic output in Sham were attenuated in ARDN group. Activity of GABAergic neurons in the NTS evaluated by immunostaining was increased in Sham compared to controls, and was attenuated in ARDN group. All of the changes in ARDN were cancelled in ARDN+BAROX group. Conclusion: Input from renal afferent nerves contributes to hypertensive heart failure with preserved systolic function through baroreflex impairment and sympathoexcitation along with increased GABAergic inhibition in the NTS.

Abstract 13250: Establishing Partition Values and Clinical Phenotype for Heart Failure Patients With Abnormal Left Atrial Function Index: A Cross-Sectional Analytical Study

Introduction: Left atrial function index (LAFI) has recently been validated for global estimation of left atrial (LA) function. LA dysfunction is critical to developing overt heart failure (HF), and getting the best tool for assessing its function is critical to HF prevention. This study attempts to establish cut-off values for LAFI among HF patients and identify which HF phenotype is associated with abnormal LAFI. Hypothesis: Is there any association between abnormal LAFI and changes in LV function? Methods: This cross-sectional study was conducted at the Delta State University Teaching Hospital, Nigeria. We recruited 80 hypertensive HF patients and 40 healthy normotensive controls. LAFI = (LAEF x LVOT-VTI)/LAESVI. (LAEF = left atrial emptying fraction; LAESVI = left atrial end-systolic volume index; LVOT-VTI = left ventricular outflow tract velocity time integral). Relationships between variables were determined using an independent student’s t-test, and a P-value of &lt;0.05 was significant. Results: In the control arm, the LAFI reference range was estimated to be 24.07-76.24. Abnormal LAFI was defined as LAFI &lt; 24 and 77.5% of the individuals with HF were found to have abnormal LAFI. There was no difference in age (61.83±7.48 vs. 63.22±6.75, p=0.46), BMI (28.27±4.47 vs. 29.52±5.91, p=0.33) and systolic BP (127.34±19.28 vs. 120.94±19.94, p=0.22) of hypertensive HF patients with LAFI &lt;24 and LAFI ≥24. Those with abnormal LAFI had lower EF (45.04±11.06 vs. 63.73±14.73, p&lt;0.0001), FS (25.75±8.26 vs 32.49±8.64, p=0.003) and SV (57.16±13.30 vs. 64.99±16.94, p=0.02). However, E/E’ (15.62±5.61 vs. 9.2±3.22, p&lt;0.0001) and LAVI (37.22±5.80 vs. 16.48±5.65, p&lt;0.0001) were higher among patients with lower LAFI. Contrarily, E/A (1.87±0.97 vs. 1.87±0.83, p=0.98) and TAPSE (17.87±3.67 vs. 19.54±2.47, p=0.06) did not show any difference among the groups. Conclusions: This study shows that abnormal LAFI was associated with impaired LV function and it is crucial to deploy this non-invasive modality of cardiac assessment in hypertensive patients. Early identification of abnormal left atrial mechanics is pertinent to preventing overt HF, especially in parts of the world where access to advanced cardiovascular care is limited.

Blood pressure, hypertension, and the risk of heart failure: a systematic review and meta-analysis of cohort studies.

Several observational studies have investigated the association between hypertension or elevated systolic blood pressure and diastolic blood pressure and risk of heart failure, but not all the studies have been consistent. This systematic review and meta-analysis aimed to summarize the available data from cohort studies on the association between hypertension, systolic and diastolic blood pressure, and the risk of heart failure. PubMed and Embase databases were searched for relevant articles from inception to 10 June 2022. Cohort studies on hypertension or blood pressure and heart failure were included. Random effect models were used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) for the association between hypertension or blood pressure and heart failure. Forty-seven cohort studies were included. The summary RR was 1.71 (95% CI: 1.53-1.90, I2 = 98.4%) for hypertension vs. no hypertension (n = 43 studies, 166 798 cases, 20 359 997 participants), 1.28 (95% CI: 1.22-1.35, I2 = 90.3%) per 20 mmHg of systolic blood pressure (24 studies, 31 639 cases and 2 557 975 participants), and 1.12 (95% CI: 1.04-1.21, I2 = 92.6%) per 10 mmHg of diastolic blood pressure (16 studies, 23 127 cases and 2 419 972 participants). There was a steeper increase in heart failure risk at higher blood pressure levels and a three- to five-fold increase in RR at around 180/120 mmHg of systolic and diastolic blood pressure compared with 100/60 mmHg, respectively. There was little indication of publication bias across analyses. This meta-analysis suggests a strong positive association between hypertension and systolic and diastolic blood pressure and the risk of heart failure. These results support efforts to reduce blood pressure in the general population to reduce the risk of heart failure.

Ambulatory 7-day mechanical circulatory support in sheep model of pulmonary hypertension and right heart failure

Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure. In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed. Six subjects underwent the chronic disease model for 56 to 71days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit. Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.

Nationwide Trends and Outcomes for Coronary Artery Bypass Grafting in End-Stage Kidney Disease and Stable Coronary Artery Disease

Patients with end-stage kidney disease (ESKD) on dialysis have an increased burden of coronary artery disease (CAD). This study assessed the trend and outcomes for coronary artery bypass surgery (CABG) in patients with ESKD and stable CAD. We conducted a longitudinal study using the United States Renal Data System of patients with ESKD and stable CAD who underwent CABG from the years 2009 to 2017. The outcomes included in-hospital, long-term mortality, and repeat revascularization. The follow-up was until death, end of Medicare AB coverage, or December 31, 2018. A total of 11,952 patients were identified. The mean age was 62.8years, 68% were male, and 67% were white. The common co-morbidities included hypertension (97%), diabetes mellitus (75%), and congestive heart failure (53%). A significant decrease in CABG procedures from 2.9 to 1.3 procedures per 1,000 patients with ESKD (p <0.001) was noted during the years studied. The overall in-hospital mortality rate was 5.9%, and there was a significant decrease over the study period (p=0.01). Although the 30-day mortality rate was 6.9% and remained steady (p=0.14), the 1-year mortality rate was 22.8% and decreased significantly (p <0.001). At 5years, the overall survival rate was 35%, and patients with internal mammary artery grafts showed better survival than those without (36% vs 25%). In conclusion, there has been a decrease in CABG procedures performed in patients with ESKD with stable CAD with decreasing in-hospital and 1-year mortality. Those with an internal mammary artery graft do better, but the overall long-term survival remains dismal in this population. There remains need for caution and individualization of revascularization decisions in this high-risk population.

Dapagliflozin and Apparent Treatment-Resistant Hypertension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: The DELIVER Trial.

Apparent treatment-resistant hypertension (aTRH) is prevalent and associated with adverse outcomes in heart failure with mildly reduced or preserved ejection fraction. Less is known about the potential role of sodium-glucose co-transporter 2 inhibition in this high-risk population. In this post hoc analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), we evaluated clinical profiles and treatment effects of dapagliflozin among participants with aTRH. DELIVER participants were categorized on the basis of baseline blood pressure (BP), with aTRH defined as BP ≥140/90 mm Hg (≥130/80 mm Hg if diabetes) despite treatment with 3 antihypertensive drugs including a diuretic. Nonresistant hypertension was defined as BP above threshold but not meeting aTRH criteria. Controlled BP was defined as BP under threshold. Incidence of the primary outcome (cardiovascular death or worsening heart failure event), key secondary outcomes, and safety events was assessed by baseline BP category. Among 6263 DELIVER participants, 3766 (60.1%) had controlled BP, 1779 (28.4%) had nonresistant hypertension, and 718 (11.5%) had aTRH at baseline. Participants with aTRH had more cardiometabolic comorbidities and tended to have higher left ventricular ejection fraction and worse kidney function. Rates of the primary outcome were 8.7 per 100 patient-years in those with controlled BP, 8.5 per 100 patient-years in the nonresistant hypertension group, and 9.5 per 100 patient-years in the aTRH group. Relative treatment benefits of dapagliflozin versus placebo on the primary outcome were consistent across BP categories (Pinteraction=0.114). Participants with aTRH exhibited the greatest absolute reduction in the rate of primary events with dapagliflozin (4.1 per 100 patient-years) compared with nonresistant hypertension (2.7 per 100 patient-years) and controlled BP (0.8 per 100 patient-years). Irrespective of assigned treatment, participants with aTRH experienced a higher rate of reported vascular events, including myocardial infarction and stroke, over study follow-up. Dapagliflozin modestly reduced systolic BP (by ≈1 to 3 mm Hg) without increasing risk of hypotension, hypovolemia, or other serious adverse events, irrespective of BP category, but did not improve the proportion of participants with aTRH attaining goal BP over time. aTRH was identified in >1 in 10 patients with heart failure and left ventricular ejection fraction >40% in DELIVER. Dapagliflozin consistently improved clinical outcomes and was well-tolerated, including among those with aTRH. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.