Hypertension Heart Failure Research Articles

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF.

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

Deep Learning Approach for Detecting Cardiovascular Arrhythmias in Seven Lead ECG Signal from Holter

Cardiac arrhythmias are abnormalities caused by irregularities in the heart’s electrical conduction system. Cardiovascular diseases (CVD) have been identified as the leading cause of death worldwide. Premature ventricular contraction (PVC) is one of these diseases. It is an arrhythmia that can be linked to a several heart diseases that affect between 40% and 75% of the population. Ventricular bigeminy occurs when one or two premature beats are detected on an electrocardiogram when there is ventricular contraction between two normal heartbeats or trigeminy. The appearance of ventricular bigeminy or trigeminy rhythms is related to angina. Myocardial infarction, hypertension, and congestive heart failure are also possible conditions. Based on deep learning, this paper proposes creating a robust approach for automatically detecting and classifying cardiovascular arrhythmias in long-term electrocardiogram (ECG) recordings from halters based on deep learning (DL). We present a convolutional neural network (CNN) and long-short-time memory (LSTM) model that identifies cardiovascular arrhythmias. We have designed and implemented the proposed model using Python. The model was trained and validated on a database that includes a total of 17 long-recorded ECG signals (24 h) from 17 subjects, which were obtained from Yfa Hospital. The signals were recorded with seven leads holter. The CNN classifier achieved an accuracy of 91.14% as a final result, validated through a 10-fold cross-validation. Moreover, the proposed model was found to be capable of analyzing ECG recordings to classify multiple cardiovascular arrhythmias in the ECG record signals efficiently.

FRI249 New Onset Heart Failure In A Patient With Rapidly Progressive Adrenocortical Carcinoma

Abstract Disclosure: J. Peeples: None. S. Shu: None. K.G. Romo: None. J. Tereul: None. B.B. Grissett: None. Background: Adrenocortical carcinomas (ACC) are rare, relatively large (>4cm), lipid-rich, and often aggressive tumors. They may be functional, which typically presents as Cushing’s syndrome and/or virilization, or non-functional, which typically presents as an abdominal mass or incidental finding. They occur in two peak incidences: at the first decade of life and between 40-50 years of age. Over half of adult patients with ACC present with an advanced tumor stage. This case describes a young man with new onset heart failure and adrenal mass with metastases who was found to have biopsy-confirmed ACC. Clinical Case: A 20-year-old man with a history of cigarette smoking and marijuana use, but otherwise in prior good health, presented as a transfer for new onset heart failure in the setting of hypertensive emergency (SBP 260s), and CT findings of left adrenal mass, with multiple lung and liver masses. He noted 2 months of rapidly progressive weight gain, easy fatigability, dyspnea on exertion, and leg swelling. Exam revealed central adiposity with abdominal striae, bilateral clavicular and cervical fat pad, and bilateral lower extremity swelling. Investigations revealed hypercortisolism and ventricular ejection fraction 20-25%. Liver mass biopsy revealed metastatic ACC. Family history was significant for multiple members with early onset hypertension and congestive heart failure, including the death of maternal grandmother at age 40. The patient was initially managed in the ICU with an etomidate drip for adrenal suppression. Cortisol levels appropriately decreased to goal. Additionally, he started IV dexamethasone while inpatient. He was discharged once euvolemic on PO furosemide and follow-up was scheduled with cardiology, oncology, and endocrinology. At discharge, he transitioned to PO hydrocortisone (HC) and was placed on trimethoprim/sulfamethoxazole for PJP prophylaxis, doxazosin, and ketoconazole. He also started mitotane for his cancer treatment, with HC to prevent adrenal insufficiency while on mitotane. Subsequently, he started and failed carboplatin plus etoposide palliative chemotherapy with a continued increase in adrenal mass size. Now, he is on second line pembrolizumab with an ECOG score of 2. Conclusion: ACC is a rare and often aggressive tumor that should be considered in the setting of hypercortisolism and cushingoid features. This is particularly important for patients with a relatively unremarkable history and new onset heart failure with dyspnea on exertion. In these cases, mitotane can be used for hypercortisolism associated with ACC. Unfortunately, these tumors are usually diagnosed when they have already progressed to a late stage, and the prognosis for ACC is poor. Presentation: Friday, June 16, 2023

Correlation of Plasma Iron Profile and Intradialytic Hypotension in Hemodialysis Patients

Abstract: Intradialytic hypotension (IDH) has been a common complication which should be aware of, in hemodialysis procedure. Its pathogenesis is multifactorial, and severe anemia is considered as one of the most notable risk factors on IDH. This study aimed to evaluate the correlation between plasma iron profile and intradialytic hypotension in hemodialysis patients. This was an analytical and retrospective study using medical records of hemodialysis patients at Prof. Dr. R. D. Kandou Hospital, Manado from January to May 2022. Sampling was conducted through consecutive sampling method, on available records. Patients with CKD grade 5 which undergoes routine HD twice a week for >3 weeks, aged 18-60 years old were included, while subjects with sepsis, malignancy, autoimmune disease, crisis hypertension, and unstable congestive heart failure were excluded for further studies. The details on iron profile and blood pressure measurement were then extracted, which then analyzed with descriptive analysis and Pearson correlation using IBM SPSS Statistics 26.0. The results obtained a total of 35 patients; 57.1% were male. The Pearson correlation analysis on all variables reported several notable significant results, with a correlation between iron profile and blood pressure measurement were seen in TIBC and systole pre- and post-procedure (-.496 and -.611 respectively) with strong negative relationship; and serum ferritin value with systole post-procedure (.373) implying moderate positive relationship. The results suggested that the increase of ferritin value and decrease of TIBC value were correlated with the increase of systole blood pressure. Meanwhile, the TIBC had a strong positive correlation with systolic changes (.473) meanwhile serum iron had a moderate negative correlation with diastolic changes (-.365). In conclusion, there is a significant correlation between iron profile and changes in blood pressure, with higher iron profile value (lower TIBC) is positively correlated with the increase of both systole and diastole measurement; also negatively correlated with the reduction of blood pressure in hemodialysis patients Keywords: iron; ferritin; intradialytic hypotension; hemodialysis; transferrin; total iron binding capacity

Dominant cardiovascular diseases treated by traditional Chinese medicine: Clinical evidence and distinctive therapeutic characteristics

Abstract Traditional Chinese medicine (TCM) with a long history in China has demonstrated unique advantages in treating a variety of cardiovascular diseases, with promising prospects. We exemplify the TCM advantages with 3 major cardiovascular diseases: coronary heart disease, hypertension, and chronic heart failure. With both national and international guidelines, consensus, systematic reviews, and randomized controlled trials as evidence, we used the modified Jadad and AMSTAR-1 scales to evaluate the evidence quality and then systematically evaluated the clinical effects and benefits of TCM on cardiovascular diseases, aiming to provide fresh insights into the research methodologies and future development directions for TCM-dominant diseases.

Right ventricular dysfunction secondary to hyperthyroidism with total reversal after thyroidectomy: case report

Thyrotoxicosis is a condition caused by an increase in thyroid hormone, commonly associated with Graves' disease and toxic multinodular goiter. Hyperthyroidism is known to increase the risk of pulmonary hypertension and right heart failure, although the underlying mechanisms are still unclear. The identification of these conditions is crucial, as they are potentially reversible with the achievement of euthyroidism. This case report describes a 40-year-old woman with right ventricular dysfunction and pulmonary hypertension due to hyperthyroidism, which was successfully treated with total thyroidectomy. The case highlights the importance of considering thyrotoxicosis as a potential cause of pulmonary hypertension and the need to rule out other underlying causes. Echocardiography is a valuable tool in assessing right ventricular dysfunction, and achieving euthyroidism can result in the reversal of structural and functional cardiac alterations.

What Is the Current Best Drug Treatment for Hypertensive Heart Failure With Preserved Ejection Fraction? Review of the Totality of Evidence.

More than 90% of patients developing heart failure (HF) have an epidemiological background of hypertension. The most frequent concomitant conditions are type 2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease, all disorders/diseases closely related to hypertension. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and nonsteroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). However, subsequently, they have been investigated and, as we see it, documented as beneficial in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) and mostly hypertensive etiology, with effect estimates assessed partly on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated.

Hypertensive Heart Failure.

Despite overwhelming epidemiological evidence, the contribution of hypertension (HTN) to heart failure (HF) development has been undermined in current clinical practice. This is because approximately half of HF patients have been labeled as suffering from HF with preserved left ventricular (LV) ejection fraction (EF) (HFpEF), with HTN, obesity, and diabetes mellitus (DM) being considered virtually equally responsible for its development. However, this suggestion is obviously inaccurate, since HTN is by far the most frequent and devastating morbidity present in HFpEF. Further, HF development in obesity or DM is rare in the absence of HTN or coronary artery disease (CAD), whereas HTN often causes HF per se. Finally, unlike HTN, for most major comorbidities present in HFpEF, including anemia, chronic kidney disease, pulmonary disease, DM, atrial fibrillation, sleep apnea, and depression, it is unknown whether they precede HF or result from it. The purpose of this paper is to provide a contemporary overview on hypertensive HF, with a special emphasis on its inflammatory nature and association with autonomic nervous system (ANS) imbalance, since both are of pathophysiologic and therapeutic interest.

Safety of Lumason® (SonoVue®) in special populations and critically ill patients.

Evidence for the safe use of Lumason® (SonoVue®), an ultrasound enhancing agent (UEA), in special patient populations is critical to enable healthcare professionals to make informed decisions concerning its use in such patients. Herein, we provide insight on the safety and tolerability of Lumason® in special patient populations. Findings are presented from clinical pharmacology studies conducted in patients with compromised cardiopulmonary conditions, from a retrospective study performed in critically ill patients, and from post-marketing surveillance data from over 20 years of market use of Lumason® (SonoVue®). No detrimental effects of Lumason® on cardiac electrophysiology were observed in patients with coronary artery disease (CAD), and no significant effects on pulmonary hemodynamics were noted in patients with pulmonary hypertension or congestive heart failure. Similarly, no effects on several assessments of pulmonary function (e.g., FVC) were observed in patients with chronic obstructive pulmonary disease (COPD), and no clinically meaningful changes in O2 saturation or other safety parameters were observed after administration of Lumason® to patients with diffuse interstitial pulmonary fibrosis (DIPF). The retrospective study of critically ill patients revealed no significant difference for in-hospital mortality between patients administered Lumason® for echocardiography versus those who had undergone echocardiography without contrast agent. Post-marketing surveillance revealed very low reporting rates (RR) for non-serious and serious adverse events and that serious hypersensitivity reactions were rare. These findings confirm that Lumason® is a safe and well tolerated UEA for use in special populations and critically ill patients.

Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor.

Background Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction. Methods and Results We leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14 861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14 861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg/m2). An unbiased phenome-wide association study identified diabetes as the most statistically significant clinical International Classifications of Diseases, Ninth Revision (ICD-9) code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2-sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress. Conclusions Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.

Blood Immune Cell Alterations in Patients with Hypertensive Left Ventricular Hypertrophy and Heart Failure with Preserved Ejection Fraction.

(1) Background: Chronic inflammation and fibrosis are key players in cardiac remodeling associated with left ventricular hypertrophy (LVH) and heart failure with a preserved ejection fraction (HFpEF). Monocytes and T-helpers (Th) are involved in both pro-inflammatory and fibrotic processes, while regulatory T-cells (Treg) could be considered to suppress chronic inflammation in the hypertrophied myocardium. We aimed to estimate the relationship between the frequencies of circulating CD4+ T-cell and monocyte subpopulations and the variables of left ventricular (LV) diastolic function in patients with LVH depending on the presence of HFpEF. (2) Methods: We enrolled 57 patients with asymptomatic hypertensive LVH (n = 21), or LVH associated with HFpEF (n = 36). A clinical assessment and echocardiographs were analyzed. CD4+ Treg, activated Th (Th-act), and monocyte (classical, intermediate, and non-classical) subpopulations were evaluated via direct immunofluorescence and flow cytometry. (3) Results: Patients with HFpEF had a lower Treg/Th-act ratio (p = 0.001). Though asymptomatic patients and patients with HFpEF were comparable in terms of both the total monocyte number and monocyte subsets, there were moderate correlations between intermediate monocyte count and conventional and novel echocardiographic variables of LV diastolic dysfunction in patients with HFpEF. (4) Conclusions: In patients with LVH, the clinical deterioration (transition to HFpEF) and progression of LV diastolic dysfunction are probably associated with T-cell disbalance and an increase in intermediate monocyte counts.

Atrial septal defect-associated pulmonary hypertension with decompensated heart failure: outcomes after fenestrated device closure.

Up to 90% of adults with untreated atrial septal defect will be symptomatic by 4th decade, and 30-49% will develop heart failure. 8-10% of these patients have pulmonary arterial hypertension with a female predominance regardless of age. We aimed to demonstrate that fenestrated closure can be safely performed in patients with decompensated heart failure and atrial septal defect-associated pulmonary arterial hypertension with improved outcome. Transcatheter fenestrated atrial septal defect closures (Occlutech GmbH, Jena, Germany) were performed on a compassionate-use basis in 5 consecutive adult patients with atrial septal defect-associated pulmonary arterial hypertension and severe heart failure with prohibitive surgical mortality risks. Change in systemic oxygen saturation, 6-minute walk test, NYHA class, echocardiographic and haemodynamic parameters were used as parameters of outcome. All patients were female, mean age 48.8 ± 13.5 years, followed up for a median of 29 months (max 64 months). Significant improvements observed in the 6-minute walk test, and oxygen saturation comparing day 0 time point to all other follow-up time points data (B = 1.32, SE = 0.28, t (22.7) = -4.77, p = 0.0001); and in the haemodynamic data (including pulmonary vascular resistance and pulmonary pressure) (B = -0.60, SE = 0.22, t (40.2) = 2.74, p = .009). All patients showed improved right ventricular size and function along with NYHA class. There were no procedure-related complications. Fenestrated atrial septal defect closure is feasible in adults with decompensated heart failure and atrial septal defect-associated pulmonary arterial hypertension. It results in sustained haemodynamic and functional improvement.

The Impact of Vaccination Among Hospitalized Patients with the Diagnosis of COVID-19.

We aimed to investigate the vaccination status and the risk factors for the intensive care unit (ICU) support need of the laboratory-confirmed breakthrough COVID-19 infection inpatients. This multi-center point-prevalence study was conducted on inpatients, divided into two groups as 'fully' and 'partially' vaccinated according to COVID-19 vaccination status. Totally 516 patients were included in the study. The median age was 65 (55-77), and 53.5% (n=276) of the patients were male. Hypertension (41.9%, n=216), diabetes mellitus (DM) (31.8%, n=164), and coronary artery disease (CAD) (16.3%, n=84) were the predominant comorbidities. Patients were divided into two groups ICU (n=196) and non-ICU (n=301). Hypertension (p=0.026), DM (p=0.048), and congestive heart failure (CHF) (p=0.005) were significantly higher in ICU patients and the median age was younger among non-ICU patients (p=0.033). Of patients, 16.9% (n=87) were fully vaccinated, and this group's need for ICU support was statistically significantly lower (p=0.021). We conclude that older age, hypertension, DM, CHF, and being partially vaccinated were associated with the need for ICU support. Therefore, all countries should continuously monitor post-vaccination breakthrough COVID-19 infections to determine the national booster vaccine administration approach that will provide vulnerable individuals the highest protection.

Nature of intestinal microflora disorders in cardiovascular diseases

The article reviews the literature on the relationship between intestinal microflora and cardiometabolic disorders. The pathophysiological significance of microflora disturbance in the development of intestinal pathology has long been known and proven. However, scientific research in recent decades has convincingly proven that the positive role of intestinal microbiota is not limited only to the intestines. Disturbances of the intestinal microbiota can affect other organs and systems, in particular, cardiometabolic processes. The mechanism of the relationship between dysbiotic disorders and the cardiovascular system can occur due to the deterioration of the intestinal barrier function and through the influence of various metabolites of the intestinal microflora on cardiometabolic processes. When the intestinal barrier deteriorates, pro-inflammatory harmful components of the intestinal microflora such as lipopolysaccharides can have a negative effect on the cardiovascular system. Short-chain fatty acids, bile acids, and trimethylamine N-oxide are of the greatest importance among the metabolites of the intestinal microflora, which can have a diverse effect on cardiometabolic processes. Accumulated research data indicate the possible impact of intestinal microflora disturbances on atherosclerosis, hypertension, and chronic heart failure. The search for methods of correcting the intestinal flora is underway, which would allow to eliminate the specified negative impact.

Formulation, optimization and in vitro evaluation of polymer-coated liposomes encapsulating nebivolol hydrochloride

Hypertension, also known as high blood pressure, is a serious medical condition that affects billions of people worldwide. Nebivolol hydrochloride, a β1–adrenergic blocking agent, is used by the oral route in the treatment of hypertension and congestive heart failure. However, its lipophilic nature and poor aqueous solubility restricts its oral bioavailability. To overcome limitations related with conventional oral formulations of the drug, uncoated and polymer–coated liposomes were developed and evaluated. Liposomes loaded with nebivolol hydrochloride were prepared by thin–film hydration method and characterized. The influence of chitosan or pluronic (F127) coating on the liposome properties was evaluated in terms of physicochemical characteristics, stability in simulated gastrointestinal fluids, mucin interaction, in vitro drug release and cytotoxicity studies. It was observed that coating the liposomes with either chitosan or pluronic affected the size, surface charge and encapsulation efficiency of the formulations. The surface morphology studies confirmed the vesicular shape of liposomes. The results obtained indicated that both polymer–coated liposome formulations maintained their stability in simulated gastrointestinal fluids and showed significant in vitro interaction with mucin. Polymer–coated liposome formulations showed much better cumulative release of the drug than uncoated liposomes. No aggregation was observed at the end of four–week storage period and low toxicity in Caco–2 cells was measured. The results demonstrated that polymer coating of liposomes could enhance the in vitro release of nebivolol hydrochloride and interaction with mucin following oral administration and might be attractive alternative nanocarriers to traditional oral formulations.

Identification and characterization of the new generation soluble guanylate cyclase stimulator BAY-747 designed for the treatment of resistant hypertension.

First-generation soluble guanylate cyclase (sGC) stimulators have shown clinical benefit in pulmonary hypertension (riociguat) and chronic heart failure (vericiguat). However, given the broad therapeutic opportunities for sGC stimulators, tailored molecules for distinct indications are required. We report the high-throughput screening (HTS)-based discovery of a second generation of sGC stimulators from a novel imidazo[1,2-a]pyridine lead series. An intense medicinal chemistry programme resulted in the discovery of the sGC stimulator BAY 1165747 (BAY-747). The pharmacokinetic profile of BAY-747 was determined in different species, and it was broadly characterized in pharmacological model systems relevant for vasodilatation and hypertension. BAY-747 is a highly potent sGC stimulator in vitro. In addition, BAY-747 showed an excellent pharmacokinetic profile with long half-life and low peak-to-trough ratio. BAY-747 was investigated in experimental in vivo models of malignant and resistant hypertension (rHT). In spontaneously hypertensive (SH) rats, BAY-747 caused a dose-related and long-lasting decrease in mean arterial blood pressure (MAP). Oral treatment over 12 days resulted in a persistent decrease. BAY-747 provided additional benefit when dosed on top of losartan, amlodipine or spironolactone and even on top of triple combinations of frequently used antihypertensive drugs. In a new canine model of rHT, BAY-747 caused a dose-related and long-lasting (>6 h) MAP decrease. BAY-747 is a potent, orally available sGC stimulator. BAY-747 shows long-acting pharmacodynamic effects with a very low peak-to-trough ratio. BAY-747 could be a treatment alternative for patients with hypertension, especially those not responding to standard-of-care therapy.

The effect of antiplatelet therapy on outcomes in patients who underwent laparoscopic radical nephrectomy: A Japanese single-center study.

The number of patients receiving antiplatelet therapy (APT) who have undergone laparoscopic radical nephrectomy is increasing. However, it is unclear whether APT affects the outcomes of patients undergoing radical nephrectomy. We investigated the perioperative outcomes of radical nephrectomy in patients with and without APT. We retrospectively collected data from 89 Japanese patients who underwent laparoscopic radical nephrectomy for clinically diagnosed renal cell carcinoma (RCC) at Kokura Memorial Hospital between March 2013 and March 2022. We analyzed information related to APT. We divided the patients into two groups: the APT group (patients receiving APT) and the N-APT group (patients not receiving APT). Moreover, the APT group was further divided into the C-APT group (patients with continuous APT) and the I-APT group (patients with interrupted APT). We compared the surgical outcomes of these groups. Among 89 patients eligible for the study, 25 received APT and 10 continued APT. Even though the patients who received APT had a high American Society of Anesthesiologists physical status and many complications, including smoking, diabetes, hypertension, and chronic heart failure, no significant difference in the intra- or postoperative outcomes, including bleeding complications, was observed regardless of whether the patients received APT or continued APT. We concluded that in laparoscopic radical nephrectomy, continuation of APT is an acceptable strategy for patients with thromboembolic risk caused by interruption of APT.

840-P: Dual Amylin and Calcitonin Receptor Agonist Treatment Improves Blood Pressure and Glucose Control in ZSF1 Rats

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on both body weight, glucose control and insulin action. However, whether DACRAs affect hypertension, and diabetes-related cardiovascular complications remain unknown. In this study, the cardiovascular protective effect of the DACRA KBP-336 was evaluated in obese Zucker diabetic fatty-Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Obese ZSF1 rats were treated for 60 days with the KBP-336 (4.5 nmol/kg Q3D) and treatment efficacy on glucose control and blood pressure measured by tail cuff was evaluated. Furthermore, serum biomarkers of cardiovascular complications were evaluated. KBP-336 treatment significantly lowered fasting blood glucose levels compared to vehicle (P<0.001). This was also illustrated in the HbA1c levels at study end, where KBP-336 resulted in significantly (P<0.001) lower levels than vehicle. Importantly, KBP-336 significantly reduced both systolic (AUC levels reduced by 13.3%, P<0.001) and diastolic (AUC levels reduced by 17.0%, P<0.001) blood pressure compared to vehicle without affecting the heart rate. Notably, the beneficial effects on both glucose control and blood pressure were obtained independent of weight loss as KBP-336 only resulted in a small and transient weight reduction. Furthermore, serum levels of the marker of cardiovascular disease, rPRO-C6 (collagen type VI formation marker) were 6.4% lower in KBP-336 treated rats compared to vehicle, supporting improvement in cardiovascular parameters. In summary, we show for the first time that KBP-336 benefits blood pressure in a metabolic rat model suffering from hypertension. In addition, KBP-336 improved glucose control independent of weight loss. These data highlight KBP-336 as a promising candidate for treating obesity and related comorbidities including type 2 diabetes and hypertension. Disclosure S.A.Melander: None. A.T.Larsen: Employee; Nordic Bioscience A/S. K.Mohamed: Employee; Nordic Bioscience. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. Funding Danish Research Foundation; Innovation Fund Denmark; European Union’s Horizon 2020 Research and Innovation Program (814244)

Agenesis of the Right Pulmonary Artery Associated with Patent Ductus Arteriosus: A Case Report

Introduction: Unilateral pulmonary artery agenesis is a rare congenital malformation that can be the source of serious complications. Its diagnosis must be considered in the presence of recurrent respiratory infections. Adult patients are often asymptomatic, which makes the diagnosis difficult. Chest CT angiography is the reference examination. We report a case of agenesis of the right pulmonary artery associated with patent ductus arteriosus revealed at the age of 50 years on a thoracic CT angiography. Observation: A 50-year-old female patient, treated for pulmonary tuberculosis in childhood, presented with exertional dyspnea. Thoracic CT angiography showed agenesis of the right pulmonary artery with patent ductus arteriosus and right pulmonary hypoplasia. There was significant systemic vascularity with evidence of pulmonary hypertension and right heart failure. Discussion: Unilateral pulmonary artery agenesis has been rarely reported in association with a patent ductus arteriosus. Right pulmonary artery agenesis often presents as an isolated, asymptomatic finding without associated congenital heart defects. CT angiography is used to make the diagnosis. Management is often limited to surveillance. Conclusion: Isolated pulmonary artery agenesis is a rare congenital malformation but its true frequency is not well known because of the inherent difficulties in its diagnosis. The main problem remains the risk of serious complications which requires regular follow-up.

Immune profiling of murine cardiac leukocytes identifies triggering receptor expressed on myeloid cells 2 as a novel mediator of hypertensive heart failure.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, microvascular dysfunction, and myocardial fibrosis with recent evidence implicating the immune system in orchestrating cardiac remodelling. Here, we show the mouse model of deoxycorticosterone acetate (DOCA)-salt hypertension induces key elements of HFpEF, including diastolic dysfunction, exercise intolerance, and pulmonary congestion in the setting of preserved ejection fraction. A modified single-cell sequencing approach, cellular indexing of transcriptomes and epitopes by sequencing, of cardiac immune cells reveals an altered abundance and transcriptional signature in multiple cell types, most notably cardiac macrophages. The DOCA-salt model results in differential expression of several known and novel genes in cardiac macrophages, including up-regulation of Trem2, which has been recently implicated in obesity and atherosclerosis. The role of Trem2 in hypertensive heart failure, however, is unknown. We found that mice with genetic deletion of Trem2 exhibit increased cardiac hypertrophy, diastolic dysfunction, renal injury, and decreased cardiac capillary density after DOCA-salt treatment compared to wild-type controls. Moreover, Trem2-deficient macrophages have impaired expression of pro-angiogenic gene programmes and increased expression of pro-inflammatory cytokines. Furthermore, we found that plasma levels of soluble TREM2 are elevated in DOCA-salt treated mice and humans with heart failure. Together, our data provide an atlas of immunological alterations that can lead to improved diagnostic and therapeutic strategies for HFpEF. We provide our dataset in an easy to explore and freely accessible web application making it a useful resource for the community. Finally, our results suggest a novel cardioprotective role for Trem2 in hypertensive heart failure.