Abbreviated lipid guidelines for clinical practice : Based on ESC lipid guidelines 2019 and ESC cardiovascular disease prevention in clinical practice guidelines 2021.

BACKGROUND: Lipid disorders are now considered causal for atherosclerotic cardiovascular disease (ASCVD) which remains one of the most important contributors to morbidity and mortality in the developed world. Identification and early treatment of lipid disarrays remains the cornerstone of good clinical practice to prevent, halt and even reverse ASCVD. Guidelines for lipid management are imperative to help promote good clinical practice. Given the detail involved in comprehensive guidelines and the multiple areas of knowledge required by clinical practitioners, abbreviated, easy to understand, practical versions of guidelines are required to ensure dissemination of the most important information. The recent ESC lipid guidelines 2019 and the ESC guidelines on CVD prevention in clinical practice 2021 (1,2), provide an excellent detailed summary of all the latest evidence supporting lipid interventions that reduce ASCVD. METHOD: We therefore developed a single-page document with hyperlinks to help practitioners gain easy access to practical information on lipid management. It has been developed for future electronic use in clinical practice. CONCLUSION: It is presented here in a tabular format together with printable versions of the associated hyperlinks that provide the additional information required in decision making. It is hoped to audit the impact of this approach to help guide future ways of disseminating the latest clinical guideline updates.

The DA VINCI study: is Ireland achieving ESC/EAS guideline-directed LDL-C goals?

BACKGROUND: The EU-wide, cross-sectional observational study of lipid-lowering therapy (LLT) use in secondary and primary care (DA VINCI) assessed the proportion of patients achieving low-density lipoprotein cholesterol (LDL-C) goals recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines and provided an insight into regional use of LLT in Europe, including Ireland. AIMS: This analysis focuses on data from patients in Ireland who participated in the DA VINCI study. METHODS: The DA VINCI study enrolled patients receiving LLT at primary and secondary care sites across 18 European countries between June 2017 and November 2018. The study assessed the achievement of risk-based 2016 and 2019 ESC/EAS LDL-C goals. This subgroup analysis aimed to evaluate LDL-C goal attainment in an Irish cohort of primary and secondary care patients. RESULTS: In total, 198 patients from Ireland were enrolled from three primary care and three secondary care centres. Most patients were White and male, and were receiving moderate- or high-intensity statin therapy (most frequently atorvastatin or rosuvastatin). Few patients (< 10%) were receiving combination therapy of statin and ezetimibe. Approximately 60% of patients achieved their 2016 ESC/EAC LDL-C goals while less than half the patients achieved their 2019 ESC/EAS goals. Approximately half of secondary prevention patients achieved their 2016 ESC/EAS goals and only 20% of secondary prevention patients achieved their 2019 ESC/EAS goals. CONCLUSIONS: These results highlight the disparity between dyslipidaemia management in clinical practice in Ireland and guideline recommendations. TRIAL REGISTRATION: ENCePP; EU PAS 22,075; date registered 06 February 2018.

When Surgeons Are "Too Old" to Practice Surgery: Recommendations to Balance the Imperatives of Public Safety and Practical Necessity.

Few countries have legally set a maximum age for practicing surgery. This is difficult to sustain as surgeon shortages in many localities require hospitals to grant surgical privileges based on internal peer review systems. This approach is not without problems. Some hospitals and medical societies have developed competency assessment programs. Based on the literature and the experience of various jurisdictions, the authors recommend a policy approach that does not mandate a retirement age for surgeons, but rather a mandatory age of 65 at which surgeons shall be legally subject to periodic assessment of physical dexterity, eye/hand coordination, and cognitive skills.

Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study From DA VINCI.

PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

Criminal Liability for Nursing and Medical Harm.

There is a ubiquitous problem with medical errors and the concomitant costs it brings in terms of human suffering and financial loss for patients, families, and caregivers. Professional caregivers, including physicians, nurses, and others who have made clinical errors normally will fall under the risk management and quality improvement policies of the organization at which they are employed and subsequent investigation and response occurs internally. Sometimes further consequences can entail the caregiver being named as a defendant or codefendant in a civil lawsuit, and sometimes the caregiver can have professional licensure restricted or even revoked. More rarely, a caregiver can be prosecuted in a criminal legal action. When criminal prosecution occurred, it was usually for purposeful wrongdoing such as fraud, diversion of drugs, or even the intentional or reckless killing of elderly or other vulnerable people. The recent criminal prosecution of a Tennessee nurse for the reckless series of mistakes that led to the death of a single patient opens new considerations for nurses, physicians, and all caregivers, along with hospitals and healthcare systems that employ and/or work with them. The "dynamic tension" of encouraging all caregivers to own up to mistakes with patients as quickly as possible in healthcare organizations seems to be especially challenged now by the Vaught decision. This was mitigated somewhat by a relatively lenient sentence ordered by the judge in this noteworthy case.

The impact of a virtual cardiology outpatient clinic in the COVID-19 era.

BACKGROUND: Restrictions as a result of the COVID-19 pandemic have demanded an innovative approach to provide appropriate patient review. We have been running virtual cardiology clinics as per Health Service Executive guidance. AIMS: Our study aims to determine how virtual clinics change practice vs traditional clinics. METHODS: A retrospective cohort analysis was conducted on patients attending cardiology clinics in our hospital from 6 January to 13 March 2020 ('traditional clinic', n = 1644), compared with clinics during the COVID-19 outbreak, from 16 March to 22 April 2020 ('virtual clinic', n = 691), with the same medical staff. RESULTS: There was no difference in age (61 vs 60), case mix or new vs return appointments in virtual vs traditional clinics. There were similar rates of clinic participation, 71.8% vs 74.2%. A lower proportion of investigations (e.g. imaging) were booked in virtual (38.5%) vs traditional (55.7%) clinics, p < 0.00001. Management changes (e.g. medication changes) were less frequent in virtual (19.9%) vs traditional (38.5%) clinics, p < 0.00001. However, the discharge rate was higher in virtual (28.8%) vs traditional (19.5%) clinics, p = 0.00003. CONCLUSION: This study highlights that virtual clinic consultations are associated with fewer investigations, fewer management changes, and increased discharge rates compared with traditional consultations. These practice changes would reduce costs and hospital outpatient congestion by avoiding unnecessary hospital reviews. Nonetheless, it is unknown whether patients requiring face-to-face consultations could be missed as a result of this virtual approach. Longitudinal studies are required to assess clinical outcomes as a result of these practice changes and whether patient satisfaction is altered.

EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.

Low Dose Resistance Exercise: A Pilot Study Examining Effects on Blood Pressure and Augmentation Index Between Intensities.

INTRODUCTION: The effects of resistance exercise on vascular function are unclear. AIM: To investigate the acute haemodynamic (blood pressure and augmentation index) and rate of perceived exertion (RPE) response to two types of resistance exercises of equal workload-a set of unilateral 35% of one repetition maximum (1RM) quadriceps extension and a set of unilateral 70% 1RM quadriceps extension. METHODS: Twenty two young healthy males completed both exercises on separate days. Heart rate, central and peripheral systolic and diastolic blood pressure (BP), augmentation pressure, augmentation index (AIx), augmentation index at a heart rate of 75 beats per minute (AIx75), and RPE were measured using applanation tonometry before exercise, immediately after exercise, 5 min after exercise and 15 min after exercise. RESULTS: AIx75 was significantly lower 5 min after exercising at 35% of 1RM than 70% of 1RM. Systolic blood pressure was significantly lower at 5 min post exercise for both intensities. There was no significant difference in RPE between conditions or time points. CONCLUSIONS: Results suggest that changes in blood pressure and augmentation index vary depending on the intensity of resistance exercise regardless of the volume of exercise carried out. Changes in AIx75 in response to resistance exercise may be independent of changes in BP.

Evaluation of lipid services in the Republic of Ireland.

BACKGROUND: Abnormal cholesterol profiles are a major risk factor for cardiovascular disease and severe triglyceride disorders cause life threatening pancreatitis. Identification and treatment of these disorders are essential. AIM: We evaluated the services available in Ireland to manage these problems. METHODS: We contacted key personnel in 40 hospitals, 32 public and 8 private providing lipid measurements to assess investigation and treatment availability during 2017/2018. RESULTS: In public hospitals, 4 had designated lipid clinics (Dublin 3, Galway 1) (2.9 times < UK), 19 had general clinics and 9 had no service. In private hospitals, 2 had designated clinics, Limerick and Cork, and others had interested physicians. Clinics were run by cardiologists, chemical pathologists, endocrinologists or clinical pharmacologists. One clinic had a lipid nurse versus 75% in the UK. All but one provided full lipid profiles, 15 ordered Lp(a), 9 apoproteins B/A-1 and 9 genetic testing. Lp(a) and apoprotein measurements were provided locally in one hospital and one provided genetic testing. Lipid-lowering drugs were used in all hospitals and 45% had access to PCSK-9 inhibitors. No hospital provided LDL apheresis or plasma exchange. Limitations for service provision included lack of physician interest n = 9, nursing support n = 22, office space n = 13, clinic space n = 22, laboratory support n = 16, nutritional support n = 12 and pharmacy support n = 5. CONCLUSIONS: There are very limited resources available to manage lipid problems in the republic of Ireland relative to the under-resourced UK. Most services rely on interested physicians but ancillary resources are lacking. Where services are available, all drug treatments are utilised.

Presentation of Severe Rheumatic Mitral Stenosis at the Peak of the COVID-19 Pandemic and the Presumptive Treatment as Severe Coronavirus Illness.

This case report describes a young female Caucasian patient with newly presenting severe mitral stenosis at the peak of the coronavirus pandemic in the Republic of Ireland. The initial presumptive diagnosis was of severe coronavirus illness. This case report highlights the importance of keeping an open mind to alternative diagnoses and examines some of the challenges in the diagnosis and management of a rare condition in the pandemic environment. This patient gained 10 kg of weight within 6 weeks of percutaneous balloon mitral valvuloplasty, highlighting the contribution of cardiac cachexia to her low body weight and demonstrating the exceptional benefit that this treatment can offer to patients. LEARNING POINTS: To highlight mitral stenosis as a cause of cardiac cachexia and to examine the benefits gained from percutaneous balloon commissurotomy.To highlight the potential for other serious conditions to masquerade as COVID-19 and the importance of keeping an open mind to diagnoses.To examine the use of bedside echocardiography in the patient presenting with presumed coronavirus illness.

Latest Updates on Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses.

A snapshot of lipid levels in the Republic of Ireland in 2017.

BACKGROUND: Abnormalities in blood lipid levels are causally linked with cardiovascular disease and pancreatitis. Data is limited regarding lipid abnormalities in Ireland. AIMS: As part of a cholesterol awareness campaign, we performed a pilot study of current lipid levels to preliminarily assess the extent and pattern of lipid abnormalities in Ireland. METHODS: Non-fasting, full lipid profiles and glucose measurements were performed in 259 people (32 on lipid-lowering medication and 225 untreated) using a validated Cholestech LDX machine. Untreated participants included 95 men and 130 women, aged 51 ± 16 years. RESULTS: The mean ± SD, total, low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL) and median(IQR) non-HDL cholesterol and triglyceride levels in untreated individuals were 5.0 ± 1.1, 2.8 ± 1.0, 1.5 ± 0.5 and 3.4 (2.8-4.3), 1.6 (1.0-2.3) mmol/l respectively. Glucose was 5.3 (4.8-5.8) mmol/l. Glucose > 7.8 mmol/l occurred in 10 individuals (4%). Using defined criteria for non-fasting lipid levels, 60% of participants had some form of lipid abnormality with a frequency of 47% having a total cholesterol > 5, 35% with LDL > 3.0, 26% with HDL < 1.0/1.2, 33% with triglycerides > 2.0 and 32% with non-HDL cholesterol > 3.9 mmol/l. Three individuals had untreated LDL > 5 mmol/l (i.e. a ratio of 1:75 of those tested) and eight people had HDLc < 0.7 (1:28) and four had triglyceride above 7.3 mmol/l (1:56). CONCLUSIONS: This pilot study reveals significant lipid abnormalities which require further larger more detailed lipid studies to assess the true burden of lipid abnormalities in Ireland. Cascade screening and genetic testing of relatives of those with severe lipid abnormalities should be considered.

Evolving use of natriuretic peptide receptor type-C as part of strategies for the treatment of pulmonary hypertension due to left ventricle heart failure.

Pulmonary hypertension (PH) due to left ventricular heart failure (LV-HF) is a disabling and life-threatening disease for which there is currently no single marketed pharmacological agent approved. Despite recent advances in the pathophysiological understanding, there is as yet no prospect of cure, and the majority of patients continue to progress to right ventricular failure and die. There is, therefore an urgent unmet need to identify novel pharmacological agents that will prevent or reverse the increase in pulmonary artery pressures while enhancing cardiac performance in PH due to LV-HF. In the present article, we first focused on the Natriuretic Peptide Receptor type C (NPR-C) based therapeutic strategies aimed at lowering pulmonary artery pressure. Second, we reviewed potential NPR-C therapeutic strategies to reverse or least halt the detrimental effects of diastolic dysfunction and impaired nitic oxide signalling pathways, as well as possibilities for neurohumoral modulation.

Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC).

BACKGROUND AND AIMS: Management of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries. METHODS: Lead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management. RESULTS: 63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited. CONCLUSIONS: FH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

Dynamic changes of the composition of plasma HDL particles in patients with cardiac disease: Spotlight on sphingosine-1-phosphate/serum amyloid A ratio.

Several epidemiological studies reported an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and atherosclerotic cardiovascular disease (ASCVD). However, therapeutic interventions targeted at raising HDL-cholesterol failed to improve cardiovascular outcomes, suggesting that HDL components distinct from cholesterol may account for the anti-atherothrombotic effects attributed to this lipoprotein. Sphingosine-1-phosphate (S1P) and the acute phase protein serum amyloid A (SAA) have been identified as integral constituents of HDL particles. Evidence suggests that S1P and SAA levels within HDL particles may be affected by inflammation and oxidative stress, which are coexisting processes underlying ASCVD. Because SAA, an inflammation-related marker, and S1P, an anti-atherothrombotic marker, have relatively clear opposite characteristics among the HDL-associated proteins, the approach of assessing the two markers simultaneously may provide new insights in clinical practice (S1P/SAA Index). This review focuses on evidence in support of the concept that the S1P/SAA Index may affect the HDL atheroprotective properties and may, therefore represent a potential target for therapeutic interventions.

Time to redefine body mass index categories in chronic diseases? Spotlight on obesity paradox.

Obesity is a complex condition classically characterised by excessive body fat accumulation and represents one of the most important public health problems worldwide. Although several epidemiological studies have shown that elevated BMI is associated with higher morbidity, and with increased rate of death from all causes and from cardiovascular disease, accumulating evidence suggests that being overweight or obese may be protective (the so-called obesity paradox), at least in chronic diseases. These observations, not only question the validity of the BMI system, but also raise the intriguing question of whether we should redefine what the normal range of BMI is in individuals suffering from a chronic disease. In the present article, we review the available information on the association between elevated BMI and increased morbidity and mortality including obesity-related paradoxes, explore key aspects of the role and limitations of BMI as a measure of increased adiposity and outline potential solutions to address the current controversies regarding the impact of obesity on human health.

Erratum: New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.

[This corrects the article on p. 112 in vol. 9, PMID: 28951773.].

New insights and new hope for pulmonary arterial hypertension: natriuretic peptides clearance receptor as a novel therapeutic target for a complex disease.

BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a deadly and disabling disease for which there is no marketed drug that addresses the underlying disease mechanism and targets to cure patients. The lack of understanding of the disease mechanism represents the main challenges in developing curative therapies. We here report, for the first time, that mice lacking natriuretic peptides clearance receptor develop PAH. METHODS AND RESULTS: Initial studies assessed cardiac structure and function in NPR-C+/+ (wild type) and age matched, littermate NPR-C-/- mice by echocardiography. Mice lacking NPR-C had right atrial dilation, tricuspid regurgitation as well as echocardiographic signs of right ventricular pressure overload, including flattening and paradoxical bulging of the septum into the left ventricle during systole, and hypertrophy of the right ventricular free wall. Among the 10 NPR-C-/- mice aged between 12 and 20 weeks studied, 8 showed the above typical echocardiographic features of PAH [80%, 95% CI: (0.4439-0.9748)], and only one had pericardial effusion [10%, 95% CI: (0.0025-0.4450)], finding that has a prognostic significance in subjects affected by this clinical entity. To confirm the presence of increased right ventricular systolic pressure (RVSP) among NPR-C-/- mice, right heart catheterization was performed. Strikingly, RVSP was significantly elevated in NPR-C-/- mice compared to their age matched, littermate NPR-C+/+ mice, at baseline (21.95±0.56 mmHg vs. 5.3±0.6 mmHg, respectively (P<0.001)). CONCLUSION: The above results suggest that NPR-C-mediated signalling pathways play a critical role in the development of PAH, indicating that NPR-C is an important protective receptor in the heart rather than just being a clearance receptor.

Determination of Sphingosine-1-Phosphate in Human Plasma Using Liquid Chromatography Coupled with Q-Tof Mass Spectrometry.

Evidence suggests that high-density lipoprotein (HDL) components distinct from cholesterol, such as sphingosine-1-phosphate (S1P), may account for the anti-atherothrombotic effects attributed to this lipoprotein. The current method for the determination of plasma levels of S1P as well as levels associated with HDL particles is still cumbersome an assay method to be worldwide practical. Recently, a simplified protocol based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the sensitive and specific quantification of plasma levels of S1P with good accuracy has been reported. This work utilized a triple quadrupole (QqQ)-based LC-MS/MS system. Here we adapt that method for the determination of plasma levels of S1P using a quadrupole time of flight (Q-Tof) based LC-MS system. Calibration curves were linear in the range of 0.05 to 2 µM. The lower limit of quantification (LOQ) was 0.05 µM. The concentration of S1P in human plasma was determined to be 1 ± 0.09 µM (n = 6). The average accuracy over the stated range of the method was found to be 100 ± 5.9% with precision at the LOQ better than 10% when predicting the calibration standards. The concentration of plasma S1P in the prepared samples was stable for 24 h at room temperature. We have demonstrated the quantification of plasma S1P using Q-Tof based LC-MS with very good sensitivity, accuracy, and precision that can used for future studies in this field.

A natriuretic peptides clearance receptor's agonist reduces pulmonary artery pressures and enhances cardiac performance in preclinical models: New hope for patients with pulmonary hypertension due to left ventricular heart failure.

BACKGROUND: In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) is common and represents a strong predictor of death. Despite recent advances in the pathophysiological understanding there is as yet no prospect of cure of this deadly clinical entity and the majority of patients continue to progress to right ventricular failure and die. Furthermore, there is no single medical treatment currently approved for PH related to HF. There is, therefore an urgent unmet need to identify novel pharmacological agents that will prevent the progressive increased or reverse the elevated pulmonary arterial pressures while enhancing cardiac performance in HF. METHOD AND RESULTS: We here reported, for the first time, using a pressure-loop (P-V) conductance catheter system, that a specific natriuretic peptides clearance receptors' agonist, the ring-deleted atrial natriuretic peptide analogue, cANF4-23 (cANF) reduces pulmonary artery pressures. Strikingly, the administration of the cANF in these mice decreased the RVSP by 50% (n=5, F 25.687, DF 14, p<0.001) and heart rate (HR) by 11% (n=5, F 25.69, DF 14, p<0.001) as well as enhancing cardiac performance including left ventricular contractility in mice. Most strikingly, mice lacking NPR-C were much more susceptible to develop HF, indicating that NPR-C is a critical protective receptor in the heart. CONCLUSION: Natriuretic peptides clearance receptors' agonists may, therefore represent a novel and attractive therapeutic strategy for PH related to HF, and ultimately improves the life expectancy and quality for millions of people around the planet.