Renal Congestion in Heart Failure: Insights in Novel Diagnostic Modalities.

Heart failure is increasingly prevalent and is estimated to increase its burden in the following years. A well-reported comorbidity of heart failure is renal dysfunction, where predominantly changes in the patient's volume status, tubular necrosis or other mechanical and neurohormonal mechanisms seem to drive this impairment. Currently, there are established biomarkers evaluating the patient's clinical status solely regarding the cardiovascular or renal system. However, as the coexistence of heart and renal failure is common and related to increased mortality and hospitalization for heart failure, it is of major importance to establish novel diagnostic techniques, which could identify patients with or at risk for cardiorenal syndrome and assist in selecting the appropriate management for these patients. Such techniques include biomarkers and imaging. In regards to biomarkers, several peptides and miRNAs indicative of renal or tubular dysfunction seem to properly identify patients with cardiorenal syndrome early on in the course of the disease, while changes in their serum levels can also be helpful in identifying response to diuretic treatment. Current and novel imaging techniques can also identify heart failure patients with early renal insufficiency and assess the volume status and the effect of treatment of each patient. Furthermore, by assessing the renal morphology, these techniques could also help identify those at risk of kidney impairment. This review aims to present all relevant clinical and trial data available in order to provide an up-to-date summary of the modalities available to properly assess cardiorenal syndrome.

Unravelling the effect of renal denervation on glucose homeostasis: more questions than answers?

Renal Denervation (RDN) is an interventional, endovascular procedure used for the management of hypertension. The procedure itself aims to ablate the renal sympathetic nerves and to interrupt the renal sympathetic nervous system overactivation, thus decreasing blood pressure (BP) levels and total sympathetic drive in the body. Recent favorable evidence for RDN resulted in the procedure being included in the recent European Guidelines for the management of Hypertension, while RDN is considered the third pillar, along with pharmacotherapy, for managing hypertension. Sympathetic overactivation, however, is associated with numerous other pathologies, including diabetes, metabolic syndrome and glycemic control, which are linked to adverse cardiovascular health and outcomes. Therefore, RDN, via ameliorating sympathetic response, could be also proven beneficial for maintaining an euglycemic status in patients with cardiovascular disease, alongside its BP-lowering effects. Several studies have aimed, over the years, to provide evidence regarding the pathophysiological effects of RDN in glucose homeostasis as well as investigate the potential clinical benefits of the procedure in glucose and insulin homeostasis. The purpose of this review is, thus, to analyze the pathophysiological links between the autonomous nervous system and glycemic control, as well as provide an overview of the available preclinical and clinical data regarding the effect of RDN in glycemic control.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

One-year outcomes following a hypertensive urgency or emergency.

There are scarce data on the comparative prognosis between patients with hypertensive emergencies (HE), urgencies (HU), and those without HU or HE (HP). Our study aimed to compare cardiovascular (CV) outcomes of HE, HU, and HP during a 12-month follow-up period. The population consisted of 353 consecutive patients presenting with HE or HU in a third-care emergency department and subsequently referred to our hypertension center for follow-up. After both groups completed scheduled follow-up visits, patients with HU were matched one-to-one by age, sex, and hypertension history with HP who attended our hypertension center during the same period. Primary outcomes were 1) a recurrent hypertensive HU or HE event and 2) non-fatal CV events (coronary heart disease, stroke, heart failure, or CV interventions), while secondary outcomes were 1) all-cause death, 2) CV death, 3) non-CV death, and 4) any-cause hospitalization. Events were prospectively registered for all three groups. During the study period, 81 patients were excluded for not completing follow-up. Among eligible patients(HE = 94; HU = 178), a total of 90 hospitalizations and 14 deaths were recorded; HE registered greater CV morbidity when compared with HU (29 vs. 9, HR 3.43, 95 % CI 1.7-6.9, p = 0.001), and increased CV mortality (8 vs. 1, HR 13.2, 95 % CI 1.57-110.8, p = 0.017). When opposing HU to HP, events did not differ substantially. Cox regression models were adjusted for age, sex, CV and chronic kidney disease, diabetes mellitus, and smoking. During 1-year follow-up, the prognosis of HU was better than HE but not different compared to HP. These results highlight the need for improved care of HU and HE.

LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis.

Low-density lipoprotein (LDL) and oxidized LDL (oxLDL) are major contributors to atherogenesis, as endogenous antigens, via several receptors such as LOX 1. A PubMed search was conducted in order to identify relevant articles regarding LOX-1's role in the atherosclerosis, diagnosis, prognostic use and molecules that could be used for therapy. The references of the manuscripts obtained were also reviewed, in order to find additional relevant bibliography. LOX-1 is a lectin-like pattern recognition receptor, mostly expressed in endothelial cells (ECs) which can bind a variety of molecules, including oxLDL and C-reactive protein (CRP). LOX-1 plays a key role in oxLDL's role as a causative agent of atherosclerosis through several pathologic mechanisms, such as oxLDL deposition in the subintima, foam cell formation and endothelial dysfunction. Additionally, LOX-1 acts a scavenger receptor for oxLDL in macrophages and can be responsible for oxLDL uptake, when stimulated. Serum LOX-1 (sLOX-1) has emerged as a new, potential biomarker for diagnosis of acute coronary syndromes, and it seems promising for use along with other common biomarkers in everyday clinical practice. In a therapeutic perspective, natural as well as synthetic molecules exert anti-LOX-1 properties and attain the receptor's pathophysiological effects, thus extensive research is ongoing to further evaluate molecules with therapeutic potential. However, most of these molecules need further trials in order to properly assess their safety and efficacy for clinical use. The aim of this review is to investigate LOX-1 role in atherogenesis and explore its potential as diagnostic tool and therapeutic target.

Your Heart Function Has Normalized-What Next After TRED-HF?

PURPOSE OF REVIEW: With the widespread implementation of contemporary disease-modifying heart failure therapy, the rates of normalization of ejection fraction are continuously increasing. The TRED-HF trial confirmed that heart failure remission rather than complete recovery is typical in patients with dilated cardiomyopathy who respond to therapy. The present review outlines key points related to the management and knowledge gaps of this growing patient group, focusing on patients with non-ischaemic dilated cardiomyopathy. RECENT FINDINGS: There is substantial heterogeneity among patients with normalized ejection fraction. The specific etiology is likely to affect the outcome, although a multiple-hit phenotype is frequent and may not be identified without comprehensive characterization. A monogenic or polygenic genetic susceptibility is common. Ongoing pathophysiological processes may be unraveled with advanced cardiac imaging, biomarkers, multi-omics, and machine learning technologies. There are limited studies that have investigated the withdrawal of specific heart failure therapies in these patients. Diuretics may be safely withdrawn if there is no evidence of congestion, while continued therapy with at least some disease-modifying therapy is likely to be required to reduce myocardial workload and sustain remission for the vast majority. Understanding the underlying disease mechanisms of patients with normalized ejection fraction is crucial in identifying markers of myocardial relapse and guiding individualized therapy in the future. Ongoing clinical trials should inform personalized approaches to therapy.

Ethnic and sex-related differences at presentation in apical hypertrophic cardiomyopathy: An observational cross-sectional study.

BACKGROUND: We investigated whether ethnicity and sex are associated with different clinical presentations and cardiovascular magnetic resonance (CMR) findings in individuals with apical hypertrophic cardiomyopathy (ApHCM). METHODS: A retrospective observational cohort study of consecutive ApHCM patients from a large tertiary referral center in the United Kingdom (UK). Demographic, clinical, 12­lead electrocardiogram (ECG) and CMR findings were collected. Participants presented in our clinics between 2010 and 2020. 'Pure' ApHCM was defined as isolated apical hypertrophy and 'mixed' with both apical and septal hypertrophy but with the apical segments of a greater wall thickness. Deep T-wave inversion was defined as ≥5 mm in any electrocardiogram lead. RESULTS: A total of 150 consecutive ApHCM patients (75% men, 25% women; 37% White, 25% Black, 24% Asian and 15% of Mixed/Other ethnicity) were included. Females were diagnosed at an older age compared to men, had less prominent ECG changes, had higher left atrial area index, and were more hypertensive. Black patients had higher left ventricular mass index, more hypertension, and more of the 'mixed' type of ApHCM. The majority of hypertensive male patients showed the 'mixed' phenotype. CONCLUSIONS: Individuals of Black ethnicity and hypertensive male patients are more likely to present with mixed apical and basal hypertrophy, whereas White, Asian and non-hypertensive male patients tend to have hypertrophy limited to the apex. Females present at an older age and are less likely to have deep T wave inversion on ECG.

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

BACKGROUND AND AIM: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. METHODS: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. RESULTS: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. CONCLUSIONS: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms.

Cardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review.

Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension. Attention to the specific clinical/biochemical phenotypes of these conditions may assist clinicians to screen for and confirm secondary forms of hypertension. Thereby, early signs of heart damage can be recognized and monitored, allowing individualized treatment to delay or prevent evolution toward more advanced disease.

Profile and management of hypertensive urgencies and emergencies in the emergency cardiology department of a tertiary hospital: a 12-month registry.

AIMS: Currently there are scarce epidemiological data regarding prevalence, clinical phenotype, and therapy of hypertensive urgencies (HU) and emergencies (HE). The aim of this article was to record the prevalence, clinical characteristics, and management of patients with HU and HE assessed in an emergency department (ED) of a tertiary hospital. METHODS AND RESULTS: The population consisted of patients presenting with HE and HU in the ED (acute increase in systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥120 mmHg with and without acute target organ damage, respectively). Of the 38 589 patients assessed in the ED during a 12-month period, 353 (0.91%) had HU and HE. There were 256 (72.5%) cases presented as HU and 97 (27.5%) as HE. Primary causes for both HU and HE were stress/anxiety (44.9%), increased salt intake (33.9%), and non-adherence to medication (16.2%). Patients with HU reported mainly dizziness/headache (46.8%) and chest pain (27.4%), whereas those with HE presented dyspnoea (67%), chest pain (30.2%), dizziness/headache (10.3%), and neurological disorders (8.2%). In HE, the underlying associated conditions were pulmonary oedema (58%), acute coronary syndrome (22.6%), and neurological disorders/stroke (7.2%). All HE cases were hospitalized and received intensive healthcare, including dialysis. CONCLUSION: This 1-year single-centre registry demonstrates a reasonable prevalence of HU and HE contributing to the high volume of visits to the ED. Stress, increased salt intake and non-adherence were main triggers of HE and HU. Dizziness and headache were the prevalent symptoms of HU patients while heart failure was the most common underlying disease in patients with HE.

Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension.

Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.

Joint ESH excellence centers' national meeting on renal sympathetic denervation: A Greek experts' survey.

OBJECTIVE: The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. METHODS: A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. RESULTS: A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. CONCLUSION: The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

Rationale and Design of the ACS-BP Study: Prognostic Value of In-Hospital Blood Pressure and Indices of Atherosclerosis in Acute Coronary Syndromes.

BACKGROUND: High blood pressure (BP) is a leading risk factor for coronary artery disease and other major cardiovascular events. OBJECTIVE: Blood pressure variability (BPV), ambulatory arterial stiffness index (AASI) and ankle- brachial index (ABI) have been proposed as indices that can improve risk stratification for an adverse cardiac outcome. However, their utility in the setting of acute coronary syndromes (ACS) is unclear. METHODS: The ACS-BP study is a single-centre observational cohort study designed to investigate the prognostic role of haemodynamic load and arterial stiffness indices for cardio-renal outcomes in patients with acute myocardial infarction (AMI). All consecutive patients admitted with a diagnosis of acute AMI with or without ST segment elevation were screened for inclusion in the study. The management of AMI will follow current guidelines. RESULTS AND DISCUSSION: Data from baseline clinical and laboratory parameters during their hospitalization were collected. The haemodynamic load of each patient was determined by clinical BP values as well as 24-h ambulatory BP monitoring. The AASI was calculated from the raw 24-h BP data and ABI was measured after the third day of hospitalization using a certified device. Patients were followed-up for 12 months in order to collect data for hard cardiovascular and renal endpoints. CONCLUSION: The study results should clarify the role of these non-invasive tools in secondary risk stratification of such patients.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

Exercise: The ultimate treatment to all ailments?

Extensive clinical research has provided robust evidence that exercise is a cost-effective measure to substantially alleviate the burden of a large number of diseases, many of which belong to the cardiovascular (CV) spectrum. In terms of cardiac benefit, the positive effects of exercise are attributed to improvements in standard risk factors for atherosclerosis, as well as to its positive impact on several pathophysiological mechanisms for CV diseases. For secondary prevention, exercise, optimally in the context of a cardiac rehabilitation program, has been shown to improve functional capacity and survival. Clinicians should encourage physical activity and provide exercise recommendations for all patients, taking into consideration any underlying pathology. In the present review, the benefits of exercise for the prevention and treatment of major CV risk factors and heart conditions are analyzed.

Hypertension and patients with acute coronary syndrome: Putting blood pressure levels into perspective.

Arterial hypertension is a well-established cardiovascular risk factor, and blood pressure (BP) control has largely improved the prognosis of hypertensive patients. A number of studies have assessed the role of BP levels in the prognosis of patients with acute coronary syndromes. Pathophysiologic links of hypertension to acute myocardial infarction (MI) include endothelial dysfunction, autonomic nervous system dysregulation, impaired vasoreactivity, and a genetic substrate. A history of hypertension is highly prevalent among patients presenting with MI, and some, but not all, studies have associated it with a worse prognosis. Some data support that low levels of admission and in-hospital BP may indicate an increased risk for subsequent events. Risk scores used in patients with MI have, therefore, included BP levels and a history of hypertension in their variables. Of note, good long-term BP control, ideally initiated prior to discharge, should be pursued in order to improve secondary prevention.

Effects of oral paricalcitol therapy on arterial stiffness and osteopontin in hypertensive patients with chronic kidney disease and secondary hyperparathyroidism.

BACKGROUND: Arterial stiffness is linked to the progression of atherosclerosis, while activation of vitamin D receptor exerts favorable cardiovascular effects in patients with renal insufficiency. In this study, we investigated the effects of oral treatment with paricalcitol, a potent vitamin D receptor activator, on arterial stiffness and osteopontin, a marker of atherosclerosis, in hypertensive patients with chronic kidney disease (CKD) and secondary hyperparathyroidism. METHODS: We followed up 29 treated hypertensive patients (mean age: 74.1 years, 19 men, office blood pressure = 132/85 mmHg) with CKD stages 3-5 (mean glomerular filtration rate [GFR] = 19.4 ml/min/1.73 m2) who were on therapy with oral paricalcitol for 1 year. The control group consisted of 10 age-, sex-, and GFR-matched hypertensive patients with secondary hyperparathyroidism. RESULTS: After 1 year of treatment with paricalcitol compared to baseline, there was no statistical difference in levels of GFR, office blood pressure, and osteopontin (p = NS for all), while carotid-femoral PWV was reduced from 11.8 ± 2.6 m/s to 11.2 ± 2.4 m/s (p < 0.05). The control group exhibited no significant changes in carotid-femoral PWV (p = NS). CONCLUSIONS: Treatment with oral paricalcitol in hypertensive subjects suffering from CKD stages 3-5 and secondary hyperparathyroidism is accompanied by amelioration of arterial stiffness as reflected by the reduction of carotid-femoral PWV.

Renal resistive index in hypertensive patients.

Spectral Doppler ultrasonography provides the evaluation of renal resistive index (RRI), a noninvasive and reproducible measure to investigate arterial compliance and/or resistance. RRI seems to possess an important role in the evaluation of diverse cases of secondary hypertension. In essential hypertension, RRI is associated with subclinical markers of target organ damage and reflects renal disease progression beyond albuminuria and creatinine clearance. Also, RRI can estimate cardiovascular and renal risk. The evaluation of RRI may also help the therapeutic decisions. Given its simple assessment, RRI emerges as a simple method and a "multifunctional" tool that could help on the cardiovascular risk evaluation of the hypertensive patient.