Implementation of a cardiogenic shock team in a tertiary academic center.

OBJECTIVE: Observational studies have shown that the management of patients with cardiogenic shock (CS) by dedicated multidisciplinary teams improves clinical outcomes. Nevertheless, these studies reflect a specific organizational setting with most patients being transferred from referring hospitals, hospitalized in cardiac intensive care units (ICU), or treated with mechanical circulatory support (MCS) devices. The purpose of this study was to document the organization and outcomes of a CS team offering acute care in an all-comer population. METHODS: A CS team was developed in a large academic tertiary institution. The team consisted of emergency care physicians, critical care cardiologists, interventional cardiologists, cardiac surgeons, ICU physicians, and heart failure specialists and was supported by a predefined operating protocol, a dedicated communication platform, and regular team meetings. RESULTS: Over 12 months, 70 CS patients (69 ± 13 years old, 67% males) were included. Acute myocardial infarction (AMI-CS) was the most common cause (64%); 31% of the patients presented post-resuscitated cardiac arrest and 56% needed invasive mechanical ventilation (IMV). Coronary angiography was performed in 70% and 53% had percutaneous coronary intervention. MCS was used in 10% and 6% were referred for urgent cardiac surgery. The in-hospital mortality in our center was 40% with 39% of the patients dying within 24 h from presentation. Overall, 76% of the live patients were discharged home. CONCLUSION: Across an all-comer population, AMI was the most common cause of CS. A significant number of patients presented post-cardiac arrest, and the majority required IMV. Mortality was high with a significant number dying within hours of presentation.

Transoesophageal echocardiography beyond the echo-laboratory. An expert consensus paper of the working group of echocardiography of the hellenic society of cardiology.

Transoesophageal echocardiography (TOE) is a well-established and valid imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for several specific diagnoses and recently a useful guide of an increasing number of catheter-based and surgical interventions. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Society of Cardiology to state the essential steps of the TOE exam performed beyond the echo lab: a) in the operating rooms intraoperatively during either transcatheter interventions, or cardiothoracic surgery and b) in the intensive care unit for critically ill patients' monitoring. This paper includes information and tips and tricks about the pre-procedural evaluation, the procedural echocardiographic guidance, and post-procedural evaluation of the result and potential complications.

Evaluation of Polygenic Risk Scores for Prediction of Coronary Artery Disease in a Greek Case-Control Study.

Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R2 metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (p-value = 2.63 × 10-25). PGS000012 was associated with a modest increase in CAD risk by 2.2% (p-value = 9.58 × 10-4). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.

Is premorbid stress assessed by hair cortisol concentration linked to Takotsubo syndrome? Results from a pilot study.

INTRODUCTION: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS. METHODS: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection. RESULTS: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001). CONCLUSIONS: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology.

Practical guidance and clinical applications of transoesophageal echocardiography. A position paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for a wide spectrum cardiac and extra-cardiac diseases. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Cardiology Society to state the essential steps of the typical TOE exam performed in echo lab. This is an educational text, describing the minimal requirements and the preparation of a meticulous TOE examination. Most importantly, it gives practical instructions to obtain and optimize TOE views and analyses the implementation of a combined two-and multi-dimensional protocol for the imaging of the most common cardiac structures during a TOE. In the second part of the article a comprehensive review of the contemporary use of TOE in a wide spectrum of valvular and non-valvular cardiac diseases is provided, based on the current guidelines and the experience of the WG members.

Inclisiran: the preclinical discovery and development of a novel therapy for the treatment of atherosclerosis.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. Lipid lowering therapy (LLT) constitutes the cornerstone of ASCVD prevention and treatment. However, several patients fail to achieve therapeutic goals due to low treatment adherence or limitations of standard-of-care (SoC) LLTs. Inclisiran represents a pivotal low-density lipoprotein cholesterol (LDL-C) lowering agent aiming to address current unmet needs in LLT. It is the first available small interfering RNA (siRNA) LLT, specifically targeting PCSK9 mRNA and leading to post-transcriptional gene silencing (PTGS) of the PCSK9 gene. AREAS COVERED: Promising phase III trials revealed an ~ 50% reduction in LDL-C levels with subcutaneous inclisiran administration on days 1 and 90, followed by semiannual booster shots. Coupled with inclisiran's favorable safety profile, these findings led to its approval by both the EMA and FDA. Herein, the authors highlight the preclinical discovery and development of this agent and provide the reader with their expert perspectives. EXPERT OPINION: The evolution of gene-silencing treatments offers new perspectives in therapeutics. Inclisiran appears to have the potential to revolutionize ASCVD prevention and treatment, benefiting millions of patients. Ensuring widespread availability of Inclisiran, as well as managing additional healthcare costs that may arise, should be of paramount importance.

Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease [PAD]), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.

Gender Differences Among Very Young Patients With Acute Coronary Syndrome: Long-Term Follow-Up of the STAMINA Study.

The rate of hospitalization for acute coronary syndrome (ACS) among young patients is increasing. Healthcare disparities remain unsolved among female patients. We explored gender differences regarding risk factors, clinical presentation, in-hospital treatment, and long-term outcomes among ACS patients. A total of 445 patients with very early ACS (men ≤ 35 years and women ≤ 40 years of age) were followed for a median of 5 years. Primary clinical endpoint was the composite of cardiac death, non-fatal myocardial infarction, stroke, and coronary revascularization. Women accounted for 16% of cases. Smoking was the most prevalent risk factor, 56% and 60% of the females and males, respectively, continued to smoke after ACS. Chest pain was typical in 85% and 83% of the female and male patients, respectively. In-hospital treatment (pharmacological and reperfusion) as well as the composite clinical endpoint during follow-up did not differ between female and male patients. Lipid-lowering therapy was suboptimal in both genders, and persistence of smoking was the sole predictor for the composite clinical endpoint (hazard ratio: 2.30 [95% CI: 1.26-4.20]; P = .007). In conclusion, in-hospital treatment was similar between male and female patients. However, the majority of them continued smoking, and this was an independent predictor for future adverse outcomes.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

NT-proBNP/cardiac troponin T ratio >7.5 on the second day of admission can differentiate Takotsubo from acute coronary syndrome with good accuracy.

BACKGROUND: Takotsubo syndrome (TTS) is not usually diagnosed until patients with suspected acute coronary syndrome (ACS) and echocardiographically detected apical aneurysm are found to have "normal" coronary angiography (CA). Our aim was to explore whether cardiac biomarkers can contribute to the early diagnosis of TTS. METHODS: Ratios of N-terminal-pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT) both expressed in pg/mL [admission and the 3 following days] were compared in 38 patients with TTS and 114 ACS patients of whom 58 had non-ST-elevation myocardial infarction (NSTEMI). RESULTS: NT-proBNP/cTnT ratio at admission and during the following 3 days was significantly higher in TTS compared to patients with ACS [18.4 (8.7-41.7) vs 2.9 (0.8-6.8), 29.6 (14.3-53.7) vs 1.2 (0.5-2.7), 30.0 (11.6-50.9) vs 1.7 (0.5-3.0), 27.8 (11.3-42.6) vs 1.4 (0.6-2.8), respectively, all <0.001]. Βest discrimination of TTS from ACS was possible with the ratio of NT-proBNP/cTnT on the 2nd day. A cut-off value of NT-proBNP/cTnT ratio >7.5 had a sensitivity of 97.3%, a specificity of 95.4% and an accuracy of ∼96% in detecting TTS as opposed to ACS. Furthermore, the ratio of NT-proBNP/cTnT preserved its discriminatory value in the subgroup of patients with NSTEMI. In particular, an NT-proBNP/cTnT ratio >7.5 on the 2nd day had a sensitivity of 97.3%, a specificity of 91.4%, and an accuracy of 93.7% in differentiating TTS from NSTEMI. CONCLUSIONS: An NT-proBNP/cTnT ratio >7.5 on the 2nd day of admission can be useful for the early identification of TTS among selected patients initially presenting with ACS, a ratio more clinically useful in the setting of NSTEMI.

Is inverse association between lipoprotein(a) and diabetes mellitus another paradox in cardiometabolic medicine?

INTRODUCTION: The impact of Type II Diabetes mellitus (T2DM) on cardiovascular disease (CVD) is well-established, while lipoprotein(a) [Lp(a)] has recently emerged as a recognized CVD risk factor. The rising prevalence of T2DM resulting from modern lifestyles and the development of specific Lp(a)-lowering agents brought the association between T2DM and Lp(a) in the forefront. AREAS COVERED: Despite advancements in T2DM treatment, diabetic patients remain at very-high risk of CVD. Lp(a) may, to some extent, contribute to the persistent CVD risk seen in diabetic patients, and the coexistence of T2DM and elevated Lp(a) levels appears to synergistically amplify overall CVD risk. The relationship between T2DM and Lp(a) is paradoxical. On one hand, high Lp(a) plasma concentrations elevate the risk of diabetic microvascular and macrovascular complications. On the other hand, low Lp(a) plasma concentrations have been linked to an increased risk of developing T2DM. EXPERT OPINION: Comprehending the association between T2DM and Lp(a) is critical due to the pivotal roles both entities play in overall CVD risk, as well as the unique aspects of their relationship. The mechanisms underlying the inverse association between T2DM and Lp(a) remain incompletely understood, necessitating further meticulous research.

A Posteriori Dietary Patterns and Coronary Artery Disease in a Greek Case-Control Study.

INTRODUCTION: Diet is one of the most important modifiable risk factors associated with cardiovascular health (CH). Research identifying dietary patterns (DPs) through data-driven analysis and reporting associations between DPs and coronary artery disease (CAD) outcomes is rather limited. OBJECTIVE: The aim of the present report was to generate DPs through factor analysis (FA) and to examine their association with CAD risk. METHODS: Participants (n = 1017) consisted of cases diagnosed with CAD (n = 356) and controls (n = 661) drawn from the THISEAS study. Demographic, anthropometric and lifestyle data were collected. Dietary components were generated through FA. Logistic regression analysis was performed to estimate CAD relative risks. RESULTS: FA generated seven dietary components, explaining 53.5% of the total variation in intake. The Western-type DP showed a modest significant association with CAD risk, after controlling for confounders (OR = 1.20; 95% CI = 1.09-1.32, p < 0.001). The vegetarian-type DP was not significantly associated with the likelihood of CAD (OR = 0.95; 95% CI = 0.84-1.04, p = 0.259). DISCUSSION: The Western-type DP was positively associated with CAD risk and the odds were further increased after controlling for confounders. This finding is in concordance with previously reported positive associations between Western patterns and CAD risk. Limited data exist regarding a posteriori DPs and their effect on CAD risk.

Novel Pharmacological Therapies for the Management of Hyperlipoproteinemia(a).

Lipoprotein(a) [Lp(a)] is a well-established risk factor for cardiovascular disease, predisposing to major cardiovascular events, including coronary heart disease, stroke, aortic valve calcification and abdominal aortic aneurysm. Lp(a) is differentiated from other lipoprotein molecules through apolipoprotein(a), which possesses atherogenic and antithrombolytic properties attributed to its structure. Lp(a) levels are mostly genetically predetermined and influenced by the size of LPA gene variants, with smaller isoforms resulting in a greater synthesis rate of apo(a) and, ultimately, elevated Lp(a) levels. As a result, serum Lp(a) levels may highly vary from extremely low to extremely high. Hyperlipoproteinemia(a) is defined as Lp(a) levels > 30 mg/dL in the US and >50 mg/dL in Europe. Because of its association with CVD, Lp(a) levels should be measured at least once a lifetime in adults. The ultimate goal is to identify individuals with increased risk of CVD and intervene accordingly. Traditional pharmacological interventions like niacin, statins, ezetimibe, aspirin, PCSK-9 inhibitors, mipomersen, estrogens and CETP inhibitors have not yet yielded satisfactory results. The mean Lp(a) reduction, if any, is barely 50% for all agents, with statins increasing Lp(a) levels, whereas a reduction of 80-90% appears to be required to achieve a significant decrease in major cardiovascular events. Novel RNA-interfering agents that specifically target hepatocytes are aimed in this direction. Pelacarsen is an antisense oligonucleotide, while olpasiran, LY3819469 and SLN360 are small interfering RNAs, all conjugated with a N-acetylgalactosamine molecule. Their ultimate objective is to genetically silence LPA, reduce apo(a) production and lower serum Lp(a) levels. Evidence thus so far demonstrates that monthly subcutaneous administration of a single dose yields optimal results with persisting substantial reductions in Lp(a) levels, potentially enhancing CVD risk reduction. The Lp(a) reduction achieved with novel RNA agents may exceed 95%. The results of ongoing and future clinical trials are eagerly anticipated, and it is hoped that guidelines for the tailored management of Lp(a) levels with these novel agents may not be far off.

Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1ß) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/ß2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

Lipoprotein(a) is associated with premature coronary artery disease: a meta-analysis.

BACKGROUND: Lipoprotein(a) is associated with adverse cardiovascular outcomes and its association with premature coronary artery disease (pCAD) is underexamined. The primary aim of the study is to compare serum lipoprotein(a) levels between pCAD cases and controls. METHODS: We conducted a systematic review and the MEDLINE database, ClinicalTrials.gov, medRxiv and Cochrane Library were searched for studies evaluating lipoprotein(a) and pCAD. Standardized mean differences (SMD) of lipoprotein(a) in pCAD patients versus the controls were pooled by a random-effects meta-analysis. The presence of statistical heterogeneity was evaluated with the Cochran Q chi-square test and the quality of the included studies was assessed via the Newcastle-Ottawa Scale. RESULTS: A total of 11 studies were found eligible, reporting on the difference in lipoprotein(a) levels between pCAD patients and controls. Serum lipoprotein(a) concentration was found significantly increased in patients with pCAD (SMD = 0.97; 95% confidence intervals, 0.52-1.42; P < 0.0001; I2 = 98%) as compared to controls. High statistical heterogeneity and relatively small case-control studies of moderate quality are the main limitations of this meta-analysis. CONCLUSION: Lipoprotein(a) levels are significantly increased in patients with pCAD as compared to controls. Further studies are needed to clarify the clinical significance of this finding.

Lipoprotein(a): Its Association with Calcific Aortic Valve Stenosis, the Emerging RNA-Related Treatments and the Hope for a New Era in "Treating" Aortic Valve Calcification.

The treatment of patients with aortic valve calcification (AVC) and calcific aortic valve stenosis (CAVS) remains challenging as, until today, all non-invasive interventions have proven fruitless in preventing the disease's onset and progression. Despite the similarities in the pathogenesis of AVC and atherosclerosis, statins failed to show a favorable effect in preventing AVC progression. The recognition of lipoprotein(a) [Lp(a)] as a strong and potentially modifiable risk factor for the development and, perhaps, the progression of AVC and CAVS and the evolution of novel agents leading in a robust Lp(a) reduction, have rekindled hope for a promising future in the treatment of those patients. Lp(a) seems to promote AVC via a 'three hit' mechanism including lipid deposition, inflammation and autotaxin transportation. All of these lead to valve interstitial cells transition into osteoblast-like cells and, thus, to parenchymal calcification. Currently available lipid-lowering therapies have shown a neutral or mild effect on Lp(a), which was proven insufficient to contribute to clinical benefits. The short-term safety and the efficacy of the emerging agents in reducing Lp(a) have been proven; nevertheless, their effect on cardiovascular risk is currently under investigation in phase 3 clinical trials. A positive result of these trials will probably be the spark to test the hypothesis of the modification of AVC's natural history with the novel Lp(a)-lowering agents.