Left Ventricular Overload Research Articles

Left ventricular decompression in veno-arterial extracorporeal membrane oxygenation.

Despite the survival benefit of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for treatment of refractory cardiogenic shock, it can also have potentially deleterious effects of left ventricular overload and pulmonary edema. The objective of this review was to investigate the current evidence on the incidence, diagnosis, risk factors, prevention, and interventions for left ventricular overload in adult and pediatric VA-ECMO patients. Five electronic databases, including MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews, were searched for original published studies from their dates of inception to January 2018. All types of adult and pediatric studies that investigated LV overload in VA-ECMO and were published in the English language were reviewed. Exclusion criteria included abstracts and conference presentations. The reported incidence and sequelae of LV overload in VA-ECMO are highly variable, with presentations ranging from pulmonary arterial diastolic pressures of greater than 25 mmHg and LV distention on echocardiography, to severe pulmonary edema, LV thrombosis, and refractory ventricular arrhythmias. Currently, there are no standardized diagnostic criteria or guidelines for the type and timing of intervention for LV overload. Techniques for LV decompression have included direct surgical LV venting with catheter insertion via sternotomy or a minimally invasive incision; percutaneous catheterization via a transaortic, transseptal, or transpulmonary approach; ventricular assist devices; and intra-aortic balloon pumps. Left ventricular volume distention is a significant problem in VA-ECMO patients, with sequelae including myocardial ischemia, severe pulmonary edema, and intracardiac thrombosis. Further research is required on its incidence, diagnostic criteria, and risk factors, as well as the optimal timing and method for LV decompression, given the diversity of surgical and percutaneous techniques that are available.

Reduction of left ventricular mass, left atrial size, and N-terminal pro-B-type natriuretic peptide level following alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy.

Alcohol septal ablation (ASA) is an alternative to surgical treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM). Through alcohol-induced necrosis, ASA leads to an increase in left ventricular outflow tract (LVOT) diameter and a decrease in LVOT pressure gradient. We sought to assess the effect of ASA on left ventricular (LV) wall thickness and mass, left atrial (LA) size, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. The study cohort consisted of 50 patients with HOCM (30 in the ASA group, 20 in the optimal pharmacotherapy group [OPG]). Transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and NT-proBNP level analysis were performed at baseline and at six months. All parameters are presented as means. In the ASA group, the maximal LVOT pressure gradient decreased from 122.7 to 54.8 mmHg directly after ASA and to 37.2 mmHg after a further six months (p < 0.0001). The NT-proBNP level decreased from 2174.4 to 1103.4 pg/mL (p < 0.001). On TTE, the interventricular septum (IVS) thickness decreased to from 23.6 to 19.4 mm (p < 0.0001) and the lateral wall (LW) thickness decreased from 15.9 to 14.2 mm (p < 0.007). On CMR, basal IVS thickness decreased from 23.7 to 18.0 mm (p < 0.0001) and the LW thickness decreased from 13.2 to 12.2 mm (p = 0.02). IVS mass reduced from 108.9 to 91.5 g (-16%; p < 0.001). All of the above parameters remained unchanged in the OPG. Successful ASA reduces LV hypertrophy and improves parameters of the LV overload, resulting in LV wall hy-pertrophy regression, and LA size and NT-proBNP level reduction. The above parameters may be as useful in assessing the efficacy of ASA as the LVOT gradient itself.

Unloading of the Left Ventricle During Venoarterial Extracorporeal Membrane Oxygenation Therapy in Cardiogenic Shock

ObjectivesThis report relates the authors' ongoing experience with percutaneous left ventricular (LV) unloading by using a transaortic LV assist device in combination with venoarterial extracorporeal membrane oxygenation (VA-ECMO) and provides an in-depth analysis of the hemodynamic benefit of this approach. BackgroundVA-ECMO is increasingly used in cases of severe cardiogenic shock. However, increase in afterload with subsequent LV overload is a major drawback of VA-ECMO. MethodsConsecutive patients were treated with a transaortic LV assist device in addition to VA-ECMO for cardiogenic shock. The primary endpoint was 30-day all-cause mortality. Additional endpoints included weaning from VA-ECMO and safety endpoints. ResultsBetween September 2013 and January 2018, 106 patients were treated with percutaneous LV unloading, using a transaortic LV assist device in combination with VA-ECMO. Successful weaning from VA-ECMO support was achieved in 51.9% of all patients. In the overall cohort, survival at day 30 was 35.8%, which was higher than predicted by the SAVE score (20%) or by the SAPS-II score (6.9%). Right heart catheterization indicated a marked decrease of PCWP after addition of the device to VA-ECMO. ConclusionsThe strategy of percutaneous LV unloading using a transaortic LV assist device in combination with VA-ECMO improved outcome in an all-comers cohort compared to established risk scores. A prospective, randomized study is needed to further investigate this approach.

Prediction of premature ventricular complex origin in left vs. right ventricular outflow tract: a novel anatomical imaging approach.

Left ventricular (LV) outflow tract ventricular arrhythmias (OTVA) are associated with hypertension (HT), older age, and LV dysfunction, suggesting that LV overload plays a role in the aetiopathogenesis. We hypothesized that anatomical modifications of the LV outflow tract (LVOT) could predict left vs. right OTVA site of origin (SOO). Fifty-six (32 men, 53 ± 18 years old) consecutive patients referred for OTVA ablation were included. Cardiac multidetector computed tomography was performed before ablation and then imported to the CARTO system to aid the mapping and ablation procedure. Anatomical characteristics of the aortic root as well as aortopulmonary valvular planar angulation (APVPA) were analysed. The LV was the OTVA SOO (LVOT-VA) in 32 (57%) patients. These patients were more frequently male (78% vs. 22%, P = 0.001), older (57 ± 18 vs. 47 ± 18 years, P = 0.055), and more likely to have HT (59% vs. 21%, P = 0.004), compared to right OTVA patients. Aortopulmonary valvular planar angulation was higher in LVOT-VA patients (68 ± 5° vs. 55 ± 6°, respectively; P < 0.001). Absolute size of all aortic root diameters was associated with LVOT origin. However, after indexing by body surface area, only sinotubular junction diameter maintained a significant association (P = 0.049). Multivariable analysis showed that APVPA was an independent predictor of LVOT origin. Aortopulmonary valvular planar angulation ≥62° reached 94% sensitivity and 83% specificity (area under the curve 0.95) for predicting LVOT origin. The measurement of APVPA as a marker of chronic LV overload is useful for the prediction of left vs. right ventricular OTVA origin.

Physical activity and structured exercise in patients with type 2 diabetes mellitus and heart failure

Patients with type 2 diabetes mellitus (T2DM) or heart failure (HF) are encouraged to adopt a physically active lifestyle and participation in structured exercise is endorsed as a safe and effective adjunct to medical therapy in both conditions. This article aims to provide health care professionals with the information required to tailor guidance relating to physical activity and exercise for individuals with T2DM and HF by: (1) presenting an overview of current guidelines, and (2) providing practical suggestions for their implementation. ‘Traditional’ forms of exercise training include moderate to vigorous-intensity aerobic exercise and dynamic resistance exercise. Benefits of exercise training include improved cardiorespiratory fitness and physical function, more favourable body composition, lower metabolic risk and enhanced quality of life. Before engaging in structured exercise, medical clearance may be required for certain types of activities, and precautions should be taken to minimise the risk of hypoglycaemia and left-ventricular overload in patients with T2DM and HF. Importantly, patients with HF should be educated to distinguish severe adverse symptoms during exercise from expected feelings of breathlessness and fatigue. The latter should not be a reason to discourage patients from engaging in as much physical activity and structured exercise as possible. In order to optimise adherence, exercise prescription should be driven by patient preferences, motivations and individual circumstances. Consideration should also be given to more novel approaches, such as reducing sedentary behaviour and high-intensity interval training. Copyright © 2018 John Wiley & Sons.

Hypertension and Aortic Stenosis: A Review.

Aortic stenosis is a common form of valvular heart disease which often coexists with hypertension. These diseases represent two distinct forms of left ventricular systolic overload and in combination may be associated with disadvantageous left ventricular remodeling, increased mortality and heart failure. The treatment of hypertension in aortic stenosis remains a challenging problem with limited data to guide clinical practice. We performed a comprehensive online literature review to find relevant published literature on the topic of hypertension and aortic stenosis. In the present manuscript, we review the pathophysiology of aortic stenosis in combination with hypertension and the effects on the left ventricle. We also provide general recommendations for medical therapy for treatment of hypertension in aortic stenosis and review the available data on specific antihypertensive agents in this context. Aortic stenosis and hypertension commonly coexist and significantly impact the diagnosis and classification of aortic stenosis severity and symptoms. Treatment of hypertension among patients with severe aortic stenosis can be challenging. Among specific antihypertensive agents studied in this context, ACE-inhibitors are the most well studied.

Tips and tricks for using extracorporeal life support devices in the intensive cardiac care unit

In patients with severe cardiac dysfunction refractory to conventional therapies, extracorporeal membrane oxygenation used in veno-arterious modality can provide temporary circulatory assistance (extracorporeal life support, ECLS). Since it is an invasive and complex technique, its use is potentially burdened by severe complications, thus requiring careful nursing and medical care during intensive cardiac care unit stay. The use of ECLS requires specific skills such as knowledge of protective mechanical invasive ventilation, specific echocardiographic evaluation, accurate monitoring of hemodynamics and laboratory tests. A patient on ECLS is at high risk of thrombotic and hemorrhagic complications that could be fatal, hence specific pro- and anti-hemostatic therapy is needed. Moreover, the knowledge of some peculiar aspects of ECLS system and management can help doctors to avoid several complications such as limb ischemia, left ventricular overload and regional perfusion discrepancy. In conclusion, careful management by adequately trained personnel is required.

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients

BackgroundLeft ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. MethodsEighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. ResultsPearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 μg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 μg/ml was associated with LVH. ConclusionsHA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients.

Insufficient left ventricular unloading after extracorporeal membrane oxygenation : Acase-series observational study.

Extracorporeal membrane oxygenation (ECMO) is amethod widely used to support circulation in patients with fulminant myocarditis (FM). However, acommon complication associated with ECMO is left ventricular (LV) overload. This case series observed the effects of intra-aortic balloon pump (IABP) and beta-blockers for the treatment of LV overload after ECMO. The cases of eightpatients with FM who underwent ECMO from September 2009 to July 2016 were reviewed. Six of the eightpatients survived. After ECMO treatment, insufficient LV unloading occurred in sixpatients. Among these sixpatients, threeexperienced electrical storm but spontaneous circulation returned after interventions with beta-blockers and IABP. The survivors demonstrated full recovery of cardiac function. Beta-blockers may prevent the occurrence of electrical storm, and IABP is feasible for the treatment of LV overload after ECMO application.

The cardiac profile and electrocardiographic standard of at-height workers

The Medical Control Program for Occupational Health establishes the required supplementary exams, according to the activity exercised by the worker and its inherent risks. The Regulatory Norm No. 35, recently deployed, stipulates that at-height workers must undergo electrocardiogram exams as an additional routine examination. To evaluate the electrocardiographic standard in at-height. A cross-sectional study, developed from May 2014 to January 2015 with male at-height workers. Anthropometric and clinical data were collected after the electrocardiogram (ECG). The workers included in the program were evaluated by an occupational medicine service of Serra Gaúcha, responsible for medical assessment and occupational tests. All workers were assessed by the researcher. A total of 561 at-height workers participated in the study. The average age was 35.9 ± 12.2 years. A total of 176 (31%) presented electrocardiographic changes in the analysis of the resting ECG. Regarding the amendments in the resting ECG, 15.7% were attributed to changes in ventricular repolarization, 8% as blocks conductions, and 5.8% as left ventricular overload. Demographic variables were not associated with changes in the electrocardiographic tracing. This study demonstrated the electrocardiographic alterations and the profile of at-height workers. These findings can help determine prevention strategies and provide warnings of possible future harms to the health of these workers.

NT-proBNP and Cardiovascular Dysfunction in Chronic Liver Disease

Plasma NT-proBNP levels are elevated in heart disease, especially in the presence of ascites-edema syndrome and left ventricular overload. Previous studies have reported cardiovascular dysfunction correlated with the severity of liver damage. This prospective study enrolled 65 subjects with the diagnosis of liver cirrhosis, 82 with chronic hepatitis and 65 healthy subjects in the control group. In chronic hepatitis, NT-proBNP has been shown to be an early marker of diastolic dysfunction and left ventricular remodeling, while in liver cirrhosis it also correlated with portopulmonary hypertension.

Correlation of tricuspid regurgitation and new pacemaker implantation in patients undergoing transcatheter aortic valve implantation

AimsConduction abnormalities (CA), in particular complete atrioventricular block (CAVB), requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). However, the potential mechanisms are still incompletely understood. The objective of this retrospective study was to determine further predictors of CAVB after TAVI in patients without the known predictors. Methods and resultsThis study included patients without prior CA/PPM who underwent TAVI of a balloon-expandable valve (Sapien or Sapien XT or Sapien 3). Of 563 patients (81.2 ± 6.9 years, 245 men [43.5%], logistic EuroSCORE 22.2 ± 14.1%, STS PROM 5.9 [3.4–8.0]) who were treated by TAVI at our institution between July 2008 and January 2016, 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB after TAVI. Moreover, patients with more pronounced TR presented with increased left and right ventricular overload (left ventricular (LV) end-diastolic diameter, LV end-diastolic pressure), pulmonary pressures, NT-proBNP, and prevalence of mitral regurgitation ≥II, whereas LV ejection fraction, TAPSE and cardiac output were decreased. ConclusionsPPM implantation is a frequent complication in patients undergoing TAVI. Increasing severity of TR seems to be a consequence of left and right ventricular overload caused by severe AS and is a significant predictor of new CAVB after TAVI. Condensed abstractConduction abnormalities (CA) requiring permanent pacemaker (PPM) implantation, are frequent complications after transcatheter aortic valve implantation (TAVI). This study included patients without prior CA/PPM who underwent TAVI. Of 563 patients 61 (10.8%) developed a permanent CAVB after the procedure. In a multivariable logistic regression analysis moderate/severe tricuspid regurgitation (TR) (OR 2.05; 95% CI 1.18–3.55; p = 0.010) was identified as an independent predictor for new CAVB. Therefore, in patients with moderate/severe TR utmost care should be taken to avoid procedural factors conducive to mechanical irritation of the conduction system, resulting in pacemaker dependency.

Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study.

Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella™ enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.

P1500A novel means to assess left ventricular overload: pacemaker with sleep apnea monitor

P1500A novel means to assess left ventricular overload: pacemaker with sleep apnea monitor

Cardiogenic shock: can the well-forgotten old become the new?

Cardiogenic shock (CS) is considered to be the most severe variant of acute heart failure. It occurs against the background of myocardial infarction or non-coronary myocardial disease with the loss of 40-50% contractile ability by the left ventricular mass and acute heart overload of another genesis. The marked decrease of blood pressure is accompanied by generalized impairment of microcirculation in all organs. The acting recommendations for emergency assistance suggest to recover blood perfusion pressure in ischemic tissues by inotropic drugs vasopressors, crystalloids that eliminate hypovolemia. However, the recovery of hemodynamic parameters using these medicines is accompanied by increased load on the myocardium and causes only a slight temporary increase of blood pressure. Death rapidly occurs in almost 100% of cases because offast heart energy depletion There is no doubt that stable recovery of hemodynamic in CS is not possible without sustainable recovery of myocardial contractility. The effective discharge of myocardium by drugs should not be accompanied by deterioration of blood supply to peripheral organs. Taking into account the literature data and pharmacological properties of different groups of drugs, there is every reason to believe that nitroglycerin may be the drug of choice for the treatment of cardiogenic shock. It reduces myocardium preload without impairment of microcirculation in the peripheral organs. This conclusion is preliminary and requires verification in randomized trials.

Severe aortic coarctation incidentally discovered in a young university student

Coarctation of the aorta is a narrowing of the descending aorta, resulting in left ventricular overload, arterial hypertension and cardiovascular and neurological complications. It is frequently diagnosed in infancy and childhood; first-time presentation in adults is rare. The classic symptom is arterial hypertension; most patients are asymptomatic unless hypertension is present. We report the case of a 19-year-old woman who presented with a headache, tiredness and arterial hypertension. Clinical examination revealed that blood pressure was significantly lower in the lower extremities than in the upper extremities and radiofemoral delay (delayed femoral pulses). Severe aortic coarctation was confirmed by computerized tomography aortography; echocardiography was inconclusive. The lesion was successfully treated with balloon dilatation and mesh stent placement.

Left ventricular hypertrophy in adults with previous repair of coarctation of the aorta; association with systolic blood pressure in the high normal range

BackgroundArterial hypertension is common in adults with repaired coarctation of the aorta (CoA). The associations between the diagnosis of hypertension, actual blood pressure, other factors affecting left ventricular overload, and left ventricular hypertrophy (LVH) are not yet fully explored in this population. Material and resultsFrom the national register for congenital heart disease, 506 adult patients (≥18years old) with previous repair of CoA were identified (37.0% female, mean age 35.7±13.8years, with an average of 26.8±12.4years post repair). Echocardiographic data were available for all patients, and showed LVH in 114 (22.5%) of these. Systolic blood pressure (SBP) (mmHg) (OR 1.02, CI 1.01–1.04), aortic valve disease, (OR 2.17, CI 1.33–3.53), age (years) (OR 1.03, CI 1.01–1.05), diagnosis of arterial hypertension (OR 3.02, CI 1.81–5.02), and sex (female) (OR 0.41, CI 0.24–0.72) were independently associated with LVH. There was an association with LVH at SBP within the upper reference limits [130, 140] mmHg (OR 2.23, CI 1.05–4.73) that further increased for SBP>140mmHg (OR 8.02, CI 3.76–17.12). ConclusionsLVH is common post repair of CoA and is associated with SBP even below the currently recommended target level. Lower target levels may therefore become justified in this population.

Dyssynchronous CA Removal in Atrial Cardiac Myocytes

In heart failure atrial remodeling (AR) leads to impaired contractility, relaxation and atrial fibrillation and contributes to negative clinical outcomes. In myocytes cytosolic Ca-removal after systolic release is primarily achieved by SERCA-pump and Na/Ca-exchange (NCX) activity, allowing atrial relaxation. In atrial myocytes that lack a transverse-tubule system, NCX is located exclusively in the cell periphery where it is exposed to high concentrations of Ca during the cardiac cycle. Previously we found that the relative contribution of NCX to Ca-removal was increased in AR and was associated with a higher propensity of arrhythmogenic Ca waves, i.e. Ca waves triggering action potentials (APs). We hypothesize that dyssynchrony of Ca-removal globally (whole-cell) and locally (peripheral subsarcolemmal (SS) and central (CT) domains) is responsible for impaired relaxation and increased arrhythmogenicity. We used confocal linescan-imaging and Ca sensitive dyes to investigate Ca-removal in remodeled atrial myocytes from a rabbit left ventricular volume-pressure overload systolic HF model. In control atrial myocytes Ca-removal (assessed by the time constant of decay (TAU) of local SS and CT AP-induced Ca transients) is faster in the cell center (CT region) compared to the SS domain (342 ± 32 vs. 393 ± 31 ms, n = 10 cells). In AR myocytes however, CT TAU was not different from SS TAU (196 ± 11 vs. 190 + 14 ms, n = 10 cells). In addition, in AR cells local dyssynchrony (defined as the standard deviation of TAU divided by mean TAU) in the CT domain was significantly increased compared to control (0.11 ± 0.03 vs. 0.04 ± 0.01, n = 10 AR and CTRL cells). However despite the increased dyssynchrony, CT Ca-removal was 50% and SS Ca-removal 56% faster in AR myocytes as compared to control (n = 10 AR and CTRL cells). In summary, AR myocytes show accelerated but dyssynchronous diastolic Ca-removal which may result in impaired relaxation and increased susceptibility to rhythm disorders.

Left ventricle unloading during veno-arterial extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation in veno-arterial configuration (VA-ECMO) is a method widely used to support circulation during the most severe conditions of heart failure or refractory cardiac arrest. It frequently bridges this otherwise fatal status to recovery, therapeutic intervention or other circulatory support. However, the use of VA-ECMO in critical situations of severely impaired heart function is associated with specific limitations. One common complication is left ventricular overload and distension, primarily due to the increased afterload caused by extracorporeal blood flow. To date, various techniques has been proposed to decrease left ventricular distension and improve its function, including insertion of intra-aortic balloon pump or percutaneous left ventricular assist device, left atrial and left ventricular venting, or switch to surgically inserted left ventricular support with or without oxygenator. The present review summarizes current minimally invasive approaches to unload overloaded left ventricle during VA-ECMO support.

Protective Effect of Aortic Stenosis on the Coronary Arteries. Hypothetic Considerations to an Old Enigma

A literature overview of angiographic studies has shown that the prevalence of significant coronary disease in patients with aortic stenosis (AS) varies from 20 to 60%. Early necropsy studies suggested that patients with AS had a lower than expected incidence of coronary artery disease (CAD), originating the concept of a protective effect of AS on the coronary arteries. The myth of AS protection against CAD would be better explained as endothelium-myocardial interaction (crosstalk) protection triggered by left ventricular overload. Therefore, the cGMP/NO pathway induced by the AS overload pressure would explain the low incidence of CAD, which is compatible with the amazing natural long-term evolution of this cardiac valve disease.