Targeting left atrial dysfunction: A new way to prevent cardiovascular disease?

Clinical and biochemical factorsassociated with worsening of left atrial function, as assessed by speckle tracking echocardiography (i.e. left atrial reservoir strain = LARS) in a population-based cohortover a five-year period of follow-up.

Differential effects of renal denervation on skin and muscle sympathetic nerve traffic in resistant and uncontrolled hypertension.

PURPOSE: Renal denervation (RDN) exerts sympathoinhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behavior. METHODS: In 14 patients with resistant hypertension (RHT, age 58.3 ± 2.2 years, mean ± SEM), we recorded muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) using the microneurographic technique, before, 1 month, and 3 months after RDN. Measurements included clinic blood pressure (BP), heart rate (HR), 24-h BP and HR, as well as routine laboratory and echocardiographic variables. Ten age-matched RHT patients who did not undergo RDN served as controls. RESULTS: MSNA, but not SSNA, was markedly higher in RHT. RDN caused a significant reduction in MSNA 1 month after RDN, with this reduction increasing after 3 months (from 68.1 ± 2.5 to 64.8 ± 2.4 and 63.1 ± 2.6 bursts/100 heartbeats, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 13.1 ± 0.5 to 13.4 ± 0.6 and 13.3 ± 0.4 bursts/min, P = NS). No quantitative or, in some cases, qualitative relationship was found between BP and the MSNA reduction induced by RDN. No significant changes in various sympathetic markers were detected in the control group who did not undergo RDN and were followed for 3-months observation. CONCLUSIONS: These data provide the first evidence that RDN exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition.These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.

Phenotyping the hypertensive heart.

Arterial hypertension remains the most frequent cardiovascular (CV) risk factor, and is responsible for a huge global burden of disease. Echocardiography is the first-line imaging method for the evaluation of cardiac damage in hypertensive patients and novel techniques, such as 2D and D speckle tracking and myocardial work, provide insight in subclinical left ventricular (LV) impairment that would not be possible to detect with conventional echocardiography. The structural, functional, and mechanical cardiac remodelling that are detected with imaging are intermediate stages in the genesis of CV events, and initiation or intensification of antihypertensive therapy in response to these findings may prevent or delay progressive remodelling and CV events. However, LV remodelling-especially LV hypertrophy-is not specific to hypertensive heart disease (HHD) and there are circumstances when other causes of hypertrophy such as athlete heart, aortic stenosis, or different cardiomyopathies need exclusion. Tissue characterization obtained by LV strain, cardiac magnetic resonance, or computed tomography might significantly help in the distinction of different LV phenotypes, as well as being sensitive to subclinical disease. Selective use of multimodality imaging may therefore improve the detection of HHD and guide treatment to avoid disease progression. The current review summarizes the advanced imaging tests that provide morphological and functional data about the hypertensive cardiac injury.

The role of TAVR in patients with heart failure: do we have the responses to all questions?

Severe aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries. Heart failure (HF) is a frequent comorbidity of this condition and represents a diagnostic and therapeutic challenge. The spectrum of both conditions has become progressively wider in the last decade; HF has been divided in three groups according to left ventricular ejection fraction (LVEF) and severe AS has been reclassified into four groups according to aortic valve (AV) gradient, AV flow measured by LV stroke index, and LVEF. Although all four AS types may be found in patients with signs and symptoms of HF, low-flow AS with low or normal gradient is the most common type in these patients. Several studies have documented that patients with low-flow severe AS have a higher mortality risk than patients with normal-flow and high-gradient AS not only during the natural progression of the disease, but also after either interventional or surgical AV replacement. Existing data support transcatheter AV replacement (TAVR) in patients with severe AS, irrespective of AV gradient, AV flow, and LVEF. Controversial issues, however, are still present on this topic, which has not been adequately addressed by large studies and trials. This clinical review summarizes the epidemiology of the different HF types in patients with severe AS, as well as the impact of HF and LVEF on clinical outcomes of AS patients either untreated or after AV replacement. In particular, we addressed the influence of AV gradient and AV flow on all-cause and cardiovascular mortality in AS patients after TAVR.

Functional tricuspid regurgitation, related right heart remodeling, and available treatment options: good news for patients with heart failure?

Significant functional tricuspid regurgitation (FTR) represents a poor prognostic factor independent of right ventricular (RV) function. It is usually the consequence of left-sided cardiac diseases that induce RV dilatation and dysfunction, but it can also resulted from right atrial (RA) enlargement and consequent tricuspid annular dilatation. FTR is very frequent among patients with heart failure, particularly in those with reduced LVEF and concomitant functional mitral regurgitation. The development of three-dimensional echocardiography enabled detailed assessment of tricuspid valve anatomy, subvavlular apparatus, and RA and RV changes, as well as accurate evaluation of FTR etiology. Due to high in-hospital mortality risk in patients who were operatively treated for isolated FTR, it has been treated only medically for a long time. Percutaneous approach considers mainly transcatheter tricuspid valve repair (edge-to-edge and annuloplasty) and represents a very attractive option for the high-risk patients. Studies that investigated the effects of different devices showed excellent feasibility and safety, followed by significant reduction in FTR grade, improvement in functional capacity and NYHA class, quality of life, and reduction in hospitalization due to heart failure. Some investigations also reported a decreased mortality in FTR patients. Nevertheless, the results of these investigations should be interpreted with cautious due to the small number of participants and relatively short follow-up. The aim of this review was to summarize the existing data about the clinical importance of FTR and FTR-induced right heart remodeling and currently existing therapeutic approaches for treatment of FTR.

New antidiabetic therapy and HFpEF: light at the end of tunnel?

New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Findings from the meta-analyses are sending positive message about the use of GLP-1R agonists in HFrEF therapy and revealed the improvement of left ventricular (LV) diastolic function in HFpEF. Nevertheless, the relevant medical societies still consider their effect as neutral or insufficiently investigated in HF patients. The impact of DPP-4 inhibitors in HF is the most controversial due to conflicting data that range from negative impact and increased risk of hospitalization due to HF, throughout neutral effect, to beneficial influence on LV diastolic dysfunction. However, this is a very heterogeneous group of medications and some professional societies made clear discrepancy between saxagliptin that might increase risk of HF hospitalization and those DPP-4 inhibitors that have no effect on hospitalization. The aim of this review is to summarize current clinical evidence about the effect of new antidiabetic medications on LV diastolic function and their potential benefits in HFpEF patients.

Obstructive sleep apnea and cardiac mechanics: how strain could help us?

Obstructive sleep apnea (OSA) syndrome is the most common sleep-breathing disorder, which is associated with increase cardiovascular morbidity and mortality. OSA increases risk of resistant arterial hypertension, coronary artery disease, heart failure, pulmonary hypertension, and stroke. Studies showed the significant relationship between OSA and cardiac remodeling. The majority of investigations were focused on the left ventricle and its hypertrophy and function. Fewer studies investigated right ventricular structure and function revealing deteriorated diastolic and systolic function. Data regarding left and right ventricular mechanics in OSA patients are scarce and controversial. The results of the studies that were focused on the influence of continuous positive airway pressure and weight reduction on cardiac remodeling revealed favorable effect on left and right ventricular structure and function. Recently published analyses confirmed positive effect of treatment on cardiac mechanics. Deterioration of left and right ventricular mechanics occurs before functional and structural cardiac impairments in the cascade of cardiac remodeling and therefore the assessment of left and right ventricular strain may represent a cornerstone in detection of subtle cardiac changes that develop significantly before other, often irreversible, alterations. Considering the fact that left and right ventricular strains have important predictive value in wide range of cardiovascular diseases, one should consider the evaluation of left and right ventricular strains in the routine echocardiographic assessment at all stages of disease-from diagnosis, during follow-up and evaluation of therapeutic effects. The main aim of this review is to provide the current overview of cardiac mechanics in OSA patients before and after (during) therapy, as well as mechanisms that could be responsible for cardiac changes.

Cardiorespiratory fitness in patients with type 2 diabetes: A missing piece of the puzzle.

Functional capacity represents an important predictor for cardiovascular and all-cause mortality in patients with diabetes mellitus (DM). Impaired cardiopulmonary fitness is frequently seen in DM patients, and it might partly explain morbidity and mortality in these patients. There are several potential reasons that could explain impaired functional capacity in DM patients: hyperglycemia, insulin resistance, endothelial dysfunction, inflammation, microvascular impairment, myocardial dysfunction, and skeletal muscle changes. These changes are partly reversible, and improvement of any of these components might increase functional capacity in DM patients and improve their outcome. Physical activity is related with decreased cardiovascular disease and all-cause mortality in patients with type 2 DM. Diabetic cardiomyopathy is the most important clinical entity in DM patients that involves left ventricular diastolic dysfunction and cardiac autonomic neuropathy, which potentially induce heart failure with preserved ejection fraction. Development of diabetic cardiomyopathy may slow oxygen uptake kinetics and affect the cardiorespiratory fitness in DM patients, but it can also induce development of heart failure. Improvement of functional capacity in DM patients represents an important therapeutic task, and it can be achieved mainly with exercise training and significantly less with pharmacological treatment. Exercise training reduces body weight and improves glycemic control, as well as left ventricular structure and function. The aim of this review was to summarize current knowledge about importance of functional capacity in DM patients, as well as possible mechanisms that could explain the relationship between DM and oxygen kinetics.

Diagnostic algorithm for HFpEF: how much is the recent consensus applicable in clinical practice?

Heart failure with preserved ejection fraction (HFpEF) represents an important cardiovascular entity with increasing prevalence and relatively high mortality. The agreement about diagnostic algorithm for HFpEF is still missing. Echocardiographic approach remains the cornerstone in HFpEF diagnosis. Echocardiographic diastolic stress test provides numerous useful parameters that correlated well with indexes obtained by cardiac catheterization. Recently published consensus recommended new scoring system that included functional and structural echocardiographic parameters, as well as biomarkers. The new score for evaluation of HFpEF introduces a new set of parameters and proposed novel cutoff values for some of them. There are several important points that need to be resolved before full acceptance and clinical usage. First, some cutoff values are new and represent the result of expert consensus, without previous validation. Second, many patients with hypertension, obesity, and diabetes would be referred for further investigations as the result of this scoring, which is difficult to achieve in clinical circumstances. Third, the consensus equalized non-invasive and invasive diastolic stress tests in diagnosing of HFpEF, which is not a small issue. Namely, even though cardiac catheterization provides the final confirmation of elevated left ventricular filling pressures, it is still an invasive method, associated with procedural risk and other limitations. The aim of this review was to summarize the current knowledge diagnosis of HFpEF, as well as the recent consensus about diagnostic algorithm in patients with suspected HFpEF with its advantages and disadvantages.

The role of cardiac magnetic resonance in diagnosis of cardiac sarcoidosis.

Sarcoidosis is a systemic granulomatous disease with a high prevalence of cardiac involvement in autopsic studies. Cardiac sarcoidosis is associated with increased cardiovascular morbidity and mortality. Endomyocardial biopsy is a specific technique, but unfortunately not sensitive enough. Non-invasive cardiac imaging has an important role in the evaluation of patients with suspected or confirmed cardiac sarcoidosis. Echocardiography remains the first choice imaging technique because of its availability and low cost. However, this method could not provide tissue characterization or evaluation of disease activity level. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has essential role in diagnosis and monitoring of patients with suspected or confirmed cardiac sarcoidosis. Nevertheless, more recently it has been shown that cardiac magnetic resonance (CMR) might provide useful information about cardiac sarcoidosis. Hybrid imaging approach that includes PET-CMR and PET-CT is particularly interesting for diagnosis, assessment of activity and follow-up in these patients. Diagnostic algorithm in sarcoidosis patients should include clinical data, hybrid imaging and biopsy. Use of different CMR sequences such as cine imaging, late gadolinium enhancement, T1 and T2 mapping, as well as strain imaging, may significantly contribute to diagnosis and monitoring of patients with cardiac sarcoidosis. However, validation of these techniques and particularly T1 and T2 mapping in sarcoidosis patients in large studies is necessary. This review aimed to summarize current knowledge about clinical usefulness of CMR in patients with cardiac sarcoidosis.

Comprehensive assessment of hypertensive heart disease: cardiac magnetic resonance in focus.

Arterial hypertension represents the most frequent cardiovascular risk factor that is associated with cardiac remodeling. Hypertensive heart disease was defined by the presence of left ventricular hypertrophy (LVH) and diastolic dysfunction, and it has been diagnosed by echocardiography in everyday clinical practice. Interstitial myocardial fibrosis is the underlying cause of hypertension-induced cardiac remodeling, and it could not be visualized with different echocardiographic methods. Cardiac magnetic resonance (CMR) and its methods such as late gadolinium enhancement, and T1 mapping provides qualitative and quantitative assessment of interstitial myocardial fibrosis in hypertensive patients. Furthermore, CMR can provide differentiation of LVH between hypertensive patients and cardiomyopathies (hypertrophic or Fabry disease). Timely diagnosis of cardiac impairment and early treatment is essential because regression of LVH could be achieved with adequate treatment. Diffuse cardiac fibrosis in hypertensive patients might be an underlying mechanism that explains the increased cardiovascular morbidity and mortality in this population. Future longitudinal investigations are necessary to determine causal relationship between diffuse fibrosis and cardiovascular outcome in these patients. The aim of this review is to summarize the current knowledge regarding CMR techniques and their potential usage in patients with hypertensive heart disease.

Association between myocardial work and functional capacity in patients with arterial hypertension: an echocardiographic study.

PURPOSE: The aim of this study was to examine myocardial performance using pressure-strain loops in hypertensive patients with different level of blood pressure control. MATERIAL AND METHODS: This cross-sectional study included 204 subjects (45 controls, 70 patients with well-controlled hypertension, 58 patients with uncontrolled hypertension and 31 patients with resistant hypertension) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine global myocardial work, constructive work, wasted work and work efficiency in all study participants. RESULTS: Left ventricular (LV) longitudinal strain gradually reduced from controls throughout well-controlled hypertensive patients, to patients with uncontrolled and resistant hypertension. Global myocardial work was higher in patients with uncontrolled and resistant hypertension than in controls and well-controlled hypertension. Constructive work was also higher in all hypertensive patients than in controls. Global wasted work and work efficiency were similar between different groups. Global myocardial work index was associated with peak oxygen consumption independently of sex, age, body mass index (BMI), LV structural and functional parameters in all hypertensive participants. CONCLUSIONS: Myocardial work was significantly deteriorated in patients with uncontrolled and resistant arterial hypertension compared to controls and well-controlled hypertensive patients. Global myocardial work was associated with functional capacity independent of clinical and echocardiographic parameters.

Limited reproducibility of MUCH and WUCH: evidence from the ELSA study.

AIMS: To evaluate the long-term reproducibility of masked (MUCH) and white-coat uncontrolled hypertension (WUCH), an information crucial for determining the long-term prognostic impact of these conditions. METHODS AND RESULTS: Reproducibility of MUCH and WUCH was assessed in 1664 hypertensive patients recruited for the European Lacidipine Study on Atherosclerosis and treated with atenolol or lacidipine (±additional drugs) during a 4-year period. Office and 24 h blood pressure (BP) was measured at baseline and every year during treatment, allowing repeated classification of either condition. After 1 year of treatment 21.1% and 17.8% of the patients were classified as MUCH and WUCH, respectively. For both conditions the prevalence was similar in the following years, although with a large change in patients composition because only about 1/3 of patients classified as MUCH or WUCH at one set of office and ambulatory BP measurements maintained the same classification at a subsequent set of measurements. In only 4.5% and 6.2% MUCH and WUCH persisted throughout the treatment period. MUCH and WUCH reproducibility was worse than that of patients showing control or lack of control of both office and ambulatory BP, i.e. controlled and uncontrolled hypertension, respectively. CONCLUSION: Both MUCH and WUCH display poor reproducibility over time. This should be taken into account in studies assessing the long-term prognostic value of these conditions based on only one set of BP measurements.

COVID-19, hypertension and cardiovascular diseases: Should we change the therapy?

The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.

Right heart masses in a patient with endometrial stromal sarcoma.

We present the case of a 61-year-old woman with a large tumoral infiltration extending from the pelvis throughout the inferior vena cava inferior to the right atrium, protruding into the right ventricle and right ventricular outflow tract. She had been treated 10 years before for low-grade endometrial stromal sarcoma by hysterectomy and adnexectomy followed by hormone- and radio-therapy. Due to cancer recurrence, she underwent peritonectomy, appendectomy, and resection of terminal ileum.

Obesity and heart failure with preserved ejection fraction: a paradox or something else?

Obesity represents one of the most common comorbidities in patients with heart failure and preserved ejection fraction (HFpEF). Studies have shown that obesity is not only a comorbidity, but it could also be an important risk factor for HFpEF development. The mechanisms that connect obesity and HFpEF vary from obesity-induced hemodynamic changes to important biohumoral systems such as adipocitokines, renin-angiotensin-aldosterone and sympathetic nervous systems, natriuretic peptide, and oxidative stress. Studies agree about the negative influence of morbid obesity on cardiac remodeling and HFpEF development. However, there is still no agreement regarding the relationship between body mass index, as the most commonly used parameter of obesity, and HFpEF incidence or outcome in patients who already have HFpEF. The relationship varies from the linear to the U-shaped and, therefore, the "obesity paradox," which refers to the reduced risk in mildly overweight subjects in comparison with normal and underweight individuals, deserves more attention not only in the research but also in the clinical approach to these patients. In the absence of a satisfactory pharmacological approach, which would improve the outcome of this large group of patients, alternative methods such as weight loss and physical activity seem to provide encouraging results. This review article provides a clinical overview of the available data about the mechanisms that connect obesity and HFpEF, the most relevant studies on this topic, clinical relevance of the obesity paradox, and the therapeutic approach including weight loss and physical activity in obese patients with HFpEF.

The influence of sex on left ventricular remodeling in arterial hypertension.

Hypertension represents one of the most important and most frequent cardiovascular risk factors responsible for heart failure (HF) development. Both sexes are equally affected by arterial hypertension. The difference is lying in the fact that prevalence of hypertension as well as hypertension-induced target organ damage varies during lifetime due to substantial variation of sex hormones in women. Left ventricular (LV) structural, functional, and mechanical changes induced by hypertension are well-known complications that occur in both sexes and they are responsible for HF development. However, their prevalence is significantly different between women and men, which could potentially explain the variation in HF occurrence and prognosis between the sexes. Studies have shown that the prevalence of left ventricular hypertrophy is higher in men. The data are not consistent regarding LV diastolic dysfunction and a similar report has been given for LV mechanical changes. Most investigations agree that LV longitudinal strain is lower among hypertensive men. However, even in the healthy population, men have lower LV longitudinal strain and the cutoff values are still missing. Therefore, it would be difficult to draw the conclusion that LV mechanical dysfunction is more prevalent among men. The main mechanisms responsible for sex-related LV remodeling are sex hormones and their influence on biohumoral systems. This review provides an updated overview of the available data about sex-related LV remodeling, as well as potential mechanisms for these changes, in the patients with arterial hypertension.

Intriguing relationship between antihypertensive therapy and cancer.

Arterial hypertension is the most frequent cardiovascular risk factor in the cancer patients. Anti-cancer therapy very often induces arterial hypertension and the treatment with antihypertensive medications is inevitable. Additionally, anti-cancer therapy frequently induces cardiotoxicity that has been treated or even could be prevented by use of antihypertensive medications - primarily angiotensin converting enzyme inhibitors and beta-blockers. The association between antihypertensive drugs and cancer is matter of large debate in the last several years because of the conflicting results from available studies ranging from adverse to beneficial effect of various antihypertensive classes. The mechanisms of the relationship between antihypertensives and cancer are still in domain of hypothesis. Some studies described the association between different antihypertensive groups and malignancies. There are investigations that denied negative effects of antihypertensive medications on cancer occurrence, recurrence, cancer-related complications and mortality. On the other hand, there are researches that reported a beneficial effect of antihypertensive medication by decreasing mortality in the cancer patients. One should be aware of the discrepancy of investigated antihypertensives in these researches and heterogeneity of included patients - different age, cancer type, comorbidities, demographic characteristics, and anti-cancer therapy. This comprehensive review article aimed to summarize the current knowledge regarding the relationship between antihypertensive medications and cancer.

Gender-specific therapeutic approach in arterial hypertension - Challenges ahead.

Hypertension was thought to be more important cardiovascular risk factor in men than in women. However, studies showed that overall incidence of hypertension-related cardiovascular diseases is higher in women comparing with men and this is particularly valid in menopause when prevalence of hypertension and its complications sharply and suddenly rises. It was also noticed that the effect of various antihypertensive groups was different in women and men. Some medications are prescribed more often in women, but it does not necessary mean that these drugs are more effective in this gender. There are several important reasons that could explain gender-induced differences in blood pressure levels, blood pressure control and antihypertensive treatment. They involve sex hormones, the renin-angiotensin-aldosterone and sympathetic nervous system, and arterial stiffness. However, taking into account many observational studies and trials, there are no consistent data regarding the impact of gender on effect of antihypertensive medications. Longitudinal study focused on gender and current antihypertensive groups would significantly help to understand the impact of gender. This might change therapeutic approach and improve cost-effectiveness in antihypertensive therapy in both genders. A full understanding of the pathophysiological characteristics of variations between genders demands additional research. This review article summarized the current knowledge regarding differences in the prevalence and awareness of arterial hypertension in women and men; alterations in pathophysiological mechanisms of hypertension between sexes; as well as the impact of sex on the effects of main antihypertensive groups of medications.

Left atrial volume in elite athletes: A meta-analysis of echocardiographic studies.

AIM: Information on left atrium (LA) enlargement, as assessed by LA volume (LAV) instead of LA diameter, in the athletic population is scanty. To expand current knowledge on this issue, we performed an updated meta-analysis of echocardiographic studies. DESIGN: The Ovid MEDLINE, PubMed, and Cochrane CENTRAL databases were searched for English language articles without time restriction up to February 2018 through focused, high sensitive search strategies. Studies were identified by crossing the following search terms: "athletes," "physical training," "left atrial size," "left atrial volume," "atrial function," and "echocardiography.". RESULTS: Overall, 3145 subjects (2425 elite athletes and 720 active but not trained healthy controls) were included in 16 studies. Average LAV indexed to BSA (LAVI) was 37% higher in athletes as compared to nonathletic controls (31.0 ± 1.4 mL/m2 vs 22.2 ± 0.9 mL/m2 ), the standard means difference (SMD) being 1.12 ± 0.13 (CI: 0.86-1.89, P < 0.0001). SMD was higher in high-dynamic/high-static trained athletes (1.78 ± 0.24, CI: 1.30-2.20, P < 0.001) than in high-dynamic/low-static trained athletes 1.00 ± 0.16, CI: 0.70-1.30, P < 0.001). The statistical difference did not change after correction for publication bias and was not affected by a single study effect. CONCLUSIONS: Our meta-analysis suggests that the adaptation of LA to intensive physical training in elite athletes is characterized by a marked increase in LAVI; LA dilation is more pronounced in the subgroup of high-dynamic/high-static trained athletes. The functional and clinical implications related to advanced LA dilation in athletes and particularly in those engaged in high-dynamic/high-static disciplines deserve further investigations.