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The cardiovascular risk associated with left ventricular hypertrophy (LVH) in the community and, particularly, in the hypertensive fraction of the general population, represents the rationale for its timely and accurate identification in order to implement adequate preventive strategies. Although electrocardiography (ECG) is the first-line and most economical method of diagnosing LVH its accuracy is largely suboptimal. Over the last 70 years, dozens of different ECG criteria, mostly based on measurements of QRS voltages, have been proposed. In this long journey, a few years ago Peguero et al. developed a novel ECG voltage criterion, currently recognized as Peguero–Lo Presti (PLP) suggesting that it has greater sensitivity than traditional ECG-LVH criteria. Considering that in the last 5 years numerous studies have investigated the diagnostic value of this new index, this review aimed to summarize the data published so far on this topic focusing both on the accuracy in identifying the presence of LVH compared with imaging techniques such as echocardiography (ECHO) and magnetic resonance imaging (MRI) and the value in predicting hard outcomes. The evidence in favor of the greater diagnostic accuracy of the PLP criterion in detecting LVH, phenotyped by ECHO or MRI, and in the stratification of hard outcomes compared with traditional ECG criteria does not appear to be sufficiently proven. Given that the diagnosis of LVH by all ECG criteria (including the PLP) exclusively based on the QRS amplitude is largely imprecise, the development of new multiparametric ECG criteria based on artificial intelligence could represent a real improvement in the diagnostic capacity of the ECG.

BACKGROUND: Emerging evidence suggests that a hypertensive response to exercise (HRE) during dynamic or isometric stress tests assessing cardiac function is predictive of hypertension and cardiovascular events such coronary artery disease, heart failure and stroke. Whether HRE represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. This is also the case for the association between MH and hypertension-mediated organ damage (HMOD) in the HRE setting. METHODS: We addressed this issue through a review and a meta-analysis of studies providing data on this topic in normotensive individuals undergone both to dynamic or static exercise and to 24-h blood pressure monitoring (ABPM). A systematic search was performed using Pub-Med, OVID, EMBASE and Cochrane library databases from inception up to February 28th 2023. RESULTS: Six studies including a total of 1,155 untreated clinically normotensive individuals were considered for the review. Data provided by the selected studies can be summarized as follows: (i) HRE is a BP phenotype linked to a high prevalence of MH (27.3% in the pooled population); (ii) MH is, in turn, associated with a greater, consistent likelihood of echocardiographic left ventricular hypertrophy (OR: 4.93, CI: 2.16-12.2, P < 0.0001) and vascular organ damage, as assessed by pulse wave velocity, (SMD: 0.34 ± 0.11, CI: 0.12-0.56, P = 0002). CONCLUSIONS: On the basis of this, albeit limited, evidence, the diagnostic work-up in individuals with HRE should primarily be addressed to look for MH as well as for markers of HMOD, a highly prevalent alteration in MH.

Background: Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study. Methods: The study included 239 out of 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP),blood examinations, echocardiography and CAVI measurements. Results: In the whole study sample (age 69+9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with LVM index (p< 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6+2.8 vs 9.2+1.8 m/sec. P<0.001), larger left atrial diameter and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/sec was the best cut-off for prediction of LVH in the whole sample. Conclusions: Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH.

Objectives:In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV.Methods:In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared.Results:Twenty-four-hour SBP-CV was about 20% less than office SBP-CV (P < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values.Conclusion:Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability.

Aim:Gender-based evidence on the association between serum uric acid (SUA) and left ventricular hypertrophy (LVH), as assessed by echocardiography, is still based on single studies. Thus, we performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue.Methods:The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from the inception up to March 31, 2023. Studies were identified by using MeSH terms and crossing the following search items: 'uric acid', 'hyperuricemia', 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography', 'female', 'male'.Results:Six studies including 2791 normotensive and hypertensive individuals were considered for the analysis. In women, increasing values of SUA were associated with progressively higher values of age, body mass index (BMI) and systolic blood pressure (SBP). This was not the case for men. In women, the meta-analysis comparing LV mass index (LVMI) in low versus high SUA group showed a greater pooled LVMI in the high SUA group [standard means difference (SMD): 0.81 ± 0. 24, confidence interval (CI) 0.34-1.27, P < 0.0001]. On the contrary, in men no statistical difference was found between the low group and high SUA group (SMD: 0.27 ± 0.27, CI: -0.27/0.81, P = 0.32).Conclusions:Our meta-analysis suggests that hyperuricemia portends the likely presence of increased LVMI in women but not in men. However, as hyperuricemia in the female pooled population, different from men, was associated with older age, higher BMI and SBP, the present findings do not support an independent role of the SUA in LV remodelling process in women.

Objectives: Heterogeneous are the results of the published studies aimed at determining the long-term effects of habitual coffee consumption on blood pressure (BP). Specifically, no data are available on the longitudinal association between habitual coffee consumption and office, home and 24 h BP profile and variability. Methods: In 1408 subjects recruited in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, followed for a 10 year follow-up period and classified as coffee consumers and nonconsumers (self-reporting), we prospectically investigated the association between habitual coffee consumption and office, home and 24-h ambulatory BP; 24-h BP variability; and development of a new hypertensive state. Data were also analysed according to gender. Results: When data were adjusted for confounders habitual coffee nonconsumers and consumers displayed similar long-term BP changes during the follow-up in office, home, and ambulatory BP. No difference was found between heavy and moderate coffee consumers. Furthermore, also new-onset hypertension and patterns of BP variability were superimposable in coffee nonconsumers and consumers, independently on confounders including gender, number, and characteristics of the antihypertensive drug treatment. Conclusion: The present study, which is the first longitudinal investigation never performed examining in a prospective fashion the long-term (10 year) effects of coffee consumption on office, home, and ambulatory BP, provides conclusive evidence that habitual coffee consumption is associated with neutral effects on in-office and out-of-office BP values and related variabilities. This is the also the case for the new-onset hypertensive state.

Introduction: Although a number of pathophysiological aspects of childhood obesity have been reported, few information are available on obesity-related cardiac organ damage. Aim: The present study was aimed at assessing the impact of anthropometric, blood pressure (BP) and metabolic variable on cardiac structure and function in youth. Methods: In 78 subjects aged 5–16 years attending the outpatient clinic of cardiovascular risk (Valencia, Spain) anthropometric and metabolic variables, clinic and ambulatory BP and echocardiographic parameters were assessed. Subjects were also classified according to the presence of insulin resistance. Results: Subjects mean age (± SD) amounted to 12.03 ± 2.4 years and males to 53.8%. Ten subjects were normoweight, 11 overweight, 39 obese, and 18 severely obese. No significant difference in office and ambulatory BP was detected among different bodyweight groups. A significant direct correlation was observed between left ventricular mass index (LVMI) and obesity markers [body mass index (BMI): r = 0.38, waist circumference (WC): r = 0.46, P < 0.04 for both]. Left ventricular hypertrophy, relative wall thickness and left atrial diameter were significantly related to BMI and WC. In contrast, office and ambulatory BP were unrelated to other variables, and differences in LVMI among different BP phenotypes were not significant. When partitioning the population by insulin resistance, LVMI, adjusted for confounders, was significantly greater in the insulin-resistant group. Conclusions: In children and adolescents characterized by different body weight patterns, weight factors “per se” and the related insulin resistance state appear to represent the main determinants of LVMI and left ventricular hypertrophy, independently on BP values and BP phenotypes.

The injury of the left ventricle (LV) during anticancer therapy has long been recognized, and guidelines recommend a specific set of parameters for determination of LV impairment. The influence of anticancer therapy on the right ventricle (RV) has been insufficiently investigated, and there are only a few studies that have considered the effect of radiotherapy on RV remodeling. On the other hand, large number of patients with different types of cancers located in the chest are treated with radiotherapy, and the negative clinical effects of this treatment such as accelerated coronary artery disease, valve degeneration and heart failure have been documented. The anatomical position of the RV, which is in the front of the chest, is responsible for its large exposure during radiation treatment, particularly in patients with left-sided breast and lung cancers and mediastinal cancers (hematological malignancies, esophagus cancers, thymomas, etc.). For the same reason, but also due to its anatomical complexity, the RV remains under-investigated during echocardiographic examination, which remains the cornerstone of cardiac imaging in everyday practice. In the last decade many new echocardiographic imaging techniques that enable better evaluation of RV structure, function and mechanics appeared, and they have been used in detection of early and late signs of RV injuries in oncological patients. These investigations are related to some important restrictions that include limited numbers of patients, used parameters and imaging techniques. Many questions about the potential impact of these changes and possible predictions of adverse events remain to be evaluated in future large longitudinal studies. The current body of evidence indicates an important role of radiotherapy in RV remodeling, and therefore, the aim of this review is to summarize currently available data regarding RV changes in patients with various oncological conditions and help clinicians in the assessment of po

BACKGROUND: Numerous studies targeting left ventricular (LV) systolic function by measuring LV ejection fraction (LVEF) in patients with pheochromocytoma and paraganglioma (PPGL) either failed to reveal any impairment of this parameter or found a super-normal systolic function compared to essential hypertensives or normotensive controls. To provide an updated piece of information on LV systolic dysfunction in the PPGL setting, we performed a meta-analysis of speckle tracking echocardiography (STE) studies investigating LV mechanics via global longitudinal strain (GLS), a more sensitive index of LV systolic function than LVEF. METHODS: A computerized search was performed using PubMed, OVID, EMBASE, and Cochrane library databases from inception until September 30, 2022. Full articles reporting data on LV GLS and LVEF in patients with PPGL and controls were considered suitable. RESULTS: A total of 252 patients with PPGL and 187 controls were included in 6 studies. LV GLS was worse in the pooled PPGL group than in the control group (-17.3 ± 1.2 vs. -20.0 ± 0.6) with a standard means difference (SMD) of 1.13 ± 0.36 confidence interval (CI: 0.43-1.84, P = 0.002), whereas this was not the case for LVEF (67.3 ± 1.9 and 66.4 ± 1.6%, respectively), SMD: 0.12 ± 0.03, (CI: -0.41/0.65, P = 0.66). A meta-regression analysis in PPGL patients showed an inverse relationship between adrenergic activity and GLS (P < 0.0001). CONCLUSIONS: Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the PPGL setting can be revealed by STE; therefore, STE implementation in the workup of patients with PPGL may improve the detection of subclinical systolic dysfunction.

Obstructive sleep apnea (OSA) syndrome is a very important sleep-related breathing disorder related to increased cardiovascular and overall morbidity and mortality. It is associated with multisystemic target organ damage due to micro- and macrovascular changes, resulting in carotid and coronary atherosclerosis, increased arterial stiffness, retinal damage, microalbuminuria, and cardiac remodeling. The latter consists of left ventricular (LV) hypertrophy, as well as diastolic and systolic dysfunction. The increasing burden of evidence shows that OSA also induces right ventricular (RV) remodeling that is more difficult to diagnose, but may also contribute to cardiovascular morbidity and mortality in these patients. Conventional echocardiographic parameters for assessment of RV systolic and diastolic functions are often not sensitive enough to detect subclinical and subtle changes in the RV function. Data published over last decade showed that the RV function, particularly systolic, is impaired in OSA patients and related with its severity. However, the introduction of speckle tracking echocardiography and the particularly longitudinal strain enabled the earlier detection of functional and mechanical changes even when conventional echocardiographic parameters of RV systolic function remained unchanged. The 3D echocardiography provided the possibility to evaluate the entire RV, with its unique shape, and determine 3D RV ejection fraction, which is comparable with results obtained by cardiac magnetic resonance. The use of this modality also provided a new insight into RV systolic (dys)function in OSA patients. In addition to weight loss, which has been proven very helpful in OSA patients, the only approved therapeutic approach is continuous positive airway pressure (CPAP) therapy. It is very important to assess if this therapy induces any improvement in cardiac structure and function. Limited data on this topic show that RV longitudinal strain is a more sensitive paramet

BACKGROUND: There is evidence that a reduced nocturnal fall in blood pressure (BP) entails an increased risk of hypertensive-mediated organ damage (HMOD) and cardiovascular events. Most studies focusing on left ventricular (LV) systolic function, assessed by conventional LV ejection fraction (LVEF) in non-dippers compared to dippers failed to detect significant differences. To provide a new piece of information on LV systolic dysfunction in the non-dipping setting, we performed a meta-analysis of speckle tracking echocardiography (STE) studies investigating LV global longitudinal strain (GLS), a more sensitive index of LV systolic function. METHODS: A computerized search was performed using PubMed, OVID, EMBASE, and Cochrane library databases from inception until 31 July, 2022. Full articles reporting data on LV GLS and LVEF in non-dippers and dippers were considered suitable. RESULTS: A total of 648 non-dipper and 530 dipper individuals were included in 9 studies. LV GLS was worse in non-dipper than in their dipper counterparts (-18.4 ± 0.30 vs. -20.1 ± 0.23%, standard means difference [SMD]: 0.73 ± 0.14, confidence interval [CI]: 0.46/1.00, P < 0.0001) whereas this was not the case for LVEF (61.4 ± 0.8 and 62.0 ± 0.8%, respectively), SMD: --0.15 ± 0.09, CI: -0.32/0.03, P = 1.01). A meta-regression analysis between nighttime systolic BP and myocardial GLS showed a significant, relationship between these variables (coefficient 0.085, P < 0.0001). CONCLUSIONS: Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the non-dipping setting can be unmasked by STE; implementation of STE in current practice may improve the detection of HMOD of adverse prognostic significance in individuals with altered circadian BP rhythm.

Subclinical alterations in cardiac structure and function include a variety of abnormal phenotypes of recognized adverse prognostic values, such as left ventricular hypertrophy (LVH), concentric remodeling, systolic/diastolic dysfunction, left atrial dilatation, and alterations of LV geometry. The excess cardiovascular risk associated with these markers has been documented in multiple clinical settings, such as the general population, hypertensive cohorts, patients with coronary heart disease, diabetes mellitus, chronic heart failure, and chronic kidney disease. On the contrary, the value of aortic root (AR) and ascending aortic diameter in predicting cardiovascular outcomes and all-cause mortality in populations free from overt aortic pathology is still debated. The present review, aimed at pointing out the prognostic implications of thoracic aortic dimensions in populations free from known connective and aortic diseases, suggests that available evidence supporting an association between aortic diameter and cardiovascular events, and all-cause mortality is based on the limited number of studies, conducted with different imaging techniques and definition of the aortic phenotype.

The authors investigated the association between obstructive sleep apnea (OSA) and right ventricular (RV) systolic dysfunction trough a meta-analysis of echocardiographic studies providing data on RV mechanics as assessed by longitudinal strain (LS). A systematic search was conducted using PubMed, OVID-MEDLINE, and Cochrane library databases to search English-language review papers published from inception to March 31, 2022. Only studies reporting data on RV free-wall or global LS in patients with OSA of different severity and non-OSA controls were reviewed. Data of interest were pooled to obtain standard means difference (SMD) with 95% confidence interval (CI). The meta-analysis included 628 participants (436 with OSA and 192 controls) from eight studies. Compared to controls, RV free wall LS was significantly reduced in the pooled OSA group (SMD 1.02 ±.33, CI:.17/1.24, P <.002); this was also the case for RV global LS (SMD:.72 ±.11, CI:.50/.93, P <.0001). Notably, compared to patients with mild-OSA those with moderate and severe OSA exhibited significantly lower RV free-wall LS and global LS values; this was not the case for tricuspid annular plane excursion. In conclusions, both RV free-wall and global LS are impaired in patients with OSA; deterioration of these indices, unlike TAPSE, was already evident in the early stages and was related to the severity of the syndrome. Thus, RV myocardial strain should be considered to be included in echocardiographic evaluation of OSA patients in order to detect subclinical cardiac damage in these patients regardless of its degree of severity.

Current evidence on the effects of continuous positive airway pressure (CPAP) on cardiac mechanics in patients with obstructive sleep apnea (OSA) is based on a few single studies. The authors investigated this topic through a meta-analysis of speckle tracking echocardiography (STE) studies that provided data on left ventricular (LV) and right ventricular (RV) mechanics as assessed by global longitudinal strain (GLS). The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language review papers published from inception to January 31, 2022. Studies were identified by crossing the following terms: “obstructive sleep apnea”, “sleep quality”, “sleep disordered breathing”, “continuous positive airway pressure therapy”, “noninvasive ventilation”, “left ventricular hypertrophy”, “systolic dysfunction”, “global longitudinal strain”, “left ventricular mechanics”, “right ventricular mechanics”, “echocardiography” and “STE echocardiography”. The meta-analysis, including a total of 337 patients with OSA from nine studies (follow-up 2–24 months) showed a significant GLS improvement in both LV and RV after CPAP, standard mean difference (SMD) being 0.51±0.08, CI:0.36–0.66, p =.0001 and 0.28±0.07, CI:0.15–0.42, p =.0001), respectively. Corresponding SMD values for LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) were 0.20±0.06, CI:0.08–0.33, p =.001 and 0.08±0.06, CI: -0.04/0.20, p =.21. Our meta-analysis suggests that: I) CPAP treatment exerts beneficial effects on biventricular function in patients with OSA; II) the assessment of cardiac mechanics by STE should be routinely recommended for monitoring cardiac function in this setting, due to limitations of conventional echocardiography in evaluating biventricular performance.

Background: Aortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We investigated the incidence of new-onset aortic root (AR) dilatation and its principal correlates among middle-aged adults over a 25-year time period. Methods: A total of 471 participants with measurable echocardiographic parameters at baseline and after a 25-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from healthy normotensive PAMELA participants. Results: New AR dilatation occurred in 7.4% (AR/BSA), 9.1% (AR/height) and 14.6% (absolute AR), respectively. According to the AR/height index, the risk of new dilation was similar in men and women. As for echocardiographic parameters, baseline AR diameter emerged as a key predictor of AR dilation, regardless of the diagnostic criteria and the 10-year change in LVMI was positively associated to new AR/height dilatation. No significant relationship was observed between baseline office and ambulatory systolic/diastolic blood pressure or their changes over time with incident AR dilatation. Baseline and the 25-year change in 24-h pulse pressure were negatively related to new AR dilatation. Conclusions: The incidence of AR dilatation from mid to late adulthood occurs in a small but clinically relevant fraction of participants and is unaffected by both office and out-office BP. It is significant related to baseline AR diameter and to the 25-year change in LVMI. Our data suggest that echocardiography performed in middle-aged individuals of both sexes may identify those at increased risk of future AR dilatation; moreover, preventing LVH may reduce the risk of progressive AR enlargement.

Hypertension-mediated organ damage (HMOD) at cardiac level include a variety of abnormal phenotypes of recognized adverse prognostic value. Although the risk of cardiac HMOD is related with the severity of BP elevation, the interaction of numerous non-hemodynamic factors plays a relevant role in this unfavorable dynamic process. In particular, sex-related differences in cardiovascular (CV) risk factors and HMOD have been increasingly described. The objective of the present review is to provide comprehensive, updated information on sex-related differences in cardiac HMOD, focusing on the most important manifestations of subclinical hypertensive heart disease such as left ventricular hypertrophy (LVH), LV systolic and diastolic dysfunction, left atrial and aortic dilatation. Current evidence, based on cross-sectional and longitudinal observational studies as well as real-world registries and randomized controlled trials, suggests that women are more at risk of developing (and maintaining) LVH, concentric remodeling and subclinical LV dysfunction, namely the morpho-functional features of heart failure with preserved ejection fraction. It should be pointed out, however, that further studies are needed to fill the gap in defining gender-based optimal therapeutic strategies in order to protect women’s hearts.

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.

Aim:We investigated the association between obstructive sleep apnoea (OSA) and subclinical systolic dysfunction through a meta-analysis of echocardiographic studies that provided data on left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS).Design:The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language articles published from inception to 31 December 2021. Studies were detected by using the following terms: 'obstructive sleep apnea', 'sleep quality', 'sleep disordered breathing', 'cardiac damage', 'left ventricular hypertrophy', 'systolic dysfunction', 'global longitudinal strain', 'left ventricular mechanics', 'echocardiography' and 'speckle tracking echocardiography'.Results:The meta-analysis included 889 patients with OSA and 364 non-OSA controls from 12 studies. Compared with controls, GLS was significantly reduced in the pooled OSA group (SMD -1.24 ± 0.17, CI: -1.58 to -0.90, P < 0.0001), as well as in the normotensive OSA subgroup (SMD: -1.17 ± 0.12 CI:-1.40 to -0.95, P < 0.0001). Similar findings were obtained in sub-analyses performed separately in mild, moderate and severe OSA. This was not the case for LV ejection fraction (LVEF) (i.e. comparisons between controls vs. mild OSA, mild vs. moderate OSA, moderate vs. severe OSA).Conclusion:GLS is impaired in patients with OSA (independently from hypertension), worsening progressively from mild to moderate and severe forms, thus allowing to identify subclinical alterations of the systolic function not captured by LVEF. Therefore, myocardial strain assessment should be implemented systematically in the OSA setting to timely detect systolic dysfunction.

Right ventricular remodeling has been neglected in patients with arterial hypertension as all studies have concentrated on the left ventricle and left atrial-ventricular and ventricular-arterial coupling. The development of novel imaging techniques has revealed significant impairment in the RV structure, systolic and diastolic function, and, afterwards, RV longitudinal mechanics. However, these changes are subclinical and can be detected only after comprehensive imaging analysis. The latest findings confirm the importance of RV hypertrophy, systolic, and diastolic dysfunction in the prediction of cardiovascular adverse events in the hypertensive population, representing an important clinical implication of these parameters. In clinical practice, 2D echocardiography is widely used for the evaluation of RV remodeling. However, existing techniques are largely underused and limited to a few basic parameters (RV thickness and TAPSE), which are not nearly enough for a detailed assessment of RV remodeling. In addition, 3D echocardiography provides the possibility of accurate evaluation of RV volumes and ejection fraction, which are comparable with results obtained by cardiac magnetic resonance (CMR)—a gold standard for the evaluation of the RV. The use of 3D echocardiography is limited due to its low availability, the lack of adequate software necessary for the calculation of results, and the necessity for a higher level of expertise. CMR provides all information required for a detailed assessment of RV structural, functional, and mechanical remodeling, and it is considered the reference method for this type of evaluation. Furthermore, it is the only technique that may provide tissue characterization and evaluation of the interstitial space, which is essential for hypertensive heart disease. The aim of this review is to provide the current level of evidence regarding RV remodeling in patients with arterial hypertension evaluated with different imaging techniques and variou

Aortic stenosis (AS) is the most frequent degenerative valvular disease in developed countries. Its incidence has been constantly rising due to population aging. The diagnosis of AS was considered straightforward for a very long time. High gradients and reduced aortic valve area were considered as "sine qua non" in diagnosis of AS until a growing body of evidence showed that patients with low gradients could also have severe AS with the same or even worse outcome. This completely changed the paradigm of AS diagnosis and involved large numbers of parameters that had never been used in the evaluation of AS severity. Low gradient AS patients may present with heart failure (HF) with preserved or reduced left ventricular ejection fraction (LVEF), associated with changes in cardiac output and flow across the aortic valve. These patients with low-flow low-gradient or paradoxical low-flow low-gradient AS are particularly challenging to diagnose, and cardiac output and flow across the aortic valve have become the most relevant parameters in evaluation of AS, besides gradients and aortic valve area. The introduction of other imaging modalities in the diagnosis of AS significantly improved our knowledge about cardiac mechanics, tissue characterization of myocardium, calcium and inflammation burden of the aortic valve, and their impact on severity, progression and prognosis of AS, not only in symptomatic but also in asymptomatic patients. However, a variety of novel parameters also brought uncertainty regarding the clinical relevance of these indices, as well as the necessity for their validation in everyday practice. The aim of this review is to summarize the prevalence of HF in patients with severe AS and elaborate on the diagnostic challenges and advantages of comprehensive multimodality cardiac imaging to identify the patients that may benefit from surgical or transcatheter aortic valve replacement, as well as parameters that may help during follow-up.

Aim:We sought to assess the long-term changes in aortic root diameter in a population-based sample, focusing on new-onset aortic root dilatation, as well as on the demographic and clinical variables independently related to this dynamic process.Methods:A total of 1122 participants with measurable echocardiographic parameters at baseline and after a 10-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute aortic root diameter, aortic root diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants.Results:Over the 10-year follow-up, new aortic root dilatation occurred in 3.4% (aortic root /BSA), 4.4% (aortic root /height) and 7.3% (absolute aortic root), respectively. No substantial relationship was observed between baseline office and ambulatory blood pressure (BP) or their changes over time and incident aortic root /BSA and aortic root /height dilatation. Baseline aortic root diameter and left ventricular mass index (LVMI) emerged as important predictors of aortic root dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between nonhemodynamic variables and new-onset aortic root dilatation was variable, depending on the definition of the aortic phenotype.Conclusion:The incidence of aortic root dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of aortic root dilatation in the community.

Aim: Information on systolic dysfunction, as assessed by left ventricular (LV) mechanics in secondary hypertension is still largely limited. We performed a systematic meta- analysis of 2D/3D speckle tracking studies in order to provide an updated comprehensive information on this topic. Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search for articles published from the inception up to March 31st 2021. Studies were identified by using MeSH terms and crossing the following search items: “myocardial strain” “left ventricular mechanics”, “speckle tracking echocardiography”, “systolic dysfunction”, “hypertensive heart disease”, “left ventricular hypertrophy”, “secondary hypertension”, “primary aldosteronism”, “pheochromocytoma”, “Cushing disease”, “renal artery stenosis”. Results: On the whole, 515 patients with secondary hypertension (169 pheochromocytoma, 165 primary aldosteronism, 144 renal artery stenosis and 37 Cushing's syndrome) and 601 essential hypertensive patients from 11 studies were considered. Pooled ejection fraction (EF) was similar in essential hypertensive controls and in patients with secondary hypertension (SMD 0.12±0.06, CI: 0.001/0.25, p=0.05). Of note, EF was higher in patients with pheochromocytoma than in essential hypertensives (0.50±0.11, CI: 0.27/0.73, p<0.001). In contrast, pooled GLS was impaired in patients with secondary hypertension compared to their essential hypertensive counterparts (SMD 0.83±0.26, CI: 0.32/1.30, p< 0.001). Conclusions: The present meta-analysis adds a new piece of evidence by showing that GLS performs better than EF in identifying systolic dysfunction in the setting of secondary hypertension. In particular, this is true in patients with pheochromocytoma in whom conventional EF suggests a normal or even super-normal systolic function.

The aim of this study was to evaluate the short- and long-term blood pressure (BP) variability and right ventricular (RV) remodeling in women with gestational hypertension and preeclampsia, as well as their association. This cross-sectional study included 161 pregnant women (56 normotensive controls, 55 patients with gestational hypertension, and 50 patients with preeclampsia) after 20 weeks of gestation. All women underwent 24-h ambulatory BP monitoring and echocardiographic examination. Our findings showed that 24-h, daytime and nighttime systolic and diastolic BPs, as well as visit-to-visit systolic and diastolic BPs, were significantly higher in women with gestational hypertension and preeclampsia than in control group. Parameters of short- and long-term BP variability gradually increased from controls, throughout women with preeclampsia, to those with gestational hypertension. RV diameter, E/e′ and PAP were significantly higher in women with gestational hypertension and preeclampsia than in controls. Global and free wall RV longitudinal strains, as well as corresponding endo- and epicardial strains, gradually reduced from controls to women with preeclampsia. Parameters of short- and long-term BP variability were independently associated with global and free wall RV longitudinal strain. In conclusion, short- and long-term BP variability was higher in women with pregnancy-induced hypertensive disorders. RV diastolic function and mechanics were deteriorated in these women comparing with controls. A significant association between BP variability and RV longitudinal strain underlines the importance of determination of short- and long-term BP variability during pregnancy.

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.

We sought to investigate echocardiography-derived myocardial work in hypertensive patients with different left ventricular (LV) geometric patterns. This cross-sectional study included 211 hypertensive patients (74 with normal LV geometry, 53 with concentric remodeling, 46 with eccentric LV hypertrophy (LVH) and 38 with concentric LVH) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine parameters of myocardial work. Our findings showed that multidirectional LV strain was lower in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global myocardial work index and global constructive work were higher in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global wasted work and global efficacy work were similar between groups with different LV geometry. E/e' and LV mass index were associated with global myocardial work index and global constructive work independently of clinical and echocardiographic parameters. In conclusion, myocardial work was higher in patients with eccentric and concentric LVH than in patients with normal LV geometry and concentric remodeling. Increased blood pressure in patients with concentric LVH in comparison with other LV geometric patterns has significant impact on the final result. LV geometry has significant impact on myocardial work in hypertensive patients.

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.

Subclinical alterations in cardiac structure and function include a variety of abnormal phenotypes of established adverse prognostic significance such as left ventricular hypertrophy (LVH), alterations of LV geometry, left atrial (LA) enlargement, and aortic root (AR) dilatation. The excess cardiovascular (CV) risk associated with these phenotypes has been consistently demonstrated in different clinical settings such in patients with systemic hypertension, coronary heart disease, diabetes mellitus, chronic kidney disease, heart failure and in geneal population samples. The Pressioni Monitorate e Loro Associazioni (PAMELA), a longitudinal population-based study originally designed to assess the normality values, prognostic significance of office, home and 24-hour blood pressure, including among the many clinical and laboratory variables the collection of echocardiographic data, allowed to gather important information on the clinical prognostic significance of subclinical cardiac damage during a long follow-up period. This article summarizes the original findings provided by the PAMELA study on the clinical correlates and prognostic significance of echocardiographic markers of subclinical organa damage namely LVH, left atrial enlargement (LA) and AR dilatation at the community level. Graphical Abstract: [Figure not available: see fulltext.].

Epidemiological studies have unequivocally shown that elevated heart rate values measured at rest have an adverse prognostic impact in the hypertensive patient, being associated with an increased risk of cardiovascular events and complications. In recent years new data have been collected on this issue, strengthening the clinical relevance of elevated heart rate as a specific hypertensive phenotype. The present paper will review old and new data on the prognostic importance of resting tachycardia in the hypertensive patient. It will also examine the role of the sympathetic nervous system in the development of this alteration as well as its therapeutic implications. The different approaches to dynamically assess heart rate values in the clinical setting will be finally discussed.

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.

Background: Left ventricular hypertrophy (LVH) is an independent predictor of cardiovascular events, and evidence has been obtained that an increase of a normal left ventricular mass (LVM) or new-onset LVH over time augments cardiovascular outcomes. Methods: We addressed this issue in a sample of a general population at relatively low cardiovascular risk. We analyzed subjects with normal echocardiographic LVM enrolled in the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study to follow the increase of LVM over time and assess the prognostic impact of this change on the incidence of cardiovascular events (mean follow-up 18.5 years). Results: In 990 subjects with no LVH at baseline, there was a significant average increase of LVM (21.2%), LVMIBSA(18.9%), and LVMIHT(22.3%) more than 10 years later. About a quarter developed LVH. The LVMIBSAchange exhibited an association with the cardiovascular risk mortality during the following 18.5 years, and the association remained significant after adjustment for confounders (hazard ratio, 1.2 [1.0-1.5]). Similar findings were obtained for LVM in absolute values or indexed for height. The association was seen in both genders, but the link with the cardiovascular risk was statistically significant in males only. Conclusions: Thus, although over 10 years, the LVM increase does not reach a LVH status, it is associated with an augmented cardiovascular mortality risk. This suggests that it might be important to consider periodical LVM assessment, even when LVM is within the normal range, to timely detect its increase and cope with the need of cardiovascular risk restratification.

The hypertensive response to exercise testing, defined as exaggerated blood pressure response (EBPR), has been documented to be independently associated with unhealthy conditions, carrying an increased risk of future hypertension, cardiovascular (CV) morbidity and mortality. In treated hypertensives, EBPR is a marker of uncontrolled hypertension, a condition previously undetected by office blood pressure (BP) measurements at rest; EBPR may also detect masked hypertension, a phenotype characterized by normal BP values in the medical environment but elevated home or ambulatory BP monitoring (ABPM). The aim of the present review is to provide a comprehensive and up-dated information on the clinical importance of EBPR targeting the following issues: (I) definition and prevalence; (II) underlying mechanisms; (III) clinical correlates and association with subclinical organ damage; (IV) predictive value; (V) clinical decision making.

Aim: Whether exaggerated blood pressure response (EBPR) to exercise represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. We investigated this issue through a review and a meta-analysis of studies providing data on this association in normotensive individuals undergone both to dynamic or static exercise and to 24 h blood pressure monitoring (ABPM). Design: A systematic search was performed using Pub-Med, OVID, EMBASE, and Cochrane library databases from inception up to 31 December 2022. Studies were identified by using the following search terms: “masked hypertension”, “out-of-office hypertension”, “exercise blood pressure”, “exaggerated blood pressure exercise”, “exercise hypertension”. Results: Nine studies including a total of 387 participants with MH and 406 true normotensive controls were considered. Systolic BP (SBP) and diastolic BP (DBP) at rest were significantly higher in MH individuals than in sustained normotensives: 126.4 ± 1.4/78.5 ± 1.8 versus 124.0 ± 1.4/76.3 ± 1.3 mmHg (SMD: 0.21 ± 0.08, CI: 0.06–0.37, p = 0.007 for SBP; 0.24 ± 0.07, CI: 0.08–0.39, p = 0.002 for DBP). The same was true for BP values at peak exercise: 190.0 ± 9.5/96.8 ± 3.7 versus 173.3 ± 11.0/88.5 ± 1.8 mmHg (SMD 1.02 ± 0.32, CI: 0.39–1.65, p = 0.002 for SBP and 0.97 ± 0.25, CI: 0.47–1.96, p < 0.0001 for DBP). The likelihood of having an EBPR was significantly greater in MH than in their normotensive counterparts (OR: 3.33, CI: 1.83–6.03, p < 0.0001). Conclusions: Our meta-analysis suggests that EBPR reflects an increased risk of MH and that BP measurement during physical exercise aimed to assess cardiovascular health may unmask the presence of MH. This underscores the importance of BP measured in the medical setting at rest and in dynamic conditions in order to identify individuals at high cardiovascular risk due to unrecognized hypertension.

Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal denervation (RDN) are associated with a central sympathoinhibition is controversial. We examined this issue by performing a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT). Methods: This analysis comprised 11 studies including a total of >400 RHT patients undergoing RDN and were followed up for 6 months. Evaluation was extended to the relationships of MSNA with clinic heart rate and BP changes associated with RDN. Results: MSNA showed a significant reduction after RDN (-4.78 bursts/100 heart beats; P<0.04), which was also accompanied by a significant systolic (-11.45 mm Hg; P<0.002) and diastolic (-5.24 mm Hg; P=0.0001) BP decrease. No significant quantitative relationship was found between MSNA and systolic (r=-0.96, P=0.19) or diastolic BP (r=-0.97, P=0.23) responses to RDN. This was also the case for clinic heart rate (r=0.53, P=0.78, respectively), whose post RDN values were not significant different from the pre-RDN ones. More than 10 renal nerves ablations were found to be needed for obtaining a significant sympathoinhibition. Conclusions: This meta-analysis, the first ever done on the MSNA responses to RDN, shows that in a consistent number of RHT patients RDN is associated with a significant, although modest, central sympathoinhibition, which appears to be unrelated to the BP lowering effects of the procedure. Thus factors other than the central sympathetic outflow inhibition may concur at the BP lowering effects of RDN.