Targeting Hypertensive Response to Exercise and the Association of Masked Hypertension With Subclinical Organ Damage: A Mini-Review and Meta-Analysis.

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 ±â€…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.

Uric acid and left ventricular hypertrophy: a gender-based meta-analysis of echocardiographic studies.

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 ±â€Š0. 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 ±â€Š0.27, 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.

Platelet Cyclic GMP Levels Are Reduced in Patients with Primary Aldosteronism.

BACKGROUND AND AIM: Nitric oxide inhibits platelet aggregation by increasing the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) through the activation of soluble guanylyl cyclase in target cells. Within this context, the oxidative stress associated with the aldosterone excess impairs the nitric oxide availability. Thus, the aim of the present study was to assess the impact of chronic aldosterone excess on the platelet nitric oxide/cGMP pathway in humans. METHODS: The levels of cGMP were evaluated in platelets of male patients, 12 with primary aldosteronism (PA) and 32 with uncomplicated essential hypertension (EH), matched for age and blood pressure (BP) values. RESULTS: PA and EH patients were 52.8 ± 3 years old and 51.6 ± 1.6 years old, respectively. Systolic and diastolic BP were 158 ± 5.0 mmHg and 105.9 ± 2.3 mmHg in PA and did not differ compared to EH patients (156.6 ± 2.4 mmHg and 104.7 ± 1.2 mmHg). Mean aldosterone levels were significantly higher in PA (25.5 ± 8.8 ng/dL) compared toEH (8.11 ± 0.73 ng/dL), whereas potassium was significantly lower in PA (3.52 ± 0.18 mEq/L) compared to EH (4.08 ± 0.04 mEq/L). Aldosterone and potassium were inversely related (r = -0.49, p = 0.0006) in the whole study population (n = 44). Platelet cGMP was significantly lower in PA (5.1 ± 0.36 pM/109 cells) than in EH (7.1 ± 0.53 pM/109 cells), and in the entire study cohort, it was directly related to plasma potassium (r = 0.43, p = 0.0321). CONCLUSIONS: These results show an impairment of nitric oxide/cGMP signaling in platelets of PA patients. This effect is likely related to the potassium-depleting effect of chronic aldosterone excess. Future studies are needed to understand whether the platelet nitric oxide/cGMP system is involved in the atherothrombotic events in these patients.

Masked Hypertension and Exaggerated Blood Pressure Response to Exercise: A Review and Meta-Analysis.

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.

Targeting Left Ventricular Mechanics In Patients With Pheochromocytoma/Paraganglioma: An Updated Meta-analysis.

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.

Unmasking left ventricular systolic dysfunction in masked hypertension: looking at myocardial strain. A review and meta-analysis.

BACKGROUND AND AIM: A growing body of evidence supports the view that masked hypertension (MH) (i.e. normal office and elevated out-of-office BP) is a blood pressure (BP) phenotype associated with increased risk of subclinical organ damage, cardiovascular disease and death as compared to true normotension. Whether left ventricular (LV) systolic function is impaired in individuals with MH is still a poorly defined topic. Therefore, we aimed to provide a new piece of information on LV systolic dysfunction in the untreated MH setting, focusing on speckle tracking echocardiography (STE) studies investigating LV global longitudinal strain (GLS), a more sensitive index of systolic function than conventional LV ejection fraction (LVEF). METHODS: A computerized search was performed using Pub-Med, OVID, EMBASE and Cochrane library databases from inception until June 30, 2022. Full articles reporting data on LV GLS in MH, as assessed by ambulatory BP monitoring (ABPM), and normotensive controls were considered suitable for the purposes of review and meta-analysis. RESULTS: A total of 329 untreated individuals with MH and 376 normotensive controls were included in six studies. While pooled average LVEF was not different between groups [64.5 ±â€Š1.5 and 64.5 ±â€Š1.3%, respectively, standard means difference (SMD): -0.002 ±â€Š0.08, confidence interval (CI): 0.15/-0.15, P = 0.98), LV GLS was worse in MH patients than in normotensive counterparts (-18.5 ±â€Š0.70 vs. -20.0 ±â€Š0.34%, SMD: 0.68 ±â€Š0.28, CI: 0.12/1.24, P < 0.01). CONCLUSIONS: Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the MH setting can be unmasked by STE and that its implementation of STE in current practice may improve the detection of subclinical organ damage of adverse prognostic significance.

Sex, gender, and subclinical hypertensiveorgan damage-heart.

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.

Early Left Ventricular Dysfunction and Non-Dipping: When Ejection Fraction is Not Enough. A Meta-Analysis of Speckle tracking Echocardiography Studies.

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.

Obstructive sleep apnea and right ventricular function: A meta-analysis of speckle tracking echocardiographic studies.

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.

Bariatric Surgery and Myocardial Mechanics: A Meta-Analysis of Speckle Tracking Echocardiographic Studies.

Aim: Current evidence on the effects of bariatric surgery on cardiac mechanics in patients with obesity is based on a few single studies. We investigated this issue through a meta-analysis of speckle tracking echocardiography (STE) studies that reported data on changes in left ventricular (LV) mechanics as assessed by global longitudinal strain (GLS). Methods: The PubMed, OVID-MEDLINE and Cochrane library databases were systematically analysed to search English-language articles published from inception to 31 May 2022. Studies were identified by using Me-SH terms and crossing the following terms: "obesity", "bariatric surgery", "left ventricular mechanics", "left ventricular hypertrophy", "systolic dysfunction", "global longitudinal strain", "echocardiography" and "STE echocardiography". Results: The meta-analysis, including a total of 512 patients with obesity from 13 studies (follow-up 1−23 months), showed a significant GLS improvement after bariatric procedures, with standard mean difference (SMD) being 0.50 ± 0.08, CI: 0.34/0.65, p < 0.0001. Corresponding SMD value for LV ejection fraction (LVEF) was 0.15 ± 0.09, CI: −0.04/0.34, p = 0.11. A sensitivity analysis restricted to 11 studies with follow-up ≥ 6 months confirmed that GLS (SMD: 0.47 ± 0.08, CI: 0.30/0.63, p < 0.0001) but not LVEF (SMD: 0.14 ± 0.11, CI: −0.08/0.37, p = 0.21) improved after surgery. Conclusions: Our meta-analysis adds a new piece of information on the beneficial effects of bariatric surgery on LV systolic function and, more importantly, suggests that the assessment of myocardial strain should be routinely implemented for a comprehensive evaluation of cardiac functional changes associated with bariatric procedures.

Is myocardial strain an early marker of systolic dysfunction in obstructive sleep apnoea? Findings from a meta-analysis of echocardiographic studies.

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 ±â€Š0.17, CI: -1.58 to -0.90, P  < 0.0001), as well as in the normotensive OSA subgroup (SMD: -1.17 ±â€Š0.12 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.

The impact of continuous positive airway pressure on cardiac mechanics: Findings from a meta-analysis of echocardiographic studies.

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.

Is Thoracic Aortic Diameter an Independent Predictor of Cardiovascular Disease and Mortality? A Narrative Review.

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.

Effects of Sacubitril/Valsartan on biomarkers of fibrosis and inflammation in patients with heart failure with reduced ejection fraction.

AIMS: To evaluate the circulating levels of remodeling biomarkers procollagen type 1 C-terminal propeptide (PICP), human cartilage glycoprotein-39 (YKL-40), plasma renin activity (PRA), aldosterone (Aldo) as well as clinical and echocardiographic parameters in patients with heart failure with reduced ejection fraction (HFrEF), before and after treatment with Sacubitril/Valsartan (S/V). METHODS AND RESULTS: A total of 26 consecutive patients with HFrEF on stable clinical conditions were studied. Clinical, echocardiographic parameters and circulating biomarkers were measured at baseline, after 30 and 60 days of S/V treatment. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased, from 126 ± 15 to 113 ± 4 mmHg (p < 0.001) and from 77 ± 11 to 72 ± 9 mmHg (p = 0.005), respectively, at the end of study. Concomitantly, left ventricular ejection fraction (LVEF) increased by 22.8% from 29.5 ± 5% to 36.2 ± 5%, (p < 0.001) and indexed left ventricular end-systolic volume (LVESVi) decreased by 12% from 38.6 ± 8.7 ml/m2 to 34.0 ± 10.0 ml/m2. (p = 0.007). Circulating levels of PICP, YKL-40, PRA and Aldo decreased by - 42.2%, - 46.8%, - 79.1% and - 76.7%, respectively (p < 0.001 for all), the decrements being already maximal within 30 days of S/V treatment. No significant changes of plasma electrolytes and creatinine were observed during the study (all p > 0.05). CONCLUSIONS: A decrease of circulating markers of inflammation and fibrosis during chronic treatment with S/V is associated with an improvement of hemodynamic and echographic parameters in patients with HRrEF. These data are compatible with an anti-fibrotic and anti-inflammatory effect of S/V, that may contribute to the beneficial outcomes of the drug in this clinical setting.

Effect of long-term antihypertensive therapy on myocardial strain: a meta-analysis.

AIM: Evidence on the impact of blood pressure (BP)-lowering drugs on left ventricular (LV) mechanics in hypertension is still limited. We performed a meta-analysis of speckle-tracking echocardiographic studies in order to provide a new piece of 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 31 October 2021. Studies were identified by using MeSH terms and crossing the following search items: 'myocardial strain', 'left ventricular mechanics', 'speckle tracking echocardiography', 'systolic dysfunction', 'left ventricular hypertrophy', 'systemic hypertension', 'BP lowering drugs,' 'antihypertensive therapy'. RESULTS: A total of 1140 hypertensive patients (mean age 55.4 years, 50% men, follow-up 6-36 months) were included in eight studies. Pretreatment and posttreatment pooled SBP/DBPs were 148.4 ±â€Š3.5/88.7 ±â€Š2 vs. 127.4 ±â€Š1.9/77.8 ±â€Š0.9 mmHg. Corresponding values for ejection fraction (EF), LV mass (LVM) index, and global longitudinal strain (GLS) were 64 ±â€Š2.3 vs. 65.9 ±â€Š1.7% (SMD: 0.14 ±â€Š0.03, CI 0.08- 0.20, P = 0.001); 108.4 ±â€Š11.2 vs. 100.2 ±â€Š11.0 g/m2 (SMD: -0.27 ±â€Š0.10, CI -0.46 to -0.08, P < 0.01); -17.7 ±â€Š0.6 vs. -19.6 ±â€Š0.4%, (SMD 0.26 ±â€Š0.03, CI 0.20-0.32, P < 0.0001), respectively. A meta-regression analysis showed a significant relation between GLS improvement and the extent of reduction of LVMI (P = 0.0003), but not of SBP (P = 0.27). CONCLUSION: Our meta-analysis suggests that antihypertensive treatment has a clear beneficial effect on LV mechanisms, and the improvement in GLS is mainly related to the reduction in LVMI rather than SBP.

Sleep Apnea Syndrome and Large Artery Subclinical Damage: Targeting Thoracic Aortic Dilatation.

AIM: Whether obstructive sleep apnea (OSA) actually represents an independent risk factor for aortic dilation in the general population is unclear. We investigated this issue through a review and a meta-analysis of cardiac imaging studies that provided data on this vascular phenotype measured at the root or ascending tract level. DESIGN: A computerized search was performed using Pub-Med, OVID, EMBASE, and Cochrane library databases from inception up to 30 November 2021. Studies were identified by using the following search terms: "aortic root," "ascending aorta," "vascular damage," "echocardiography," "computed tomography," "magnetic resonance imaging," "obstructive sleep apnea," "sleep disordered breathing." RESULTS: Eleven studies including a total of 1,860 patients with OSA (without aortic aneurysms and connective tissue diseases) and 233 non-OSA controls were considered. Aortic diameter was significantly higher in patients with OSA than in non-OSA controls (standard means difference [SMD] = 0.73 ± 0.08, confidence interval [CI]: 0.57-0.88, P < 0.0001). This was also the case for patients with severe OSA as compared with their counterparts with mild OSA (SMD = 0.42 ± 0.07, CI: 0.28-0.56, P < 0.0001). CONCLUSIONS: Our findings suggest an association between OSA and aortic enlargement and particularly in the severe OSA setting. However, this conclusion must be taken with caution in relation to 2 types of factors: (i) the paucity of available data, and (ii) the limits deriving from the methodological differences of the various studies. Larger prospective and carefully designed studies are needed to shed light on this relevant public health topic.

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.

Left ventricular global longitudinal strain in secondary hypertension: A meta-analysis of echocardiographic studies.

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.

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.

The influence of left ventricular geometry on myocardial work in essential hypertension.

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.