Effect of multicomponent therapy on left ventricular diastolic function in resistant hypertension patients

The aim – to determine prognostic factors of improving left ventricular diastolic function (LV DF) in resistant hypertension (RH) patients (pts) treated with multicomponent antihypertensive therapy during three years.Materials and methods. 102 patients with true RH were included. Patients received triple fixed combination (blocker of the renin-angiotensin-aldosterone system / calcium antagonist / diuretic), to which has been added a fourth drug (spironolactone, eplerenone, moxonidine, torasemide or nebivolol). The state of LV DF was studied at the beginning and at the end of the study. Office and 24-h ambulatory blood pressure (BP) measurements, echocardiography, clinical characteristics, neurohumoral and proinflammatory status were assessed.Results and discussion. Impairment LV DF was detected in 75.5 % of pts. The first degree of LV diastolic dysfunction (DD) was observed in 63.7 %. The patients were divided into 2 groups: the first group included persons without initial impairment of LV DF (n=25), the second – pts with LV DD (n=77). Patients with LV DD were older, had a longer duration of hypertension, higher body mass index, 24-h urinary albumin excretion, office BP and 24-h ambulatory BP, more often (in 2 times) disorders of circadian BP rhythm and concomitant diabetes mellitus (DM). Left ventricular DD in 100 % of cases was associated with severe LV hypertrophy (LVH), increased plasma concentration of inflammatory proteins (CRP, fibrinogen), cytokines (IL-6, TNF-α), increased activity of leukocyte elastase, macrophage matrix metalloproteinase-12. The concentration in the blood of aldosterone, active renin, 24-h urinary excretion of metanephrines did not differ between the groups.Conclusions. Improvement and stabilization of LV DF occurred in parallel with regression of LVH (normalization of LVMI in 35.1 % of pts and significant decrease of LVMI in 64.9 %) against the background of decrease of BP and in the proportion of pts with disturbed circadian BP rhythm. The independent factors of the E/E’ ratio were the initial plasma concentrations of aldosterone (β=0.556; р=0.0001), glucose (β=0.366; р=0.0001), active renin (β=–0.223; р=0.004), 24-h urinary albumin excretion (β=0.188; р=0.016), age (β=0,192; р=0,023). The odds of an improvement in LV DF increased by 3.7 times, if the patient with RH had no DM, LVH regression occurred.

Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford Progeria Syndrome

Clinical trials have demonstrated that lonafarnib, a farnesyltransferase inhibitor, extends lifespan in patients afflicted by Hutchinson-Gilford progeria syndrome, a devastating condition that accelerates many characteristics of aging and results in premature death due to cardiovascular sequelae. The US Food and Drug Administration approved ZokinvyTM (lonafarnib) in November 2020 for treating these patients, yet a detailed examination of drug-associated effects on cardiovascular structure, properties, and function has remained wanting. In this paper, we report encouraging outcomes of daily post-weaning treatment with lonafarnib on the composition and biomechanical phenotype of elastic and muscular arteries as well as associated cardiac function in a well-accepted mouse model of progeria that exhibits severe end-stage cardiovascular disease. Lonafarnib resulted in 100% survival of the treated progeria mice to the study end-point (time of 50% survival of untreated mice), with associated improvements in arterial structure and function working together to significantly reduce pulse wave velocity and improve left ventricular diastolic function. By contrast, dual treatment with lonafarnib and rapamycin did not improve outcomes over that achieved with lonafarnib monotherapy.

Assessment of Left Ventricle Myocardial Function in Hypertensive Patients Using Three-Dimensional Speckle-Tracking Echocardiography (3D-STE)

Background: Increased myocardial fibrosis in hypertension leads to abnormalities in left ventricular diastolic function. 3D-speckle-tracking imaging (3D-STI) is a primary imaging modality used to detect early changes in the left ventricle (LV). The aim of this study was to assess the left ventricular myocardial function in hypertensive patients using 3D-speckle tracking imaging (3D-STI). Methods and Results: A case control, nonintervention, descriptive study was conducted in the Department of Ultrasound Diagnosis of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (Wuhan, Hubei, China). The study subjects included 64 patients with hypertension (HT) and, as control group, 44 normotensives. HT patients were divided into HT-I group (SBP of 130-139 mmHg or DBP of 80-89 mmHg, and HT-II group (SBP >140 mmHg or DBP >90 mmHg). In this study, LV geometry and function were assessed using conventional 2D- and 3D-echocardiography in a total of 108 consecutive subjects. LV volumes, global and regional strains were measured using 3D-STI. LV ejection fraction (LVEF) was in normal range in three groups, but in general, it slightly decreased in HT-II patients, compared with control and HT-I groups (62.5±2.1%, 68.0±2.2%, and 67.5±1.3%, respectively, P=0.00). Global systolic strain demonstrated a significant decrease in GLS, GCS, and GRS in the HT-II group, compared with control and HT-I groups. All regional strain parameters (longitudinal, circumferential, and radial) significantly decreased in HT-II patients, compared with control and HT-I groups. Conclusion: A significant deterioration of global LV systolic functions is found in hypertensive patients with well-preserved LVEF, especially in patients with hypertension stage II.

Pulmonary Hypertension Is Associated With Systemic Arterial Hypertension Among Patients With Normal Left Ventricular Diastolic Function

Background The association of pulmonary and systemic arterial hypertension is believed to be mediated through hypertensive left heart disease. The purpose of the current study was to investigate whether pulmonary hypertension (PHT) is associated with systemic arterial hypertension among patients with apparently normal left ventricular diastolic function. Methods and Results Consecutive patients who had echocardiographic evaluation between 2007 and 2019 were enrolled. Patients with disease states that are known to be associated with PHT, including diastolic dysfunction, were excluded from the analysis. Estimated right ventricular systolic pressure was extracted for all patients from the echocardiographic reports. PHT was defined as estimated right ventricular systolic pressure >40 mm Hg. Multivariate logistic regression models were applied. Final study population included 25 916 patients with a median age of 59 (interquartile range, 44–69) years, of whom 12 501 (48%) were men and 13 265 (51%) had systemic arterial hypertension. Compared with normotensive patients, hypertensive patients were 3.2 times more likely to have PHT (95% CI, 2.91–3.53; P <0.001). A multivariate model adjusted for clinical and echocardiographic parameters that are known to be associated with PHT demonstrated that hypertensive patients are almost 3 times more likely to have PHT (95% CI, 2.45–3.15; P <0.001). The association was significant in multiple subgroups but was more significant among women compared with men (odds ratio, 3.1 versus 2.4; P for interaction <0.001). Conclusions PHT is associated with systemic arterial hypertension irrespective of left heart disease. The association is more pronounced among women.

582 Changes on diastolic and atrial functions following a single bout of two different exercise modalities in patients with hypertension and ischaemic heart disease

Aims Concurrent aerobic plus resistance exercise (RAE) and high intensive interval exercise (HIIE) are both effective on inducing post-exercise hypotension (PEH) in patients with hypertension. However central haemodynamic changes associated to PEH in hypertensive subjects with underlying ischaemic heart disease (IHD) have been poorly investigated. To compare the acute effects produced by these two exercise modalities on left ventricular diastolic function and left atrial function. Methods and results Twenty untrained male patients with history of hypertension and IHD under stable pharmacological therapy were enrolled. Each patient underwent three exercise sessions: RAE, HIIE, and a control session without exercise each lasting 45 min. Echocardiography examination was performed before and between 30 and 40 min from the end of the exercise sessions. In the first hour post exercise, BP values decreased in a similar way in RAE and HIIE and were unchanged after control. Compared to pre-session, E/E1 ratio increased after HIIE and remained unchanged after both RAE and control sessions (between-sessions P 0.002). PALS increased slightly after RAE (+1.4 ± 1.1%), decreased after HIIE (−4.6 ± 2.4%). and was unchanged after control. (between-sessions P 0.03). PACS was mildly increased after RAE, was reduced after HIIE, and was unchanged after control. Atrial volume was unchanged after both sessions. Left ventricular and left atrial stiffness increased significantly after HIEE while remained unchanged after RAE and control. Stroke volume and cardiac output increased after RAE, decreased after HIIE, and were unchanged after control. Conclusions Single sessions of RAE and HIIE determined similar PEHs in hypertensive subjects with IHD, while they evoked different central haemodynamic adjustments. Given its neutral effects of on diastolic and atrial functions, RAE seems more suitable for reducing blood pressure in hypertensive patients with IHD.