STEP Study: Intensive vs. Standard Blood Pressure Control Among Older Hypertensive Patients

In a Hot Line session, Cai J, presented a STEP study at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which assessed whether intensive therapy (systolic blood pressure [SBP] target below 130 mmHg but no lower than 110 mmHg) could decrease the risk of cardiovascular (CV) events compared to standard therapy (SBP target 130–150 mmHg).

Total 8,511 patients aged 60–80 years with SBP 140–190 mmHg was randomised in three screening visits or who were taking antihypertensive medication. All patients had regular follow-up clinic visits and at collaborating hospitals, the same validated office BP measurement tool was used. A smartphone-based app was used to analyse home BP changes as an addition to office BP in follow-up. The primary outcome was a composite of stroke, acute coronary syndrome (ACS), acute decompensated heart failure, coronary revascularisation, atrial fibrillation, or death from CV causes. Secondary outcomes were the individual components of the primary endpoint, death from any cause, major adverse cardiac events and renal outcomes (a decrease in renal function or the development of end-stage renal disease).

The intensive therapy showed mean reduction in SBP by 19.4 mmHg from baseline and 10.1 mmHg with standard treatment across a median follow-up period of 3.34 years. Average SBP was 126.7 mmHg and 135.9 mmHg in the intensive and standard groups, respectively, with an average between-group difference of 9.2 mmHg. Intensive therapy was correlated with a 26% relative-risk reduction in the number of primary outcome events than standard therapy (3.5% vs. 4.6%; hazard ratio 0.74; 95% confidence interval [CI] 0.60 to 0.92). Intensive therapy was also correlated with a 33% lower relative risk of stroke (95% CI 0.47 to 0.97) and a 33% lower relative risk of ACS (95% CI 0.47 to 0.94). The occurrence of safety outcomes and renal outcomes did not vary among the groups, except for hypotension, which happened in 3.4% of patients in the intensive group and 2.6% in the standard group (p=0.03).

Active control of SBP to below 130 mmHg showed lower occurrence of major CV events as compared to below 150 mmHg  in older hypertensive patients, with no increase in renal injuries, Home BP monitoring more precisely reflected long-term variations in BP as compared to office measurements.


2021 ESC Clinical Practice Guidelines on Cardiovascular Disease Prevention in Clinical Practice

Current developments in prediction of cardiovascular disease (CVD) risk and therapy advantage, as well as unique therapies and therapy goals, entailed new, up-to-date guidelines. Visseren F, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which disclosed the 2021 ESC Guidelines on CVD prevention in clinical practice.

Analysis of CVD risk remains the cornerstone of the guidelines and emerges at the forefront of proposed new management schemes. Individualised decisions using risk estimation and a stepwise approach to treatments is more complex as compared to a one-size-fits-all approach, however it reflects the diversity of patients and patient characteristics in everyday clinical practice, and is necessary to give the right patient the right treatment. A new section is assigned to communication of risk in the shared decision-making procedure. The goals are for individuals to understand their risk, the anticipated risk reduction with preventive actions, the pros and cons of intervention, and their own priorities. For the first time, the guidelines directly state that smoking cessation is recommended nevertheless of weight gain, as weight gain does not decrease the advantages of cessation. Concerning exercise, adults of all ages should strive for at least 150−300 minutes a week of moderate-intensity, or 75−150 minutes a week of vigorous-intensity, aerobic physical activity, or an equivalent combination. A recommendation to decrease sedentary time and engage in at least light activity throughout the day to decrease all-cause and CV mortality and morbidity is new in the guidelines.

Concerning nutrition, recommendations now incorporate the adoption of a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink contains 8 to 14 g); eating fish, preferably fatty, at least once a week; and restricting consumption of meat, particularly processed meat. For the first time, the guidelines declare that bariatric surgery should be considered for obese individuals at high risk of CVD when a healthy diet and exercise do not result in maintained weight loss.

It is now recognized that patients with mental disorders require intensified attention and support to enhance adherence to lifestyle changes and drug therapy. Furthermore, the guidelines reveal that atherosclerotic CVD patients with stress should be contemplated for referral to psychotherapeutic stress treatment to decrease stress symptoms and improve CV outcomes. The guidelines extend to policy interventions at the population level, with a new section that recommends reducing the use of fossil fuels and limiting carbon dioxide release.


IAMI: Influenza Vaccination After Myocardial Infarction Randomised Trial

Influenza vaccination may protect against cardiovascular (CV) incidents, however it is not standard hospital practice for patients who have experienced an acute myocardial infarction (MI), although it is recommended for patients with chronic coronary syndromes.

In a Hot Line session today, Frobert O, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which reported findings from the IAMI trial, the largest study to date to analyse whether influenza vaccination decreases CV events in high-risk patients with recent MI. Conducted at 30 hospitals in 8 countries (Sweden, Denmark, Norway, Latvia, the UK, Czech Republic, Bangladesh and Australia), the trial covered four influenza seasons (October 2016 through February 2020).

Patients were randomised 1:1 to acquire influenza vaccine or saline (placebo) within 72 hours following coronary angiography or hospital admission for MI. The primary endpoint was a composite of all-cause death, MI, or stent thrombosis at 12 months. Key secondary outcomes incorporated the individual components of the primary endpoint along with CV death. Following enrolment of 2,571 patients (58% of the target), the trial was halted prematurely because of the COVID-19 pandemic. The average age of participants was 60 years and 18% were women. Around three-quarters of patients showed percutaneous coronary intervention and one-quarter received medical therapy alone. Vaccination was correlated with a 28% reduction in the risk of the primary composite endpoint (67 patients, 5.3%) than placebo (91 patients, 7.2%) (hazard ratio [HR] 0.72; 95% confidence interval [CI] 0.52 to 0.99; p=0.040). Vaccination also caused 41% reductions in the risk of all-cause death (HR 0.59; 95% CI 0.39 to 0.89; p=0.010) and CV death (HR 0.59; 95% CI 0.39 to 0.90; p=0.014). No difference was seen between the vaccination and placebo groups in the rate of MI, which happened in 25 (2.0%) and 29 (2.4%) patients, respectively (HR 0.86; 95% CI 0.50 to 1.46; p=0.57). Serious adverse events were rare and of similar type and event in both groups.

It was concluded that influenza vaccination should be contemplated as part of in-hospital therapy following MI.

Non-invasive Risk Prediction Based on Right Ventricular Function in Patients with Pulmonary Arterial Hypertension

Individual risk evaluation in patients with pulmonary arterial hypertension (PAH) is basic to enhance their effect. While right ventricular (RV) dysfunction is a vital factor of result in PAH, echocardiographic estimates of RV function are poorly constituted by current risk models.

Qaderi V, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which recognized echocardiographic measures of RV function, which are correlated with adverse outcome and to develop a non-invasive, echocardiography-based risk score for PAH patients.

A functional status, laboratory results, pulmonary function and echocardiographic measures were assessed in 254 patients with PAH. Echocardiographic measures consisted RV chamber diameters, right atrial area, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), 2D RV strain and pericardial effusion. Cox regression models were used to evaluate the correlation with the composite endpoint of 5-year all-cause death or lung transplantation. The examination incorporated a conventional model with only guideline-recommended variables and a model adding substantial echocardiographic measures. Based on the final multivariable model a point risk score was obtained, indicating the correlation with the primary outcome.

33.9% were females with median age was 65.5 years. 74 patients died (n=63) or underwent lung transplantation (n=11) in a median follow-up time of 4.18 years. In univariable evaluations, low systolic blood pressure (Hazard ratio [HR] 0.99, 95% Confidence Interval [CI] 0.98,1.00), NYHA functional class IV (HR 3.23, 95%CI 1.48,7.07), 6-minute walk distance (HR 1.00, 95%CI 1.00,1.00), NT-proBNP concentrations (HR 1.00, 95%CI 1.00,1.00), renal impairment (HR 0.99, 95%CI 0.98,1.00), decreased diffusion capacity for carbon monoxide (HR 0.99, 95%CI 0.98,1.00), decreased TAPSE (HR 0.90, 95%CI 0.85,0.96) and decreased FAC (HR 0.97, 95%CI 0.94,1.00) were correlated with the endpoint.  A multivariable, conventional risk model, incorporating NYHA functional class, 6-minute walk distance, NT-proBNP concentrations, pericardial effusion and right atrial area, showed a C-Index of 0.539. Addition of TAPSE and FAC to this model enhanced the execution substantially (C-index 0.639, p-value 0.017). This model was translated to a 12-point score with the greatest weighting allocated to TAPSE, FAC, pericardial effusion and 6-minute walk distance (Figure).

An easily applicable score combining non-invasive, echocardiographic factors of RV function enhances prognosis of adverse effect in PAH patients.

Treatment Effect of Selexipag on Time to Disease Progression When Initiated Early in Pulmonary Arterial Hypertension (PAH) Patients: GRIPHON and TRITON Pooled Analysis

In PAH clinical practice, drugs targeting the prostacyclin pathway, including the oral prostacyclin receptor agonist selexipag, are generally initiated years following diagnosis. The GRIPHON and TRITON randomised controlled trials analysed the effect of selexipag on disease progression, primary and secondary endpoints, respectively. In GRIPHON, selexipag substantially decreased the risk of disease progression (composite primary endpoint) in a PAH population (N=1156) with a mean time from diagnosis of 2.4 years, as part of an oral triple, double or monotherapy regimen versus placebo. In TRITON, a prospective signal for decreased risk of disease improvement was noticed with initial triple oral therapy (selexipag, macitentan, tadalafil) versus initial double oral therapy (placebo, macitentan, tadalafil) in 247 newly diagnosed, treatment naïve patients. Coghlan JG, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which analysed the effect of initiating selexipag within 6 months of diagnosis on disease progression in a large PAH population.

Patients were selected from GRIPHON and TRITON diagnosed within 6 months of randomization and compared those on active treatment with selexipag (selexipag group) versus patients on control therapy with placebo (control group). Disease development endpoints were described as in the GRIPHON and TRITON studies, respectively. Hazard ratios (HR) and 95% CI for time to first disease progression incident up to end of double-blind therapy (selexipag/placebo) + 7 days were analysed by a Cox regression model which incorporated therapy as a factor, and baseline prognostic factors and study as covariates.

Altogether, 649 patients met the criteria (diagnosis ≤ 6 months) for these evaluations: 329 in the selexipag group (207 from GRIPHON and 122 from TRITON) and 320 in the control group (197 from GRIPHON and 123 from TRITON). Patient characteristics at baseline and therapy regimens were balanced among the groups. Selexipag/placebo was given as part of triple therapy in 44%, double therapy in 32% and monotherapy in 24% of patients with respect to therapy regimen. The median (range) exposure to study therapy was 510 (4 – 1280) and 409 (3 – 1318) days in the selexipag and control groups, respectively. There were 67 (20%) and 116 (36%) patients who experienced a disease development incident in the selexipag and control groups, respectively. Selexipag showed reduction in the risk of disorder development (first event) by 52% than control (HR 0.48 [95% CI 0.35, 0.66]) (Figure).

This post-hoc pooled evaluation of GRIPHON and TRITON patients diagnosed within 6 months recommends that targeting the prostacylin pathway with selexipag within a short time following detection may decrease the risk of disorder development in a broad PAH population.


Mechanistic Insights from A Multiparametric Magnetic Resonance Imaging Study Regarding the Role of Sodium Glucose Co-transporter 2 Inhibitors

Type 2 diabetes (T2D) is correlated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-co transporter-2 (SGLT2) inhibitors decrease the risk of major adverse CV events and hospitalisation for HF in T2D patients with high cardiovascular risk, in spite of only a modest enhancement in glycaemic control. Restoring cellular energy homeostasis and reversing adverse cardiac remodelling in diabetes have been postulated as a prospective metabolic modulatory impact of SGLT2 inhibitors causes their advantageous CV outcomes. Myocardial energy deficient states can be diagnosed non-invasively using 31-phosphorus magnetic resonance spectroscopy (31P-MRS).

Thiru S, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which analyse the impacts of the selective SGLT2 inhibitor empagliflozin on myocardial energetics, function, perfusion, and myocardial cellular volume in patients with T2D using cardiovascular magnetic resonance imaging (CMR) and 31P-MRS in a single centre longitudinal cohort study.

18 successive T2D patients who were started on empagliflozin in cardiometabolic optimisation clinics underwent CMR and 31P-MRS scans before and following 12-week empagliflozin therapy, and plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were estimated. 10 controls with no diabetes underwent an identical 31P-MRS and CMR protocol on a single visit.

Patients with T2D exhibited lower myocardial energetics (1.52±0.40 vs 2.20±0.5, p=0.0005), lower stress myocardial blood flow (1.60±0.50 vs 2.10±0.50, p=0.02) and lower left ventricular ejection fraction (52±13% vs 63±4%, p=0.01) as compared to controls. Empagliflozin treatment exhibited substantial enhancements in myocardial energetics (PCr/ATP: 1.52 to 1.76, p=0.009). This was followed with a relative 13% enhancement in left ventricular ejection fraction (p=0.001), 3% improvement in global longitudinal strain (p=0.01), 61% reduction in NTproBNP (p=0.05), and 9% reduction in myocardial cell volume (p=0.04). No substantial change in myocardial blood flow or diastolic strain was diagnosed.

For the first time, Empagliflozin enhances myocardial energetics and function, decreases myocardial cellular volume, and decreases NT-proBNP levels in patients with T2D.


Adoption of a New Automated Optical Coherence Tomography Software to Obtain a Lipid Plaque Spread-out Plot

Results from the study – Adoption of a new automated optical coherence tomography software to obtain a lipid plaque spread-out plot, were presented by Biccire FG, at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021. Near infrared spectroscopy – intravascular ultrasound (NIRS-IVUS) imaging provides a fully automated estimation of lipid burden. It provides a two-dimensional (2D) spread-out plot and Lipid Core Burden Index (LCBI) which are associated with higher incidence of cardiac events. Identification of lipid component with high accuracy can be achieved with Optical coherence tomography (OCT) and can potentially measure its longitudinal extension in a dedicated 2D LCBI spread-out plot. Validation of a novel automated approach to assess OCT images, providing a dedicated LCBI spread-out plot plus other features of plaque vulnerability was performed in this study.

The results obtained with a novel automated OCT algorithm, were developed utilising a convolutional neural network, and were compared with those obtained with conventional (manual) OCT and with NIRS-IVUS in 40 patients with coronary artery disease. The new OCT algorithm was examined and validated to calculate the lipid core longitudinal extension in a dedicated 2D LCBI spread-out plot. With NIRS-IVUS, each coronary plaque was measured for: 1) minimum lumen area (MLA), 2) vessel area at MLA site, 3) plaque burden (%) at MLA site, 4) NIRS-defined lipid pool arch and 5) maximum LCBI measurement within a 4 mm length. OCT features with: 1) the MLA cross section, 2) the minimum fibrous cap thickness (FCT) in presence of lipid components and measured as the average of three measurements obtained in the same cross-section and 3) maximum LCBI within a 4 mm length were obtained.

3 lesions groups identified were 1) culprit lesions in patients with acute coronary syndrome (ACS, n=16), 2) non-culprit lesions in patients with ACS (n=12) and 3) lesions in patients with stable angina (n=12). According to conventional OCT, a larger lipid arc and significant thinner FCT (p=0.028) were responsible for ACS plaques. NIRS-IVUS showed a more complex anatomy contributing to ACS plaques. Increased maximum LPBI in 4mm segments was found in the culprit ACS group, irrespective of the imaging modality used (p=0.184 and p=0.066, respectively, figure 1). A fair correlation was obtained for the maximum 4 mm LCBI measured by NIRS-IVUS and automated OCT (r=0.75). For automated OCT, after applying a validated 400 cut off, the sensitivity and specificity to detect significant LCBI were 90.5 and 84.2, respectively.

The automated OCT software promoted and improved OCT clinical application for the identification of patients at risk of hard events by providing a dedicated lipid plaque spread-out plot to address plaque vulnerability.


Anxiety and Depression Associate with Heightened Risk of Deep Venous Thrombosis: Mediation Through Neural Pathways

Mezue K, elucidated the association of anxiety and depression with heightened risk of deep venous thrombosis at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021. An increased risk of deep venous thrombosis (DVT) is observed with anxiety disorders and depression. Evidences suggest that anxiety and depression lead to heightened stress-associated neural activity (notably in the amygdala: AmygA), promoting chronic inflammation, a driver of thrombosis syndromes. This study evaluates whether the association between anxiety/depression and DVT risk: A) persists after robustly accounting for potential confounders, and B) is mediated by upregulated stress-associated neural activity (namely AmygA).

Data of 1520 subjects (median age 57 years, 58.4% females) who underwent clinical 18F-fluorodeoxyglucose positron emission tomography imaging during the follow up period were obtained from the Mass General Brigham Biobank. AmygA was measured as the ratio of amygdalar to regulatory (ventromedial pre-frontal cortex) activity. International Classification of Disease (ICD) codes in the medical record were used to define anxiety disorders, depression, and lower extremity DVT. Individuals on anticoagulant therapies for atrial fibrillation prior to enrolment and/or imaging were excluded. Cox analysis were performed wherein patients who developed DVT prior to Biobank enrolment and mediation analysis was used to examine the role of AmygA in mediating the link between anxiety/depression and DVT.

1231 participants (1.2%) incurred DVT over a median follow up period of 3.3 years (IQR 3.0). Anxiety disorders and depression were independent predictors of incident DVT after controlling for confounders. In the subset of 1383 participants who underwent brain imaging, anxiety disorders and depression associated with increased AmygA activity after controlling for risk factors. AmygA was associated with DVT and increased AmgyA led to both anxiety and depression in DVT.

Anxiety disorders and depression were linked with increased risk of DVT via heightened stress-related neurobiological activity.

Longitudinal Strain Measurement by 3D Modelling from Cine CMR: Feasibility and Comparison to 2D Speckle Tracking Echocardiography

Global longitudinal strain (GLS) has emerged as a sensitive index of left ventricular (LV) systolic function with greater prognostic value than LV ejection fraction (LVEF) in a variety of cardiac disorders. While GLS is routinely derived from 2D speckle tracking echocardiography (STE) and feature tracking in cardiac magnetic resonance (CMR) imaging, calculation of strain via 3D geometric modelling enables analyses of deformation that are independent of 2D image plane constraints. Zhao D, presented a session at the European Society of Cardiology (ESC) Congress 2021: The Digital Experience on 30th August 2021 which compared longitudinal strain measurements extracted from geometric 3D analysis of CMR against values obtained from conventional 2D‑STE.

Successive 2D-echocardiography (2D-echo) and steady-state free precession multiplanar cine CMR scans were executed in 80 prospectively recruited participants (48 healthy controls with LVEF range 53-74%, 30 patients with non-ischaemic cardiac disease with LVEF range 25‑77%, and 2 heart transplant recipients with LVEF 53 % and 58 %), <1 hour apart. Average endocardial peak GLS from 2D‑STE was measured offline by vendor-independent clinical software from apical triplane (2, 3 and 4-chamber) images for each of the standardised LV walls (anterior, anteroseptal, inferoseptal, inferior, inferolateral, anterolateral). Dynamic 3D geometric models of the LV were reconstructed from 3 long- and 6 short-axis CMR slices across one cardiac cycle. An extracting analogous endocardial arc lengths (apex to base of each LV wall) from the 3D LV model analysed corresponding longitudinal strain estimations. Eventually, an average peak GLS was estimated as the mean of the peak longitudinal strains in each LV wall.

2D-STE calculated GLS ranged between -6.5 % to -27.9 % for the study population. A two-way mixed-impacts intraclass correlation coefficient (ICC) for absolute agreement of 0.820 (95 % CI: [0.720, 0.885]) showed good association among average GLS acquired from 2D-STE and CMR. A Bland-Altman evaluation showed a minimal bias (<1 %) and 95 % limits of agreement (LOA) between ‑6.3 % to 5.5 %, with no apparent proportional bias. Each LV wall had comparatively lower correlation and wider LOA between longitudinal strains from 2D-STE and CMR.

Fully automated calculation of LV GLS can be acquired from geometric 3D CMR evaluation. Average peak GLS from cine CMR shows good agreement with 2D-STE, in spite of exhibiting only moderate concurrence at each LV wall. The increased discrepancy in regional longitudinal strain may be characterized to subjective plane positioning in 2D-echo, which can be expected to enhance with advances in 3D-STE. The computation of GLS with 3D geometric modelling may enhance the diagnostic value of routine cine CMR examinations for LV systolic function evaluation.