Blood Pressure Measurements Research Articles

Hypertensive myocardial disease screening in low-income settings using smartphone-based technologies: a prospective multicenter trial

Abstract Background Mobile health technologies are revolutionizing cardiovascular (CV) medicine. However, more than 80% of heart disease related deaths occur in low-income settings, that are unable to take advantage of such technologies for healthcare awareness and prevention. Purpose To assess the feasibility of a pilot telemedicine-based CV screening campaign with D-Heart, a validated low-cost 8-lead smartphone portable ECG, coupled with blood-pressure (BP) monitoring in three regions of Africa. Methods A total of 950 patients (60%) men, age 29±21) were enrolled at 5 African rural dispensaries, 2 in Kenya, 2 in Senegal and at a hospital (Uganda). ECGs recording were obtained by community health workers with D- Heart smartphone ECG; BP was measured with a validated smartphone BP recorder. Global burden of ECG abnormalities was defined by a semi-quantitative score based on the sum of 9 criteria, identifying four classes of increasing severity. ECGs that were moderately and severely abnormal and from patients with severe hypertension, were sent for consultation via smartphone to D-Heart tele-cardiology centre: an advice on how to manage the patient was sent back to the community health worker’s smartphone within 15 minutes. If referral was needed, patients were sent to the local hospital. Results Mean BMI was 26.2 ± 8.5 (men 22.3±1.5 vs women 27.2±1.1, p<0.01). Active/recent history of smoking and alcohol intake were 327 (45%, 298 men) and 232/590 (40%, 198 men) respectively. A total of 142 (15%) patients had been previously diagnosed with diabetes, 199(25%) had known hypertension of whom 95/199 on treatment), whereas 43(4%) had a previous myocardial infarction. A total of 487 (51%) patients never had their blood pressure measured, whereas 798(91%) never received an ECG. Mean SBP/DBP were 138±31/71±12 mmHg respectively. Patients with normal BP were 304(32%), whereas 380(40%) were mildly-moderately hypertensive (SBP/DBP 148±7/91±5 mmHg) and 130 (29%) with severe hypertension (SBP/DBP 162±8/99±6 mmHg). D-Heart ECGs tracings were respectively classified as: normal: 361(38%); mildly abnormal: 332(35%); moderately abnormal: 199 (21%) and severely abnormal 58(6%). Most common ECG abnormality was a positive Romhilt-Estes index in 361, 38%. For 174(18%) patients smartphone tele-report advised referral to the local hospital, but only 121 69%) presented to the visit: 9 (8%) were found to have normal hearts, 57(47%) with hypertensive heart disease, 35 (29%) with rheumatic heart disease, 20 (16%) with HFrEF. Visit time was 8±2 minutes; cost of screening per patient was 1.10€: 0,30€ for consumable electrodes, 0.80€ for the community health worker visit time. Conclusions D-Heart ECG screening combined with smartphone BP measurement proved feasible and cost-effective. This should encourage to develop and extend low-cost/high-technology community-based CV screening programs in low-income settings.

The diagnostic role of myocardial work indices in stable coronary disease - global wasted work as a novel important non-invasive parameter?

Abstract Introduction Although the non-invasive diagnostic tools for stable coronary artery disease (CAD) have developed significantly over the past years, there is no resting parameter available to recognize functionally significant CAD. The role of the novel myocardial work index (myocardial work index - MWI) calculated by the pressure-strain loop created with the help of speckle-tracking analysis and blood pressure measurement in the diagnosis of ischemic heart disease is not yet fully clarified. In our research, we examined the parameters of myocardial work analysis in stable coronary disease patients. Purpose Clarification of the diagnostic role of the myocardial work analysis, in patients with stable coronary artery disease. Methods In our prospective, single-center study, we examined 13 patients who had at least moderate stenosis (≥50%) in one main coronary branch detected on coronary CTA. A fractional flow reserve (FFR) test was performed for functional coronary assessment. Based on this measurement, we divided our patients into FFRneg (FFR value>0.8) and FFRpos groups. Echocardiography was performed before coronary angiography in all patients. In addition to the standard echocardiographic parameters, global myocardial work index (GWI), global constructive work (GCW) and global wasted work (GWW) were calculated. In the case of the FFRpos group, we performed the above examination both before and after revascularization (2 months). Results Our results show that neither the standard parameters (GLS, EF), nor the GWI and GCW showed any difference between the FFRpos and FFRneg groups. However, there was a significant difference regarding GWW (172.3±21.8 FFRneg vs. 258.2±38.4 FFRpos, p=0.048) at baseline. In the case of the FFRpos group, the analysis of our data showed that there was no significant difference in EF, GLS, GWI and GWE parameters before and after revascularization. However, global wasted work (GWW) showed a significant improvement after revascularization (preGWW 258.2±38.4 vs. postGWW 139.5±14.5, p=0.041). NT-proBNP levels were normal in our patient population and we could not detect. Conclusion Based on our results, the GWW may be suitable for non-invasive assessment of the functional significance of stable coronary disease, as it showed a significant difference in the case of functionally significant and non-significant stenosis and improved after revascularization in patients with single-vessel CAD.

Gradual hypertensive response in aortic alterations and myocardial inflammatory activation in progressing HFpEF in mice

Abstract Introduction Hypertension is the most common comorbidity in patients affected by heart failure with preserved ejection fraction (HFpEF). Early effects of pressure overload and its contribution to the gradual development of cardiac and vascular pathology leading to HFpEF are not well recognized, as patients are diagnosed when the disease has already advanced and show symptoms. Several hypertensive HFpEF mouse models possessing the hallmarks of the clinical-like phenotype are available. Nonetheless, initial and gradual pathological manifestations of hypertensive HFpEF have not been comprehensively described. Purpose This study aimed to investigate the gradual progression of HFpEF phenotype development in mice from the early manifestation of cardiac and vascular pathology to global cardiac dysfunction to multiorgan syndrome in response to hypertension. Methods Hypertensive HFpEF was induced by angiotensin II infusion in C57BL/6JOlaHsd 18-20-week-old male mice that were given low, moderate and high doses (0.5mg/kg/day - 1.5 mg/kg/day) subcutaneously for 4 weeks. Cardiac physiology and alterations in haemodynamics were assessed with echocardiography of heart and aorta, weekly ECG monitoring, and blood pressure measurements from the mouse tail. Extensive histology and immunohistochemistry analyses of cardiac tissue, microvasculature, lungs and kidneys were performed. Results In the low dose group, loss of aortic wall flexibility and presence of aortic root dilatation were detected. This group also demonstrated initiation of concentric remodelling process with the upsurge in macrophage infiltration in myocardium, but the signs of diastolic dysfunction were not yet present. The high dose group exhibited characteristic HFpEF features with diastolic dysfunction, left ventricular hypertrophy and fibrosis. Pathology in cardiac conduction system was noticed in all groups, with prominent ECG waveform abnormalities already on week one. However, only the high dose group experienced non-recovery in impulse propagation, accompanied by significant prolongation of ventricular depolarization. Conclusion This study demonstrates that change in aortic root dimensions and aortic wall dynamics are the first hypertension-sensitive alterations together with myocardial inflammatory cell infiltration that may contribute to myocardial remodelling and subsequent development of HFpEF and systemic effects. Hypertensive angiotensin II-induced HFpEF is a relevant mouse model, recapitulating not only hallmarks of cardiac pathology but also an extensive range of vascular and multiorgan alterations, demonstrating similarities with the clinical phenotype.

Raised blood pressure affects reactivity to expressive music features

Abstract Background Music has been shown to lower hypertensive patients’ blood pressure in the long-term, but predominant approaches overlook the wide range of complex real-time responses. Mapping the acute dynamics of music features can help discern blood pressure (BP) reactivity. Understanding the mechanisms of music BP effects can broaden the scope for precision medicine. Purpose The aims of this study are to determine: (1) if reshaped music features alter BP reactivity; and, (2) whether BP reactivity differs for individuals with high and normal BP. Methods Participants listened to music with computationally altered tempo and loudness played back on a Disklavier piano. We compared continuous BP measurements in 40 participants (23 females, mean age of 41.3 y (95%CI: 37.2-45.4)), 20 with baseline BP measurement above 140/90 mmHg (H-bBP) and 20 with bBP below (N-bBP), paired by playlist. Continuous BP was recorded while listening to a playlist of 9 reshaped versions of 8 distinct pieces (≈40 min) after a 5-minute baseline silence. Results The mean increase in systolic and diastolic BP during music (reactivity) was significantly higher for N-bBP than H-bBP (mean (95%CI); mmHg): systolic 8.6 (6.2-11.1) vs 5.0 (2.7-7.3); p=0.031; diastolic 7.7 (5.9-9.5) vs 4.6 (2.9-6.3); p=0.0046. No significant difference in pulse pressure (PP) reactivity was found; however, the N-bBP subjects had significantly lower mean PP during music than H-bBP subjects (45.2 (40.2-44.8) vs 54.2 (51.7-56.7) ; p<0.001). Based on mean tempos, N-bBP subjects had significantly lower average PP than H-bBP subjects during slow (<60bpm; 44.6 (40.6-48.6) vs 52.6 (48.9-56.3); p=0.016) and fast (>120bpm; 43.9 (39.9-47.9) vs 57.2 (52.9-61.5); p<0.001) music, though not medium pace music. Similarly, N-bBP participants had significantly lower PP during quiet (<13 dB; 44.0 (39.6-48.4) vs 55.7 (50.7-60.7); p<0.001) and loud (>17 dB; 44.0 (39.6-48.4) vs 55.5 (51.1-59.9); p<0.001) music, but not during moderately loud music. H-bBP and N-bBP participants’ PP measures are more similar during moderately fast and moderately loud music. In addition, N-bBP’s baseline-normalised mean PP was significantly lower only during fast music (3.3 (-2.3-8.6) vs 12.9 (6.9-18.9); p = 0.04). Separating responses to unaltered vs reshaped music––i.e. music made faster and/or louder, in the case of one piece, slower and/or quieter––significant differences are found between N-bBP and H-bBP groups only for reshaped music in baseline-normalised diastolic BP (6.8 (4.7-8.9) vs 3.9 (2.1-5.7); p=0.02) and PP (45.0 (42.2-47.8) vs 54.8 (51.8-57.8); p<0.001). Conclusions H-bBP subjects had less BP reactivity to music, especially in resting vascular tone PP. Reshaping of music can modulate the level of differences between groups, particularly for immoderate tempo and loudness. Music can induce significant changes in BP profile, which indicates that it could potentially be utilised as a tailored anti-hypertensive therapy.Differences between music and baselineDifferences in tempos and loudness cat.

Incorporating intrathoracic pressure fluctuation can improve noninvasive prediction of left ventricular end-diastolic pressure

Abstract Introduction Heart failure (HF) is a leading cause of mortality and morbidity, with a prevalence above 10% in elderly population (1). Left ventricular end-diastolic pressure (LVEDP) is a known indicator for all types of HF. An invasive pressure catheter is the gold standard for measuring LVEDP (2). However, it involves an in-hospital procedure and is costly, which limits the accessibility. A noninvasive strategy would improve early diagnosis and reduce the burden on secondary care. Several noninvasive classifiers are able to detect elevated LVEDP (3-5), with some receiving FDA clearance (6). While beneficial for triaging patients, these classifiers cannot quantify the severity and track disease progression. Developing a noninvasive LVEDP regression model requires accounting for respiration dynamics. Even invasively, the dynamics make measuring LVEDP challenging. This study uses an error metric from ANSI/AAMI/ISO 81060-2:2019 (AAMI) (7) to evaluate the effect of respiration on noninvasive LVEDP regression results. Methods The dataset (147 patients, 21+ yrs old, mean 65 ± 10 yrs; 68% male) consisted of patients referred for nonemergent left heart catheterisation inclusive of direct assessment of LVEDP. Noninvasive data was collected by a modified brachial cuff with a single-lead electrocardiogram (ECG). Invasive data was acquired using a Millar pressure catheter. LVEDP was derived based on the time of the R-wave of the ECG (8). For each patient, 40 secs of noninvasive data with synchronised catheter signals were analysed to build an LVEDP regression model. Inputs were generated from the ECG and brachial pressure waves based on fiducials identified in both signals. Leave-one-subject-out cross-validation (LOSO CV) was used to train and test the algorithm. The impact of respirophasic variation on the model was analysed by comparing the prediction with the mean LVEDP and the range of the mean ± standard deviation (std) (i.e. AAMI error metric). Results The results, evaluated using Bland-Altman and correlation analysis, showed a decrease in the mean absolute error (MAE) from 3.6 mmHg to 1.4 mmHg, the std from 4.9 mmHg to 3.0 mmHg, and the correlation (r) from 0.57 to 0.77 when incorporating intrathoracic pressure swings (Fig.1 and Fig.2). A Levene test on the residuals of the two error determinations showed a significant difference (p-value < 0.01). Conclusion Irrespective of the error metric, the model performance meets the AAMI standard for blood pressure (BP) measurement. Moreover, when respiratory motion is included, agreement with invasive LVEDP improves considerably. From a clinical perspective, this emphasises the importance of targeting end-expiratory LVEDP. With respect to noninvasive BP measurement, it suggests that both brachial BP evaluation and LVEDP prediction should attempt to quantify fluctuations. While the challenge remains, these results indicate that noninvasive LVEDP prediction could be realised in the near future.Fig.1 Prediction vs mean LVEDP.Fig. 2 Prediction vs mean +/- std.

Correlation between postdialysis blood pressure assessed at different time points and home blood pressure monitoring

Abstract Background Hemodialysis patients undergo blood pressure (BP) measurements during the predialysis, intradialytic and postdialysis (POSBP) periods at the dialysis sessions. However, there is no consensus regarding the time point when POSBP measurement should be performed. Purpose This study investigated the relationship of POSBP measurements performed at different time points with home blood pressure monitoring (HBPM). Methods This prospective study included 98 long-term dialysis patients (67% men; age=59.4 ±17.7 years; 79% using antihypertensive medications). During one week, POSBP measurements were obtained in sitting patients by trained health staff using oscillometric BP monitors lodged in the dialysis machines at all dialysis sessions in three different periods: 1) immediately after the dialysis period ended (POSBP1); 2) after returning the patient's blood (POSBP2) and 3) after hemostasis of the fistula or catheter sealing (POSBP3). In the same week, HBPM was performed using validated devices and was calculated as the mean of BP measurements obtained on six consecutive days, comprising three readings in the morning and in the evening after at least 3 min of rest, before antihypertensive medications were taken, with the patients seated. Abnormal BP was defined as HBPM≥135/85 mmHg. Based on the optimal cut-point values derived from ROC curves analysis, we built cutoffs for POSBP1 (143/79 mmHg), POSBP2 (153/78 mmHg) and POSBP3 (151/80 mmHg) corresponding to HBPM values of 135/85 mmHg. Results The values of POSBP1, POSBP2, POSBP3 and HBPM were 138±21/72±13, 143±24/73±13, 142±22/72±13 and 128±19/76±13 mmHg, respectively. Systolic HBPM showed greater correlation with systolic POSBP3 (r=0.71), followed by POSBP1 (r=0.68), POSBP2 (r=0.67), while diastolic HBPM showed greater correlation with diastolic POSBP2 and POSBP3 (both r=0.56), followed by POSBP1 (r=0.49) (all p<0.05). The POSBP3 cutoff showed the highest association (odds ratio [95% CI]= 8.06 [3.21, 20.27]), accuracy (area under the curve [95% CI]= 0.74 [0.65, 0.83]) and concordance (kappa coefficient=0.47) to identify elevated BP at HBPM in comparison with the POSBP1 and POSBP2 cutoffs (Figure). Conclusion(s) POSBP3 exhibited the strongest correlation with HBPM and had the highest accuracy to detect elevated HBPM in dialysis patients and may be a potentially preferable POSBP measurement in clinical practice.

Smartphone application for improving self-awareness of adherence to edoxaban treatment: a randomised controlled trial (ADHERE-APP)

Abstract Background Adherence to oral anticoagulants is essential for stroke prevention in patients with atrial fibrillation (AF). This study aims to test the feasibility and effectiveness of the smartphone app-based intervention to improve drug adherence in patients with AF. Methods This prospective, randomised, open-label, multicentre trial (ADHERE-APP) enrolled a total of 502 patients at 9 university hospitals in South Korea from November 2021 to January 2023. Patients with AF aged ≥19 years requiring oral anticoagulation,and were treated with edoxaban were enrolled. Patients were randomized in a 1:1 ratio to the conventional treatment group and the app conditional feedback group. Patients in the app conditional feedback group used a smartphone application that pushed alarms for taking medication and measuring blood pressure (BP) and heart rate (HR) at specific times of the day. In addition to medication alarms, the habit of measuring one’s BP and HR could improve drug adherence by increasing self-awareness of the disease. The automatic BP machine was connected to the smartphone via Bluetooth and the measured BP and HR were automatically updated on the smartphone app. The primary endpoint was adherence to edoxaban as measured by pill count at 12 and 24 weeks. In addition, we evaluated the differential effect of the smartphone application by age on the primary endpoint. Results Among the 502 patients, the mean age was 66.0±10.0 years and 67.7% were male. Of the 372 patients who completed 12-weeks trial, edoxaban adherence at 12 weeks was high in both arms, with no difference in the primary outcome (96.5% [92.5%-100.0%] vs. 98.0% [93.2%-99.5%], P = 0.488). or in secondary outcomes, including the proportion of patients achieving adherence ≥ 80% or 95%. In patients aged >65 years, adherence to edoxaban was higher in the app conditional feedback group than in the conventional treatment group (95.8% [93.0%-99.5%] vs. 98.0% [95.8%-99.5%], P = 0.049). Conclusions Overall adherence to edoxaban was much higher than expected in patients with AF. There was no difference in edoxaban adherence between the app conditional feedback group and the conventional treatment group, however, in older patients, app feedback increased medication adherence.

Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH) study

Abstract Introduction Pulmonary arterial hypertension (PAH) is characterised by pre-capillary pulmonary vascular remodelling. Imatinib, a tyrosine kinase inhibitor, was the first treatment investigated in PAH patients with the primary aim of targeting vascular remodelling. A Phase 3 study showed that imatinib 400mg daily reduces pulmonary vascular resistance and increases exercise capacity but only 43% of patients continued the drug for 6 months. Concerns about safety prevented regulatory approval. Purpose To identify a safe and tolerated dose of oral Imatinib and evaluate efficacy in the dose range 100-400mg daily. Methods Oral Imatinib was added to the background therapy of 17 patients with PAH; prior intracranial haemorrhage was excluded by cross sectional imaging and none were receiving an anticoagulant. The first patient started on 100mg daily. The next 12 patients were recruited serially at a minimum of 4 week intervals and started on 200mg, 300mg or 400mg, according to a Bayesian adaptive design (Continuous Reassessment Method, CRM). Patients 14-17 were recruited as an extension cohort to better understand the safety and tolerability of the 100mg and 200mg doses. The primary endpoint was safety and tolerability at 4 weeks. Imatinib was continued for up to 24 weeks. Thirteen patients had implanted devices that provided remote daily measurements of cardiopulmonary haemodynamics and heart rate and rhythm and physical activity. Non-invasive measures of systemic blood pressure, weight and oxygen saturations were made remotely. We compared the time-haemodynamic response relationship with that produced by licensed treatments in a similar patient cohort. Results The recommended starting dose from the CRM was 200mg daily. The most common side effect was nausea. Imatinib reduced mean pulmonary artery pressure (P<0.01), increased cardiac output (P=0.08) and reduced total pulmonary resistance (TPR, P<0.001, Figure). There was a clear dose-TPR response relationship (r2=0.52, p<0.01). A reduction in TPR was evident within the first week and plateaued at 4-5 weeks. Withdrawal of Imatinib led to an increase to baseline in TPR over 4-5 weeks. This contrasts with a sharp fall in TPR with licensed therapy and rapid increase on treatment withdrawal. There was a small reduction in systemic vascular resistance (P<0.05) with Imatinib that reached plateau before TPR. Conclusions Oral Imatinib 200mg daily is well tolerated and effective as an add-on treatment in PAH. The time course of the initial haemodynamic response and the gradual return to baseline on withdrawal distinguishes Imatinib from licensed treatments and is supportive of a mechanism of action beyond reliance on vasodilation. Remote monitoring enables the safe evaluation of the withdrawal of an investigational drug in patients established on best medical therapy.Figure 1.

The added value of device measured physical activity to the prediction of incident cardiovascular disease.

Abstract Background Conventional risk prediction models for Major Adverse Cardio/Cerebrovascular Events (MACCE) primarily rely on non-modifiable factors such as age, sex, and physiological measurements, including LDL/HDL cholesterol and blood pressure readings, that are prone to variations across medical practices and are often unavailable in many parts of the world. In this study, we investigate the potential of inexpensive wearable measurements of physical activity to enhance MACCE prediction when physiological measurements are unavailable. Purpose To assess the added value of physical activity measurements, collected via wrist-worn accelerometers, to established cardiovascular risk prediction models. Additionally, we seek to investigate whether physical activity measurements can substitute for common physiological measurements in established cardiovascular risk models. Methods We obtained accelerometer-measured physical activity over 7 days between 2013 and 2015 from 69,898 UK Biobank (UKB) participants without a prior history of MACCE, defined as death or hospitalisation due to (1) myocardial infarction, (2) heart failure, or (3) Stroke/transient ischaemic attack. We assessed the added value of daily step counts, sleep duration, and a deep learning-derived activity health score (Fig 1), calculated from complete 7-day accelerometer recordings, to established clinical risk models (SCORE2, QRISK3 and AHA) before and after excluding measurements of cholesterol and systolic blood pressure (SBP). The primary outcome was the first recorded MACCE within 6 years. Risk scores were developed in men and women using Cox proportional hazards models. We assessed predictive performance using Harrel’s C-index, net reclassification index (NRI), and net benefit at the recommended treatment threshold for each model. Results Of the 69,898 UKB participants in the study, 3,386 (4.8%) experienced a MACCE over a 6-year follow-up period. In place of HDL ratio and SBP, the addition of deep-learned activity health scores modestly improved performance in the best clinical baseline, QRISK3 for Female participants ΔC-index women:0.003 (95% CI 0.002-0.004); Δnet benefit 0.02(0.01-0.03); NRI 0.04, (0.02-0.07), and outperformed manually extracted steps and sleep measurements. We report no significant improvements for men. We find a greater increase in model performance when both HDL ratio and SBP, plus activity health scores, are included in the model. ΔC-index women:0.008, (0.007-0.009); men: 0.003 (0.002-0.004) (Fig 2). Conclusion Our findings indicate that in the absence of cholesterol and systolic blood pressure, the addition of device-measured physical activity modestly improves the performance of clinical risk scores among individuals without prior cardiovascular disease (CVD). These findings could further refine intervention strategies for targeted prevention of CVD, particularly in settings where physiological measurements may be unavailable.

Remote management of worsening heart failure events and subsequent rate of emergency department admission

Abstract Background Worsening heart failure (WHF) is the leading cause of hospitalization among individuals aged ≥ 65 years and constitutes a substantial burden for both the patient and the healthcare systems. Moreover, heart failure contributes to exacerbate the pressure on emergency departments which are involved in 64% of heart failure hospital admission (1). Remote management of heart failure as been shown to reduce the number of days lost due to unplanned cardiovascular hospitalizations and all-cause mortality (2, 3), but little is known about the effect on the emergency healthcare use. We aimed to describe the effect of a telemonitoring program on the rate of emergency admissions for WHF in chronic heart failure patients. Methods All patients enrolled in the heart failure remote management program of two French centers between 13 April 2020 and 31 January 2023 were included in the study. Follow-up data were collected until 31 January 2023. Inclusion criteria were chronic heart failure (HF) with New York Heart Association ≥II and an elevated B-type natriuretic peptide (BNP > 100 pg/mL or N-terminal-pro-BNP > 1000 pg/mL). Remote evaluation included measurements of body weight, blood pressure, heart rate, symptoms, biochemical parameters, and data from cardiac implantable electronic devices when available. Results A total of 1,095 patients (72±11.8 years old, 69.7% male), were followed for a median [IQR] of 437 [182; 739] days with a mean adherence to the remote monitoring system of 67.6±30.3%. Over this period, 198 (18.1%) patients had 949 WHF events, the majority of whom were remotely detected: 830 (87.5%). Overall, 246 (26%) of the WHF episodes required hospitalisation and 109 (11%) prompted an emergency department visit. When the WHF event was remotely detected, hospitalization was only required in 127 (15%) cases and the rate of emergency department visit was reduced to 3%. Conclusion In HF patients engaged in a multiparametric remote management program, the rate of emergency department admission is very low. Adopting such a strategy for patients with chronic HF may be useful in reducing emergency department overcrowding.Baseline characteristics of patientsPatients course and use of resources

Association between autonomic dysfunction, 12-year mortality and 10-year incident cardiovascular disease

Abstract Background Standing from a supine position requires a co-ordinated response in peripheral and central haemodynamic signals to protect the brain and body from sudden drops in blood pressure (BP) and has previously been shown to be an important measure of neuro-cardiovascular health (1-3). Previous studies have found an association between BP and heart rate recovery (HRR) to standing with all-cause mortality, cardiovascular disease and other health outcomes (4-8). However, almost all of these studies have exclusively investigated the association of consensus-defined HR/BP phenotypes measured at specific timepoints during standing. Purpose We hypothesised that assessing information from the entire haemodynamic response to orthostasis - instead of discrete timepoints or consensus definitions - may uncover novel associations between BP/HR responses to active stand and neuro-cardiovascular health in older adults. This may afford better physiological understanding of the longitudinal relationships between the response to standing and both Cardiovascular Disease (CVD) and mortality. Methods We used functional Principal Components Analysis (FPCA) to examine the determinants of variability in the complete haemodynamic response to active stand and examine which components were related to mortality and incident CVD in >4500 community-dwelling adults aged 50+. Results Figure 1 shows the mean response curve according to mortality status and Figure 2 the mean curve for participants free of CVD at baseline who later have CVD vs those who remain CVD-free during 10 year follow-up. All-cause mortality was associated with functional principal components which discriminate higher baseline HR, blunted HR peak and impaired HRR up to ~25 seconds after standing. Components that discriminated high baseline and impaired recovery of SBP from the post-stand nadir to 60 seconds post stand were also associated with all-cause mortality. This association remained even after covariate adjustment. Interestingly, neither baseline SBP nor orthostatic hypotension (OH) were associated with mortality. Components which discriminate high baseline and blunted HR peak; elevated stroke volume index and impaired recovery of DBP from ~25 seconds post stand were associated with 10-year incident CVD. Conclusions To our knowledge this is the first study to incorporate data driven information over the entire trace of the haemodynamic response to standing to investigate associations with incident CVD and mortality. The fact that components which discriminated high BP and impaired recovery of BP were associated with 12-year mortality and 10-year incident CVD when traditional summary measures of OH and baseline BP were not; suggests that incorporating information across the entire response to standing allows for richer and more flexible associations with health outcomes to be uncovered and allows for a better understanding of the underlying physiology leading to such associations.Figure 1:Mean trace of Mortality StatusFigure 2:Mean Trace of CVD Status

Effect of renal dialysis session on novel echocardiographic parameters of left and right ventricle in patients with end-stage renal disease

Abstract Introduction Chronic heart disease is among the leading causes of end-stage renal disease (ESR). On the other hand, patients with ESR undergoing dialysis demonstrate often subclinically impaired left and/or right ventricular function according to small studies, and higher prevalence of chronic heart disease. However, data regarding the effect of renal dialysis on novel echocardiographic parameters among renal dialysis patients remain limited.The purpose of our study, was to study the effect of renal dialysis on novel echocardiographic parameters of left and right ventricle. Methods All 50 patients (14 females) of mean age 62.9 years undergoing renal dialysis in our kidney unit regularly were included in our study. Blood pressure, heart rate and weight measurements and heart echocardiogram with measurement of LV GLS, RV GLS, RV FWS, LA ResS, E/e’ ratio, Right Ventricular Systolic pressure (PASP) and inferior vena cava (IVC) diameter, before and after renal dialysis session, were carried out. Results Mean values of body weight (79,9 vs 77,6 kg), heart rate (74,2 vs 73,5 bpm) and blood pressure (131,5/80,6 vs 123,5/76,9 mmHg) were as expected statistically significant reduced after renal dialysis (p<0,001). Values of PASP (36,1 vs 27,8 mmHg), E/e’ ratio (14 vs 12,5) and IVC diameter (1,6 vs 1,3 cm), were statistically significant reduced after renal dialysis (p<0,001). Furthermore, values of RV GLS (-19,3 vs -20,3 %), RV FWS (-21,2 vs -22,6 %) and LA ResS (29,6 vs 30,7%), were statistically significant improved after renal dialysis session (p <0,001), while LV GLS depicted a minor improvement (-17,9% vs 18,2%) not statistically significant. Conclusion In conclusion, renal dialysis session had a beneficial effect on novel echocardiographic parameters of left and right ventricle (RV GLS, RV FWS, LA ResS) due to improvement of hemodynamic parameters (blood pressure, heart rate, PASP and IVC diameter) and intravascular volume reduction. Larger clinical studies should be organized to further investigate the effect of renal dialysis on those parameters and the underlying mechanisms in the chronic setting of hemodialysis.

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend <0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend <0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

Mitochondrial Oxidative Stress and Cardiac Dysfunction in TERT Knockout Mice

Abstract Background Heart failure (HF) is a major cause of hospitalization in the elderly, with its incidence increasing due to aging and associated risk factors like hypertension, diabetes, and myocardial fibrosis. Aging-related myocardial fibrosis, characterized by alterations in the extracellular matrix and myocardial structure, impairs cardiac function. Mitochondrial oxidative stress plays a pivotal role in cardiac electrical and structural remodeling, necessitating a deeper understanding of its involvement in aging-related heart failure. Purpose The purpose of this study is to investigate the mechanisms of aging-related ventricular electrical and structural remodeling by constructing an aging mouse model. This research aims to provide potential therapeutic targets for heart failure associated with aging. Methods We developed a third-generation homozygous telomerase reverse transcriptase (TERT) knockout mouse model. Comparing third-generation homozygous TERT knockout mice (F3 group) with age-matched wild-type males (WT group). The study encompassed blood pressure measurement, electrocardiographic analysis, echocardiography, ELISA for cardiac biomarkers, ventricular tissue electrophysiology, fibrosis assessment through staining, transcriptomic profiling via RNA-seq, and electron microscopy of ventricular mitochondria. Results Compared to the WT group, the F3 group demonstrated increased P53 and P16 protein expression. Decreased LVEF and FS, along with increased interventricular septum thickness, left ventricular diameter, and left ventricular volume. Elevated serum NT-pro-BNP and troponin I (cTnI) levels, with prolonged QRS duration. Decreased left and right ventricular conduction velocity, accompanied by increased conduction dispersion. Notable elevation in COLI, TGFβ, and α-SMA gene transcription and protein expression in ventricular tissue. Significant differences in mitochondrial oxidative stress signal pathways via RNA-seq analysis. Elevated serum MDA levels and decreased SOD levels, with up-regulated Mn-SOD gene transcription and protein expression, and down-regulated MFN2 and Drp1 gene transcription and protein expression in ventricular tissue. Electron microscopy revealed mitochondrial abnormalities such as loose arrangement, decreased number, swelling, vacuolation, and myofilament disintegration or breakage in the F3 group. Conclusion Third-generation TERT-/- senescent mice exhibit notable cardiac impairments, including electrical remodeling, structural changes, and mitochondrial dysfunction. These findings suggest a potential link between mitochondrial oxidative stress and aging-related heart failure, indicating novel therapeutic opportunities targeting mitochondrial dysfunction for managing such conditions.

Time-series clustering of raw recordings of 24-hour ambulatory blood presssure for risk stratification in general population

Abstract Objective 24-hour ambulatory blood pressure measurements (ABPM) is the best out-of-office BP measurement used to refine cardiovascular (CV) risk stratification. Currently, only summary ABPM indexes are used in the clinical practice while the temporal characteristics of the raw BP recordings have not been explored. Therefore, in this study we employed an unsupervised machine learning (ML) algorithm suitable for multivariate time-series analysis to identify distinct BP and heart rate (HR) profiles associated with the incidence of adverse CV events. Design and Method In 1391 community-dwelling individuals (mean age, 46.9 years; 50.97% women), we acquired 24-hour ABPM and clinical data and collected CV events (n=399) on average 22 years later. We employed multivariate dynamic time warping and k-medoids algorithm on the raw recordings of systolic and diastolic BP and HR. To assess the clinical significance of the derived clusters, we compared the clinical characteristics and the incidence of adverse events. We validated the trained model using 24-hour ABPM obtained from external population cohort (n=1137). Results The silhouette score and Dunn index showed that the optimal number of clusters was 4. Across all clusters we observed significant difference in age and sex distribution. Cluster 4 had the worst CV risk factors profiling, with higher office BP and anti-hypertensive medication intake compared to the other clusters. We observed differences in the incidence of adverse events between clusters (Figure), with cluster 1 representing the lowest risk group and cluster 4 the highest. After adjusting for traditional CV risk factors, including office systolic BP, cluster 1 had the lowest risk (HR:0.92; 95%CI:0.84-0.99; P=0.036) and cluster 4 the highest (HR:1.13; 95%CI:1.03-1.24; P=0.006) as compared to the average population risk. The analysis of the external validation cohort revealed similar ABPM patterns and clinical characteristics. Conclusion Employing an unsupervised ML model on the raw ABPM recordings we identified clinically meaningful clusters associated with an increasing cumulative incidence of CV events. This ML analysis paves the way towards utilization of temporal BP and HR information and subsequently optimization of CV risk stratification.

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP >210mmHg in men and >190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=<0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p<0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=<0.0001), MSNA levels (36vs28 bursts, p=<0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Genome-wide association study of CMR image-based aortic stiffness in 45,789 individuals identifies loci linked with cardiovascular diseases

Abstract Background The use of artificial intelligence on large-scale cardiac magnetic resonance (CMR) imaging data has enabled detailed characterisation of cardiac shape and function for use in genome-wide association studies (GWAS), leading to improved understanding of genetic aetiology of cardiovascular diseases (CVDs). Aortic stiffness is associated with increased risk of cardiovascular events in observational studies. Here, we present a novel CMR-based pressure-independent measure of aortic stiffness, identify genetic associations and explore links with CVDs. Purpose Identify genetic contributions to pressure-independent aortic stiffness and links to CVDs using large-scale GWAS analysis on the UK Biobank cohort. Methods A pre-trained neural network was used to segment CMR images of participants in the UK Biobank to quantify ascending aorta diameter, which together with contemporaneous systolic and diastolic blood pressure measurements (SBP, DBP, respectively) were used to calculate a pressure-independent measure of aortic stiffness (β0). The measurement assumes an exponential relationship between pressure and aortic diameter. We then performed a GWAS on β0 in 45,789 participants of European ancestry without CVDs. A multi-trait-based conditional & joint analysis (mtCOJO) was performed to estimate genetic effects independent of SBP, DBP and aortic area. We mapped the independent lead variants associated with aortic stiffness at P < 5x10-8 to nearest gene, and characterised shared genetic association across CVDs using Open Targets Platform database. Results The GWAS identified 17 independent lead variants, including 6 that remained significant in the conditional analysis. Four of these lead variants, not previously reported in GWAS of other aortic traits, were located near CTD-2203A3.1, MCF2L, CFDP1 and CDH13 genes (red annotations in the Figure). MCF2L, CFDP1 and CDH13 have been associated with coronary artery disease, and CFDP1 with myocardial infarction and coronary atherosclerosis in previous studies. Conclusion A GWAS of CMR-derived aortic stiffness identified 4 loci distinct from other aortic traits that also associate with other CVDs, suggesting genetic links between aortic stiffness and CVDs. Further analyses are required to explore biological mechanisms underlying these genetic associations.Aortic Stiffness Manhattan Plot

Evaluation of myocardial work indexes in patients with cardiac sarcoidosis

Abstract Background Cardiac involvement is associated with worse prognosis and mortality in sarcoidosis. Diagnosis often requires expensive and less available tests. Purpose The aim of this study is to evaluate whether non-invasive measurement of myocardial work by transthoracic echocardiogram has incremental value in the diagnosis of cardiac involvement compared to left ventricular (LV) global longitudinal strain (GLS). Methods This is a cross-sectional, non-blinded, single-center pilot study. Patients of both genders > 18 years old, with confirmed diagnosis of cardiac sarcoidosis according to the Heart Rhythm Society criteria, and controls consisting of individuals diagnosed with systemic sarcoidosis without cardiac involvement, were included. Patients with obesity grade 2 or higher , moderate or severe primary heart valve disease, myocardial diseases of other etiologies, established coronary artery disease, and inadequate acoustic window were excluded. All patients underwent transthoracic echocardiography and non-invasive blood pressure measurement, followed by subsequent analysis involving the construction of a pression-strain curve. The following LV indexes were calculated: GLS, global work index, global constructive work, global wasted work, and global work efficiency. ROC curves were calculated for all variables using the EasyROC online tool (v 1.3.1), and these were later compared to GLS. Confidence intervals were established by the DeLong method, and curves were compared by the Bonferroni method. A two-tailed p value of 0.05 was considered significant. Results Twenty patients with cardiac involvement and twenty patients without cardiac involvement were evaluated. The results of the variables are presented in table 1. Conclusions With exception of wasted work, all other LV myocardial work variables showed statistical correlation with cardiac involvement in sarcoidosis patients. However, there was no incremental value of myocardial work indexes compared to the isolated use of GLS.

Blood pressure response to exercise in endurance athletes with and without paroxysmal atrial fibrillation.

Abstract Background Atrial fibrillation (AF) is more prevalent among endurance-trained athletes when compared to non-athletes. The underlying pathophysiology and mechanisms for this phenomenon remain unknown but repeated exposure to an exaggerated blood pressure (BP) response during exercise may contribute to the development of AF in this population. Purpose We aimed to assess whether endurance athletes with AF have a higher maximal systolic BP (SBP) or a higher BP relative to exercise intensity compared to endurance athletes without AF. Methods Endurance athletes with paroxysmal AF (n=66, 96% male) from the ProAFHeart, NEXAF Detraining and Master@Heart studies were matched for age and sex to endurance athletes without AF (n=66, 96% male). Participants with a history of hypertension were excluded. All athletes underwent a maximal graded cardiopulmonary exercise test on a cycle ergometer to assess exercise BP using an automated auscultatory BP machine, maximal oxygen uptake (VO2peak) and peak workload. All athletes were in sinus rhythm at the time of testing and BP was measured pre-exercise seated on the bike and every 2 min throughout the test. Exercise BP measurements included the maximum exercise SBP (SBPmax) and the slopes of the relationships between SBP, diastolic BP (DBP) and workload (W) as determined from linear regression analysis (SBP/W-slope and DBP/W-slope, respectively). The resting SBP and DBP were measured in the supine position after 10min of rest. Independent T-test (parametric data) or the Mann-Whitney U-test (non-parametric data) assessed for the differences between the two groups. Results The 66 athletes with AF were of similar age and sex as the 66 athletes without AF, median age (55 [IQR 45, 61] vs 54 [IQR 44, 62] years, p=0.839), 4% female. There was no difference in (mean±SD) VO2peak (46 ±9 vs 49±10 mL/kg/min, p=0.114) and peak workload (365±67 vs 385±83 W, p=0.136), nor resting SBP (131±13 vs 128±13 mmHg, p=0.169) and resting DBP (76±9 vs 75±11 mmHg, p=0.465) between athletes with and without AF respectively (Table 1). Athletes with AF showed no significant difference to athletes without AF for exercise BP responses (Figure 1) including SBPmax (222±22 vs 219±28 mmHg, p=0.479), SBP/W-slope (0.22±0.07 vs 0.24±0.08 mmHg/W, p=0.310) and median DBP/W-slope (-0.01 [IQR -0.02, 0.01] vs -0.01 [IQR -0.03, 0.02] mmHg/W, p=0.703). Conclusion When comparing endurance athletes with and without paroxysmal AF, there were no differences in the maximal BP attained during exercise or in their BP response indexed to external workload (SBP/W-slope) suggesting that exercise-induced hypertension does not explain the athletic predisposition to AF.

Measuring only sitting blood pressure without considering supine blood pressure underestimates cardiovascular risk in the elderly

Abstract Background and Objective Elderly individuals exhibit greater variability in blood pressure (BP) readings between sitting and supine positions. Nocturnal hypertension (supine position) is closely associated with cardiovascular diseases and mortality. However, the relationship between supine BP and cardiovascular risk remains unclear. This study aims to investigate the association between the occurrence of major adverse cardiovascular events (MACEs) with BP in sitting and supine positions. Methodologies A total of 3363 participants aged 65 years or older from the Northern Shanghai Study were included. Each participant is given 3 consecutive sitting SBP readings (SBP1, SBP2, SBP3) at 2-minute intervals, we then calculated the SBP1-2 (average of SBP1 and SBP2), SBP2-3 (average of SBP2 and SBP3), SBP1-2-3 (average of SBP1, SBP2 and SBP3). we also collected two supine BP readings (S-SBP1, S-SBP2). Kaplan-Meier and Cox proportional hazard regression were used to investigate the association of sitting and supine BP with MACEs (composite of nonfatal myocardial infarction, nonfatal stroke, or death). Results The mean age of participants was 71.5 years, and 1467(43.6%) were men. After a median of 6.4-year follow-up, a total of 362 events were recorded. Among 3 successive BP readings, SBP2-3 had strongest association with MACEs incidence (hazard ratio, 1.12 [1.00-1.26] per SD). Multiple cox proportional hazard regression showed supine BP had significant value in predicting MACEs, acute myocardial infarction (AMI) and mortality compared to sitting BP. Kaplan-Meier revealed significant differences in MACEs rates among participants without hypertension (HTN) in both sitting and supine positions, with HTN in both positions, or those with HTN in either position (Log rank P < 0.01). Compared to participants without HTN in both sitting and supine positions, those with HTN in both positions had a 1.4-fold (hazard ratio,1.40[1.08-1.82]) higher risk of MACEs and 2-fold (hazard ratio,2.01[1.24-3.26]) higher risk of stroke. Conclusion Supine BP measurements are more valuable than sitting BP in predicting MACEs in elderly individuals. Hypertension in both positions significantly increases the risk of MACEs. Taken together, supine BP may also need to be emphasized in the elderly.central illustration