scholarly journals Acute Hemodynamic Effects and Tolerability of Phosphodiesterase-1 Inhibition With ITI-214 in Human Systolic Heart Failure

2021 ◽  
Author(s):  
Nisha A. Gilotra ◽  
Adam D. DeVore ◽  
Thomas J. Povsic ◽  
Allison G. Hays ◽  
Virginia S. Hahn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Single Dose ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Systolic Heart Failure ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Reduced Ejection Fraction

Background: PDE1 (phosphodiesterase type 1) hydrolyzes cyclic adenosine and guanosine monophosphate. ITI-214 is a highly selective PDE1 inhibitor that induces arterial vasodilation and positive inotropy in larger mammals. Here, we assessed pharmacokinetics, hemodynamics, and tolerability of single-dose ITI-214 in humans with stable heart failure with reduced ejection fraction. Methods: Patients with heart failure with reduced ejection fraction were randomized 3:1 to 10, 30, or 90 mg ITI-214 single oral dose or placebo (n=9/group). Vital signs and electrocardiography were monitored predose to 5 hours postdose and transthoracic echoDoppler cardiography predose and 2-hours postdose. Results: Patient age averaged 54 years; 42% female, and 60% Black. Mean systolic blood pressure decreased 3 to 8 mm Hg ( P <0.001) and heart rate increased 5 to 9 bpm ( P ≤0.001 for 10, 30 mg doses, RM-ANCOVA). After 4 hours, neither blood pressure or heart rate significantly differed among cohorts (supine or standing). ITI-214 increased mean left ventricular power index, a relatively load-insensitive inotropic index, by 0.143 Watts/mL 2 ·10 4 ( P =0.03, a +41% rise; 5–71 CI) and cardiac output by 0.83 L/min ( P =0.002, +31%, 13–49 CI) both at the 30 mg dose. Systemic vascular resistance declined with 30 mg (–564 dynes·s/cm– 5 , P <0.001) and 90 mg (–370, P =0.016). Diastolic changes were minimal, and no parameters were significantly altered with placebo. ITI-214 was well-tolerated. Five patients had mild-moderate hypotension or orthostatic hypotension recorded adverse events. There were no significant changes in arrhythmia outcome and no serious adverse events. Conclusions: Single-dose ITI-214 is well-tolerated and confers inodilator effects in humans with heart failure with reduced ejection fraction. Further investigations of its therapeutic utility are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03387215.

Abstract 13421: Ventricular and Arterial Elastance During Isometric Handgrip Exercise and Post-exercise Circulatory Arrest in Heart Failure With and Without Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Naoki Fujimoto ◽  
Keishi Moriwaki ◽  
Issei Kameda ◽  
Masaki Ishiyama ◽  
Taku Omori ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Circulatory Arrest ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Isometric Handgrip ◽  
Arterial Elastance ◽  
Post Exercise

Introduction: Isometric handgrip (IHG) training at 30% maximal voluntary contraction (MVC) lowers blood pressure in hypertensive patients. Impacts of IHG exercise and post-exercise circulatory arrest (PECA), which isolates metaboreflex control, have been unclear in heart failure (HF). Purpose: To investigate the impacts of IHG exercise and PECA on ventricular-arterial stiffness and left ventricular (LV) relaxation in HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). Methods: We invasively obtained LV pressure-volume (PV) loops in 20 patients (10 HFpEF, 10 HFrEF) using conductance catheter with microtip-manometer during 3 minutes of IHG at 30%MVC and 3 minutes of PECA. Hemodynamics and LV-arterial function including LV end-systolic elastance (Ees) by the single-beat method, effective arterial elastance (Ea), and time constant of LV relaxation (Tau) were evaluated every minute. Results: At rest, HFpEF had higher LV end-systolic pressure (ESP) and lower heart rate than HFrEF with similar LV end-diastolic pressure (EDP). The coupling ratio (Ees/Ea) was greater in HFpEF than HFrEF (1.0±0.3 vs. 0.6±0.3, p<0.01). IHG for 3minutes similarly increased heart rate in HFpEF (by 10±8 bpm) and HFrEF (by 14±6 bpm). IHG also increased end-diastolic and LVESP (134±21 vs. 158±30 mmHg and 113±25 vs. 139±25 mmHg) in both groups (groupхtime effect p≥0.25). In HFpEF, Ees, Ea and Ees/Ea (1.0±0.3 vs. 1.1±0.4) were unaffected during IHG. In HFrEF, IHG induced variable increases in Ea. LV end-systolic volume and the ESPV volume-axis intercept were larger, and Ees at IHG 3 rd min was greater (1.30±0.7 vs. 3.1±2.1 mmHg/ml, p<0.01) than baseline, resulting in unchanged Ees/Ea at IHG 3 rd min (0.6±0.3 vs. 0.8±0.4, p≥0.37). Tau was prolonged only in HFrEF during IHG and was returned to the baseline value during PECA. During the first 2 minutes of PECA, LVESP was lower than that at IHG 3 rd min only in HFpEF, suggesting less metaboreflex control of blood pressure in HFpEF during IHG. Conclusions: IHG exercise at 30%MVC induced modest increases in LV end-systolic and end-diastolic pressures in HFpEF and HFrEF. Although the prolongation of LV relaxation was observed only in HFrEF, the ventricular and arterial coupling was maintained throughout the IHG exercise in both groups.

scholarly journals Real-world treatment switching to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: A cohort study

Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001305
Author(s):  
Sashiananthan Ganesananthan ◽  
Nisar Shah ◽  
Parin Shah ◽  
Hossam Elsayed ◽  
Julie Phillips ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Clinical Trial ◽  
Ejection Fraction ◽  
Real World ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Treatment Switching

BackgroundSacubitril/valsartan is an effective treatment for heart failure with reduced ejection fraction (HFrEF) based on clinical trial data. However, little is known about its use or impact in real-world practice. The aim of this study was to describe our routine clinical experience of switching otherwise optimally treated patients with HFrEF to sacubitril/valsartan with respect to patient outcomes such as quality of life (QoL) and echocardiographic variables.Methods and resultsFrom June 2017 to May 2019, 80 consecutive stable patients with HFrEF on established and maximally tolerated guideline-directed HF therapies were initiated on sacubitril/valsartan with bimonthly uptitration. Clinical assessment, biochemistry, echocardiography and QoL were compared pretreatment and post-treatment switching. We were able to successfully switch 89% of patients from renin–angiotensin axis inhibitors to sacubitril/valsartan (71 of 80 patients). After 3 months of switch therapy, we observed clinically significant and incremental improvements in blood pressure (systolic blood pressure 123 vs 112 mm Hg, p<0.001; diastolic blood pressure 72 vs 68 mm Hg, p=0.004), New York Heart Association functional classification score (2.3 vs 1.9, p<0.001), Minnesota Living with Heart Failure Questionnaire score (46 vs 38, p=0.016), left ventricular ejection fraction (26% vs 33%, p<0.001) and left ventricular end systolic diameter (5.2 vs 4.9 cm, p=0.013) compared with baseline. There were no significant changes in renal function or serum potassium.ConclusionThis study provides real-world clinical practice data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan. The data provide evidence beyond that observed in clinical trial settings of the potential benefits of sacubitril/valsartan when used as part of a multidisciplinary heart failure programme.

scholarly journals Telemonitoring in subjects with newly diagnosed heart failure with reduced ejection fraction: From clinical research to everyday practice

2018 ◽  
Vol 25 (3) ◽  
pp. 167-171 ◽  
Author(s):  
G Koulaouzidis ◽  
D Barrett ◽  
K Mohee ◽  
AL Clark
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Electronic Devices ◽  
Newly Diagnosed ◽  
Online Database ◽  
Reduced Ejection Fraction ◽  
Real World Setting

Introduction Heart failure is increasingly common, and characterised by frequent admissions to hospital. To try and reduce the risk of hospitalisation, techniques such as telemonitoring (TM) may have a role. We wanted to determine if TM in patients with newly diagnosed heart failure and ejection fraction <40% reduces the risk of readmission or death from any cause in a ‘real-world’ setting. Methods This is a retrospective study of 124 patients (78.2% male; 68.6 ± 12.6 years) who underwent TM and 345 patients (68.5% male; 70.2 ± 10.7 years) who underwent the usual care (UC). The TM group were assessed daily by body weight, blood pressure and heart rate using electronic devices with automatic transfer of data to an online database. Follow-up was 12 months. Results Death from any cause occurred in 8.1% of the TM group and 19% of the UC group ( p = 0.002). There was no difference between the two groups in all-cause hospitalisation, either in the number of subjects hospitalised ( p = 0.7) or in the number of admissions per patient ( p = 0.6). There was no difference in the number of heart-failure-related readmissions per person between the two groups ( p = 0.5), but the number of days in hospital per person was higher in the UC group ( p = 0.03). Also, there were a significantly greater number of days alive and out of hospital for the patients in the TM group compared with the UC group ( p = 0.0001). Discussion TM is associated with lower any-cause mortality and also has the potential to reduce the number of days lost to hospitalisation and death.

scholarly journals Association of Blood Pressure and Heart Rate Responses to Submaximal Exercise With Incident Heart Failure: The Framingham Heart Study

2021 ◽  
Author(s):  
Herman A. Carneiro ◽  
Rebecca J. Song ◽  
Joowon Lee ◽  
Brian Schwartz ◽  
Ramachandran S. Vasan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Pulse Pressure ◽  
Framingham Heart Study ◽  
Submaximal Exercise ◽  
Exercise Stress ◽  
Reduced Ejection Fraction ◽  
Heart Study

Background Exercise stress tests are conventionally performed to assess risk of coronary artery disease. Using the FHS (Framingham Heart Study) Offspring cohort, we related blood pressure (BP) and heart rate responses during and after submaximal exercise to the incidence of heart failure (HF). Methods and Results We evaluated Framingham Offspring Study participants (n=2066; mean age, 58 years; 53% women) who completed 2 stages of an exercise test (Bruce protocol) at their seventh examination (1998–2002). We measured pulse pressure, systolic BP, diastolic BP, and heart rate responses during stage 2 exercise (2.5 mph at 12% grade). We calculated the changes in systolic BP, diastolic BP, and heart rate from stage 2 to recovery 3 minutes after exercise. We used Cox proportional hazards regression to relate each standardized exercise variable (during stage 2, and at 3 minutes of recovery) individually to HF incidence, adjusting for standard risk factors. On follow‐up (median, 16.8 years), 85 participants developed new‐onset HF. Higher exercise diastolic BP was associated with higher HF with reduced ejection fraction (ejection fraction <50%) risk (hazard ratio [HR] per SD increment, 1.26; 95% CI, 1.01–1.59). Lower stage 2 pulse pressure and rapid postexercise recovery of heart rate and systolic BP were associated with higher HF with reduced ejection fraction risk (HR per SD increment, 0.73 [95% CI, 0.57–0.94]; 0.52 [95% CI, 0.35–0.76]; and 0.63 [95% CI, 0.47–0.84], respectively). BP and heart rate responses to submaximal exercise were not associated with risk of HF with preserved ejection fraction (ejection fraction ≥50%). Conclusions Accentuated diastolic BP during exercise with slower systolic BP and heart rate recovery after exercise are markers of HF with reduced ejection fraction risk.

scholarly journals A Comparative Study of Bisoprolol with Carvedilol on LV Systolic Function in Patients with Chronic Heart Failure

2018 ◽  
Vol 14 (1) ◽  
pp. 3-8
Author(s):  
Mohammad Ashraf Hossain ◽  
Khurshed Ahmed ◽  
Md Faisal Ibn Kabir ◽  
Md Fakhrul Islam Khaled ◽  
Rakibul H Rashed ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Systolic Volume ◽  
End Diastolic Volume ◽  
Group I ◽  
End Systolic Volume ◽  
Group Ii

Background: Chronic heart failure (CHF) is the most common and prognostically unfavorable outcome of many diseases of the cardiovascular system. Recent data suggest that beta-blockers are beneficial in patients with CHF. Among β-blocker class of drugs, bisoprolol is a highly selective β1-adrenergic receptor blocker whereas Carvedilol is non-selective. Many large-scale trials have confirmed that both these β-blockers are superior to placebo and other β-blockers. This study was designed to compare the effects of carvedilol and bisoprolol in patients with chronic HF in a single center.Methods: It was a quasi experimental study. A total of 288 cases of heart failure were selected by purposive sampling, from January 2017 to June 2017. Each patient was allocated into either of the two groups, and was continued receiving treatment with either bisoprolol (Group-I) or carvedilol (Group-II). Each patient was evaluated clinically and echocardiographically at the beginning of treatment (baseline) and at the end of 3rd month. Echocardiography was performed to find out change in left ventricular systolic function.Result: After 3 months of treatment, ejection fraction was found higher in the bisoprolol group (42.6 ± 6.5 versus 38.3 ± 4.6%; P < 0.05). Ejection fraction (EF) changes were 8.4% in bisoprolol group and 4.1% in carvedilol group. A significant reduction in left ventricular end-systolic volume (21.9±2.5 in group I versus 14.9±5.7 in group II; P < 0.05) and left ventricular systolic diameter (3.2±0.1 in group I versus 2.3±0.5 in group II; P<0.05) occurred after 3 months of treatment. But no significant differences were observed in left ventricular end-diastolic volume (10.1±3.2 versus 6.1±6.4; P=0.101) and left ventricular diastolic diameter (1.7±0.8 versus 1.3±0.8; P=0.081) between groups. Three months after treatment, heart rate was reduced in the bisoprolol group from 87.7±9 to 74.5±8.1 and carvedilol group from 88.8±9.1 to 80.1±8.7. Differences in heart rate responses between 2 groups were not statistically significant (P=0.113). Assessment of blood pressure three months later of treatment shows, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were improved in both group but difference between two groups were statistically non significant (p>0.05).Conclusion: In this study, bisoprolol was superior to carvedilol in increasing left-ventricular ejection fraction, improving left ventricular end systolic volume and left ventricular end systolic diameter but no significant difference was observed in LV end diastolic volume, LV end diastolic diameter, heart rate and blood pressure.University Heart Journal Vol. 14, No. 1, Jan 2018; 3-8

scholarly journals SAT-470 When The Heart Can’t Clap To The Thyroid’s Beat

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aditi Thakkar ◽  
Maria Camila Trejo-Parades ◽  
Anantha Sriharsha Madgula ◽  
Margaret Stevenson
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Dilated Cardiomyopathy ◽  
Ischemic Cardiomyopathy ◽  
Left Ventricular ◽  
Reduced Ejection Fraction ◽  
Tachycardia Induced Cardiomyopathy

Abstract Hyperthyroidism is associated with multiple cardiac pathologies including dilated cardiomyopathy, isolated right ventricular heart failure, and atrial fibrillation (AF). Long standing untreated hyperthyroidism in conjunction with AF can cause severe dilated cardiomyopathy with reduced ejection fraction that is completely reversible with treatment. We present the case of a previously healthy male who presented with florid congestive heart failure (CHF) as an initial presentation for hyperthyroidism. A 37-year-old male presented to the emergency department with progressively worsening dyspnea on exertion and lower extremity edema for one month. His heart rate was noted to be 172 bpm and an EKG was done that showed AF. He was clinically noted to be in heart failure and was admitted for further management. He was started on metoprolol with good heart rate control and was started on furosemide for diuresis. A transthoracic echocardiogram was done and showed severe global hypokinesis with left ventricular ejection fraction reduced to 20% along with bi-atrial enlargement and dilated left ventricular cavity. Ischemic cardiomyopathy was ruled out with left heart catheterization. A TSH level was checked as a part of workup for non-ischemic cardiomyopathy and atrial fibrillation and was markedly reduced to &lt;0.01mIU/L with free T4 of 1.49ng/dL and free T3 of 6.7ng/dL. A diagnosis of hyperthyroid cardiomyopathy with concomitant tachycardia induced cardiomyopathy was made. Autoimmune workup was negative for anti-thyroid-peroxidase and anti-thyroid-stimulating antibodies. Ultrasound of his thyroid gland revealed multiple thyroid nodules concerning for toxic multinodular goiter. He was started on methimazole and discharged after volume optimization with diuresis to closely follow up with endocrinology and cardiology for further management. CHF can be the primary presentation in about 6% of patients with hyperthyroidism. T3 is the main thyroid hormone that binds to cardiomyocytes. It increases the expression of beta-adrenergic receptors on cardiomyocytes and subsequently increases heart rate and contractility. T3 can also cause atrial arrhythmias such as AF by decreasing the parasympathetic tone. Concomitant AF and hyperthyroidism can cause reduced ejection fraction due to tachycardia induced cardiomyopathy and dilated cardiomyopathy. Treatment mainly is with beta-blockers that slow down the heart as well decrease serum T3 levels by blocking 5-monodeiodinase which converts T4 to T3. Our patient was started on beta-blocker and methimazole with good reduction in heart rate and improvement of symptoms. Recovery of cardiac function will be assessed with longitudinal follow up. As hyperthyroidism is one of the few causes of CHF that is completely reversible, clinicians must maintain low degree of suspicion in patients with new onset heart failure especially when associated with AF.

Increased Ratio of sST2/LVMI Predicted Cardiovascular Mortality and Heart Failure Rehospitalization in Heart Failure with Reduced Ejection Fraction Patients: A Prospective Cohort Study

2020 ◽  
Author(s):  
Fuhai Li ◽  
Mengying Xu ◽  
Mingqiang Fu ◽  
Xiaotong Cui ◽  
Jingmin Zhou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Cohort Study ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Prognostic Impact ◽  
Composite Outcome ◽  
Cox Regression Analysis ◽  
Reduced Ejection Fraction ◽  
Increased Risk

Abstract Background: Inflammation is considered to be one of the principal triggering mechanisms for Left ventricular (LV) fibroblast and remodeling in heart failure(HF), which are related to adverse events in HF failure patients. Soluble ST2 (sST2), a member of the interleukin-1 receptor family, is assumed to play a significant role in the inflammatory response of fibroblasts. The present study aimed to investigate the prognostic value of sST2/ left ventricular mass index (LVMI), a parameter of the pre-fibrotic inflammatory phase of heart failure in comparative to remodeling, in the heart failure with reduced ejection fraction (HFrEF).Methods: The present study was a cohort study. A total of 45 consecutive patients with suspected HFrEF from 1/9/2015 to 31/12/2016 were prospectively enrolled. The target-independent variable was the ratio of sST2/LVMI measured at baseline. The primary endpoint was the composite endpoint of cardiovascular-cause mortality or heart failure readmission. The prognostic impact of the ratio of sST2/LVMI was evaluated by multivariable Cox proportional-hazards regression model.Results: 45 patients were enrolled, the average age was 48±14 years old, and about 20% of them were male. Patients were followed for 9 months, during which the primary outcome occurred in 15 patients. By Kaplan–Meier analysis, patients with high ratio of the ratio of sST2/LVMI ≥ 0.39 had shorter event-free survival than the middle ( ratio of sST2/LVMI between 0.39 and 0.24) and low ratio of sST2/LVMI (ratio of sST2/LVMI < 0.24) patients (log-rank, P = 0.022). Results of fully-adjusted multivariable Cox regression analysis showed the ratio of sST2/LVMI was positively associated with the composite outcome of HFrEF patients after adjusting confounders hazard ratio (HR) 1.64, 95% CI (1.06, 2.54). By subgroup analysis, a stronger association was found in patients whose ages between 40 and 55 years old, systolic blood pressure ＜115 or≥129mmHg, diastolic blood pressure< 74 mmHg, hematocrit < 44.5%, and interventricular septum ≥8.5mm.Conclusion: In HFrEF patients, the relationship between the ratio of sST2/LVMI and the composite outcome is linear. A higher baseline ratio of sST2/LVMI levels is associated with increased risk of cardiovascular-cause mortality and HF rehospitalization in patients with HFrEF in the short term follow up.

scholarly journals Differences in medical treatment and clinical characteristics between men and women with heart failure – a single-centre multivariable analysis

2020 ◽  
Vol 76 (4) ◽  
pp. 539-546 ◽  
Author(s):  
Helena Norberg ◽  
Veronica Pranic ◽  
Ellinor Bergdahl ◽  
Krister Lindmark
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Heart Rate ◽  
Renal Function ◽  
Body Weight ◽  
Ejection Fraction ◽  
Associated Factors ◽  
Lower Body ◽  
Reduced Ejection Fraction ◽  
Lower Body Weight

Abstract Purpose The aims of this study were to examine sex differences in a heart failure population with regards to treatment and patient characteristics and to investigate the impact of sex on achieved doses of heart failure medications. Methods and results A total of 1924 patients with heart failure in a regional hospital were analysed, 622 patients had ejection fraction ≤ 40% of which 30% were women. In patients with reduced ejection fraction, women were older (79 ± 11 vs. 74 ± 12 years, P < 0.001), had lower body weight (70 ± 17 vs. 86 ± 18 kg, P < 0.001), lower estimated glomerular filtration rate (eGFR) (49 ± 24 vs. 71 ± 30 ml/min, P < 0.001) and received lower doses of heart failure medications than men. Multivariable linear regression on patients with reduced ejection fraction showed that sex was not associated with achieved dose of any heart failure medication. For angiotensin-converting enzyme inhibitors and angiotensin receptor blockers associated factors were eGFR, systolic blood pressure, age, ejection fraction, and heart rate. For beta-blockers associated factors were body weight, atrial fibrillation and age. For mineralocorticoid receptor antagonists associated factors were eGFR, serum potassium, age, systolic blood pressure, ejection fraction and heart rate. Conclusion Women with heart failure and reduced ejection fraction were prescribed lower doses of heart failure medications, were older, had worse renal function, and lower body weight than men. Sex was not independently associated with achieved doses of heart failure medications, instead age, renal function and body weight explained the differences in treatment.

scholarly journals Mid- to Late-Life Time-Averaged Cumulative Blood Pressure and Late-Life Cardiac Structure, Function, and Heart Failure

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 808-818
Author(s):  
Kanako Teramoto ◽  
Wilson Nadruz Junior ◽  
Kunihiro Matsushita ◽  
Brian Claggett ◽  
Jenine E. John ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Specific Effect ◽  
Late Life ◽  
Left Ventricular ◽  
Observation Time ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction

Limited data exist regarding systolic blood pressure (SBP) through mid- to late-life and late-life cardiac function and heart failure (HF) risk. Among 4578 HF-free participants in the ARIC study (Atherosclerosis Risk in Communities) attending the fifth visit (2011–2013; age 75±5 years), time-averaged cumulative SBP was calculated as the sum of averaged SBPs from adjacent consecutive visits (visits 1–5) indexed to total observation time (24±1 years). Calculations were performed using measured SBPs and also incorporating antihypertensive medication specific effect constants (underlying SBP). Outcomes included comprehensive echocardiography at visit 5 and post-visit 5 incident HF, HF with preserved ejection fraction, and reduced ejection fraction. Higher cumulative SBP was associated with greater left ventricular mass and worse diastolic measures (all P <0.001), associations that were stronger with underlying compared with cumulative SBP (all P <0.05). At 5.6±1.2 years follow-up post-visit 5, higher cumulative measured and underlying SBP were associated with incident HF (hazard ratio per 10 mm Hg for measured: 1.12 [1.01–1.24]; underlying: 1.19 [95% CI, 1.10–1.30]) and HF with preserved ejection fraction (measured: 1.15 [1.00–1.33]; underlying: 1.28 [1.14–1.45]), but not HF with reduced ejection fraction (measured: 1.11 [0.94–1.32]; underlying: 1.11 [0.96–1.24]). Associations with HF and HF with preserved ejection fraction were more robust with cumulative underlying compared with measured SBP (all P <0.05). Time-averaged cumulative SBP in mid to late life is associated with worse cardiac function and risk of incident HF, especially HF with preserved ejection fraction, in late life. These associations were stronger considering underlying as opposed to measured SBP, highlighting the importance of prevention and effective treatment of hypertension to prevent late-life cardiac dysfunction and HF.

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