The Heart Initiative

Our Mission

The Heart Initiative is a non-profit organization created in 2009 whose mission is, through research, to:

  • Increase public awareness and knowledge of cardiovascular diseases particularly heart failure
  • Improve the early diagnosis and treatment of cardiovascular diseases, through increasing usage of proven therapies and improving adherence.

Our initial focus was in sub-Saharan Africa where public attention, research, intervention and funding has been focused on infectious and parasitic diseases, despite the fact that cardiovascular disease morbidity and mortality rates nearly equal those from infectious and parasitic diseases and will surpass them by 2020. And, in sub-Saharan Africa, cardiovascular disorders affect women and men in their prime (ages 40-50) impeding their ability to work and care for their families.

Heart failure is a global health burden, both socially and financially. Data have shown that inexpensive, proven, life-saving medications are underutilized on every continent. While research identifying new, effective therapies is certainly important, resources could be directed towards finding ways to enhance uptake of therapies that have already been proven to improve cardiovascular health.

ROBUST-HF

ROBUST-HF is a multicenter, international research registry of patients who are about to be discharged from a hospital admission for acute heart failure (AHF). Patients will be enrolled who are not treated with optimal doses of oral medications for HF including renin-angiotensin system inhibitors (RASI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and SGLT-2 inhibitors.

The STRONG-HF study showed that rapid up-titration of renin-angiotensin inhibitor (RASI), beta-blocker, and mineralocorticoid receptor antagonist (MRA) to full optimal doses within 2 weeks post-discharge from a hospital admission for acute heart failure (AHF), using frequent safety assessments, significantly reduced the 180-day risk of HF readmission or death and significantly increased 90-day quality of life regardless of left ventricular ejection fraction (LVEF). Recent evidence from the PIONEER-HF, EMPULSE, SOLOIST, and AFFIRM-AHF studies also suggests that initiation of angiotensin-receptor neprilysin inhibitor (ARNI) and SGLT-2 inhibitors close to the time of discharge regardless of LVEF, and iron supplementation where indicated, improve patient prognosis. The main barriers to implementation of this new approach are related to two main issues: first, the need for successive visits during the first weeks after discharge including lab work, and, second, the need to acquire skills to safely up-titrate oral HF medications during the rapid up-titration phase.

The Registry Of Best Up-titration STrategies in acute Heart Failure (ROBUST-HF): a registry of post-acute heart failure management initiative is designed to help care givers for AHF patients globally implement a rapid uptitration strategy for the 4 main pillars of AHF therapy quickly and efficiently. Sites that will be willing to participate in the registry part of the initiative will be provided with access to an eCRF where patient data will be recorded.

The protocol for the registry is attached here – PROTOCOL

Sites willing to participate in the registry should contact bethdavison@worldheartinitiative.org and can download a form to request a grant for participation here – FESABILITY FORM

Strong-HF

Heart failure medication management

Data have shown that oral medications proven to prolong survival and/or reduce readmissions are underutilized by patients as well as under-prescribed by physicians. The Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-proBNP testinG, of Heart Failure Therapies (STRONG-HF) study is a randomized, controlled study comparing a strategy designed to encourage physicians to optimize doses of these guideline-recommended medications as soon as possible following discharge from a hospital admission for acute heart failure, with the usual care strategy. The safe up-titrations of these medications will be guided by frequent physical assessments as well as laboratory measures. Funding is being provided in part by Roche Diagnostics International Ltd.

Patients admitted for AHF with clinical signs of congestion and elevated circulating NT-proBNP and who are not treated with optimal doses of oral HF therapies within 2 days before hospital discharge for AHF and who are hemodynamically stable will be randomized in a 1:1 ratio to either usual care (named “usual care” arm) or intensification of treatment with beta-blockers, and ACEi (or ARB) or ARNi and a MRA (named “high intensity care” arm). In the latter arm, repeated assessments of clinical signs and symptoms of heart failure, routine clinical laboratory measures including potassium, sodium, and creatinine as well as biomarkers including NT-ProBNP will ensure the safety of the optimization of oral heart failure therapies. Patients will be followed through 90 days from randomization. AHF patients who were screened but did not meet inclusion criteria, including low circulating NT-proBNP at visit 2, will also be followed for 90-day outcome. Randomized patients will be contacted at 180 days from randomization to assess vital status, occurrence of rehospitalizations, and oral HF medications.

The study’s primary endpoint is 180-day all-cause death or heart failure readmission. Secondary endpoints include change in quality of life measured using the EQ-5D questionnaire from randomization to Day 90, 180-day all-cause mortality, and 90-day all-cause death or heart failure readmission.

The protocol for Strong-HF can be found here. Strong-HF Protocol (v3.0)

The trial is registered on ClinicalTrials.gov (NCT03412201).

The study was stopped early based on a recommendation by the study’s Data and Safety Monitoring Board due to a significantly lower risk of the primary endpoint in the “high intensity care” arm compared with the “usual care” arm. press release

Cotter G, Davison B, Metra M, Sliwa K, Voors AA, Addad F, Celutkiene J, Chioncel O, Cohen Solal A, Diaz R, Damasceno A, Duengen HD, Filippatos G, Goncalvesova E, Merai I, Ponikowski P, Privalov D, Sani MU, Takagi K, Shogenov Z, Saidu H, Mebazaa A. Amended STRONG-HF study design. Eur J Heart Fail. 2021 Nov;23(11):1981-1982. doi: 10.1002/ejhf.2348. Epub 2021 Oct 4.More details.

Kimmoun A, Cotter G, Davison B, Takagi K, Addad F, Celutkiene J, Chioncel O, Solal AC, Diaz R, Damasceno A, Duengen HD, Filippatos G, Goncalvesova E, Merai I, Metra M, Ponikowski P, Privalov D, Sliwa K, Sani MU, Voors AA, Shogenov Z, Mebazaa A. Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP and GDF-15, of Heart Failure therapies (STRONG-HF): rationale and design for a multicentre, randomized, parallel-group study. Eur J Heart Fail. 2019 Nov;21(11):1459-1467. doi: 10.1002/ejhf.1575. Epub 2019 Aug 19.More details.

CORTAHF

Effect of Short-term Prednisone Therapy on C-reactive protein change in Emergency Department Patients with Acute Heart Failure and elevated inflammatory markers

Acute heart failure (AHF) is a common discharge diagnosis in the emergency department (ED), associated with 1-month mortality of 6%, and a 30% risk rate of 1-month rehospitalization. Current guidelines recommend the use of nitrates and low dose diuretic to treat congestion, but to date, no drug has ever shown any improved clinical outcome when given at the acute phase.  Several studies suggest that there is a high inflammatory component in AHF, with elevated markers such as IL6 and C-reactive protein (CRP). As it is the case in other acute respiratory disease, a short course of steroid therapy may limit the inflammatory response and in turn, improve AHF prognosis. The objective of the study is to assess the effect of a 7-day course of steroid introduced in the ED on inflammatory response. The study is a parallel-group, randomized, open-label, controlled trial in 5 EDs in France. Patients with AHF and high CRP levels will be randomized to 7 days of prednisone therapy or control and followed for 30days. Endpoints include change in CRP levels and risk of worsening HF, HF readmission or death to day 30.

BA-HEF

Acute heart failure in sub-Saharan Africa

THESUS-HF showed that patients in Africa are rarely treated with a combination of hydralazine and nitrates, which was proven in the A-HeFT to prolong survival in African Americans.

The Heart Initiative, in collaboration with principal scientists from the THESUS-HF study, organized the BA-HEF Study (Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure), which was completed in 2015 (Sliwa et al. 2016).

The study was one of the first (if not the first) randomized, placebo-controlled trial of a medication conducted entirely in patients with acute heart failure in sub-Saharan Africa. The study did not demonstrate that the hydralazine/nitrate combination reduced the 6-month risk of death or HF readmission but did suggest effects in favor of the combination on easing breathing symptoms 1 week after admission, and on decreases in systolic blood pressure and weight and improved exercise capacity after 6 months. Support for the study was provided in part by Momentum Research, Inc., Sandoz South Africa, and Novartis Pharma AG.

Sliwa K, Damasceno A, Davison BA, Mayosi BM, Sani MU, Ogah O, Mondo C, Ojji D, Dzudie A, Kouam CK, Yonga G, Ba SA, Ogola E, Edwards C, Milo O, Cotter G. Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF). Eur J Heart Fail 2016;18(10):1248-1258. More details.

THESUS-HF

Acute heart failure in sub-Saharan Africa

When the Heart Initiative was established, a consortium of African cardiologists and heart failure experts were conducting a registry of patients admitted to the hospital for heart failure in 9 African countries called the THESUS-HF Study (The Sub-Saharan Africa Survey of Heart Failure) (Damasceno et al. 2012). This study aimed to characterize acute heart failure in Africa by describing the causes, treatment, and outcomes over 6 months of follow-up. THESUS-HF shows that survival and readmission rates of African patients with acute heart failure are similar to those observed in non-African registries, and that much of the heart failure in Africa is caused by uncontrolled hypertension, a disease that tends to affect people at a younger age than other causes of heart disease. Despite the availability of generic and inexpensive anti-hypertensive drugs, hypertension remains untreated in much of Africa. Future research could be directed towards improving routine blood pressure screening and hypertension treatment in these countries.

THESUS-HF also showed that patients in Africa are rarely treated with a combination of hydralazine and nitrates, which was proven in the A-HeFT to prolong survival in African Americans. The study data have contributed to our understanding of heart failure globally, with several manuscripts published based on THESUS-HF:

Damasceno A, Mayosi BM, Sani M, Ogah OS, Mondo C, Ojji D, et al. The Causes, Treatment, and Outcome of Acute Heart Failure in 1006 Africans From 9 Countries: Results of the Sub-Saharan Africa Survey of Heart Failure. Arch Intern Med. 2012:1-9. More details.

Dzudie A, Milo O, Edwards C, Cotter G, Davison BA, Damasceno A, et al. Prognostic significance of ECG abnormalities for mortality risk in acute heart failure: insight from the Sub-Saharan Africa Survey of Heart Failure (THESUS-HF). J Card Fail. 2014;20(1):45-52. More details.

Ogah OS, Davison BA, Sliwa K, Mayosi BM, Damasceno A, Sani MU, et al. Gender differences in clinical characteristics and outcome of acute heart failure in sub-Saharan Africa: results of the THESUS-HF study. Clin Res Cardiol. 2015;104(6):481-90. More details.

Sani MU, Cotter G, Davison BA, Mayosi BM, Damasceno A, Edwards C, Ogah OS, Mondo C, Dzudie A, Ojji DB, Kouam Kouam C, Suliman A, Yonga G, Abdou Ba S, Maru F, Alemayehu B, Sliwa K. Symptoms and Signs of Heart Failure at Admission and Discharge and Outcomes in the Sub-Saharan Acute Heart Failure (THESUS-HF) Registry. J Card Fail 2017;23(10):739-742. More details.

Sani MU, Davison BA, Cotter G, Damasceno A, Mayosi BM, Ogah OS, Mondo C, Dzudie A, Ojji DB, Kouam CK, Suliman A, Yonga G, Ba SA, Maru F, Alemayehu B, Edwards C, Sliwa K. Echocardiographic predictors of outcome in acute heart failure patients in sub-Saharan Africa: insights from THESUS-HF. Cardiovasc J Afr 2017;28(1):60-67. More details.

Sani MU, Davison BA, Cotter G, Sliwa K, Edwards C, Liu L, et al. Renal dysfunction in African patients with acute heart failure. Eur J Heart Fail. 2014;16(7):718-28. More details.

Sliwa K, Davison BA, Mayosi BM, Damasceno A, Sani M, Ogah OS, et al. Readmission and death after an acute heart failure event: predictors and outcomes in sub-Saharan Africa: results from the THESUS-HF registry. Eur Heart J. 2013;34(40):3151-9. More details.

CP&R

Cardiovascular Precision medicine & Remote intervention

Control of hypertension and hypercholesterolemia is key to reducing risk of adverse cardiovascular outcomes in patients with cardiovascular morbidity. Non-adherence to medical recommendations is the most important reason for adverse outcomes, as blood pressure remains erratic if medication-taking is also erratic. Non-adherence can be identified by multiple subjective and objective methods, but subjective methods (patients’ own reports) are not reliable, and objective methods may be misleading (if they are dependent on factors other than adherence), or cumbersome. For example, electronic monitoring of adherence tends to require the use of a specific device, and the most non-adherent patients tend not to be able to consistently use the device, resulting in study designs that favor adherent patients (in studies that purport to improve adherence..).

The present study uses a novel indicator for non-adherence based on Electronic Health Record (EHR) data: the degree of variability of blood pressure measurements over time. Risk stratification by a variability marker will be coupled with remote intervention offered only to patients who are at increased risk. The intervention will be targeted at the possible root causes of these patients’ non-adherence. The innovations in our approach are the use of a marker derived from EHR information to target the intervention (resulting in better resource allocation), the remote intervention that does not require in-person meetings which may be hard to implement – especially with patients who are non-adherent to their medical recommendations anyway, and the flexible and adaptable intervention that is customized for each patient.

Press Release

STRONG-HF study in patients admitted for acute heart failure (HF) terminated early for superior efficacy

DURHAM, NC, Sept. 28, 2022 -- Heart Initiative, the sponsor of the STRONG-HF (Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP testinG, of Heart Failure therapies) study, announced today the premature termination of the trial. The decision was made after discussion with the study’s executive committee, the study PI (Dr. Alexandre Mebazaa) and the Coordinating Center (Momentum Research, Durham, NC represented by Dr. Gad Cotter and Dr. Beth Davison), based on a recommendation from the Data Safety Monitoring Board (DSMB) to stop the study. The DSMB recommended to terminate the study early due to a significantly lower risk of the primary endpoint – 180-day all-cause death or heart failure (HF) readmission – in the “high intensity care” arm as compared to the “usual care” arm.

STRONG-HF is a randomized, multi-center, therapeutic strategy trial, designed to assess the safety and efficacy of early and rapid optimization of oral HF therapy supported by frequent visits and NT-proBNP measurements in patients after an acute HF admission. Guideline-recommended oral HF medications for patients in the “high intensity care” arm were up-titrated to half optimal doses at discharge and to full optimal doses at 2 weeks post-discharge with safety visits 1 week after any up-titration and follow-up visits at 6 weeks and 3 months. At each visit, patients were assessed by physical examination for congestion and blood tests including NT-proBNP measurements.(1,2)

It was planned to enroll 1,800 patients in STRONG-HF. The DSMB decision was based on examination of data of approximately 1,000 patients who had at least 90 days follow-up.

Acute HF is a major contributor to morbidity and mortality of patients with heart failure (HF).(3) Patients admitted for acute HF are at high risk of readmission and death, especially in the first months after hospital discharge.(4, 5) Recent analysis from a US registry showed that only a small percentage of patients with HF with reduced ejection fraction are treated with full doses of all guideline directed medical therapies.(6)

The study is an Investigator Initiated Study sponsored by Heart Initiative, Durham, North Carolina, USA and supported by Roche Diagnostics International Ltd. The coordinating center for the study was Momentum Research, Inc. from Durham, North Carolina, USA.

The full STRONG-HF trial results will be presented at the upcoming meeting of the American Heart Association, Nov 7th 2022 at 8:00 AM and submitted for publication shortly.

STRONG-HF study in patients admitted for acute heart failure (HF) terminated early for superior efficacy

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