New concepts in heart failure with preserved ejection fraction and hypertension

With the increasing age of our population, the incidence of heart failure with preserved ejection fraction (HFpEF) continues to rise . Traditional risk factors associated with HFpEF include :

•  older age,
•  female gender,
•  and common medical comorbidities such as 
• obesity, 
• chronic kidney disease, 
• diabetes mellitus and
•  obstructive sleep apnea . 

Hypertension (HTN) remains the strongest risk factor associated with HFpEF . In a community-based study using the H2FPEF score – an established score that aims to estimate the probability of underlying heart failure (HF) in patients with HFpEF – patients who were treated with 2 anti-HTN medication(s) were more likely to have an incident of HF hospitalization . In addition to traditional mechanisms such as left ventricular hypertrophy, ventricular stiffness and diastolic dysfunction, recent data suggest the increasing role of systemic inflammation, endothelial dysfunction, in the development of HFpEF in patients with HTN . 

EMERGING MEDICAL THERAPY FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION WITH HYPERTENSION PATIENTS:

In several HTN trials, angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) were associated with improved outcome therefore these agents are preferred to manage HTN . A trend toward a stronger reduction in left ventricular mass index (LVMI), a known surrogate for longstanding HTN was seen among patients treated with sacubitril–valsartan (decrease in the LVMI by –2.8 kg/m2 in sacubitril–valsartan compared to –1 9 kg/m2 in the valsartan arm). Similar findings were noted in a sub-study of the PARAGON-HF trial (NCT01920711), where 4796 patients received valsartan 80 mg twice daily for 1–2 weeks followed by sacubitril–valsartan 49–51 mg twice daily for 2– 4 weeks and were subsequently randomized 1:1 to treatment with either sacubitril–valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). Patients in the sacubitril–valsartan group achieved better control of goal systolic BP <130 mmHg by week 16 compared to the valsartan group, 47.9% vs. 34.3% respectively (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.30–2.43) in patients who previously had resistant HTN on four classes of antihypertensives agents .

Large randomized controlled trials have proved the effectiveness of sodium-glucose co-transporter-2 (SGLT2) inhibitors in reducing adverse cardiovascular outcomes such as cardiovascular mortality, cerebrovascular accidents, and HF hospitalizations . 

In the DECLARE TIMI58 trial, where 17 160 patients with diabetes at risk for atherosclerotic disease were randomized to dapagliflozin or placebo, patients in dapagliflozin group had minimal reduction in the systolic BP by 2.7 mmHg and in diastolic BP by 0.7 mmHg . In the CREDENCE Trial, the trend of BP was slightly better, on average lowering in systolic BP by 3.3 mmHg and in diastolic BP by 0.9 mmHg among the canagliflozin group. 

paper link 

the nexus between HTN and HFpEF remains both strong and complex. While traditional medications for treating HFrEF did not affect long-term outcomes, novel therapies with ARNi and SGLT2i offer promising results. Many device-based interventions in the HFpEF population are being developed with the aim to reduce left intra-atrial and ventricular pressure; however, their role in HFpEF hypertensive patients needs to be further investigated.