Treatment-Resistant Hypertension Across Heart Failure Phenotypes

Jun 02, 2022
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Authors:
Jackson AM, Benson L, Savarese G, et al.
Citation:
Apparent Treatment-Resistant Hypertension Across the Spectrum of Heart Failure Phenotypes in the Swedish HF Registry. JACC Heart Fail 2022;10:380-392.
Summary By:
Marty Tam, MD, FACC

Quick Takes

  • Apparent treatment-resistant hypertension is common in heart failure (HF) regardless of ejection fraction (EF), though prevalence increases with increasing EF.
  • Apparent treatment-resistant hypertension was associated with a lower adjusted risk of first HF hospitalization or cardiovascular death in patients with HFrEF and HFmrEF but not HFpEF.

Study Questions:

What is the relationship between apparent treatment-resistant hypertension (TRH) in patients with heart failure (HF) across the spectrum of HF phenotypes?

Methods:

The study was performed using the SwedeHF (Swedish Heart Failure Registry), which is a large, prospective Swedish registry of HF patients. The registry was linked with administrative data sets to provide additional variables and outcomes. Patients enrolled from 2006–2018 were included. Patients enrolled after a hospital discharge and those with missing key data were excluded. Apparent TRH was defined as an elevated systolic blood pressure (SBP) despite treatment with a specific combination of three antihypertensives drug classes. Non-TRH was defined an elevated SBP but not on the designated three drug class combination. Normal BP was defined as being below that normal SBP cutoff. HF phenotypes were based on left ventricular ejection fraction (EF), which included HF with reduced EF (HFrEF, EF <40%), HF with mildly reduced EF (HFmrEF, EF 40–49%), and HF with preserved EF (HFpEF, EF ≥50%). Prevalence of apparent TRH and non-TRH was determined, as well as associated patient factors. Clinical outcomes included a composite of first HF hospitalization or cardiovascular death, HF hospitalization, cardiovascular death, and all-cause death.

Results:

There were 46,597 patients studied. Apparent TRH was noted in 2,693 (10%) patients with HFrEF, 1,514 (14%) with HFmrEF, and 1,450 (17%) with HFpEF. Non-TRH was noted in 4,562 (17%) patients with HFrEF, 2,437 (22%) with HFmrEF, and 1,855 (22%) with HFpEF. After adjustment, apparent TRH and non-TRH (compared to normal BP) were associated with older age and comorbid chronic kidney disease, diabetes, and obesity across HF phenotypes. Factors associated with lower odds of TRH were longer duration of HF, presence of HF symptoms, ischemic heart disease, and atrial fibrillation.

The following are the clinical outcomes for apparent TRH compared to normal BP (adjusted hazard ratio, 95% confidence interval [CI]):

  • First HF hospitalization or cardiovascular death
    • HFrEF: 0.79 (95% CI, 0.74-0.85)*
    • HFmrEF: 0.86 (95% CI, 0.77-0.96)*
    • HFpEF: 0.93 (95% CI, 0.84-1.04)
  • HF hospitalizations
    • HFrEF: 0.80 (95% CI, 0.74-0.86)*
    • HFmrEF: 0.91 (95% CI, 0.81-1.03)
    • HFpEF: 0.92 (95% CI, 0.82-1.04)
  • Cardiovascular death
    • HFrEF: 0.63 (95% CI, 0.55-0.73)*
    • HFmrEF: 0.56 (95% CI, 0.46-0.85)*
    • HFpEF: 0.75 (95% CI, 0.64-0.89)*
  • All-cause death
    • HFrEF: 0.69 (95% CI, 0.62-0.77)*
    • HFmrEF: 0.67 (95% CI, 0.58-0.77)*
    • HFpEF: 0.68 (95% CI, 0.60-0.78)*

*Notably, with apparent TRH, there is a lower adjusted risk of the composite of first HF hospitalization or cardiovascular death in the HFrEF and HFmrEF groups but not the HFpEF group. Lower risk of cardiovascular death and all-cause death was noted across all HF phenotypes.

Conclusions:

Apparent TRH was common across HF phenotypes, but more prevalent in patients with HFpEF. Apparent TRH compared to normal BP was associated with a lower adjusted risk of a composite of first HF hospitalization or cardiovascular death for HFrEF and HFmrEF but not HFpEF.

Perspective:

Hypertension is common in patients with HF but less is known about the impact of TRH across the HF spectrum. This study provides a useful look into this issue and provides some interesting findings related to clinical outcomes. Not surprisingly, TRH is common in HF, with increasing prevalence in higher left ventricular EF groups. Patient factors like older age, chronic kidney disease, diabetes, and obesity were associated with TRH across all phenotypes despite the different demographics of the three groups. Interestingly, apparent TRH was generally associated with improved outcomes in patients with HFrEF and HFmrEF. This highlights some of the similarities between these two phenotypes and may reflect the fact that lower BP is a marker of advanced HF. In HFpEF, TRH was associated with a lower risk of death (cardiovascular and all-cause) but not the composite outcome or HF hospitalization. This may suggest a larger role of TRH on hospitalizations with HFpEF compared to the other HF phenotypes.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Hypertension

Keywords: Antihypertensive Agents, Atrial Fibrillation, Blood Pressure, Diabetes Mellitus, Heart Failure, Hypertension, Kidney Diseases, Myocardial Ischemia, Obesity, Patient Discharge, Phenotype, Renal Insufficiency, Chronic, Primary Prevention, Stroke Volume, Ventricular Function, Left


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