Sacubitril/Valsartan improves quality of life in patients with HFrEF

Contributor: Nicholas Hawkes


Quality not quantity. Why not both? It is established that sacubitril/valsartan is superior to enalapril (or dose-equivalent ACE-I) when it comes to mortality and morbidity in HFrEF. But what about quality of life (QoL)? Patients enrolled in PARADIGM-HF had increased quality of life when randomized to sacubitril/valsartan.

In the 8399 HFrEF patients of the PARADIGM-HF study, 7623 patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) at multiple time points.  This well-validated tool measures health related quality of life. The KCCQ assessment reflected improved in quality of life for patients on sacubitril/valsartan compared to dose-equivalent ACE-I. Worth mentioning, the first KCCQ was administered 5-10 weeks after randomization, following the “run-in” period after which patients were randomized in a blinded fashion to either enalapril BID or sacubitril/valsartan.

Changes in the clinical summary score (KCCQ-CS) and overall score (KCCQ-OS) were assessed between randomization and 8 months. In a multivariable model, randomization to sacubitril/valsartan remained an independent predictor of QoL improvement.

QoL scores were high in this study. The higher scores may reflect the unique study schedule of the PARADIGM-HF in that the first KCCQ survey was given following the run-in phase. Further, it is known that health related QoL perceptions can improve in the setting of a clinical trial.

In a heartbeat… 

HFrEF patients treated with Sacubitril/Valsartan reported higher QoL score compared to patients randomized to enalapril.

Study Link

Progenitor cells are decreased in heart failure and specific to HF type


Survival curves for all-cause death (A and B) and cardiovascular death (C) by CD34+, CD34+/CD133+, and CD34+/CXCR4+ cell counts. Blue lines represent counts above cutoff, and red lines represent counts below cutoff. The following cutoffs were used: 737 cells/mL for CD34+ cells, 504 cells/mL for CD34+/CD133+ cells, and 533 cells/mL for CD34+/CXCR4+ cells.


Contributor: Mat Bull


Do progenitor cells matter for patients with HF? First, what is a progenitor cell? A progenitor cell is a stem cell that has potential to differentiate into multiple different cell types. Progenitor cells are classified by cluster of differentiation surface markers, which act as receptors and ligands to their target tissue. CD34+ progenitor cells have been shown to play a role in vascular and myocardial regeneration and in this article are shown to be an important biomarker in heart failure.

Progenitor cells seem to do lots of good things. Decreased circulating progenitor cells are associated with vascular disease such as atherosclerosis and endothelial dysfunction. Low levels of progenitor cells are also associated with dysfunctional cellular regeneration and repair. Progenitor cells appear to mitigate adverse left ventricular remodeling, prevent cardiomyocyte apoptosis, and stimulate angiogenesis.

514 HF patients were analyzed (330 HFrEF and 184 HFpEF). The HFrEF cohort was further divided into ICM (286) and NICM (44). These patients were then compared to over 1400 non-HF controls. This represents the largest and most powerful study to date looking at levels of circulating progenitor cells in HF patients. A separate cohort of 582 patients (137 with HF) served as a validation cohort.

So what did they find? Patients with both HFpEF and HFrEF had decreased levels of circulating progenitor cells compared to controls without HF, and this directly correlated with NYHA symptoms. Individuals with NICM had the most depressed CD34+ counts. Interestingly, low endothelial-enriched progenitor cell counts correlated with poor outcomes in HFpEF but not in HFrEF.

In a heartbeat…

HF patients have lower circulating levels of progenitor cells compared to non-HF patients. Levels are predictive of HF outcomes and have distinct cellular patterns between HFpEF and HFrEF. Unlocking stem cells continues to be a promising, but unrealized, therapeutic strategy.

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Concentric left ventricular hypertrophy rarely leads to dilated cardiomyopathy

Contributor: Jennifer Huang


Does concentric left ventricular hypertrophy (LVH) progress to dilated cardiomyopathy (DCM)? It may not be as common as we previously thought and the transition may occur over decades.

1,386 participants of the Dallas Heart Study without baseline LV dilation were included. Ten percent of the participants had baseline LVH (7.2 g/mL0.67  for men and 5.8 g/mL0.67 for women). The study population had a mean age of 44 years, 57% women and 43% black patients. Of note, patients that developed cardiovascular disease during the study period (MI, CABG, PCI, stroke or HF) were not included in the final cohort of 1282. Baseline and follow up cardiac magnetic resonance imaging was performed a median of 7 years after baseline imaging.

An increase in LVEDV was significantly (p<0.01) more common among patients with baseline LVH. However, the change in LVEDV was small (1ml in those with LVH and -2ml in those without) over the 7 year period. Overall, the progression to DCM was 3% in those with LVH and 2% in those without LVH.

In a heartbeat…

LVH hearts tend to slightly increase LVEDV over time, but progression to DCM remains a rare phenomenon, at least in the Dallas Heart Study cohort.

Study Link