Zhang, my oldest patient, had been diagnosed with dilated cardiomyopathy and heart failure for 4 years. After standard drug treatment, his left ventricular ejection fraction has increased from 32% at the earliest stage to 51%; NT-proBNP has decreased from 7233 pg/mL to 678 pg/mL.
Doctor, I’m not shortness of breath even when I go up three flights of stairs, can I stop the medication? The problem is not uncommon in clinical practice. Zhang’s question is not uncommon in clinical practice. So, can Zhang stop the medication?
What is the definition of a heart failure patient with “recovered ejection fraction”?
Both domestic and international guidelines classify chronic heart failure into heart failure with reduced ejection fraction (HFrEF, LVEF < 40%), heart failure with preserved ejection fraction (HFpEF, LVEF ≥ 50%), and heart failure with intermediate ejection fraction (HFmrEF) according to LVEF.
HFrEF has numerous etiologies, of which dilated cardiomyopathy is a typical representative. In these patients, LVEF can be normalized after standard treatment. The latest expert consensus defines this as heart failure with recovered ejection fraction (HF recovered EF, HFrecEF), which is defined by.
1) Reduced LVEF of < 40% at baseline 2) Absolute improvement in LVEF ≥ 10% 3) Re-measurement of LVEF > 40%
What are the characteristics of patients with HFrecEF?
Patients with the following characteristics are more likely to experience ejection fraction recovery after guideline-directed drug therapy.
Can patients with HFrecEF discontinue their medication?
Let’s look at the relevant clinical studies reported in China and abroad respectively.
- Professor Jian Zhang et al. published in 2015 the results of a clinical study on left ventricular EF regression in Chinese patients with dilated cardiomyopathy, in which the researchers defined an absolute increase in LVEF > 10% from baseline values and LVEF > 50% as recovery of left ventricular systolic function, and a renewed decrease in LVEF below 45% as a recurrence of left ventricular systolic dysfunction The results showed that 382 patients diagnosed with LVEF were not diagnosed with LVEF.
Results showed that of 382 patients with confirmed dilated cardiomyopathy, 114 (29.8%) had a recovery in LVEF from (31.6 ± 6.0)% to (55.8 ± 3.7)% after 28 ± 17 months of standard treatment.
At follow-up, 19.3% of these patients who recovered cardiac function had a recurrence of LV systolic dysfunction again, with discontinuation of anti-cardiac failure drugs being an important cause of recurrence.
Heart transplant-free survival was significantly higher in patients with recovered LVEF than in those without recovery (Figure 1).
Figure 1: Results of KM survival curve analysis in patients with recovered LV systolic dysfunction versus those without recovery
Data from the Fu Wai Hospital showed that after 3 years of standard treatment, about one-third of patients with dilated heart disease recovered from left ventricular systolic dysfunction (median recovery Time of 11 months), and of those who recovered, about one-fifth would experience a recurrence.
- Also in 2015, Macro et al. published similar findings to those of the Fulbright Hospital in the JAHA.
The study included 408 patients with dilated cardiomyopathy who received standard drug/device therapy and were followed up over time. After 19 ± 4 months of follow-up, 15% of the patients had recovered more than 50% of their LVEF; of those who recovered, 40% had a decrease in ejection fraction at follow-up.
The long-term prognosis was significantly better in those with recovered ejection fraction than in those without recovered ejection fraction (Figure 2), and similar findings were validated in a larger retrospective study.
Figure 2: Results of KM survival curve analysis in patients with recovered left ventricular systolic dysfunction versus those without recovered dysfunction
From the results of the above study, it is clear that for patients with recovered ejection fraction, 20% to 40% of patients will experience a reoccurrence of ejection fraction decline, making it clear that discontinuation of the drug is not appropriate.
Does the percentage of EF decline get higher after discontinuation in HFrecEF patients?
A small clinical study published in The Lancet in 2019 could answer this question. The study was significant despite the small number of study participants included.
The study included 51 patients with dilated heart disease who were free of heart failure symptoms and improved heart failure markers (EF recovered from below 40% to above 50% and NT-proBNP < 250 ng/L) after treatment and were randomized to a continued medication group (26) versus a discontinuation group (25). After 6 months, the medication group was also discontinued.
The study endpoints were defined as recurrence of dilated heart disease (symptoms of heart failure, decrease in ejection fraction below 50% and an absolute decrease of 10%, and a 2-fold increase in NT-proBNP from baseline values and an absolute value >400 ng/L).
The results showed that after 6 months of follow-up, 44% of patients in the discontinuation group had an endpoint event, while no patients in the dosing group had an endpoint event; 36% of patients in the dosing group also had a recurrence of heart failure after discontinuation at 6 months.
The results of this study show that recovery of ejection fraction and reduction of NT-proBNP to normal values in heart failure patients do not mean that the disease is “cured”, and that more than one-third of these patients with seemingly “cured” heart disease will have a relapse after six months of discontinuation.
In summary, because discontinuation of therapy leads to a significantly higher risk of heart failure recurrence, the latest expert consensus recommends that guideline-oriented drug therapy should not be discontinued unless the underlying cause of the patient’s disease is resolved.