Heart failure (HF) is recognized as a global pandemic with still increasing prevalence (1–3%) and is projected to further increase due to the availability of life-saving medical treatments to prolong life after initial event [1]. Although cardiovascular mortality in HF patients is decreasing, it is still high with 1-year risk ranging 15–30% and 5-year risk up to 75% in specific populations [1]. Patients with HF may experience frequent hospitalizations, with each new HF hospitalization being associated with increased risk of mortality and decreased quality of life in survivors. Thus, a better and continuing understanding of the causes of hospitalizations and evolution of HF symptoms as well as patients’ status out of hospital might contribute to adjust strategies leading to improve patients’ prognosis and reduce already high health care costs.
Being a dynamic syndrome, changing clinical trajectories often demonstrated in chronic HF patients are driven by underlying pathophysiologic processes and the type and dose of administered medications. This dynamics may be captured in several ways, including alterations in cardiac structure and function and by patients’ clinical status. The meticulous and long-term follow-up, together with continuation of medical treatment or by applying interventional treatment procedures where possible and reasonable, is recommended to ensure that exacerbation or recurrence of HF symptoms or left ventricular dysfunction do not occur. Putting it simple, the key to managing HF is to diagnose or notify changes and start treatment as early as possible.
In this sense, a registry-based longitudinal study by Frankestein and coworkers, published in this issue of Cardiology, gives an important contribution to better understand HF evolution. Authors investigated the long-term evolution of clinical, echocardiographic, and laboratory parameters of cardiac function in 2,132 outpatients with chronic stable HF due to ischemic (51%) or non-ischemic origin (49%), during the mean follow-up of approximately 5 years (2.6–9.2 years) [2]. There are two unique characteristics of this study: (a) the absence of kidney failure (mean eGFR 81 [62–100] mL/min/1.73 m2) despite the fact that mean left ventricular ejection fraction (LVEF) was low (28%), and that study included patients with reduced LVEF (heart failure with reduced ejection fraction – HFrEF 86%; heart failure with mildly reduced ejection fraction – HFmrEF 14%, respectively), and (b) the long-term trajectories of analyzed parameters. This particularly relates to the N-terminal prohormone of brain natriuretic peptide (NT-proBNP), as there are a paucity of data investigating longitudinal changes of this parameter, as well as the long-term serial relationship between LVEF, LV end-diastolic diameter, NT-proBNP, and patients’ symptomatic status assessed through the New York Heart Association Classification (NYHA). Authors observed a significant improvement of LVEF and NT-proBNP levels at 1 year followed by a plateau, while, in contrast, NYHA functional class and LV end-diastolic diameter trajectories were dominantly U-shaped, with slight improvements noted over the first 4 years of follow-up. It should be emphasized that up to 1/3 of the patients at the time of inclusion in the study had no symptoms. Globally, changes in NYHA class correlated with changes in LVEF and NT-proBNP irrespective of the HF etiology, but not surprisingly, and in accordance with existing data [3], the evolution of analyzed parameters was highly variable with respect to HF category and etiology, with most favorable trajectories being observed in patients with HFrEF from non-ischemic origin. The changes in HF variables are common during long term and it is important to detect them on time as they guide decisions about the frequency of follow-up, need for repeat cardiac imaging, and additional patients’ counseling. Although authors did not report on clinical implication of parameters’ trajectories, extensive literature already provides robust evidence on the prognostic value of examined variables.
As this study confirmed, the underlying etiology of HF has important implications for treatment. Patients with HF due to ischemic origin usually have more comorbidities and probably scar tissue that cannot be repaired with medical therapy, which might lead to weaker myocardial contractility and increased filling pressures. The assumption that adequate myocardial revascularization in patients with ischemic HF and existing coronary artery disease brings benefit has shown contradictory results, depending on the modality of revascularization [4]. The study by Frankestein and associates is lacking the data on the number of patients with ischemic CMP who underwent or were denied revascularization and what could affect the trajectories of observed parameters, particularly LVEF, NT-proBNP, and NYHA classes. Although a number of patients certainly improved their functional status due to the good response to medications, a certain number of patients in ischemic HF group might owe their functional improvement to successful coronary artery revascularization.
An important limitation of the study is the incomplete application of the drugs that are the contemporary cornerstone of the HF patients’ treatment, especially with decreased LVEF [6]. Concretely, angiotensin receptor-neprilysin inhibitors or sodium-glucose cotransporter-2 inhibitors (SGLT2i) were not part of mandatory therapy because the study was conducted before the effectiveness and benefit of these drugs was demonstrated and before they have become a class I recommendation for the chronic HFrEF treatment [6]. It may be argued that full application of recommended HF medications would have produced more favorable ventricular remodeling, particularly in DCM patients. However, in everyday practice, a certain number of patients neither receive treatment with all recommended drugs or below-target doses nor devices that have been proven to positively impact morbidity and mortality. Translation of evidence-based HF treatment into practice obviously remains a challenge. This has also been confirmed in this study, as only 22% and 29% of patients reached target doses of B-blockers and ACEi/ARB blockers, respectively, with increase in doses as follow-up progressed. Improvements in HF variables were associated with optimization of HF treatment, notably with initiation and up-titration of renin-angiotensin-system blockers.
Contemporary data are unequivocal in that all HFrEF patients should receive four basic groups of drugs [6]. Yet, analyzing more broadly, this does not mean that the ”one-size fits all” approach should be implemented. The different trajectories of parameters for patients with ischemic versus non-ischemic HF confirmed that approach to the treatment of HFrEF (or HFmrEF) patients should be personalized, based on patients’ phenotype and cause of HF. In addition to adding certain drugs, personalized therapy for HF relates to application of different types of procedures and devices. With regard to this, there are wide possibilities ranging from well-known devices to newer procedures, such as cardiac contractility modulation, atrial shunting therapy, or percutaneous treatment of HF secondary to mitral or tricuspid regurgitation [7]. Finally, a personalized approach can be further directed through genetic testing for variations in the response to administered drugs or through the individual analysis of the existing inflammatory state.
We should take forward three key points from this study: (i) long-term natural history of HF demonstrates that remission period might be limited, and in majority of patients, after some time (>4 years), symptoms will re-emerge; (ii) the evolution of HF is highly dependable on HF etiology and can be reliably tracked with well-known and easily obtained parameters; and (iii) optimization of treatment is key for successful treatment. These conclusions are not new for clinical and scientific communities, but it is important and useful that they have been confirmed in a large cohort of patients and in a real-world practice setting.
The ultimate goal in HF treatment is conversion from “HF remission” to “HF healing.” We have not gotten there yet, but the current study and established research directions involving different treatment approaches [7] indicate the path and provide us with hope that this might be achievable in the near future.
Conflict of Interest Statement
The author has no conflict of interest to report.
Funding Sources
No funding was received.
Author Contributions
M.B.: design, conception, and writing.