Letters to the Editor
Is High Heart Rate Always Harmful to Heart Failure Patients?
2020 Volume 84 Issue 9 Pages 1673-1674
Details
2020 Volume 84 Issue 9 Pages 1673-1674
To the Editor:
We read with great interest the article by Tsutsui et al that reported the results of the Japanese systolic heart failure treatment with the If inhibitor ivabradine (J-SHIFT) trial.1 Ivabradine is reported to reduce the risk of hospitalization for worsening heart failure (HF) in patients with reduced ejection fraction (EF) and high sinus rate,2 and thus has been used worldwide as a Class IIA indication for these patients.3,4 The J-SHIFT trial demonstrated its consistent efficacy (and safety as well) in Japanese patients, thereby resolving drug lag and gaining its prestigious position also in Japan. The study even showed the benefit across both the prespecified and post-hoc subgroups.
High sinus rate is supposed to be the root of worse prognosis in various cardiac conditions, including HF.5–9 Favorable results from both the SHIFT and J-SHIFT trials have strengthened this notion and given us the premise that a high sinus rate should be a target to treat. However, is high heart rate (HR) always guilty? And if not, how can we identify it earlier?
There are several clinical situations where increased HR plays a role in maintaining cardiac output (CO). In the heart with little cardiac contractile reserve, HR is undoubtedly crucial to maintain CO. In other words, CO could be maintained by a compensatory increase in HR in HF patients with severe remodeling. Likewise, HR is higher and its reduction does not always improve the prognosis of HF with atrial fibrillation (AF), a state of less cardiac reserve due to fluctuating stroke volume and loss of atrial kick.10,11 Valvular insufficiency is another case because bradycardia potentially worsens regurgitation. Increased HR was reported to attenuate the left ventricular end-diastolic pressure and augment CO in patients with aortic insufficiency.12 Accordingly, the 2017 ACC/AHA hypertension guideline recommends using agents that do not slow the HR in such patients.13 The same could theoretically apply to mitral regurgitation.
Thus, a HR reduction strategy might be inappropriate for HF patients who have paroxysmal AF, valvular regurgitation, or an extremely remodeled heart. A participant of J-SHIFT from our institution would be one such case. He had suffered from idiopathic dilated cardiomyopathy for more than 15 years, taking more than the maximal dose of β-blockers. Left ventricular EF was 18% and left ventricular diastolic diameter was 95 mm. He had moderate functional mitral regurgitation, paroxysmal AF, and ventricular ectopies. He was allocated to the ivabradine group, and his HR fell from 89 to 67 beats/min at 2 weeks. However, his systolic blood pressure (BP) decreased from 105 to 93 mmHg – the opposite direction to the mean change.1 Drug dose was increased from 5 to 10 mg daily as per protocol. At 4 weeks, his HR and BP were further decreased to 62 beats/min and 81 mmHg, respectively. Bilateral leg edema emerged, and both ventricular ectopy and serum brain natriuretic peptide level increased. At 6 weeks, his BP spontaneously recovered to 117 mmHg. Intensified medication with diuresis and sotalol resolved the symptoms. He continued to take ivabradine for 20 months until study completion, and thereafter was readmitted for HF and pneumonia in a month. He died 2 months after admission.
In addition to the baseline HR and BP level,14,15 the patient’s initial response to the medication might be ominous for worse prognosis. We would like to know about the clinical outcomes among the subpopulation in which BP fell soon after ivabradine treatment. If there is an interaction, then the initial BP reduction could be an early indicator of nonresponse to the HR reduction strategy with ivabradine.
None.
None. Y.K. is a member of Circulation Journal’ Editorial Team.
