Successful β-blocker introduction under intra-aortic balloon pumping and ivabradine in a patient with new-onset dilated cardiomyopathy and pulsus alternans: a case report

Abstract Background Pulsus alternans has been considered a sign of poor prognosis in patients undergoing treatments for heart failure. However, it may be overlooked in patients with intra-aortic balloon pumps (IABPs). The use of IABP and ivabradine for a β-blocker introduction in a patient with dilated cardiomyopathy (DCM) and pulsus alternans and its consequence have never been reported. Case summary In a 16-year-old high school boy with idiopathic DCM [left ventricular end-diastolic diameter (LVDd), 72 mm; left ventricular ejection fraction (LVEF), 18%], the introduction of carvedilol therapy failed, causing cardiogenic shock under inotropes. Therefore, an IABP support was provided, and he was transferred to our hospital. The arterial pressure waveform under IABP demonstrated pulsus alternans with sinus tachycardia at 135/min. Ivabradine reduced the heart rate to ∼100/min and eliminated the pulsus alternans neither decreasing the cardiac index nor increasing the pulmonary artery wedge pressure. Subsequently, carvedilol was reintroduced, and IABP and inotropes were discontinued. Then, 112 days after his transfer to our hospital, left ventricular reverse remodelling was confirmed (LVDd, 54 mm; LVEF, 44%), and he returned to school. The carvedilol dose reached 20 mg/day in 4 months after discharge, and further improvement was observed a year after discharge (LVDd, 54 mm; LVEF, 52%). Discussion Pulsus alternans is considered a predictor of poor prognosis. However, IABP and ivabradine may stabilize the haemodynamics in pulsus alternans, leading to a successful β-blocker introduction.


Introduction
Pulsus alternans, or mechanical alternans, is the alternating arterial pressure with a regular heart rhythm, often detected in patients with decompensated heart failure. 1,2Pulsus alternans is considered a sign of low cardiac output or compromised perfusion 3 and a poor prognosis. 1,4However, patients with dilated cardiomyopathy (DCM) and pulsus alternans have been reported to achieve left ventricular reverse remodelling after starting β-blockers. 5In this article, we present the case of a patient with DCM and pulsus alternans, who was initially intolerant to a β-blocker.β-Blocker therapy was initiated, supported by an intra-aortic balloon pump (IABP) and ivabradine, and left ventricular reverse remodelling was subsequently achieved.

Discussion
This case with DCM and pulsus alternans was initially intolerant to the β-blocker; however, an IABP and ivabradine supported initiation of β-blocker therapy, and left ventricular reverse remodelling was subsequently achieved with an angiotensin-converting enzyme inhibitor and a mineral corticoid receptor antagonist.Kodama et al. 5 reported that DCM patients with pulsus alternans achieved left ventricular reverse remodelling if a β-blocker was successfully introduced.Therefore, pulsus alternans before the introduction of the β-blocker may not always be a sign of a bad prognosis.In this case, IABP was effective in reducing ventricular filling pressure and increasing CI, but did not reduce HR, and pulsus alternans remained.Tachycardia, one of the mechanisms for compensating left ventricular systolic dysfunction and low cardiac output, is characterized by the frequency and strength of the contraction, known as the force-frequency relationship.6][7][8] The force-frequency relationship is impaired in patients with DCM, 9 particularly in those with pulsus alternans. 10A heart with pulsus alternans cannot keep up with tachycardia and does not contract strongly enough during tachycardia, 11 which suggests that a heart with pulsus alternans is loaded with more calcium than the heart can use, in other words, 'calcium overload'.
An acute effect of ivabradine includes increased ventricular filling and stroke volume of each heartbeat in patients with excessive sinus tachycardia. 12In this patient with sinus tachycardia and pulsus alternans, ivabradine was prescribed before starting the use of a β-blocker, considering its negative inotropic effect.Ivabradine decreased HR and eliminated pulsus alternans, without decreasing the CI or increasing ventricular filling pressure.The reduction in 'calcium overload' may have led to the absence of an increase in filling pressure. 7,8imobendan was also possibly beneficial due to its inotropic effect as a calcium sensitizer, reducing the need for more calcium loading despite its calcium loading potential. 13t was reported that simultaneous use of ivabradine and β-blocker improved systolic function compared with β-blocker alone at 4 months. 14The chronic effects of ivabradine include left ventricular reverse remodelling and improvement in the composite outcome of cardiovascular death or hospital admission due to worsening heart failure in patients with a sinus rate > 70/min, even with basal β-blocker therapy. 15Therefore, the good clinical evolution of the case presented may not have been obtained without IABP and ivabradine.

Lead author biography
He completed his MD and PhD at Niigata University, Niigata, Japan, and learned calcium handling as a research fellow at the laboratory of Professor David Eisner, the unit of cardiac physiology of the University of Manchester, Manchester, UK.His current research interests include heart failure, cardiomyopathy, and pulmonary hypertension.

Figure 1 Figure 2
Figure 1Haemodynamic parameters before and after ivabradine.On the transfer day, the heart rate was 135/min, and arterial pressure waves of the left ventricular ejection showed pulsus alternans (A, white arrows; s, strong beat; W, weak beat).The subsequent diastolic augmentation waves by IABP also showed pulsus alternans (A, white circles).Brief cessation of IABP made pulsus alternans clearer (B, white arrows), despite the prominent dicrotic notches and reflection waves.Note that the amplitude of the pulsus alternans, or the difference between strong and weak beats, stayed at ∼10 mmHg, regardless of on IABP or off IABP.Ivabradine 2.5 mg twice daily reduced his heart rate to 95/min within 2 days.The arterial waves showed that pulsus alternans disappeared under IABP support (C, white arrows) and was not caused by a brief cessation of IABP (D, white arrows).Respiratory fluctuations of AP were parallel to PAWP.AP, arterial pressure; PAWP, pulmonary artery wedge pressure; RAP, right atrial pressure.