Cardiac Contractility Modulation Therapy in a Transplant Candidate Patient with Advanced Heart Failure to Improve Cardiac Function and Restore Sinus Rhythm

Abstract

Cardiac Contractility Modulation (CCM) is an electrical therapy based on an implantable device. This device is approved for patients with heart failure with reduced ejection fraction (HFrEF). Randomized clinical trials and thousands of described cases and studies have shown how CCM can improve exercise tolerance, quality of life, re-hospitalization for HF, and cardiac function by reverse left ventricular modelling. In this case report, we describe a patient candidate for a cardiac transplant based on dilated cardiomyopathy with severe LV dysfunction and narrow QRS. The patient had frequent heart failure-related hospitalizations, despite the optimal medical therapy. The strategy was to adopt the Cardiac Contractility Modulation (CCM) therapy while waiting for a cardiac transplant. During a consultation on all prospective therapy options, the patient refused the LVAD therapy, and was more confident in adopting a less invasive device therapy like CCM. This strategy had a very fast and beneficial impact on the patient’s health; the CCM improved heart failure symptoms, hemodynamics flow and cardiac functionality. Moreover, after a relatively short time, the patient went from persistent AF to Sinus Rhythm, although he started with a severe bi-atrial dilatation. These parameters were stable during an extended follow-up of 18 months.

1. Introduction

The Optimizer^® Smart device (Impulse Dynamics, Marlton, NJ, USA) is an implantable, commercially available technology approved by the U.S. Food and Drug Administration (FDA).

This device delivers CCM therapy approved for patients with chronic heart failure, with ejection fraction between 25–45%, and with narrow QRS non-indicated for a cardiac resynchronization therapy (CRT).This devicedeliver nonexcitatory electrical signals to enhance heart contractility without increasing oxygen consumption, benefiting patients with reduced ejection fraction not suitable for resynchronization therapy [1].

In the Evaluate Safety and Efficacy of the Optimizer^® System in Subjects with Moderate-to-Severe Heart Failure (FIX-HF-5C) study, this therapy was evaluated against optimal medical therapy, and led to both reduced heart failure hospitalizations and improvements in exercise tolerance and quality of life [2].

Initially, the CCM required atrioventricular synchrony with a 3-lead Optimizer system, but in the “Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-lead Optimizer Smart System” (FIX-HF-5C2), it has been demonstrated that the 2-lead system effectively delivers a comparable amount of CCM signals with the same clinical results [3]. Many trials and scientific studies have clarified how to treat patients with HF and a wide QRS complex. Cardiac Contractility Modulation provides a way to treat patients with symptomatic heart failure caused by moderate-to-severe systolic left ventricular dysfunction (left ventricular ejection fraction ranging from 25% to 45%), with no indication for cardiac resynchronization therapy [4,5].

This case report describes a patient with narrow QRS affected by a high degree of HF, despite optimized medical therapy and persistent atrial fibrillation (AF).

The objective is to highlight the possibility of CCM atrium remodelling and restoring Sinus Rhythm (SR) in a patient with a dilated left atrium.

2. Materials and Methods

A 60-year-old male was affected by heart failure (HF) until 2013, when he was diagnosed with Dilated Cardiomyopathy with severe left ventricular dysfunction (HFrEF), with EF 30%, narrow QRS (85 ms) and synus rhythm (SR). No evidence of significant coronary lesions. After the first diagnosis of HF, it was decided to install a dual chamber implantable cardioverter defibrillator (ICD).

The Hospital Heart Failure Ambulatory followed the patient for more than ten years.

In 2021, during a routine visit, persistent atrial fibrillation (PAF) was diagnosed, which was initially well tolerated by the patient. The ICD was programmed in VVI mode at 50 beats per minute.

Only eight months after the PAF diagnosis, the HF symptoms worsened, and the patient came to the emergency room (ER). The ER cardiac visit showed a reduced EF of 20% and worsening HF symptoms. The patient underwent optimized guided medical therapy (OGMT) during this hospitalization (sacubitril/valsartan 49/51 mg bis in die, metoprolol 100 mg bis in die, SGLT2 10 mg once daily, diuretics) (

Table 1. Pharmacologic therapy.

Drug	Dose	Dosage
sacubitril/valsartan	49/51 mg	Bis in die
metoprolol	100 mg	Bis in die
SGLT2	10 mg	Once daily
Digoxin	0.125 mg	Once daily
Rivaroxaban	20 mg	Once daily
Furosemide	0.250 mg	Bis in die
Canrenone	100 mg	½ cp daily

).

Despite the OGMT, the worsening HF has induced the patient to undergo further hospitalizations.

In June 2022, the patient came to the ER with dyspnea, acute pulmonary edema, and AF with high ventricular response (Figure 1). During the hospital stay, The MLWHFQ was 60 points, the KCCQ was 79.1 points, and the NT-pro-BNP was 2376 pg/mL.

The echocardiographic exam shows an EF of 15%, LVEDV of 144 mL, LVESV of 122 mL, GLS of −5.4%, left atrium volume of 64 mL, and area of 22.6 cm² (Figure 2).

The blood pressure was shallow, and it was decided to add the patient to the transplant list.

Waiting for the Transplant Center’s response, we showed the patient two different solutions for the HF treatment: the LVAD, or the less invasive Cardiac Contractility Modulation (CCM) device, to treat the symptoms and improve his quality of life. The patient refused the LVAD, as it was too invasive, and accepted a CCM implant (Figure 3).

The implant is performed by placing 2 active fixation bipolar leads on the right ventricular septum (RVS), with a distance between them of approximately 2 cm.

All the conventional electrical parameters (impedance, threshold and sensing) were evaluated and confirmed before and after the fixation of the leads.

The leads were connected to the Optimizer Smart device, and a significant spike in the spontaneous QRS on the continuous heartbeat monitor confirmed the correct delivery of the therapy.

The device was programmed to deliver 7.5 V@20 ms for 7 cycles of 1 h per day (1 h therapy, 2.4 h of pause).

The procedure was tolerated well by the patient, who was dismissed from the hospital after three days.

3. Results

It was decided to schedule a series of follow-ups at 3, 6, 9, and 18 months after the implant was installed to collect as much data as possible regarding hemodynamics factors and QoL improvements (

Table 2. At the scheduled FUs, the patient underwent echocardiography for the evaluation of the ejection fraction (EF), the left ventricular end-diastolic volume (LVEDV), the left ventricular end-systolic volume (LVESV), the global longitudinal strain (GLS), the left atrium area (LAa) and the left atrium volume (LAv). At the same time, NT-proBNP, the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) are evaluated.

	06/2022	09/2022	12/2022	03/2023	01/2024
EF 2ch (%)	15	46	46	48	47
LVEDV (mL)	144	102	66	106	104
LVESV (mL)	122	56	36	49	51
GLS (%)	−5.4	−12.8	−11.4	−14.6	−12.5
LAa (cm2)	22.6	26.1	21.3	19.5	11.8
LAv (mL)	64	90	67	56	23.4
NT-proBNP	2376	984	496	323	214
KCCQ	79.1	80.9	90	90	90
MLWHFQ	60	16	16	13	0

).

Only three months after the implant’s insertion, the patient showed a very rapid improvement in his physical state. This is confirmed by an MLWHFQ of 16 points and a KCCQ of 80.9 points.

However, the improvement in quality of life (QoL) was followed by the ECO graphic exam, which shows impressive results, with an EF of 46% and a GLS of −12.8% (Figure 4).

At the 6-month FU, the patient’s health status continued to improve regarding QoL and echocardiographic parameters. During the 9-month FU, we observed the return of sinus rhythm at the surface ECG (Figure 5).

Since we programmed the ICD in VVI mode, we don’t know how often the patient was in SR. However, the device diagnostic gives the frequency histogram showing how the cardiac frequency decreased and is now stable (Figure 6). This had an excellent impact on the CCM function because this way, the device can deliver the maximum percentage of the therapy associated with the stability of the cardiac frequency and a heart rate under 110 bpm (the maximum CCM two leads only tracking frequency).

4. Discussion

This Case Report showed how, in complex patients, CCM therapy could be effective and quickly improve quality of life and cardiac function. This patient doesn’t have another chance other than the transplant, but CCM gives him a new life and a new perspective on life. Another important observation is the reduced volume and area of the left atrium. This could be caused by the reverse modelling of atrial myocytes, which decreases left atrial pressure, prevents left atrial remodelling and precipitates AF [4]. This case shows that additional investigation into the association between AF and CCM therapy is needed.

5. Conclusions

In this case report, we described for the first time a case of 18-month follow-up and sinus rhythm restoration in a cardiac transplant candidate patient with advanced HFrEF treated with CCM therapy. Based on our case, we believe CCM could be used as a bridge to transplant strategy in selected patients with advanced HFrEF.