History
A 68-year-old man previously underwent implantation of a cardiac resynchronization therapy defibrillator (CRT-D) device (February 2007) after a class I indication for CRT at the time—symptomatic drug-refractory ischemic-based heart failure disease, New York Heart Association (NYHA) class III, severe left ventricular dysfunction, and left bundle branch block (LBBB) ventricular conduction delay, with a 130-msec duration QRS complex. Despite CRT, clinical follow-up of the patient was characterized by gradually worsening heart failure progression with further reduction of left ventricular function (left ventricular ejection fraction [LVEF] <20%), dilation of the left ventricle, and, as a result of dilation of the mitral annulus, progression of mitral regurgitation to grade III. Therefore the patient underwent successful positioning of a MitraClip (Abbott Vascular, Abbott Park, Ill.) device in September 2009, thus achieving mitral regurgitation reduction to grade I or II. Paroxysmal atrial fibrillation gradually progressed to become permanent, and ablation of the atrioventricular node was performed to achieve adequate CRT delivery. Other comorbidities included chronic renal insufficiency (reduced glomerular filtration rate of 40 to 50 mL/min/1.73 m2), previous nephrectomy for renal papillary carcinoma, and hyperuricemia.
Because of persistent severe heart failure symptoms (NYHA class IIII to IV), in May 2011 the patient consented to participate in a prospective multicenter safety and feasibility study evaluating a wireless cardiac stimulation system of the left ventricular endocardium (wireless cardiac stimulation cardiac resynchronization therapy [WiCS-CRT]).
Current Medications
At presentation, the patient’s therapeutic scheme included maximally tolerated dosages of beta blocker, an angiotensin-converting enzyme [ACE] inhibitor, and other relevant drugs: clopidogrel 75 mg daily, acenodecumerol 1 mg to maintain international normalized ratio between 2 and 3, carvedilol 12.5 mg daily, enalapril 40 mg daily, spironolactone 25 mg daily, atorvastatin 40 mg daily, and aspirin 100 mg daily.
Current Symptoms
The patient exhibited breathlessness at mild exertion and had NYHA class III to IV heart disease.
Physical Examination
Laboratory Data
Electrocardiogram
Findings
The electrocardiogram of conventionally delivered CRT is shown in Figure 20-1 (left panel). Vertical QRS axis (160 msec) coupled with R wave in V1 indicates regular epicardial biventricular pacing in VVI modality at 70 bpm. Left ventricular stimulation from a bipolar left ventricular tip positioned in a postero-lateral branch of the coronary sinus (red circle) confers a vertical axis to the QRS complex and QS morphology in the inferior leads.
Chest Radiograph
Findings
Anteroposterior and right lateral (Figure 20-2, upper panels) show the positioning of the three leads with the transvenous left ventricular lead positioned in a posterolateral branch of the cornonary sinus (red circle) and reaching a posterolateral apical position.
Echocardiogram
Findings
At baseline, echocardiographic examination revealed a severely dilated left ventricle with diffuse hypokinesia and highly compromised left ventricular function (LVEF 19%). Despite MitraClip implantation, residual moderate mitral insufficiency was present; moderate tricuspid insufficiency was also present (Figure 20-3, left panel, and video left panel). Pulmonary pressures were increased, with an estimated arterial pulmonary pressure of 40 mm Hg (see video baseline).
Focused Clinical Questions and Discussion Points
Question
What is the pathophysiologic basis for considering left ventricular endocardial pacing to deliver CRT?
Discussion
Impulse propagation physiologically travels from the endocardium to the epicardium. Most of the evidence in animal models has been supplied by the Maastricht group.1–3 The experimental data have demonstrated that CRT delivered from the left ventricular endocardium allows quicker propagation of the electrical impulse through the myocardium in contrast to epicardium.1 Better impulse propagation translates to greater mechanical and hemodynamic effect, in terms of both systolic and diastolic functions.2 These data have been further substantiated by favorable hemodynamic effects in animal models with induced ischemic heart failure and the presence of electrical dyssynchrony.3 This study concluded that endocardial CRT improved, to a greater extent, electrical synchrony of activation and left ventricular pump function in contrast to conventional epicardial CRT in compromised canine hearts with LBBB. This benefit was explained by a shorter path length along the endocardium and faster circumferential and transmural impulse conduction during endocardial left ventricular pacing.
FIGURE 20-2
Question
Has clinical evidence shown that left ventricular endocardially delivered CRT can confer clinical benefits?
Discussion
Some evidence is available from isolated case-based reports or small patient series on the clinical benefits of left ventricular endocardially delivered CRT.4–6 Access to the left ventricular endocardium is achieved through transseptal catheterization of an active fixation lead into the left ventricle. Besides being technically challenging because transseptal catheterization is required, higher risk for thromboembolic complications and the likelihood of lead dislocation are possible issues that may arise. These potential risks have discouraged the diffusion of this approach.
FIGURE 20-3 See expertconsult.com for video. 
Spragg and colleagues5 performed an acute study in heart failure patients with LBBB. Comparison between endocardial and conventional epicardial CRT revealed a greater hemodynamic response for the former modality of cardiac stimulation. Hemodynamic response during endocardial pacing was typically superior when the lead was placed remotely from an infarct zone. This study advocates that endocardial lead position may require individual patient tailoring for clinical response.
Question
What are the most important aspects that should be evaluated when planning to treat a patient with WiCS-CRT?
Discussion
Several factors contributed to achieving the clinical response. Assessment of global and regional left ventricular contractility represents key information derived form transthoracic echocardiography. In the present case, preprocedural transthoracic echocardiogram allowed detection of diffuse hypokinesia in the absence of akinetic segments, particularly in the lateral and posterolateral regions of the left ventricle. Preserved kinetics indicated myocardial vitality, thus suggesting that functional recruitment of myocardial tissue through cardiac stimulation was possible.
Preprocedural ultrasound examination using a vascular probe is indispensable to precisely define the intercostal acoustic window in which the transmitter pulse generator should be fixed during the implant procedure.7 The transmitter pulse should be fixed within this predefined acoustic window during the implantation procedure.
Anchoring of the receiver electrode of the WiCS-CRT system to the endocardial left ventricular lateral wall represents the most important part of the procedure and is technically challenging. Competence to perform this part of the procedure requires both interventional cardiologic skills (for dye contrast injection in the left ventricle) and electrophysiologic skills (for manipulation of long sheath and interpretation of electrical measures and signals) for procedural success.
Final Diagnosis
This patient was a CRT nonresponder considered eligible for wireless left ventricular endocardial cardiac stimulation for CRT.
Plan of Action
The plan for this patient was implantation of a WiCS.
Intervention
Under general anesthesia, using a retrograde transaortic approach, a long steerable sheath was placed into the left ventricle and gently brought against the endocardial wall. Then, another internal delivery catheter at the tip of which the receiver electrode was mounted was carefully advanced to the distal portion of the outer sheath. Before injecting and releasing the receiver electrode, sensing and pacing were repeatedly measured and the receiver electrode position was monitored using conventional transthoracic echocardiography; contrast dye was injected to ensure good and perpendicular contact (Figure 20-4). The receiver electrode was then released and the delivery system removed. A pocket for the pulse generator was surgically created in the left lateral abdominal wall, and another pocket was made in the anterolateral part of the chest (at approximately the fifth and sixth intercostal spaces) in a position that was within the acoustic window mentioned previously; this position should allow for the best communication and interaction between the transmitter and the endocardial receiver electrode. Finally, the transmitter and the pulse generator were connected and the electrical and pacing integrity of the entire system was tested. Device control performed the next day confirmed adequate functioning of the entire system and ECG showed effective and continuous biventicular capture (Figure 20-1). Post-implantation chest radiograph (Figure 20-2, lower panels) show the wireless endocardial electrode, implanted subendocardially in the lateral apical region of the left ventricle and the transmitter pulse generator fixed subcutaneously in the sixth intercostal space. The battery is implanted subcutaneously in the upper left abdominal quadrant (not visible on the chest radiograph).
FIGURE 20-4
Outcome
The outcome was clinically favorable. During the month of September, 16 months after WiCS positioning, hospitalization was planned for device change.
Findings
In the clinical follow-up of more than 1 year the patient’s global clinical status gradually improved. Although the patient was hospitalized two times over 1 year for noncardiac reasons (gastric bleeding and worsening renal insufficiency), he was not hospitalized for heart failure. NYHA functional class gradually improved to II. Device controls as well as serial ECGs confirmed effective and continuous biventricular pacing. On the ECG (Figure 20-1, center panel) greater right axis deviation coupled with low-amplitude negative QS in D1 and greater R wave in V1 lead are suggestive of greater (and quicker) electrical depolarization of the left ventricle in contrast to conventional CRT. Transthoracic echocardiogram revealed effective reversal of maladaptive remodeling, with reduction of both left ventricular systolic and diastolic volumes, clear recovery of left ventricular lateral wall movement and kinetics, and overall increase of global left ventricular contractile function, with the LVEF increasing from 19% to 35% (see Figure 20-3, right panel and video loop 1 B 
).
).Comments
The WiCS system determined mechanical recovery of previously hypokinetic lateral wall, thus conferring clinical benefit.
Wireless Cardiac Stimulation Technology For Cardiac Resynchronization Therapy
WiCS-CRT is a novel cardiac stimulation system that converts ultrasound energy to electrical energy to stimulate the myocardium.8 For cardiac resynchronization this system functions in parallel to a conventional coimplanted device, either a pacemaker or an implantable cardioverter-defibrillator. The system is composed of three components: (1) a target wireless endocardial electrode, which is implanted endocardially and receives ultrasound impulses converting these to electrical energy; (2) the impulse transmitter, localized and fixed in the intercostal space (usually fifth or sixth), which produces ultrasound pulses that are triggered through sensing of the right ventricular pacing activity of the coimplanted device; and (3) the battery component, which is implanted subcutaneously in the upper abdominal quadrant.
At present, the feasibility and safety of the WiCS-CRT system are being evaluated in the scheme of a multicenter, prospective, longitudinal study (the WISE-CRT study).8 The study has been momentarily halted because of technical issues with the delivery system of the endocardial receiver electrode.
Selected References
1. Van Deursen C., Van Geldrop I., Van Hunnik A. et al. Improved myocardial repolarization and left ventricular systolic and diastolic function during endocardial cardiac resynchronization. Heart Rhythm. 2008;5:S188.
2. Van Deursen C., van Geldorp I.E., Rademakers L.M. et al. Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts. Circ Arrhythm Electrophysiol. 2009;2:580–587.
3. Strik M., Rademakers L.M., van Deursen C.J. et al. Circ Arrhythm Electrophysiol. 2012;5:191–200.
4. Garrigue S., Jaïs P., Espil G. et al. Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure. Am J Cardiol. 2001;88:858–862.
5. Spragg D.D., Dong J., Fetics B.J. et al. Effective LV endocardial pacing sites for cardiac resynchronization in patients with ischemic cardiomyopathy. Heart Rhythm. 2010;7:S75–S76.
6. Kutyifa V., Merkely B., Szilágyi S. et al. Usefulness of electroanatomical mapping during transseptal endocardial left ventricular lead implantation. Europace. 2012;14:599–604.
7. DeFaria Yeh D., Lonergan K.L. et al. Clinical factors and echocardiographic techniques related to the presence, size, and location of acoustic windows for leadless cardiac pacing. Europace. 2011;13:1760–1765.
8. Auricchio A., Delnoy P.P., Regoli F. et al. First-in-man implantation of leadless ultrasound-based cardiac stimulation pacing system: novel endocardial left ventricular resynchronization therapy in heart failure patients. Europace. 2013;15:1191–1197.
