Cardiac resynchronization therapy (CRT) – heart failure device therapy

Cardiac resynchronization therapy (CRT) – heart failure device therapy

What is the role for devices in heart failure management?

All patients need optimal pharmacological therapy and lifestyle modifications. But in a small subset, there is a definite role for devices. Ventricular tachycardia in a scar of old myocardial infarction may necessitate the implantation of an implantable cardioverter defibrillator (ICD). Hypotensive ventricular tachycardia in heart failure is an important cause for sudden cardiac death (SCD) as it can degenerate into ventricular fibrillation in a short time. Those who have survived a SCD are those at a higher risk of recurrence and benefit maximum with an ICD implantation. ICD improves the life expectancy by 6 years in these high risk individuals.

Intraventricular dyssynchrony in the presence of severe left ventricular dysfunction is an important indication for cardiac resynchronization therapy (CRT). Delay between the contractions of the septum and the lateral left ventricular wall causes reduced left ventricular stroke volume. The important surrogate of ventricular dyssynchrony is an increased QRS duration. In CRT, septum and lateral left ventricular wall contracts simultaneously producing improvement in the left ventricular stroke volume. This is achieved by pacing the lateral wall of the left ventricle through a coronary vein along with right ventricular endocardial pacing. CRT improves the symptomatic status and survival of heart failure patients with left ventricular dyssynchrony. But still there is a 30% non-responder rate of patients who do not respond to CRT.

QRS duration of more than 120 milliseconds with LBBB pattern in a person with refractory heart failure will be an indication for cardiac resynchronization therapy (CRT, biventricular pacing, heart failure device). It is often associated with mechanical dyssynchrony and wasted systolic effort of the left ventricle. CRT produces a narrowing of the QRS complexes as the right ventricle and posterolateral left ventricle are paced in synchrony, to produce a better left ventricular output.

Selection criteria for cardiac resynchronization therapy (CRT)

Following are the current selection criteria for cardiac resynchronization therapy (CRT; also known as heart failure device or biventricular pacing):

Severe heart failure (New York Heart Association (NYHA) class III or IV)

Depressed left ventricular ejection fraction (LVEF) (<35%)

Echocardiographic parameters:

M- Mode: Septal posterior wall motion delay at papillary muscle level in parasternal short axis view > 130 ms has a sensitivity of 24% specificity of 66%

Interventricular mechanical delay: difference between LV and RV pre-ejection period. Beginning of QRS to beginning of LV ejection in apical 4 chamber view; Beginning of QRS to beginning of RV ejection in short axis view; difference > 40 ms is significant

Tissue Doppler Imaging: Septal to lateral wall delay in time to peak velocity > 60 sec is suggestive of dyssynchrony.

Most widely used marker of dyssynchrony is surface ECG. But it is not an absolute marker as it may not have complete correlation with mechanical dyssynchrony. Left bundle branch block is associated with dyssynchrony of lateral wall compared to the septum. QRS duration > 120 ms is an important selection criteria for CRT implantation.

Should be in sinus rhythm for better synchronization and should be on optimal medical therapy.

Those with recent myocardial infarction or have undergone coronary revascularisation within 3 months as well as those scheduled for coronary revascularisation are excluded. This is in view of the potential for improvement in left ventricular function in the short term.

Non responders to cardiac resynchronization therapy

About 30 % of patients do not respond to CRT. The reasons could be any one of the following:

Not every patient with wide QRS has dyssynchrony and vice versa. Leads may be too close to each other to produce synchronous contraction of septum and lateral wall. Scarred region of left ventricle can cause poor capture and synchronization. Consistent ventricular capture by spontaneous impulses can also prevent resynchronization. This is more likely to occur in atrial fibrillation with fast ventricular rate. Attempts at AV nodal ablation to counter this problem have been tried. In sinus rhythm, this problem can be reduced by programming a lower AV delay. Dislodgement of LV lead can occur since it has neither active fixation nor passive fixation mechanisms. V to V timing may not be optimal every case.

Levophase of left coronary angiogram to see tributaries of coronary sinus

Levophase of the angiogram is obtained when you continue the cine recording till the contrast passes from the arterial tree through the capillaries to the venous system. Levophase angiogram gives an outline of the coronary sinus and its major tributaries. But it will not be enough for an excellent visualisation of the venous anatomy for left ventricular lead placement for cardiac resynchronization therapy (CRT). While planning to locate a good vein for CRT, coronary sinus angiography is directly performed by retrograde cannulation of the coronary sinus ostium from the right atrium. Care is needed to avoid dissection of the coronary sinus or its tributaries which are thin walled structures compared to the coronary arteries. Since the flow in the venous system is against the direction of contrast injection, proximal balloon occlusion is needed for good visualisation of the tributaries of the coronary sinus.

Technique of CRT implantation

Basic cannulation of coronary sinus

Start ventricular to tricuspid valve and withdraw applying counterclockwise torque to stay septally to cannulate the coronary sinus ostium. LAO is lined upon the interventricular septum. The orthogonal view is RAO. A prominent Thebesian valve with an associated pouch causes the lead to fall into it and cause difficulty in cannulating the coronary sinus (CS). Injecting a whiff of dye will help delineate the position of the sheath in the pouch, which causes transient dye stasis.

Inability to advance in coronary sinus

Inability to advance in CS could be due to stenosis, valves, subselection, dissection and tortuosity. Vieussens valve is an embryonic remnant, seen at the origin of the posterolateral ventricular vein. If there is a prominent valve in the posterolateral vein, we can cannulate the middle cardiac vein and go into a lateral branch of this vein. CS stenosis can be balloon dilated, but branch vein stenosis is better left alone. Search for other veins which could be used. This will also reduce the dye load in attempted dilatation. Dissections can occur due to dye injections and by sheath advancement. In most of the dissections it is still possible to get a wire across and proceed. Otherwise if the dissection is distal, try using the lateral branch of the middle cardiac vein. Pushing a catheter which is sub selected without recognizing it is one of the reasons for dissection. If it is atrial vein subselection, withdraw it. If it is ventricular vein subselection, your cannulation is over! So try to recognize it with appropriate views.

Inability to get lateral veins

In case of inability to get to lateral veins through a posterolateral vein, try lateral branches of middle cardiac vein or anterior interventricular vein. It is not important how you reach the lateral wall. The ideal site to aim for the left ventricular lead is the lateral wall, mid position.

Need for ICD lead in left ventricle

When there is a mechanical tricuspid valve which you don’t want to cross, an ICD lead can be placed in a coronary vein.

CRT implantation pearls

Screw in lead for LV pacing can be used only if the sheath can be taken deep down into the vein as it is not introduced over a guide wire. If after screwing in, the lead has a high impedance and the threshold is high, it is likely to be one the pericardial side of the vein. It may be unscrewed and another position sought. Screw tip is only 1 mm and may not produce significant bleeding on unscrewing from the pericardial side. Screwing to the myocardial side typically shows ST elevation on the lead tip electrogram due to the injury current. If threshold is not good, electronic configuration with pacing from proximal electrode or other combinations can be tried to improve efficacy. Issue with previous active fixation leads were that future removal or repositioning was not possible and they were also unipolar, preventing electronic configuration of pacing.

Unlike in conventional pacing where we want to minimise ventricular pacing, in CRT we want full biventricular pacing to occur. This may mean programming shorter AV delay to prevent intrinsic conduction. Inappropriately long AV delay can also cause a tendency for MR. E-A fusion can cause diastolic MR, which in turn can worsen heart failure. Unduly short AV delay causes A wave truncation, which can also be associated with MR. Intra-atrial conduction delay due to atrial fibrosis can increase AV delay. Atrial septal pacing is useful in reducing intra-atrial conduction delay. Biatrial pacing is another option to synchronise the atrium. Drug therapy to slow therapy AV conduction and prevent fusion is also useful to improve biventricular pacing in CRT. Echo guided optimisation of AV delay is also possible (Ritter’s method).

During V-V delay optimisation, in some cases an LV offset causing pre-excitation of the LV may improve cardiac output. In interventricular dyssynchrony RV ejects at LV end diastole.

Intraventricular dyssynchrony is manifest as QRS onset to pulmonary ejection compared to aortic ejection of more than 40 milliseconds, septal to posterior wall delay of more than 160 milliseconds or septal to lateral wall delay of more than 60 milliseconds in TVI. 3D synchronization is with colour coding of early and late contracting segments – early as green and late as red.

Maximum tracking rate has to be increased as heart failure status improves. This is for consistent pacing at higher rates needed during more activities permitted by better effort tolerance.

Transient worsening of renal function may be seen after CRT implantation due to the long procedure time. This may also cause worsening of heart failure. The longer procedure time also enhances the chances for infection. Subclavian vein thrombosis is another potential problem due to the presence of three leads and a sluggish circulation due to heart failure.

Phrenic nerve stimulation with LV lead in CRT

First response is to try another vein. Another way is to try is to try bipolar stimulation, deeper in a vein. Stimulation deeper in a vein can produce ventricular ectopy, which usually resolves in a few days. Bipolar stimulation is less likely to produce phrenic nerve stimulation. Direct diaphragmatic stimulation should also be considered, rather than phrenic nerve stimulation. Another method is to go in for an epicardial implantation. During surgery, it is possible to pull the phrenic nerve away and even anchor it a different site. While checking for diaphragmatic pacing during epicardial pacing muscle relaxants should be withdrawn prior to checking for diaphragmatic stimulation. Same applies to implantation in the cath lab under general anaesthesia.

Reverse remodeling of left ventricle with CRT

Cardiac resynchronization therapy (CRT) or biventricular pacing is now an established mode of therapy for severe heart failure, which has been shown to produce significant improvement in the clinical status. The therapy is used mostly in those with severe left ventricular dysfunction and a wide QRS complex indicating dyssynchrony, though the correlation between mechanical dyssynchrony and the electrical counterpart may not always be absolute. A substudy of MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy) was published (Circulation. 2010;122:985-992.), which evaluated the alterations in cardiac size and function echocardiographically in those who received CRT with an ICD (implantable cardioverter defibrillator). The study involved over 1800 patients who were randomly assigned to CRT plus an ICD or an ICD alone, in a 3:2 ratio. Echocardiographic data at baseline and at 1 year was available for about 1400 patients. The combo device (CRT + ICD) group had greater improvements in left ventricular end-diastolic volume index, left ventricular end-systolic volume index, left ventricular ejection fraction, left atrial volume index and right ventricular fractional area change. The P value was less than 0.001 for all the parameter comparisons. Forty percent reduction of risk of death or heart failure was noted with every 10% decrease in left ventricular end diastolic volume at one year.

Reverse remodeling with CRT reduces life threatening ventricular arrhythmias

There have been some reports of whether the altered sequence of ventricular depolarization with cardiac resynchronization therapy (CRT) can be arrhythmogenic. Investigators of MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy) in a sub study analyzed whether this is true in their study patients [J Am Coll Cardiol, 2011; 57:2416-2423]. They grouped the subjects into three – those with 25% or more reduction in left ventricular end systolic volume (LVESV) at one year compared with baseline, those with less than 25% reductions and those who received only ICD (implantable cardioverter defibrillator) and not CRT-D (CRT defibrillator). The first group was the CRT responders and the second one CRT non responders. The highest rates of ventricular tachyarrhythmias (including ventricular tachycardia, ventricular fibrillation, and ventricular flutter) was highest in the non responders (28%) and lowest in the responders (12%). The ICD only group had an intermediate value of 21%. This was for the cumulative probability of first ventricular tachyarrhythmia at two years after the initial assessment. Multivariate analysis showed a 55% risk reduction between CRT responders and ICD only patients, while the difference was not significant between non responders and ICD only patients. The authors conclude that reverse remodeling with CRT is associated with a significant risk reduction for life threatening ventricular arrhythmias.

Left ventricular endocardial pacing for CRT

Cardiac resynchronization therapy (CRT) is now an established mode of therapy for heart failure with ejection fraction below 35%, QRS width above 120 msec and NYHA class III or more. Conventionally, left ventricular pacing in CRT is achieved by epicardial pacing, either through the coronary veins or direct access by thoracotomy. Left ventricular endocardial pacing has not been very popular because of the difficulty in pacing by trans septal approach and the need for anticoagulation to cover the risk of thromboembolism.

Bordachar P et al [J Am Coll Cardiol, 2010; 56:747-753] reviewed the current data on left ventricular (LV) endocardial stimulation for heart failure. They suggest that the implementation of LV endocardial pacing will depend on development of safe, effective and durable devices which could provide reliable pacing and methods to identify optimal sites for pacing. Long term controlled trials should document the benefits and superiority of LV endocardial pacing before it can be put to clinical practice.

A study by Spragg DD et al [J Am Coll Cardiol, 2010; 56:774-781] tried to identify optimal sites for LV endocardial pacing in ischemic cardiomyopathy. They could document that LV endocardial BiV (biventricular) pacing improved the dP/dtmax over right ventricular apical pacing in all patients. In those with pre-existing coronary venous leads, pacing at transmural sites gave similar values of dP/dtmax. Optimal endocardial sites of LV pacing were located at the extreme basal lateral wall and provided better dP/dtmax than the pre-existing CRT leads. These optimal pacing sites were remote from the sites of myocardial scars at an average distance of about 9 cm.

Advancement in CRT – volume status monitoring

Measurement of transthoracic impedance has been used to assess the volume status and the tendency to go in for pulmonary edema can be detected. An an audible alert is given when the volume threshold status is exceeded. A small study has shown that this reduces the number of hospitalizations due to worsening of heart failure as the physician can be contacted when the alert is received to take appropriate therapeutic measures.

CRT for high operative risk functional MR

Cardiac resynchronization therapy (CRT) is being explored as an option for high operative risk moderate to severe functional mitral regurgitation. Functional mitral regurgitation is common in heart failure with dilated cardiomyopathy and has implications in the prognosis of the patient. But these patients are seldom offered surgical correction because of the high surgical risk.

van Bommel and colleagues studied the role of cardiac resynchronization therapy in this group of patients {Cardiac Resynchronization Therapy as a Therapeutic Option in Patients With Moderate-Severe Functional Mitral Regurgitation and High Operative Risk. Circulation. 2011 Aug 1. [Epub ahead of print]}. About hundred patients with moderate-severe functional mitral regurgitation and high operative risk as per the current guidelines. About half of them had one or more grades of improvement in mitral regurgitation and were considered as mitral regurgitation improvers. Superior survival was noted in those who had reduction of mitral regurgitation compared to those who did not improve. Improvement in mitral regurgitation was noted to be an independent predictor of survival with a hazard ratio of 0.35. The authors conclude that CRT is a potential option for those in heart failure with moderate-severe functional mitral regurgitation.

CRT in children with CHD and heart failure

Any CHD patient with heart failure and dyssynchrony will benefit from CRT regardless of QRS morphology. LBBB is far less common in children with heart failure than in adults.

Pacing induced cardiomyopathy can be improved by either cardiac resynchronization therapy or by turning the pacemaker off.

Cardiac Resynchronization Therapy and Ventricular Arrhythmias

Cardiac resynchronisation therapy (CRT) using biventricular pacing prolongs survival in patients with heart failure by improving the pump function of the ventricle. But reversal of normal sequence of myocardial activation during epicardial pacing in CRT increases the transmural dispersion of repolarization (TDR), which is known to predispose to cardiac arrhythmias. Leyva et al has reviewed this aspect in the Indian Pacing and Electrophysiology Journal [Leyva F et al. Indian Pacing Electrophysiol. J. 2008;8(4):268-280].

The investigators of The InSync ICD (Implantable Cardioverter-Defibrillator) Italian Registry report that [Di Biase L et al. J Am Coll Cardiol 2008:52:1442-1449] in patients treated with CRT defibrillators, there is in fact a reduction in ventricular arrhythmic events during the initial 12 months after implantation. This has been correlated with the degree of reverse remodelling of the left ventricle induced by CRT. Those with reverse remodelling show a pronounced long term improvement and better survival. The recurrence rate of ventricular arrhythmias were significantly lesser in the responders than in non – responders to CRT (32% vs. 43%, p = 0.024). In this study of 398 patients, 227 (57%) were defined as responders as they showed 10% or more reduction in end systolic left ventricular volume. The minimum follow up period was 12 months.

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