B P6 C58 Devices for Monitoring and Managing Heart Failure

Question 1

Conduction delay resulting in a QRS duration ______________ on the surface electrocardiogram has been termed ______________________

Answer 1

Greater than 120 msec

Electrical dyssynchrony

Question 2

The difference in the timing of mechanical contraction or relaxation between different segments of the left ventricle that results from electrical dyssynchrony has been termed ________________ and can result in suboptimal ventricular filling, a reduction in left ventricular (LV) contractility, greater degree and prolonged duration of mitral regurgitation (MR), and paradoxical septal wall motion.

Answer 2

Mechanical dyssynchrony

Question 3

Optimal placement of two leads, one on the ____________ and a second in the __________ at the site of latest LV activation allows for simultaneous or near simultaneous activation of both ventricles and improves inter- and intra-ventricular synchrony. E

Answer 3

Right ventricular septum

Coronary sinus

Question 4

Assessed the clinical efficacy and safety of cardiac resynchronization therapy (CRT) with transvenous atrio-biventricular (BiV) pacemakers in patients with severe heart failure, left ventricular (LV) systolic dysfunction, and electrical conduction abnormalities

Population: NYHA class III CHF on stable medical therapy, LV ejection fraction <35%, LV end-diastolic diameter >60 mm, Sinus rhythm with a QRS duration >150 ms

This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing (CRT on vs CRT off)

BiV pacing with transvenous systems, compared with an inactive pacing mode, was associated with improvements in six-minute walk distance, peak oxygen consumption, and QOL scores in patients with severe heart failure, LV systolic dysfunction, and electrical conduction abnormalities.

Answer 4

MUSTIC trial (Multisite Stimulation in Cardiomyopathies Study)

Question 5

Compared the effect of cardiac resynchronization therapy (CRT) versus no CRT on the quality of life and functional capacity in patients with chronic heart failure (CHF) and ventricular dysynchrony

Population: NYHA class III, IV CHF, LV ejection fraction </=35%, LV end-diastolic diameter at least 55 mm, QRS duration at least 130 ms

Patients underwent a predischarge randomization to the control group (no CRT, n=225) or CRT group (n=228), then underwent a six-month period of double-blinded study with follow-up at one, three, and six months. (CRT on vs CRT off)

Compared with placebo, CRT was associated with a significantly improved six-minute walk distance, improved New York Heart Association (NYHA) class by at least one class, quality of life, time on the treadmill during exercise testing, and ejection fraction. CRT was also associated with a significantly improved peak oxygen consumption. The QRS duration was significantly lower in CRT patients compared with control. The trial also provided evidence of substantial LV reverse remodeling

Answer 5

MIRACLE Trial (Multicenter InSync Randomized Clinical Evaluation)

Question 6

Examined the efficacy and safety of combined CRT and ICD therapy in patients with New York Heart Association (NYHA) class III or IV congestive HF despite appropriate medical management.

Population: NYHA class III, IV CHF, LV ejection fraction </=35%, LV end-diastolic diameter >/= 55 mm, QRS duration >/= 130 ms, cardiac arrest due to ventricular fibrillation or ventricular tachyarrhythmia, or spontaneously sustained ventricular tachyarrhythmia, or inducible ventricular fibrillation or sustained ventricular tachyarrhythmia

Of 369 randomized patients, 182 were controls (ICD activated, CRT off) and 187 were in the CRT group (ICD activated, CRT on)

Patients assigned to CRT had a greater improvement in median
quality of life score and functional class than controls but were no different in the change in distance walked in 6 minutes. No significant differences were observed in changes in left ventricular size or function, overall HF status, survival, and rates of hospitalization.

Answer 6

MIRACLE - ICD trial (Combined Cardiac Resynchronization and Implantable Cardioversion Defibrillation in Advanced Chronic Heart Failure)

The combined CRT-ICD device used in this study was approved by the FDA in June 2002 for use in NYHA Class III and IV HFrEF patients with ventricular dyssynchrony and an ICD indication.

Question 7

Determined if bi-ventricular pacing could reduce short-term morbidity and mortality in patients with heart failure

Population: NYHA class II - IV CHF, LV ejection fraction </=35%, LV end-diastolic diameter >/= 55 mm, QRS duration >120 ms, indication for ICD

A total of 581 patients were randomized, 248 into the 3-month crossover study and 333 into the 6-month parallel controlled trial (ICD activated, CRT off) vs (ICD activated, CRT on)

The primary end point was a composite of mortality, hospitalizations for heart failure, and episodes of ventricular tachycardia or ventricular fibrillation. For the primary composite end point, the study demonstrated an insignificant trend favoring the resynchronization group. However, peak V̇o2, 6-minute hall walk distance, quality of life, and NYHA class were significantly improved in the active pacing group. There was also a reduction in LV end-systolic and end-diastolic dimensions

Answer 7

CONTAK CD trial

Question 8

Randomized trial that tested the hypothesis that CRT-D or CRT-P would reduce the risk of death or hospitalizations in patients with advanced HF and prolonged intraventricular conduction

Population: NYHA class III, IV CHF, LV ejection fraction </=35%, QRS duration >120 ms

A total of 1520 patients in New York Heart Association (NYHA) class III or IV with ischemic or dilated cardiomyopathy and QRS duration >120 ms were randomly assigned in a 1:2:2 ratio to OPT, CRT-P, or CRT-D

Among patients with advanced CHF, treatment with CRT or CRT-D was associated with a reduction in the composite of all-cause mortality or all-cause hospitalizations at a median follow-up of 14 months. The trial was discontinued early, due to the superior efficacy in the resynchronization arms.

Answer 8

COMPANION trial (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure)

Mean systolic blood pressure was significantly higher in both the CRT-P and CRT-D groups compared to the OPT group at 3, 6, and 12 months

Question 9

Evaluated the addition of cardiac resynchronization therapy (CRT) to optimal pharmacological therapy in patients with advanced heart failure and cardiac dyssynchrony despite standard pharmacological therapy.

Population: NYHA class III, IV CHF, LV ejection fraction </=35%, QRS duration >150 ms or 120m-150 ms with echo dyssynchrony

Patients were randomized in an open-label manner to continued standard pharmacological therapy alone (n=404) or standard pharmacological therapy combined with CRT (n=409). OMT vs OMT+CRT

Among patients with advanced heart failure and cardiac dyssynchrony despite standard pharmacological therapy, treatment with CRT was associated with a reduction in the primary endpoint of all-cause mortality and hospitalization for major cardiovascular events compared with standard pharmacological therapy.

Answer 9

CARE HF trial (Cardiac Resynchronization Heart Failure Study)

CRT also led to a significant reduction in MR area by echocardiography and significant myocardial reverse remodeling and reduced N-terminal pro B-type natriuretic peptide (NT-proBNP) at 18 months. In addition, the mean systolic blood pressure was 5.8 mm Hg (CI, 3.5 to 8.2, p = 0.001) higher in the CRT group.

Question 10

Evaluated cardiac resynchronization therapy (CRT) compared with optimal medical therapy among patients with New York Heart Association (NYHA) class I-II heart failure (left ventricular ejection fraction [LVEF] <40%) and ventricular dyssynchrony

Population: LV dysfunction (≤40%), Prolonged QRS duration (≥120 ms), NYHA class I-II, LVEDD ≥55 mm

Patients with LV dysfunction and NYHA class I-II underwent CRT implant and were randomized to CRT ON (n = 419) or CRT OFF with optimal medical therapy (n = 191)

The use of CRT in patients with mildly symptomatic heart failure did not reduce the proportion of patients who clinically worsened at 12 months, but it did delay the time to first hospitalization for heart failure. There was no difference in mortality. This therapy resulted in significant reverse LV remodeling, which remained stable to 5 years. The role of this therapy among patients with mildly symptomatic heart failure remains unknown.

Answer 10

REVERSE trial (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction)

Question 11

Determine the utility of CRT-D in reducing all-cause mortality and congestive heart failure (CHF) events in patients meeting criteria for an ICD, but with NYHA class I/II symptoms.

Population: NYHA class I or II (ICM), class II (NICM), LV ejection fraction </=3-%, sinus rhythm, QRS duration >/=130 ms

Patients were randomized in a 3:2 fashion to receive either CRT-D or ICD alone

The results of the MADIT-CRT trial indicate that CRT-D implantation in patients with systolic CHF (LVEF ≤30%), with a wide QRS, and NYHA class I/II symptoms (asymptomatic or mildly symptomatic patients) is associated with a significant reduction in the primary endpoint of CHF events or mortality, as compared with ICD implantation alone, primarily due to a reduction in CHF events.

Benefit of CRT was seen only in those with a left bundle branch block (LBBB). 14 A larger benefit of CRT was noted for women (HR = 0.37, CI 0.22 to 0.62) than men (HR = 0.76, CI 0.59 to 0.97, p = 0.01 for interaction) and in patients with a QRS of 150 milliseconds or longer

Answer 11

MADIT CRT trial (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

The MADIT-CRT trial led the FDA to expand the indication for CRT to NYHA Class II or ischemic Class I patients, with LVEF less than 30%, QRS duration longer than 130 milliseconds, and LBBB. MADIT-CRT also demonstrated substantial improvement in ventricular size and function in patients randomized to CRT, with the outcomes benefit directly related to the degree of reverse remodeling

Question 12

Studied the safety and efficacy of CRT-D, as compared with ICD alone in patients with mild to moderate symptoms (NYHA class II/III), LV systolic dysfunction (ejection fraction [EF] ≤30%), and wide QRS complex.

Population: NYHA class II or III, EF ≤30% (ischemic and nonischemic), Intrinsic QRS duration ≥120 msec, or ≥200 msec if paced rhythm, Sinus rhythm or permanent atrial fibrillation or flutter with a controlled ventricular rate, Planned ICD implantation for indicated primary or secondary prevention of sudden cardiac death

Patients were randomized in a 1:1 fashion to receive either ICD or CRT-D

The results of the RAFT trial indicate that in patients with NYHA class II or III LV systolic dysfunction (EF <30%) and a wide QRS complex, who were optimally medically treated, CRT-D is superior to ICD alone in reducing the rates of all-cause mortality, CHF hospitalization, and their composite endpoint. On subgroup analysis, the results of the primary endpoint seemed to be enhanced in patients with a wider QRS complex at baseline and those with LBBB morphology. The benefit of CRT-D over ICD appeared sustained on long-term follow-up, although data were available for 58.4% of the total population.

Answer 12

RAFT trial (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial)

There is, however, a significant increase in the risk of device- or procedure-related complications at 30 days in the CRT-D arm, including a higher risk of hospitalization for device-related causes.

Question 13

Patients who do not have reductions in symptoms or HF hospitalizations and do not achieve LV reverse remodeling are called

Answer 13

Nonresponders

Question 14

Factors reported to contribute to the nonresponder rate include

Answer 14

Suboptimal LV lead placement
Suboptimal atrioventricular (AV) and ventricular-ventricular (VV) timing
Ventricular scar
HF disease progression

Question 15

_________ show a large benefit—some as “super” as normalization of ventricular function

Answer 15

Super responders

Question 16

Some patients, ________________, do not show a measurable benefit of CRT, but also do not have the predicted worsening HF over time as do nonresponders.

Answer 16

Nonprogressors

Question 17

______________ who have clinical worsening of their disease after CRT implantation

Answer 17

Negative responders

Question 18

Factors associated with a particularly beneficial (super) response include

Answer 18

LBBB
Longer QRS duration
Female sex
Lack of prior myocardial infarction
Smaller left atrial volume

Question 19

Evaluated the prophylactic benefit of implantable cardioverter-defibrillator (ICD) placement in patients with coronary artery disease and a left ventricular ejection fraction (LVEF) of ≥30%, who have had at least one myocardial infarction (MI), but require no further risk stratification.

Population: age >21 years, prior MI >1 month, LV dysfunction (EF ≤30%) within 3 months

RCT 3:2 ICD + OMT vs OMT alone

Mortality was 14.2% in the ICD arm versus 19.8% in the conventional therapy arm (p = 0.016), a 31% relative reduction (hazard ratio 0.69).

ICD implantation was associated with a 31% reduction in overall mortality compared to conventional therapy over an average follow-up period of 2 years.

Answer 19

MADIT II (Multicenter Automatic Defibrillator Implantation Trial II)

Question 20

Evaluated whether standard medical therapy plus an implantable cardioverter defibrillator (ICD) will be associated with improvements in survival compared with standard medical therapy alone in patients with nonischemic dilated cardiomyopathy, ejection fraction (EF) ≤35%, and spontaneous premature ventricular complexes or nonsustained ventricular tachycardia.

Population: nonischemic dilated cardiomyopathy, symptomatic CHF with LVEF ≤35%, and either nonsustained ventricular tachycardia or an average of 10 premature ventricular contractions (PVCs) per hour on 24-hour Holter

Patients were randomized to standard medical therapy plus implantation of a single chamber ICD (n=229) or standard medical therapy alone (n=229)

The primary endpoint of all-cause mortality at two years was 13.8% in the standard medical therapy arm and 8.1% in the ICD arm (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.40-1.06; p=0.08).

While the difference in all-cause mortality did not reach statistical significance, there was a significant reduction in sudden cardiac death in the ICD arm (n=3 vs. n=14; HR 0.20, 95% CI 0.060-0.71; p=0.006). In the subgroup of patients with New York Heart Association (NYHA) class III, all-cause mortality was signficantly lower in the ICD arm (HR 0.37, 95% CI 0.15-0.90; p=0.02).

Answer 20

DEFINITE trial (Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation)

First randomized trial of primary prevention therapy with ICDs in nonischemic cardiomyopathy patients

Question 21

Evaluated the effectiveness of amiodarone therapy or an implantable cardioverter-defibrillator (ICD) with placebo in patients with New York Heart Association (NYHA) class II and III congestive heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) ≤35%.

Population: Symptomatic CHF (NYHA class II and III) due to ischemic or nonischemic dilated cardiomyopathy, LVEF ≤35% within 3 months of enrollment

Patients were randomized in a double-blind manner to either: 1) Conventional CHF therapy and placebo, 2) conventional CHF therapy plus amiodarone, or 3) conventional CHF therapy plus a conservatively programmed single lead ICD.

Among patients with NYHA class II or III CHF and reduced LVEF, treatment with an ICD was associated with a reduction in all-cause mortality compared with placebo, but there was no difference between amiodarone and placebo.

The neutral results on ACM with amiodarone effectively ended its routine use for primary prevention of SCD in HFrEF

Answer 21

SCD-HeFT trial (Sudden Cardiac Death in Heart Failure Trial)

Provided the most robust evidence to date supporting the prophylactic use of an ICD in patients with NYHA Class II and III HFrEF irrespective of etiology.

Question 22

Evaluated treatment with an ICD compared with usual care among patients with left ventricular systolic dysfunction due to nonischemic etiology.

Population: nonischemic cardiomyopathy, LVEF ≤35%, NYHA Class II, III (IV if CRT is planned), NT proBNP >200 pg/ml

Randomized to ICD implantation (n = 556) versus usual care (n = 560)

The primary outcome, incidence of all-cause mortality, occurred in 21.6% of the ICD group versus 23.4% of the control group (p = 0.28). Younger patients (<59 years) appeared to derive greater benefit from ICD implantation versus older patients (p for interaction = 0.009).

Among patients with a nonischemic cardiomyopathy, ICD implantation did not reduce long-term mortality compared with usual care; however, there was suggestion of benefit among younger patients. Although there was lack of benefit for the primary outcome, ICD was associated with a reduction in sudden cardiac death versus usual care. Device infections were similar between the groups.

Answer 22

DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality)

Question 23

Class 1 recommendations for ICD implantation

Answer 23

In patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with LVEF </=35% and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for >1 year, ICD therapy is recommended for primary prevention of SCD to reduce total mortality

In patients at least 40 days post-MI with LVEF </= 30% and NYHA class I symptoms while receiving GDMT, who have reasonable expectation of meaningful survival for >1 year, ICD therapy is recommended for primary prevention of SCD to reduce total mortality

Question 24

Class 1 recommendations for CRT implantation

Answer 24

For patients who have LVEF </= 35%, sinus rhythm, left bundle branch block (LBBB) with a QRS duration ‡150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT, CRT is indicated to reduce total mortality, reduce hospitalizations, and improve symptoms and QOL

Question 25

The ________________ was designed to avert episodes of CSA by direct stimulation of the phrenic nerve via a transvenous lead in either the left pericardiophrenic or right brachiocephalic vein connected to a pulse generator

Answer 25

Remede system

Question 26

The _________________ enrolled 151 s jects, 96 of whom had NYHA Class I-IV HF. 32 At 6 months, the device “on” group was more likely to have a ≥50% reduction in ApneaHypopnea Index (AHI) from baseline (51% vs. 11%).

Answer 26

Remede System Pivotal Study

The Remede system (Respicardia, Minnetonka, MN) was FDA approved in 2017 for the treatment of moderate to severe CSA in adult patients

Question 27

Trial demonstrating a large benefit on HFH and ACM with transcatheter edge to edge repair (TEER) of the mitral valve in patients with HFrEF and moderately severe to severe SMR

Answer 27

COAPT Trial

2019 - MitraClip NT and NTR/ XTR Delivery System: for the treatment of symptomatic, moderateto-severe secondary MR in patients with LVEF 20%-50% and LVESD ≤70 mm

Question 28

Cardiac contractility modulation (CCM) uses the __________________ (Impulse Dynamics, Stuttgart, Germany), which includes an implantable pulse generator (IPG), one atrial and two ventricular leads, a programmer, and a transcutaneous charger

Answer 28

Optimizer Smart System

Question 29

The ____________ trial combined patients from a similar previous trial (FIX-HF-5) and 160 new subjects with an LVEF ≥25% and ≤45%, NYHA Class III or IV symptoms, QRS duration <130 msec, and normal sinus rhythm

Answer 29

FIX-HF-5C trial

2019 - Optimizer Smart system: to improve 6MHWD, QoL, and functional status of NYHA Class III HF patients who remain symptomatic despite GDMT, are in normal sinus rhythm, and not indicated for CRT and have an LVEF of 25%-45%

Question 30

_________________ is designed to restore this autonomic imbalance by inhibiting the sympathetic system and activating the parasympathetic system by electrically stimulating the baroreceptors in the carotid sinus.

Answer 30

Baroreflex activation therapy (BAT)

Question 31

The _________________ (CVRx, Inc., Minneapolis, MN), consists of a pulse generator and a carotid sinus lead implanted surgically to deliver BAT.

Answer 31

BAROSTIM NEO system

Question 32

Trial demonstrating beneficial effect of BAT with QoL, 6MHWD and NT proBNP levels

Answer 32

BEAT HF trial

2019 - BAROSTIM NEO system:

For the improvement of symptoms of HF-QoL, 6MHWD, and functional status (NYHA) for patients who are in NYHA Class III or Class II (if recent Class III) have an LVEF ≤35%, an NTproBNP < 1600 pg/mL, and no indication for CRT

Question 33

Evaluated the use of the CardioMEMs heart sensor—a device implanted in a small pulmonary artery that records highfidelity pulmonary artery pressures that are downloaded and transmitted intermittently.

Over a 6-month period, significantly fewer HFH occurred in the treatment group (83) than in the control group (120). During the entire single-blinded follow-up averaging 15 months, the treatment group had a 37% RRR in HF hospitalizations compared with the control group

Answer 33

The CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial

The results of the CHAMPION trial led to FDA approval of the first implantable hemodynamic monitoring system in 2014, for use in HFrEF and HFpEF patients with NYHA Class III symptoms and a history of HF hospitalization within the previous year.

The CHAMPION trial c firmed previous data that higher baseline estimated diastolic PAP predicts mortality and increases in PAP from baseline in PAP are also associated with increased mortality