Clinical Studies

Below is a list of clinical studies or trials, which have impacted clinical cardiac physiology practice:

Study & Publisher

Brief Description/Outcome

Applicability Of A Risk Score For Prediction Of The Long-Term (8-Year) Benefit Of The Implantable Cardioverter-Defibrillator (June 2012)


This study used a previously developed risk score including 5 clinical factors (New York Heart Association functional class II, age 70 years, blood urea nitrogen 26 mg/dl, QRS duration 0.12 s, and atrial fibrillation) to evaluate 8-year ICD survival benefit within risk score categories among 1,191 MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) patients.

Outcome: The findings in this study suggest that a simple risk score can identify patients who derive significant long-term benefit from primary ICD therapy. High-risk patients with multiple comorbidities composed 17% of the MADIT-II population and did not derive long-term benefit from non-resynchronisation device therapy.

Reduction In The Risk Of Heart Failure With Preventive Cardiac Resynchronization Therapy: MADIT-CRT Trial (September 2009)

This trial enrolled 1820 patients from 110 centres in Europe, Canada, and the United States with 3:2 randomization of CRT-D to ICD-only between Dec. 22, 2004 and April 23, 2008. The Independent Data & Safety Monitoring Board recommended trial termination on June 22, 2009 when the difference in the primary end point between the two treatment groups reached the pre-specified efficacy boundary. All patients received optimal medical therapy for heart failure during the clinical trial.

Outcome: Preventive cardiac resynchronization therapy in asymptomatic or mildly symptomatic cardiac patients with a reduced ejection fraction and wide QRS complex is associated with a significant 34% decrease in the risk of death or heart failure, with the CRT-D benefit dominated by a reduction in heart-failure events.

The DAVID (Dual Chamber And VVI Implantable Defibrillator) II Trial (March 2009)
 

In all, 600 patients with impaired ventricular function from 29 North American sites, who required an implanted defibrillator for primary or secondary prevention, with no clinical indication for pacing, were randomly assigned to atrial pacing (at 70 beats/min) versus minimal ventricular pacing (at 40 beats/min) and followed up for a mean of 2.7 years.

Outcome: The effect of atrial pacing on event-free survival and quality of life was not substantially worse than, and was likely equivalent to, backup-only ventricular pacing. Atrial pacing may be considered a “safe alternative” when pacing is desired in defibrillator recipients, but affords no clear advantage or disadvantage over a ventricular pacing mode that minimizes pacing altogether.

Randomized Trial Of Cardiac Resynchronization In Mildly Symptomatic Heart Failure Patients And In Asymptomatic Patients With Left Ventricular Dysfunction And Previous Heart Failure Symptoms (November 2008)
 

610 patients with NYHA functional class I or II heart failure with a QRS 120 ms and a LV ejection fraction 40% received a CRT device (defibrillator) and were randomly assigned to active CRT (CRT-ON) or control (CRT-OFF) for 12 months.

Outcome: The REVERSE Trial demonstrates that CRT, in combination with optimal medical therapy (defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I patients with previous HF symptoms.

Strategic Programming Of Detection And Therapy Parameters In Implantable Cardioverter-Defibrillators Reduces Shocks In Primary Prevention Patients (Auugust 2008)
 

The PREPARE study was a prospective, cohort-controlled study that analysed 700 patients (CRT-D and non–CRT ICD) with primary prevention indications for an ICD from 38 centres followed-up for 1 year. VT/VF was detected for rates of 182 beats/min that were maintained for at least 30 of 40 beats. Anti-tachycardia pacing was programmed as the first therapy for regular rhythms with rates of 182 to 250 beats/min, and supraventricular tachycardia discriminators were used for rhythms of 200 beats/min. The control cohort consisted of 689 primary prevention patients from the EMPIRIC (Comparison of Empiric to Physician-Tailored Programming of Implantable Cardioverter Defibrillators Trial) (non–Bi-V ICD, physician arm only) and MIRACLE ICD (Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation) (Bi-V ICD) trials for whom VT/VF detection and therapy programming were not controlled.

Outcome: Strategically chosen VT/VF detection and therapy parameters can safely reduce shocks and other morbidities associated with ICD therapy in patients receiving an ICD for primary prevention indications.

Minimizing Ventricular Pacing to Reduce Atrial Fibrillation in Sinus-Node Disease (September 2007)

1065 patients with sinus-node disease, with intact atrio-ventricular conduction, and a normal QRS interval received conventional dual-chamber pacing or a dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrio-ventricular conduction, preserve ventricular conduction, and prevent ventricular desynchronisation.

Outcome: Dual-chamber minimal ventricular pacing, as compared with conventional dual-chamber pacing, prevents ventricular desynchronisation and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease.

A Comparison Of Empiric To Physician-Tailored Programming Of Implantable Cardioverter-Defibrillators (July 2006)
 

A total of 900 ICD patients were randomly assigned to standardised or physician-tailored VT/VF programming and followed-up for 1 year.

Outcome: Standardised empiric ICD programming for VT/VF settings is at least as effective as patient-specific, physician-tailored programming, as measured by many clinical outcomes. Simplified and pre-specified ICD programming is possible without an increase in shock related morbidity.

Single-chamber versus dual-chamber pacing: which is most efficacious in elderly patients with atrio-ventricular block?
United Kingdom Pacing and Cardiovascular Events (UKPACE) Trial (July 2005)

In a multicentre, randomized, parallel-group trial, 2021 patients 70 years of age or older who were undergoing their first pacemaker implant for high-grade atrio-ventricular block were randomly assigned to receive a single-chamber ventricular pacemaker or a dual-chamber pacemaker. In the single-chamber group, patients were randomly assigned to receive either VVI or VVI,R pacemaker.

Outcome:The key finding from this randomized trial was that in elderly patients with high-grade atrio-ventricular block, dual-chamber pacing provided no survival advantage over single-chamber pacing.

This result contrasts with the findings of nonrandomized studies that suggested there was improved survival with dual-chamber pacing, which probably reflected selection bias.

The Effect Of Cardiac Resynchronization On Morbidity And Mortality In Heart Failure (April 2005)

Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving standard pharmacologic therapy were randomly assigned to receive medical therapy alone or with cardiac resynchronization.

Outcome: In patients with heart failure and cardiac dyssynchrony, cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients.

Permanent Pacing Is A Risk Factor For The Development Of Heart Failure? (March 2005)

No previous study has examined the importance of right ventricular pacing as a risk factor for the development of heart failure (HF) in subjects without a history of HF. A cohort study of patients who underwent initial pacemaker implantation was conducted to test the hypothesis that patients with ventricular dyssynchrony created by permanent pacing would develop HF, as shown by new HF hospitalizations or HF-related deaths, at a higher rate than matched controls.

Outcome: The findings of this study support the concept that right ventricular pacing represents a risk factor for developing HF and implicates ventricular dyssynchrony or a lack of appropriate atrio-ventricular sequence as a potential cause of adverse outcomes in patients without HF.

Amiodarone Or An Implantable Cardioverter–Defibrillator For Congestive Heart Failure (January 2005)

2521 patients with New York Heart Association (NYHA) class II or III, CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less were randomised to receive conventional therapy for CHF plus placebo, conventional therapy plus amiodarone, or conventional therapy plus a conservatively programmed, shock only, single-lead ICD. Placebo and amiodarone were administered in a double-blind fashion.

Outcome: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favourable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.

Cardiac-Resynchronization Therapy With Or Without An Implantable Defibrillator In Advanced Chronic Heart Failure (May 2005)

A total of 1520 patients who had advanced heart failure (New York Heart Association class III or IV) due to ischemic or non-ischemic cardiomyopathies and a QRS interval of at least 120 msec were randomly assigned in a 1:2:2 ratio to receive optimal pharmacologic therapy alone or in combination with cardiac-resynchronization therapy with either a pacemaker or a pacemaker–defibrillator.

Outcome: In patients with advanced heart failure and a prolonged QRS interval, cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and, when combined with an implantable defibrillator, significantly reduces mortality.

Analysis Of Implantable Cardioverter Defibrillator Therapy In The Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial (September 2003)

The therapy delivered by the ICD was examined in 449 patients randomized to ICD therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Events triggering ICD shocks or anti-tachycardia pacing (ATP) were reviewed for arrhythmia diagnosis, clinical symptoms, activity at the onset of the arrhythmia, and appropriateness and results of therapy.

Outcome: Delivery of ICD therapy in AVID patients was common, primarily due to VT. Inappropriate ICD therapy occurred frequently. Use of ICD therapy as a surrogate endpoint for death in clinical trials should be avoided.

A Randomized Comparison of Atrial and Dual-Chamber Pacing in 177 Consecutive Patients With Sick Sinus Syndrome (August 2003)
 

This is a randomized trial done to compare single-chamber atrial (AAI) and dual-chamber (DDD) pacing in patients with sick sinus syndrome (SSS). Primary end points were changes in left atrial (LA) size and left ventricular (LV) size and function as measured by M-mode echocardiography.

Outcome: During a mean follow-up of 2.9 years, DDDR pacing causes increased LA diameter, and DDDR pacing with a short atrio-ventricular delay also causes decreased LVFS. But in comparison DDDR with short atrio-ventricular shown more AF than with long atrio-ventricular. No changes occur in LA or LV diameters or LVFS during AAIR pacing. Atrial fibrillation is significantly less common during AAIR pacing.

Dual-Chamber Pacing Or Ventricular Backup Pacing In Patients With An Implantable Defibrillator. The Dual Chamber And VVI Implantable Defibrillator (DAVID) Trial (April 2003)
 

A dual-chamber pacemaker/ICD was implanted in 506 patients who had a standard indication for ICD implantation, an ejection fraction of 40% and no indication for anti-bradycardia pacing.

Post-implantation, patients were randomly assigned to ventricular pacing at a rate of 40/min (VVI-40) or DDDR pacing with a lower rate of 70/min (DDDR-70). Pharmacologic therapy for left ventricular dysfunction was prescribed for all patients.

Outcome: In patients with a low EF who require an ICD, compared to ventricular backup pacing, dual-chamber pacing increases the risk of death and hospitalization for HF.

Ventricular Pacing or Dual-Chamber Pacing For Sinus-Node Dysfunction - The Mode Selection Trial in Sinus-Node Dysfunction (MOST) (June 2002)

A total of 2010 patients with sinus-node dysfunction with dual-chamber pacing or with ventricular pacing were followed-up for a median of 33.1 months.

Outcome: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.

Prophylactic Implantation Of A Defibrillator In Patients With Myocardial Infarction And Reduced Ejection Fraction (March 2002)

Over the course of four years, 1232 patients were enrolled with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned to receive an implantable defibrillator or conventional medical therapy. Invasive electrophysiological testing for risk stratification was not required.

Outcome: In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.

Effects of Physiologic Pacing Versus Ventricular Pacing on The Risk Of Stroke and Death Due To Cardiovascular Causes The Canadian Trial of Physiologic Pacing Trial (CTOPP) (May 2000)

At 32 Canadian centres, patients without chronic atrial fibrillation who were scheduled for a first implantation of a pacemaker to treat symptomatic bradycardia were eligible for enrolment. Patients were randomly assigned to receive either a ventricular pacemaker or a physiologic pacemaker (DDD) and followed for an average of three years.

Outcome: Physiologic pacing provides little benefit over ventricular pacing for the prevention of stroke or death due to cardiovascular causes.

Randomized Comparison Of Antiarrhythmic Drug Therapy With Implantable Defibrillators In Patients Resuscitated From Cardiac Arrest The Cardiac Arrest Study Hamburg (CASH) (March 2000)
 

From 1987, eligible patients were randomized to an ICD, amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents randomization ratio 1:3). Assignment to propafenone was discontinued in March 1992, after an interim analysis conducted in 58 patients showed a 61% higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months. The study continued to recruit 288 patients in the remaining 3 study groups. The study was terminated in March 1998, when all patients had concluded a minimum 2-year follow-up.

Outcome: During long-term follow-up of cardiac arrest survivors, therapy with an ICD is associated with a 23% (non-significant) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol. The benefit of ICD therapy is more evident during the first 5 years after the index event.

Canadian Implantable Defibrillator Study (CIDS) A Randomized Trial Of The Implantable Cardioverter Defibrillator Against Amiodarone (October 1999)
 

A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone.

Outcome: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone.

Long-term follow-up of patients from a randomised trial of atrial
versus ventricular pacing for sick-sinus syndrome (October 1997)

 

In a previous study of 225 patients with sick sinus syndrome randomised to either single-chamber atrial pacing or single-chamber ventricular pacing, it found that after a mean follow-up of 3•3 years, atrial pacing was associated with significantly less atrial fibrillation and thromboembolism whereas there was no significant difference in mortality and heart failure between the two groups. Therefore this study had a aim of find out whether this beneficial effect of atrial pacing is maintained during extended follow-up of up to 8 years.

Outcome: The beneficial effect of atrial pacing found in previous studies is enhanced substantially over time. Patients with sick-sinus syndrome should be treated with an atrial rather than ventricular-pacing system because after long-term follow-up, atrial pacing is associated with a significantly higher survival, less atrial fibrillation, fewer thromboembolic complications, less heart failure, and a low-risk of atrio-ventricular block.

Improved Survival With An Implanted Defibrillator In Patients With Coronary Disease At High Risk For Ventricular Arrhythmia (December 1996)

Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; left ventricular ejection fraction of 30% or less; a documented episode of asymptomatic unstained ventricular tachycardia; and inducible, non-suppressible ventricular tachyarrhythmia on a electrophysiological study were randomly assigned to receive an implanted defibrillator or conventional medical therapy

Outcomes: In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.