BLOCK-HF: Replace RV Pacing With BiV in AV-Block Heart Failure

November 08, 2012

LOS ANGELES — Substituting biventricular (BiV) pacing for standard right ventricular pacing led to significant improvements in survival and hospitalization for heart-failure patients with atrioventricular (AV) block in a major randomized trial.

Dr Anne B Curtis

Its patients didn't have the standard QRS indication for cardiac resynchronization therapy (CRT), and most had only moderately low ejection fractions, but CRT benefited them anyway, presumably by allowing them to avoid RV-only pacing and its well-documented hazards, observed Dr Anne B Curtis (University at Buffalo, NY) when speaking with heartwire .

"This opens up a whole new niche of patients whose ejection fractions are high enough so they are not indicated for primary-prevention defibrillators but now would be candidates for a CRT device," said Curtis, who is principal investigator for the Biventricular versus Right Ventricular Pacing in Patients with Left Ventricular Dysfunction and Atrioventricular Block (BLOCK HF) trial. She presented the study here at the American Heart Association 2012 Scientific Sessions.

Potentially, "this will increase the demand for CRT-P devices," she said, referring to biventricular pacemakers that do not offer defibrillation--now far less commonly used than defibrillating CRT devices (CRT-D).

The trial randomized patients with an LVEF of <50%, NYHA class 1 to 3 heart failure, and AV block after implantation with pacemakers (with a full complement of CRT leads to preserve blinding and present the same degree of risk to both groups) set to BiV pacing or apical RV pacing.

The BiV group showed a significant 26% reduction in the primary composite end point of all-cause mortality, HF-related urgent care, or a >15% increase in LV end-systolic volume index (LVESVI) over about three years. The benefit was driven almost entirely by the end point's two clinical components, which together fell by 27%.

 
This opens up a whole new niche of patients whose ejection fractions are high enough so they are not indicated for primary-prevention defibrillators but now would be candidates for a CRT device.
 

That speaks to the likely mechanism of CRT benefit in the trial, which would not involve correction of dyssynchrony by QRS criteria; most patients with that crucial indication for CRT could not have been randomized in BLOCK HF. All patients were appropriate for RV pacing by current standards, but RV pacing has generally been something to avoid, if possible, since several trials, DAVID and MOST in particular, showed that it can worsen ventricular function and outcomes over the long term.

In BLOCK HF, therefore, CRT improved outcomes compared with RV pacing, probably by preventing the deterioration of ventricular function that would likely have occurred otherwise.

Benefit Not Just in Low-EF Patients

Dr Gerasimos Filippatos

As the assigned discussant following Curtis's formal presentation of BLOCK HF, Dr Gerasimos Filippatos (Athens University Hospital Attikon, Greece) pointed out that current guidelines give "a very weak recommendation" to CRT for patients with conventional pacing indications, but that BLOCK HF deserves a chance at changing that in future updates.As part of a panel discussion on the trial, Dr Douglas P Zipes (Krannert Institute of Cardiology, Indianapolis, IN) asked Curtis whether CRT had similar effects regardless of heart-failure severity; for example, was the benefit different in NYHA class 3 patients from class 1 patients? Curtis had noted that at enrollment, 16% of the patients were in NYHA class 1 and 57% and 27% were in class 2 and 3, respectively.

She said the analysis by NYHA class is in the future, but first impressions of outcomes by LVEF suggest that the benefit is across the board. "It doesn't seem to make a whole lot of difference. The benefit was not just seen in the low-EF patients." Mean LVEF in the trial at enrollment was 40%.

"I think BLOCK-HF is exciting and will change how we think about pacemaker implants in the [kind of] patients included in the trial, but there are a few caveats," though none too serious, Dr Brian Olshansky (University of Iowa Hospitals, Iowa City) commented to heartwire by email. Olshansky was the principal investigator for the INTRINSIC-RV trial.

For example, he observed, many patients were censored for the primary end point. Curtis had reported that occurred for 83 CRT patients and 71 RV-pacing patients due to missing LVESVI data.

Olshansky also noted that 10 CRT patients and 34 RV-pacing patients crossed over to the other therapy without having already met the primary end point.

And "the population was not all complete heart block, and thus there was confusion about the meaning of the LBBB."

The unconventional primary end point was "rather contrived," he said, and "it took a very long time to enroll, so it is not clear that this really represents the entire population at risk." Curtis had noted that in BLOCK-HF, which launched in December 2003, AV block was first degree in 20%, type 1 second degree in 11%, type 2 second degree in 21%, and complete in 48%.

Finally, Curtis had mentioned to heartwire that some potentially referring physicians had enough confidence in CRT, even off-guidelines for their BLOCK-HF-like patients, that they didn't want them randomized. That added to the time required for enrolling enough patients for adequate statistical power. By the same token, the inclusion of LVESVI, an echocardiographic parameter, in the primary end point that otherwise consisted of mortality and a broadly defined HF end point, was part of the strategy for enhancing the number of events to assess, she had said.

"Well Worth It for What You Get Long Term"

The trial entered 691 patients with a mean age of 73 years, of whom three-quarters were men, at 60 sites in the US and Canada. They were required to have AV block necessitating pacing but no history of pacemaker or defibrillator implantation and an LVEF <50% and to be in NYHA class 1 to 3; they could not have a class I indication for CRT.

After implantation with CRT pacemakers with their full complement of leads, the patients were put on medical therapy and allowed 30 to 60 days for its optimization, during which time all received RV pacing. They were then randomized double-blindly to BiV pacing or RV pacing, in 349 and 342 patients, respectively.

Hazard Ratio (HR) for Primary End Point and Other End Points in BLOCK HF, BiV vs RV Pacing

End point HR (95% CI)
Primary end point* 0.74 (0.60–0.90)
All-cause mortality, HF urgent care 0.73 (0.57–0.92)
All-cause mortality, HF hospitalization 0.78 (0.61–0.99)
HF hospitalization 0.70 (0.52–0.93)
Mortality 0.83 (0.61–1.14)

*By intention to treat, a composite of all-cause mortality, HF-related urgent care (any unplanned hospital visit requiring intravenous heart-failure therapy), or >15% increase in left ventricular end-systolic volume index by echocardiography, over a mean 36-month follow-up

Curtis said one of the trial's main purposes was to determine whether the extra risks of BiV devices that are largely due to their LV lead compared with an RV pacing device, are worth it. Right ventricular leads "very rarely" dislodge, for example, Curtis observed for heartwire , but LV leads pose a well-recognized risk of dislodgement, often with adverse consequences such as coronary sinus dissection or phrenic-nerve pacing.

BLOCK HF, she said, indeed shows that there's a trade-off of extra risk from BiV pacing for the benefits it confers, but "short term I think it is well worth it for what you get long term."

Complication Rates by Type of Pacing (BiV or RV) and Type of Pacemaker (CRT-P or CRT-D) in BLOCK HF

Type of complications BiV CRT-P, n=23 (%) RV CRT-P, n=241 (%) BiV CRT-D, n=106 (%) RV CRT-D, n=101 (%)
Procedural 17 10 17 16
All system-related* 15 13 38 24
Generator-related 4 5 30 12
Lead-related 6 5 6 9

BiV=biventricular

RV=right ventricular

CRT-P, CRT-D=cardiac resynchronization therapy pacing only or with defibrillator

*Includes RA- or RV-related complications

Medtronic sponsored BLOCK HF. Curtis discloses receiving honoraria from St Jude Medical, Sanofi, and Medtronic and serving as consultant or on an advisory board for St Jude Medical, Sanofi, Medtronic, Janssen Pharmaceuticals, Bristol-Myers Squibb, and Biosense Webster. Filippatos discloses receiving research grants from Bayer and Corthera/Novartis and consulting or serving on an advisory board for Corthera.

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