Conduction System Disease Recast as Preventive Therapy Target

An analysis of SPRINT trial data may recast disorders of left ventricular (LV) conduction, usually considered something to manage after the fact, as preventable.

The study points to hypertension as a likely cause and to intensive blood- pressure-lowering drug therapy, the kind highlighted in SPRINT, as a possible preventive measure.

In the new analysis, the adjusted risk of new-onset conduction disorders fell by 26% over an average 3.5 years (P = .038) for SPRINT patients with hypertension managed to a 120 mm Hg or lower systolic BP level compared with a control group's 140 mm Hg target, which was the recommendation at the time.

The finding suggests that "clinically important cardiac conduction disease is not inevitable among those that ultimately develop it, but rather that it is a modifiable outcome susceptible to prevention strategies," said Katrine Emilie Frimodt-Møller, MB, University of Copenhagen, Denmark. "A more aggressive blood pressure treatment may be an accessible strategy to prevent left ventricular conduction disease."

Frimodt-Møller presented the post-hoc SPRINT analysis April 29 at the Heart Rhythm Society (HRS) 2022 Scientific Sessions, held virtually and live in San Francisco.

The randomized, open-label SPRINT trial captivated in 2015 with its finding of a 25% drop in mortality and risk of cardiovascular (CV) events in nondiabetic patients with hypertension managed to the more aggressive systolic BP target.

In the new analysis, a total of 203 incident cases of LV conduction disease were observed during the trial. They included left bundle-branch block (LBBB), left-sided fascicular block, and intraventricular conduction delay.

The nonmodifiable risk factors of older age and male sex also significantly predicted incident LV conduction disease; the risk in men was 2.3 times that of women.

"Prevention of conduction disease has not been really an emphasis of research," observed senior author Gregory M. Marcus, MD, MAS, at a press conference held after the presentation. Marcus, of the University of California San Francisco, said he hopes the new findings "will shift the way we think about and approach" LV conduction disease. "There's no reason to believe that hypertension is the only modifiable risk factor."

"This is new knowledge, that modifying the blood pressure can affect the incidence of conduction disease," said John L. Sapp, MD, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, as an invited discussant after results were presented.

A "new box" has been opened for exploration, Sapp proposed. "We should see the conduction system as a vulnerable structure in the heart." Although it's unclear whether LV conduction system disease is more a marker for myocardial injury in general, "maybe we should now be thinking of the conduction system as something that we should protect. And ultimately we'll have to test that in randomized trials."

SPRINT's more than 9300 patients entered the trial with a systolic BP of at least 130 mm Hg and at least one major CV risk factor such as clinical or subclinical CV disease, chronic kidney disease (CKD), advanced age, or a high Framingham 10-year risk score. They had been randomly assigned to the two BP-management strategies at 102 US centers.  

The new analysis included 3918 in the intensive management group, and 3956 assigned to standard care after exclusion of patients with LV conduction system disease at baseline. The groups were similar with respect to clinical or subclinical CV disease, including LV hypertrophy and heart failure, and to prevalence of CKD.

The hazard ratio (HR) for incident LV conduction system disease in the intensive-management group vs standard management was 0.74 (95% CI, 0.56 - 0.98) after adjustment for age, sex, race, clinical or subclinical CV disease, heart failure, and CKD. The corresponding HR for LV conduction system disease or new ventricular pacing was 0.77 (95% CI, 0.60 - 0.98), Frimodt-Møller reported.

A similar analysis for the endpoint of new right ventricular (RV) conduction disease, performed as a negative control, she said, did not show a significant association; the HR was 0.95 (95% CI, 0.71 - 1.27).

That's consistent with a proposed mechanism behind the link between BP and LV conduction system disease seen in the analysis, Marcus observed. Generalized arterial hypertension can stress the LV by subjecting its chamber walls to increased pressures, which may promote fibrosis and damage the LV conduction system. But the same hypertension would not stress the right ventricle in the same way.

SPRINT was funded by the National Institutes of Health. Frimodt-Møller reports that she has no relevant disclosures. Marcus discloses owning stock in InCarda Therapeutics; receiving honoraria or fees for speaking or consulting from Johnson & Johnson and InCarda Therapeutics; and receiving research grants from Medtronic and Baylis Medical. Sapp discloses receiving honoraria or fees for speaking or consulting from Medtronic, Biosense-Webster, Abbott, and Varian Medical Systems; and receiving research grants from Abbott and Biosense-Webster.

Heart Rhythm Society 2022 Scientific Sessions.
LB-735 - Late-Breaking Clinical Trials: Updates and Registries.
LB-735-01 - Effect of Intensive Versus Standard Blood Pressure Treatment on Incident Left-Ventricular Conduction Disease.
Presented April 29, 2022.

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Cite this: Conduction System Disease Recast as Preventive Therapy Target - Medscape - May 05, 2022.