Low QRS voltages (LQRSV) are commonly found in patients with cardiac amyloidosis (CA), but not always. Alberto Cipriani, MD, of the University of Padua Medical School in Italy, and colleagues reported that LQRSV is more frequent in patients with light chain amyloidosis (AL)-CA than in patients with transthyretin amyloidosis (ATTR)-CA. Findings from the multicenter, retrospective study were published in JACC: CardioOncology.
Dr. Cipriani and colleagues reported that LQRSV reflects an advanced disease stage and can independently predict cardiovascular mortality. They concluded that, for patients with ATTR-CA with intermediate risk, LQRSV can provide incremental prognostic accuracy over the National Amyloidosis Centre (NAC) staging system, thereby leading to a faster diagnosis with a more appropriate aggressive treatment.
To diagnose CA, invasive or noninvasive criteria are used to demonstrate amyloid fibrils within the myocardium. An essential diagnostic test that is not included in these criteria is the 12-lead electrocardiogram (ECG), according to the researchers, which “can raise or support the clinical suspicion of CA, by revealing various red flags like … LQRSV.”
The researchers recruited 120 patients with AL-CA and 291 patients with ATTR-CA from tertiary centers in Italy and identified LQRSV in 41% of all patients. LQRSV was more common in patients with AL-CA (55%) than in patients with ATTR-CA (35%; p<0.001). At the start of the study, the primary endpoint was all-cause death.
“The COVID pandemic significantly impacted our study in that we had to change this primary endpoint,” Dr. Cipriani explained. The team changed the endpoint to cardiovascular death when, in 2020, at least 10 patients in the study died from COVID-19 pneumonia.
In patients with AL-CA, LQRSV was independently associated with younger age (p=0.015), higher New York Heart Association (NYHA) class (p=0.016), and natriuretic peptides (p=0.041). In patients with ATTR-CA, LQRSV was independently associated with pericardial effusion (p=0.008) and lower tricuspid annular plane systolic excursion (TAPSE; p=0.038). Patients with ATTR and LQRSV had similar NYHA class natriuretic peptide levels and left ventricular systolic and diastolic function as those without LQRSV but lower left ventricular mass, lower TAPSE, and more frequent atrial fibrillation and pericardial effusion than those without LQRSV.
“I was surprised by the fact that, in ATTR, LQRSV were associated with lower left ventricular mass,” Dr. Cipriani said, noting that the association became evident as they examined more patients.
Patients with LQRSV, both AL-CA and ATTR-CA, experienced a shorter survival versus those without LQRSV. During a median follow-up of 33 moths, LQRSV independently predicted cardiovascular death in both AL-CA (hazard ratio [HR] = 1.76, 95% CI 2.41-10.18; p=0.031) and ATTR-CA (HR=2.64, 95% CI 1.82-20.17; p=0.005). LQRSV and NAC staging together provided incremental prognostic value in ATTR-CA (area under the curve [AUC] for NAC model = 0.83, 95% CI 0.77-0.89; AUC for NAC+LQRSV model = 0.87, 95% CI 0.81-0.93; p=0.040).
“The results are helpful for doctors when facing an ECG of an adult with a hypertrophic cardiomyopathy phenotype,” Dr. Cipriani said. “The presence of LQRSV must raise the suspicion of CA and orient first to the AL form, but the absence of LQRSV should not discourage doctors from proceeding with the diagnostic workup for CA if other red flags of the disease (e.g., carpal tunnel syndrome) are present.”
This new information about the clinical correlates of LQRSV may be helpful for further understanding the LQRSV phenomenon, Dr. Cipriani said. The higher prevalence of LQRSV in AL-CA as opposed to ATTR-CA suggests there may be distinct pathophysiologic mechanisms underlying the two subtypes, he added. For example, study data indicate inflammation may play a role in AL-CA, whereas myocyte loss may underlie the pathophysiology in ATTR-CA.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Cipriani A, De Michieli L, Porcari A, et al. Low QRS voltage in cardiac amyloidosis: clinical correlates and prognostic value [published online, 2022 Sept 7]. JACC: CardioOncology. doi: 10.1016/j.jaccao.2022.08.007.
