Clinical Investigations
Longitudinal Relationship Between Left Ventricular Ejection Fraction and Risk For Ventricular Arrhythmia in Nonischemic Dilated Cardiomyopathy
Longitudinal Arrhythmic Risk Assessment Based on Ejection Fraction in Patients with Recent-Onset Nonischemic Dilated Cardiomyopathy

https://doi.org/10.1016/j.echo.2022.03.019Get rights and content

Highlights

  • Primary prevention ICD indications in nonischemic DCM are still a matter of debate.

  • Strategies based on LVEF after 3 months of therapy failed to demonstrate efficacy.

  • Twenty-four months may be better for evaluation of DCM patients for ICD implantation.

  • Early reduction of LV diameter on therapy identifies patients improving LVEF to >35%.

  • Such late improvement is associated with lower long-term arrhythmic risk.

Background

Practice guidelines suggest the use of implantable cardioverter-defibrillators in patients with left ventricular ejection fractions (LVEF) ≤ 35% despite 3 to 6 months of guideline-directed medical therapy (GDMT). It remains unclear whether this strategy is appropriate for patients with dilated cardiomyopathy (DCM), who can experience reverse ventricular remodeling for up to 24 months after the initiation of GDMT. The aim of this study was to assess the longitudinal dynamic relationship between LVEF ≤ 35% and arrhythmic risk in patients with recent-onset nonischemic DCM on GDMT.

Methods

A retrospective analysis was conducted among patients with recent-onset DCM (≤6 months) and recent initiation of GDMT (≤3 months) consecutively enrolled in a longitudinal registry. Risk for major ventricular arrhythmic events or sudden cardiac death was assessed in relationship to LVEF ≤ 35% at enrollment and 6 and 24 months after initiation of GDMT.

Results

Five hundred forty-four patients met the inclusion criteria. LVEF ≤ 35% identified patients with increased risk for major ventricular arrhythmic events or sudden cardiac death starting from 24 months after initiation of GDMT (hazard ratio, 2.126; 95% CI, 1.065-4.245; P = .03). However, LVEF ≤ 35% at presentation or 6 months after enrollment did not have prognostic significance. Sixty-seven percent of 131 patients with LVEF ≤ 35% at 6 months after initiation of GDMT had improved LVEFs (to >35%) by 24 months. This late LVEF improvement correlated with lower arrhythmic risk (P = .012) and was preceded by a reduction of LV dimensions in the first 6 months of GDMT.

Conclusions

In patients with DCM, the present findings suggest that risk stratification for major ventricular arrhythmic events or sudden cardiac death on the basis of LVEF ≤ 35% is effective after 2 years of GDMT, but not after 6 months. In selected patients with DCM, it would be appropriate to wait 24 months before primary prevention ICD implantation.

Section snippets

Study Population and Design

All patients with DCM consecutively enrolled in the Heart Muscle Disease Registry (HMDR) of Trieste between January 1, 1993, and December 31, 2017, were retrospectively reviewed. The HMDR has been previously described.6 The registry defines DCM as the presence of left ventricular (LV) systolic dysfunction (LVEF ≤ 50%) in the absence of either pressure or volume overload or significant coronary artery disease.7 Coronary angiography or coronary computed tomography is performed in patients

Phase 1: Risk for Major Arrhythmic Events during the First 2 Years of GDMT

Among 1,207 patients with DCM consecutively enrolled in the HMDR of Trieste during the study period, 544 met the inclusion criteria and had echocardiographic data available at enrollment, 355 (65%) had echocardiographic data collected at the 6-month evaluation (median, 5 months; interquartile range, 3-6 months), and 403 (73%) had echocardiographic data collected at the 24-month evaluation (median, 24 months; interquartile range, 19-28 months). Data from all these patients were included in the

Discussion

We provide for the first time a longitudinal assessment of arrhythmic risk in a large and well-characterized cohort of patients with recent-onset nonischemic DCM treated with GDMT. We found that (1) before 24 months, the occurrence of MVAs or SCD in patients with DCM is rare and is not associated with LVEF ≤ 35%, but conversely, after 2 years of GDMT, LVEF ≤ 35% portends a higher arrhythmic risk during follow-up (Figures 2 and 3); (2) a high proportion of patients (>60%) have improved LVEFs (to

Conclusion

In response to GDMT, patients with DCM experience LVRR and improvement in LVEF for up to 2 years. Arrhythmic risk stratification on the basis of a single measurement of LVEF soon after the initiation of GDMT is therefore not effective in this patient population. We found that LVEF ≤ 35% becomes a valuable single parameter to stratify arrhythmic risk for patients with DCM after 2 years of GDMT. We also found that in unselected patients with DCM, the risk for adverse arrhythmic events is low

Acknowledgments

We would like to thank Fondazione CRTrieste, Fondazione CariGO, Fincantieri, and all the health care professionals of Azienda Sanitaria Universitaria Giuliano Isontina for their continuous support of the clinical management of patients affected by cardiomyopathies within the Heart Failure Outpatient Clinic of Trieste.

References (22)

  • T.A. McDonagh et al.

    2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure

    Eur Heart J

    (2021)
  • Drs. De Angelis and Merlo share first authorship.

    Drs. Adamo and Sinagra share last authorship.

    Drs. Merlo and Sinagra are Members of ERN GUARD-HEART (European Reference Network for Rare and Complex Diseases of the Heart; http://guardheart.ern-net.eu).

    Dr. Adamo was supported by National Institutes of Health grant 1K08HL145108-01A1.

    Conflicts of Interest: None.

    View full text