Cardiac resynchronization therapy in patients with cancer: A single cancer center experience

Key Findings.

• ▪Cardiac resynchronization therapy (CRT) implantation in patients with cancer is safe with a low risk of procedure-related complications comparable with the general population.
• ▪CRT in patients with cancer resulted in significant improvement in New York Heart Association class and objective improvement in left ventricular ejection fraction and left ventricular and left atrial volumes.
• ▪Active but potentially treatable malignancy with reasonable prognosis should not preclude therapy such as CRT, which improves symptoms and quality of life.

Most clinical trials of cardiac resynchronization therapy (CRT) excluded patients with active or recent cancer, and CRT is underutilized in this population, with one study reporting an implantation rate of only 21.3% in eligible patients.¹ Our study sought to investigate the benefit of CRT in patients with cancer by retrospectively analyzing the outcomes of patients who underwent CRT implantation across a 12-year period at our tertiary cancer hospital.

Procedure logs from a single-center tertiary cancer hospital were used to identify patients who underwent CRT procedures from September 2012 to February 2024. Patients were included if they underwent a successful CRT device implant. Data were extracted from the electronic health record. This study was approved by the institutional review board, and the need for an informed consent was waived given the retrospective nature of the study. The research reported has adhered to the relevant ethical guidelines.

49 patients with a new CRT device implantation were identified. Baseline patient characteristics are presented in Table 1. Most patients had nonischemic cardiomyopathy (36 of 49). Anthracycline-associated cardiomyopathy was recorded for 8 patients. 3 patients (6%) had a procedural complication including a small pericardial effusion, a coronary sinus dissection, and a small middle cardiac vein dissection with right atrial lead dislodgement needing revision with no procedure-related death. 46 of 49 patients (94%) had clinical follow-up at our center, and 43 of 49 (88%) had follow-up echocardiograms available.

Table 1.

Cohort demographics

Characteristics	N = 49	Malignancy (any)	n (%)
	Mean ± SD/ n (%)		46 (94)
Age (year)	68 ± 11	Malignancy type:
Sex (male)	37 (75)	Solid	29 (59)
Hypertension	39 (80)	Hematologic	17 (35)
Hyperlipidemia	35 (71)	Malignancy active at CRT	26 (53)
Diabetes	21 (43)	Cardiomyopathy cause:
Chronic kidney disease	11 (22)	Ischemic	13 (27)
Atrial fibrillation	14 (29)	Nonischemic	36 (74)
Coronary artery disease	21 (42)	Anthracycline induced	8 (22.2)
History of PCI	7 (14)	GDMT:
History of CABG	3 (6)	Beta blocker	42 (86)
Peripheral arterial disease	1 (2)	RAAS inhibitor	36 (74)
Prior cardiac arrest	3 (6)	MRA	7 (14.3)
Smoker	22 (45)	Nitrate/hydralazine	5 (10)
Conduction disease:		Any GDMT	48 (98)
2nd degree	2 (4)	CRT indication:
3rd degree	6 (13)	BBB with prolonged QRS	37 (76)
LBBB	26 (53)	High pacing burden	9 (18)
RBBB	7 (14)	Both high pacing burden and BBB	3 (6)

AV = atrio-ventricular; BBB = bundle branch block; CABG = coronary artery bypass graft; CRT = cardiac resynchronization therapy; GDMT = guideline-directed medical therapy; ICD = implantable cardioverter defibrillator; LBBB = left bundle branch block; MRA = mineralocorticoid receptor antagonist; PCI = percutaneous coronary intervention; RAAS = renin-angiotensin-aldosterone system; RBBB = right bundle branch block.

At a median follow-up of 109 days (interquartile range 10–520 days), there were significant improvements in QRS duration (Table 2) and New York Heart Association class (Table 3). Follow-up echocardiogram performed at a median of 139 days (interquartile range 20–539) showed statistically significant improvements in left ventricular (LV) ejection fraction (LVEF), LV end diastolic and end systolic volumes by biplane, and left atrial (LA) volume index (Table 2); 5 of 49 (10%) died of noncardiac causes, unrelated to device implant within 1 year.

Table 2.

QRS duration and echocardiographic measurements following CRT implant

Outcome	n	Pre-CRT (mean ± SD)	Post-CRT (mean ± SD)	Δ pre - post (mean ± SD)	P value
QRS duration (ms)	47	156 ± 18	143 ± 25	−13 ± 25	.0009∗
LVEF (%)	43	28 ± 6	38 ± 9	10 ± 10	<0.0001∗
LVEDVi biplane (mL/m2)	43	138 ± 92	114 ± 75	−24 ± 40	0.0003∗
LVESVi biplane (mL/m2)	43	101 ± 72	76 ± 59	−24 ± 31	<0.0001∗
LAVi biplane (mL/m2)	43	34 ± 11	31 ± 12	−3 ± 9	0.028∗

CRT = cardiac resynchronization therapy; IQR = interquartile range; LAVi = left atrial volume index; LVEDVi = left ventricular end diastolic volume index; LVEF = left ventricular ejection fraction; LVESVi = left ventricular end systolic volume index; SD = standard deviation.

^∗P values indicate statistical significance of < .05.

Table 3.

Improvement in NYHA Class following CRT

NYHA Class (N=46)	Pre-CRT n (%)	Post-CRT n (%)	Δ pre - post n (%)	P value
Class 1	1 (2%)	20 (44%)	+19 (42%)
Class 2	15 (33%)	22 (48%)	+7 (15%)
Class 3	30 (65%)	4 (9%)	−26 (54%)	<0.0001∗

NHYA = New York Heart Association.

^∗P value indicate statistical significance of < .05.

This study examined a single cancer center’s real-world experience of CRT implantation in individuals with active cancer and cancer survivors. We found that CRT implantation was safe, with a low risk of procedure-related complications and no deaths. CRT therapy resulted in significant improvements in patient symptoms as assessed by New York Heart Association class and an objective improvement in LVEF, LV, and LA volumes.

CRT is a critical tool in improving morbidity and mortality in selected patients with heart failure (HF) with reduced ejection fraction (HFrEF), carrying a strong recommendation in guidelines supported by multiple trials across ischemic and nonischemic etiologies.² However, patients with active or recent cancer were excluded from the landmark trials. As cancer management evolves and more patients either survive their cancer diagnosis or live with chronic malignancy, they can experience morbidity and mortality from cardiovascular disease including HF.³

Our findings are consistent with a small previous multicenter prospective cohort of 30 patients with chemotherapy-induced cardiomyopathy and HF (MADIT-CHIC), which demonstrated improvements in LVEF and echocardiographic LV and LA volumes at 6 months after CRT implantation.⁴ However, unlike our study in which 53% patients had active cancer at the time of CRT, patients with active cancer who received chemotherapy within 6 months were excluded from MADIT-CHIC. Another retrospective study comparing 29 patients with chemotherapy-induced cardiomyopathy with 58 patients with nonchemotherapy-induced nonischemic cardiomyopathy found that both groups experienced similar improvements in LVEF and echocardiographic volumes after CRT implantation.⁵ CRT is likely underutilized in this population of patients with HFrEF and cancer. A previous study looking at CRT-eligible patients (LVEF ≤35%; QRS duration ≥120 ms) over a 2-year period from 2010 to 2012 at our institution found an implantation rate of only 21% (58 of 272; 27 ischemic; 31 nonischemic).¹ Despite limitations of our study including a modest number of patients, follow-up echocardiograms at different time points after CRT, and the inability to account for further changes in medical therapy after CRT, our study adds to the literature supporting consideration of CRT in appropriate patients with HFrEF and cancer, including selected patients with active cancer. Such improvements in LVEF and symptoms may qualify some patients with cancer for expanded oncologic therapeutics. Although CRT or other device-related management of HFrEF should be used judiciously in patients with an expected survival of less than 1 year, these findings highlight the role of multidisciplinary discussion between the cardiologist and oncologist given that an active but treatable malignancy with a reasonable prognosis should not preclude therapy such as CRT, which improves symptoms and quality of life.