Usefulness of Total 12-Lead QRS Voltage as a Clue to Diagnosis of Patients With Cardiac Sarcoidosis Severe Enough to Warrant Orthotopic Heart Transplant

Key Points

Question  Is total 12-lead electrocardiographic QRS voltage a diagnostic clue for patients with cardiac sarcoidosis severe enough to warrant orthotopic heart transplant?

Findings  In this case-series study, the mean total 12-lead QRS voltage in 16 patients with severe heart failure caused by extensive cardiac sarcoidosis (101 mm) was similar to that determined in patients with cardiac amyloidosis, carcinoid heart disease, and severe cardiac adiposity. In contrast, patients with fatal idiopathic dilated cardiomyopathy had a mean total 12-lead QRS voltage (153 mm).

Meaning  The low total 12-lead QRS voltage measurement on electrocardiogram in patients with cardiac sarcoidosis, despite increased weight of the native heart, may be a clue to its correct diagnosis before orthotopic heart transplant.

Importance  Severe heart failure caused by cardiac sarcoidosis is difficult to diagnosis without biopsy.

Objective  To assess whether total electrocardiographic 12-lead QRS voltage may be a clue to diagnosis.

Design, Setting, Participants  Case-series study with cases collected at Baylor University Medical Center at Dallas, Dallas, Texas, from January 13, 2005, to January 24, 2017. The clinical records of 16 patients with severe heart failure caused by cardiac sarcoidosis were studied. Examination of total 12-lead electrocardiographic QRS voltage (peak of the R wave to the nadir of either the Q or S wave, whichever was deeper) was performed prior to orthotopic heart transplant (OHT). Gross and microscopic pathologic specimens of the native hearts were studied.

Main Outcomes and Measures  The primary outcome was to correlate the total 12-lead QRS voltage measurement with various morphologic features in the native diseased heart.

Results  The 16-patient study group consisted of 8 men and 8 women; 12 (75%) were white and 4 (25%) were black. At the time of OHT, patient age ranged from 50 to 67 years (mean, 57 years). Cardiac sarcoidosis was diagnosed by pre-OHT biopsy results in 2 (13%) patients and by examination of the native heart after OHT in 14 (87%) patients. Total nonpaced 12-lead QRS voltage mean was 117 mm (range, 52-155 mm) for 8 patients and total paced 12-lead QRS voltage was 90 mm (range, 67-161 mm) for 12 patients. These low mean values were similar to those of patients with carcinoid heart disease (mean [SD], 105 [40] mm), cardiac amyloidosis (104 [35] mm), and severe cardiac adiposity (120 [31] mm) studied at necropsy or after OHT. In contrast, mean (SD) values were 323 (109) mm in patients with massive cardiomegaly, 257 mm in patients with severe aortic stenosis, 272 (86) mm in patients with severe pure aortic regurgitation, 220 (67) mm in patients with severe pure mitral regurgitation, 197 (64) mm in patients with hypertrophic cardiomyopathy, and 153 (40) mm in patients with idiopathic dilated cardiomyopathy.

Conclusions and Relevance  Most patients diagnosed with cardiac sarcoidosis causing severe heart failure and warranting OHT had low total 12-lead QRS voltage measurements despite having native hearts of increased weight. This finding may provide a clue to the diagnosis of this disease.

The first study of the utility of total 12-lead electrocardiographic QRS voltage was published in 1982 and reported findings for patients with aortic valve stenosis.¹ Subsequently, total 12-lead QRS voltage has been reported in a number of other conditions.² In each of those studies, the total 12-lead QRS voltage was compared with the weight of the native diseased heart at necropsy or after orthotopic heart transplant (OHT). The present report describes total 12-lead QRS voltage of 16 patients undergoing OHT because of severe heart failure due to cardiac sarcoidosis.

From January 13, 2005, through January 24, 2017, 16 patients at Baylor University Medical Center at Dallas (BUMC), Dallas, Texas, had OHT because of cardiac sarcoidosis. The study was approved by the Baylor Research Institute Institutional Review Board, which also waived the need for informed patient consent.

Each patient’s native heart was examined by one of us (W.C.R.), and he prepared the final report. Accurate scales were used to weigh the native heart after fixation in formaldehyde for several days. The aorta and pulmonary trunk were excised about 2 cm above the sinotubular junction; all extraneous tissue was removed before weighing. Prior to weighing, the heart was opened and excessive water or formaldehyde was removed from its surfaces by gentle patting with paper towels. Clinical records and all electrocardiograms recorded at BUMC were reviewed and examined. The total 12-lead QRS voltage (defined as the distance in millimeters from the peak of the R wave to the nadir of either the Q or S wave, whichever was deeper) was measured by 2 of us (W.C.R. and T.M.B.). The statistics performed were limited to the calculation of the mean and SD. No statistical package or system was required for these calculations.

The 16-patient study group consisted of 8 men and 8 women; 12 were white and 4 were black. Pertinent morphologic and electrocardiographic findings for the 16 patients are detailed in the Table and illustrated in Figure 1 and Figure 2. At the time of OHT, the patient age ranged from 50 to 67 (mean, 57) years. Cardiac sarcoidosis was diagnosed by biopsy in 2 patients (13%) and by examination of the native heart after OHT in 14 patients (87%). The body mass index (calculated as the weight in kilograms divided by height in meters squared) ranged from 18.8 to 32.9 (mean, 27.1). Before OHT, 6 of the 16 patients (37%) had atrial fibrillation; 12 (75%) had bundle branch block (4 with left bundle branch block and 8 with right bundle branch block), and 7 (44%) had complete heart block. The low-density lipoprotein cholesterol levels before OHT ranged from 52 to 147 mg/dL (mean, 93 mg/dL) (to convert to millimoles per liter, multiply by 0.0259). Only patient 12 (Table) had greater than 75% in cross-sectional area narrowing of 1 or more major epicardial coronary arteries (defined as the right, left main, left anterior descending, and left circumflex).

The native heart weighed from 420 to 605 g (mean, 509 g) for the 8 men and from 370 to 600 g (mean, 442 g) for the 8 women. The quantity of cardiac adipose tissue was excessive such that the heart floated in a container of formaldehyde in 7 of the 11 hearts (64%) in which that determination was made. (Cardiac adipose tissue weighs less than myocardium.) Typical sarcoid granulomas were found in the walls of the right and left ventricles and in the ventricular spectrum in all patients. In 1 patient, however, granulomas were seen in the left ventricular wall (“button”) removed for insertion of a left ventricular assist device but were not seen in the heart specimen after OHT. The number of granulomas and extent of ventricular wall scarring were subjectively quantified on a scale of 1+ (mild scarring) to 3+ (severe scarring). The distribution of sarcoid lesions is shown in the gross pathologic heart specimens for 3 of the 16 patients (Figure 2).

QRS voltage was measured using a 10-mm standard scale (10 mm = 1 mV) in all 12 leads of an electrocardiogram for all 16 patients. Mean total nonpaced 12-lead QRS voltage was 117 mm (range, 52-155 mm) for 8 patients: 3 men (mean, 137 mm [range, 121-155 mm]) and 5 women (mean, 105 mm [range, 52-144 mm]). Mean total paced 12-lead QRS voltage was 90 mm (range, 67-161 mm) for 12 patients: 6 men (mean, 81 mm [range, 47-103 mm]) and 6 women (mean, 98 mm [range, 67-161 mm]).

Described herein are findings from measurement of total 12-lead electrocardiographic QRS voltage and findings from the examination of the native heart in 16 patients who underwent OHT because of severe heart failure due to cardiac sarcoidosis. These low total 12-lead nonpaced (mean, 117 mm) and paced (mean, 90 mm) QRS voltage values are similar to those values previously reported in patients with a variety of other conditions after OHT or necropsy.² The mean (SD) total 12-lead QRS voltage for several cardiac diseases is as follows: 105 (40) mm in 19 patients with carcinoid heart disease,³ 104 (35) mm in 30 patients with cardiac amyloidosis,⁴ and 120 (31) mm in 30 patients with severe cardiac adiposity.⁵ In contrast, mean (SD) total 12-lead QRS voltage was 323 (109) mm in 17 patients with massive cardiomegaly (weight of native heart, >1000 g),⁶ 257 mm in 50 patients with severe aortic stenosis,¹ 272 (86) mm in 30 patients with severe pure aortic regurgitation,⁷ 220 (67) mm in 24 patients with pure mitral regurgitation,⁸ 197 (64) mm in 57 patients with hypertrophic cardiomyopathy,^9,10 and 153 (40) mm in 49 patients with idiopathic dilated cardiomyopathy.¹¹ Thus, most of our patients (15 of 16 [94%]) with severe cardiac sarcoidosis, despite having native hearts of increased weight (>350 g in women and >400 g in men), had low total 12-lead QRS voltages.

A limitation of the present report is that the time interval between the recording of the electrocardiogram tracing and the OHT procedure was rather long for some patients. It is likely, however, as described previously in patients with idiopathic dilated cardiomyopathy,¹² that the total 12-lead QRS voltage would decrease as the time interval increases between initially developing cardiac sarcoidosis and OHT procedure.¹²

The strong features of the present report are that both the weight of the native heart and the extent of the cardiac sarcoid lesions were known for all 16 patients. To our knowledge, electrocardiographic QRS voltage has not been described previously in patients with cardiac sarcoidosis.¹²

Most patients diagnosed with cardiac sarcoidosis causing severe heart failure and warranting OHT had low total 12-lead QRS voltage measurements despite having native hearts of increased weight. This finding may provide a clue to the diagnosis of this disease.

Corresponding Author: William C. Roberts, MD, Baylor Heart and Vascular Institute, 621 N Hall St, Ste H030, Dallas, TX 75226 (william.roberts1@bswhealth.org).

Accepted for Publication: September 19, 2017.

Published Online: November 15, 2017. doi:10.1001/jamacardio.2017.4172

Author Contributions: Dr Roberts and Ms Becker had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Roberts, Becker.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Roberts.

Critical revision of the manuscript for important intellectual content: Roberts.

Administrative, technical, or material support: Hall.

Study supervision: Roberts.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.