Bradyarrhythmia in dogs can trigger syncope, activity intolerance, heart failure, and sudden death. The causes of bradyarrhythmia are varied, such as 2nd atrioventricular (AV) block Mobitz type 1, 3rd degree AV block, and sinus node disease (12). However, the etiology remains unclear, despite various hypotheses regarding the underlying pathology of the myocardial conduction system, including fibrosis, endocarditis, amyloidosis, and myocarditis (7,12). When bradycardia is accompanied with symptoms such as syncope, it is called symptomatic bradyarrhythmia, and it is an indication for pacemaker implantation. Cardiac pacemaker implantation is the only effective and permanent treatment in symptomatic bradycardia (11). Cardiac pacing prevents congestive heart failure, which is caused by AV block, or sudden death due to bradyarrhythmia (16).

Hypertension is a common compensatory mechanism of bradycardia in human medicine (14). Also, persistent reduction in heart rate might reset the baroreflex which is one of the homeostatic mechanisms to maintain normal blood pressure (8). However, there is no previous report of severe hypertension due to persistent bradycardia in veterinary medicine (1).

A 10-year-old spayed female Cocker spaniel weighing 6.64 kg was was presented with a sign of syncope. The etiology, which led to bradycardia and severe hypertension was suspected to be myxomatous mitral valve disease and insufficient cardiovascular circulation; therefore, pimobendan 0.25 mg/kg, enalapril 0.5 mg/kg, furosemide 1 mg/kg, and spironolactone 1 mg/kg per oral (PO) q 12 hr were prescribed in a local animal hospital. However, there was no improvement in clinical signs and two other episodes of syncope were also reported (Day 1).

Physical examination showed that the dog’s heart rate was 54 beats/min (reference range, 100 to 140 beats/min), and systolic blood pressure was 200 mmHg (reference range, 90 to 140 mmHg; Doppler method) (10). When auscultation was performed, the patient had grade 4/6 murmur bilaterally and lung sound was normal. Blood examination showed only a mild elevation of blood urea nitrogen (BUN, 49 mg/dL; reference range 7-27 mg/d) level. Electrolyte imbalance and hypothyroidism, which could be the cause of bradycardia, was excluded with blood analysis (Table 1).

Table 1 . Blood analysis of the patient.

Parameter	Reference range	Result
WBC (103/μL)	5.05-16.76	13.76
RBC (106/μL)	5.65-8.87	7.02
PLT (103/μL)	148-484	471
BUN(mg/dL)	9.6-31.4	35.9
Creatinine(mg/dL)	0.4-1.3	0.96
Ca (mg/dL)	9.0-11.9	8.4
P(mg/dL)	2.3-6.3	4
SDMA (mg/dL)	0-14	8
Glucose (mg/dL)	70-143	102
ALT (U/L)	5.8-83.3	49
AST (U/L)	11.7-42.5	25
ALP (U/L)	0-97.9	65
Total bilirubin (mg/dL)	0-14	10
Albumin(g/dL)	2.6-4.4	3.22
NH3 (μg/dL)	16-75	29
Na (mmol/L)	145.1-152.6	148
K (mmol/L)	3.6-5.5	5.3
Cl (mmol/L)	113.2-122.9	116
total T4 (μg/dL)	1.0-4.0	1.45
free T4 (ng/dL)	0.77-3.49	1.25
TSH (ng/dL)	0.05-0.42	0.21
D-dimer	< 0.2	< 0.1

Thoracic radiograph showed a straight shape of the left atrium (LA), a round cardiac apex, and right cardiac silhouette. The vertebral heart score (VHS) was 11.5 vertebra (Fig. 1A, B). On the echocardiogram, the left ventricular internal dimension at diastole (LVIDd) was found to increase to 3.712 cm which was calculated as 2.127 for normalized LVIDd. LA to aorta ratio had also increased to 1.72, indicating dilation of LV and LA. Peak E velocity was 0.75 m/s. There were mild degenerative changes of the mitral and tricuspid valves with mild regurgitation in both valves. Aortic regurgitation was also detected. Evidence of infection or tumor was not found (Fig. 1C, D).

Figure 1. (A, B) Thoracic radiograph of the patient before pacemaker implantation. The left lateral (A) and ventrodorsal (B) image show a straight shape of the left atrium, a round cardiac apex, and right cardiac silhouette. (C, D) Echocardiograph of the patient before pacemaker implantation. Right parasternal long four chamber view (C) and M-mode of short axis (D) shows mild degenerative changes of the mitral valve and enlarged left ventricle.

Electrocardiographic (ECG) findings revealed atrioventricular (AV) block alternating 3rd degree AV block (Fig. 2A). Atropine test was performed to distinguish intrinsic cardiac disease to vagal tone induced bradycardia. However, despite an intravenous (IV) injection of atropine 0.04 mg/kg, the heart rate did not increase above 150% before the injection and there was no change in the QRS complex (Fig. 2B).

Figure 2. Lead II ECG record of the patient revealed 3rd degree AV block (A). Heart rate and AV block was not significantly changed even 5 mins after atropine injection (B). Paper speed: 50 mm/s; sensitivity: 1.0 cm/1.0 mV.

To investigate the cause of the severe hypertension, abdominal sonography was performed. The size of bilateral adrenal glands and echogenicity were normal. Echogenicity of both kidneys was slightly increased. To correct the hypertension, enalapril was prescribed at a dose of 0.5 mg/kg PO q12 hr as an antihypertensive medication, but blood pressure did not decrease after 1-week administration. On day 8, blood pressure was rechecked and measured as 200 mmHg, so hydralazine was prescribed at a dose of 0.5 mg/kg PO q12 hr for 2 weeks. However, there was no change in blood pressure, so amlodipine was added at a dose of 0.3 mg/kg PO q12 hr for 2 weeks. Even though three types of antihypertensive medications were prescribed, blood pressure was still measured above 200 mmHg.

We hypothesized that severe hypertension and dilation of the left LA and LV correlated with the AV block and there was no sufficient indication for cardiac medication. Therefore, we halted all cardiac and antihypertensive medications and decided to insert a pacemaker to correct the bradycardia and monitored the hypertension (Day 36).

A permanent single-chamber pacemaker (Medtronic CapSure^® EPI 4965, Pacemaker generators, Medtronic Inc, MN, USA) was implanted in this patient (Day 40). Before implantation of the permanent pacemaker, response to pacemaker was evaluated using a temporary pacemaker (Medtronic Inc). For this procedure, only midazolam (0.3 mg/kg, IV; Bukwang Midazolam Inj., Bukwang Pharm Co., Seoul, Korea) and remifentanil (6-12 μg/kg/h, continuous rate infusion; Kabi Remifentanil Inj., Fresenius Kabi Korea, Seoul, Korea) were used, because bradycardia of the patient had high risk for general anesthesia. During the procedure, arterial blood pressure (ABP) was monitored using an invasive blood pressure measuring method using arterial catheter which was connected to a transducer system (Truwave, Edward Lifescience, Germany; CARESCAPE Monitor B650, GE Healthcare Finland Oy). Under fluoroscopic guidance, we approached the left jugular vein and the 5 Fr transvenous temporary pacing lead was placed on the apex of right ventricle. The minimum rate of pacing was set at 80 beats/min according to previous study (6). After setting the temporary pacemaker, the heart rate was immediately corrected from 40 to 80 beats/min and systolic ABP decreased from 200 to 120 mmHg (Fig. 3). Since the response to the temporary pacemaker was good, we decided to anesthetize the patient and implant the permanent pacemaker approaching the right jugular vein. For the procedure, propofol (4 mg/kg, IV; Anepol Inj., Hana Pharm Co., Seoul, Korea) was used for induction, and general anesthesia was maintained with isoflurane (Ifran Liq., Hana Pharm Co.). The minimum heart rate was set at 80 beats/min, just like the temporary pacemaker, and the maximum heart rate was set at 180 beats/min according to previous study (6). The temporary pacing generator was then removed under fluoroscopy. The patient was stable and recovered from general anesthesia, and the heart rate and systolic ABP were maintained in post-anesthesia monitoring.

Figure 3. Arterial blood pressure (A) and heart rate (B) records during pacemaker implantation procedure. Right after pacing stimulation, heart rate and blood pressure were corrected and maintained until recovery from anesthesia.

Eight weeks after pacemaker implantation, a recheck examination was performed to evaluate the pacemaker program and clinical signs. The owner said that the dog had not shown any sign of syncope. The sensing and pacing capability of the pacemaker were all within the normal range. The stable heart rate and blood pressure were maintained at 96 beats/mins and 140 mmHg (Fig. 4A-C).

Figure 4. Thoracic radiograph of the patient after pacemaker implantation. The left lateral (A) and ventrodorsal (B) image show pacing lead, positioned properly in the apex of right ventricle. Lead II ECG record after pacemaker implantation (C). Pacing spike followed by QRS complex regularly sustained with 96 beats/min. P waves were not matched with QRS complex which means the patient still has 3rd degree AV block. Paper speed: 50 mm/s; sensitivity: 1.0 cm/1.0 mV.

In this case, sinus bradyarrhythmia was observed with syncope occurrence, and 3rd degree AV block was revealed on ECG monitoring. Moreover, considering negative response to atropine challenge test, we estimated that the etiology of bradyarrhythmia was a structural disease of the conduction system (8). Therefore, pacemaker implantation was strongly recommended in this patient.

In addition, the patient also had severe hypertension (systolic ABP > 200 mmHg) which remained despite prescription of three anti-hypersensitive drugs. Through general examination, mild elevation of BUN concentration and echogenicity of bilateral kidneys suggest that subclinical chronic kidney disease might be the etiology of hypertension (2). In addition, endocrine tumors such as phechromocytoma could not be ruled out in this patient, because we could not evaluate serum catecholamine or metanephrine concentration. However, through abdominal ultrasound, we detected normal size of adrenal glands.

We assumed that the stroke volume increased due to LV and LA dilation which was shown in echocardiography because of the 3rd degree AV block, and this provoked hypertension (9). Moreover, activation of the sympathetic nervous system could also be an important factor in the development and progression of systemic hypertension (15). The impaired heart function caused by the complete heart block might activate the sympathetic nervous system and release hormones such as norepinephrine (5), thus additionally worsening the hypertension.

When the pacemaker was implanted, heart rate and severe hypertension improved remarkably. Although clinical history of severe systemic hypertension can affect the prognosis, we expect that this case would have a good clinical outcome as in other pacemaker implantation cases (4,6), because the patient remained asymptomatic and the blood pressure was within the normal range for 6 months postoperatively. Given that severe hypertension was resolved immediately after the pacemaker implantation, the main cause might be the increased stroke volume.

In human medicine, there are a few reports that complete heart block and malignant hypertension have been resolved after pacemaker implantation (3,4,13). However, in veterinary medicine, there is no previous report of severe malignant hypertension accompanied with bradycardia which was resolved by pacemaker implantation.

To the best of our knowledge, this is the first report in veterinary medicine on the resolution of an AV block and severe systemic hypertension by implanting permanent pacemaker. The authors propose that if a patient has malignant hypertension with an AV block and there is no additional pathological cause of hypertension, it could be corrected after pacemaker implantation.

This research was supported by the 2022 scientific promotion program funded by Jeju National University.

We are very grateful to Seung-Woo Jung (DVM, DACVIM Cardiology) for the best advice and support.

The authors have no conflicting interests.