Incidence of Atrioventricular Block After Valve Replacement in Carcinoid Heart Disease
Carcinoid heart disease (CaHD) is a rare condition that has a high impact on the morbidity and mortality of its patients. Once heart failure symptoms develop in the patient with CaHD, cardiac valve surgery is often the only effective treatment. Although atrioventricular block (AVB) is a known postoperative complication of the valve surgery, the incidence of AVB in this population has not been well described.
Comprehensive records were collected retrospectively on consecutive patients with CaHD who underwent a valve surgery at a tertiary medical center from January 2001 to December 2015. We excluded patients with pre-existing permanent pacemaker (PPM).
Nineteen consecutive patients were included in this study and 18 of them underwent at least dual valve (tricuspid and pulmonary valve) replacement surgery. Our 30-day post-surgical mortality was 0%. During the 6-month observation period following the surgery, 31.5% (n = 6) required PPM implantation due to complete AVB. There was no statistical difference in baseline characteristics and electrocardiographic and echocardiographic parameters between the patients who did or did not require PPM placement.
Our study revealed that almost one-third of CaHD patients who underwent a valve replacement surgery developed AVB requiring PPM implantation. Due to high incidence of PPM requirement, we believe that prophylactic placement of an epicardial lead during the valve surgery can be helpful in these patients to reduce serious complication from placement of pacemaker lead on a later date through a prosthetic valve.
Carcinoid heart disease (CaHD) is a fibrotic valvular process that occurs in patients with longstanding carcinoid syndrome and highly elevated levels of circulating serotonin . Prior to development of effective systemic treatments for reduction of circulating serotonin levels, CaHD was reported to develop in approximately 50% of carcinoid syndrome patients . In CaHD, the right-sided heart valves are primarily affected because of their direct exposure to circulating blood serotonin, leading to right heart failure. Once patients with CaHD develop heart failure symptoms, the only effective treatment option is valve surgery, which has shown to decrease mortality and improve functional symptoms [3-8]. Majority of those patients required both tricuspid valve (TV) and pulmonary valve (PV) surgeries, preferably replacement [7, 9]. In 1995, Connolly and colleagues reported that 30-day mortality in CaHD patients undergoing cardiac surgery was 35% . Subsequent studies have demonstrated a decline in overall operative mortality to 10% or lower after 2000 [7, 10].
A potential complication of the valve surgery for CaHD patients is atrioventricular block (AVB). However, prior studies have not focused on the morbidity associated with this event and the appropriate management of this complication. We therefore sought to examine the incidence of AVB and permanent pacemaker (PPM) implantation following valve replacement in CaHD patients.
Materials and Methods
This retrospective chart review was conducted on consecutive patients with CaHD who were evaluated by a cardiothoracic surgeon for a valve replacement surgery at a tertiary medical center between January 2001 and December 2015. This study was approved by Institutional Review Board of University of South Florida and Tampa General Hospital, and was conducted in accordance with the ethical standards of the institutions and with the Helsinki Declaration.
CaHD was diagnosed with echocardiography and presence of valvular thickening associated with regurgitation or stenosis. Valve surgery was recommended in stable CaHD patients if they had functional symptoms consistent with worsening heart failure or severe valvular dysfunction. Diagnoses of comorbid conditions were determined by the International Statistical Classification of Diseases and Related Health Problems (ICD)-9 or ICD-10 codes, with the exception of coronary artery disease, which had to be confirmed by left heart catheterization. Pre- and post-surgical electrocardiogram (EKG) and transthoracic echocardiogram data were collected and reviewed by an independent cardiologist.
Cardiopulmonary bypass was preformed through midline sternotomy. Inflow arterial cannula was placed in the ascending aorta and outflow cannulas placed in the superior and inferior vena cava. Operation was performed on a beating heart at normothermia. Bioprosthetic valve was used due to favorable outcomes without need for lifetime anticoagulation . The biggest valve possible on the pulmonic position was used in order to maximize the unload of the weak right ventricle (RV). Our valve of choice was a 29-mm freestyle bioprosthesis. In order to fit the valve, the RV outflow track was consistently enlarged with a patch.
Difference in categorical and continuous variables was analyzed using Fisher’s exact test or Chi-square test and t-tests, respectively. Data were presented as mean ± standard deviation (SD) or as proportion (%). All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and STATA version 12.1 (Stata Corp., College Station, TX, USA). Reported probability values were two-sided and a P < 0.05 was considered statistically significant.
In total, 27 patients were identified with CaHD seeking surgical evaluation for valve replacement during the study period. Among them, seven patients did not undergo surgery due to extensive metastatic disease or comorbid conditions. One patient was excluded due to the presence of a PPM upon initial preoperative evaluation. After these exclusions, 19 patients were finally included in this study.
Table 1 demonstrates characteristics of study participants. The average age was 60.4 ± 1.9 years old and 57.9% were male gender. All 19 patients had symptomatic heart failure (New York Heart Association class III/IV) and were on octreotide therapy prior to the surgery. Two patients had had prior valve replacement and underwent redo valve surgery as a result of worsening disease. Sixteen patients underwent dual valve replacement (TV and PV), two patients underwent triple valve replacement (TV, PV, and aortic valve), and the other one underwent PV replacement.
|Overall (n = 19)||Post-surgical PPM placement|
|PPM (n = 6)||No PPM (n = 13)||P valuea|
|Demographic and comorbidity profile|
|Ageb, years||60.4 ± 1.9||63.2 ± 1.9||59.2 ± 2.6||0.331|
|Male||11 (57.9)||1 (16.7)||10 (76.9)||0.041|
|Hypertension||12 (63.2)||1 (16.7)||11 (84.6)||0.010|
|Diabetes mellitus||3 (15.8)||1 (16.7)||2 (15.4)||1.000|
|Hyperlipidemia||4 (21.1)||1 (16.7)||3 (23.1)||1.000|
|Coronary artery diseasec||2 (10.5)||1 (16.7)||1 (7.7)||1.000|
|Atrial fibrillation||7 (36.9)||4 (66.7)||3 (23.1)||0.129|
|Obesityd||4 (21.1)||0 (0.0)||4 (33.8)||0.255|
|NYHA class III/IV||19 (100)||6 (100)||13 (100)||–|
|Prior valve surgery||2 (10.5)||1 (16.7)||1 (7.7)||1.000|
|Prior octreotide treatment||19 (100)||6 (100)||13 (100)||–|
|Pre-surgical EKG parameters|
|First degree AVB||3 (15.8)||0 (0.0)||3 (23.1)||0.522|
|≥ Second degree AVB||0 (0)||0 (0)||0 (0)||–|
|RBBB||3 (15.8)||0 (0.0)||3 (23.1)||0.517|
|Left fascicular block||2 (10.5)||1 (16.7)||1 (7.7)||1.000|
|PR interval (ms)||167.6 ± 13.0||158.8 ± 9.8||171.6 ± 18.6||0.660|
|QRS interval (ms)||102.3 ± 4.0||104.2 ± 10.7||101.5 ± 3.7||0.765|
|Pre-surgical TTE parameters|
|LVEF (%)||54.6 ± 1.2||56.8 ± 1.9||53.5 ± 1.5||0.236|
|Reduced RV function||15 (79.0)||4 (66.7)||11 (84.6)||0.557|
|RVSP (mm Hg)||32.0 ± 3.0||35.0 ± 9.1||30.9 ± 2.8||0.566|
|Pulmonary insufficiency, moderate to severe||12 (63.2)||2 (33.3)||10 (76.9)||0.129|
|Pulmonary stenosis||11 (58.9)||3 (50.0)||8 (61.5)||1.000|
|Tricuspid regurgitation, moderate to severe||18 (94.7)||6 (100.0)||12 (92.3)||1.000|
|Tricuspid stenosis||6 (31.6)||1 (16.7)||5 (38.5)||0.605|
|Post-surgical TTE parametersa|
|LVEF (%)||55.6 ± 2.2||55.8 ± 4.0||55.5 ± 2.8||0.945|
|Reduced RV function||7 (43.8)||3 (50.0)||4 (40.0)||1.000|
|RVSP (mm Hg)||30.3 ± 2.5||36.0 ± 5.1||28.0 ± 2.7||0.161|
|Type of surgery||0.088|
|PVR||1 (6.3)||0 (0.0)||1 (7.7)|
|PVR + TVR||16 (84.2)||4 (66.7)||12 (92.3)|
|PVR + TVR + AVR||2 (10.5)||2 (33.3)||0 (0.0)|
|Post-surgical mortality||2 (10.5)||1 (16.7)||1 (7.7)||1.000|
|Operative (30 days)||0 (0.0)||0 (0.0)||0 (0.0)||–|
|During 6-months follow up||2 (10.5)||1 (16.7)||1 (7.7)||1.000|
Values are number (%) or mean ± standard deviation. aFisher’s exact test or t-test. bAverage age in years at time of surgery or during last visit. cDiagnosed via left heart catheterization. dBody mass index ≥ 30 kg/m2. AVB: atrioventricular block; AVR: aortic valve replacement; EKG: electrocardiogram; LVEF: left ventricular ejection fraction; ms: millisecond; NYHA: New York Heart Association; PPM: permanent pacemaker; PVR: pulmonary valve replacement; RBBB: right bundle branch block; RV: right ventricle; RVSP: right ventricular systolic pressure; TTE: transthoracic echocardiogram; TVR: tricuspid valve replacement.
During the 6-month observation period following surgery, 31.5% (n = 6) required PPM implantation due to complete AVB. There was no statistically significant difference in demographic and comorbidity profile, pre-procedural EKG parameters, and pre- and post-procedural echocardiographic parameters between PPM and non-PPM groups. Also, there was no significant difference in type of surgery between the two groups (P = 0.088). All two patients who underwent triple valve replacement developed AVB and required PPM placement, but number was too small to detect statistical difference. Our 30-day surgical mortality was 0%. Two patients died during the follow-up period, approximately 4 months after the surgery.
Table 2 demonstrates characteristics of patients who developed AVB and required PPM placement following the valve surgery. The mean time to PPM implantation after the surgery was 6.3 ± 0.5 days (median, 6.5 days). Device interrogation done in at least 4 months after the PPM implantation revealed that all patients were still dependent to the PPM except one patient whose interrogation result was not available.
|Patient||Surgery||Year of surgery||Prior valve surgery||Reason for PPM||Time to PPM (days)||PPM type||PPM burden in several months|
|1||TVR, PVR||2012||Yes (TVR, PVR)||CHB||6||Dual-chamber||100% V-paced|
|2||TVR, PVR, AVR||2014||None||CHB||8||Dual-chamber||NA|
|3||TVR, PVR||2015||None||CHB||7||Dual-chamber||33% A-paced|
|4||TVR, PVR||2015||None||CHB||7||Dual-chamber||19% A-paced, 100% V-paced|
|5||TVR, PVR||2004||None||CHB||5||Dual-chamber||100% V-paced|
|6||TVR, PVR, AVR||2012||None||CHB||5||Dual-chamber||87% A-paced, 11% V-paced|
AVR: aortic valve replacement; CHB: complete heart block; NA: not available; PPM: permanent pacemaker: PVR: pulmonary valve replacement; TVR: tricuspid valve replacement; A: atrial; V: ventricular.