RADIATION HEART DISEASE: MANAGEMENT STRATEGIES AMMAR CHAUDHARY MBChB, ABIM, FRCPC ASSOCIATE CONSULTANT CARDIOLOGIST KING FAISAL SPECIALIST HOSPITAL & RESEARCH CENTER - JEDDAH
Scope of the Problem ~ 50 million people worldwide have received thoracic radiation Once thought to be a radio-resistant organ, the heart is considered the most critical dose-limiting organ in radiation therapy All cardiac structures in field of radiation are at risk Main culprits: breast cancer, Hodgkin s disease, and lung cancer Relative risk of fatal MI: HD 2.2-8.8, left-sided breast cancer 2.2 Weintraub N, et al. JACC Vol. 55, No. 12, 2010
Spectrum of Cardiac Complications a. Coronary Stenosis b. Pericardial Syndromes c. Valvular Disease d. Cardiomyopathy e. Conduction Disease
Factors Increasing CV Risk in Mediastinal Radiation Carvel J, et al. J Clin Oncol 2007, 25:3991-4008
Prevention Features of modern-era radiotherapy and future goals RR of fatal MI over time 1940s RR 6.3 1980s RR 1.6 Carvel J, et al. J Clin Oncol 2007, 25:3991-4008
a. Coronary Stenosis Long latency period > 5-10 yrs (range 3-30 yrs) Animal models and clinical observation support a causal association Lesions mature after initial injury mimicking atherosclerosis, but with higher fibrosis to lipid ratio Traditional risk factors accelerate disease Incidence 5.5% - 12% Weintraub N, et al. JACC Vol. 55, No. 12, 2010 Miltényi Z, et al. Cardiovasc Radiat Med. 2004;5(1):38-43
Angiographic Features of RI CAD Ostial or proximal vessel distribution LM, LAD and RCA are susceptible in mediastinal radiotherapy LM, LAD more susceptible in left-sided chest radiation Lesions are longer and tubular compared to conventional atherosclerosis Jaworski C, et al. JACC Vol. 61, No. 23, 2013
Angiographic Features of RI CAD 19 years post mediastinal irradiation for HD
Revascularization for RI CAD Alsara O, et al. Case Rep Med. 2013;2013:834164 60 year old female Stage III NSCLC 8 years earlier Radiotherapy and chemotherapy Stable angina, positive ETT Clinical SYNTAX Score 12% EuroSCORE 1.2% CABG / PCI offered to patient
Revascularization for RI CAD Multi vessel and proximal disease distribution favour CABG Non-coronary disease can be concomitantly addressed in CABG Factors complicating surgical outcomes Sub-sternal scarring and mediastinal fibrosis Pulmonary dysfunction IMAs friable, difficult to suture, prone to premature closure Heidenreich P, et al. Heart 2009;95:252 258
CABG for RI CAD IMA suitability as surgical conduit has been questioned by clinical observations and case reports of diseased IMA Conflicting data from limited case series Screening the grafts during angiography or CTCA is advocated van Son J, et al. J Thorac Cardiovasc Surg. 1992 Dec;104(6):1539-44 Schömig K, et al. Catheter Cardiovasc Interv. 2007 Sep;70(3):359-65 Chang A, et al. J Thorac Cardiovasc Surg 2007;133:404 13
Outcome after CABG in RI CAD N = 173 retrospective Matched controls n = 305 Breast CA (53%), HD (27%) Radiation history was an independent predictor of survival Risk scores overestimated survival Wu W, et al. Circ. 2013;127:1476-1484
PCI for RI CAD Discrete lesions are appealing targets for PCI Technically feasible in low-intermediate complexity CAD Lower procedural risk compared to CABG Higher rate of restenosis post BMS PCI (86% angiographic restenosis at 6 months vs. 26% in controls)* No data on newer generation stents *Schömig K, et al. Catheter Cardiovasc Interv. 2007 Sep;70(3):359-65
PCI or CABG? No specific guideline recommendations for RI CAD Mode of revascularization should be guided by appropriateness criteria for revascularization and further individualized based on patientspecific factors Estimating operative risk in individual patients should consider additional factors not accounted for in risk scores Screen the IMAs
Back to Case 60 year old female, radiotherapy 8 years earlier and in remission CABG or PCI? Patient opts for CABG Severe bleeding secondary to adhesions Alsara O, et al. Case Rep Med. 2013;2013:834164
Therapies Under Investigation ACE inhibitors Statins Nuclear Factor - Kappa B inhibitors Weintraub N, et al. JACC Vol. 55, No. 12, 2010
b. Pericardial Syndromes: Acute Pericarditis Incidence has decreased from 20% to 2.5% with modern radiation techniques Similar clinical presentation to viral pericarditis 2015 ESC guidelines provide no specific recommendations for radiation-induced acute pericarditis 10-20% develop chronic pericarditis 70% of patients at autopsy have evidence of injury Jaworski C, et al. JACC Vol. 61, No. 23, 2013
Medical Therapy for Acute Pericarditis
Clinical Trials of Colchicine CORE (Circ, 2005) CORP (Ann Int Med, 2011) ICAP (NEJM, 2013) Design Open label RCT Double-blinded RCT Double-blind RCT Colchicine dose Colchicine 1-2 mg daily Colchicine 1-2 mg day one then 0.5 mg maintenance 0.5 mg daily (wt < 70) 1 mg (wt > 70) Patients First episode of acute pericarditis First recurrence of pericarditis First episode of acute pericarditis Outcome First recurrence at 18 months Recurrence at 18 months Incessant or recurrent pericarditis Result 32% vs 11% (p = 0.004) 55% vs. 24% (p < 0.001) 38% vs 17% (p < 0.001) Pericarditis due to viral, idiopathic, post cardiac injury, CTD
ESC Recommendations for Medical Therapy
Medical Therapy for Acute Pericarditis
b. Pericardial Syndromes: Recurrent Pericarditis
Tamponade Asymptomatic pericardial effusion is the most common pericardial syndrome Spontaneous resolution is common Cardiac tamponade requires pericardiocentesis Recurrent / persistent refractory effusions treated with a pericardial window Pericardiectomy if required is higher risk (adhesions, myopathy)
c. Valvular Disease Fibrotic thickening, retraction, and calcification Left-sided valve lesions more common (hemodynamic stress) Early occurrence (<10yrs) of regurgitation. Stenosis occurs late (20 yrs) Valve repair limited by poor outcomes (32% early severe dysfunction, 16% re-operation)* Valve replacement with lower threshold to employ minimally invasive techniques (e.g. TAVR) *Crestanello J, et al. Ann Thorac Surg 2004;78:826 31
d. Cardiomyopathy Diastolic dysfunction predominates over systolic dysfunction This population is not well represented in RCTs of evidence-based therapies for LV dysfunction, but treatment is according to HF guidelines When indicated, a sub-pectoral ICD implantation may be needed Advanced HF therapies require careful assessment of cancer-free survival Cardiac transplantation is associated with higher risks of early death, severe infections, and second cancers Terminal cancer patients undergoing palliation require therapy tailored to quality of life Jaworski C, et al. JACC Vol. 61, No. 23, 2013
e. Conduction Disease Least common consequence of radiation-induced heart disease Latency 1-23 years. Average 12 years Wide spectrum: BBB, AV block (first degree - complete heart block) Unusual to occur in isolation - a marker of myocardial fibrosis Management as per guideline recommendations. No specific considerations Yusuf SW, et al. Cardiol Res Pract. 2011 Feb 27;2011:317659
Conclusions Wide spectrum of cardiac complications Increasing cancer rates require effective prevention and treatment Outcomes with DES for RI CAD should be formally tested Optimal intervention is an individualized decision, based on a thorough risk / benefit assessment
b. Acute Pericarditis - When to Admit