Martinez, Matthew W.

Abstract Exercise training improves cardiovascular health and reduces the risk for future cardiovascular events and mortality. However, emerging evidence suggests that Masters athletes may have a higher prevalence of cardiovascular abnormalities, such as atrial arrhythmias, coronary atherosclerosis, aortic dilatation, and myocardial fibrosis, compared to their less active peers. The clinical management of Masters athletes may be challenging as available guidelines for such conditions are generally based on data derived from symptomatic sedentary patients, limiting their applicability to highly trained individuals. Other unique challenges in the clinical assessment of Masters athletes include differences in symptomatic presentations compared to sedentary individuals, potential resistance to the initiation of pharmacologic treatment, and the increasing availability of consumer wearable health data that may provide relevant information on their cardiovascular health status. The purpose of this joint EAPC/ESC and ACC Clinical Consensus Statement is to provide an in-depth update on the current state of knowledge on abnormal cardiovascular findings in Masters athletes. We present an expert-based approach on the diagnostic assessment, management, and prognosis of (i) atrial fibrillation, (ii) bradyarrhythmias, (iii) ventricular arrhythmias, (iv) coronary atherosclerosis, (v) aortic dilatation, (vi) myocardial fibrosis, and (vii) exercise-induced arrhythmogenic cardiomyopathy. Clinical challenges, areas of ongoing controversy, and uncertainty and the potential underlying mechanisms are discussed. We also present future perspectives and research directives to further refine current best practice strategies. This includes the need for clinical outcome studies, dedicated randomized controlled trials in athletes, and international registries with diverse populations and longitudinal follow-up to evaluate the natural history of cardiac abnormalities and facilitate development of evidence-based approaches in the clinical management of Masters athletes with cardiovascular abnormalities.

Introduction Multi-detector computed tomography (MDCT) is commonly used to identify pulmonary vein and left atrial anatomy prior to catheter ablation for atrial fibrillation (CAAF). Additionally, transesophageal echocardiography (TEE) is utilized to exclude left atrial/left atrial appendage thrombus (ICT). Whether MDCT alone can be used to exclude thrombus obviating the need for TEE is unknown. Methods All Pts referred for CAAF at Mayo Clinic between March 2004 and October 2006 were included. Clinical data (including CHADS score), 64 slice MDCT (non-ECG gated), TEE and intra-cardiac echocardiograph (ICE) were all performed and recorded. Image data was reviewed independently and blinded. The left atrial appendage (LAA) was defined as fully opacified or underfilled. An underfilled LAA was further interrogated using a region of interest over the filling defect and mean attenuation in Hounsfield Units (HU) were recorded. Results In total 400 Pts (mean age 56 ± 10 yrs; 76% male; EF 56 ± 10 % ) were included. 362 had no ICT by TEE nor filling defect by MDCT. 38 patients had an underfilled LAA in whom ICT was confirmed by TEE in 7. Sensitivity and specificity of MDCT for ICT was 100% and 92% respectively with a NPV of 100%. In 19 Pts with underfilled LAA’s, a mean LAA emptying velocity was found to be significantly reduced at 26 cm/s (6 – 61 cm/s). Those with a thrombus had a mean attenuation value below 70 HU. CHADS2 score was higher (2.0 versus 1.0) in Pts with LAA filling defect versus those without LAA filling defect. All Pts with confirmed thrombus were taking Warfarin. ICT was not seen in any Pts aged <52 yrs with CHADS score ≤1. Conclusions Sensitivity and specificity of MDCT for detection of LAA thrombus is high. LAA filling defects on MDCT correlate with low emptying velocities by TEE and low attenuation value in HU. These data would suggest that in the absence of MDCT filling defect, no further imaging is required. TEE should be utilized prior to CAAF to investigate MDCT filling defects. Multidetector Computed Tomography for the Detection of LAA Thrombus

Background: Radiation therapy (RT) to the chest may induce various combined cardiac problems such as constrictive pericarditis (CP), restrictive myocardial disease, and coronary artery disease. Therefore, it was hypothesized that the MRI and transthoracic echocardiographic (TTE) findings in patients with CP may differ according to the history of RT. Methods: A total of 68 patients with CP who performed both TTE and MRI study at Mayo Clinic from 2002 to 2008 were reviewed and divided into two groups according to the history of RT; RT group (group I, n=13, 53.6±9.8 years, 8 males) versus no RT group (group II, n=55, 59.0±14.8, 45 males). Results: The results of TTE study were summarized in table . Early diastolic velocity of septal mitral annulus (E′) and deceleration time (DT) of mitral inflow was significantly lower, and the ratio of early diastolic mitral inflow velocity (E) to E′ is significantly higher in group I than in group II. Left atrial volume index (LAVI) was significantly lower and LA area and left ventricular end-diastolic dimension (LVEDD) was significantly smaller in group I than in group II. Delayed enhancement of pericardium was the only significant finding in MRI and significantly prevalent in group I than in group II (100.0% in group I vs 63.6% in group II, p=0.012). The other MRI findings including pericardial thickness, left ventricular and right ventricular ejection fraction, and the presence of pericardial and pleural effusion were not different between the groups. Conclusion: In CP patients with the history of RT compared to patients without history of RT, E′ and DT was significantly lower, LAVI and LVEDD were smaller, pericardial DE in MRI was invariably found. The lower E′ velocity and decreased chamber size and volumes may be explained by RT induced coexisting myocardial disease. TTE findings of the patients

Objective: Recent MRI studies have demonstrated the common occurrence of late gadolinium enhancement (LGE) in cardiac amyloidosis (CA). However, the association of LGE presence and pattern with other clinical, morphological, functional, and biochemical parameters has not yet been demonstrated. It is important to define this association, since many of these parameters (NYHA class, ventricular thickness, cardiac biomarkers) have prognostic implications. Methods: Of 151 patients with confirmed systemic amyloidosis who underwent LGE cardiac MRI between January 2006 and December 2007 to evaluate for possible CA, 120 (AL 100, senile 9, and familial 11) were included after meeting of inclusion and exclusion criteria. Cine MRI images were analyzed for morphologic and functional data. LGE images were analyzed for presence and pattern of LGE. Clinical data including ECG’s and cardiac biomarkers was obtained. Results: LGE evidence of CA was present in 95 patients and absent in 25 patients. Three main patterns of LGE were observed. These were global diffuse transmural (homogenous or heterogenous) or subendocardial, suboptimally nulled myocardium without clear hyperenhancement, and focal patchy LGE. Symptoms, morphologic/functional variables, ECG voltages, and cardiac biomarker levels were worst in patients with global diffuse LGE, followed by suboptimally nulled myocardium, focal patchy LGE, and absent LGE groups (Table 1 ). Conclusions: The presence of LGE in amyloidosis patients is associated with worse clinical, morphologic, functional, and biochemical parameters. Amongst patients with abnormal LGE, global diffuse (transmural or subendocardial) LGE is associated with the worst profile. This provides initial evidence that the presence and pattern of LGE in CA is associated with other markers of prognosis.

Objective: In AL amyloidosis, early detection of cardiac involvement is desirable because of prognostic and therapeutic implications. Recent pilot MRI studies have demonstrated that late gadolinium enhancement (LGE) is a common finding in cardiac amyloidosis (CA) and reflects interstitial expansion due to amyloid infiltration. However it is not known whether evaluation of the myocardial substrate via LGE MRI may allow for earlier detection of CA compared with morphological assessment on the basis of increased left ventricular thickness (LVT). Methods: Between January 2006 and December 2007, 100 patients with confirmed AL amyloidosis underwent LGE MRI at our institution to evaluate for CA. Morphological evidence of CA was considered to be present when LVT was increased (mean of septum and inferolateral wall > 12 mm). LGE images were analyzed for presence and pattern of LGE. Clinical data was also reviewed. Results: Increased LVT was present in 69 patients. Abnormal LGE images were present in 76 patients (global diffuse transmural or subendocardial LGE in 43, suboptimally nulled myocardium in 18, and focal patchy LGE in 15 patients). LGE was present in 21 of 22 patients with a diagnosis of CA on cardiac biopsy. Seven patients (10%) with increased LVT did not have LGE. Conversely of 31 pts with normal LVT, 14 (45%) had abnormal LGE on MRI (usually suboptimally nulled myocardium or focal patchy LGE) and also had significantly higher incidence of low voltage ECG (50% vs. 0%), lower absolute limb lead voltage (6.5±3 vs. 9.7±2.6 mm), increased RV thickness (4.9±1.1 vs. 4.1±1) and higher BNP (316±376 vs. 107±103) compared to 17 patients without LGE (Table 1 ). Conclusions: MRI LGE is common in patients with CA and evaluation of the myocardial substrate using this technique may allow for earlier detection of cardiac involvement in AL amyloidosis compared with morphological assessment on the basis of increased LVT.

Background— Constrictive pericarditis (CP) is a disabling disease, and usually requires pericardiectomy to relieve heart failure. Reversible CP has been described, but there is no known method to predict the reversibility. Pericardial inflammation may be a marker for reversibility. As a pilot study, we assessed whether cardiac magnetic resonance imaging pericardial late gadolinium enhancement (LGE) and inflammatory biomarkers could predict the reversibility of CP after antiinflammatory therapy. Method and Results— Twenty-nine CP patients received antiinflammatory medications after cardiac magnetic resonance imaging. Fourteen patients had resolution of CP, whereas 15 patients had persistent CP after 13 months of follow-up. Baseline LGE pericardial thickness was greater in the group with reversible CP than in the persistent CP group (4±1 versus 2±1 mm, P =0.001). Qualitative intensity of pericardial LGE was moderate or severe in 93% of the group with reversible CP and in 33% of the persistent CP group ( P =0.002). Cardiac magnetic resonance imaging LGE pericardial thickness ≥3 mm had 86% sensitivity and 80% specificity to predict CP reversibility. The group with reversible CP also had higher baseline C-reactive protein and erythrocyte sedimentation rate than the persistent CP group (59±52 versus 12±14 mg/L, P =0.04 and 49±25 versus 15±16 mm/h, P =0.04, respectively). Antiinflammatory therapy was associated with a reduction in C-reactive protein, erythrocyte sedimentation rate, and pericardial LGE in the group with reversible CP but not in the persistent CP group. Conclusions— Reversible CP was associated with pericardial and systemic inflammation. Antiinflammatory therapy was associated with a reduction in pericardial and systemic inflammation and LGE pericardial thickness, with resolution of CP physiology and symptoms. Further studies in a larger number of patients are needed.

Background— Primary amyloidosis has a poor prognosis as a result of frequent cardiac involvement. We recently reported a high prevalence of intracardiac thrombus in cardiac amyloid patients at autopsy. However, neither the prevalence nor the effect of anticoagulation on intracardiac thrombus has been evaluated antemortem. Methods and Results— We studied all transthoracic and transesophageal echocardiograms of cardiac amyloid patients at the Mayo Clinic. The prevalence of intracardiac thrombosis, clinical and transthoracic/transesophageal echocardiographic risks for intracardiac thrombosis, and effect of anticoagulation were investigated. We identified 156 patients with cardiac amyloidosis who underwent transesophageal echocardiograms. Amyloidosis was the primary type (AL) in 80; other types occurred in 76 patients, including 56 with the wild transthyretin type, 17 with the mutant transthyretin type, and 3 with the secondary type. Fifth-eight intracardiac thrombi were identified in 42 patients (27%). AL amyloid had more frequent intracardiac thrombus than the other types (35% versus 18%; P =0.02), although the AL patients were younger and had less atrial fibrillation. Multivariate analysis showed that atrial fibrillation, poor left ventricular diastolic function, and lower left atrial appendage emptying velocity were independently associated with increased risk for intracardiac thrombosis, whereas anticoagulation was associated with a significantly decreased risk (odds ratio, 0.09; 95% CI, 0.01 to 0.51; P <0.006). Conclusions— Intracardiac thrombosis occurs frequently in cardiac amyloid patients, especially in the AL type and in those with atrial fibrillation. Risk for thrombosis increased if left ventricular diastolic dysfunction and atrial mechanical dysfunction were present. Anticoagulation therapy appears protective. Timely screening in high-risk patients may allow early detection of intracardiac thrombus. Anticoagulation should be carefully considered.

Background— Patients with primary amyloidosis (AL type) have a poor prognosis, in part due to frequent cardiac involvement. Although intracardiac thrombus has been reported in anecdotal cases, neither its frequency nor its role in causing mortality is known. Furthermore, the clinical and echocardiographic variables that may be associated with thromboembolism in cardiac amyloidosis have not been defined. Methods and Results— A total of 116 autopsy or explanted cases of cardiac amyloidosis (55 AL and 61 other type) were identified in the Mayo Clinic. Forty-six fatal nonamyloid trauma cases served as controls. Each heart was examined for intracardiac thrombus. The cause of death was determined from autopsy and clinical notes. Intracardiac thrombosis was identified in 38 hearts (33%). Twenty-three had 1 thrombus, whereas 15 had 2 to 5 thrombi. Although subjects in the AL group were younger and had less atrial fibrillation than those with other types of amyloidosis, the AL group had significantly more intracardiac thrombus (51% versus 16%, P <0.001) and more fatal embolic events (26% versus 8%, P <0.03). Control hearts had no intracardiac thrombus. The presence of both atrial fibrillation and AL was associated with an extremely high risk for thromboembolism (odds ratio 55.0 [95% confidence interval 8.1 to 1131.4]). By multivariate analysis, AL type (odds ratio 8.4 [95% confidence interval 1.8 to 51.2]) and left ventricular diastolic dysfunction (odds ratio 12.2 [95% confidence interval 2.7 to 72.7]) were independently associated with thromboembolism. Conclusions— A high frequency of intracardiac thrombosis was present in cardiac amyloidosis. Furthermore, thromboembolism caused significant fatality. Several risk factors for thromboembolism were identified. Early screening, especially in high-risk patients, and early anticoagulation might reduce morbidity and mortality.