Rory O’Hanlon

Association of Fibrosis With Mortality and Sudden Cardiac Death in Patients With Nonischemic Dilated Cardiomyopathy

IMPORTANCE Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. OBJECTIVE To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. DESIGN, SETTING, AND PATIENTS Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. MAIN OUTCOME MEASURES Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. RESULTS Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). CONCLUSIONS AND RELEVANCE Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.

Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.

IMPORTANCE Prevention strategies for heart failure are needed. OBJECTIVE To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS The St Vincents Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years). INTERVENTION Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service. MAIN OUTCOMES AND MEASURES The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure. RESULTS A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P<.001) and received more renin-angiotensin-aldosterone system-based therapy at follow-up (control, 49.6%; intervention, 56.5%; P=.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002). CONCLUSION AND RELEVANCE Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00921960.

Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies

Cardiovascular Magnetic Resonance (CMR) is recognised as a valuable clinical tool which in a single scan setting can assess ventricular volumes and function, myocardial fibrosis, iron loading, flow quantification, tissue characterisation and myocardial perfusion imaging. The advent of CMR using extrinsic and intrinsic contrast-enhanced protocols for tissue characterisation have dramatically changed the non-invasive work-up of patients with suspected or known cardiomyopathy. Although the technique initially focused on the in vivo identification of myocardial necrosis through the late gadolinium enhancement (LGE) technique, recent work highlighted the ability of CMR to provide more detailed in vivo tissue characterisation to help establish a differential diagnosis of the underlying aetiology, to exclude an ischaemic substrate and to provide important prognostic markers. The potential application of CMR in the clinical approach of a patient with suspected non-ischaemic cardiomyopathy is discussed in this review.

Recognition and Significance of Pathological T-Wave Inversions in Athletes

Background— Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1–V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations. Methods and Results— Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease. Conclusions— PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.

Cardiovascular function and the veteran athlete.

The cardiovascular benefits of exercise are well known. In contrast, the impact of lifelong endurance exercise is less well understood. Long-term high-intensity endurance exercise is associated with changes in cardiac morphology together with electrocardiographic alterations that are believed to be physiologic in nature. Recent data however has suggested a number of deleterious adaptive changes in cardiac structure, function and electrical activity, together with peripheral and cerebral vascular structure and function. This review serves to detail knowledge in relation to; (1) Cardiac structure and function in veteran endurance athletes focusing on the differentiation of physiological and pathological changes in cardiac remodelling; (2) Cardiac electrical activity and the veteran endurance athlete with attention to arrhythmias, the substrate for arrhythmia generation and the clinical significance of such arrhythmias; (3) Peripheral and cerebral vascular structure and function in ageing and endurance-trained individuals; and (4) directions for future research.

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy. AIM We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control. DESIGN A cross-sectional study in a population at risk for heart failure. METHODS Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol. RESULTS In total, 1399 patients enrolled in the St Vincents Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048]. CONCLUSION In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Aspirin Use in Heart Failure Is Low-Dose Therapy Associated With Mortality and Morbidity Benefits in a Large Community Population?

Background— Aspirin use in heart failure (HF) is controversial. The drug has proven benefit in comorbidities associated with HF; however, retrospective analysis of angiotensin-converting enzyme inhibitor trials and prospective comparisons with warfarin have shown increased risk of morbidity with aspirin use. This study aims to evaluate the association of low-dose aspirin with mortality and morbidity risk in a large community-based cohort. Methods and Results— This was a retrospective cohort study of patients attending an HF disease management program. Aspirin use at baseline and its association with mortality and HF hospitalization in the population was examined. Of 1476 patients (mean age, 70.4±12.4 years; 63% men), 892 (60.4%) were prescribed aspirin. Low-dose aspirin (75 mg/d) was prescribed to 828 (92.8%) patients. Median follow-up time was 2.6 (0.8–4.5) years. During the follow-up period, 464 (31.4%) patients died. In adjusted analysis, low-dose aspirin use was associated with reduced mortality risk compared with nonaspirin use (hazard ratio=0.58; 95% confidence interval, 0.46–0.74), and this was confirmed by a propensity-matched subgroup analysis. Low-dose aspirin use was associated with reduced risk of HF hospitalization compared with nonaspirin use in the total population (adjusted hazard ratio=0.70; 95% confidence interval, 0.54–0.90). In adjusted analysis, there was no difference in mortality or HF hospitalization between high-dose aspirin users (>75 mg/d) and nonaspirin users. Conclusions— In this study, low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk during long-term follow-up. These results suggest that low-dose aspirin may have a continuing role in secondary prevention in HF and underline the need for more trials of low-dose aspirin use in HF.Background— Aspirin use in heart failure (HF) is controversial. The drug has proven benefit in comorbidities associated with HF; however, retrospective analysis of angiotensin-converting enzyme inhibitor trials and prospective comparisons with warfarin have shown increased risk of morbidity with aspirin use. This study aims to evaluate the association of low-dose aspirin with mortality and morbidity risk in a large community-based cohort. Methods and Results— This was a retrospective cohort study of patients attending an HF disease management program. Aspirin use at baseline and its association with mortality and HF hospitalization in the population was examined. Of 1476 patients (mean age, 70.4±12.4 years; 63% men), 892 (60.4%) were prescribed aspirin. Low-dose aspirin (75 mg/d) was prescribed to 828 (92.8%) patients. Median follow-up time was 2.6 (0.8–4.5) years. During the follow-up period, 464 (31.4%) patients died. In adjusted analysis, low-dose aspirin use was associated with reduced mortality risk compared with nonaspirin use (hazard ratio=0.58; 95% confidence interval, 0.46–0.74), and this was confirmed by a propensity-matched subgroup analysis. Low-dose aspirin use was associated with reduced risk of HF hospitalization compared with nonaspirin use in the total population (adjusted hazard ratio=0.70; 95% confidence interval, 0.54–0.90). In adjusted analysis, there was no difference in mortality or HF hospitalization between high-dose aspirin users (>75 mg/d) and nonaspirin users. Conclusions— In this study, low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk during long-term follow-up. These results suggest that low-dose aspirin may have a continuing role in secondary prevention in HF and underline the need for more trials of low-dose aspirin use in HF.

Acute myocardial infarction in the presence of normal coronaries and the absence of risk factors in a young, lifelong regular exerciser.

Around 6% of patients suffering an acute myocardial infarction (AMI) have normal coronary arteries. The mechanisms responsible are not fully known, but include hypercoagulable state, coronary endothelial dysfunction, aortic dissection, inflammation, coronary thrombosis, aortic wall stiffening, cocaine abuse, carbon monoxide poisoning and paradoxical embolism. Here, the case of a lifelong regular exerciser without risk factors for cardiovascular disease who suffered an AMI with normal coronaries is reported. Despite normal cardiac function on left ventriculography and echocardiography, late gadolinium enhancement by cardiac magnetic resonance (CMR) revealed significant cardiac necrosis. The long-term prognosis is favourable with low rates of coronary morbidity and mortality. Acute chest pain should not be considered as benign and warrants medical investigation.

LV Apical Rupture Complicating Acute Myocardial Infarction: The Role of CMR

PURPOSE This case illustrates an acute myocardial infarction with occlusion of the left anterior descending coronary artery complicated by apical ventricular rupture and apical thrombus. PROCEDURES An electrocardiogram, transthoracic echocardiogram (TTE), coronary angiography and cardiac magnetic resonance imaging (CMR) guided optimal management of the patient. FINDINGS Coronary angiography revealed multivessel disease with an ostial occlusion of the LAD. Echocardiography showed apical dilatation of the left ventricle with a large, echogenic mass at the apex. Contrast echocardiography confirmed the presence of a large apical thrombus, separated from the LV cavity by myocardium. A CMR showed a completed LAD infarct and a filling thrombus was noted in the aneurysmal apical region inferring a contained rupture of the LV apex. PRINCIPLE CONCLUSIONS Accurate and definitive delineation of unusual cardiac anatomy is best provided by complementary multimodality cardiac imaging, echocardiography and CMR. TTE can miss LV thrombi, particularly when they are large, aneurysmal and apical in nature. CMR provides the cardiac surgeon the ability to visualise in 3D the functional and morphological abnormalities, helping guide necessary intervention. Optimal management of patients with ventricular rupture remains controversial both in terms of timing and choice of intervention.

Multiple Myocardial Clefts on Cardiac Magnetic Resonance Imaging

Myocardial clefts are a recently described finding and are increasingly noted with the growing use of cardiac MRI. We describe a patient with multiple myocardial clefts on MRI. A 45-year-old man came for cardiac screening evaluation because of an abnormal ECG. He had undergone occupational health screening 8 years previously and had been noted to have T-wave inversion from V2 to V4. He had not pursued any further investigations. He was asymptomatic, with no history of syncope. Examination results were within normal limits. A 12-lead ECG again showed anterior T-wave inversion, with no associated Q waves (Figure 1). A transthoracic echocardiogram showed mild asymmetrical interventricular septum thickening, measuring 14 mm …